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Functional specificity in the human brain: A window into the functional architecture of the mind
Kanwisher, Nancy
Functional specificity in the human brain: A window into the functional architecture of the mind for review February 22, 2010) Is the human mind/brain composed of a set of highly specialized components, proponents of specialized organs or modules of the mind and brain--from the phrenologists to Broca to Chomsky
Task-specific functional brain geometry from model maps.
Langs, Georg; Samaras, Dimitris; Paragios, Nikos; Honorio, Jean; Alia-Klein, Nelly; Tomasi, Dardo; Volkow, Nora D; Goldstein, Rita Z
In this paper we propose model maps to derive and represent the intrinsic functional geometry of a brain from functional magnetic resonance imaging (fMRI) data for a specific task. Model maps represent the coherence of behavior of individual fMRI-measurements for a set of observations, or a time sequence. The maps establish a relation between individual positions in the brain by encoding the blood oxygen level dependent (BOLD) signal over a time period in a Markov chain. They represent this relation by mapping spatial positions to a new metric space, the model map. In this map the Euclidean distance between two points relates to the joint modeling behavior of their signals and thus the co-dependencies of the corresponding signals. The map reflects the functional as opposed to the anatomical geometry of the brain. It provides a quantitative tool to explore and study global and local patterns of resource allocation in the brain. To demonstrate the merit of this representation, we report quantitative experimental results on 29 fMRI time sequences, each with sub-sequences corresponding to 4 different conditions for two groups of individuals. We demonstrate that drug abusers exhibit lower differentiation in brain interactivity between baseline and reward related tasks, which could not be quantified until now. PMID:18979834
Functional specificity for high-level linguistic processing in the human brain
Kanwisher, Nancy
brain region previously implicated in language (e.g., Broca's area), without a direct demonstrationFunctional specificity for high-level linguistic processing in the human brain Evelina Fedorenkoa,1 , Michael K. Behra , and Nancy Kanwishera,b,1 a Brain and Cognitive Sciences Department and b Mc
Isolating human brain functional connectivity associated with a specific cognitive process
NASA Astrophysics Data System (ADS)
Silver, Michael A.; Landau, Ayelet N.; Lauritzen, Thomas Z.; Prinzmetal, William; Robertson, Lynn C.
The use of functional magnetic resonance imaging (fMRI) to measure functional connectivity among brain areas has the potential to identify neural networks associated with particular cognitive processes. However, fMRI signals are not a direct measure of neural activity but rather represent blood oxygenation level-dependent (BOLD) signals. Correlated BOLD signals between two brain regions are therefore a combination of neural, neurovascular, and vascular coupling. Here, we describe a procedure for isolating brain functional connectivity associated with a specific cognitive process. Coherency magnitude (measuring the strength of coupling between two time series) and phase (measuring the temporal latency differences between two time series) are computed during performance of a particular cognitive task and also for a control condition. Subtraction of the coherency magnitude and phase differences for the two conditions removes sources of correlated BOLD signals that do not modulate as a function of cognitive task, resulting in a more direct measure of functional connectivity associated with changes in neuronal activity. We present two applications of this task subtraction procedure, one to measure changes in strength of coupling associated with sustained visual spatial attention, and one to measure changes in temporal latencies between brain areas associated with voluntary visual spatial attention.
Molecular and functional characterization of riboflavin specific transport system in rat brain capillary endothelial cells
Patel, Mitesh; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K.
Riboflavin is an important water soluble vitamin (B2) required for metabolic reactions, normal cellular growth, differentiation and function. Mammalian brain cells cannot synthesize riboflavin and must import from systemic circulation. However, the uptake mechanism, cellular translocation and intracellular trafficking of riboflavin in brain capillary endothelial cells are poorly understood. The primary objective of this study is to investigate the existence of riboflavin-specific transport system and delineate the uptake and intracellular regulation of riboflavin in immortalized rat brain capillary endothelial cells (RBE4). The uptake of [3H]-Riboflavin is sodium, temperature and energy dependent but pH independent. [3H]-Riboflavin uptake is saturable with Km and Vmax values of 19 ± 3 µM and 0.235 ± 0.012 picomoles/min/mg protein, respectively. The uptake process is inhibited by unlabelled structural analogs (lumiflavin, lumichrome) but not by structurally unrelated vitamins. Ca++/calmodulin and protein kinase A (PKA) pathways are found to play an important role in the intracellular regulation of [3H]-Riboflavin. Apical and baso-lateral uptake of [3H]-Riboflavin clearly indicate that riboflavin specific transport system is predominantly localized on the apical side of RBE4 cells. A 628 bp band corresponding to riboflavin transporter is revealed in RT-PCR analysis. These findings, for the first time report the existence of a specialized and high affinity transport system for riboflavin in RBE4 cells. Blood-brain barrier (BBB) is a major obstacle limiting drug transport inside the brain as it regulates drug permeation from systemic circulation. This transporter can be utilized for targeted delivery in enhancing brain permeation of highly potent drugs on systemic administration. PMID:22683359
Non-verbal emotion communication training induces specific changes in brain function and structure
Kreifelts, Benjamin; Jacob, Heike; Brück, Carolin; Erb, Michael; Ethofer, Thomas; Wildgruber, Dirk
The perception of emotional cues from voice and face is essential for social interaction. However, this process is altered in various psychiatric conditions along with impaired social functioning. Emotion communication trainings have been demonstrated to improve social interaction in healthy individuals and to reduce emotional communication deficits in psychiatric patients. Here, we investigated the impact of a non-verbal emotion communication training (NECT) on cerebral activation and brain structure in a controlled and combined functional magnetic resonance imaging (fMRI) and voxel-based morphometry study. NECT-specific reductions in brain activity occurred in a distributed set of brain regions including face and voice processing regions as well as emotion processing- and motor-related regions presumably reflecting training-induced familiarization with the evaluation of face/voice stimuli. Training-induced changes in non-verbal emotion sensitivity at the behavioral level and the respective cerebral activation patterns were correlated in the face-selective cortical areas in the posterior superior temporal sulcus and fusiform gyrus for valence ratings and in the temporal pole, lateral prefrontal cortex and midbrain/thalamus for the response times. A NECT-induced increase in gray matter (GM) volume was observed in the fusiform face area. Thus, NECT induces both functional and structural plasticity in the face processing system as well as functional plasticity in the emotion perception and evaluation system. We propose that functional alterations are presumably related to changes in sensory tuning in the decoding of emotional expressions. Taken together, these findings highlight that the present experimental design may serve as a valuable tool to investigate the altered behavioral and neuronal processing of emotional cues in psychiatric disorders as well as the impact of therapeutic interventions on brain function and structure. PMID:24146641
Co-localisation of abnormal brain structure and function in specific language impairment
Badcock, Nicholas A.; Bishop, Dorothy V.M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.
We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. PMID:22137677
Electrical brain stimulation improves cognitive performance by modulating functional connectivity and task-specific activation.
Meinzer, Marcus; Antonenko, Daria; Lindenberg, Robert; Hetzer, Stefan; Ulm, Lena; Avirame, Keren; Flaisch, Tobias; Flöel, Agnes
Excitatory anodal transcranial direct current stimulation (atDCS) can improve human cognitive functions, but neural underpinnings of its mode of action remain elusive. In a cross-over placebo ("sham") controlled study we used functional magnetic resonance imaging (fMRI) to investigate neurofunctional correlates of improved language functions induced by atDCS over a core language area, the left inferior frontal gyrus (IFG). Intrascanner transcranial direct current stimulation-induced changes in overt semantic word generation assessed behavioral modulation; task-related and task-independent (resting-state) fMRI characterized language network changes. Improved word-retrieval during atDCS was paralleled by selectively reduced task-related activation in the left ventral IFG, an area specifically implicated in semantic retrieval processes. Under atDCS, resting-state fMRI revealed increased connectivity of the left IFG and additional major hubs overlapping with the language network. In conclusion, atDCS modulates endogenous low-frequency oscillations in a distributed set of functionally connected brain areas, possibly inducing more efficient processing in critical task-relevant areas and improved behavioral performance. PMID:22302824
Specificity of Hemodynamic Brain Responses to Painful Stimuli: A functional near-infrared spectroscopy study
Yücel, Meryem A.; Aasted, Christopher M.; Petkov, Mihayl P.; Borsook, David; Boas, David A.; Becerra, Lino
Assessing pain in individuals not able to communicate (e.g. infants, under surgery, or following stroke) is difficult due to the lack of non-verbal objective measures of pain. Near-infrared spectroscopy (NIRS) being a portable, non-invasive and inexpensive method of monitoring cerebral hemodynamic activity has the potential to provide such a measure. Here we used functional NIRS to evaluate brain activation to an innocuous and a noxious electrical stimulus on healthy human subjects (n = 11). For both innocuous and noxious stimuli, we observed a signal change in the primary somatosensory cortex contralateral to the stimulus. The painful and non-painful stimuli can be differentiated based on their signal size and profile. We also observed that repetitive noxious stimuli resulted in adaptation of the signal. Furthermore, the signal was distinguishable from a skin sympathetic response to pain that tended to mask it. Our results support the notion that functional NIRS has a potential utility as an objective measure of pain. PMID:25820289
Isolating human brain functional connectivity associated with a specific cognitive process
Robertson, Lynn
a combination of neural, neurovascular, and vascular coupling. Here, we describe a procedure for isolating brain) associated with a particular perceptual or cognitive state are a mixture of neural, neurovascular
Brain morphology is individual-specific information.
Takao, Hidemasa; Hayashi, Naoto; Ohtomo, Kuni
The identification of individual differences in brain morphology is important to understand the background of individual differences in brain functions. In the present study, we investigated whether brain morphology is discernibly different among individuals and is personally identifiable information. Using structural magnetic resonance imaging data from 215 healthy subjects scanned twice (scan interval = 1.0 ± 0.1 years), we performed brain recognition by image normalization using a voxel-based morphometry approach, feature extraction based on principal component analysis, and calculating the Euclidean distances between image pairs projected into the subspace. Even with only 32 dimensions used for projection, the rank-one identification rate was 99.5%. With ?112 dimensions used, the rank-one identification rate was 100%. At a false accept rate of 0.01%, the genuine accept rates were 95.8% and 100% with 32 and ?128 dimensions used for projection, respectively. There was little difference in the Euclidean distances among different combinations of scanners used or between probe-gallery image pairs with and without scanner upgrade. These results indicate that brain morphology can identify a specific individual; i.e., brain morphology is personally identifiable information. Individually different brain morphology may occur as a collection of differences in brain structures that reflect individual differences in a variety of performances and various psychological characteristics and behavior patterns, and may provide the background of individual differences in personality and brain function. PMID:25863137
Executive Summary Objective The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer's disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson's disease (PD). Clinical Need: Target Population and Condition Alzheimer's disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006. In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging. Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci. Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be due to a combination of etiologies, including genetic and environmental components. The prevalence of MS in Canada is 240 cases per 100,000 people. Parkinson's disease is the most prevalent movement disorder; it affects an estimated 100,000 Canadians. Currently, the standard for measuring disease progression is through the use of scales, which are subjective measures of disease progression. Functional brain imaging may provide an objective measure of disease progression, differentiation between parkinsonian syndromes, and response to therapy. The Technology Being Reviewed Functional Brain Imaging Functional brain imaging technologies measure blood flow and metabolism. The results of these tests are often used in conjunction with structural imaging (e.g., MRI or CT). Positron emission tomography and MRS identify abnormalities in brain tissues. The former measures abnormalities through uptake of radiotracers in the brain, while the latter measures chemical shifts in metabolite ratios to identify abnormalities. The potential role of functional MRI (fMRI) is to identify the areas of the brain responsible for language, sensory and motor function (sensorimotor cortex), rather than identifying abnormalities in tissues. Magnetoencephalography measures magnetic fields of the electric currents in the brain, identifying aberrant activity. Magnetoencephalography may have the potential to localize seizure foci and to identify the sensorimotor cortex, visual cortex and auditory cortex. In terms of regulatory status, MEG and PET are licensed by Health Canada. Both MRS and fMRI use a MRI platform; thus, they do not have a separate licence from Health Canada. The radiotracers used in PET scanning are not licensed by Health Canada for general use but can be used through a Clinical Trials Application. Review Strategy The literature published up to September 2006 was searched in the following databases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, and International Network of Agencies for H
Functional Brain Basis of Hypnotizability
Hoeft, Fumiko; Gabrieli, John D.E.; Whitfield-Gabrieli, Susan; Haas, Brian W.; Bammer, Roland; Menon, Vinod; Spiegel, David
Context Focused hypnotic concentration is a model for brain control over sensation and behavior. Pain and anxiety can be effectively alleviated by hypnotic suggestion, which modulates activity in brain regions associated with focused attention, but the specific neural network underlying this phenomenon is not known. Objective The main goal of the study was to investigate the brain basis of hypnotizability. Design Cross sectional, in-vivo neuroimaging study. Setting Academic medical center at Stanford University School of Medicine. Patients 12 adults with high and 12 adults with low hypnotizability. Main Outcome Measures (1) functional MRI (fMRI) to measure functional connectivity networks at rest including default-mode, salience and executive-control networks, (2) structural T1 MRI to measure regional grey and white matter volumes, and (3) diffusion tensor imaging (DTI) to measure white matter microstructural integrity. Results High-compared to low-hypnotizable individuals showed greater functional connectivity between left dorsolateral prefrontal cortex (DLPFC), an executive-control region of the brain, and the salience network composed of the dorsal anterior cingulate cortex (dACC), anterior insula, amygdala, and ventral striatum, involved in detecting, integrating, and filtering relevant somatic, autonomic, and emotional information, using independent component analysis (ICA). Seed based analysis confirmed elevated functional coupling between the dACC and the DLPFC in high, compared to low, hypnotizables. These functional differences were not due to variation in brain structure in these regions, including regional grey and white matter volumes and white matter microstructure. Conclusions Our results provide novel evidence that altered functional connectivity in DLPFC and dACC may underlie hypnotizability. Future studies focusing on how these functional networks change and interact during hypnosis are warranted. PMID:23026956
Cell type-specific spatial and functional coupling between mammalian brain Kv2.1 K+ channels and ryanodine receptors.
Mandikian, Danielle; Bocksteins, Elke; Parajuli, Laxmi Kumar; Bishop, Hannah I; Cerda, Oscar; Shigemoto, Ryuichi; Trimmer, James S
The Kv2.1 voltage-gated K+ channel is widely expressed throughout mammalian brain, where it contributes to dynamic activity-dependent regulation of intrinsic neuronal excitability. Here we show that somatic plasma membrane Kv2.1 clusters are juxtaposed to clusters of intracellular ryanodine receptor (RyR) Ca2+ -release channels in mouse brain neurons, most prominently in medium spiny neurons (MSNs) of the striatum. Electron microscopy-immunogold labeling shows that in MSNs, plasma membrane Kv2.1 clusters are adjacent to subsurface cisternae, placing Kv2.1 in close proximity to sites of RyR-mediated Ca2+ release. Immunofluorescence labeling in transgenic mice expressing green fluorescent protein in specific MSN populations reveals the most prominent juxtaposed Kv2.1:RyR clusters in indirect pathway MSNs. Kv2.1 in both direct and indirect pathway MSNs exhibits markedly lower levels of labeling with phosphospecific antibodies directed against the S453, S563, and S603 phosphorylation site compared with levels observed in neocortical neurons, although labeling for Kv2.1 phosphorylation at S563 was significantly lower in indirect pathway MSNs compared with those in the direct pathway. Finally, acute stimulation of RyRs in heterologous cells causes a rapid hyperpolarizing shift in the voltage dependence of activation of Kv2.1, typical of Ca2+ /calcineurin-dependent Kv2.1 dephosphorylation. Together, these studies reveal that striatal MSNs are distinct in their expression of clustered Kv2.1 at plasma membrane sites juxtaposed to intracellular RyRs, as well as in Kv2.1 phosphorylation state. Differences in Kv2.1 expression and phosphorylation between MSNs in direct and indirect pathways provide a cell- and circuit-specific mechanism for coupling intracellular Ca2+ release to phosphorylation-dependent regulation of Kv2.1 to dynamically impact intrinsic excitability. PMID:24962901
Functional Aspects of Creatine Kinase in Brain
Wolfram Hemmer; Theo Wallimann
The distinct isoenzyme-specific localization of creatine kinase (CK) isoenzymes found recently in brain suggests an important function for CK in brain energetics and points to adaptation of the CK system to the special energy requirements of different neuronal and glial cell types. For example, the presence of brain-type B-CK in Bergmann glial cells and astrocytes is very likely related to
The brain timewise: how timing shapes and supports brain function
Hari, Riitta; Parkkonen, Lauri
We discuss the importance of timing in brain function: how temporal dynamics of the world has left its traces in the brain during evolution and how we can monitor the dynamics of the human brain with non-invasive measurements. Accurate timing is important for the interplay of neurons, neuronal circuitries, brain areas and human individuals. In the human brain, multiple temporal integration windows are hierarchically organized, with temporal scales ranging from microseconds to tens and hundreds of milliseconds for perceptual, motor and cognitive functions, and up to minutes, hours and even months for hormonal and mood changes. Accurate timing is impaired in several brain diseases. From the current repertoire of non-invasive brain imaging methods, only magnetoencephalography (MEG) and scalp electroencephalography (EEG) provide millisecond time-resolution; our focus in this paper is on MEG. Since the introduction of high-density whole-scalp MEG/EEG coverage in the 1990s, the instrumentation has not changed drastically; yet, novel data analyses are advancing the field rapidly by shifting the focus from the mere pinpointing of activity hotspots to seeking stimulus- or task-specific information and to characterizing functional networks. During the next decades, we can expect increased spatial resolution and accuracy of the time-resolved brain imaging and better understanding of brain function, especially its temporal constraints, with the development of novel instrumentation and finer-grained, physiologically inspired generative models of local and network activity. Merging both spatial and temporal information with increasing accuracy and carrying out recordings in naturalistic conditions, including social interaction, will bring much new information about human brain function. PMID:25823867
Functional Lateralization of the Brain.
ERIC Educational Resources Information Center
Dean, Raymond S.
Research concerning lateralization of human brain functions is examined in light of the recent publication of the Kaufman Assessment Battery for Children. Following a review of research methodologies and functions ascribed to the hemispheres of the brain, differences are portrayed as complementary and coexisting modes of cognitive processing.…
Functional brain mapping of psychopathology
Honey, G; Fletcher, P; Bullmore, E
In this paper, we consider the impact that the novel functional neuroimaging techniques may have upon psychiatric illness. Functional neuroimaging has rapidly developed as a powerful tool in cognitive neuroscience and, in recent years, has seen widespread application in psychiatry. Although such studies have produced evidence for abnormal patterns of brain response in association with some pathological conditions, the core pathophysiologies remain unresolved. Although imaging techniques provide an unprecedented opportunity for investigation of physiological function of the living human brain, there are fundamental questions and assumptions which remain to be addressed. In this review we examine these conceptual issues under three broad sections: (1) characterising the clinical population of interest, (2) defining appropriate levels of description of normal brain function, and (3) relating these models to pathophysiological conditions. Parallel advances in each of these questions will be required before imaging techniques can impact on clinical decisions in psychiatry. PMID:11909899
Modeling of region-specific fMRI BOLD neurovascular response functions in rat brain reveals residual differences that correlate with the differences in regional evoked potentials
Pawela, Christopher P.; Hudetz, Anthony G.; Ward, B. Douglas; Schulte, Marie L.; Li, Rupeng; Kao, Dennis S.; Mauck, Matthew C.; Cho, Younghoon R.; Neitz, Jay; Hyde, James S.
The response of the rat visual system to flashes of blue light has been studied by blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). The BOLD temporal response is dependent on the number of flashes presented and demonstrates a refractory period that depends on flash frequency. Activated brain regions included the primary and secondary visual cortex, superior colliculus (SC), dorsal Lateral Geniculate (DLG), and Lateral Posterior Nucleus (LP), which were found to exhibit differing temporal responses. To explain these differences, the BOLD neurovascular response function was modeled. A second order differential equation was developed and solved numerically to arrive at region-specific response functions. Included in the model are the light input from the diode (duty cycle), a refractory period, a transient response following onset and cessation of stimulus, and a slow adjustment to changes in the average level of the signal. Constants in the differential equation were evaluated for each region by fitting the model to the experimental BOLD response from a single flash, and the equation was then solved for multiple flashes. The simulation mimics the major features of the data; however, remaining differences in the frequency dependence of the response between the cortical and subcortical regions were unexplained. We hypothesized that these discrepancies were due to regional-specific differences in neuronal response to flash frequency. To test this hypothesis, cortical visual evoked potentials (VEPs) were recorded using the same stimulation protocol as the fMRI. Cortical VEPs were more suppressed than subcortical VEPs as flash frequency increased, supporting our hypothesis. This is the first report that regional differences in neuronal activation to the same stimulus lead to differential BOLD activation. PMID:18406628
Organization, development and function of complex brain networks
Olaf Sporns; Dante R. Chialvo; Marcus Kaiser; Claus C. Hilgetag
Recent research has revealed general principles in the structural and functional organization of complex networks which are shared by various natural, social and technological systems. This review examines these principles as applied to the organization, development and function of complex brain networks. Specifically, we examine the structural properties of large-scale anatomical and functional brain networks and discuss how they might
Natriuretic hormones in brain function.
Hodes, Anastasia; Lichtstein, David
Natriuretic hormones (NH) include three groups of compounds: the natriuretic peptides (ANP, BNP and CNP), the gastrointestinal peptides (guanylin and uroguanylin), and endogenous cardiac steroids. These substances induce the kidney to excrete sodium and therefore participate in the regulation of sodium and water homeostasis, blood volume, and blood pressure (BP). In addition to their peripheral functions, these hormones act as neurotransmitters or neuromodulators in the brain. In this review, the established information on the biosynthesis, release and function of NH is discussed, with particular focus on their role in brain function. The available literature on the expression patterns of each of the NH and their receptors in the brain is summarized, followed by the evidence for their roles in modulating brain function. Although numerous open questions exist regarding this issue, the available data support the notion that NH participate in the central regulation of BP, neuroprotection, satiety, and various psychiatric conditions, including anxiety, addiction, and depressive disorders. In addition, the interactions between the different NH in the periphery and the brain are discussed. PMID:25506340
Natriuretic Hormones in Brain Function
Hodes, Anastasia; Lichtstein, David
Natriuretic hormones (NH) include three groups of compounds: the natriuretic peptides (ANP, BNP and CNP), the gastrointestinal peptides (guanylin and uroguanylin), and endogenous cardiac steroids. These substances induce the kidney to excrete sodium and therefore participate in the regulation of sodium and water homeostasis, blood volume, and blood pressure (BP). In addition to their peripheral functions, these hormones act as neurotransmitters or neuromodulators in the brain. In this review, the established information on the biosynthesis, release and function of NH is discussed, with particular focus on their role in brain function. The available literature on the expression patterns of each of the NH and their receptors in the brain is summarized, followed by the evidence for their roles in modulating brain function. Although numerous open questions exist regarding this issue, the available data support the notion that NH participate in the central regulation of BP, neuroprotection, satiety, and various psychiatric conditions, including anxiety, addiction, and depressive disorders. In addition, the interactions between the different NH in the periphery and the brain are discussed. PMID:25506340
Specific binding of atrial natriuretic factor in brain microvessels
Chabrier, P.E.; Roubert, P.; Braquet, P.
Cerebral capillaries constitute the blood-brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. The authors examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using /sup 125/I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity and with a binding capacity of 58 fmol/mg of protein. The binding of /sup 125/I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood-brain barrier function.
Functional photoacoustic tomography of animal brains
Wang, Xueding
-dimensional tissue structures in intact brains, including lesions and tumors in brain cerebral cortex. Physiological changes and functional activities in brains, including cerebral blood volume and blood oxygenation in addition to anatomical information, were also...
Advantages in functional imaging of the brain
Mier, Walter; Mier, Daniela
As neuronal pathologies cause only minor morphological alterations, molecular imaging techniques are a prerequisite for the study of diseases of the brain. The development of molecular probes that specifically bind biochemical markers and the advances of instrumentation have revolutionized the possibilities to gain insight into the human brain organization and beyond this—visualize structure-function and brain-behavior relationships. The review describes the development and current applications of functional brain imaging techniques with a focus on applications in psychiatry. A historical overview of the development of functional imaging is followed by the portrayal of the principles and applications of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), two key molecular imaging techniques that have revolutionized the ability to image molecular processes in the brain. We conclude that the juxtaposition of PET and fMRI in hybrid PET/MRI scanners enhances the significance of both modalities for research in neurology and psychiatry and might pave the way for a new area of personalized medicine. PMID:26042013
Brain diffusivity pattern is individual-specific information.
Takao, H; Hayashi, N; Ohtomo, K
The human brain is composed of complex networks of 100 billion neurons that underlie its higher functions. The set of neural connections in the brain has recently attracted growing interest from the scientific community. It is important to identify individual differences in these neural connections to study the background of individual differences in brain function and performance. In the present study, we investigated whether the pattern of brain diffusion, reflecting neural connections, is discernibly different among individuals; i.e., whether brain diffusivity is personally identifiable information. Using diffusion tensor imaging data from 224 healthy subjects scanned twice at an interval of about 1year, we performed brain recognition by spatial normalization of fractional anisotropy maps, feature extraction based on Principal Component Analysis, and calculation of the Euclidean distances between image pairs projected into the subspace. Even with only 16 dimensions used for projection, the rank-one identification rate was 99.1%. The rank-one identification rate was 100% with ?32 dimensions used for projection. The genuine accept rates were 95.1% and 100% at a false accept rate of 0.001%, with 16 and ?32 dimensions used for projection, respectively. There were no large differences in the Euclidean distance among different combinations of scanners used or between image pairs with and without scanner upgrade. The results indicate that brain diffusivity can identify a specific individual; i.e., the pattern of brain diffusion is personally identifiable information. Individual differences in brain diffusivity will form the basis of individual differences in personality and brain function. PMID:26116520
Modeling of region-specific fMRI BOLD neurovascular response functions in rat brain reveals residual differences that correlate with the differences in regional evoked potentials
Christopher P. Pawela; Anthony G. Hudetz; B. Douglas Ward; Marie L. Schulte; Rupeng Li; Dennis S. Kao; Matthew C. Mauck; Younghoon R. Cho; Jay Neitz; James S. Hyde
The response of the rat visual system to flashes of blue light has been studied by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). The BOLD temporal response is dependent on the number of flashes presented and demonstrates a refractory period that depends on flash frequency. Activated brain regions included the primary and secondary visual cortex, superior colliculus (SC),
Organization and Functions of the Brain
Lubica Benuskova; Nikola Kasabov
\\u000a This chapter gives an overview of the brain organization and functions performed by different parts of the brain. We will\\u000a try to answer the following questions: How is the human brain organized at the macroscopic and microscopic levels? Which functions\\u000a are performed by the brain? How is the organization of the human brain related to its functions? These and many
Non-Invasive Brain-to-Brain Interface (BBI): Establishing Functional Links between Two Brains
Yoo, Seung-Schik; Kim, Hyungmin; Filandrianos, Emmanuel; Taghados, Seyed Javid; Park, Shinsuk
Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer's intention to stimulate a rat's brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer's intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications. PMID:23573251
Non-invasive brain-to-brain interface (BBI): establishing functional links between two brains.
Yoo, Seung-Schik; Kim, Hyungmin; Filandrianos, Emmanuel; Taghados, Seyed Javid; Park, Shinsuk
Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer's intention to stimulate a rat's brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer's intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications. PMID:23573251
Specific In Vivo Staining of Astrocytes in the Whole Brain after Intravenous Injection of Sulforhodamine Dyes
Paris-Sud XI, Université de
Specific In Vivo Staining of Astrocytes in the Whole Brain after Intravenous Injection In Vivo Staining of Astrocytes in the Whole Brain after Intravenous Injection of Sulforhodamine Dyes. PLo brain [10,11,12] and has opened a new field of dynamic and functional studies on neuron-astrocytes
IN VIVO STAINING OF ASTROCYTES Specific in vivo staining of astrocytes in the whole brain
Boyer, Edmond
IN VIVO STAINING OF ASTROCYTES 1 Specific in vivo staining of astrocytes in the whole brain after of astrocytes without damaging or interfering with normal brain functions is essential for intravital microscopy in vivo studies of astrocytes in the intact brain [10,11,12] and has opened a new field of dynamic
Dynamic geometry, brain function modeling, and consciousness.
Roy, Sisir; Llinás, Rodolfo
Pellionisz and Llinás proposed, years ago, a geometric interpretation towards understanding brain function. This interpretation assumes that the relation between the brain and the external world is determined by the ability of the central nervous system (CNS) to construct an internal model of the external world using an interactive geometrical relationship between sensory and motor expression. This approach opened new vistas not only in brain research but also in understanding the foundations of geometry itself. The approach named tensor network theory is sufficiently rich to allow specific computational modeling and addressed the issue of prediction, based on Taylor series expansion properties of the system, at the neuronal level, as a basic property of brain function. It was actually proposed that the evolutionary realm is the backbone for the development of an internal functional space that, while being purely representational, can interact successfully with the totally different world of the so-called "external reality". Now if the internal space or functional space is endowed with stochastic metric tensor properties, then there will be a dynamic correspondence between events in the external world and their specification in the internal space. We shall call this dynamic geometry since the minimal time resolution of the brain (10-15 ms), associated with 40 Hz oscillations of neurons and their network dynamics, is considered to be responsible for recognizing external events and generating the concept of simultaneity. The stochastic metric tensor in dynamic geometry can be written as five-dimensional space-time where the fifth dimension is a probability space as well as a metric space. This extra dimension is considered an imbedded degree of freedom. It is worth noticing that the above-mentioned 40 Hz oscillation is present both in awake and dream states where the central difference is the inability of phase resetting in the latter. This framework of dynamic geometry makes it possible to distinguish one individual from another. In this paper we shall investigate the role of dynamic geometry in brain function modeling and the neuronal basis of consciousness. PMID:18166391
Detecting Disease-Specific Patterns of Brain Structure using
Thompson, Paul
and a Population-Based Probabilistic Brain Atlas 1 Paul Thompson PhD, 1,2 Michael S. Mega MD PhD, 1 Christine Vidal-Specific Patterns of Brain Structure using Cortical Pattern Matching and a Population-Based Probabilistic Brain subjects. Nonetheless, design of population-based brain atlases presents considerable challenges, since
Neural Differentiation Modulates the Vertebrate Brain Specific Splicing Program
Madgwick, Alicia; Fort, Philippe; Hanson, Peter S.; Thibault, Philippe; Gaudreau, Marie-Claude; Lutfalla, Georges; Möröy, Tarik; Abou Elela, Sherif; Chaudhry, Bill; Elliott, David J.; Morris, Christopher M.; Venables, Julian P.
Alternative splicing patterns are known to vary between tissues but these patterns have been found to be predominantly peculiar to one species or another, implying only a limited function in fundamental neural biology. Here we used high-throughput RT-PCR to monitor the expression pattern of all the annotated simple alternative splicing events (ASEs) in the Reference Sequence Database, in different mouse tissues and identified 93 brain-specific events that shift from one isoform to another (switch-like) between brain and other tissues. Consistent with an important function, regulation of a core set of 9 conserved switch-like ASEs is highly conserved, as they have the same pattern of tissue-specific splicing in all vertebrates tested: human, mouse and zebrafish. Several of these ASEs are embedded within genes that encode proteins associated with the neuronal microtubule network, and show a dramatic and concerted shift within a short time window of human neural stem cell differentiation. Similarly these exons are dynamically regulated in zebrafish development. These data demonstrate that although alternative splicing patterns often vary between species, there is nonetheless a core set of vertebrate brain-specific ASEs that are conserved between species and associated with neural differentiation. PMID:25993117
Brain Surface Conformal Parameterization with Algebraic Functions
Wang, Yalin
Brain Surface Conformal Parameterization with Algebraic Functions Yalin Wang1,2 , Xianfeng Gu3 a brain surface to a multi-hole disk. The re- sulting parameterizations do not have any singularities of anatomical surfaces in MRI scans of the brain, in- cluding the hippocampi and the cerebral cortices
Brain dynamics promotes function Carlos Lourenco
Lisboa, Universidade Técnica de
Brain dynamics promotes function Carlos Louren¸co 1 Faculty of Sciences of the University of Lisbon, 1049-001 Lisboa - Portugal Abstract. Dynamical structure in the brain promotes biological func- tion. Computational scientists have new opportunities to receive 'algorithmic' inspiration from brain processes
Brain Surface Conformal Parameterization with Algebraic Functions
Wang, Yalin
Brain Surface Conformal Parameterization with Algebraic Functions 1,2Yalin Wang , 3Xianfeng Gu, 1 Angeles, CA, USA. 2Laboratory of Neuro Imaging, Brain Mapping Division, Department of Neurology, UCLA previous work conformally parameterizes various brain anatomical surfaces with several planar
Can we observe epigenetic effects on human brain function?
Nikolova, Yuliya S; Hariri, Ahmad R
Imaging genetics has identified many contributions of DNA sequence variation to individual differences in brain function, behavior, and risk for psychopathology. Recent studies have extended this work beyond the genome by mapping epigenetic differences, specifically gene methylation in peripherally assessed DNA, onto variability in behaviorally and clinically relevant brain function. These data have generated understandable enthusiasm for the potential of such research to illuminate biological mechanisms of risk. We use our research on the effects of genetic and epigenetic variation in the human serotonin transporter on brain function to generate a guardedly optimistic opinion that the available data encourage continued research in this direction, and suggest strategies to promote faster progress. PMID:26051383
Functional brain imaging using near-infrared technology
Meltem Izzetoglu; SCOTT C. BUNCE; Kurtulus Izzetoglu; Banu Onaral; A. K. Pourrezaei
In the last decade, functional near-infrared spectroscopy (fNIR) has been introduced as a new neuroimaging modality with which to conduct functional brain imaging studies [1]?[24]. fNIR technology uses specific wavelengths of light, irradiated through the scalp, to enable the noninvasive measurement of changes in the relative ratios of deoxygenated hemoglobin (deoxy-Hb) and oxygenated hemoglobin (oxy-Hb) during brain activity. This technology
AVC Advantage: Hardware Functional Specifications
Singh, Jaswinder Pal
the functionality of the AVC Advantage hardware, broken down into a number of subsystems. We have attemptedAVC Advantage: Hardware Functional Specifications J. Alex Halderman and Ariel J. Feldman {jhalderm of $82 for the lot [1], and we reverse engineered one of these machines to develop these functional
The restless brain: how intrinsic activity organizes brain function
Raichle, Marcus E.
Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease. PMID:25823869
Bioengineered functional brain-like cortical tissue
Tang-Schomer, Min D.; White, James D.; Tien, Lee W.; Schmitt, L. Ian; Valentin, Thomas M.; Graziano, Daniel J.; Hopkins, Amy M.; Omenetto, Fiorenzo G.; Haydon, Philip G.; Kaplan, David L.
The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury. PMID:25114234
Location, location: using functional magnetic resonance imaging to pinpoint brain differences
Squire, Larry R.
Location, location: using functional magnetic resonance imaging to pinpoint brain differences is that stimulant- dependent individuals show specific, rather than generic, brain activation differences, i.e. instead of showing more or less brain activation regardless of task, they exhibit process-related brain
Focused ultrasound modulates region-specific brain activity
Yoo, Seung-Schik; Bystritsky, Alexander; Lee, Jong-Hwan; Zhang, Yongzhi; Fischer, Krisztina; Min, Byoung-Kyong; McDannold, Nathan J.; Pascual-Leone, Alvaro; Jolesz, Ferenc A.
We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animal's somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using image-guided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders. PMID:21354315
Energetic cost of brain functional connectivity
Tomasi, Dardo; Wang, Gene-Jack; Volkow, Nora D.
The brain's functional connectivity is complex, has high energetic cost, and requires efficient use of glucose, the brain's main energy source. It has been proposed that regions with a high degree of functional connectivity are energy efficient and can minimize consumption of glucose. However, the relationship between functional connectivity and energy consumption in the brain is poorly understood. To address this neglect, here we propose a simple model for the energy demands of brain functional connectivity, which we tested with positron emission tomography and MRI in 54 healthy volunteers at rest. Higher glucose metabolism was associated with proportionally larger MRI signal amplitudes, and a higher degree of connectivity was associated with nonlinear increases in metabolism, supporting our hypothesis for the energy efficiency of the connectivity hubs. Basal metabolism (in the absence of connectivity) accounted for 30% of brain glucose utilization, which suggests that the spontaneous brain activity accounts for 70% of the energy consumed by the brain. The energy efficiency of the connectivity hubs was higher for ventral precuneus, cerebellum, and subcortical hubs than for cortical hubs. The higher energy demands of brain communication that hinges upon higher connectivity could render brain hubs more vulnerable to deficits in energy delivery or utilization and help explain their sensitivity to neurodegenerative conditions, such as Alzheimer's disease. PMID:23898179
[Regulation of brain microvessel function].
Kobayashi, Hideyuki; Yokoo, Hiroki; Yanagita, Toshihiko; Wada, Akihiko
The brain microvessels are formed by a specialized endothelium and regulate the movement of solutes between blood and brain. The endothelial cells are sealed together by tight junctions and play a role as the blood-brain barrier. The brain microvessels express GLUT1 as the major form of glucose transporter, aquaporin-4 as a water channel, and p-glycoprotein as a xenobiotic transporter. Occludin and claudin-5 have been identified as the components of tight junction. Increasing evidence suggests that the activities of the transporters are regulated by adrenergic nerve activity as well as by bioactive peptides such as adrenomedullin. The regulation of the activity as well as expression of these transporters may become a strategy for prophylaxis and treatment of not only cerebral vascular diseases but also neurodegenerative disorders, developmental abnormalities and aging of the brain. PMID:12061139
Detecting disease-specific patterns of brain structure using cortical pattern matching and a population-based probabilistic brain atlas
Thompson, Paul M.; Mega, Michael S.; Vidal, Christine; Rapoport, Judith L.; Toga, Arthur W.
The rapid creation of comprehensive brain image databases mandates the development of mathematical algorithms to uncover disease specific patterns of brain structure and function in human populations. We describe our construction of probabilistic atlases that store detailed information on how the brain varies across age and gender, across time, in health and disease, and in large human populations. Specifically, we introduce a mathematical framework based on covariant partial differential equations (PDEs), pull-backs of mappings under harmonic flows, and high-dimensional random tensor fields to encode variations in cortical patterning, asymmetry and tissue distribution in a population-based brain image database (N =94 scans). We use this information to detect disease-specific abnormalities in Alzheimer's disease and schizophrenia, including dynamic changes over time. Illustrative examples are chosen to show how group patterns of cortical organization, asymmetry, and disease-specific trends can be resolved that are not apparent in individual brain images. Finally, we create four-dimensional (4D) maps that store probabilistic information on the dynamics of brain change in development and disease. Digital atlases that generate these maps show considerable promise in identifying general patterns of structural and functional variation in diseased populations, and revealing how these features depend on demographic, genetic, clinical and therapeutic parameters. PMID:21218175
Functional connectivity hubs of the mouse brain.
Liska, Adam; Galbusera, Alberto; Schwarz, Adam J; Gozzi, Alessandro
Recent advances in functional connectivity methods have made it possible to identify brain hubs - a set of highly connected regions serving as integrators of distributed neuronal activity. The integrative role of hub nodes makes these areas points of high vulnerability to dysfunction in brain disorders, and abnormal hub connectivity profiles have been described for several neuropsychiatric disorders. The identification of analogous functional connectivity hubs in preclinical species like the mouse may provide critical insight into the elusive biological underpinnings of these connectional alterations. To spatially locate functional connectivity hubs in the mouse brain, here we applied a fully-weighted network analysis to map whole-brain intrinsic functional connectivity (i.e., the functional connectome) at a high-resolution voxel-scale. Analysis of a large resting-state functional magnetic resonance imaging (rsfMRI) dataset revealed the presence of six distinct functional modules related to known large-scale functional partitions of the brain, including a default-mode network (DMN). Consistent with human studies, highly-connected functional hubs were identified in several sub-regions of the DMN, including the anterior and posterior cingulate and prefrontal cortices, in the thalamus, and in small foci within well-known integrative cortical structures such as the insular and temporal association cortices. According to their integrative role, the identified hubs exhibited mutual preferential interconnections. These findings highlight the presence of evolutionarily-conserved, mutually-interconnected functional hubs in the mouse brain, and may guide future investigations of the biological foundations of aberrant rsfMRI hub connectivity associated with brain pathological states. PMID:25913701
Altered brain functional networks in heavy smokers.
Lin, Fuchun; Wu, Guangyao; Zhu, Ling; Lei, Hao
Recent neuroimaging studies have demonstrated that cigarette smoking is associated with changed brain structure and function. However, little is known about alterations of the topological organization of brain functional networks in heavy smokers. Thirty-one heavy smokers and 33 non-smokers underwent a resting-state functional magnetic resonance imaging scan. The whole-brain functional networks were constructed by thresholding the correlation matrices of 90 brain regions and their topological properties were analyzed using graph network analysis. Non-parametric permutation tests were performed to investigate group differences in network topological measures and multiple regression analysis was conducted to determine the relationships between the network metrics and smoking-related variables. Both heavy smokers and non-smokers exhibited small-world architecture in their brain functional networks. Compared with non-smokers, however, heavy smokers showed altered topological measurements characterized by lower global efficiency, higher local efficiency and clustering coefficients and greater path length. Furthermore, heavy smokers demonstrated decreased nodal global efficiency mainly in brain regions within the default mode network, whereas increased nodal local efficiency predominated in the visual-related regions. In addition, heavy smokers exhibited an association between the altered network metrics and the duration of cigarette use or the severity of nicotine dependence. Our results suggest that heavy smokers may have less efficient network architecture in the brain, and chronic cigarette smoking is associated with disruptions in the topological organization of brain networks. Our findings may further the understanding of the effects of chronic cigarette smoking on the brain and the pathophysiological mechanisms underlying nicotine dependence. PMID:24962385
Isoform-Specific Effects of Human Apolipoprotein E on Brain Function Revealed in ApoE Knockout Mice: Increased Susceptibility of Females
Jacob Raber; Derek Wong; Manuel Buttini; Matthias Orth; Stefano Bellosta; Robert E. Pitas; Robert W. Mahley; Lennart Mucke
Apolipoprotein E (apoE) mediates the redistribution of lipids among cells and is expressed at highest levels in brain and liver. Human apoE exists in three major isoforms encoded by distinct alleles (? 2, ? 3, and ? 4). Compared with APOE ? 2 and ? 3, APOE ? 4 increases the risk of cognitive impairments, lowers the age of onset
Astrocytes and Brain Function: Implications for Reproduction
Recent evidence suggests that astrocytes have important neu- roregulatory functions in addition to their classic functions of support and segregation of neurons. These newly revealed functions include regulation of neuron communication, neuro- secretion, and synaptic plasticity. Although these actions occur throughout the brain, this review will focus on astrocyte- neuron interactions in the hypothalamus, particularly with re- spect to their
Functional brain development in humans
Mark H. Johnson
There is a continuing debate in developmental neuroscience about the importance of activity-dependent processes. The relatively delayed rate of development of the human brain, compared with that of other mammals, might make it more susceptible to the influence of postnatal experience. The human infant is well adapted to capitalize on this opportunity through primitive biases to attend to relevant stimuli
Project X functional requirements specification
Holmes, S.D.; Henderson, S.D.; Kephart, R.; Kerby, J.; Kourbanis, I.; Lebedev, V.; Mishra, S.; Nagaitsev, S.; Solyak, N.; Tschirhart, R.; /Fermilab
Project X is a multi-megawatt proton facility being developed to support a world-leading program in Intensity Frontier physics at Fermilab. The facility is designed to support programs in elementary particle and nuclear physics, with possible applications to nuclear energy research. A Functional Requirements Specification has been developed in order to establish performance criteria for the Project X complex in support of these multiple missions, and to assure that the facility is designed with sufficient upgrade capability to provide U.S. leadership for many decades to come. This paper will briefly review the previously described Functional Requirements, and then discuss their recent evolution.
Functional Specificity of Ras Isoforms
Castellano, Esther; Santos, Eugenio
H-ras, N-ras, and K-ras are canonical ras gene family members frequently activated by point mutation in human cancers and coding for 4 different, highly related protein isoforms (H-Ras, N-Ras, K-Ras4A, and K-Ras4B). Their expression is nearly ubiquitous and broadly conserved across eukaryotic species, although there are quantitative and qualitative differences of expression depending on the tissue and/or developmental stage under consideration. Extensive functional studies have determined during the last quarter century that these Ras gene products are critical components of signaling pathways that control eukaryotic cell proliferation, survival, and differentiation. However, because of their homology and frequent coexpression in various cellular contexts, it remained unclear whether the different Ras proteins play specific or overlapping functional roles in physiological and pathological processes. Initially, their high degree of sequence homology and the observation that all Ras isoforms share common sets of downstream effectors and upstream activators suggested that they were mostly redundant functionally. In contrast, the notion of functional specificity for each of the different Ras isoforms is supported at present by an increasing body of experimental observations, including 1) the fact that different ras isoforms are preferentially mutated in specific types of tumors or developmental disorders; 2) the different transforming potential of transfected ras genes in different cell contexts; 3) the distinct sensitivities exhibited by the various Ras family members for modulation by different GAPs or GEFs; 4) the demonstration that different Ras isoforms follow distinct intracellular processing pathways and localize to different membrane microdomains or subcellular compartments; 5) the different phenotypes displayed by genetically modified animal strains for each of the 3 ras loci; and 6) the specific transcriptional networks controlled by each isoform in different cellular settings. PMID:21779495
Endocannabinoid Functions in Neurogenesis, Neuronal Migration, and Specification
Tibor Harkany; Manuel Guzmán; Yasmin L. Hurd
Endocannabinoids act as retrograde messengers thus controlling many synapses in the postnatal brain. In contrast, the concept\\u000a that endocannabinoid functions are pivotal to fundamental developmental processes, including progenitor proliferation and\\u000a fate specification, lineage segregation, neuronal migration, differentiation and survival, in the embryonic brain has just\\u000a begun to emerge. Understanding the basic developmental and signaling principles controlled by endocannabinoids is pertinent
Functional brain network efficiency predicts intelligence.
Langer, Nicolas; Pedroni, Andreas; Gianotti, Lorena R R; Hänggi, Jürgen; Knoch, Daria; Jäncke, Lutz
The neuronal causes of individual differences in mental abilities such as intelligence are complex and profoundly important. Understanding these abilities has the potential to facilitate their enhancement. The purpose of this study was to identify the functional brain network characteristics and their relation to psychometric intelligence. In particular, we examined whether the functional network exhibits efficient small-world network attributes (high clustering and short path length) and whether these small-world network parameters are associated with intellectual performance. High-density resting state electroencephalography (EEG) was recorded in 74 healthy subjects to analyze graph-theoretical functional network characteristics at an intracortical level. Ravens advanced progressive matrices were used to assess intelligence. We found that the clustering coefficient and path length of the functional network are strongly related to intelligence. Thus, the more intelligent the subjects are the more the functional brain network resembles a small-world network. We further identified the parietal cortex as a main hub of this resting state network as indicated by increased degree centrality that is associated with higher intelligence. Taken together, this is the first study that substantiates the neural efficiency hypothesis as well as the Parieto-Frontal Integration Theory (P-FIT) of intelligence in the context of functional brain network characteristics. These theories are currently the most established intelligence theories in neuroscience. Our findings revealed robust evidence of an efficiently organized resting state functional brain network for highly productive cognitions. PMID:21557387
The illiterate brain. Learning to read and write during childhood influences the functional organization of the adult brain
A. Castro-Caldas; K. M. Petersson; A. Reis; S. Stone-Elander; M. Ingvar
Summary Learning a specific skill during childhood may partly determine the functional organization of the adult brain. This hypothesis led us to study oral language processing in illiterate subjects who, for social reasons, had never entered school and had no knowledge of reading or writing. In a brain activation study using PET and statistical parametric mapping, we compared word and
Specific ways brain SPECT imaging enhances clinical psychiatric practice.
Amen, Daniel G; Highum, Diane; Licata, Robert; Annibali, Joseph A; Somner, Lillian; Pigott, H Edmund; Taylor, Derek V; Trujillo, Manuel; Newberg, Andrew; Henderson, Theodore; Willeumier, Kristen
Our objective was to ascertain in a prospective case series how often brain single photon emission computed tomography (SPECT) neuroimaging adds relevant information for diagnosis and/or treatment beyond current standard assessment tools in complex psychiatric cases. Charts of 109 consecutively evaluated outpatients from four psychiatrics clinics that routinely utilize SPECT imaging for complex cases were analyzed in two stages. In stage one, psychiatrists reviewed detailed clinical histories, mental status exams, and the structured clinical interview for DSM-IV, but not the results of SPECT studies, assigned a diagnosis based on DSM-IV criteria, and then developed a comprehensive treatment plan. In stage two, evaluators were given access to the SPECT studies for each patient. The addition of SPECT modified the diagnosis or treatment plan in 78.9% (n=86; rated level 2 or 3 change) of cases. The most clinically significant changes were undetected brain trauma (22.9%), toxicity patterns (22.9%) and the need for a structural imaging study (9.2%). Specific functional abnormalities were seen as follows that potentially could impact treatment: temporal lobe dysfunction (66.1%) and prefrontal hypoperfusion (47.7%). SPECT has the potential to add clinically meaningful information to enhance patient care beyond current assessment tools in complex or treatment resistant cases. PMID:22880537
Gilbert, P F
An outline of how the brain may compute is proposed. In the cerebral cortex memories are stored through long-term potentiation at synapses from layer 1 cortical inputs (representing contexts) on layer 2/3 pyramidal cells linked with the thalamus in a cortico-thalamic (CT) unit. The signals which are memorized are the layer 3 inputs from the thalamus or other cortical areas. Signals are memorized (and later recalled) at the gamma frequency. A conscious thought comprises the outputs of layer 5 cells in CT units in different cortical regions firing in synchrony through the contribution of oscillatory thalamic and cortical inputs. This cortical output influences sub-cortical areas to cause or participate in a movement. Cerebral cortical outputs may be stored in the cerebellum and generated later in a particular context by the basal ganglia and cerebellum. Thus the brain may either generate 'conscious' outputs using the cerebral cortex or 'automatic' outputs using the basal ganglia and cerebellum. When contexts are recognized by the basal ganglia it permits outputs stored in the cerebellum to commence and in this way the basal ganglia can control complex sequences of outputs or movements. Working memory involves the prefrontal cortex using similarly the basal ganglia and cerebellum. The hippocampus has a role in the storage and recall of cortical outputs by providing unique layer 1 contexts to all the CT loops in different cortical areas in a conscious thought. With further recall of the thought new layer 1 contexts may become associated with the CT loops enabling recall without the hippocampal input. PMID:11489610
See the brain at work: intraoperative laser Doppler functional brain imaging
E. J. Martin-Williams; A. Raabe; D. van de Ville; M. Leutenegger; A. Szelényi; E. Hattingen; R. Gerlach; V. Seifert; C. Hauger; A. Lopez; R. Leitgeb; M. Unser; T. Lasser
During open brain surgery we acquire perfusion images non-invasively using laser Doppler imaging. The regions of brain activity show a distinct signal in response to stimulation providing intraoperative functional brain maps of remarkably strong contrast.
Dissociations between behavioural and functional magnetic resonance imaging-based evaluations of cognitive function after brain injury
Bardin, Jonathan C.; Fins, Joseph J.; Katz, Douglas I.; Hersh, Jennifer; Heier, Linda A.; Tabelow, Karsten; Dyke, Jonathan P.; Ballon, Douglas J.; Schiff, Nicholas D.
Functional neuroimaging methods hold promise for the identification of cognitive function and communication capacity in some severely brain-injured patients who may not retain sufficient motor function to demonstrate their abilities. We studied seven severely brain-injured patients and a control group of 14 subjects using a novel hierarchical functional magnetic resonance imaging assessment utilizing mental imagery responses. Whereas the control group showed consistent and accurate (for communication) blood-oxygen-level-dependent responses without exception, the brain-injured subjects showed a wide variation in the correlation of blood-oxygen-level-dependent responses and overt behavioural responses. Specifically, the brain-injured subjects dissociated bedside and functional magnetic resonance imaging-based command following and communication capabilities. These observations reveal significant challenges in developing validated functional magnetic resonance imaging-based methods for clinical use and raise interesting questions about underlying brain function assayed using these methods in brain-injured subjects. PMID:21354974
Whole-Brain Functional Connectivity Identification of Functional Dyspepsia
Nan, Jiaofen; Liu, Jixin; Li, Guoying; Xiong, Shiwei; Yan, Xuemei; Yin, Qing; Zeng, Fang; von Deneen, Karen M.; Liang, Fanrong; Gong, Qiyong; Qin, Wei; Tian, Jie
Recent neuroimaging studies have shown local brain aberrations in functional dyspepsia (FD) patients, yet little attention has been paid to the whole-brain resting-state functional network abnormalities. The purpose of this study was to investigate whether FD disrupts the patterns of whole-brain networks and the abnormal functional connectivity could reflect the severity of the disease. The dysfunctional interactions between brain regions at rest were investigated in FD patients as compared with 40 age- and gender- matched healthy controls. Multivariate pattern analysis was used to evaluate the discriminative power of our results for classifying patients from controls. In our findings, the abnormal brain functional connections were mainly situated within or across the limbic/paralimbic system, the prefrontal cortex, the tempo-parietal areas and the visual cortex. About 96% of the subjects among the original dataset were correctly classified by a leave one-out cross-validation approach, and 88% accuracy was also validated in a replication dataset. The classification features were significantly associated with the patients' dyspepsia symptoms, the self-rating depression scale and self-rating anxiety scale, but it was not correlated with duration of FD patients (p>0.05). Our results may indicate the effectiveness of the altered brain functional connections reflecting the disease pathophysiology underling FD. These dysfunctional connections may be the epiphenomena or causative agents of FD, which may be affected by clinical severity and its related emotional dimension of the disease rather than the clinical course. PMID:23799056
Integrating Retinoic Acid Signaling with Brain Function
ERIC Educational Resources Information Center
Luo, Tuanlian; Wagner, Elisabeth; Drager, Ursula C.
The vitamin A derivative retinoic acid (RA) regulates the transcription of about a 6th of the human genome. Compelling evidence indicates a role of RA in cognitive activities, but its integration with the molecular mechanisms of higher brain functions is not known. Here we describe the properties of RA signaling in the mouse, which point to…
Press Release Fingerprints of higher brain functions
Tübingen, Universität
Seite 1/3 Press Release Fingerprints of higher brain functions Neuroscientists uncover novel during information processing, may be `fingerprints' of these basic calculations. Such basic calculations of brainwaves, also known as oscillations, are `spec- tral fingerprints' of canonical neuronal computations
On the Relationship Between Lateralized Brain Function and Orienting Asymmetries
Ghazanfar, Asif
areas of the brain (Broca, 1861; Wernicke, 1874). The loci of brain lesions detected by postmortemOn the Relationship Between Lateralized Brain Function and Orienting Asymmetries Christoph Teufel will require a much better understanding of how lateralized brain functions interact with overt behaviors
Regulatory RNAs in Brain Function and Disorders
Iacoangeli, Anna; Bianchi, Riccardo; Tiedge, Henri
Regulatory RNAs are being increasingly investigated in neurons, and important roles in brain function have been revealed. Regulatory RNAs are non-protein-coding RNAs (npcRNAs) that comprise a heterogeneous group of molecules, varying in size and mechanism of action. Regulatory RNAs often exert post-transcriptional control of gene expression, resulting in gene silencing or gene expression stimulation. Here, we review evidence that regulatory RNAs are implicated in neuronal development, differentiation, and plasticity. We will also discuss npcRNA dysregulation that may be involved in pathological states of the brain such as neurodevelopmental disorders, neurodegeneration, and epilepsy. PMID:20307503
Common and specific brain responses to scenic emotional stimuli.
Radua, Joaquim; Sarró, Salvador; Vigo, Teresa; Alonso-Lana, Silvia; Bonnín, C Mar; Ortiz-Gil, Jordi; Canales-Rodríguez, Erick J; Maristany, Teresa; Vieta, Eduard; Mckenna, Peter J; Salvador, Raymond; Pomarol-Clotet, Edith
Processing of emotions has been an enduring topic of interest in neuroimaging research, but studies have mostly used facial emotional stimuli. The aim of this study was to determine neural networks involved in emotion processing using scenic emotional visual stimuli. One hundred and twenty photographs from the International Affective Picture System (IAPS), including ecological scenes of disgust, fear, happiness, and sadness, were presented to 40 healthy participants while they underwent functional magnetic imaging resonance (fMRI). Afterwards they evaluated the emotional content of the pictures in an offline task. The occipito-temporal cortex and the amygdala-hippocampal complex showed a non-specific emotion-related activation, which was more marked in response to negative emotions than to happiness. The temporo-parietal cortex and the ventral anterior cingulate gyrus showed deactivation, with the former being marked for all emotions except fear and the latter being most marked for disgust. The fusiform gyrus showed activation in response to disgust and deactivation in response to happiness or sadness. Brain regions involved in processing of scenic emotion therefore resemble those reported for facial expressions of emotion in that they respond to a range of different emotions, although there appears to be specificity in the intensity and direction of the response. PMID:23700105
Projection-specific characteristics of retinal input to the brain.
Gauvain, Gregory; Murphy, Gabe J
The brain receives information about the direction of object motion from several types of retinal ganglion cells (RGCs). On-Off direction-selective (DS) RGCs respond preferentially to stimuli moving quickly in one of four directions and provide a significant (but difficult to quantify) fraction of RGC input to the SC. On DS RGCs, in comparison, respond preferentially to stimuli moving slowly in one of three directions and are thought to only target retinorecipient nuclei comprising the accessory optic system, e.g., the medial terminal nucleus (MTN). To determine the fraction of SC-projecting RGCs that exhibit direction selectivity, and the specificity with which On-Off and On DS RGCs target retinorecipient areas, we performed optical and electrophysiological recordings from RGCs retrogradely labeled from the mouse SC and MTN. We found, surprisingly, that both On-Off and On DS RGCs innervate the SC; collectively they constitute nearly 40% of SC-projecting RGCs. In comparison, only On DS RGCs project to the MTN. Subsequent experiments revealed that individual On DS RGCs innervate either the SC or MTN and exhibit robust projection-specific differences in somatodendritic morphology, cellular excitability, and light-evoked activity; several projection-specific differences in the output of On DS RGCs correspond closely to differences in excitatory synaptic input the cells receive. Our results reveal a robust projection of On DS RGCs to the SC, projection-specific differences in the response properties of On DS RGCs, and biophysical and synaptic mechanisms that underlie these functional differences. PMID:25904807
Electromagnetic inverse applications for functional brain imaging
Wood, C.C.
This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). This project addresses an important mathematical and computational problem in functional brain imaging, namely the electromagnetic {open_quotes}inverse problem.{close_quotes} Electromagnetic brain imaging techniques, magnetoencephalography (MEG) and electroencephalography (EEG), are based on measurements of electrical potentials and magnetic fields at hundreds of locations outside the human head. The inverse problem is the estimation of the locations, magnitudes, and time-sources of electrical currents in the brain from surface measurements. This project extends recent progress on the inverse problem by combining the use of anatomical constraints derived from magnetic resonance imaging (MRI) with Bayesian and other novel algorithmic approaches. The results suggest that we can achieve significant improvements in the accuracy and robustness of inverse solutions by these two approaches.
Sustained deep-tissue pain alters functional brain connectivity Jieun Kim a,
Napadow, Vitaly
Sustained deep-tissue pain alters functional brain connectivity Jieun Kim a, , Marco L. Loggia a connec- tivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific connectivity a b s t r a c t Recent functional brain connectivity studies have contributed to our understanding
The construction of common and specific significance subnetworks of Alzheimer's disease from multiple brain regions.
Kong, Wei; Mou, Xiaoyang; Zhang, Na; Zeng, Weiming; Li, Shasha; Yang, Yang
Alzheimer's disease (AD) is a progressively and fatally neurodegenerative disorder and leads to irreversibly cognitive and memorial damage in different brain regions. The identification and analysis of the dysregulated pathways and subnetworks among affected brain regions will provide deep insights for the pathogenetic mechanism of AD. In this paper, commonly and specifically significant subnetworks were identified from six AD brain regions. Protein-protein interaction (PPI) data were integrated to add molecular biological information to construct the functional modules of six AD brain regions by Heinz algorithm. Then, the simulated annealing algorithm based on edge weight is applied to predicting and optimizing the maximal scoring networks for common and specific genes, respectively, which can remove the weak interactions and add the prediction of strong interactions to increase the accuracy of the networks. The identified common subnetworks showed that inflammation of the brain nerves is one of the critical factors of AD and calcium imbalance may be a link among several causative factors in AD pathogenesis. In addition, the extracted specific subnetworks for each brain region revealed many biologically functional mechanisms to understand AD pathogenesis. PMID:25866779
Retinoic Acid Signaling in the Functioning Brain
NSDL National Science Digital Library
Ursula C. Drager (University of Massachusetts Medical School; Eunice Kennedy Shriver Center REV)
Retinoic acid, an active form of vitamin A, regulates gene expression throughout the body, and many components of the signaling system through which it acts are present in the brain. Very little is known, however, about how retinoic acid functions in neurobiological systems. Several studies have provided evidence that retinoic acid plays a role in sleep, learning, and memory, but the precise mechanisms through which it influences these processes remain unclear. All of these processes involve local or long-range inhibition and synchronized neuronal activity between separate locations in the brain. A critical component in the generation of the synchronized firing of cortical neurons (cortical synchrony) is a network of inhibitory interneurons containing parvalbumin, a cell population affected by retinoid perturbations, such as exposure to a vitamin A overdose. An understanding of the role of retinoids in normal brain function would provide clues to the long-standing question of whether abnormalities in retinoic acid signaling contribute to the pathogenesis of some brain diseases with uncertain etiologies that involve both genetic and environmental factors.
Generative models, brain function and neuroimaging.
Friston, K J; Price, C J
The representational capacity and inherent function of any neuron, neuronal population or cortical area in the brain is dynamic and context-sensitive. Functional integration, or interactions among brain systems, that employ driving (bottom up) and backward (top-down) connections, mediate this adaptive and contextual specialisation. A critical consequence is that neuronal responses, in any given cortical area, can represent different things at different times. This can have fundamental implications for the design of brain imaging experiments and the interpretation of their results. Our arguments are developed under generative models of brain function, where higher-level systems provide a prediction of the inputs to lower-level regions. Conflict between the two is resolved by changes in the higher-level representations, which are driven by the ensuing error in lower regions, until the mismatch is "cancelled". From this perspective the specialisation of any region is determined both by bottom-up driving inputs and by top-down predictions. Specialisation is therefore not an intrinsic property of any region but depends on both forward and backward connections with other areas. Because the latter have access to the context in which the inputs are generated they are in a position to modulate the selectivity or specialisation of lower areas. The implications for classical models (e.g., classical receptive fields in electrophysiology, classical specialisation in neuroimaging and connectionism in cognitive models) are severe and suggest these models may provide incomplete accounts of real brain architectures. Here we focus on the implications for cognitive neuroscience in the context of neuroimaging. PMID:11501732
Transcriptome analyses of adult mouse brain reveal enrichment of lncRNAs in specific brain regions and neuronal populations
Kadakkuzha, Beena M.; Liu, Xin-An; McCrate, Jennifer; Shankar, Gautam; Rizzo, Valerio; Afinogenova, Alina; Young, Brandon; Fallahi, Mohammad; Carvalloza, Anthony C.; Raveendra, Bindu; Puthanveettil, Sathyanarayanan V.
Despite the importance of the long non-coding RNAs (lncRNAs) in regulating biological functions, the expression profiles of lncRNAs in the sub-regions of the mammalian brain and neuronal populations remain largely uncharacterized. By analyzing RNASeq datasets, we demonstrate region specific enrichment of populations of lncRNAs and mRNAs in the mouse hippocampus and pre-frontal cortex (PFC), the two major regions of the brain involved in memory storage and neuropsychiatric disorders. We identified 2759 lncRNAs and 17,859 mRNAs in the hippocampus and 2561 lncRNAs and 17,464 mRNAs expressed in the PFC. The lncRNAs identified correspond to ~14% of the transcriptome of the hippocampus and PFC and ~70% of the lncRNAs annotated in the mouse genome (NCBIM37) and are localized along the chromosomes as varying numbers of clusters. Importantly, we also found that a few of the tested lncRNA-mRNA pairs that share a genomic locus display specific co-expression in a region-specific manner. Furthermore, we find that sub-regions of the brain and specific neuronal populations have characteristic lncRNA expression signatures. These results reveal an unexpected complexity of the lncRNA expression in the mouse brain. PMID:25798087
Functional brain imaging in respiratory medicine.
Pattinson, Kyle
Discordance of clinical symptoms with markers of disease severity remains a conundrum in a variety of respiratory conditions. The breathlessness of chronic lung disease correlates poorly with spirometry, yet is a better predictor of mortality. In chronic cough, symptoms are often evident without clear physical cause. In asthma, the terms 'over perceivers' and 'under perceivers' are common parlance. In all these examples, aberrant brain mechanisms may explain the mismatch between symptoms and pathology. Functional MRI is a non-invasive method of measuring brain function. It has recently become significantly advanced enough to be useful in clinical research and to address these potential mechanisms. This article explains how FMRI works, current understanding from FMRI in breathlessness, cough and asthma and suggests possibilities for future research. PMID:25589519
ventral veins lacking is required for specification of the tritocerebrum in embryonic brain development of Drosophila
Stefan Meier; Simon G. Sprecher; Heinrich Reichert; Frank Hirth
The homeotic or Hox genes encode a network of conserved transcription factors which provide axial positional information and control segment morphology in development and evolution. During embryonic brain development of Drosophila, the Hox gene labial (lab) is essential for tritocerebral neuromere specification; lab loss of function results in tritocerebral cells that fail to adopt a neuronal identity, causing axonal pathfinding
When "altering brain function" becomes "mind control"
Koivuniemi, Andrew; Otto, Kevin
Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. "Under what conditions does 'altering brain function' qualify as 'mind control'?" In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control. PMID:25352789
The degree to which genes and environment determine brain structure and function is of fundamental importance. Large-
Thompson, Paul
significantly influenced cortical structure in Broca's and Wernicke's language areas, as well as frontal brainThe degree to which genes and environment determine brain structure and function is of fundamental-specific patterns of gene and brain function in large human populations1,2. Yet, little is known about the genetic
A Bayesian Model of Category-Specific Emotional Brain Responses
Wager, Tor D.; Kang, Jian; Johnson, Timothy D.; Nichols, Thomas E.; Satpute, Ajay B.; Barrett, Lisa Feldman
Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories—fear, anger, disgust, sadness, or happiness—is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. PMID:25853490
Age-related reorganizational changes in modularity and functional connectivity of human brain networks.
Song, Jie; Birn, Rasmus M; Boly, Mélanie; Meier, Timothy B; Nair, Veena A; Meyerand, Mary E; Prabhakaran, Vivek
The human brain undergoes both morphological and functional modifications across the human lifespan. It is important to understand the aspects of brain reorganization that are critical in normal aging. To address this question, one approach is to investigate age-related topological changes of the brain. In this study, we developed a brain network model using graph theory methods applied to the resting-state functional magnetic resonance imaging data acquired from two groups of normal healthy adults classified by age. We found that brain functional networks demonstrated modular organization in both groups with modularity decreased with aging, suggesting less distinct functional divisions across whole brain networks. Local efficiency was also decreased with aging but not with global efficiency. Besides these brain-wide observations, we also observed consistent alterations of network properties at the regional level in the elderly, particularly in two major functional networks-the default mode network (DMN) and the sensorimotor network. Specifically, we found that measures of regional strength, local and global efficiency of functional connectivity were increased in the sensorimotor network while decreased in the DMN with aging. These results indicate that global reorganization of brain functional networks may reflect overall topological changes with aging and that aging likely alters individual brain networks differently depending on the functional properties. Moreover, these findings highly correspond to the observation of decline in cognitive functions but maintenance of primary information processing in normal healthy aging, implying an underlying compensation mechanism evolving with aging to support higher-level cognitive functioning. PMID:25183440
Studying newt brain regeneration following subtype specific neuronal ablation.
Kirkham, Matthew; Joven, Alberto
The realization that neuronal injury does not result in permanent functional or cellular loss in all vertebrates has fascinated regenerative biologists. Neuronal regeneration occurs in a subset of species, including lizards, teleost fish, axolotls, and newts. One tool for studying neuronal regeneration in the adult brain is intraventricular injection of selective neuronal toxins, which leads to loss of subpopulations of neurons. To trace cells involved in the regeneration process, plasmids encoding reporter proteins can be electroporated in vivo into the cells of interest. This protocol describes methods to label the ependymoglial cells of the brain of the red spotted newt Notophthalmus viridescens and follow their response after ablation of dopaminergic neurons. PMID:25740479
Data-driven analysis of functional brain interactions during free listening to music and speech.
Fang, Jun; Hu, Xintao; Han, Junwei; Jiang, Xi; Zhu, Dajiang; Guo, Lei; Liu, Tianming
Natural stimulus functional magnetic resonance imaging (N-fMRI) such as fMRI acquired when participants were watching video streams or listening to audio streams has been increasingly used to investigate functional mechanisms of the human brain in recent years. One of the fundamental challenges in functional brain mapping based on N-fMRI is to model the brain's functional responses to continuous, naturalistic and dynamic natural stimuli. To address this challenge, in this paper we present a data-driven approach to exploring functional interactions in the human brain during free listening to music and speech streams. Specifically, we model the brain responses using N-fMRI by measuring the functional interactions on large-scale brain networks with intrinsically established structural correspondence, and perform music and speech classification tasks to guide the systematic identification of consistent and discriminative functional interactions when multiple subjects were listening music and speech in multiple categories. The underlying premise is that the functional interactions derived from N-fMRI data of multiple subjects should exhibit both consistency and discriminability. Our experimental results show that a variety of brain systems including attention, memory, auditory/language, emotion, and action networks are among the most relevant brain systems involved in classic music, pop music and speech differentiation. Our study provides an alternative approach to investigating the human brain's mechanism in comprehension of complex natural music and speech. PMID:24526569
Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks
Michaelides, Michael; Anderson, Sarah Ann R.; Ananth, Mala; Smirnov, Denis; Thanos, Panayotis K.; Neumaier, John F.; Wang, Gene-Jack; Volkow, Nora D.; Hurd, Yasmin L.
The ability to map the functional connectivity of discrete cell types in the intact mammalian brain during behavior is crucial for advancing our understanding of brain function in normal and disease states. We combined designer receptor exclusively activated by designer drug (DREADD) technology and behavioral imaging with ?PET and [18F]fluorodeoxyglucose (FDG) to generate whole-brain metabolic maps of cell-specific functional circuits during the awake, freely moving state. We have termed this approach DREADD-assisted metabolic mapping (DREAMM) and documented its ability in rats to map whole-brain functional anatomy. We applied this strategy to evaluating changes in the brain associated with inhibition of prodynorphin-expressing (Pdyn-expressing) and of proenkephalin-expressing (Penk-expressing) medium spiny neurons (MSNs) of the nucleus accumbens shell (NAcSh), which have been implicated in neuropsychiatric disorders. DREAMM revealed discrete behavioral manifestations and concurrent engagement of distinct corticolimbic networks associated with dysregulation of Pdyn and Penk in MSNs of the NAcSh. Furthermore, distinct neuronal networks were recruited in awake versus anesthetized conditions. These data demonstrate that DREAMM is a highly sensitive, molecular, high-resolution quantitative imaging approach. PMID:24231358
A new algorithm for spatiotemporal analysis of brain functional connectivity.
Mheich, A; Hassan, M; Khalil, M; Berrou, C; Wendling, F
Specific networks of interacting neuronal assemblies distributed within and across distinct brain regions underlie brain functions. In most cognitive tasks, these interactions are dynamic and take place at the millisecond time scale. Among neuroimaging techniques, magneto/electroencephalography - M/EEG - allows for detection of very short-duration events and offers the single opportunity to follow, in time, the dynamic properties of cognitive processes (sub-millisecond temporal resolution). In this paper, we propose a new algorithm to track the functional brain connectivity dynamics. During a picture naming task, this algorithm aims at segmenting high-resolution EEG signals (hr-EEG) into functional connectivity microstates. The proposed algorithm is based on the K-means clustering of the connectivity graphs obtained from the phase locking value (PLV) method applied on hr-EEG. Results show that the analyzed evoked responses can be divided into six clusters representing distinct networks sequentially involved during the cognitive task, from the picture presentation and recognition to the motor response. PMID:25583381
Imaging emotional brain functions: conceptual and methodological issues.
Peper, Martin
This article reviews the psychophysiological and brain imaging literature on emotional brain function from a methodological point of view. The difficulties in defining, operationalising and measuring emotional activation and, in particular, aversive learning will be considered. Emotion is a response of the organism during an episode of major significance and involves physiological activation, motivational, perceptual, evaluative and learning processes, motor expression, action tendencies and monitoring/subjective feelings. Despite the advances in assessing the physiological correlates of emotional perception and learning processes, a critical appraisal shows that functional neuroimaging approaches encounter methodological difficulties regarding measurement precision (e.g., response scaling and reproducibility) and validity (e.g., response specificity, generalisation to other paradigms, subjects or settings). Since emotional processes are not only the result of localised but also of widely distributed activation, a more representative model of assessment is needed that systematically relates the hierarchy of high- and low-level emotion constructs with the corresponding patterns of activity and functional connectivity of the brain. PMID:16740378
Category-specific brain activation in fMRI during picture naming.
Spitzer, M; Kwong, K K; Kennedy, W; Rosen, B R; Belliveau, J W
Neuropsychological, computational, and psycholinguistic data suggest the existence of semantic maps, i.e. localized representations of semantic information in the brain. Using functional magnetic resonance imaging, this hypothesis was directly tested with a picture naming task involving items from four different semantic categories. Small left lateralized fronto-temporal cortical sites of category-specific activation were found when brain activation signals were averaged. Data suggest the existence of multiple maps coding high-level representations of objects, such that meaningful distinctions, at least in part, govern the physical distribution of cortical semantic storage. PMID:8595181
Integrating in vitro organ-specific function with the microcirculation
Moya, Monica L.; George, Steven C.
There is significant interest within the tissue engineering and pharmaceutical industries to create 3D microphysiological systems of human organ function. The interest stems from a growing concern that animal models and simple 2D culture systems cannot replicate essential features of human physiology that are critical to predict drug response, or simply to develop new therapeutic strategies to repair or replace damaged organs. Central to human organ function is a microcirculation that not only enhances the rate of nutrient and waste transport by convection, but also provides essential additional physiological functions that can be specific to each organ. This review highlights progress in the creation of in vitro functional microvessel networks, and emphasizes organ-specific functional and structural characteristics that should be considered in the future mimicry of four organ systems that are of primary interest: lung, brain, liver, and muscle (skeletal and cardiac). PMID:24729953
Order and disorder in the brain function.
Quadens, Olga
The interest in studying the brain electrical activity as a function of the development of intelligence has been spurred by the need to understand how the brain responds to environmental information. The description of sleep in mentally retarded children reveals deviant patterns of the EEG-spindles and of the eye movement activity (REM sleep) when compared to normal children. The patterns may be considered as a valuable index of mental function. According to experimental evidence, the distribution of the eye movements of sleep appears either as random or ordered. The latter are altered in the mentally handicapped in whom the appearance out of chaos, of the order which is needed for intelligence and memory to function, is altered. The sleep signs are redundant as from birth. Their pattern is also related to the psychomotor development of the infant. If their distribution remains random, or appears in long uninterrupted sequences of waves as in epilepsy, intelligence does not develop. A similar strategy appears to function in the foetus when nature organizes the structures that will lead to the development of intelligence. The eye movement patterns of sleep change in the pregnant women as a function of term and resemble those of premature babies of a similar gestational age. They also change as a function of the menstrual cycle and more generally as a function of age. The hypothesis that attention is the diurnal equivalent of REM sleep is discussed. Attempts at modelling the eye movement patterns of REM sleep as a function of near zero gravity environments have been made. 1) By means of a Montecarlo simulation using the semi Markov model during the Spacelab 1 flight. 2) With the method of the single and multiple g-phase transition analysis of the strange attractor dimension (d) during parabolic flights. The implication of the latter for the neural processes involved in learning is that the central nervous system can preserve intact, from input to output, over a period of several days, all the information it receives 3) The relation between spindles and eye movements has also been viewed by a quantum approach which is another medium between the information and the way of describing it. PMID:14523349
ScaleScale--free Brain Functional Networksfree Brain Functional Networks email@example.com www.imedea.uib.es/~victor
Oro, Daniel
ScaleScale--free Brain Functional Networksfree Brain Functional Networks firstname.lastname@example.com wwwPlan Motivation: Networks & Brain How to get functional networks from fMRI Characterization of brain functional) Co-authorship of scientific papers #12;...... and the brainand the brain #12;""In catalogue" cortical
Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain
Lee, Won Hee; Sonntag, William E.; Mitschelen, Matthew; Yan, Han; Lee, Yong Woo
Purpose Pro-inflammatory environments in the brain have been implicated in the onset and progression of neurological disorders. In the present study, we investigate the hypothesis that brain irradiation induces regionally specific alterations in cytokine gene and protein expression. Materials and methods Four month old F344 × BN rats received either whole brain irradiation with a single dose of 10 Gy ?-rays or sham-irradiation, and were maintained for 4, 8, and 24 h following irradiation. The mRNA and protein expression levels of pro-inflammatory mediators were analysed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. To elucidate the molecular mechanisms of irradiation-induced brain inflammation, effects of irradiation on the DNA-binding activity of pro-inflammatory transcription factors were also examined. Results A significant and marked up-regulation of mRNA and protein expression of pro-inflammatory mediators, including tumour necrosis factor-? (TNF-?), interleukin-1? (IL-1?), and monocyte chemoattractant protein-1 (MCP-1), was observed in hippocampal and cortical regions isolated from irradiated brain. Cytokine expression was regionally specific since TNF-? levels were significantly elevated in cortex compared to hippocampus (57% greater) and IL-1? levels were elevated in hippocampus compared to cortical samples (126% greater). Increases in cytokine levels also were observed after irradiation of mouse BV-2 microglial cells. A series of electrophoretic mobility shift assays (EMSA) demonstrated that irradiation significantly increased activation of activator protein-1 (AP-1), nuclear factor-?B (NF-?B), and cAMP response element-binding protein (CREB). Conclusion The present study demonstrated that whole brain irradiation induces regionally specific pro-inflammatory environments through activation of AP-1, NF-?B, and CREB and overexpression of TNF-?, IL-1?, and MCP-1 in rat brain and may contribute to unique pathways for the radiation-induced impairments in tissue function. PMID:20148699
Maturation of Widely Distributed Brain Function Subserves Cognitive Development
Beatriz Luna; Keith R. Thulborn; Douglas P. Munoz; Elisha P. Merriam; Krista E. Garver; Nancy J. Minshew; Matcheri S. Keshavan; Christopher R. Genovese; William F. Eddy; John A. Sweeney
Cognitive and brain maturational changes continue throughout late childhood and adolescence. During this time, increasing cognitive control over behavior enhances the voluntary suppression of reflexive\\/impulsive response tendencies. Recently, with the advent of functional MRI, it has become possible to characterize changes in brain activity during cognitive development. In order to investigate the cognitive and brain maturation subserving the ability to
Chemotherapy Altered Brain Functional Connectivity in Women with Breast Cancer: A Pilot Study
Dumas, Julie A.; Makarewicz, Jenna; Schaubhut, Geoffrey J.; Devins, Robert; Albert, Kimberly; Dittus, Kim; Newhouse, Paul A.
Adjuvant chemotherapy is associated with improvements in long-term cancer survival. However, reports of cognitive impairment following treatment emphasize the importance of understanding the long-term effects of chemotherapy on brain functioning. Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning. This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer. Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to understand how brain networks support specific cognitive functions. Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging (fMRI) session before chemotherapy, one month after, and one year after the completion of chemotherapy. Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus (IPS) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex (PCC) to examine connectivity in the default mode network. Results showed decreased functional connectivity one month after chemotherapy that partially returned to baseline at one year in the dorsal attention network. Decreased connectivity was seen in the default mode network at one month and one year following chemotherapy. In addition, increased subjective memory complaints were noted at one month and one year post-chemotherapy. These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment. PMID:23852814
Mapping distributed brain function and networks with diffuse optical tomography.
Eggebrecht, Adam T; Ferradal, Silvina L; Robichaux-Viehoever, Amy; Hassanpour, Mahlega S; Dehghani, Hamid; Snyder, Abraham Z; Hershey, Tamara; Culver, Joseph P
Mapping of human brain function has revolutionized systems neuroscience. However, traditional functional neuroimaging by positron emission tomography or functional magnetic resonance imaging cannot be used when applications require portability, or are contraindicated because of ionizing radiation (positron emission tomography) or implanted metal (functional magnetic resonance imaging). Optical neuroimaging offers a non-invasive alternative that is radiation free and compatible with implanted metal and electronic devices (for example, pacemakers). However, optical imaging technology has heretofore lacked the combination of spatial resolution and wide field of view sufficient to map distributed brain functions. Here, we present a high-density diffuse optical tomography imaging array that can map higher-order, distributed brain function. The system was tested by imaging four hierarchical language tasks and multiple resting-state networks including the dorsal attention and default mode networks. Finally, we imaged brain function in patients with Parkinson's disease and implanted deep brain stimulators that preclude functional magnetic resonance imaging. PMID:25083161
Brain structural and functional development: genetics and experience.
Berardi, Nicoletta; Sale, Alessandro; Maffei, Lamberto
Brain development is the result of the combined work of genes and environment. In this paper we first briefly discuss how, in terms of cellular and molecular plasticity mechanisms, the richness of early environment can control developmental trajectories and can induce long-term changes in neural circuits that underlie enduring changes in brain structure and function. We then see that experience most effectively moulds neural circuit development during specific time windows called critical periods. After the closure of these privileged windows for plasticity, it is very difficult to promote repair from 'errors' in brain development. As an example, congenital cataracts, refractive defects, or strabismus, if not precociously corrected during development, cause permanent deficit in visual acuity of the affected eye, a condition known as amblyopia. Little or no recovery from amblyopia is possible in the adult. However, recent results show that by using protocols of enriched environment it is possible to design interventions, which, by acting on specific plasticity factors, enhance adult cortical plasticity and allow recovery from amblyopia. This suggests that a better knowledge of how experience and environment engage endogenous plasticity factors could help to design interventions aimed at promoting recovery from neurodevelopmental defects, even after the end of critical periods. PMID:25690109
Reduced brain functional reserve and altered functional connectivity in patients with multiple sclerosis.
Cader, Sarah; Cifelli, Alberto; Abu-Omar, Yasir; Palace, Jacqueline; Matthews, Paul M
Cognitive dysfunction (affecting particularly attention and working memory) occurs early in patients with multiple sclerosis. Previous studies have focused on identifying potentially adaptive functional reorganization through recruitment of new brain regions that could limit expression of these deficits. However, lesion studies remind us that functional specializations in the brain make certain brain regions necessary for a given task. We therefore have asked whether altered functional interactions between regions normally recruited provide an alternative adaptive mechanism with multiple sclerosis pathology. We used a version of the n-back task to probe working memory in patients with early multiple sclerosis. We applied a functional connectivity analysis to test whether relationships between relative activations in different brain regions change in potentially adaptive ways with multiple sclerosis. We studied 21 patients with relapsing-remitting multiple sclerosis and 16 age- and sex-matched healthy controls with 3T functional MRI. The two groups performed equally well on the task. Task-related activations were found in similar regions for patients and controls. However, patients showed relatively reduced activation in the superior frontal and anterior cingulate gyri (P > 0.01). Patients also showed a variable, but generally substantially smaller increase in activation than healthy controls with greater task complexity, depending on the specific brain region assessed (P < 0.001). Functional connectivity analysis defined further differences not apparent from the univariate contrast of the task-associated activation patterns. Control subjects showed significantly greater correlations between right dorsolateral prefrontal and superior frontal/anterior cingulate activations (P < 0.05). Patients showed correlations between activations in the right and left prefrontal cortices, although this relationship was not significant in healthy controls (P < 0.05). We interpret these results as showing that, while cognitive processing in the task appears to be performed using similar brain regions in patients and controls, the patients have reduced functional reserve for cognition relevant to memory. Functional connectivity analysis suggests that altered inter-hemispheric interactions between dorsal and lateral prefrontal regions may provide an adaptive mechanism that could limit clinical expression of the disease distinct from recruitment of novel processing regions. Together, these results suggest that therapeutic enhancement of the coherence of interactions between brain regions normally recruited (functional enhancement), as well as recruitment of alternative areas or use of complementary cognitive strategies (both forms of adaptive functional change), may limit expression of cognitive impairments in multiple sclerosis. PMID:16251214
A new procedure for detecting brain-specific proteins in cerebrospinal fluid
P. Davidsson; R. Ekman; K. Blennow
Summary We have developed a new procedure, including three affinity chromatography steps, micro-reversed phase high pressure liquid chromatography (mR-HPLC) and Western blotting\\/mass spectrometric analysis to study central nervous system (CNS) specific proteins in human cerebrospinal fluid (CSF) in order to find biochemical markers for neuronal and synaptic function and pathology in degenerative brain disorders. After the three affinity chromatography steps,
A default mode of brain function
Marcus E. Raichle; Ann Mary MacLeod; Abraham Z. Snyder; William J. Powers; Debra A. Gusnard; Gordon L. Shulman
A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain
Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling.
Brankatschk, Marko; Dunst, Sebastian; Nemetschke, Linda; Eaton, Suzanne
The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation. This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content. PMID:25275323
Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling
Brankatschk, Marko; Dunst, Sebastian; Nemetschke, Linda; Eaton, Suzanne
The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation. This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content. DOI: http://dx.doi.org/10.7554/eLife.02862.001 PMID:25275323
Imaging structural and functional brain networks in temporal lobe epilepsy
Bernhardt, Boris C.; Hong, SeokJun; Bernasconi, Andrea; Bernasconi, Neda
Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy. PMID:24098281
Ribosome Profiling Reveals a Cell-Type-Specific Translational Landscape in Brain Tumors
Gonzalez, Christian; Sims, Jennifer S.; Hornstein, Nicholas; Mela, Angeliki; Garcia, Franklin; Lei, Liang; Gass, David A.; Amendolara, Benjamin; Bruce, Jeffrey N.
Glioma growth is driven by signaling that ultimately regulates protein synthesis. Gliomas are also complex at the cellular level and involve multiple cell types, including transformed and reactive cells in the brain tumor microenvironment. The distinct functions of the various cell types likely lead to different requirements and regulatory paradigms for protein synthesis. Proneural gliomas can arise from transformation of glial progenitors that are driven to proliferate via mitogenic signaling that affects translation. To investigate translational regulation in this system, we developed a RiboTag glioma mouse model that enables cell-type-specific, genome-wide ribosome profiling of tumor tissue. Infecting glial progenitors with Cre-recombinant retrovirus simultaneously activates expression of tagged ribosomes and delivers a tumor-initiating mutation. Remarkably, we find that although genes specific to transformed cells are highly translated, their translation efficiencies are low compared with normal brain. Ribosome positioning reveals sequence-dependent regulation of ribosomal activity in 5?-leaders upstream of annotated start codons, leading to differential translation in glioma compared with normal brain. Additionally, although transformed cells express a proneural signature, untransformed tumor-associated cells, including reactive astrocytes and microglia, express a mesenchymal signature. Finally, we observe the same phenomena in human disease by combining ribosome profiling of human proneural tumor and non-neoplastic brain tissue with computational deconvolution to assess cell-type-specific translational regulation. PMID:25122893
Topographic Brain Mapping: A Window on Brain Function?
ERIC Educational Resources Information Center
Karniski, Walt M.
The article reviews the method of topographic mapping of the brain's electrical activity. Multiple electroencephalogram (EEG) electrodes and computerized analysis of the EEG signal are used to generate maps of frequency and voltage (evoked potential). This relatively new technique holds promise in the evaluation of children with behavioral and…
Structure-function relationships in human brain development
Saygin, Zeynep Mevhibe
The integration of anatomical, functional, and developmental approaches in cognitive neuroscience is essential for generating mechanistic explanations of brain function. In this thesis, I first establish a proof-of-principle ...
Anticorrelated Resting-state Functional Connectivity in Awake Rat Brain
Liang, Zhifeng; King, Jean; Zhang, Nanyin
Resting-state functional connectivity (RSFC) measured by functional magnetic resonance imaging has played an essential role in understanding neural circuitry and brain diseases. The vast majority of RSFC studies have been focused on positive RSFC, whereas our understanding about its conceptual counterpart—negative RSFC (i.e. anticorrelation)—remains elusive. To date, anticorrelated RSFC has yet been observed without the commonly used preprocessing step of global signal correction. However, this step can induce artifactual anticorrelation (Murphy et al., 2009), making it difficult to determine whether the observed anticorrelation in humans is a processing artifact (Fox et al., 2005). In this report we demonstrated robust anticorrelated RSFC in a well characterized frontolimbic circuit between the infralimbic cortex (IL) and amygdala in the awake rat. This anticorrelation was anatomically specific, highly reproducible and independent of preprocessing methods. Interestingly, this anticorrelated relationship was absent in anesthetized rats even with global signal regression, further supporting its functional significance. Establishing negative RSFC independent of data preprocessing methods will significantly enhance the applicability of RSFC in better understanding neural circuitries and brain networks. In addition, combining the neurobiological data of the IL-amygdala circuit in rodents, the finding of the present study will enable further investigation of the neurobiological basis underlying anticorrelation. PMID:21864689
Manifold learning on brain functional networks in aging.
Qiu, Anqi; Lee, Annie; Tan, Mingzhen; Chung, Moo K
We propose a new analysis framework to utilize the full information of brain functional networks for computing the mean of a set of brain functional networks and embedding brain functional networks into a low-dimensional space in which traditional regression and classification analyses can be easily employed. For this, we first represent the brain functional network by a symmetric positive matrix computed using sparse inverse covariance estimation. We then impose a Log-Euclidean Riemannian manifold structure on brain functional networks whose norm gives a convenient and practical way to define a mean. Finally, based on the fact that the computation of linear operations can be done in the tangent space of this Riemannian manifold, we adopt Locally Linear Embedding (LLE) to the Log-Euclidean Riemannian manifold space in order to embed the brain functional networks into a low-dimensional space. We show that the integration of the Log-Euclidean manifold with LLE provides more efficient and succinct representation of the functional network and facilitates regression analysis, such as ridge regression, on the brain functional network to more accurately predict age when compared to that of the Euclidean space of functional networks with LLE. Interestingly, using the Log-Euclidean analysis framework, we demonstrate the integration and segregation of cortical-subcortical networks as well as among the salience, executive, and emotional networks across lifespan. PMID:25476411
The Dynamic Dielectric at a Brain Functional Site and an EM Wave Approach to Functional Brain Imaging
Li, X. P.; Xia, Q.; Qu, D.; Wu, T. C.; Yang, D. G.; Hao, W. D.; Jiang, X.; Li, X. M.
Functional brain imaging has tremendous applications. The existing methods for functional brain imaging include functional Magnetic Resonant Imaging (fMRI), scalp electroencephalography (EEG), implanted EEG, magnetoencephalography (MEG) and Positron Emission Tomography (PET), which have been widely and successfully applied to various brain imaging studies. To develop a new method for functional brain imaging, here we show that the dielectric at a brain functional site has a dynamic nature, varying with local neuronal activation as the permittivity of the dielectric varies with the ion concentration of the extracellular fluid surrounding neurons in activation. Therefore, the neuronal activation can be sensed by a radiofrequency (RF) electromagnetic (EM) wave propagating through the site as the phase change of the EM wave varies with the permittivity. Such a dynamic nature of the dielectric at a brain functional site provides the basis for an RF EM wave approach to detecting and imaging neuronal activation at brain functional sites, leading to an RF EM wave approach to functional brain imaging. PMID:25367217
Dynamic reorganization of brain functional networks during cognition.
Bola, Micha?; Sabel, Bernhard A
How does cognition emerge from neural dynamics? The dominant hypothesis states that interactions among distributed brain regions through phase synchronization give basis for cognitive processing. Such phase-synchronized networks are transient and dynamic, established on the timescale of milliseconds in order to perform specific cognitive operations. But unlike resting-state networks, the complex organization of transient cognitive networks is typically not characterized within the graph theory framework. Thus, it is not known whether cognitive processing merely changes the strength of functional connections or, conversely, requires qualitatively new topological arrangements of functional networks. To address this question, we recorded high-density EEG while subjects performed a visual discrimination task. We conducted an event-related network analysis (ERNA) where source-space weighted functional networks were characterized with graph measures. ERNA revealed rapid, transient, and frequency-specific reorganization of the network's topology during cognition. Specifically, cognitive networks were characterized by strong clustering, low modularity, and strong interactions between hub-nodes. Our findings suggest that dense and clustered connectivity between the hub nodes belonging to different modules is the "network fingerprint" of cognition. Such reorganization patterns might facilitate global integration of information and provide a substrate for a "global workspace" necessary for cognition and consciousness to occur. Thus, characterizing topology of the event-related networks opens new vistas to interpret cognitive dynamics in the broader conceptual framework of graph theory. PMID:25828884
The blind brain: how (lack of) vision shapes the morphological and functional architecture of the human brain.
Ricciardi, Emiliano; Handjaras, Giacomo; Pietrini, Pietro
Since the early days, how we represent the world around us has been a matter of philosophical speculation. Over the last few decades, modern neuroscience, and specifically the development of methodologies for the structural and the functional exploration of the brain have made it possible to investigate old questions with an innovative approach. In this brief review, we discuss the main findings from a series of brain anatomical and functional studies conducted in sighted and congenitally blind individuals by our's and others' laboratories. Historically, research on the 'blind brain' has focused mainly on the cross-modal plastic changes that follow sensory deprivation. More recently, a novel line of research has been developed to determine to what extent visual experience is truly required to achieve a representation of the surrounding environment. Overall, the results of these studies indicate that most of the brain fine morphological and functional architecture is programmed to develop and function independently from any visual experience. Distinct cortical areas are able to process information in a supramodal fashion, that is, independently from the sensory modality that carries that information to the brain. These observations strongly support the hypothesis of a modality-independent, i.e. more abstract, cortical organization, and may contribute to explain how congenitally blind individuals may interact efficiently with an external world that they have never seen. PMID:24962172
Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128
MicroRNAs, the non-coding single-stranded RNA of 19–25 nucleotides are emerging as robust players of gene regulation. Plethora of evidences support that the ability of microRNAs to regulate several genes of a pathway or even multiple cross talking pathways have significant impact on a complex regulatory network and ultimately the physiological processes and diseases. Brain being a complex organ with several cell types, expresses more distinct miRNAs than any other tissues. This review aims to discuss about the microRNAs in brain development, function and their dysfunction in brain tumors. We also provide a comprehensive summary of targets of brain specific and brain enriched miRNAs that contribute to the diversity and plasticity of the brain. In particular, we uncover recent findings on miRNA-128, a brain-enriched microRNA that is induced during neuronal differentiation and whose aberrant expression has been reported in several cancers. This review describes the wide spectrum of targets of miRNA-128 that have been identified till date with potential roles in apoptosis, angiogenesis, proliferation, cholesterol metabolism, self renewal, invasion and cancer progression and how this knowledge might be exploited for the development of future miRNA-128 based therapies for the treatment of cancer as well as metabolic diseases. PMID:24555688
Evidence for hubs in human functional brain networks
Power, Jonathan D; Schlaggar, Bradley L; Lessov-Schlaggar, Christina N; Petersen, Steven E
Summary Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting state functional connectivity MRI reports have implicated regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: 1) finding network nodes that participate in multiple sub-networks of the brain, and 2) finding spatial locations where several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity. PMID:23972601
Decoding brain states using functional magnetic resonance imaging
Dongha Lee; Changwon Jang; Hae-Jeong Park
Most leading research in basic and clinical neuroscience has been carried out by functional magnetic resonance imaging (fMRI),\\u000a which detects the blood oxygenation level dependent signals associated with neural activities. Among new fMRI applications,\\u000a brain decoding is an emerging research area, which infers mental states from fMRI signals. Brain decoding using fMRI includes\\u000a classification, identification, and reconstruction of brain states.
Functional specializations for music processing in the human newborn brain.
Perani, Daniela; Saccuman, Maria Cristina; Scifo, Paola; Spada, Danilo; Andreolli, Guido; Rovelli, Rosanna; Baldoli, Cristina; Koelsch, Stefan
In adults, specific neural systems with right-hemispheric weighting are necessary to process pitch, melody, and harmony as well as structure and meaning emerging from musical sequences. It is not known to what extent the specialization of these systems results from long-term exposure to music or from neurobiological constraints. One way to address this question is to examine how these systems function at birth, when auditory experience is minimal. We used functional MRI to measure brain activity in 1- to 3-day-old newborns while they heard excerpts of Western tonal music and altered versions of the same excerpts. Altered versions either included changes of the tonal key or were permanently dissonant. Music evoked predominantly right-hemispheric activations in primary and higher order auditory cortex. During presentation of the altered excerpts, hemodynamic responses were significantly reduced in the right auditory cortex, and activations emerged in the left inferior frontal cortex and limbic structures. These results demonstrate that the infant brain shows a hemispheric specialization in processing music as early as the first postnatal hours. Results also indicate that the neural architecture underlying music processing in newborns is sensitive to changes in tonal key as well as to differences in consonance and dissonance. PMID:20176953
Angiogenesis, neurogenesis and brain recovery of function following injury.
Xiong, Ye; Mahmood, Asim; Chopp, Michael
Stroke and traumatic brain injury (TBI) are major causes of mortality and morbidity worldwide. Unfortunately, almost all phase III clinical trials of neuroprotective agents for stroke and TBI have demonstrated no benefit, raising concerns regarding the use of neuroprotective strategies alone as therapy for acute brain injuries. Therefore, a compelling need exists to develop treatments that promote both the repair and regeneration of injured brain tissue, and functional recovery. Recent data suggest that strategies to enhance neurogenesis and angiogenesis following brain injuries may provide promising opportunities to improve clinical outcomes and brain functional recovery. This review discusses neurogenesis and angiogenesis in the adult brain following stroke or TBI. Selected cell-based and pharmacological therapies are highlighted that promote neurogenesis and angiogenesis and are designed to restore neurological function after brain injuries. These discoveries emphasize the need for an improved understanding of injury- and therapy-induced neurogenesis and angiogenesis in the adult brain, and suggest that the manipulation of endogenous neural precursors and endothelial cells is a potential therapy for brain injury. PMID:20178043
Mapping Functional Brain Development: Building a Social Brain Through Interactive Specialization
Mark H. Johnson; Tobias Grossmann; Kathrin Cohen Kadosh
The authors review a viewpoint on human functional brain development, interactive specialization (IS), and its application to the emerging network of cortical regions referred to as the social brain. They advance the IS view in 2 new ways. First, they extend IS into a domain to which it has not previously been applied—the emergence of social cognition and mentalizing computations
Mapping Functional Brain Development: Building a Social Brain through Interactive Specialization
ERIC Educational Resources Information Center
Johnson, Mark H.; Grossmann, Tobias; Kadosh, Kathrin Cohen
The authors review a viewpoint on human functional brain development, interactive specialization (IS), and its application to the emerging network of cortical regions referred to as the "social brain." They advance the IS view in 2 new ways. First, they extend IS into a domain to which it has not previously been applied--the emergence of social…
Modeling Brain Energy Metabolism and Function: A Multiparametric Monitoring Approach
Larisa Vatova; Sigal Meilin; Tamar Manor
Mathematical modeling of brain function is an important tool needed for a better understanding of experimental results and clinical situations. In the present study, we are constructing and testing a mathematical model capable of simulating changes in brain energy metabolism that develop in real time under various pathophysiological conditions. The model incorporates the following pa- rameters: cerebral blood flow, partial
Magnetic resonance imaging mapping of brain function. Human visual cortex
J. W. Belliveau; K. K. Kwong; D. N. Kennedy; J. R. Baker; C. E. Stern; R. Benson; D. A. Chesler; R. M. Weisskoff; M. S. Cohen; R. B. Tootell; P. T. Fox; T. J. Brady
Magnetic resonance imaging (MRI) studies of human brain activity are described. Task-induced changes in brain cognitive state were measured using high-speed MRI techniques sensitive to changes in cerebral blood volume (CBV), blood flow (CBF), and blood oxygenation. These techniques were used to generate the first functional MRI maps of human task activation, by using a visual stimulus paradigm. The methodology
Anomalous brain functional connectivity contributing to poor adaptive behavior in Down syndrome.
Pujol, Jesus; del Hoyo, Laura; Blanco-Hinojo, Laura; de Sola, Susana; Maciŕ, Dídac; Martínez-Vilavella, Gerard; Amor, Marta; Deus, Joan; Rodríguez, Joan; Farré, Magí; Dierssen, Mara; de la Torre, Rafael
Research in Down syndrome has substantially progressed in the understanding of the effect of gene overexpression at the molecular level, but there is a paucity of information on the ultimate consequences on overall brain functional organization. We have assessed the brain functional status in Down syndrome using functional connectivity MRI. Resting-state whole-brain connectivity degree maps were generated in 20 Down syndrome individuals and 20 control subjects to identify sites showing anomalous synchrony with other areas. A subsequent region-of-interest mapping served to detail the anomalies and to assess their potential contribution to poor adaptive behavior. Down syndrome individuals showed higher regional connectivity in a ventral brain system involving the amygdala/anterior temporal region and the ventral aspect of both the anterior cingulate and frontal cortices. By contrast, lower functional connectivity was identified in dorsal executive networks involving dorsal prefrontal and anterior cingulate cortices and posterior insula. Both functional connectivity increases and decreases contributed to account for patient scoring on adaptive behavior related to communication skills. The data overall suggest a distinctive functional organization with system-specific anomalies associated with reduced adaptive efficiency. Opposite effects were identified on distinct frontal and anterior temporal structures and relative sparing of posterior brain areas, which is generally consistent with Down syndrome cognitive profile. Relevantly, measurable connectivity changes, as a marker of the brain functional anomaly, could have a role in the development of therapeutic strategies addressed to improve the quality of life in Down syndrome individuals. PMID:25461715
Intersubject Variability of and Genetic Effects on the Brain's Functional Connectivity during Infancy
Elton, Amanda; Zhu, Hongtu; Alcauter, Sarael; Smith, J. Keith; Gilmore, John H.; Lin, Weili
Infancy is a period featuring a high level of intersubject variability but the brain basis for such variability and the potential genetic/environmental contributions remain largely unexplored. The assessment of the brain's functional connectivity during infancy by the resting state functional magnetic resonance imaging (rsfMRI) technique (Biswal et al., 1995) provides a unique means to probe the brain basis of intersubject variability during infancy. In this study, an unusually large typically developing human infant sample including 58 singletons, 132 dizygotic twins, and 98 monozygotic twins with rsfMRI scans during the first 2 years of life was recruited to delineate the spatial and temporal developmental patterns of both the intersubject variability of and genetic effects on the brain's functional connectivity. Through systematic voxelwise functional connectivity analyses, our results revealed that the intersubject variability at birth features lower variability in primary functional areas but higher values in association areas. Although the relative pattern remains largely consistent, the magnitude of intersubject variability undergoes an interesting U-shaped growth during the first 2 years of life. Overall, the intersubject variability patterns during infancy show both adult-like and infant-specific characteristics (Mueller et al., 2013). On the other hand, age-dependent genetic effects were observed showing significant but bidirectional relationships with intersubject variability. The temporal and spatial patterns of the intersubject variability of and genetic contributions to the brain's functional connectivity documented in this study shed light on the largely uncharted functional development of the brain during infancy. PMID:25143609
Brain functional connectivity and the pathophysiology of schizophrenia.
Angelopoulos, E
In the last decade there is extensive evidence to suggest that cognitive functions depending on coordination of distributed neuronal responses are associated with synchronized oscillatory activity in various frequency ranges suggesting a functional mechanism of neural oscillations in cortical networks. In addition to their role in normal brain functioning, there is increasing evidence that altered oscillatory activity may be associated with certain neuropsychiatric disorders, such as schizophrenia. Consequently, disturbances in neural synchronization may represent the functional relationship of disordered connectivity of cortical networks underlying the characteristic fragmentation of mind and behavior in schizophrenia. In recent studies the synchronization of oscillatory activity in the experience of characteristic symptoms such as auditory verbal hallucinations and thought blocks have been studied in patients with schizophrenia. Studies involving analysis of EEG activity obtained from individuals in resting state (in cage Faraday, isolated from external influences and with eyes closed). In patients with schizophrenia and persistent auditory verbal hallucinations (AVHs) observed a temporary increase in the synchronization phase of ? and high ? oscillations of the electroencephalogram (EEG) compared with those of healthy controls and patients without AVHs . This functional hyper-connection manifested in time windows corresponding to experience AVHs, as noted by the patients during the recording of EEG and observed in speech related cortical areas. In another study an interaction of theta and gamma oscillations engages in the production and experience of AVHs. The results showed increased phase coupling between theta and gamma EEG rhythms in the left temporal cortex during AVHs experiences. A more recent study, approaches the thought blocking experience in terms of functional brain connectivity. Thought blocks (TBs) are characterized by regular interruptions of the flow of thought. Outward signs are abrupt and repeated interruptions in the flow of conversation or actions while subjective experience is that of a total and uncontrollable emptying of the mind. In the very limited bibliography regarding TB, the phenomenon is thought to be conceptualized as a disturbance of consciousness that can be attributed to stoppages of continuous information processing due to an increase in the volume of information to be processed. In an attempt to investigate potential expression of the phenomenon on the functional properties of electroencephalographic (EEG) activity, an EEG study was contacted in schizophrenic patients with persisting auditory verbal hallucinations (AVHs) who additionally exhibited TBs. Phase synchronization analyses performed on EEG segments during the experience of TBs showed that synchrony values exhibited a long-range common mode of coupling (grouped behavior) among the left temporal area and the remaining central and frontal brain areas. These common synchrony-fluctuation schemes were observed for 0.5 to 2 s and were detected in a 4-s window following the estimated initiation of the phenomenon. The observation was frequency specific and detected in the broad alpha band region (6-12 Hz). The introduction of synchrony entropy (SE) analysis applied on the cumulative synchrony distribution showed that TB states were characterized by an explicit preference of the system to be functioned at low values of synchrony, while the synchrony values are broadly distributed during the recovery state. The results indicate that during TB states, the phase locking of several brain areas were converged uniformly in a narrow band of low synchrony values and in a distinct time window, impeding thus the ability of the system to recruit and to process information during this time window. The results of this study seem to have greater importance on neuronal correlation of consciousness. The brain is a highly distributed system in which numerous operations are executed in parallel and that lacks a single coordinating center. This rais
Functional brain imaging of trigeminal neuralgia.
Moisset, Xavier; Villain, Nicolas; Ducreux, Denis; Serrie, Alain; Cunin, Gérard; Valade, Dominique; Calvino, Bernard; Bouhassira, Didier
We used functional magnetic resonance imaging (fMRI) to analyze changes in brain activity associated with stimulation of the cutaneous trigger zone in patients with classic trigeminal neuralgia (CTN). Fifteen consecutive patients with CTN in the second or third division of the nerve, were included in this study. The fMRI paradigm consisted of light tactile stimuli of the trigger zone and the homologous contralateral area. Stimulation of the affected side induced pain in seven patients, but was not painful in eight patients on the day of the experiment. Painful stimuli were associated with significantly increased activity in the spinal trigeminal nucleus (SpV), thalamus, primary and secondary somatosensory cortices (S1, S2), anterior cingulate cortex (ACC), insula, premotor/motor cortex, prefrontal areas, putamen, hippocampus and brainstem. Nonpainful stimulation of the trigger zone activated all but three of these structures (SpV, brainstem and ACC). After a successful surgical treatment, activation induced by stimulation of the operated side was confined to S1 and S2. Our data demonstrate the pathological hyperexcitability of the trigeminal nociceptive system, including the second order trigeminal sensory neurons during evoked attacks of CTN. Such sensitization may depend on pain modulatory systems involving both the brainstem (i.e. periaqueductal gray and adjacent structures) and interconnected cortical structures (i.e. ACC). The fact that large portions of the classical 'pain neuromatrix' were also activated during nonpainful stimulation of the trigger zone, could reflect a state of maintained sensitization of the trigeminal nociceptive systems in CTN. PMID:20609605
Complex Networks - A Key to Understanding Brain Function
Olaf Sporns
The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life. How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood. In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.
Complex Networks - A Key to Understanding Brain Function
Olaf Sporns
The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life. How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood. In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.
Leahy, Richard M.
SEGMENTATION OF PATIENT SPECIFIC MEG/EEG SKULL, SCALP, AND BRAIN MODELS FROM MRI Belma Dogdas California, LA, CA 90089-2564 ABSTRACT We present an automated method for segmenting skull, scalp, and brain and morphology to produce a scalp mask. The brain and scalp masks provide boundaries between which the skull must
Automatic Brain Tumor Segmentation by Subject Specific Modification of Atlas Priors1
Prastawa, Marcel
Automatic Brain Tumor Segmentation by Subject Specific Modification of Atlas Priors1 Marcel and Objectives. Manual segmentation of brain tumors from magnetic resonance images is a challenging and time-consuming task. An automated system has been developed for brain tumor segmentation that will provide objective
Brain Responses to Acupuncture Are Probably Dependent on the Brain Functional Status
Sun, Jinbo; Xu, Chunsheng; Zhu, Yuanqiang; Qin, Wei; Tian, Jie
In recent years, neuroimaging studies of acupuncture have explored extensive aspects of brain responses to acupuncture in finding its underlying mechanisms. Most of these studies have been performed on healthy adults. Only a few studies have been performed on patients with diseases. Brain responses to acupuncture in patients with the same disease at different pathological stages have not been explored, although it may be more important and helpful in uncovering its underlying mechanisms. In the present study, we used fMRI to compare brain responses to acupuncture in patients with Bell's palsy at different pathological stages with normal controls and found that the brain response to acupuncture varied at different pathological stages of Bell's palsy. The brain response to acupuncture decreased in the early stages, increased in the later stages, and nearly returned to normal in the recovered group. All of the changes in the brain response to acupuncture could be explained as resulting from the changes in the brain functional status. Therefore, we proposed that the brain response to acupuncture is dependent on the brain functional status, while further investigation is needed to provide more evidence in support of this proposition. PMID:23737817
Fish Oil Tied to Better Brain Function in Older Adults
... nlm.nih.gov/medlineplus/news/fullstory_152697.html Fish Oil Tied to Better Brain Function in Older ... 3 fatty acids -- found in many types of fish -- may benefit people at risk for Alzheimer's disease, ...
Functional geometry alignment and localization of brain areas
Langs, Georg
Matching functional brain regions across individuals is a challenging task, largely due to the variability in their location and extent. It is particularly difficult, but highly relevant, for patients with pathologies such ...
Functional imaging of the brain with/sup 18/F-fluorodeoxyglucose
Reivich, M; Greenberg, J; Alavi, A; Hand, P; Rintelmann, W; Rosenquist, A; Christman, D; Fowler, J; MacGregor, R; Wolf, A
A techniques is reported by which it is possible to determine which regions of the human brain become functionally active in response to a specific stimulus. The method utilizes /sup 18/F-2-fluoro-2-deoxyglucose ((/sup 18/F)-FDG) administered as a bolus. (/sup 18/F)-FDG is used as a tracer for the exchange of glucose between plasma and brain and its phosphorylation. The subject is then scanned during administration of a physiologic stimulus by position emission tomography and the three-dimensional distribution of /sup 18/F activity in the brain determined. (ACR)
Brain-specific rescue of Clock reveals system-driven transcriptional rhythms in peripheral tissue.
Hughes, Michael E; Hong, Hee-Kyung; Chong, Jason L; Indacochea, Alejandra A; Lee, Samuel S; Han, Michael; Takahashi, Joseph S; Hogenesch, John B
The circadian regulatory network is organized in a hierarchical fashion, with a central oscillator in the suprachiasmatic nuclei (SCN) orchestrating circadian oscillations in peripheral tissues. The nature of the relationship between central and peripheral oscillators, however, is poorly understood. We used the tetOFF expression system to specifically restore Clock function in the brains of Clock(?19) mice, which have compromised circadian clocks. Rescued mice showed normal locomotor rhythms in constant darkness, with activity period lengths approximating wildtype controls. We used microarray analysis to assess whether brain-specific rescue of circadian rhythmicity was sufficient to restore circadian transcriptional output in the liver. Compared to Clock mutants, Clock-rescue mice showed significantly larger numbers of cycling transcripts with appropriate phase and period lengths, including many components of the core circadian oscillator. This indicates that the SCN oscillator overcomes local circadian defects and signals directly to the molecular clock. Interestingly, the vast majority of core clock genes in liver were responsive to Clock expression in the SCN, suggesting that core clock genes in peripheral tissues are intrinsically sensitive to SCN cues. Nevertheless, most circadian output in the liver was absent or severely low-amplitude in Clock-rescue animals, demonstrating that the majority of peripheral transcriptional rhythms depend on a fully functional local circadian oscillator. We identified several new system-driven rhythmic genes in the liver, including Alas1 and Mfsd2. Finally, we show that 12-hour transcriptional rhythms (i.e., circadian "harmonics") are disrupted by Clock loss-of-function. Brain-specific rescue of Clock converted 12-hour rhythms into 24-hour rhythms, suggesting that signaling via the central circadian oscillator is required to generate one of the two daily peaks of expression. Based on these data, we conclude that 12-hour rhythms are driven by interactions between central and peripheral circadian oscillators. PMID:22844252
Selectionist and Evolutionary Approaches to Brain Function: A Critical Appraisal
Fernando, Chrisantha; Szathmáry, Eörs; Husbands, Phil
We consider approaches to brain dynamics and function that have been claimed to be Darwinian. These include Edelman's theory of neuronal group selection, Changeux's theory of synaptic selection and selective stabilization of pre-representations, Seung's Darwinian synapse, Loewenstein's synaptic melioration, Adam's selfish synapse, and Calvin's replicating activity patterns. Except for the last two, the proposed mechanisms are selectionist but not truly Darwinian, because no replicators with information transfer to copies and hereditary variation can be identified in them. All of them fit, however, a generalized selectionist framework conforming to the picture of Price's covariance formulation, which deliberately was not specific even to selection in biology, and therefore does not imply an algorithmic picture of biological evolution. Bayesian models and reinforcement learning are formally in agreement with selection dynamics. A classification of search algorithms is shown to include Darwinian replicators (evolutionary units with multiplication, heredity, and variability) as the most powerful mechanism for search in a sparsely occupied search space. Examples are given of cases where parallel competitive search with information transfer among the units is more efficient than search without information transfer between units. Finally, we review our recent attempts to construct and analyze simple models of true Darwinian evolutionary units in the brain in terms of connectivity and activity copying of neuronal groups. Although none of the proposed neuronal replicators include miraculous mechanisms, their identification remains a challenge but also a great promise. PMID:22557963
Changes in functional brain organization and behavioral correlations after rehabilitative therapy using a brain-computer interface
Young, Brittany M.; Nigogosyan, Zack; Walton, Léo M.; Song, Jie; Nair, Veena A.; Grogan, Scott W.; Tyler, Mitchell E.; Edwards, Dorothy F.; Caldera, Kristin; Sattin, Justin A.; Williams, Justin C.; Prabhakaran, Vivek
This study aims to examine the changes in task-related brain activity induced by rehabilitative therapy using brain-computer interface (BCI) technologies and whether these changes are relevant to functional gains achieved through the use of these therapies. Stroke patients with persistent upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device (n = 8) or no therapy (n = 6). Behavioral assessments using the Stroke Impact Scale, the Action Research Arm Test (ARAT), and the Nine-Hole Peg Test (9-HPT) as well as task-based fMRI scans were conducted before, during, after, and 1 month after therapy administration or at analogous intervals in the absence of therapy. Laterality Index (LI) values during finger tapping of each hand were calculated for each time point and assessed for correlation with behavioral outcomes. Brain activity during finger tapping of each hand shifted over the course of BCI therapy, but not in the absence of therapy, to greater involvement of the non-lesioned hemisphere (and lesser involvement of the stroke-lesioned hemisphere) as measured by LI. Moreover, changes from baseline LI values during finger tapping of the impaired hand were correlated with gains in both objective and subjective behavioral measures. These findings suggest that the administration of interventional BCI therapy can induce differential changes in brain activity patterns between the lesioned and non-lesioned hemispheres and that these brain changes are associated with changes in specific motor functions. PMID:25076886
Changes in functional brain organization and behavioral correlations after rehabilitative therapy using a brain-computer interface.
Young, Brittany M; Nigogosyan, Zack; Walton, Léo M; Song, Jie; Nair, Veena A; Grogan, Scott W; Tyler, Mitchell E; Edwards, Dorothy F; Caldera, Kristin; Sattin, Justin A; Williams, Justin C; Prabhakaran, Vivek
This study aims to examine the changes in task-related brain activity induced by rehabilitative therapy using brain-computer interface (BCI) technologies and whether these changes are relevant to functional gains achieved through the use of these therapies. Stroke patients with persistent upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device (n = 8) or no therapy (n = 6). Behavioral assessments using the Stroke Impact Scale, the Action Research Arm Test (ARAT), and the Nine-Hole Peg Test (9-HPT) as well as task-based fMRI scans were conducted before, during, after, and 1 month after therapy administration or at analogous intervals in the absence of therapy. Laterality Index (LI) values during finger tapping of each hand were calculated for each time point and assessed for correlation with behavioral outcomes. Brain activity during finger tapping of each hand shifted over the course of BCI therapy, but not in the absence of therapy, to greater involvement of the non-lesioned hemisphere (and lesser involvement of the stroke-lesioned hemisphere) as measured by LI. Moreover, changes from baseline LI values during finger tapping of the impaired hand were correlated with gains in both objective and subjective behavioral measures. These findings suggest that the administration of interventional BCI therapy can induce differential changes in brain activity patterns between the lesioned and non-lesioned hemispheres and that these brain changes are associated with changes in specific motor functions. PMID:25076886
PATH57 Altered structural and functional network connectivity predicts cognitive function after traumatic brain injury
D Sharp; Powell J Leech R; V Bonnelle; C F Beckmann; X De Boissezon; R Greenwood; K Kinnunen
Traumatic brain injury (TBI) often results in cognitive impairments that limit recovery. The key pathophysiological predictors of recovery are uncertain, but the disruption of brain networks by diffuse axonal injury (DAI) is likely to be important. Here we use MRI to investigate the effect of TBI on structural and functional connections within cognitive brain networks. We studied 21 patients after
Micro-compartment specific T2? relaxation in the brain
Sati, Pascal; van Gelderen, Peter; Silva, Afonso C.; Reich, Daniel S.; Merkle, Hellmut; de Zwart, Jacco A.; Duyn, Jeff H.
MRI at high field can be sensitized to the magnetic properties of tissues, which introduces a signal dependence on the orientation of white matter (WM) fiber bundles relative to the magnetic field. In addition, study of the NMR relaxation properties of this signal has indicated contributions from compartmentalized water environments inside and outside the myelin sheath that may be separable. Here we further investigated the effects of water compartmentalization on the MRI signal with the goal of extracting compartment-specific information. By comparing MRI measurements of human and marmoset brain at 7 T with magnetic field modeling, we show that: (1) water between the myelin lipid bilayers, in the axonal, and in the interstitial space each experience characteristic magnetic field effects that depend on fiber orientation (2) these field effects result in characteristic relaxation properties and frequency shifts for these compartments; and (3) compartmental contributions may be separated by multi-component fitting of the MRI signal relaxation (i.e. decay) curve. We further show the potential application of these findings to the direct mapping of myelin content and assessment of WM fiber integrity with high field MRI. PMID:23528924
Studying brain function with concurrent near-infrared spectroscopy (NIRS) and functional magnetic resonance
Fantini, Sergio
Studying brain function with concurrent near-infrared spectroscopy (NIRS) and functional magnetic collected with a frequency domain experimental apparatus (ISS, Inc., Champaign IL) comprising sixteen laser brain monitor for functional studies. Keywords: Near-infrared spectroscopy, frequency-domain, f
Altered host behaviour and brain serotonergic activity caused by acanthocephalans: evidence for specificity
Tain, Luke; Perrot-Minnot, Marie-Jeanne; Cézilly, Frank
Manipulative parasites can alter the phenotype of intermediate hosts in various ways. However, it is unclear whether such changes are just by-products of infection or adaptive and enhance transmission to the final host. Here, we show that the alteration of serotonergic activity is functionally linked to the alteration of specific behaviour in the amphipod Gammarus pulex infected with acanthocephalan parasites. Pomphorhynchus laevis and, to a lesser extent, Pomphorhynchus tereticollis altered phototactism, but not geotactism, in G. pulex, whereas the reverse was true for Polymorphus minutus. Serotonin (5-hydroxytryptamine, 5-HT) injected to uninfected G. pulex mimicked the altered phototactism, but had no effect on geotactism. Photophilic G. pulex infected with P. laevis or P. tereticollis showed a 40% increase in brain 5-HT immunoreactivity compared to photophobic, uninfected individuals. In contrast, brain 5-HT immunoreactivity did not differ between P. minutus-infected and uninfected G. pulex. Finally, brain 5-HT immunoreactivity differed significantly among P. tereticollis-infected individuals in accordance with their degree of manipulation. Our results demonstrate that altered 5-HT activity is not the mere consequence of infection by acanthocephalans but is specifically linked to the disruption of host photophobic behaviour, whereas the alteration of other behaviours such as geotactism may rely on distinct physiological routes. PMID:17015346
Integrated technology for evaluation of brain function and neural plasticity.
Rossini, Paolo M; Dal Forno, Gloria
The study of neural plasticity has expanded rapidly in the past decades and has shown the remarkable ability of the developing, adult, and aging brain to be shaped by environmental inputs in health and after a lesion. Robust experimental evidence supports the hypothesis that neuronal aggregates adjacent to a lesion in the sensorimotor brain areas can take over progressively the function previously played by the damaged neurons. It definitely is accepted that such a reorganization modifies sensibly the interhemispheric differences in somatotopic organization of the sensorimotor cortices. This reorganization largely subtends clinical recovery of motor performances and sensorimotor integration after a stroke. Brain functional imaging studies show that recovery from hemiplegic strokes is associated with a marked reorganization of the activation patterns of specific brain structures. To regain hand motor control, the recovery process tends over time to bring the bilateral motor network activation toward a more normal intensity/extent, while overrecruiting simultaneously new areas, perhaps to sustain this process. Considerable intersubject variability exists in activation/hyperactivation pattern changes over time. Some patients display late-appearing dorsolateral prefrontal cortex activation, suggesting the development of "executive" strategies to compensate for the lost function. The AH in stroke often undergoes a significant "remodeling" of sensory and motor hand somatotopy outside the "normal" areas, or enlargement of the hand representation. The UH also undergoes reorganization, although to a lesser degree. Although absolute values of the investigated parameters fluctuate across subjects, secondary to individual anatomic variability, variation is minimal with regards to interhemispheric differences, due to the fact that individual morphometric characters are mirrored in the two hemispheres. Excessive interhemispheric asymmetry of the sensorimotor hand areas seems to be the parameter with highest sensitivity in describing brain reorganization after a monohemispheric lesion, and mapping motor and somatosensory cortical areas through focal TMS, fMRI, PET, EEG, and MEG is useful in studying hand representation and interhemispheric asymmetries in normal and pathologic conditions. TMS and MEG allow the detection of sensorimotor areas reshaping, as a result of either neuronal reorganization or recovery of the previously damaged neural network. These techniques have the advantage of high temporal resolution but also have limitations. TMS provides only bidimensional scalp maps, whereas MEG, even if giving three-dimensional mapping of generator sources, does so by means of inverse procedures that rely on the choice of a mathematical model of the head and the sources. These techniques do not test movement execution and sensorimotor integration as used in everyday life. fMRI and PET may provide the ideal means to integrate the findings obtained with the other two techniques. This multitechnology combined approach is at present the best way to test the presence and amount of plasticity phenomena underlying partial or total recovery of several functions, sensorimotor above all. Dynamic patterns of recovery are emerging progressively from the relevant literature. Enhanced recruitment of the affected cortex, be it spared perilesional tissue, as in the case of cortical stroke, or intact but deafferented cortex, as in subcortical strokes, seems to be the rule, a mechanism especially important in early postinsult stages. The transfer over time of preferential activation toward contralesional cortices, as observed in some cases, seems, however, to reflect a less efficient type of plastic reorganization, with some aspects of maladaptive plasticity. Reinforcing the use of the affected side can cause activation to increase again in the affected side with a corresponding enhancement of clinical function. Activation of the UH MI may represent recruitment of direct (uncrossed) corticospinal tracts and relate more to mi
Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging
Bell, Robert D.; Winkler, Ethan A.; Sagare, Abhay P.; Singh, Itender; LaRue, Barb; Deane, Rashid; Zlokovic, Berislav V.
SUMMARY Pericytes play a key role in the development of cerebral microcirculation. The exact role of pericytes in the neurovascular unit in the adult brain and during brain aging remains, however, elusive. Using adult viable pericyte-deficient mice, we show that pericyte loss leads to brain vascular damage by two parallel pathways: (1) reduction in brain microcirculation causing diminished brain capillary perfusion, cerebral blood flow and cerebral blood flow responses to brain activation which ultimately mediates chronic perfusion stress and hypoxia, and (2) blood-brain barrier breakdown associated with brain accumulation of serum proteins and several vasculotoxic and/or neurotoxic macromolecules ultimately leading to secondary neuronal degenerative changes. We show that age-dependent vascular damage in pericyte-deficient mice precedes neuronal degenerative changes, learning and memory impairment and the neuroinflammatory response. Thus, pericytes control key neurovascular functions that are necessary for proper neuronal structure and function, and pericytes loss results in a progressive age-dependent vascular-mediated neurodegeneration. PMID:21040844
Connectivity and functional profiling of abnormal brain structures in pedophilia.
Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo
Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. Hum Brain Mapp 36:2374-2386, 2015. © 2015 Wiley Periodicals, Inc. PMID:25733379
Brain covariance selection: better individual functional connectivity models using population prior
Paris-Sud XI, Université de
Brain covariance selection: better individual functional connectivity models using population prior firstname.lastname@example.com Abstract Spontaneous brain activity, as observed in functional neuroimaging, has been shown to display reproducible structure that expresses brain architecture and car- ries markers
Frontal brain asymmetry and immune function
Duck-hee Kang; Richard J. Davidson; Christopher L. Coe; Robert E. Wheeler
The relation between brain activity and the immune system was evaluated by assessing immune responses in 20 healthy women who manifested extreme differences in the asymmetry of frontal cortex activation. One group showed extreme and stable left frontal activation; the other group showed extreme and stable right frontal activation. As predicted, women with extreme right frontal activation had significantly lower
Disease and anatomic specificity of ethanolamine plasmalogen deficiency in Alzheimer's disease brain
Lionel Ginsberg; Samina Rafique; John H. Xuereb; Stanley I. Rapoport; Norman L. Gershfeld
A significant and selective deficiency of ethanolamine plasmalogen (PPE) relative to phosphatidylethanolamine was identified in post mortem brain samples from patients with Alzheimer's disease (AD). This lipid defect showed anatomic specificity, being more marked at a site of neurodegeneration in AD brain than in a region relatively spared by the disease (mid-temporal cortex vs. cerebellum) and disease specificity for AD:
Functional brain connectivity phenotypes for schizophrenia drug discovery.
Dawson, Neil; Morris, Brian J; Pratt, Judith A
While our knowledge of the pathophysiology of schizophrenia has increased dramatically, this has not translated into the development of new and improved drugs to treat this disorder. Human brain imaging and electrophysiological studies have provided dramatic new insight into the mechanisms of brain dysfunction in the disease, with a swathe of recent studies highlighting the differences in functional brain network and neural system connectivity present in the disorder. Only recently has the value of applying these approaches in preclinical rodent models relevant to the disorder started to be recognised. Here we highlight recent findings of altered functional brain connectivity in preclinical rodent models and consider their relevance to those alterations seen in the brains of schizophrenia patients. Furthermore, we highlight the potential translational value of using the paradigm of functional brain connectivity phenotypes in the context of preclinical schizophrenia drug discovery, as a means both to understand the mechanisms of brain dysfunction in the disorder and to reduce the current high attrition rate in schizophrenia drug discovery. PMID:25567554
Functional brain connectivity using fMRI in aging and Alzheimer's disease.
Dennis, Emily L; Thompson, Paul M
Normal aging and Alzheimer's disease (AD) cause profound changes in the brain's structure and function. AD in particular is accompanied by widespread cortical neuronal loss, and loss of connections between brain systems. This degeneration of neural pathways disrupts the functional coherence of brain activation. Recent innovations in brain imaging have detected characteristic disruptions in functional networks. Here we review studies examining changes in functional connectivity, measured through fMRI (functional magnetic resonance imaging), starting with healthy aging and then Alzheimer's disease. We cover studies that employ the three primary methods to analyze functional connectivity--seed-based, ICA (independent components analysis), and graph theory. At the end we include a brief discussion of other methodologies, such as EEG (electroencephalography), MEG (magnetoencephalography), and PET (positron emission tomography). We also describe multi-modal studies that combine rsfMRI (resting state fMRI) with PET imaging, as well as studies examining the effects of medications. Overall, connectivity and network integrity appear to decrease in healthy aging, but this decrease is accelerated in AD, with specific systems hit hardest, such as the default mode network (DMN). Functional connectivity is a relatively new topic of research, but it holds great promise in revealing how brain network dynamics change across the lifespan and in disease. PMID:24562737
Connectomics and new approaches for analyzing human brain functional connectivity.
Craddock, R Cameron; Tungaraza, Rosalia L; Milham, Michael P
Estimating the functional interactions between brain regions and mapping those connections to corresponding inter-individual differences in cognitive, behavioral and psychiatric domains are central pursuits for understanding the human connectome. The number and complexity of functional interactions within the connectome and the large amounts of data required to study them position functional connectivity research as a "big data" problem. Maximizing the degree to which knowledge about human brain function can be extracted from the connectome will require developing a new generation of neuroimaging analysis algorithms and tools. This review describes several outstanding problems in brain functional connectomics with the goal of engaging researchers from a broad spectrum of data sciences to help solve these problems. Additionally it provides information about open science resources consisting of raw and preprocessed data to help interested researchers get started. PMID:25810900
Functional Specialization in the Human Brain Estimated By Intrinsic Hemispheric Interaction
Wang, Danhong; Buckner, Randy L.
The human brain demonstrates functional specialization, including strong hemispheric asymmetries. Here specialization was explored using fMRI by examining the degree to which brain networks preferentially interact with ipsilateral as opposed to contralateral networks. Preferential within-hemisphere interaction was prominent in the heteromodal association cortices and minimal in the sensorimotor cortices. The frontoparietal control network exhibited strong within-hemisphere interactions but with distinct patterns in each hemisphere. The frontoparietal control network preferentially coupled to the default network and language-related regions in the left hemisphere but to attention networks in the right hemisphere. This arrangement may facilitate control of processing functions that are lateralized. Moreover, the regions most linked to asymmetric specialization also display the highest degree of evolutionary cortical expansion. Functional specialization that emphasizes processing within a hemisphere may allow the expanded hominin brain to minimize between-hemisphere connectivity and distribute domain-specific processing functions. PMID:25209275
Neuronal Migration Depends on Intact Peroxisomal Function in Brain and in Extraneuronal Tissues
Anneleen Janssen; Pierre Gressens; Markus Grabenbauer; Eveline Baumgart; Arno Schad; Ilse Vanhorebeek; Annelies Brouwers; Peter E. Declercq; Dariush Fahimi; Philippe Evrard; Luc Schoonjans; Peter Carmeliet; Guy Mannaerts; Paul Van Veldhoven; Myriam Baes
Functional peroxisome deficiency, as encountered in Zellweger syndrome, causes a specific impairment of neuronal migration. Although the molecular mechanisms underlying the neuronal migration defect are at present unknown, the excess of very long chain fatty acids in brain, a consequence of peroxisomal-oxidation deficiency, has often been hypothesized to play a major role. The purpose of the present study was to
Human brain functional MRI and DTI visualization with virtual reality
Chen, Bin; Moreland, John; Zhang, Jingyu
Magnetic resonance diffusion tensor imaging (DTI) and functional MRI (fMRI) are two active research areas in neuroimaging. DTI is sensitive to the anisotropic diffusion of water exerted by its macromolecular environment and has been shown useful in characterizing structures of ordered tissues such as the brain white matter, myocardium, and cartilage. The diffusion tensor provides two new types of information of water diffusion: the magnitude and the spatial orientation of water diffusivity inside the tissue. This information has been used for white matter fiber tracking to review physical neuronal pathways inside the brain. Functional MRI measures brain activations using the hemodynamic response. The statistically derived activation map corresponds to human brain functional activities caused by neuronal activities. The combination of these two methods provides a new way to understand human brain from the anatomical neuronal fiber connectivity to functional activities between different brain regions. In this study, virtual reality (VR) based MR DTI and fMRI visualization with high resolution anatomical image segmentation and registration, ROI definition and neuronal white matter fiber tractography visualization and fMRI activation map integration is proposed. Rationale and methods for producing and distributing stereoscopic videos are also discussed. PMID:23256049
A pilot study of functional magnetic resonance imaging brain correlates of deception in healthy young men.
Kozel, F Andrew; Revell, Letty J; Lorberbaum, Jeffrey P; Shastri, Ananda; Elhai, Jon D; Horner, Michael David; Smith, Adam; Nahas, Ziad; Bohning, Daryl E; George, Mark S
We hypothesized that specific brain regions would activate during deception, and these areas would correlate with changes in electrodermal activity (EDA). Eight men were asked to find money hidden under various objects. While functional MRI images were acquired and EDA was recorded, the subjects gave both truthful and deceptive answers regarding the money's location. The group analysis revealed significant activation during deception in the orbitofrontal cortex (OFCx) and anterior cingulate (AC), but individual results were not consistent. Individually and as a group, EDA correlated with blood flow changes in the OFCx and AC. Specific brain regions were activated during deception, but the present technique lacks good predictive power for individuals. PMID:15377736
Allelic Specificity of Ube3a Expression in the Mouse Brain during Postnatal Development
Genetic alterations of the maternal UBE3A allele result in Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, lack of speech, and difficulty with movement and balance. The combined effects of maternal UBE3A mutation and cell type-specific epigenetic silencing of paternal UBE3A are hypothesized to result in a complete loss of functional UBE3A protein in neurons. However, the allelic specificity of UBE3A expression in neurons and other cell types in the brain has yet to be characterized throughout development, including the early postnatal period when AS phenotypes emerge. Here we define maternal and paternal allele-specific Ube3a protein expression throughout postnatal brain development in the mouse, a species which exhibits orthologous epigenetic silencing of paternal Ube3a in neurons and AS-like behavioral phenotypes subsequent to maternal Ube3a deletion. We find that neurons downregulate paternal Ube3a protein expression as they mature and, with the exception of neurons born from postnatal stem cell niches, do not express detectable paternal Ube3a beyond the first postnatal week. By contrast, neurons express maternal Ube3a throughout postnatal development, during which time localization of the protein becomes increasingly nuclear. Unlike neurons, astrocytes and oligodendrotyes biallelically express Ube3a. Notably, mature oligodendrocytes emerge as the predominant Ube3a-expressing glial cell type in the cortex and white matter tracts during postnatal development. These findings demonstrate the spatiotemporal characteristics of allele-specific Ube3a expression in key brain cell types, thereby improving our understanding of the developmental parameters of paternal Ube3a silencing and the cellular basis of AS. PMID:24254964
Maintaining older brain functionality: A targeted review.
Ballesteros, Soledad; Kraft, Eduard; Santana, Silvina; Tziraki, Chariklia
The unprecedented growth in the number of older adults in our society is accompanied by the exponential increase in the number of elderly people who will suffer cognitive decline and dementia in the next decades. This will create an enormous cost for governments, families and individuals. Brain plasticity and its role in brain adaptation to the process of aging is influenced by other changes as a result of co-morbidities, environmental factors, personality traits (psychosocial variables) and genetic and epigenetic factors. This review summarizes recent findings obtained mostly from interventional studies that aim to prevent and/or delay age-related cognitive decline in healthy adults. There are a multitude of such studies. In this paper, we focused our review on physical activity, computerized cognitive training and social enhancement interventions on improving cognition, physical health, independent living and wellbeing of older adults. The methodological limitations of some of these studies, and the need for new multi-domain synergistic interventions, based on current advances in neuroscience and social-brain theories, are discussed. PMID:26054789
Effect of tumor resection on the characteristics of functional brain networks J. M. Hernndez,1
Van Mieghem, Piet
Effect of tumor resection on the characteristics of functional brain networks H. Wang,1 L. Douw,2 J. The functional brain networks of a group of patients with brain tumors are measured before and after tumor with brain tumors before and after surgery, the aim of which was to remove the tumor. In brain tumor patients
The Mouse Blood-Brain Barrier Transcriptome: A New Resource for Understanding the Development and Function of Brain Endothelial Cells
Daneman, Richard; Zhou, Lu; Agalliu, Dritan; Cahoy, John D.; Kaushal, Amit; Barres, Ben A.
The blood-brain barrier (BBB) maintains brain homeostasis and limits the entry of toxins and pathogens into the brain. Despite its importance, little is known about the molecular mechanisms regulating the development and function of this crucial barrier. In this study we have developed methods to highly purify and gene profile endothelial cells from different tissues, and by comparing the transcriptional profile of brain endothelial cells with those purified from the liver and lung, we have generated a comprehensive resource of transcripts that are enriched in the BBB forming endothelial cells of the brain. Through this comparison we have identified novel tight junction proteins, transporters, metabolic enzymes, signaling components, and unknown transcripts whose expression is enriched in central nervous system (CNS) endothelial cells. This analysis has identified that RXRalpha signaling cascade is specifically enriched at the BBB, implicating this pathway in regulating this vital barrier. This dataset provides a resource for understanding CNS endothelial cells and their interaction with neural and hematogenous cells. PMID:21060791
Apolipoprotein E ?4 modulates functional brain connectome in Alzheimer's disease.
Wang, Jinhui; Wang, Xiao; He, Yi; Yu, Xin; Wang, Huali; He, Yong
The apolipoprotein E (APOE) ?4 allele is a well-established genetic risk factor for Alzheimer's disease (AD). Recent research has demonstrated an APOE ?4-mediated modulation of intrinsic functional brain networks in cognitively normal individuals. However, it remains largely unknown whether and how APOE ?4 affects the brain's functional network architecture in patients with AD. Using resting-state functional MRI and graph-theory approaches, we systematically investigated the topological organization of whole-brain functional networks in 16 APOE ?4 carriers and 26 matched noncarriers with AD at three levels: global whole-brain, intermediate module, and regional node/connection. Neuropsychological analysis showed that the APOE ?4 carriers performed worse on delayed memory but better on a late item generation of a verbal fluency task (associated with executive function) than noncarriers. Whole-brain graph analyses revealed that APOE ?4 significantly disrupted whole-brain topological organization as characterized by (i) reduced parallel information transformation efficiency; (ii) decreased intramodular connectivity within the posterior default mode network (pDMN) and intermodular connectivity of the pDMN and executive control network (ECN) with other neuroanatomical systems; and (iii) impaired functional hubs and their rich-club connectivities that primarily involve the pDMN, ECN, and sensorimotor systems. Further simulation analysis indicated that these altered connectivity profiles of the pDMN and ECN largely accounted for the abnormal global network topology. Finally, the changes in network topology exhibited significant correlations with the patients' cognitive performances. Together, our findings suggest that the APOE genotype modulates large-scale brain networks in AD and shed new light on the gene-connectome interaction in this disease. PMID:25619771
Modeling Brain Energy Metabolism and Function: A Multiparametric Monitoring Approach
Larisa Vatov; Ziv Kizner; Eytan Ruppin; Sigal Meilin; Tamar Manor; Avraham Mayevsky
Mathematical modeling of brain function is an important tool needed for a better understanding of experimental results and\\u000a clinical situations. In the present study, we are constructing and testing a mathematical model capable of simulating changes\\u000a in brain energy metabolism that develop in real time under various pathophysiological conditions. The model incorporates the\\u000a following parameters: cerebral blood flow, partial oxygen
Rationally Designed MicroRNA-Based Genetic Classifiers Target Specific Neurons in the Brain.
Sayeg, Marianna K; Weinberg, Benjamin H; Cha, Susie S; Goodloe, Michael; Wong, Wilson W; Han, Xue
Targeting transgene expression to specific cell types in vivo has proven instrumental in characterizing the functional role of defined cell populations. Genetic classifiers, synthetic transgene constructs designed to restrict expression to particular classes of cells, commonly rely on transcriptional promoters to define cellular specificity. However, the large size of many natural promoters complicates their use in viral vectors, an important mode of transgene delivery in the brain and in human gene therapy. Here, we expanded upon an emerging classifier platform, orthogonal to promoter-based strategies, that exploits endogenous microRNA regulation to target gene expression. Such classifiers have been extensively explored in other tissues; however, their use in the nervous system has thus far been limited to targeting gene expression between neurons and supporting cells. Here, we tested the possibility of using combinatory microRNA regulation to specify gene targeting between neuronal subtypes, and successfully targeted inhibitory cells in the neocortex. These classifiers demonstrate the feasibility of designing a new generation of microRNA-based neuron-type- and brain-region-specific gene expression targeting neurotechnologies. PMID:25848814
Human Functional Neuroimaging of Brain Changes Associated with Practice
A. M. Clare Kelly; Hugh Garavan
The discovery that experience-driven changes in the human brain can occur from a neural to a cortical level throughout the lifespan has stimulated a proliferation of research into how neural function changes in response to experience, enabled by neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging. Studies attempt to characterize these changes by examining how practice
RESEARCH Open Access Brain-Computer Interface Controlled Functional
Nenadic, Zoran
RESEARCH Open Access Brain-Computer Interface Controlled Functional Electrical Stimulation System provide only a limited degree of motor function recovery in these individuals, and therefore novel to restore, substitute, or augment lost motor behaviors in patients with neurological injuries. Here, we
Adaptation of Brain Functional and Structural Networks in Aging
Lee, Annie; Ratnarajah, Nagulan; Tuan, Ta Anh; Chen, Shen-Hsing Annabel; Qiu, Anqi
The human brain, especially the prefrontal cortex (PFC), is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI), and high angular resolution diffusion imaging (HARDI), and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging. PMID:25875816
Species-specific functional evolution of neuroglobin.
Wakasugi, Keisuke; Takahashi, Nozomu; Uchida, Hiroyuki; Watanabe, Seiji
Neuroglobin (Ngb) is a recently discovered vertebrate heme protein that is expressed in the brain and can reversibly bind oxygen. Human Ngb is involved in neuroprotection under oxidative stress conditions such as ischemia and reperfusion. We previously demonstrated that, on the one hand, human ferric Ngb binds to the ?-subunit of heterotrimeric G proteins (G?(i)) and acts as a guanine nucleotide dissociation inhibitor (GDI) for G?(i). On the other hand, zebrafish Ngb does not exhibit GDI activity. By using wild-type and Ngb mutants, we demonstrated that the GDI activity of human Ngb is tightly correlated with its neuroprotective activity. The crucial residues for both GDI and neuroprotective activity, corresponding to Glu53, Arg97, Glu118, and Glu151 of human Ngb, are conserved among boreotheria of mammalia. Recently, we found that zebrafish, but not human, Ngb can translocate into cells and clarified that module M1 of zebrafish Ngb is important for protein transduction. By performing site-directed mutagenesis, we showed that Lys7, Lys9, Lys21, and Lys23 of zebrafish Ngb are crucial for protein transduction activity. Because these residues are conserved among fishes, but not among mammals, birds, reptilians, or amphibians, the ability to penetrate cell membranes may be a unique characteristic of fish Ngb proteins. Moreover, we clarified that zebrafish Ngb interacts with negatively charged cell-surface glycosaminoglycan. Taken together, these results suggest that the function of Ngb proteins has been changing dynamically throughout the evolution of life. PMID:21867964
Analyzing complex functional brain networks: Fusing statistics and network science to understand the brain*†
Simpson, Sean L.; Bowman, F. DuBois; Laurienti, Paul J.
Complex functional brain network analyses have exploded over the last decade, gaining traction due to their profound clinical implications. The application of network science (an interdisciplinary offshoot of graph theory) has facilitated these analyses and enabled examining the brain as an integrated system that produces complex behaviors. While the field of statistics has been integral in advancing activation analyses and some connectivity analyses in functional neuroimaging research, it has yet to play a commensurate role in complex network analyses. Fusing novel statistical methods with network-based functional neuroimage analysis will engender powerful analytical tools that will aid in our understanding of normal brain function as well as alterations due to various brain disorders. Here we survey widely used statistical and network science tools for analyzing fMRI network data and discuss the challenges faced in filling some of the remaining methodological gaps. When applied and interpreted correctly, the fusion of network scientific and statistical methods has a chance to revolutionize the understanding of brain function. PMID:25309643
Understanding entangled cerebral networks: a prerequisite for restoring brain function with brain-computer interfaces
Mandonnet, Emmanuel; Duffau, Hugues
Historically, cerebral processing has been conceptualized as a framework based on statically localized functions. However, a growing amount of evidence supports a hodotopical (delocalized) and flexible organization. A number of studies have reported absence of a permanent neurological deficit after massive surgical resections of eloquent brain tissue. These results highlight the tremendous plastic potential of the brain. Understanding anatomo-functional correlates underlying this cerebral reorganization is a prerequisite to restore brain functions through brain-computer interfaces (BCIs) in patients with cerebral diseases, or even to potentiate brain functions in healthy individuals. Here, we review current knowledge of neural networks that could be utilized in the BCIs that enable movements and language. To this end, intraoperative electrical stimulation in awake patients provides valuable information on the cerebral functional maps, their connectomics and plasticity. Overall, these studies indicate that the complex cerebral circuitry that underpins interactions between action, cognition and behavior should be throughly investigated before progress in BCI approaches can be achieved. PMID:24834030
PET scans relate clinical picture to more specific nerve function
Ziporyn, T.
This article describes the historical development of the use of positron emission tomography in studies of brain chemistry and the specific pathways associated with specific disease states. Fluorine-18 is used to label dopa since dopa can cross the blood-brain barrier. This radiopharmaceutical has been used to study the role of dopamine in Parkinson's disease and other motor disorders. The new PET technologies may also allow insight into the cause of variable responses to levo-dopa therapy.
Brain-site-specific proteome changes induced by neuronal P60TRP expression.
Manavalan, Arulmani; Mishra, Manisha; Sze, Siu Kwan; Heese, Klaus
p60 transcription regulator protein (p60TRP) facilitates the processing of the amyloid precursor protein towards the non-amyloidogenic pathway by inhibiting the ?-secretase action. This protein was initially identified to be downregulated in the temporal lobe of brains from Alzheimer's disease patients. p60TRP is one of the G-protein-coupled receptor (GPCR)-associated proteins which directly influences the signalling capacity of GPCRs. In the present study, we investigated the brain-region-specific proteome profile of transgenic p60TRP mice to gain an insight into the molecular events mediated by the long-term effect of neuronal p60TRP overexpression on brain proteome changes and its potential implication for neuronal functions in the central nervous system. Using a proteomics research approach based on isobaric tags for relative and absolute quantitation, we identified 2,025 proteins, whereby 1,735 proteins were quantified, out of which 56 were found to be significantly altered in the cortex and/or hippocampus of neuronal transgenic neuronal p60TRP mice. Our data suggests that in vivo overexpression of neuronal p60TRP significantly affects cognitive and neuroprotective capacities. PMID:23391701
Space shuttle configuration accounting functional design specification
NASA Technical Reports Server (NTRS)
An analysis is presented of the requirements for an on-line automated system which must be capable of tracking the status of requirements and engineering changes and of providing accurate and timely records. The functional design specification provides the definition, description, and character length of the required data elements and the interrelationship of data elements to adequately track, display, and report the status of active configuration changes. As changes to the space shuttle program levels II and III configuration are proposed, evaluated, and dispositioned, it is the function of the configuration management office to maintain records regarding changes to the baseline and to track and report the status of those changes. The configuration accounting system will consist of a combination of computers, computer terminals, software, and procedures, all of which are designed to store, retrieve, display, and process information required to track proposed and proved engineering changes to maintain baseline documentation of the space shuttle program levels II and III.
[Functional brain lateralization in children: developmental theories and implication for developmental diseases].
Hommet, C; Billard, C; de Toffol, B; Autret, A
The functional specialization of each hemisphere in adults is now well accepted. Neuropsychology of hemispheric functioning in young children is a more debatable issue and must take into account additional factors such as development and maturation, characterized by complex changes in anatomy and organization. The first part of this review describes the theory behind the development of the functional organization of the brain. Second, we discuss data regarding brain lesions in children with brain damage and with normal development. We comment on the concept of plasticity and the critical period. We also discuss the neurobiological processes underlying the functional organization of the brain in the model of developmental disorders in children. We chose three disorders involving the left hemisphere (developmental dysphasia), both hemispheres (benign rolandic epilepsy) or the right hemisphere (congenital hydrocephalus) in order to examine their relationship to a specific hemispheric functional organization. We used classic neuropsychological tests such as the dichotic listening task, the dichaptic palpation and the time-sharing paradigm. The patterns observed in each pathology are discussed in light of data obtained in children with brain lesions. PMID:14710020
Functional Representation of Enzymes by Specific Peptides
Kunik, Vered; Meroz, Yasmine; Solan, Zach; Sandbank, Ben; Weingart, Uri; Ruppin, Eytan; Horn, David
Predicting the function of a protein from its sequence is a long-standing goal of bioinformatic research. While sequence similarity is the most popular tool used for this purpose, sequence motifs may also subserve this goal. Here we develop a motif-based method consisting of applying an unsupervised motif extraction algorithm (MEX) to all enzyme sequences, and filtering the results by the four-level classification hierarchy of the Enzyme Commission (EC). The resulting motifs serve as specific peptides (SPs), appearing on single branches of the EC. In contrast to previous motif-based methods, the new method does not require any preprocessing by multiple sequence alignment, nor does it rely on over-representation of motifs within EC branches. The SPs obtained comprise on average 8.4 ± 4.5 amino acids, and specify the functions of 93% of all enzymes, which is much higher than the coverage of 63% provided by ProSite motifs. The SP classification thus compares favorably with previous function annotation methods and successfully demonstrates an added value in extreme cases where sequence similarity fails. Interestingly, SPs cover most of the annotated active and binding site amino acids, and occur in active-site neighboring 3-D pockets in a highly statistically significant manner. The latter are assumed to have strong biological relevance to the activity of the enzyme. Further filtering of SPs by biological functional annotations results in reduced small subsets of SPs that possess very large enzyme coverage. Overall, SPs both form a very useful tool for enzyme functional classification and bear responsibility for the catalytic biological function carried out by enzymes. PMID:17722976
Linking structure and function: Information processing in the brain
Gremillion, M.A.V.
Traditionally, theories of function in neuroscience have emerged from physiology. Physiologists have suggested a number of means by which information in the brain can be processed, yet the principles underlying the generation of these phenomena are not well understood. A complex systems approach would be to examine the overall structure and function of the system and to attempt to establish a common framework for information processing interactions. This paper will use the structure-function relationship as a basis for exploring units of information processing. It will examine the brain as a whole, first providing the non-specialists with an short overview of the structure and some of the functions or outputs of the brain. It then very briefly reviews three of the prominent theoretical concepts that have emerged in the last few decades: receptive fields, feature extraction, and parallel processing. Next, it addresses the question of information processing and outlines the structures which have traditionally been proposed to be the basic unit of information processing. An alternative unit on which information processing in the brain might be based is then proposed, and data outlined to support it. Finally, the implications of this different mode of processing are discussed, both for the brain and for other complex systems. 40 refs., 4 figs., 2 tabs.
Assortative mixing in functional brain networks during epileptic seizures
NASA Astrophysics Data System (ADS)
Bialonski, Stephan; Lehnertz, Klaus
We investigate assortativity of functional brain networks before, during, and after one-hundred epileptic seizures with different anatomical onset locations. We construct binary functional networks from multi-channel electroencephalographic data recorded from 60 epilepsy patients; and from time-resolved estimates of the assortativity coefficient, we conclude that positive degree-degree correlations are inherent to seizure dynamics. While seizures evolve, an increasing assortativity indicates a segregation of the underlying functional network into groups of brain regions that are only sparsely interconnected, if at all. Interestingly, assortativity decreases already prior to seizure end. Together with previous observations of characteristic temporal evolutions of global statistical properties and synchronizability of epileptic brain networks, our findings may help to gain deeper insights into the complicated dynamics underlying generation, propagation, and termination of seizures.
Imagery or meaning? Evidence for a semantic origin of category-specific brain activity in metabolic imaging
Hauk, Olaf; Davis, Matthew H; Kherif, Ferath; Pulvermüller, Friedemann
Category-specific brain activation distinguishing between semantic word types has imposed challenges on theories of semantic representations and processes. However, existing metabolic imaging data are still ambiguous about whether these category-specific activations reflect processes involved in accessing the semantic representation of the stimuli, or secondary processes such as deliberate mental imagery. Further information about the response characteristics of category-specific activation is still required. Our study for the first time investigated the differential impact of word frequency on functional magnetic resonance imaging (fMRI) responses to action-related words and visually related words, respectively. First, we corroborated previous results showing that action-relatedness modulates neural responses in action-related areas, while word imageability modulates activation in object processing areas. Second, we provide novel results showing that activation negatively correlated with word frequency in the left fusiform gyrus was specific for visually related words, while in the left middle temporal gyrus word frequency effects emerged only for action-related words. Following the dominant view in the literature that effects of word frequency mainly reflect access to lexico-semantic information, we suggest that category-specific brain activation reflects distributed neuronal ensembles, which ground language and concepts in perception-action systems of the human brain. Our approach can be applied to any event-related data using single-stimulus presentation, and allows a detailed characterization of the functional role of category-specific activation patterns. PMID:18380676
Functionally Enigmatic Genes: A Case Study of the Brain Ignorome
Pandey, Ashutosh K.; Lu, Lu; Wang, Xusheng; Homayouni, Ramin; Williams, Robert W.
What proportion of genes with intense and selective expression in specific tissues, cells, or systems are still almost completely uncharacterized with respect to biological function? In what ways do these functionally enigmatic genes differ from well-studied genes? To address these two questions, we devised a computational approach that defines so-called ignoromes. As proof of principle, we extracted and analyzed a large subset of genes with intense and selective expression in brain. We find that publications associated with this set are highly skewed—the top 5% of genes absorb 70% of the relevant literature. In contrast, approximately 20% of genes have essentially no neuroscience literature. Analysis of the ignorome over the past decade demonstrates that it is stubbornly persistent, and the rapid expansion of the neuroscience literature has not had the expected effect on numbers of these genes. Surprisingly, ignorome genes do not differ from well-studied genes in terms of connectivity in coexpression networks. Nor do they differ with respect to numbers of orthologs, paralogs, or protein domains. The major distinguishing characteristic between these sets of genes is date of discovery, early discovery being associated with greater research momentum—a genomic bandwagon effect. Finally we ask to what extent massive genomic, imaging, and phenotype data sets can be used to provide high-throughput functional annotation for an entire ignorome. In a majority of cases we have been able to extract and add significant information for these neglected genes. In several cases—ELMOD1, TMEM88B, and DZANK1—we have exploited sequence polymorphisms, large phenome data sets, and reverse genetic methods to evaluate the function of ignorome genes. PMID:24523945
Democratic reinforcement: A principle for brain function
Stassinopoulos, D.; Bak, P. [Brookhaven National Laboratory, Upton, New York 11973 (United States)] [Brookhaven National Laboratory, Upton, New York 11973 (United States)
We introduce a simple ``toy`` brain model. The model consists of a set of randomly connected, or layered integrate-and-fire neurons. Inputs to and outputs from the environment are connected randomly to subsets of neurons. The connections between firing neurons are strengthened or weakened according to whether the action was successful or not. Unlike previous reinforcement learning algorithms, the feedback from the environment is democratic: it affects all neurons in the same way, irrespective of their position in the network and independent of the output signal. Thus no unrealistic back propagation or other external computation is needed. This is accomplished by a global threshold regulation which allows the system to self-organize into a highly susceptible, possibly ``critical`` state with low activity and sparse connections between firing neurons. The low activity permits memory in quiescent areas to be conserved since only firing neurons are modified when new information is being taught.
Brain-specific noncoding RNAs are likely to originate in repeats and may play a role in up-regulating genes in cis.
Francescatto, Margherita; Vitezic, Morana; Heutink, Peter; Saxena, Alka
The mouse and human brain express a large number of noncoding RNAs (ncRNAs). Some of these are known to participate in neural progenitor cell fate determination, cell differentiation, neuronal and synaptic plasticity and transposable elements derived ncRNAs contribute to somatic variation. Dysregulation of specific long ncRNAs (lncRNAs) has been shown in neuro-developmental and neuro-degenerative diseases thus highlighting the importance of lncRNAs in brain function. Even though it is known that lncRNAs are expressed in cells at low levels in a tissue-specific manner, bioinformatics analyses of brain-specific ncRNAs has not been performed. We analyzed previously published custom microarray ncRNA expression data generated from twelve human tissues to identify tissue-specific ncRNAs. We find that among the 12 tissues studied, brain has the largest number of ncRNAs. Our analyses show that genes in the vicinity of brain-specific ncRNAs are significantly up regulated in the brain. Investigations of repeat representation show that brain-specific ncRNAs are significantly more likely to originate in repeat regions especially DNA/TcMar-Tigger compared with non-tissue-specific ncRNAs. We find SINE/Alus depleted from brain-specific dataset when compared with non-tissue-specific ncRNAs. Our data provide a bioinformatics comparison between brain-specific and non tissue-specific ncRNAs. This article is part of a Directed Issue entitled: The Non-coding RNA Revolution. PMID:24993078
Specific role of polysorbate 80 coating on the targeting of nanoparticles to the brain
Wangqiang Sun; Changsheng Xie; Huafang Wang; Yu Hu
It was reported that nanoparticles with polysorbate 80 (Tween 80, T-80) coating represented tools used for delivering drugs to brain. Nevertheless, disputations were once aroused for some complications. Aimed to have a better understanding of the specific role of T-80 coating on nanoparticles and simplify the problem, the direct observation of brain targeting combined with in vivo experiments was carried
Increased serum creatine kinase BB and neuron specific enolase following head injury indicates brain damage
I. M. Skogseid; H. K. Nordby; P. Urdal; E. Paus; F. Lilleaas
Summary The aim of this study was to examine whether an increase in the serum concentrations of the two brain enzymes creatine kinase BB (CK-BB) and neuron specific enolase (NSE) can be demonstrated in patiens with acute head injury and whether such an increase reflects release from damaged brain tissue. In 60 patients who had suffered minor to severe head
Steroid receptor coactivator-1 (SRC-1) mediates the development of sex-specific brain morphology
Steroid receptor coactivator-1 (SRC-1) mediates the development of sex-specific brain morphology March 1, 2000) Steroid hormone action during brain development exerts profound effects on reproductive physiology and behavior that last into adulthood. A variety of in vitro studies indicate that steroid
Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.
Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom
Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses. PMID:24566670
Brain systems mediating semantic and syntactic processing in deaf native signers: biological invariance and modality specificity.
Capek, Cheryl M; Grossi, Giordana; Newman, Aaron J; McBurney, Susan L; Corina, David; Roeder, Brigitte; Neville, Helen J
Studies of written and spoken language suggest that nonidentical brain networks support semantic and syntactic processing. Event-related brain potential (ERP) studies of spoken and written languages show that semantic anomalies elicit a posterior bilateral N400, whereas syntactic anomalies elicit a left anterior negativity, followed by a broadly distributed late positivity. The present study assessed whether these ERP indicators index the activity of language systems specific for the processing of aural-oral language or if they index neural systems underlying any natural language, including sign language. The syntax of a signed language is mediated through space. Thus the question arises of whether the comprehension of a signed language requires neural systems specific for this kind of code. Deaf native users of American Sign Language (ASL) were presented signed sentences that were either correct or that contained either a semantic or a syntactic error (1 of 2 types of verb agreement errors). ASL sentences were presented at the natural rate of signing, while the electroencephalogram was recorded. As predicted on the basis of earlier studies, an N400 was elicited by semantic violations. In addition, signed syntactic violations elicited an early frontal negativity and a later posterior positivity. Crucially, the distribution of the anterior negativity varied as a function of the type of syntactic violation, suggesting a unique involvement of spatial processing in signed syntax. Together, these findings suggest that biological constraints and experience shape the development of neural systems important for language. PMID:19433795
Long intervening non-coding RNA 00320 is human brain-specific and highly expressed in the cortical white matter.
Mills, James D; Chen, Jieqiong; Kim, Woojin S; Waters, Paul D; Prabowo, Avanita S; Aronica, Eleonora; Halliday, Glenda M; Janitz, Michael
Pervasive transcription of the genome produces a diverse array of functional non-coding RNAs (ncRNAs). One particular class of ncRNAs, long intervening non-coding RNAs (lincRNAs) are thought to play a role in regulating gene expression and may be a major contributor to organism and tissue complexity. The human brain with its heterogeneous cellular make-up is a rich source of lincRNAs; however, the functions of the majority of lincRNAs are unknown. Recently, by completing RNA sequencing (RNA-Seq) of the human frontal cortex, we identified linc00320 as being highly expressed in the white matter compared to grey matter in multiple system atrophy (MSA) brain. Here, we further investigate the expression patterns of linc00320 and conclude that it is involved in specific brain regions rather than having involvement in the MSA disease process. We also show that the full-length linc00320 is only expressed in human brain tissue and not in other primates, suggesting that it may be involved in improved functional connectivity for higher human brain cognition. PMID:25819921
Joseph Colombo; Kevan Iffrig; Elif Aysin; Ben Aysin; Charles C Wo; William C Shoemaker; Adam Colombo
Introduction: Current methods in evaluating brain function to determine viability of life typically involves brain flow studies after cerebral edema or ischemia has occurred. We present data demonstrating earlier determination of lack of brain stem activity which can lead to earlier clinical decision-making, earlier family involvement in end-of-life issues, including organ donation, and decreased intensive care unit and ventilator-management time
Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain.
Onaivi, Emmanuel S; Ishiguro, Hiroki; Gong, Jian-Ping; Patel, Sejal; Perchuk, Alex; Meozzi, Paul A; Myers, Lester; Mora, Zoila; Tagliaferro, Patricia; Gardner, Eileen; Brusco, Alicia; Akinshola, Babatunde E; Liu, Qing-Rong; Hope, Bruce; Iwasaki, Shinya; Arinami, Tadao; Teasenfitz, Lindsey; Uhl, George R
Two well-characterized cannabinoid receptors (CBrs), CB1 and CB2, mediate the effects of cannabinoids and marijuana use, with functional evidence for other CBrs. CB1 receptors are expressed primarily in brain and peripheral tissues. For over a decade several laboratories were unable to detect CB2 receptors in brain and were known to be intensely expressed in peripheral and immune tissues and have traditionally been referred to as peripheral CB2 CBrs. We have reported the discovery and functional presence of CB2 cannabinoid receptors in mammalian brain that may be involved in depression and drug abuse and this was supported by reports of identification of neuronal CB2 receptors that are involved in emesis. We used RT-PCR, immunoblotting, hippocampal cultures, immunohistochemistry, transmission electron microscopy, and stereotaxic techniques with behavioral assays to determine the functional expression of CB2 CBrs in rat brain and mice brain exposed to chronic mild stress (CMS) or those treated with abused drugs. RT-PCR analyses supported the expression of brain CB2 receptor transcripts at levels much lower than those of CB1 receptors. In situ hybridization revealed CB2 mRNA in cerebellar neurons of wild-type but not of CB2 knockout mice. Abundant CB2 receptor immunoreactivity (iCB2) in neuronal and glial processes was detected in brain and CB2 expression was detected in neuron-specific enolase (NSE) positive hippocampal cell cultures. The effect of direct CB2 antisense oligonucleotide injection into the brain and treatment with JWH015 in motor function and plus-maze tests also demonstrated the functional presence of CB2 cannabinoid receptors in the central nervous system (CNS). Thus, contrary to the prevailing view that CB2 CBrs are restricted to peripheral tissues and predominantly in immune cells, we demonstrated that CB2 CBrs and their gene transcripts are widely distributed in the brain. This multifocal expression of CB2 immunoreactivity in brain suggests that CB2 receptors may play broader roles in the brain than previously anticipated and may be exploited as new targets in the treatment of depression and substance abuse. PMID:17105950
Efficiency and Cost of Economical Brain Functional Networks
Achard, Sophie; Bullmore, Ed
Brain anatomical networks are sparse, complex, and have economical small-world properties. We investigated the efficiency and cost of human brain functional networks measured using functional magnetic resonance imaging (fMRI) in a factorial design: two groups of healthy old (N = 11; mean age = 66.5 years) and healthy young (N = 15; mean age = 24.7 years) volunteers were each scanned twice in a no-task or "resting" state following placebo or a single dose of a dopamine receptor antagonist (sulpiride 400 mg). Functional connectivity between 90 cortical and subcortical regions was estimated by wavelet correlation analysis, in the frequency interval 0.06–0.11 Hz, and thresholded to construct undirected graphs. These brain functional networks were small-world and economical in the sense of providing high global and local efficiency of parallel information processing for low connection cost. Efficiency was reduced disproportionately to cost in older people, and the detrimental effects of age on efficiency were localised to frontal and temporal cortical and subcortical regions. Dopamine antagonism also impaired global and local efficiency of the network, but this effect was differentially localised and did not interact with the effect of age. Brain functional networks have economical small-world properties—supporting efficient parallel information transfer at relatively low cost—which are differently impaired by normal aging and pharmacological blockade of dopamine transmission. PMID:17274684
Gender and brain regions specific differences in brain derived neurotrophic factor protein levels of depressed individuals who died through suicide.
Hayley, Shawn; Du, Lisheng; Litteljohn, Darcy; Palkovits, Miklós; Faludi, Gábor; Merali, Zul; Poulter, Michael O; Anisman, Hymie
Considerable evidence supports the view that depressive illness and suicidal behaviour stem from perturbations of neuroplasticity. Presently, we assessed whether depressed individuals who died by suicide displayed brain region-specific changes in brain derived neurotrophic factor (BDNF) and whether such effects varied by gender. Using postmortem samples from non-psychiatric controls and depressed individuals who died by suicide, BDNF protein levels were assessed within the hippocampus and frontopolar prefrontal cortex using Western blot. As expected, BDNF levels were reduced within the frontopolar prefrontal cortex among female depressed suicides; however, males showed no such effect. Contrastingly, within the hippocampus, depressed male but not female suicides displayed significant reductions of BDNF protein levels. Although the mechanisms driving the gender and brain region specific BDNF changes are unclear, our data do support the notion that complex alterations of neuroplasticity may be fundamentally involved in the illness. PMID:26033186
Three-Dimensional Simulation of Carmustine Delivery to a Patient-Specific Brain Tumor
Arifin, Davis Yohanes
This study presents the recent development of three-dimensional patient-specific simulation of carmustine delivery to brain tumor that highlights several crucial factors affecting the delivery. The simulation utilizes the ...
Netrin 1 regulates blood-brain barrier function and neuroinflammation.
Podjaski, Cornelia; Alvarez, Jorge I; Bourbonniere, Lyne; Larouche, Sandra; Terouz, Simone; Bin, Jenea M; Lécuyer, Marc-André; Saint-Laurent, Olivia; Larochelle, Catherine; Darlington, Peter J; Arbour, Nathalie; Antel, Jack P; Kennedy, Timothy E; Prat, Alexandre
Blood-brain barrier function is driven by the influence of astrocyte-secreted factors. During neuroinflammatory responses the blood-brain barrier is compromised resulting in central nervous system damage and exacerbated pathology. Here, we identified endothelial netrin 1 induction as a vascular response to astrocyte-derived sonic hedgehog that promotes autocrine barrier properties during homeostasis and increases with inflammation. Netrin 1 supports blood-brain barrier integrity by upregulating endothelial junctional protein expression, while netrin 1 knockout mice display disorganized tight junction protein expression and barrier breakdown. Upon inflammatory conditions, blood-brain barrier endothelial cells significantly upregulated netrin 1 levels in vitro and in situ, which prevented junctional breach and endothelial cell activation. Finally, netrin 1 treatment during experimental autoimmune encephalomyelitis significantly reduced blood-brain barrier disruption and decreased clinical and pathological indices of disease severity. Our results demonstrate that netrin 1 is an important regulator of blood-brain barrier maintenance that protects the central nervous system against inflammatory conditions such as multiple sclerosis and experimental autoimmune encephalomyelitis. PMID:25903786
Dedeurwaerdere, Stefanie; Shultz, Sandy R.; Federico, Paolo; Engel, Jerome
Summary Objectives Modern functional neuroimaging provides opportunities to visualize activity of the entire brain, making it an indispensable diagnostic tool for epilepsy. Various forms of non-invasive functional neuroimaging are now also being performed as research tools in animal models of epilepsy and provide opportunities for parallel animal/human investigations into fundamental mechanisms of epilepsy and identification of epilepsy biomarkers. Methods Recent animal studies of epilepsy using positron emission tomography, tractography, and functional magnetic resonance imaging were reviewed. Results Epilepsy is an abnormal emergent property of disturbances in neuronal networks which, even for epilepsies characterized by focal seizures, involve widely distributed systems, often in both hemispheres. Functional neuroimaging in animal models now provides opportunities to examine neuronal disturbances in the whole brain that underlie generalized and focal seizure generation as well as various types of epileptogenesis. Significance Tremendous advances in understanding the contribution of specific properties of widely distributed neuronal networks to both normal and abnormal human behavior have been provided by current functional neuroimaging methodologies. Successful application of functional neuroimaging of the whole brain in the animal laboratory now permits investigations during epileptogenesis and correlation with deep brain EEG activity. With the continuing development of these techniques and analytical methods, the potential for future translational research on epilepsy is enormous. PMID:24836499
The Anatomical Distance of Functional Connections Predicts Brain Network Topology in Health and Schizophrenia
Vértes, Petra E.; Stidd, Reva; Lalonde, François; Clasen, Liv; Rapoport, Judith; Giedd, Jay; Bullmore, Edward T.; Gogtay, Nitin
The human brain is a topologically complex network embedded in anatomical space. Here, we systematically explored relationships between functional connectivity, complex network topology, and anatomical (Euclidean) distance between connected brain regions, in the resting-state functional magnetic resonance imaging brain networks of 20 healthy volunteers and 19 patients with childhood-onset schizophrenia (COS). Normal between-subject differences in average distance of connected edges in brain graphs were strongly associated with variation in topological properties of functional networks. In addition, a club or subset of connector hubs was identified, in lateral temporal, parietal, dorsal prefrontal, and medial prefrontal/cingulate cortical regions. In COS, there was reduced strength of functional connectivity over short distances especially, and therefore, global mean connection distance of thresholded graphs was significantly greater than normal. As predicted from relationships between spatial and topological properties of normal networks, this disorder-related proportional increase in connection distance was associated with reduced clustering and modularity and increased global efficiency of COS networks. Between-group differences in connection distance were localized specifically to connector hubs of multimodal association cortex. In relation to the neurodevelopmental pathogenesis of schizophrenia, we argue that the data are consistent with the interpretation that spatial and topological disturbances of functional network organization could arise from excessive "pruning" of short-distance functional connections in schizophrenia. PMID:22275481
Nanoparticle-Mediated Brain-Specific Drug Delivery, Imaging, and Diagnosis
Hu Yang
Central nervous system (CNS) diseases represent the largest and fastest-growing area of unmet medical need. Nanotechnology\\u000a plays a unique instrumental role in the revolutionary development of brain-specific drug delivery, imaging, and diagnosis.\\u000a With the aid of nanoparticles of high specificity and multifunctionality, such as dendrimers and quantum dots, therapeutics,\\u000a imaging agents, and diagnostic molecules can be delivered to the brain
Region-Specific Protein Abundance Changes in the Brain of MPTP-induced Parkinson's Disease Mouse Model
Zhang, Xu; Zhou, Jianying; Chin, Mark H.; Schepmoes, Athena A.; Petyuk, Vladislav A.; Weitz, Karl K.; Petritis, Brianne O.; Monroe, Matthew E.; Camp, David G.; Wood, Stephen A.; Melega, William P.; Bigelow, Diana J.; Smith, Desmond J.; Qian, Weijun; Smith, Richard D.
Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 non-redundant proteins with at least two unique peptides per protein. The relative abundance changes in each analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with significant MPTP-induced changes across different brain regions. 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit significant abundance changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. One of the interesting proteins is ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF-? pathway, which exhibited altered abundances in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall picture of proteome changes underlying both nigrostriatal pathways and other brain regions potentially involved in MPTP-induced neurodegeneration. The observed molecular changes provide a valuable reference resource for future hypothesis-driven functional studies of PD.
Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain
Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel
Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS. PMID:26193653
Sex hormone therapy and functional brain plasticity in postmenopausal women
U. Bayer; M. Hausmann
Several studies have shown that fluctuating levels of sex hormones (estrogen and progesterone) can affect fundamental principles of brain organization, including functional cerebral asymmetries (FCAs) and interhemispheric interactions. The majority of findings come from studies investigating younger women tested during distinct hormonal phases of the menstrual cycle, an approach that does not necessarily allow for conclusions about the causal relationship
Complexity in Quantum System and Its Application to Brain Function
Masanori Ohya
The complexity and the chaos degree can be used to examine the chaotic aspects of not only several nonlinear classical and quantum physical physics but also life sciences. We will construct a model describing the function of brain in the context of Quantum Information Dynamics.
The nicotinic cholinergic system function in the human brain.
Nees, Frauke
Research on the nicotinic cholinergic system function in the brain was previously mainly derived from animal studies, yet, research in humans is growing. Up to date, findings allow significant advances on the understanding of nicotinic cholinergic effects on human cognition, emotion and behavior using a range of functional brain imaging approaches such as pharmacological functional magnetic resonance imaging or positron emission tomography. Studies provided insights across various mechanistic psychological domains using different tasks as well as at rest in both healthy individuals and patient populations, with so far partly mixed results reporting both enhancements and decrements of neural activity related to the nicotinic cholinergic system. Moreover, studies on the relation between brain structure and the nicotinic cholinergic system add important information in this context. The present review summarizes the current status of human brain imaging studies and presents the findings within a theoretical and clinical perspective as they may be useful not only for an advancement of the understanding of basic nicotinic cholinergic-related mechanisms, but also for the development and integration of psychological and pharmacological treatment approaches. Patterns of functional neuroanatomy and neural circuitry across various cognitive and emotional domains may be used as neuropsychological markers of mental disorders such as addiction, Alzheimer's disease, Parkinson disease or schizophrenia, where nicotinic cholinergic system changes are characteristic. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. PMID:25446570
"Hotheaded": the role OF TRPV1 in brain functions.
Martins, D; Tavares, I; Morgado, C
The TRPV1 (vanilloid 1) channel is best known for its role in sensory transmission in the nociceptive neurons of the peripheral nervous system. Although first studied in the dorsal root ganglia as the receptor for capsaicin, TRPV1 has been recently recognized to have a broader distribution in the central nervous system, where it is likely to constitute an atypical neurotransmission system involved in several functions through modulation of both neuronal and glial activities. The endovanilloid-activated brain TRPV1 channels seem to be involved in somatosensory, motor and visceral functions. Recent studies suggested that TRPV1 channels also account for more complex functions, as addiction, anxiety, mood and cognition/learning. However, more studies are needed before the relevance of TRPV1 in brain activity can be clearly stated. This review highlights the increasing importance of TRPV1 as a regulator of brain function and discusses possible bases for the future development of new therapeutic approaches that by targeting brain TRPV1 receptors might be used for the treatment of several neurological disorders. PMID:24887171
Functional craniology and brain evolution: from paleontology to biomedicine
Bruner, Emiliano; de la Cuétara, José Manuel; Masters, Michael; Amano, Hideki; Ogihara, Naomichi
Anatomical systems are organized through a network of structural and functional relationships among their elements. This network of relationships is the result of evolution, it represents the actual target of selection, and it generates the set of rules orienting and constraining the morphogenetic processes. Understanding the relationship among cranial and cerebral components is necessary to investigate the factors that have influenced and characterized our neuroanatomy, and possible drawbacks associated with the evolution of large brains. The study of the spatial relationships between skull and brain in the human genus has direct relevance in cranial surgery. Geometrical modeling can provide functional perspectives in evolution and brain physiology, like in simulations to investigate metabolic heat production and dissipation in the endocranial form. Analysis of the evolutionary constraints between facial and neural blocks can provide new information on visual impairment. The study of brain form variation in fossil humans can supply a different perspective for interpreting the processes behind neurodegeneration and Alzheimer's disease. Following these examples, it is apparent that paleontology and biomedicine can exchange relevant information and contribute at the same time to the development of robust evolutionary hypotheses on brain evolution, while offering more comprehensive biological perspectives with regard to the interpretation of pathological processes. PMID:24765064
Brain covariance selection: better individual functional connectivity models using population prior
Brain covariance selection: better individual functional connectivity models using population email@example.com Abstract Spontaneous brain activity, as observed in functional neuroimaging, has been shown to display reproducible structure that expresses brain architecture and car- ries markers of brain pathologies
IR Principles for Content-based Indexing and Retrieval of Functional Brain Images
IR Principles for Content-based Indexing and Retrieval of Functional Brain Images Bing Bai, Paul(LSI)) to content-based brain image retrieval. Our results show that efficient and accurate retrieval of brain than are methods based on re- taining the full image information. Keywords fMRI, functional brain image
Voxel Scale Complex Networks of Functional Connectivity in the Rat Brain: Neurochemical State Dependence of Global and Local Topological Properties
Schwarz, Adam J.; Gozzi, Alessandro; Chessa, Alessandro; Bifone, Angelo
Network analysis of functional imaging data reveals emergent features of the brain as a function of its topological properties. However, the brain is not a homogeneous network, and the dependence of functional connectivity parameters on neuroanatomical substrate and parcellation scale is a key issue. Moreover, the extent to which these topological properties depend on underlying neurochemical changes remains unclear. In the present study, we investigated both global statistical properties and the local, voxel-scale distribution of connectivity parameters of the rat brain. Different neurotransmitter systems were stimulated by pharmacological challenge (d-amphetamine, fluoxetine, and nicotine) to discriminate between stimulus-specific functional connectivity and more general features of the rat brain architecture. Although global connectivity parameters were similar, mapping of local connectivity parameters at high spatial resolution revealed strong neuroanatomical dependence of functional connectivity in the rat brain, with clear differentiation between the neocortex and older brain regions. Localized foci of high functional connectivity independent of drug challenge were found in the sensorimotor cortices, consistent with the high neuronal connectivity in these regions. Conversely, the topological properties and node roles in subcortical regions varied with neurochemical state and were dependent on the specific dynamics of the different functional processes elicited. PMID:22919431
The Role of Noise in Brain Function
NASA Astrophysics Data System (ADS)
Roy, S.; Llinás, R.
Noise plays a fundamental role in all living organisms from the earliest prokaryotes to advanced mammalian forms, such as ourselves. In the context of living organisms, the term 'noise' usually refers to the variance amongst measurements obtained from repeated identical experimental conditions, or from output signals from these systems. It is noteworthy that both these conditions are universally characterized by the presence of background fluctuations. In non-biological systems, such as electronics or in communications sciences, where the aim is to send error-free messages, noise was generally regarded as a problem. The discovery of Stochastic Resonances (SR) in non-linear dynamics brought a shift of perception where noise, rather than representing a problem, became fundamental to system function, especially so in biology. The question now is: to what extent is biological function dependent on random noise. Indeed, it seems feasible that noise also plays an important role in neuronal communication and oscillatory synchronization. Given this approach, it follows that determining Fisher information content could be relevant in neuronal communication. It also seems possible that the principle of least time, and that of the sum over histories, could be important basic principles in understanding the coherence dynamics responsible for action and perception. Ultimately, external noise cancellation combined with intrinsic noise signal embedding and, the use of the principle of least time may be considered an essential step in the organization of central nervous system (CNS) function.
Large-scale brain networks in affective and social neuroscience: towards an integrative functional architecture of the brain.
Barrett, Lisa Feldman; Satpute, Ajay Bhaskar
Understanding how a human brain creates a human mind ultimately depends on mapping psychological categories and concepts to physical measurements of neural response. Although it has long been assumed that emotional, social, and cognitive phenomena are realized in the operations of separate brain regions or brain networks, we demonstrate that it is possible to understand the body of neuroimaging evidence using a framework that relies on domain general, distributed structure-function mappings. We review current research in affective and social neuroscience and argue that the emerging science of large-scale intrinsic brain networks provides a coherent framework for a domain-general functional architecture of the human brain. PMID:23352202
A Network Analysis Approach to fMRI Condition-Specific Functional Connectivity
Svetlana V. Shinkareva; Vladimir Gudkov; Jing Wang
In this work we focus on examination and comparison of whole-brain functional connectivity patterns measured with fMRI across experimental conditions. Direct examination and comparison of condition-specific matrices is challenging due to the large number of elements in a connectivity matrix. We present a framework that uses network analysis to describe condition-specific functional connectivity. Treating the brain as a complex system in terms of a network, we extract the most relevant connectivity information by partitioning each network into clusters representing functionally connected brain regions. Extracted clusters are used as features for predicting experimental condition in a new data set. The approach is illustrated on fMRI data examining functional connectivity patterns during processing of abstract and concrete concepts. Topological (brain regions) and functional (level of connectivity and information flow) systematic differences in the ROI-based functional networks were identified across participants for concrete and abstract concepts. These differences were sufficient for classification of previously unseen connectivity matrices as abstract or concrete based on training data derived from other people.
Functional role of endothelial adhesion molecules in the early stages of brain metastasis
Soto, Manuel Sarmiento; Serres, Sébastien; Anthony, Daniel C.; Sibson, Nicola R.
Background Cellular adhesion molecules (CAMs), which are normally associated with leukocyte trafficking, have also been shown to play an essential role in tumor metastasis to non-CNS sites. However, the role played by CAMs in brain metastasis is largely unexplored. It is known that leukocyte recruitment to the brain is very atypical and that mechanisms of disease in peripheral tissues cannot be extrapolated to the brain. Here, we have established the spatiotemporal expression of 12 key CAMs in the initial phases of tumor seeding in 2 different models of brain metastasis. Methods BALB/c or SCID mice were injected intracardially (105 cells/100 ?L phosphate-buffered saline with either 4T1-GFP or MDA231BR-GFP cells, respectively (n = 4–6/group), and expression of the CAMs was determined by immunohistochemistry and immunofluorescence colocalisation. Results Endothelial expression of E-selectin, VCAM-1, ALCAM, ICAM-1, VLA-4, and ?4 integrin was markedly increased early in tumor seeding. At the same time, the natural ligands to these adhesion molecules were highly expressed on the metastatic tumor cells both in vitro and in vivo. Two of these ligands showed particularly high tumor cell expression (ALCAM and VLA-4), and consequently their functional role in tumor seeding was determined. Antibody neutralization of either ALCAM or VLA-4 significantly reduced tumor seeding within the brain (>60% decrease in tumor number/mm2 brain; P < .05–0.01). Conclusions These findings suggest that ALCAM/ALCAM and VLA-4/VCAM-1 interactions play an important functional role in the early stages of metastasis seeding in the brain. Moreover, this work identifies a specific subset of ligand-receptor interactions that may yield new therapeutic and diagnostic targets for brain metastasis. PMID:24311639
Zinc: an underappreciated modulatory factor of brain function.
Marger, L; Schubert, C R; Bertrand, D
The divalent cation, zinc is the second most abundant metal in the human body and is indispensable for life. Zinc concentrations must however, be tightly regulated as deficiencies are associated with multiple pathological conditions while an excess can be toxic. Zinc plays an important role as a cofactor in protein folding and function, e.g. catalytic interactions, DNA recognition by zinc finger proteins and modulation ion channel activity. There are 24 mammalian proteins specific for zinc transport that are subdivided in two groups with opposing functions: ZnT proteins reduce cytosolic zinc concentration while ZIP proteins increase it. The mammalian brain contains a significant amount of zinc, with 5-15% concentrated in synaptic vesicles of glutamatergic neurons alone. Accumulated in these vesicles by the ZnT3 transporter, zinc is released into the synaptic cleft at concentrations from nanomolar at rest to high micromolar during active neurotransmission. Low concentrations of zinc modulate the activity of a multitude of voltage- or ligand-gated ion channels, indicating that this divalent cation must be taken into account in the analysis of the pathophysiology of CNS disorders including epilepsy, schizophrenia and Alzheimer's disease. In the context of the latest findings, we review the role of zinc in the central nervous system and discuss the relevance of the most recent association between the zinc transporter, ZIP8 and schizophrenia. An enhanced understanding of zinc transporters in the context of ion channel modulation may offer new avenues in identifying novel therapeutic entities that target neurological disorders. PMID:25130547
Restoration of function after brain damage using a neural prosthesis
Guggenmos, David J.; Azin, Meysam; Barbay, Scott; Mahnken, Jonathan D.; Dunham, Caleb; Mohseni, Pedram; Nudo, Randolph J.
Neural interface systems are becoming increasingly more feasible for brain repair strategies. This paper tests the hypothesis that recovery after brain injury can be facilitated by a neural prosthesis serving as a communication link between distant locations in the cerebral cortex. The primary motor area in the cerebral cortex was injured in a rat model of focal brain injury, disrupting communication between motor and somatosensory areas and resulting in impaired reaching and grasping abilities. After implantation of microelectrodes in cerebral cortex, a neural prosthesis discriminated action potentials (spikes) in premotor cortex that triggered electrical stimulation in somatosensory cortex continuously over subsequent weeks. Within 1 wk, while receiving spike-triggered stimulation, rats showed substantially improved reaching and grasping functions that were indistinguishable from prelesion levels by 2 wk. Post hoc analysis of the spikes evoked by the stimulation provides compelling evidence that the neural prosthesis enhanced functional connectivity between the two target areas. This proof-of-concept study demonstrates that neural interface systems can be used effectively to bridge damaged neural pathways functionally and promote recovery after brain injury. PMID:24324155
Joyce, Karen E; Hayasaka, Satoru; Laurienti, Paul J
Recently, we introduced a dynamic functional model of the human brain. This model, representing functional connectivity in the brain, is generated from subject-specific physiological data collected using functional magnetic resonance imaging (fMRI). The dynamics of this model are examined using agent-based modeling techniques, wherein a collection of binary agents are embedded as nodes in the network. This model is capable of producing a wide variety of complex behaviors. In this work, we use machine learning techniques to drive the model to produce desired behaviors. The solution space of the model is unreasonably large for a brute-force approach, but we demonstrate that genetic algorithms (GAs) are able to locate optimal model parameters within this space to achieve the desired behavior. We detail the design of a GA specifically suited for this model, and discuss the relevant issues that arise in GA design. Specifically, we explore several fitness functions to accurately quantify the suitability of each potential solution. We examine their strengths and weaknesses, and identify an optimal fitness function for this system. We validate the GA with the optimal fitness function by showing that it can drive the system to produce pre-defined behaviors. The ability of the model to produce pre-defined behaviors indicates that it may be possible to produce physiologically relevant outputs. The model may be very useful for studying the changes in brain dynamics due to neurological diseases or conditions. Additionally, this powerful dynamic brain model may be instrumental in many artificial intelligence settings. PMID:22846285
Two distinct forms of functional lateralization in the human brain
Gotts, Stephen J.; Jo, Hang Joon; Wallace, Gregory L.; Saad, Ziad S.; Cox, Robert W.; Martin, Alex
The hemispheric lateralization of certain faculties in the human brain has long been held to be beneficial for functioning. However, quantitative relationships between the degree of lateralization in particular brain regions and the level of functioning have yet to be established. Here we demonstrate that two distinct forms of functional lateralization are present in the left vs. the right cerebral hemisphere, with the left hemisphere showing a preference to interact more exclusively with itself, particularly for cortical regions involved in language and fine motor coordination. In contrast, right-hemisphere cortical regions involved in visuospatial and attentional processing interact in a more integrative fashion with both hemispheres. The degree of lateralization present in these distinct systems selectively predicted behavioral measures of verbal and visuospatial ability, providing direct evidence that lateralization is associated with enhanced cognitive ability. PMID:23959883
Functional Brain Network Classification With Compact Representation of SICE Matrices.
Zhang, Jianjia; Zhou, Luping; Wang, Lei; Li, Wanqing
Recently, a sparse inverse covariance estimation (SICE) technique has been employed to model functional brain connectivity. The inverse covariance matrix (SICE matrix in short) estimated for each subject is used as a representation of brain connectivity to discriminate Alzheimers disease from normal controls. However, we observed that direct use of the SICE matrix does not necessarily give satisfying discrimination, due to its high dimensionality and the scarcity of training subjects. Looking into this problem, we argue that the intrinsic dimensionality of these SICE matrices shall be much lower, considering 1) an SICE matrix resides on a Riemannian manifold of symmetric positive definiteness matrices, and 2) human brains share common patterns of connectivity across subjects. Therefore, we propose to employ manifold-based similarity measures and kernel-based PCA to extract principal connectivity components as a compact representation of brain network. Moreover, to cater for the requirement of both discrimination and interpretation in neuroimage analysis, we develop a novel preimage estimation algorithm to make the obtained connectivity components anatomically interpretable. To verify the efficacy of our method and gain insights into SICE-based brain networks, we conduct extensive experimental study on synthetic data and real rs-fMRI data from the ADNI dataset. Our method outperforms the comparable methods and improves the classification accuracy significantly. PMID:25667346
Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.
Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C; Aldana, Ileana; Teshiba, Terri M; Abaryan, Zvart; Al-Sharif, Noor B; Navarro, Linda; Tishler, Todd A; Altshuler, Lori; Bartzokis, George; Escobar, Javier I; Glahn, David C; Thompson, Paul M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Cantor, Rita M; Freimer, Nelson B; Bearden, Carrie E
Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain-behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure-function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning. PMID:25943422
Sleep restriction impairs blood-brain barrier function.
He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J; Wang, Yuping; Pan, Weihong
The blood-brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. PMID:25355222
Recruiting specialized macrophages across the borders to restore brain functions.
Corraliza, Inés
Although is well accepted that the central nervous system has an immune privilege protected by the blood-brain barrier (BBB) and maintained by the glia, it is also known that in homeostatic conditions, peripheral immune cells are able to penetrate to the deepest regions of brain without altering the structural integrity of the BBB. Nearly all neurological diseases, including degenerative, autoimmune or infectious ones, compromising brain functions, develop with a common pattern of inflammation in which macrophages and microglia activation have been regarded often as the "bad guys." However, recognizing the huge heterogeneity of macrophage populations and also the different expression properties of microglia, there is increasing evidence of alternative conditions in which these cells, if primed and addressed in the correct direction, could be essential for reparative and regenerative functions. The main proposal of this review is to integrate studies about macrophage's biology at the brain borders where the ultimate challenge is to penetrate through the BBB and contribute to change or even stop the course of disease. Thanks to the efforts made in the last century, this special wall is currently recognized as a highly regulated cooperative structure, in which their components form neurovascular units. This new scenario prompted us to review the precise cross-talk between the mind and body modes of immune response. PMID:25228859
Effect of pneumolysin on rat brain ciliary function: comparison of brain slices with cultured ependymal cells.
Hirst, R A; Rutman, A; Sikand, K; Andrew, P W; Mitchell, T J; O'Callaghan, C
This study compares two models for examining ependymal ciliary function: rat brain slices cut from the fourth ventricle and primary ependymal cells in culture. The cilia from both preparations were very reproducible; each preparation had cilia beating at a constant frequency of between 38 and 44 Hz. With the brain slices, ciliary stasis occurred after 5 d in culture. However, ependymal cells had fully functional cilia for up to 48 d in culture. The pneumococcal toxin, pneumolysin, caused a dose-dependent inhibition of cilia beat frequency within 15 min in both models. There were no significant differences in the mean log 50% inhibitory concentration (pIC50) slice = 0.65 +/- 0.05, equivalent to 4.4 hemolytic units (HU)/mL; cells = 0.57 +/- 0.14, equivalent to 3.7 HU/mL. There were also no significant differences in the mean Hill slope factors for the curves (slice = 1.4 +/- 0.05; cells = 1.6 +/- 0.4). These data demonstrate that both models can be used to examine the acute (15-min) effects of pneumolysin on cilia beat frequency. The main advantage of the primary ependymal culture model is that considerably more cultured ependymal cells (approximately 70%) are available, compared with the number of ependymal cells on the brain slices (approximately 2%), thus reducing the number of animals used. A pure ependymal culture was not achieved (approximately 30% of the cells were not ciliated). The increased survival time of the ependymal cells compared with the brain slices make cultured ependymal cells more useful for examining long-term ciliary function, whereas brain slices may be more useful for examining the interactions between ependymal and other nearby cells. PMID:10709739
Control channels in the brain and their influence on brain executive functions
NASA Astrophysics Data System (ADS)
Meng, Qinglei; Choa, Fow-Sen; Hong, Elliot; Wang, Zhiguang; Islam, Mohammad
In a computer network there are distinct data channels and control channels where massive amount of visual information are transported through data channels but the information streams are routed and controlled by intelligent algorithm through "control channels". Recent studies on cognition and consciousness have shown that the brain control channels are closely related to the brainwave beta (14-40 Hz) and alpha (7-13 Hz) oscillations. The high-beta wave is used by brain to synchronize local neural activities and the alpha oscillation is for desynchronization. When two sensory inputs are simultaneously presented to a person, the high-beta is used to select one of the inputs and the alpha is used to deselect the other so that only one input will get the attention. In this work we demonstrated that we can scan a person's brain using binaural beats technique and identify the individual's preferred control channels. The identified control channels can then be used to influence the subject's brain executive functions. In the experiment, an EEG measurement system was used to record and identify a subject's control channels. After these channels were identified, the subject was asked to do Stroop tests. Binaural beats was again used to produce these control-channel frequencies on the subject's brain when we recorded the completion time of each test. We found that the high-beta signal indeed speeded up the subject's executive function performance and reduced the time to complete incongruent tests, while the alpha signal didn't seem to be able to slow down the executive function performance.
Her versus his migraine: multiple sex differences in brain function and structure
Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David
Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a 'sex phenotype' in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs. PMID:22843414
Autism-specific maternal autoantibodies recognize critical proteins in developing brain
Cai, Long
Autism-specific maternal autoantibodies recognize critical proteins in developing brain D-Picciotto2,3,4 , IN Pessah2,3,7 and J Van de Water1,2,3 Autism spectrum disorders (ASDs of maternal autoantibody-related (MAR) autism. Exclusive reactivity to specific antigen combinations was noted
Characterization of the novel protein P9TLDR (temporal lobe down-regulated) with a brain-site-specific gene expression modality in Alzheimer's disease brain.
Yokota, Tomoko; Akatsu, Hiroyasu; Miyauchi, Takashi; Heese, Klaus
Alzheimer's disease (AD) is an aging-related neurodegenerative disorder characterized by irreversible loss of higher cognitive functions. The disease is characterized by the presence of amyloid plaques and neurofibrillary tangles (NFT). In the current study we isolated from an intra-cerebral brain-site-specific (AD temporal lobe vs. AD occipital lobe) polymerase chain reaction (PCR)-select cDNA suppression subtractive hybridization (PCR-cDNA-SSH) expression analysis the novel gene P9TLDR, potentially a microtubule-associated protein involved in neuronal migration, with an altered expression pattern: down-regulated in the temporal lobe cortex of early stage AD brains. In an in vitro AD-related cell model, amyloid-? peptide (A?)-treated neurons, reduced P9TLDR expression correlated with increased tau protein phosphorylation. In conclusion, interference with the P9TLDR signalling pathways might be a therapeutic strategy for the treatment of AD. PMID:23159938
Differences in brain function and changes with intervention in children with poor spelling and reading abilities.
Gebauer, Daniela; Fink, Andreas; Kargl, Reinhard; Reishofer, Gernot; Koschutnig, Karl; Purgstaller, Christian; Fazekas, Franz; Enzinger, Christian
Previous fMRI studies in English-speaking samples suggested that specific interventions may alter brain function in language-relevant networks in children with reading and spelling difficulties, but this research strongly focused on reading impaired individuals. Only few studies so far investigated characteristics of brain activation associated with poor spelling ability and whether a specific spelling intervention may also be associated with distinct changes in brain activity patterns. We here investigated such effects of a morpheme-based spelling intervention on brain function in 20 children with comparatively poor spelling and reading abilities using repeated fMRI. Relative to 10 matched controls, children with comparatively poor spelling and reading abilities showed increased activation in frontal medial and right hemispheric regions and decreased activation in left occipito-temporal regions prior to the intervention, during processing of a lexical decision task. After five weeks of intervention, spelling and reading comprehension significantly improved in the training group, along with increased activation in the left temporal, parahippocampal and hippocampal regions. Conversely, the waiting group showed increases in right posterior regions. Our findings could indicate an increased left temporal activation associated with the recollection of the new learnt morpheme-based strategy related to successful training. PMID:22693600
Functional magnetic resonance imaging can be used to explore tactile and nociceptive processing in the infant brain
Williams, Gemma; Fabrizi, Lorenzo; Meek, Judith; Jackson, Deborah; Tracey, Irene; Robertson, Nicola; Slater, Rebeccah; Fitzgerald, Maria
Aim Despite the importance of neonatal skin stimulation, little is known about activation of the newborn human infant brain by sensory stimulation of the skin. We carried out functional magnetic resonance imaging (fMRI) to assess the feasibility of measuring brain activation to a range of mechanical stimuli applied to the skin of neonatal infants. Methods We studied 19 term infants with a mean age of 13 days. Brain activation was measured in response to brushing, von Frey hair (vFh) punctate stimulation and, in one case, nontissue damaging pinprick stimulation of the plantar surface of the foot. Initial whole brain analysis was followed by region of interest analysis of specific brain areas. Results Distinct patterns of functional brain activation were evoked by brush and vFh punctate stimulation, which were reduced, but still present, under chloral hydrate sedation. Brain activation increased with increasing stimulus intensity. The feasibility of using pinprick stimulation in fMRI studies was established in one unsedated healthy full-term infant. Conclusion Distinct brain activity patterns can be measured in response to different modalities and intensities of skin sensory stimulation in term infants. This indicates the potential for fMRI studies in exploring tactile and nociceptive processing in the infant brain. PMID:25358870
Nuclear magnetic resonance imaging and spectroscopy of human brain function.
Shulman, R G; Blamire, A M; Rothman, D L; McCarthy, G
The techniques of in vivo magnetic resonance (MR) imaging and spectroscopy have been established over the past two decades. Recent applications of these methods to study human brain function have become a rapidly growing area of research. The development of methods using standard MR contrast agents within the cerebral vasculature has allowed measurements of regional cerebral blood volume (rCBV), which are activity dependent. Subsequent investigations linked the MR relaxation properties of brain tissue to blood oxygenation levels which are also modulated by consumption and blood flow (rCBF). These methods have allowed mapping of brain activity in human visual and motor cortex as well as in areas of the frontal lobe involved in language. The methods have high enough spatial and temporal sensitivity to be used in individual subjects. MR spectroscopy of proton and carbon-13 nuclei has been used to measure rates of glucose transport and metabolism in the human brain. The steady-state measurements of brain glucose concentrations can be used to monitor the glycolytic flux, whereas subsequent glucose metabolism--i.e., the flux into the cerebral glutamate pool--can be used to measure tricarboxylic acid cycle flux. Under visual stimulation the concentration of lactate in the visual cortex has been shown to increase by MR spectroscopy. This increase is compatible with an increase of anaerobic glycolysis under these conditions as earlier proposed from positron emission tomography studies. It is shown how MR spectroscopy can extend this understanding of brain metabolism. Images Fig. 1 Fig. 2 Fig. 3 PMID:8475050
Control of brain development, function, and behavior by the microbiome.
Sampson, Timothy R; Mazmanian, Sarkis K
Animals share an intimate and life-long partnership with a myriad of resident microbial species, collectively referred to as the microbiota. Symbiotic microbes have been shown to regulate nutrition and metabolism and are critical for the development and function of the immune system. More recently, studies have suggested that gut bacteria can impact neurological outcomes--altering behavior and potentially affecting the onset and/or severity of nervous system disorders. In this review, we highlight emerging evidence that the microbiome extends its influence to the brain via various pathways connecting the gut to the central nervous system. While understanding and appreciation of a gut microbial impact on neurological function is nascent, unraveling gut-microbiome-brain connections holds the promise of transforming the neurosciences and revealing potentially novel etiologies for psychiatric and neurodegenerative disorders. PMID:25974299
Reorganization of functionally connected brain subnetworks in high-functioning autism
Glerean, Enrico; Salmi, Juha; Kujala, Rainer; Lahnakoski, Juha; Roine, Ulrika; Nummenmaa, Lauri; Leppämäki, Sami; Wendt, Taina Nieminen-von; Tani, Pekka; Saramäki, Jari; Sams, Mikko; Jääskeläinen, Iiro P
Background: Previous functional connectivity studies have found both hypo- and hyper-connectivity in brains of individuals having autism spectrum disorder (ASD). Here we studied abnormalities in functional brain subnetworks in high-functioning individuals with ASD during free viewing of a movie containing social cues and interactions. Methods: Thirteen subjects with ASD and 13 matched-pair controls watched a 68 minutes movie during functional magnetic resonance imaging. For each subject, we computed Pearson`s correlation between haemodynamic time-courses of each pair of 6-mm isotropic voxels. From the whole-brain functional networks, we derived individual and group-level subnetworks using graph theory. Scaled inclusivity was then calculated between all subject pairs to estimate intersubject similarity of connectivity structure of each subnetwork. Additional 27 individuals with ASD from the ABIDE resting-state database were included to test the reproducibility of the results. Results: Between-group differences...
Brain basis of early parent–infant interactions: psychology, physiology, and in vivo functional neuroimaging studies
Swain, James E.; Lorberbaum, Jeffrey P.; Kose, Samet; Strathearn, Lane
Parenting behavior critically shapes human infants' current and future behavior. The parent–infant relationship provides infants with their first social experiences, forming templates of what they can expect from others and how to best meet others' expectations. In this review, we focus on the neurobiology of parenting behavior, including our own functional magnetic resonance imaging (fMRI) brain imaging experiments of parents. We begin with a discussion of background, perspectives and caveats for considering the neurobiology of parent–infant relationships. Then, we discuss aspects of the psychology of parenting that are significantly motivating some of the more basic neuroscience research. Following that, we discuss some of the neurohormones that are important for the regulation of social bonding, and the dysregulation of parenting with cocaine abuse. Then, we review the brain circuitry underlying parenting, proceeding from relevant rodent and nonhuman primate research to human work. Finally, we focus on a study-by-study review of functional neuroimaging studies in humans. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support aspects of parent response to infants, including the emotion, attention, motivation, empathy, decision-making and other thinking that are required to navigate the complexities of parenting. Specifically, infant stimuli activate basal forebrain regions, which regulate brain circuits that handle specific nurturing and caregiving responses and activate the brain's more general circuitry for handling emotions, motivation, attention, and empathy – all of which are crucial for effective parenting. We argue that an integrated understanding of the brain basis of parenting has profound implications for mental health. PMID:17355399
Sex-specific cognitive deficits and regional brain volume loss in mice exposed to chronic, sublethal hypoxia
Lan, Wen-Chun J.; Priestley, Matthew; Mayoral, Sonia R.; Tian, Lu; Shamloo, Mehrdad; Penn, Anna A.
Male sex is an independent risk factor for long-term neurologic deficits in human preterm infants. Using a chronic, sublethal hypoxia (CSH) mouse model of preterm brain injury, we recently demonstrated acute brain volume loss with an increased male susceptibility to hippocampal volume loss and hypomyelination. We now characterize the long-term, sex-specific effects of CSH on cognition and brain growth. Neonatal mice were treated with CSH for 8 days, raised in normoxia thereafter and underwent behavioral testing at 6 weeks of age. Behavioral assays sensitive to hippocampal function were chosen. CSH-treated males had impairments in associative learning, spatial memory and long-term social memory compared to control males. In contrast, CSH-treated females were less impaired. Persistent reductions in hippocampal and cerebellar volumes were found in adult CSH-treated males while regional brain volumes in CSH-treated females were indistinguishable from controls. Similar to human preterm infants, males exposed to hypoxia are especially vulnerable to short-term and long-term deficits in cognition and brain growth. PMID:21436761
Molecular Diversity of Glutamate Receptors and Implications for Brain Function
Shigetada Nakanishi
The glutamate receptors mediate excitatory neurotransmission in the brain and are important in memory acquisition, learning, and some neurodegenerative disorders. This receptor family is classified in three groups: the N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-kainate, and metabotropic receptors. Recent molecular studies have shown that many receptor subtypes exist in all three groups of the receptors and exhibit heterogeneity in function and expression
Automated Talairach Atlas labels for functional brain mapping
Jack L. Lancaster; Marty G. Woldorff; Lawrence M. Parsons; Mario Liotti; Catarina S. Freitas; Lacy Rainey; Peter V. Kochunov; Dan Nickerson; Shawn A. Mikiten; Peter T. Fox
An automated coordinate-based system to retrieve brain labels from the 1988 Talairach Atlas, called the Talairach Daemon (TD), was previously introduced (Lancaster et al., 1997). In the present study, the TD system and its 3-D database of labels for the 1988 Talairach atlas were tested for labeling of functional activation foci. TD system labels were compared with author-designated labels of
Frequency specificity of regional homogeneity in the resting-state human brain.
Song, Xiaopeng; Zhang, Yi; Liu, Yijun
Resting state-fMRI studies have found that the inter-areal correlations in cortical networks concentrate within ultra-low frequencies (0.01-0.04 Hz) while long-distance connections within subcortical networks distribute over a wider frequency range (0.01-0.14 Hz). However, the frequency characteristics of regional homogeneity (ReHo) in different areas are still unclear. To examine the ReHo properties in different frequency bands, a data-driven method, Empirical Mode Decomposition (EMD), was adopted to decompose the time series of each voxel into several components with distinct frequency bands. ReHo values in each of the components were then calculated. Our results showed that ReHo in cortical areas were higher and more frequency-dependent than those in the subcortical regions. BOLD oscillations of 0.02-0.04 Hz mainly contributed to the cortical ReHo, whereas the ReHo in limbic areas involved a wider frequency range and were dominated by higher-frequency BOLD oscillations (>0.08 Hz). The frequency characteristics of ReHo are distinct between different parts of the striatum, with the frequency band of 0.04-0.1 Hz contributing the most to ReHo in caudate nucleus, and oscillations lower than 0.02 Hz contributing more to ReHo in putamen. The distinct frequency-specific ReHo properties of different brain areas may arise from the assorted cytoarchitecture or synaptic types in these areas. Our work may advance the understanding of the neural-physiological basis of local BOLD activities and the functional specificity of different brain regions. PMID:24466256
Detecting Brain State Changes via Fiber-Centered Functional Connectivity Analysis
Li, Xiang; Lim, Chulwoo; Li, Kaiming; Guo, Lei; Liu, Tianming
Diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) have been widely used to study structural and functional brain connectivity in recent years. A common assumption used in many previous functional brain connectivity studies is the temporal stationarity. However, accumulating literature evidence has suggested that functional brain connectivity is under temporal dynamic changes in different time scales. In this paper, a novel and intuitive approach is proposed to model and detect dynamic changes of functional brain states based on multimodal fMRI/DTI data. The basic idea is that functional connectivity patterns of all fiber-connected cortical voxels are concatenated into a descriptive functional feature vector to represent the brain's state, and the temporal change points of brain states are decided by detecting the abrupt changes of the functional vector patterns via the sliding window approach. Our extensive experimental results have shown that meaningful brain state change points can be detected in task-based fMRI/DTI, resting state fMRI/DTI, and natural stimulus fMRI/DTI data sets. Particularly, the detected change points of functional brain states in task-based fMRI corresponded well to the external stimulus paradigm administered to the participating subjects, thus partially validating the proposed brain state change detection approach. The work in this paper provides novel perspective on the dynamic behaviors of functional brain connectivity and offers a starting point for future elucidation of the complex patterns of functional brain interactions and dynamics. PMID:22941508
IR Principles for Content-based Indexing and Retrieval of Functional Brain Images
IR Principles for Content-based Indexing and Retrieval of Functional Brain Images Bing Bai, Paul Indexing(LSI)) to content-based brain image retrieval. Our results show that efficient and accurate of a "library of brain images", which implies not only a repository of brain images, but also efficient search
Brain tissue- and region-specific abnormalities on volumetric MRI scans in 21 patients with Bardet-Biedl syndrome (BBS)
Background Bardet-Biedl syndrome (BBS) is a heterogeneous human disorder inherited in an autosomal recessive pattern, and characterized by the primary findings of obesity, polydactyly, hypogonadism, and learning and behavioural problems. BBS mouse models have a neuroanatomical phenotype consisting of third and lateral ventriculomegaly, thinning of the cerebral cortex, and reduction in the size of the corpus striatum and hippocampus. These abnormalities raise the question of whether humans with BBS have a characteristic morphologic brain phenotype. Further, although behavioral, developmental, neurological and motor defects have been noted in patients with BBS, to date, there are limited reports of brain findings in BBS. The present study represents the largest systematic evaluation for the presence of structural brain malformations and/or progressive changes, which may contribute to these functional problems. Methods A case-control study of 21 patients, most aged 13-35 years, except for 2 patients aged 4 and 8 years, who were diagnosed with BBS by clinical criteria and genetic analysis of known BBS genes, and were evaluated by qualitative and volumetric brain MRI scans. Healthy controls were matched 3:1 by age, sex and race. Statistical analysis was performed using SAS language with SAS STAT procedures. Results All 21 patients with BBS were found to have statistically significant region- and tissue-specific patterns of brain abnormalities. There was 1) normal intracranial volume; 2) reduced white matter in all regions of the brain, but most in the occipital region; 3) preserved gray matter volume, with increased cerebral cortex volume in only the occipital lobe; 4) reduced gray matter in the subcortical regions of the brain, including the caudate, putamen and thalamus, but not in the cerebellum; and 5) increased cerebrospinal fluid volume. Conclusions There are distinct and characteristic abnormalities in tissue- and region- specific volumes of the brain in patients with BBS, which parallel the findings, described in BBS mutant mouse models. Some of these brain abnormalities may be progressive and associated with the reported neurological and behavioral problems. Further future correlation of these MRI scan findings with detailed neurologic and neuropsychological exams together with genotype data will provide better understanding of the pathophysiology of BBS. PMID:21794117
Dynamic representations and generative models of brain function.
Friston, K J; Price, C J
The main point made in this article is that the representational capacity and inherent function of any neuron, neuronal population or cortical area is dynamic and context-sensitive. This adaptive and contextual specialisation is mediated by functional integration or interactions among brain systems with a special emphasis on backwards or top-down connections. The critical notion is that neuronal responses, in any given cortical area, can represent different things at different times. Our argument is developed under the perspective of generative models of functional brain architectures, where higher-level systems provide a prediction of the inputs to lower-level regions. Conflict between the two is resolved by changes in the higher-level representations, driven by the resulting error in lower regions, until the mismatch is 'cancelled'. In this model the specialisation of any region is determined both by bottom-up driving inputs and by top-down predictions. Specialisation is therefore not an intrinsic property of any region but depends on both forward and backward connections with other areas. Because these other areas have access to the context in which the inputs are generated they are in a position to modulate the selectivity or specialisation of lower areas. The implications for 'classical' models (e.g., classical receptive fields in electrophysiology, classical specialisation in neuroimaging and connectionism in cognitive models) are severe and suggest these models provide incomplete accounts of real brain architectures. Generative models represent a far more plausible framework for understanding selective neurophysiological responses and how representations are constructed in the brain. PMID:11287132
Imaging the ADHD brain: disorder-specificity, medication effects and clinical translation.
Rubia, Katya; Alegria, Analucia; Brinson, Helen
A plethora of magnetic resonance imaging studies have shown that ADHD is characterized by multiple functional and structural neural network abnormalities beyond the classical fronto-striatal model, including fronto-parieto-temporal, fronto-cerebellar and even fronto-limbic networks. There is evidence for a maturational delay in brain structure development which likely extends to brain function and structural and functional connectivity, but this needs corroboration by longitudinal imaging studies. Dysfunction of the ventrolateral prefrontal cortex seems to be more pronounced relative to other pediatric disorders and is also the most consistent target of acute psychostimulant medication. Future studies are likely to focus on using neuroimaging for clinical translation such as for individual diagnostic and prognostic classification and as a neurotherapy to reverse brain function abnormalities. PMID:24738703
28 CFR 0.101 - Specific functions.
Code of Federal Regulations, 2010 CFR
28 Judicial Administration 1 2010-07-01 2010-07-01... Section 0.101 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Drug Enforcement Administration § 0.101 Specific...
Effect of disease and recovery on functional anatomy in brain tumor patients: insights from functional MRI and diffusion tensor imaging
Abd-El-Barr, Muhammad M; Saleh, Emam; Huang, Raymond Y; Golby, Alexandra J
Patients with brain tumors provide a unique opportunity to understand functional brain plasticity. Using advanced imaging techniques, such as functional MRI and diffusion tensor imaging, we have gained tremendous knowledge of brain tumor behavior, transformation, infiltration and destruction of nearby structures. Using these advanced techniques as an adjunct with more proven techniques, such as direct cortical stimulation, intraoperative navigation and advanced microsurgical techniques, we now are able to better formulate safer resection trajectories, perform larger resections at reduced risk and better counsel patients and their families about possible complications. Brain mapping in patients with brain tumors and other lesions has shown us that the old idea of fixed function of the adult cerebral cortex is not entirely true. Improving care for patients with brain lesions in the future will depend on better understanding of the functional organization and plasticity of the adult brain. Advanced noninvasive brain imaging will undoubtedly play a role in advancing this understanding. PMID:24660024
Brain functional plasticity associated with the emergence of expertise in extreme language control.
Hervais-Adelman, Alexis; Moser-Mercer, Barbara; Golestani, Narly
We used functional magnetic resonance imaging (fMRI) to longitudinally examine brain plasticity arising from long-term, intensive simultaneous interpretation training. Simultaneous interpretation is a bilingual task with heavy executive control demands. We compared brain responses observed during simultaneous interpretation with those observed during simultaneous speech repetition (shadowing) in a group of trainee simultaneous interpreters, at the beginning and at the end of their professional training program. Age, sex and language-proficiency matched controls were scanned at similar intervals. Using multivariate pattern classification, we found distributed patterns of changes in functional responses from the first to second scan that distinguished the interpreters from the controls. We also found reduced recruitment of the right caudate nucleus during simultaneous interpretation as a result of training. Such practice-related change is consistent with decreased demands on multilingual language control as the task becomes more automatized with practice. These results demonstrate the impact of simultaneous interpretation training on the brain functional response in a cerebral structure that is not specifically linguistic, but that is known to be involved in learning, in motor control, and in a variety of domain-general executive functions. Along with results of recent studies showing functional and structural adaptations in the caudate nuclei of experts in a broad range of domains, our results underline the importance of this structure as a central node in expertise-related networks. PMID:25869858
Functional and Structural Brain Plasticity Enhanced by Motor and Cognitive Rehabilitation in Multiple Sclerosis
Prosperini, Luca; Piattella, Maria Cristina
Rehabilitation is recognized to be important in ameliorating motor and cognitive functions, reducing disease burden, and improving quality of life in patients with multiple sclerosis (MS). In this systematic review, we summarize the existing evidences that motor and cognitive rehabilitation may enhance functional and structural brain plasticity in patients with MS, as assessed by means of the most advanced neuroimaging techniques, including diffusion tensor imaging and task-related and resting-state functional magnetic resonance imaging (MRI). In most cases, the rehabilitation program was based on computer-assisted/video game exercises performed in either an outpatient or home setting. Despite their heterogeneity, all the included studies describe changes in white matter microarchitecture, in task-related activation, and/or in functional connectivity following both task-oriented and selective training. When explored, relevant correlation between improved function and MRI-detected brain changes was often found, supporting the hypothesis that training-induced brain plasticity is specifically linked to the trained domain. Small sample sizes, lack of randomization and/or an active control group, as well as missed relationship between MRI-detected changes and clinical performance, are the major drawbacks of the selected studies. Knowledge gaps in this field of research are also discussed to provide a framework for future investigations. PMID:26064692
The effects of methylphenidate on whole brain intrinsic functional connectivity.
Mueller, Sophia; Costa, Anna; Keeser, Daniel; Pogarell, Oliver; Berman, Albert; Coates, Ute; Reiser, Maximilian F; Riedel, Michael; Möller, Hans-Jürgen; Ettinger, Ulrich; Meindl, Thomas
Methylphenidate (MPH) is an indirect dopaminergic and noradrenergic agonist that is used to treat attention deficit hyperactivity disorder and that has shown therapeutic potential in neuropsychiatric diseases such as depression, dementia, and Parkinson's disease. While effects of MPH on task-induced brain activation have been investigated, little is known about how MPH influences the resting brain. To investigate the effects of 40 mg of oral MPH on intrinsic functional connectivity, we used resting state fMRI in 54 healthy male subjects in a double-blind, randomized, placebo-controlled study. Functional connectivity analysis employing ICA revealed seven resting state networks (RSN) of interest. Connectivity strength between the dorsal attention network and the thalamus was increased after MPH intake. Other RSN located in association cortex areas, such as the left and right frontoparietal networks and the executive control network, showed MPH-induced connectivity increase to sensory-motor and visual cortex regions and connectivity decrease to cortical and subcortical components of cortico-striato-thalamo-cortical circuits (CST). RSN located in sensory-motor cortex areas showed the opposite pattern with MPH-induced connectivity increase to CST components and connectivity decrease to sensory-motor and visual cortex regions. Our results provide evidence that MPH does not only alter intrinsic connectivity between brain areas involved in sustained attention, but that it also induces significant changes in the cortico-cortical and cortico-subcortical connectivity of many other cognitive and sensory-motor RSN. PMID:24862742
Functional transcranial brain imaging by optical-resolution photoacoustic microscopy
NASA Astrophysics Data System (ADS)
Hu, Song; Maslov, Konstantin; Tsytsarev, Vassiliy; Wang, Lihong V.
Optical-resolution photoacoustic microscopy (OR-PAM) is applied to functional brain imaging in living mice. A near-diffraction-limited bright-field optical illumination is employed to achieve micrometer lateral resolution, and a dual-wavelength measurement is utilized to extract the blood oxygenation information. The variation in hemoglobin oxygen saturation (sO2) along vascular branching has been imaged in a precapillary arteriolar tree and a postcapillary venular tree, respectively. To the best of our knowledge, this is the first report on in vivo volumetric imaging of brain microvascular morphology and oxygenation down to single capillaries through intact mouse skulls. It is anticipated that: (i) chronic imaging enabled by this minimally invasive procedure will advance the study of cortical plasticity and neurological diseases; (ii) revealing the neuroactivity-dependent changes in hemoglobin concentration and oxygenation will facilitate the understanding of neurovascular coupling at the capillary level; and (iii) combining functional OR-PAM and high-resolution blood flowmetry will have the potential to explore cellular pathways of brain energy metabolism.
Heritability of human brain functioning as assessed by electroencephalography
Beijsterveldt, C.E.M. van; Geus, E.J.C. de; Boomsma, D.I. [and others
To study the genetic and environmental contributions to individual differences in CNS functioning, the electroencephalogram (EEG) was measured in 213 twin pairs age 16 years. EEG was measured in 91 MZ and 122 DZ twins. To quantify sex differences in the genetic architecture, EEG was measured in female and male same-sex twins and in opposite-sex twins. EEG was recorded on 14 scalp positions during quiet resting with eyes closed. Spectral powers were calculated for four frequency bands: delta, theta, alpha, and beta. Twin correlations pointed toward high genetic influences for all these powers and scalp locations. Model fitting confirmed these findings; the largest part of the variance of the EEG is explained by additive genetic factors. The averaged heritabilities for the delta, theta, alpha, and beta frequencies was 76%, 89%, 89%, and 86%, respectively. Multivariate analyses suggested that the same genes for EEG alpha rhythm were expressed in different brain areas in the left and right hemisphere. This study shows that brain functioning, as indexed by rhythmic brain-electrical activity, is one of the most heritable characteristics in humans. 44 refs., 5 figs., 4 tabs.
Lateralization of Cognitive Functions in Aphasia after Right Brain Damage
Ha, Ji-Wan; Hwang, Yu Mi; Sim, Hyunsub
Purpose The lateralization of cognitive functions in crossed aphasia in dextrals (CAD) has been explored and compared mainly with cases of aphasia with left hemisphere damage. However, comparing the neuropsychological aspects of CAD and aphasia after right brain damage in left-handers (ARL) could potentially provide more insights into the effect of a shift in the laterality of handedness or language on other cognitive organization. Thus, this case study compared two cases of CAD and one case of ARL. Materials and Methods The following neuropsychological measures were obtained from three aphasic patients with right brain damage (two cases of CAD and one case of ARL); language, oral and limb praxis, and nonverbal cognitive functions (visuospatial neglect and visuospatial construction). Results All three patients showed impaired visuoconstructional abilities, whereas each patient showed a different level of performances for oral and limb praxis, and visuospatial neglect. Conclusion Based on the analysis of these three aphasic patients' performances, we highlighted the lateralization of language, handedness, oral and limb praxis, visuospatial neglect and visuospatial constructive ability in aphasic patients with right brain damage. PMID:22476990
Affect and the Brain's Functional Organization: A Resting-State Connectivity Approach
Rohr, Christiane S.; Okon-Singer, Hadas; Craddock, R. Cameron; Villringer, Arno; Margulies, Daniel S.
The question of how affective processing is organized in the brain is still a matter of controversial discussions. Based on previous initial evidence, several suggestions have been put forward regarding the involved brain areas: (a) right-lateralized dominance in emotional processing, (b) hemispheric dominance according to positive or negative valence, (c) one network for all emotional processing and (d) region-specific discrete emotion matching. We examined these hypotheses by investigating intrinsic functional connectivity patterns that covary with results of the Positive and Negative Affective Schedule (PANAS) from 65 participants. This approach has the advantage of being able to test connectivity rather than activation, and not requiring a potentially confounding task. Voxelwise functional connectivity from 200 regions-of-interest covering the whole brain was assessed. Positive and negative affect covaried with functional connectivity involving a shared set of regions, including the medial prefrontal cortex, the anterior cingulate, the visual cortex and the cerebellum. In addition, each affective domain had unique connectivity patterns, and the lateralization index showed a right hemispheric dominance for negative affect. Therefore, our results suggest a predominantly right-hemispheric network with affect-specific elements as the underlying organization of emotional processes. PMID:23935850
Resolving Anatomical and Functional Structure in Human Brain Organization: Identifying Mesoscale Organization in Weighted Network Representations
Lohse, Christian; Bassett, Danielle S.; Lim, Kelvin O.; Carlson, Jean M.
Human brain anatomy and function display a combination of modular and hierarchical organization, suggesting the importance of both cohesive structures and variable resolutions in the facilitation of healthy cognitive processes. However, tools to simultaneously probe these features of brain architecture require further development. We propose and apply a set of methods to extract cohesive structures in network representations of brain connectivity using multi-resolution techniques. We employ a combination of soft thresholding, windowed thresholding, and resolution in community detection, that enable us to identify and isolate structures associated with different weights. One such mesoscale structure is bipartivity, which quantifies the extent to which the brain is divided into two partitions with high connectivity between partitions and low connectivity within partitions. A second, complementary mesoscale structure is modularity, which quantifies the extent to which the brain is divided into multiple communities with strong connectivity within each community and weak connectivity between communities. Our methods lead to multi-resolution curves of these network diagnostics over a range of spatial, geometric, and structural scales. For statistical comparison, we contrast our results with those obtained for several benchmark null models. Our work demonstrates that multi-resolution diagnostic curves capture complex organizational profiles in weighted graphs. We apply these methods to the identification of resolution-specific characteristics of healthy weighted graph architecture and altered connectivity profiles in psychiatric disease. PMID:25275860
Testing group differences in brain functional connectivity: using correlations or partial correlations?
Kim, Junghi; Wozniak, Jeffrey R; Mueller, Bryon A; Pan, Wei
Resting-state functional magnetic resonance imaging allows one to study brain functional connectivity, partly motivated by evidence that patients with complex disorders, such as Alzheimer's disease, may have altered functional brain connectivity patterns as compared with healthy subjects. A functional connectivity network describes statistical associations of the neural activities among distinct and distant brain regions. Recently, there is a major interest in group-level functional network analysis; however, there is a relative lack of studies on statistical inference, such as significance testing for group comparisons. In particular, it is still debatable which statistic should be used to measure pairwise associations as the connectivity weights. Many functional connectivity studies have used either (full or marginal) correlations or partial correlations for pairwise associations. This article investigates the performance of using either correlations or partial correlations for testing group differences in brain connectivity, and how sparsity levels and topological structures of the connectivity would influence statistical power to detect group differences. Our results suggest that, in general, testing group differences in networks deviates from estimating networks. For example, high regularization in both covariance matrices and precision matrices may lead to higher statistical power; in particular, optimally selected regularization (e.g., by cross-validation or even at the true sparsity level) on the precision matrices with small estimation errors may have low power. Most importantly, and perhaps surprisingly, using either correlations or partial correlations may give very different testing results, depending on which of the covariance matrices and the precision matrices are sparse. Specifically, if the precision matrices are sparse, presumably and arguably a reasonable assumption, then using correlations often yields much higher powered and more stable testing results than using partial correlations; the conclusion is reversed if the covariance matrices, not the precision matrices, are sparse. These results may have useful implications to future studies on testing functional connectivity differences. PMID:25492804
Regulation of sup 35 S-TBPS binding by bicuculline is region specific in rat brain
Peris, J.; Shawley, A.; Dawson, R.; Abendschein, K.H. (Univ. of Florida Health Science Center, Gainesville (United States))
The allosteric regulation of specific {sup 35}S-TBPS binding to the convulsant site on the GABA{sub A} receptor/chloride (Cl{sup {minus}}) ionophore complex was studied in various brain regions in an attempt to characterize regional heterogeneity of the protein subunits forming the complex. Bicuculline methiodide (BIC), a GABA{sub A} antagonist, enhanced binding in cortex (CTX), substantia nigra (SN) and cerebellum (CBL), inhibited binding in inferior colliculus (IC) and did not affect binding in superior colliculus (SC). Similar results were found in CBL and IC using SR-95531, another GABA{sub A} antagonist. The levels of endogenous GABA in the different tissue samples could not account for the regional differences in binding. When the functional regulation of these receptors was measured using {sup 36}Cl{sup {minus}} uptake in microsomes, muscimol-stimulated uptake was completely blocked by BIC in CBL and IC but was not affected by BIC in SC. Additionally, picrotoxin completely blocked muscimol-stimulated uptake in CBL but had no effect in IC or SC. These findings provide a functional basis for regional heterogeneity of GABA{sub A} receptor.
Dynamic mapping of the brain in substance-dependent individuals: functional magnetic resonance imaging.
Mel'nikov, M E; Shtark, M B; Korostyshevskaya, A M; Sevelov, A A; Petrovskii, E D; Pokrovskii, M A; Rezakova, M V; Ganenko, Yu A; Il'ichevskii, I N; Mazhirina, K G; Mezentseva, M P; Kosykh, E P
Functional magnetic resonance imaging can be used to study numerous brain dysfunctions, including disorders of the self, in substance-dependent individuals. The self as the sum of human concepts about oneself is regulated by the brain system close to the default mode network: the medial prefrontal cortex, posterior cingulated gyrus, and some parietal regions. However, the composition and activity of this system in mental disease, specifically, in substance addiction, are virtually not described. Our study showed that self-appraisal task in addicts activates the superior frontal cortex, cuneus, precuneus, angular gyrus, and posterior cingulated cortex. The involvement of the parietal (postcentral and supramarginal gyri) and temporal (superior temporal and Heschl's gyri) sensory areas is diminished. Hence, published data on the involvement of the cingulate cortex and prefrontal cortex in functional regulation of the self are confirmed. Activation-deactivation patterns in the parietal and temporal regions differ significantly from the previous descriptions. PMID:25432285
Anesthetic effects of propofol in the healthy human brain: functional imaging evidence.
Song, Xiao-xing; Yu, Bu-wei
Functional imaging methods, including positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), have become important tools for studying how anesthetic drugs act in the human brain to induce the state of general anesthesia. Recent imaging studies using fMRI and PET techniques have demonstrated the regional effects of propofol on the brain. However, the pharmacological mechanism of the action of propofol in the intact human central nervous system is unclear. To explore the possible action targets of propofol in the human brain, a systematic review of the literature was performed. The literature search was performed with limiting factors of "propofol," "functional imaging," "positron emission tomography", and "functional magnetic resonance imaging" from 1966 to July 2013 (using Medline, EMBASE, CINAHL and hand searches of references). Studies meeting the inclusion criteria were reviewed and critiqued for the purpose of this literature research. Eighteen researches meeting the inclusion criteria were reviewed in terms of the appropriateness of valuation technique. In the unconscious state, propofol sharply reduces the regional glucose metabolism rate (rGMR) and regional cerebral blood flow (rCBF) in all brain regions, particularly in the thalamus. However, GMR, such as in the occipital, temporal, and frontal lobes, was obviously decreased at a sedative dosage of propofol, whereas, changes in the thalamus were not obvious. Using fMRI, several studies observed a decrease of connectivity of the thalamus versus an increase of connectivity within the pons of the brainstem during propofol-induced mild sedation. During deep sedation, propofol preserves cortical sensory reactivity, the specific thalamocortical network is moderately affected, whereas the nonspecific thalamocortical network is severely suppressed. In contrast, several recent fMRI studies are consistent on the systemic decreased effects of propofol in the frontoparietal network. Accumulating evidence suggest that propofol-induced unconsciousness is associated with a global metabolic and vascular depression in the human brain and especially with a significant reduction in the thalamocortical network and the frontoparietal network. PMID:25056258
Automatic Tissue Segmentation of Neonate Brain MR Images with Subject-specific Atlases
Cherel, Marie; Budin, Francois; Prastawa, Marcel; Gerig, Guido; Lee, Kevin; Buss, Claudia; Lyall, Amanda; Consing, Kirsten Zaldarriaga; Styner, Martin
Automatic tissue segmentation of the neonate brain using Magnetic Resonance Images (MRI) is extremely important to study brain development and perform early diagnostics but is challenging due to high variability and inhomogeneity in contrast throughout the image due to incomplete myelination of the white matter tracts. For these reasons, current methods often totally fail or give unsatisfying results. Furthermore, most of the subcortical midbrain structures are misclassified due to a lack of contrast in these regions. We have developed a novel method that creates a probabilistic subject-specific atlas based on a population atlas currently containing a number of manually segmented cases. The generated subject-specific atlas is sharp and adapted to the subject that is being processed. We then segment brain tissue classes using the newly created atlas with a single-atlas expectation maximization based method. Our proposed method leads to a much lower failure rate in our experiments. The overall segmentation results are considerably improved when compared to using a non-subject-specific, population average atlas. Additionally, we have incorporated diffusion information obtained from Diffusion Tensor Images (DTI) to improve the detection of white matter that is not visible at this early age in structural MRI (sMRI) due to a lack of myelination. Although this necessitates the acquisition of an additional sequence, the diffusion information improves the white matter segmentation throughout the brain, especially for the mid-brain structures such as the corpus callosum and the internal capsule.
Irradiation of rat brain reduces P-glycoprotein expression and function
J. Bart; W. B. Nagengast; R. P. Coppes; T. D. Wegman; H J M Groen; W. Vaalburg; E. G. F. de Vries; N. H. Hendrikse; EGE de Vries
The blood–brain barrier (BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P-glycoprotein (P-gp), expressed on brain capillary endothelial cells, is part of the BBB. P-gp expression on capillary endothelium decreases 5 days after brain irradiation, which may reduce P-gp function and increase brain levels of P-gp substrates. To elucidate whether radiation therapy reduces
Sleep-disordered breathing: effects on brain structure and function
Harper, Ronald M.; Kumar, Rajesh; Ogren, Jennifer A.; Macey, Paul M.
Sleep-disordered breathing is accompanied by neural injury that affects a wide range of physiological systems which include processes for sensing chemoreception and airflow, driving respiratory musculature, timing circuitry for coordination of breathing patterning, and integration of blood pressure mechanisms with respiration. The damage also occurs in regions mediating emotion and mood, as well as areas regulating memory and cognitive functioning, and appears in structures that serve significant glycemic control processes. The injured structures include brain areas involved in hormone release and action of major neurotransmitters, including those playing a role in depression. The injury is reflected in a range of structural magnetic resonance procedures, and also appears as functional distortions of evoked activity in brain areas mediating vital autonomic and breathing functions. The damage is preferentially unilateral, and includes axonal projections; the asymmetry of the injury poses unique concerns for sympathetic discharge and potential consequences for arrhythmia. Sleep-disordered breathing should be viewed as a condition that includes central nervous system injury and impaired function; the processes underlying injury remain unclear. PMID:23643610
Functional interactions between intrinsic brain activity and behavior.
Sadaghiani, Sepideh; Kleinschmidt, Andreas
The brain continuously maintains a remarkably high level of intrinsic activity. This activity is non-stationary and its dynamics reveal highly structured patterns across several spatial scales, from fine-grained functional architecture in sensory cortices to large-scale networks. The mechanistic function of this activity is only poorly understood. The central goal of the current review is to provide an integrated summary of recent studies on structure, dynamics and behavioral consequences of spontaneous brain activity. In light of these empirical observations we propose that the structure of ongoing activity and its itinerant nature can be understood as an indispensible memory system modeling the statistical structure of the world. We review the dynamic properties of ongoing activity, and how they are malleable over short to long temporal scales that permit adapting over a range of short- to long-term cognitive challenges. We conclude by reviewing how the functional significance of ongoing activity manifests in its impact on human action, perception, and higher cognitive function. PMID:23643921
Hubs of brain functional networks are radically reorganized in comatose patients
Boyer, Edmond
Hubs of brain functional networks are radically reorganized in comatose patients S. Achard , C Human brain networks have topological properties in common with many other complex systems, prompting the question: what aspects of brain network organization are critical for distinctive functional properties
Multivariate examination of brain abnormality using both structural and functional MRI
Yong Fan; Hengyi Rao; Hallam Hurt; Joan Giannetta; Marc Korczykowski; David Shera; Brian B. Avants; James C. Gee; Jiongjiong Wang; Dinggang Shen
A multivariate classification approach has been presented to examine the brain abnormalities, i.e., due to prenatal cocaine exposure, using both structural and functional brain images. First, a regional statistical feature extraction scheme was adopted to capture discriminative features from voxel-wise morphometric and functional representations of brain images, in order to reduce the dimensionality of the features used for classification, as
Iron in Brain Function and Dysfunction with Emphasis on Parkinson's Disease
M. B. H. Youdim; D. Ben-Shachar; P. Riederer
Metals such as lead, zinc, copper, aluminum and manganese have been implicated in neuropsychiatric disorders. However, until fairly recently the role of iron in brain function was rather obscure, because little attention was paid to its metabolism in the brain. It is now apparent that maintenance of brain iron homoeostasis is important for the normal functioning of his organ. Most
Individual differences in general intelligence correlate with brain function during nonreasoning tasks
Richard J. Haier; Nathan S. White; Michael T. Alkire
Brain imaging can help identify the functional neuroanatomy of general intelligence (i.e., "g") and indicate how brain areas salient to g relate to information processing. An important question is whether individual differences in g among subjects are related to brain function even when nonreasoning tasks are studied. If so, this would imply that individuals with high g scores may process
Adrenomedullin Improves the Blood–Brain Barrier Function Through the Expression of Claudin-5
Masaru Honda; Shinsuke Nakagawa; Kentaro Hayashi; Naoki Kitagawa; Keisuke Tsutsumi; Izumi Nagata; Masami Niwa
Summary 1. Aims: Brain vascular endothelial cells secret Adrenomedullin (AM) has multifunctional biological properties. AM affects cerebral blood flow and blood–brain barrier (BBB) function. We studied the role of AM on the permeability and tight junction proteins of brain microvascular endothelial cells (BMEC).2. Methods: BMEC were isolated from rats and a BBB in vitro model was generated. The barrier functions were
HIV and Aging Independently Affect Brain Function as Measured by Functional Magnetic Resonance Imaging
Ances, Beau M.; Vaida, Florin; Yeh, Melinda J.; Liang, Christine L.; Buxton, Richard B.; Letendre, Scott; McCutchan, J. Allen; Ellis, Ronald J.
We investigated interactions between HIV and aging on brain function demands using functional magnetic resonance imaging (fMRI). A multiple regression model studied the association and interaction between fMRI measures, HIV serostatus, and age for 26 HIV infected (HIV+) and 25 seronegative (HIV?) subjects. While HIV serostatus and age independently affected fMRI measures, no interaction occurred. Functional brain demands in HIV+ subjects were equivalent to ~15–20 year older HIV? subjects. Frailty parallels between HIV and aging could result from continued immunological challenges depleting resources and triggering increased metabolic demands. fMRI could be a non-invasive biomarker to assess HIV in the brain. PMID:20047503
Patient-specific model of brain deformation: application to medical image registration.
Wittek, Adam; Miller, Karol; Kikinis, Ron; Warfield, Simon K
This contribution presents finite element computation of the deformation field within the brain during craniotomy-induced brain shift. The results were used to illustrate the capabilities of non-linear (i.e. accounting for both geometric and material non-linearities) finite element analysis in non-rigid registration of pre- and intra-operative magnetic resonance images of the brain. We used patient-specific hexahedron-dominant finite element mesh, together with realistic material properties for the brain tissue and appropriate contact conditions at boundaries. The model was loaded by the enforced motion of nodes (i.e. through prescribed motion of a boundary) at the brain surface in the craniotomy area. We suggest using explicit time-integration scheme for discretised equations of motion, as the computational times are much shorter and accuracy, for practical purposes, the same as in the case of implicit integration schemes. Application of the computed deformation field to register (i.e. align) the pre-operative images with the intra-operative ones indicated that the model very accurately predicts the displacements of the tumour and the lateral ventricles even for limited information about the brain surface deformation. The prediction accuracy improves when information about deformation of not only exposed (during craniotomy) but also unexposed parts of the brain surface is used when prescribing loading. However, it appears that the accuracy achieved using information only about the deformation of the exposed surface, that can be determined without intra-operative imaging, is acceptable. The presented results show that non-linear biomechanical models can complement medical image processing techniques when conducting non-rigid registration. Important advantage of such models over the previously used linear ones is that they do not require unrealistic assumptions that brain deformations are infinitesimally small and brain stress-strain relationship is linear. PMID:16678834
Highly automated computer-aided diagnosis of neurological disorders using functional brain imaging
NASA Astrophysics Data System (ADS)
Spetsieris, P. G.; Ma, Y.; Dhawan, V.; Moeller, J. R.; Eidelberg, D.
We have implemented a highly automated analytical method for computer aided diagnosis (CAD) of neurological disorders using functional brain imaging that is based on the Scaled Subprofile Model (SSM). Accurate diagnosis of functional brain disorders such as Parkinson's disease is often difficult clinically, particularly in early stages. Using principal component analysis (PCA) in conjunction with SSM on brain images of patients and normals, we can identify characteristic abnormal network covariance patterns which provide a subject dependent scalar score that not only discriminates a particular disease but also correlates with independent measures of disease severity. These patterns represent disease-specific brain networks that have been shown to be highly reproducible in distinct groups of patients. Topographic Profile Rating (TPR) is a reverse SSM computational algorithm that can be used to determine subject scores for new patients on a prospective basis. In our implementation, reference values for a full range of patients and controls are automatically accessed for comparison. We also implemented an automated recalibration step to produce reference scores for images generated in a different imaging environment from that used in the initial network derivation. New subjects under the same setting can then be evaluated individually and a simple report is generated indicating the subject's classification. For scores near the normal limits, additional criteria are used to make a definitive diagnosis. With further refinement, automated TPR can be used to efficiently assess disease severity, monitor disease progression and evaluate treatment efficacy.
Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer's disease
Bajo, R.; Pusil, S.; López, M. E.; Canuet, L.; Pereda, E.; Osipova, D.; Maestú, F.; Pekkonen, E.
Scopolamine administration may be considered as a psychopharmacological model of Alzheimer's disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD. PMID:26130273
Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer's disease.
Bajo, R; Pusil, S; López, M E; Canuet, L; Pereda, E; Osipova, D; Maestú, F; Pekkonen, E
Scopolamine administration may be considered as a psychopharmacological model of Alzheimer's disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD. PMID:26130273
Natural History of Brain Function, Quality of Life, and Seizure Control in Patients With Brain Tumor Who Have Undergone Surgery | Division of Cancer Prevention
This trial studies the natural history of brain function, quality of life, and seizure control in patients with brain tumor who have undergone surgery. Learning about brain function, quality of life, and seizure control in patients with brain tumor who have undergone surgery may help doctors learn more about the disease and find better methods of treatment and on-going care.
Impact of Low-Level Thyroid Hormone Disruption Induced by Propylthiouracil on Brain Development and Function.*
The critical role of thyroid hormone (TH) in brain development is well established, severe deficiencies leading to significant neurological dysfunction. Much less information is available on more modest perturbations of TH on brain function. The present study induced varying degr...
Study-specific EPI template improves group analysis in functional MRI of young and older adults
Chih-Mao Huang; Shwu-Hua Lee; Ing-Tsung Hsiao; Wan-Chun Kuan; Yau-Yau Wai; Han-Jung Ko; Yung-Liang Wan; Yuan-Yu Hsu; Ho-Ling Liu
Spatial normalization to a common coordinate space, e.g. via the Montreal Neurological Institute (MNI) brain template, is an essential step of analyzing multi-subject functional MRI (fMRI) datasets. The imperfect compensation for individual regional discrepancies during spatial transformation, which could potentially introduce localization errors of the activation foci and\\/or reduce the detection sensitivity, may be minimized if a template specifically designed
Operating Characteristics of Executive Functioning Tests Following Traumatic Brain Injury
Demery, Jason A.; Larson, Michael J.; Dixit, Neha K.; Bauerand, Russell M.; Perlstein, William M.
The primary purposes of this study were to determine if controls, mild, and moderate/severe traumatic brain injury (TBI) patients performed differently on a battery of executive functioning (EF) tests, and to identify the operating characteristics of EF tests in this population. Participants consisted of 46 brain injured individuals and 24 healthy controls. All participants completed an extensive battery of EF tests. Results showed that mild TBI participants performed worse than controls on the Trail Making Test Part B, and that moderate/severe TBI participants consistently performed worse than either group on a variety of EF measures. Tests of EF exhibited a wide range of operating characteristics, suggesting that some EF tests are better than others in identifying TBI-related neurocognitive impairment. Predictive values were better for individuals with moderate/severe TBI than mild TBI. Overall, the Digit Span Backward Test showed the best positive predictive power in differentiating TBI. Our results provide useful data that may guide test selection in evaluating EF in patients with traumatic brain injury. PMID:21069617
Microinfarcts, brain atrophy, and cognitive function: the HAAS autopsy study
Launer, Lenore J; Hughes, Timothy M; White, Lon R
Objectives To study the association of microinfarcts (MBI) to ante-mortem global cognitive function (CF), and to investigate whether brain weight (BW), Alzheimer's lesions (neurofibrillary tangles (NFT) or neuritic plaques (NP) mediate the association. Methods Subjects are 437 well-characterized male decedents from the Honolulu Asia Aging Autopsy Study. Brain pathology was ascertained with standardized methods, CF was measured by the Cognitive Abilities Screening Instrument (CASI)and data were analyzed using formal mediation analyses, adjusted for age at death, time between last CF measure and death, education, and head size. Based on ante-mortem diagnoses, demented and non-demented subjects were examined together and separately. Results In those with no dementia, MBI were strongly associated with the last ante-mortem CF score; this was significantly mediated by BW, and not NFT or NP. In contrast, among those with an ante-mortem diagnosis of dementia, NFT had the strongest associations with BW and with CF, and MIB were modestly associated with CF. Interpretation This suggests microinfarct pathology is a significant and independent factor contributing to brain atrophy and cognitive impairment, particularly before dementia is clinically evident. The role of vascular damage as initiator, stimulator, or additive contributor to neurodegeneration may differ depending on when in the trajectory towards dementia the lesions develop. PMID:22162060
Sandwich masking eliminates both visual awareness of faces and face-specific brain activity through a
Sandwich masking eliminates both visual awareness of faces and face-specific brain activity through a sandwich-masking paradigm, a commonly used approach for attenuating conscious awareness of visual stimulus without awareness. The electrophysiological measures revealed that the sandwich masking abolished
Atrophy specific MRI brain template for Alzheimer's disease and Mild Cognitive Impairment
Paris-Sud XI, Université de
the ADNI contributed to the design and implementation of ADNI and/or provided.loni.ucla.edu/ADNI/Collaboration/ADNI Author ship list.pdf). Learning objectives: 1. To create a brain template specific of the disease of the subject, while maintaining continuous one-to-one mapping to the common stereotaxic space
California Verbal Learning Test Indicators of Malingered Neurocognitive Dysfunction: Sensitivity and Specificity in Traumatic Brain Injury
ERIC Educational Resources Information Center
Curtis, Kelly L.; Greve, Kevin W.; Bianchini, Kevin J.; Brennan, Adrianne
The present study used well-defined traumatic brain injury (TBI) and mixed neurological (other than TBI) and psychiatric samples to examine the specificity and sensitivity to Malingered Neurocognitive Dysfunction (MND) of four individual California Verbal Learning Test (CVLT) variables and eight composite CVLT malingering indicators. Participants…
Behavioral relevance of the dynamics of the functional brain connectome.
Jia, Hao; Hu, Xiaoping; Deshpande, Gopikrishna
While many previous studies assumed the functional connectivity (FC) between brain regions to be stationary, recent studies have demonstrated that FC dynamically varies across time. However, two challenges have limited the interpretability of dynamic FC information. First, a principled framework for selecting the temporal extent of the window used to examine the dynamics is lacking and this has resulted in ad-hoc selections of window lengths and subsequent divergent results. Second, it is unclear whether there is any behavioral relevance to the dynamics of the functional connectome in addition to that obtained from conventional static FC (SFC). In this work, we address these challenges by first proposing a principled framework for selecting the extent of the temporal windows in a dynamic and data-driven fashion based on statistical tests of the stationarity of time series. Further, we propose a method involving three levels of clustering-across space, time, and subjects-which allow for group-level inferences of the dynamics. Next, using a large resting-state functional magnetic resonance imaging and behavioral dataset from the Human Connectome Project, we demonstrate that metrics derived from dynamic FC can explain more than twice the variance in 75 behaviors across different domains (alertness, cognition, emotion, and personality traits) as compared with SFC in healthy individuals. Further, we found that individuals with brain networks exhibiting greater dynamics performed more favorably in behavioral tasks. This indicates that the ease with which brain regions engage or disengage may provide potential biomarkers for disorders involving altered neural circuitry. PMID:25163490
Specific Benzodiazepine Receptors in Rat Brain Characterized by High-Affinity [3H]diazepam binding
Claus Braestrup; Richard F. Squires
[3H]Diazepam appears to bind specifically to a single, saturable, binding site located on rat brain membranes, with an affinity constant near 3 nM at pH 7.4. Specific binding constitutes more than 90% of total binding at 0 degrees and less than 10% of total binding at 37 degrees. Arrhenius plots suggest a sharp conformational change in the diazepam receptor near
Quantitative Assessment of Brain Networks in Children With Sturge-Weber Syndrome Using Resting State Functional Magnetic Resonance Imaging (MRI).
Jeong, Jeong-Won; Chugani, Harry T; Behen, Michael E; Guy, William; Juhász, Csaba
In this study, we examined whether topologic network analysis, using resting state functional magnetic resonance imaging (MRI), can detect abnormalities of functional brain connectivity in children with unilateral brain injury due to Sturge-Weber syndrome. Three children with Sturge-Weber syndrome (ages 1, 3, and 10 years) underwent structural and resting state functional MRI, glucose metabolism positron emission tomography (PET), and neurocognitive evaluation. Eight different resting state networks were compared between the affected and unaffected hemispheres by quantitatively accessing communication efficiency measures. Significantly reduced efficiency values were found in all 3 patients. Visual network deficiency was present in both children with a visual field defect; frontal network abnormalities were associated with fine motor impairment. Location of network abnormalities corresponded to and, in some cases, extended beyond structural MRI and glucose PET abnormalities. The presented approach can detect early functional abnormalities of specific brain networks in children with Sturge-Weber syndrome. PMID:23271758
Crossed-Brain Representation of Verbal and Nonverbal Functions
Matute, Esmeralda; Ardila, Alfredo; Rosselli, Monica; Molina Del Rio, Jahaziel; López Elizalde, Ramiro; López, Manuel; Ontiveros, Angel
A 74-year-old, left-handed man presented with a rapidly evolving loss of strength in his right leg associated with difficulty in walking. MR images disclosed an extensive left hemisphere tumor. A neuropsychological examination revealed that language was broadly normal but that the patient presented with severe nonlinguistic abnormalities, including hemineglect (both somatic and spatial), constructional defects, and general spatial disturbances; symptoms were usually associated with right hemisphere pathologies. No ideomotor apraxia was found. The implications of crossed-brain representations of verbal and nonverbal functions are analyzed. PMID:25802778
Alcohol: Effects on Neurobehavioral Functions and the Brain
Oscar-Berman, Marlene; Marinkovi?, Ksenija
Alcoholism results from an interplay between genetic and environmental factors, and is linked to brain defects and associated cognitive, emotional, and behavioral impairments. A confluence of findings from neuroimaging, physiological, neuropathological, and neuropsychological studies of alcoholics indicate that the frontal lobes, limbic system, and cerebellum are particularly vulnerable to damage and dysfunction. An integrative approach employing a variety of neuroscientific technologies is essential for recognizing the interconnectivity of the different functional systems affected by alcoholism. In that way, relevant experimental techniques can be applied to assist in determining the degree to which abstinence and treatment contribute to the reversal of atrophy and dysfunction. PMID:17874302
Functional Connectivity among Limbic Brain Areas: Differential Effects of Incubation Temperature and Gonadal Sex in the Leopard Gecko, Eublepharis macularius
Jon T. Sakata; Patricia Coomber; F. Gonzalez-Lima; David Crews
The neural basis of individual differences in behavior has been studied primarily by analyzing the properties of specific neural areas. However, because of the organization of the nervous system, it is also plausible that differences in behavior are mediated by differences in the interactivity or functional connectivity among brain nuclei in particular neural circuits. In the leopard gecko, Eublepharis macularius,
Functional development in the infant brain for auditory pitch processing.
Homae, Fumitaka; Watanabe, Hama; Nakano, Tamami; Taga, Gentaro
Understanding how the developing brain processes auditory information is a critical step toward the clarification of infants' perception of speech and music. We have reported that the infant brain perceives pitch information in speech sounds. Here, we used multichannel near-infrared spectroscopy to examine whether the infant brain is sensitive to information of pitch changes in auditory sequences. Three types of auditory sequences with distinct temporal structures of pitch changes were presented to 3- and 6-month-old infants: a long condition of 12 successive tones constructing a chromatic scale (600 ms), a short condition of four successive tones constructing a chromatic scale (200 ms), and a random condition of random tone sequences (50 ms per tone). The difference among the conditions was only in the sequential order of the tones, which causes pitch changes between the successive tones. We found that the bilateral temporal regions of both ages of infants showed significant activation under the three conditions. The stimulus-dependent activation was observed in the right temporoparietal region of the both infant groups; the 3- and 6-month-old infants showed the most prominent activation under the random and short conditions, respectively. Our findings indicate that the infant brain, which shows functional differentiation and lateralization in auditory-related areas, is capable of responding to more than single tones of pitch information. These results suggest that the right temporoparietal region of the infants increases sensitivity to auditory sequences, which have temporal structures similar to those of syllables in speech sounds, in the course of development. PMID:21488136
Brain site-specific proteome changes in aging-related dementia.
Manavalan, Arulmani; Mishra, Manisha; Feng, Lin; Sze, Siu Kwan; Akatsu, Hiroyasu; Heese, Klaus
This study is aimed at gaining insights into the brain site-specific proteomic senescence signature while comparing physiologically aged brains with aging-related dementia brains (for example, Alzheimer's disease (AD)). Our study of proteomic differences within the hippocampus (Hp), parietal cortex (pCx) and cerebellum (Cb) could provide conceptual insights into the molecular mechanisms involved in aging-related neurodegeneration. Using an isobaric tag for relative and absolute quantitation (iTRAQ)-based two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D-LC-MS/MS) brain site-specific proteomic strategy, we identified 950 proteins in the Hp, pCx and Cb of AD brains. Of these proteins, 31 were significantly altered. Most of the differentially regulated proteins are involved in molecular transport, nervous system development, synaptic plasticity and apoptosis. Particularly, proteins such as Gelsolin (GSN), Tenascin-R (TNR) and AHNAK could potentially act as novel biomarkers of aging-related neurodegeneration. Importantly, our Ingenuity Pathway Analysis (IPA)-based network analysis further revealed ubiquitin C (UBC) as a pivotal protein to interact with diverse AD-associated pathophysiological molecular factors and suggests the reduced ubiquitin proteasome degradation system (UPS) as one of the causative factors of AD. PMID:24008896
High-resolution functional magnetic resonance imaging of the animal brain
Seong-Gi Kim; Kamil Ugurbil
To fully understand brain function, one must look beyond the level of a single neuron. By elucidating the spatial properties of the columnar and laminar functional architectures, information regarding the neural processing in the brain can be gained. To map these fine functional structures noninvasively and repeatedly, functional magnetic resonance imaging (fMRI) can be employed. In this article the basic
WLPVG approach to the analysis of EEG-based functional brain network under manual acupuncture.
Pei, Xin; Wang, Jiang; Deng, Bin; Wei, Xile; Yu, Haitao
Functional brain network, one of the main methods for brain functional studies, can provide the connectivity information among brain regions. In this research, EEG-based functional brain network is built and analyzed through a new wavelet limited penetrable visibility graph (WLPVG) approach. This approach first decompose EEG into ?, ?, ?, ? sub-bands, then extracting nonlinear features from single channel signal, in addition forming a functional brain network for each sub-band. Manual acupuncture (MA) as a stimulation to the human nerve system, may evoke varied modulating effects in brain activities. To investigating whether and how this happens, WLPVG approach is used to analyze the EEGs of 15 healthy subjects with MA at acupoint ST36 on the right leg. It is found that MA can influence the complexity of EEG sub-bands in different ways and lead the functional brain networks to obtain higher efficiency and stronger small-world property compared with pre-acupuncture control state. PMID:25206935
Functional design specification: NASA form 1510
NASA Technical Reports Server (NTRS)
The 1510 worksheet used to calculate approved facility project cost estimates is explained. Topics covered include data base considerations, program structure, relationship of the 1510 form to the 1509 form, and functions which the application must perform: WHATIF, TENENTER, TENTYPE, and data base utilities. A sample NASA form 1510 printout and a 1510 data dictionary are presented in the appendices along with the cost adjustment table, the floppy disk index, and methods for generating the calculated values (TENCALC) and for calculating cost adjustment (CONSTADJ). Storage requirements are given.
ORIGINAL RESEARCH Restored Activation of Primary Motor Area from Motor Reorganization and Improved Motor Function after Brain Tumor Resection
N. Shinoura; Y. Suzuki; R. Yamada; T. Kodama; M. Takahashi; K. Yagi
BACKGROUND AND PURPOSE: Reorganization of brain function may result in preservation of motor function in patients with brain tumors. The goal of the present study was to investigate whether function of the primary motor area (M1) was restored and whether motor function improved after brain tumor resection. METHODS: Five patients with metastatic brain tumors located within or near M1 underwent
Online Detection of Gamma Oscillations in Ongoing Intracerebral Recordings: From Functional Mapping to Brain Computer Interfaces
K. Jerbi; O. Bertrand; B. Schoendorff; D. Hoffmann; L. Minotti; P. Kahane; A. Berthoz; J.-P. Lachaux
The human brain displays rhythmic neural activity in a variety of frequencies and various spatial distributions in correlation with behavior. A growing body of evidence suggests that specific classes of oscillations can be modified voluntarily by the subject. Such endogenous modulation of brain oscillations is in principle a promising mechanism for direct brain-computer communication provided that it can be detected
Online Detection of Gamma Oscillations in Ongoing Intracerebral Recordings: From Functional Mapping to Brain Computer Interfaces
K. Jerbi; O. Bertrand; B. Schoendorff; D. Hoffmann; L. Minotti; P. Kahane; A. Berthoz
The human brain displays rhythmic neural activity in a variety of frequencies and various spatial distributions in correlation with behavior. A growing body of evidence suggests that specific classes of oscillations can be modified voluntarily by the subject. Such endogenous modulation of brain oscillations is in principle a promising mechanism for direct brain-computer communication provided that it can be detected
Larger Brains in Medication Naive High-Functioning Subjects with Pervasive Developmental Disorder
ERIC Educational Resources Information Center
Palmen, Saskia J. M. C.; Pol, Hilleke E. Hulshoff; Kemner, Chantal; Schnack, Hugo G.; Janssen, Joost; Kahn, Rene S.; van Engeland, Herman
Background: Are brain volumes of individuals with Pervasive Developmental Disorder (PDD) still enlarged in adolescence and adulthood, and if so, is this enlargement confined to the gray and/or the white matter and is it global or more prominent in specific brain regions. Methods: Brain MRI scans were made of 21 adolescents with PDD and 21 closely…
Roles for Oestrogen Receptor ? in Adult Brain Function
Handa, R. J.; Ogawa, S.; Wang, J. M.; Herbison, A. E.
Oestradiol exerts a profound influence upon multiple brain circuits. For the most part, these effects are mediated by oestrogen receptor (ER)?. We review here the roles of ER?, the other ER isoform, in mediating rodent oestradiol-regulated anxiety, aggressive and sexual behaviours, the control of gonadotrophin secretion, and adult neurogenesis. Evidence exists for: (i) ER? located in the paraventricular nucleus underpinning the suppressive influence of oestradiol on the stress axis and anxiety-like behaviour; (ii) ER? expressed in gonadotrophin-releasing hormone neurones contributing to oestrogen negative-feedback control of gonadotrophin secretion; (iii) ER? controlling the offset of lordosis behaviour; (iv) ER? suppressing aggressive behaviour in males; (v) ER? modulating responses to social stimuli; and (vi) ER? in controlling adult neurogenesis. This review highlights two major themes; first, ER? and ER? are usually tightly inter-related in the oestradiol-dependent control of a particular brain function. For example, even though oestradiol feedback to control reproduction occurs principally through ER?-dependent mechanisms, modulatory roles for ER? also exist. Second, the roles of ER? and ER? within a particular neural network may be synergistic or antagonistic. Examples of the latter include the role of ER? to enhance, and ER? to suppress, anxiety-like and aggressive behaviours. Splice variants such as ER?2, acting as dominant negative receptors, are of further particular interest because their expression levels may reflect preceeding oestradiol exposure of relevance to oestradiol replacement therapy. Together, this review highlights the predominant modulatory, but nonetheless important, roles of ER? in mediating the many effects of oestradiol upon adult brain function. PMID:21851428
Measuring cell-type specific differential methylation in human brain tissue.
Montańo, Carolina M; Irizarry, Rafael A; Kaufmann, Walter E; Talbot, Konrad; Gur, Raquel E; Feinberg, Andrew P; Taub, Margaret A
The behavior of epigenetic mechanisms in the brain is obscured by tissue heterogeneity and disease-related histological changes. Not accounting for these confounders leads to biased results. We develop a statistical methodology that estimates and adjusts for celltype composition by decomposing neuronal and non-neuronal differential signal. This method provides a conceptual framework for deconvolving heterogeneous epigenetic data from postmortem brain studies. We apply it to find cell-specific differentially methylated regions between prefrontal cortex and hippocampus. We demonstrate the utility of the method on both Infinium 450k and CHARM data. PMID:24000956
Specific In Vivo Staining of Astrocytes in the Whole Brain after Intravenous Injection of Sulforhodamine Dyes
Appaix, Florence; Girod, Sabine; Boisseau, Sylvie; Römer, Johannes; Vial, Jean-Claude; Albrieux, Mireille; Maurin, Mathieu; Depaulis, Antoine; Guillemain, Isabelle; van der Sanden, Boudewijn
Fluorescent staining of astrocytes without damaging or interfering with normal brain functions is essential for intravital microscopy studies. Current methods involved either transgenic mice or local intracerebral injection of sulforhodamine 101. Transgenic rat models rarely exist, and in mice, a backcross with GFAP transgenic mice may be difficult. Local injections of fluorescent dyes are invasive. Here, we propose a non-invasive, specific and ubiquitous method to stain astrocytes in vivo. This method is based on iv injection of sulforhodamine dyes and is applicable on rats and mice from postnatal age to adulthood. The astrocytes staining obtained after iv injection was maintained for nearly half a day and showed no adverse reaction on astrocytic calcium signals or electroencephalographic recordings in vivo. The high contrast of the staining facilitates the image processing and allows to quantify 3D morphological parameters of the astrocytes and to characterize their network. Our method may become a reference for in vivo staining of the whole astrocytes population in animal models of neurological disorders. PMID:22509398
Negative regulation of NF-?B activity by brain-specific TRIpartite Motif protein 9
Shi, Mude; Cho, Hyelim; Inn, Kyung-Soo; Yang, Aerin; Zhao, Zhen; Liang, Qiming; Versteeg, Gijs A.; Amini-Bavil-Olyaee, Samad; Wong, Lai-Yee; Zlokovic, Berislav V.; Park, Hee-Sung; García-Sastre, Adolfo; Jung, Jae
The TRIpartite Motif (TRIM) family of RING-domain-containing proteins participate in a variety of cellular functions. The ?-transducin repeat-containing protein (?-TrCP), a component of the Skp-Cullin-F-box-containing (SCF) E3 ubiquitin ligase complex, recognizes the NF-?B inhibitor I?B? and precursor p100 for proteasomal degradation and processing respectively. ?-TrCP thus plays a critical role in both canonical and non-canonical NF-?B activation. Here, we report TRIM9 is a negative regulator of NF-?Bactivation. Interaction between the phosphorylated degron motif of TRIM9 and the WD40 repeat region of ?-TrCP prevented ?-TrCP from binding its substrates, stabilizing I?B? and p100 and thereby blocking NF-?B activation. Consequently, expression or depletion of the TRIM9 gene significantly affected NF-?B-induced inflammatory cytokine production. This study not only elucidates a mechanism for TRIM9-mediated regulation of the ?-TrCP SCF complex activity, but also identifies TRIM9 as a brain-specific negative regulator of the NF-?B pro-inflammatory signaling pathway. PMID:25190485
Minimal brain dysfunction/specific learning disability: a clinical approach for the primary physician.
Levy, H B
Minimal brain dysfunction is a neurodevelopmental disorder which can be found in nearly 20% of school children. It is characterized by evidences of immaturity involving control of activity, emotions, and behavior, and by specific learning disabilities involving the communicating skills needed in reading, writing, and mathematics. The prime deficits in the classroom are an inability to maintain attention and concentration and an inability to skillfully blend the auditory and visual functions essential in language performance. Medical evaluation will reveal many of the "soft signs" of neurologic involvement, and educational appraisal will indicate a wide scatter in testing scores with a marked discrepancy between evaluated potential and actual classroom achievement. Remedial efforts directed at early detection, relief from pressure and unjust punishment or ridicule from parents and teachers, and adjustment of the educational environment with consideration of the child's individual talents, combined with the judicious use of medications to prolong attention span and improve neurodevelopmental maturity, hold promise of improving the lot of most involved children. There are valid indications that expansion of such programs can do much to prevent these youngsters from developing severe personality maladjustment and delinquent behavior, as well as emotional illness in later life. PMID:1273628
Subject-specific prediction using nonlinear population modeling: Application to early brain maturation from DTI
Sadeghi, Neda; Fletcher, P. Thomas; Prastawa, Marcel; Gilmore, John H.; Gerig, Guido
The term prediction implies expected outcome in the future, often based on a model and statistical inference. Longitudinal imaging studies offer the possibility to model temporal change trajectories of anatomy across populations of subjects. In the spirit of subject-specific analysis, such normative models can then be used to compare data from new subjects to the norm and to study progression of disease or to predict outcome. This paper follows a statistical inference approach and presents a framework for prediction of future observations based on past measurements and population statistics. We describe prediction in the context of nonlinear mixed effects modeling (NLME) where the full reference population's statistics (estimated fixed effects, variance-covariance of random effects, variance of noise) is used along with the individual's available observations to predict its trajectory. The proposed methodology is generic in regard to application domains. Here, we demonstrate analysis of early infant brain maturation from longitudinal DTI with up to three time points. Growth as observed in DTI-derived scalar invariants is modeled with a parametric function, its parameters being input to NLME population modeling. Trajectories of new subject's data are estimated when using no observation, only the first or the first two time points. Leave-one-out experiments result in statistics on differences between actual and predicted observations. We also simulate a clinical scenario of prediction on multiple categories, where trajectories predicted from multiple models are classified based on maximum likelihood criteria. PMID:25320779
Brain imaging methods used in experimental brain research such as Positron Emission Tomography (PET) and Functional
Mueller, Klaus
ABSTRACT Brain imaging methods used in experimental brain research such as Positron Emission of methods create statistical parametric maps (SPMs) of the brain on a voxel- basis. In our approach, they are best understood in the context of the underly- ing 3-D brain anatomy. However, despite the power
Ethanol, not metabolized in brain, significantly reduces brain metabolism, probably via specific GABA(A) receptors
Rae, Caroline D.; Davidson, Joanne E.; Maher, Anthony D.; Rowlands, Benjamin D.; Kashem, Mohammed A.; Nasrallah, Fatima A.; Rallapalli, Sundari K.; Cook, James M; Balcar, Vladimir J.
Ethanol is a known neuromodulatory agent with reported actions at a range of neurotransmitter receptors. Here, we used an indirect approach, measuring the effect of alcohol on metabolism of [3-13C]pyruvate in the adult Guinea pig brain cortical tissue slice and comparing the outcomes to those from a library of ligands active in the GABAergic system as well as studying the metabolic fate of [1,2-13C]ethanol. Ethanol (10, 30 and 60 mM) significantly reduced metabolic flux into all measured isotopomers and reduced all metabolic pool sizes. The metabolic profiles of these three concentrations of ethanol were similar and clustered with that of the ?4?3? positive allosteric modulator DS2 (4-Chloro-N-[2-(2-thienyl)imidazo[1,2a]-pyridin-3-yl]benzamide). Ethanol at a very low concentration (0.1 mM) produced a metabolic profile which clustered with those from inhibitors of GABA uptake, and ligands showing affinity for ?5, and to a lesser extent, ?1-containing GABA(A)R. There was no measureable metabolism of [1,2-13C]ethanol with no significant incorporation of 13C from [1,2-13C]ethanol into any measured metabolite above natural abundance, although there were measurable effects on total metabolite sizes similar to those seen with unlabeled ethanol. The reduction in metabolism seen in the presence of ethanol is therefore likely to be due to its actions at neurotransmitter receptors, particularly ?4?3? receptors, and not because ethanol is substituting as a substrate or because of the effects of ethanol catabolites acetaldehyde or acetate. We suggest that the stimulatory effects of very low concentrations of ethanol are due to release of GABA via GAT1 and the subsequent interaction of this GABA with local ?5-containing, and to a lesser extent, ?1-containing GABA(A)R. PMID:24313287
Estimating brain functional connectivity with sparse multivariate autoregression
Valdés-Sosa, Pedro A; Sánchez-Bornot, Jose M; Lage-Castellanos, Agustín; Vega-Hernández, Mayrim; Bosch-Bayard, Jorge; Melie-García, Lester; Canales-Rodríguez, Erick
There is much current interest in identifying the anatomical and functional circuits that are the basis of the brain's computations, with hope that functional neuroimaging techniques will allow the in vivo study of these neural processes through the statistical analysis of the time-series they produce. Ideally, the use of techniques such as multivariate autoregressive (MAR) modelling should allow the identification of effective connectivity by combining graphical modelling methods with the concept of Granger causality. Unfortunately, current time-series methods perform well only for the case that the length of the time-series Nt is much larger than p, the number of brain sites studied, which is exactly the reverse of the situation in neuroimaging for which relatively short time-series are measured over thousands of voxels. Methods are introduced for dealing with this situation by using sparse MAR models. These can be estimated in a two-stage process involving (i) penalized regression and (ii) pruning of unlikely connections by means of the local false discovery rate developed by Efron. Extensive simulations were performed with idealized cortical networks having small world topologies and stable dynamics. These show that the detection efficiency of connections of the proposed procedure is quite high. Application of the method to real data was illustrated by the identification of neural circuitry related to emotional processing as measured by BOLD. PMID:16087441
Functional Tissue Pulsatility Imaging of the Brain during Visual Stimulation
Kucewicz, John C.; Dunmire, Barbrina; Leotta, Daniel F.; Panagiotides, Heracles; Paun, Marla; Beach, Kirk W.
Functional tissue pulsatility imaging (fTPI) is a new ultrasonic technique being developed to map brain function by measuring changes in tissue pulsatility due to changes in blood flow with neuronal activation. The technique is based in principle on plethysmography, an older, non-ultrasound technology for measuring expansion of a whole limb or body part due to perfusion. Perfused tissue expands by a fraction of a percent early in each cardiac cycle when arterial inflow exceeds venous outflow and relaxes later in the cardiac cycle when venous drainage dominates. Tissue pulsatility imaging (TPI) uses tissue Doppler signal processing methods to measure this pulsatile "plethysmographic" signal from hundreds or thousands of sample volumes in an ultrasound image plane. A feasibility study was conducted to determine if TPI could be used to detect regional brain activation during a visual contrast-reversing checkerboard block paradigm study. During a study, ultrasound data were collected transcranially from the occipital lobe as a subject viewed alternating blocks of a reversing checkerboard (stimulus condition) and a static, gray screen (control condition). Multivariate Analysis of Variance (MANOVA) was used to identify sample volumes with significantly different pulsatility waveforms during the control and stimulus blocks. In 7 out 14 studies, consistent regions of activation were detected from tissue around the major vessels perfusing the visual cortex. PMID:17346872
Mastering Transfer Function Specification by using VolumePro Technology
Mastering Transfer Function Specification by using VolumePro TechnologyŁ Andreas H. K¨onigÝ Eduard M. Gr¨ollerŢ Institute of Computer Graphics Vienna University of Technology Ü Abstract A new user-interface paradigm for the specification of transfer func- tions is presented. The specification is usually
In vivo Visuotopic Brain Mapping with Manganese-Enhanced MRI and Resting-State Functional Connectivity MRI
Chan, Kevin C.; Fan, Shu-Juan; Chan, Russell W.; Cheng, Joe S.; Zhou, Iris Y.; Wu, Ed X.
The rodents are an increasingly important model for understanding the mechanisms of development, plasticity, functional specialization and disease in the visual system. However, limited tools have been available for assessing the structural and functional connectivity of the visual brain network globally, in vivo and longitudinally. There are also ongoing debates on whether functional brain connectivity directly reflects structural brain connectivity. In this study, we explored the feasibility of manganese-enhanced MRI (MEMRI) via 3 different routes of Mn2+ administration for visuotopic brain mapping and understanding of physiological transport in normal and visually deprived adult rats. In addition, resting-state functional connectivity MRI (RSfcMRI) was performed to evaluate the intrinsic functional network and structural-functional relationships in the corresponding anatomical visual brain connections traced by MEMRI. Upon intravitreal, subcortical, and intracortical Mn2+ injection, different topographic and layer-specific Mn enhancement patterns could be revealed in the visual cortex and subcortical visual nuclei along retinal, callosal, cortico-subcortical, transsynaptic and intracortical horizontal connections. Loss of visual input upon monocular enucleation to adult rats appeared to reduce interhemispheric polysynaptic Mn2+ transfer but not intra- or inter-hemispheric monosynaptic Mn2+ transport after Mn2+ injection into visual cortex. In normal adults, both structural and functional connectivity by MEMRI and RSfcMRI was stronger interhemispherically between bilateral primary/secondary visual cortex (V1/V2) transition zones (TZ) than between V1/V2 TZ and other cortical nuclei. Intrahemispherically, structural and functional connectivity was stronger between visual cortex and subcortical visual nuclei than between visual cortex and other subcortical nuclei. The current results demonstrated the sensitivity of MEMRI and RSfcMRI for assessing the neuroarchitecture, neurophysiology and structural-functional relationships of the visual brains in vivo. These may possess great potentials for effective monitoring and understanding of the basic anatomical and functional connections in the visual system during development, plasticity, disease, pharmacological interventions and genetic modifications in future studies. PMID:24394694
Functional Brain Correlates of Upper Limb Spasticity and Its Mitigation following Rehabilitation in Chronic Stroke Survivors
Pundik, Svetlana; Falchook, Adam D.; McCabe, Jessica; Daly, Janis J.
Background. Arm spasticity is a challenge in the care of chronic stroke survivors with motor deficits. In order to advance spasticity treatments, a better understanding of the mechanism of spasticity-related neuroplasticity is needed. Objective. To investigate brain function correlates of spasticity in chronic stroke and to identify specific regional functional brain changes related to rehabilitation-induced mitigation of spasticity. Methods. 23 stroke survivors (>6 months) were treated with an arm motor learning and spasticity therapy (5?d/wk for 12 weeks). Outcome measures included Modified Ashworth scale, sensory tests, and functional magnetic resonance imaging (fMRI) for wrist and hand movement. Results. First, at baseline, greater spasticity correlated with poorer motor function (P = 0.001) and greater sensory deficits (P = 0.003). Second, rehabilitation produced improvement in upper limb spasticity and motor function (P < 0.0001). Third, at baseline, greater spasticity correlated with higher fMRI activation in the ipsilesional thalamus (rho = 0.49, P = 0.03). Fourth, following rehabilitation, greater mitigation of spasticity correlated with enhanced fMRI activation in the contralesional primary motor (r = ?0.755, P = 0.003), premotor (r = ?0.565, P = 0.04), primary sensory (r = ?0.614, P = 0.03), and associative sensory (r = ?0.597, P = 0.03) regions while controlling for changes in motor function. Conclusions. Contralesional motor regions may contribute to restoring control of muscle tone in chronic stroke. PMID:25101190
The temporal structures and functional significance of scale-free brain activity
He, Biyu J.; Zempel, John M.; Snyder, Abraham Z.; Raichle, Marcus E.
SUMMARY Scale-free dynamics, with a power spectrum following P ? f-?, are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with ? being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications. PMID:20471349
Functional abnormalities in normally appearing athletes following mild traumatic brain injury: a functional MRI study
Semyon M. Slobounov; K. Zhang; D. Pennell; W. Ray; B. Johnson; W. Sebastianelli
Memory problems are one of the most common symptoms of sport-related mild traumatic brain injury (MTBI), known as concussion.\\u000a Surprisingly, little research has examined spatial memory in concussed athletes given its importance in athletic environments.\\u000a Here, we combine functional magnetic resonance imaging (fMRI) with a virtual reality (VR) paradigm designed to investigate\\u000a the possibility of residual functional deficits in recently
Specific localization of quercetin-3-O-glucuronide in human brain.
Ishisaka, Akari; Mukai, Rie; Terao, Junji; Shibata, Noriyuki; Kawai, Yoshichika
In recent years, many papers have suggested that dietary flavonoids may exert beneficial effects in the brain tissue for the protection of neurons against oxidative stress and inflammation. However, the bioavailability of flavonoids across the blood-brain barrier and the localization in the brain remain controversial. Thus, we examined the localization of quercetin-3-O-glucuronide (Q3GA), a major phase-II metabolite of quercetin, in the human brain tissues with or without cerebral infarction by immunohistochemical staining using anti-Q3GA antibody. A significant immunoreactivity was observed in the epithelial cells of the choroid plexus, which constitute the structural basis of the blood-cerebrospinal fluid (CSF) barrier, and in the foamy macrophages of recent infarcts. The cellular accumulation of Q3GA was also reproduced in vitro in macrophage-like RAW264, microglial MG6, and brain capillary endothelial RBEC1. It is of interest that a common feature of these cell lines is the deconjugation of Q3GA, resulting in the cellular accumulation of non-conjugated quercetin and the methylated forms. We then examined the anti-inflammatory activity of Q3GA and the deconjugated forms in the lipopolysaccharide-stimulated macrophage cells and revealed that the deconjugated forms (quercetin and a methylated form isorhamnetin), but not Q3GA itself, exhibited inhibitory effects on the inflammatory responses through attenuation of the c-Jun N-terminal kinase pathway. These results suggested that a quercetin glucuronide can pass through the blood-brain barrier, perhaps the CSF barrier, accumulate in specific types of cells, such as macrophages, and act as anti-inflammatory agents in the brain through deconjugation into the bioactive non-conjugated forms. PMID:24893148
Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.
Song, Jie; Nair, Veena A; Gaggl, Wolfgang; Prabhakaran, Vivek
The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network, and individual brain regions. At the whole-brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (although weakly connected). At the functional network level, there were significant proportions of newly formed connections between the default mode network and other networks and between the subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task control network and other networks. Individual brain regions from different functional networks, however, showed a distinct pattern of reorganizational changes in epilepsy. These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole-brain level, yet alters brain functional networks and individual brain regions differently. PMID:25647011
Pathophysiological Response to Experimental Diffuse Brain Trauma Differs as a Function of Developmental Age
Ibolja Cernak; Taeun Chang; Farid A. Ahmed; Maria I. Cruz; Robert Vink; Bogdan Stoica; Alan I. Faden
The purpose of experimental models of traumatic brain injury (TBI) is to reproduce selected aspects of human head injury such as brain edema, contusion or concussion, and functional deficits, among others. As the immature brain may be particularly vulnerable to injury during critical periods of development, and pediatric TBI may cause neurobehavioral deficits, our aim was to develop and characterize
Functional Representation of Human Embryo Brain Models Roman Durikovic Silvester Czanner
Durikovic, Roman
Functional Representation of Human Embryo Brain Models Roman Durikovic Silvester Czanner Hirofumi embryo brain is organic and has many folds that are difficult to model or animate with conventional metamorphosis during the growth of some human embryo organs, partic- ularly brain and stomach. Popular methods
Expression and function of the LIM homeodomain protein Apterous during embryonic brain development of Drosophila
Martin C. Herzig; Stefan Thor; John B. Thomas; Heinrich Reichert; Frank Hirth
We analyzed the expression and function of the LIM-homeodomain transcription factor Apterous (Ap) in embryonic brain development of Drosophila. Expression of Ap in the embryonic brain begins at early stage 12 and is subsequently found in approximately 200 protocerebral neurons and in 4 deutocerebral neurons. Brain glia do not express Ap. Most of the Ap-expressing neurons are interneurons and project
NEST Scientific Report 2007-2009 Monitoring brain function by in vivo 2-photon microscopy
Abbondandolo, Alberto
101) selectively stain and identify a population of brain cells, the astrocytes. The green dyeNEST Scientific Report 2007-2009 Monitoring brain function by in vivo 2-photon microscopy 75) transversal reconstruction of a brain neuron. The cell body is placed in cortical layer V at a depth of over
Complex brain networks: graph theoretical analysis of structural and functional systems
Olaf Sporns; Ed Bullmore
Recent developments in the quantitative analysis of complex networks, based largely on graph theory, have been rapidly translated to studies of brain network organization. The brain's structural and functional systems have features of complex networks — such as small-world topology, highly connected hubs and modularity — both at the whole-brain scale of human neuroimaging and at a cellular scale in
Distribution of drugs of abuse within specific regions of the human brain.
Stimpfl, T; Reichel, S
Since concentration of drugs of abuse found in the brain better reflect drug concentration at their site of action, brain specimens are useful in the determination of the role of drugs of abuse in the cause of death. In order to allow for the routine use of brain specimens in this field, a comprehensive database with reliable reference values is needed and should include both post-mortem data for cases where drugs have been taken in therapeutic doses as well as for cases of overdose. In this study, a semi-automated extraction procedure, in combination with gas chromatography/mass spectrometry (GC-MS) using stable isotope internal standards was applied to yield reproducible, quantitative results which could be used to investigate the distribution patterns of drugs of abuse within specific regions of the brain, by analyzing several segments of both medulla oblongata and cerebellum. A homogenous distribution of unconjugated morphine, dihydrocodeine, and benzoylecgonine within the investigated segments of medulla oblongata or cerebellum could be found. However, when these two brain regions from the same case were compared to each other, significantly higher concentrations of unconjugated morphine, dihydrocodeine, and benzoylecgonine were found in the cerebellum than in the medulla oblongata. PMID:17629644
Pulmonary Function, Cognitive Impairment and Brain Atrophy in a Middle-Aged Community Sample
P. S. Sachdev; K. J. Anstey; R. A. Parslow; W. Wen; J. Maller; R. Kumar; H. Christensen; A. F. Jorm
Objective: To determine the relationship of lung function to brain anatomical parameters and cognitive function and to examine the mediating factors for any relationships. Methods: A random sub-sample of 469 persons (men = 252) aged 60–64 years from a larger community sample underwent brain magnetic resonance imaging scans and pulmonary function tests (forced vital capacity, FVC, forced expiratory volume in
Functional and morphometric brain dissociation between dyslexia and reading ability.
Hoeft, Fumiko; Meyler, Ann; Hernandez, Arvel; Juel, Connie; Taylor-Hill, Heather; Martindale, Jennifer L; McMillon, Glenn; Kolchugina, Galena; Black, Jessica M; Faizi, Afrooz; Deutsch, Gayle K; Siok, Wai Ting; Reiss, Allan L; Whitfield-Gabrieli, Susan; Gabrieli, John D E
In functional neuroimaging studies, individuals with dyslexia frequently exhibit both hypoactivation, often in the left parietotemporal cortex, and hyperactivation, often in the left inferior frontal cortex, but there has been no evidence to suggest how to interpret the differential relations of hypoactivation and hyperactivation to dyslexia. To address this question, we measured brain activation by functional MRI during visual word rhyme judgment compared with visual cross-hair fixation rest, and we measured gray matter morphology by voxel-based morphometry in dyslexic adolescents in comparison with (i) an age-matched group, and (ii) a reading-matched group younger than the dyslexic group but equal to the dyslexic group in reading performance. Relative to the age-matched group (n = 19; mean 14.4 years), the dyslexic group (n = 19; mean 14.4 years) exhibited hypoactivation in left parietal and bilateral fusiform cortices and hyperactivation in left inferior and middle frontal gyri, caudate, and thalamus. Relative to the reading-matched group (n = 12; mean 9.8 years), the dyslexic group (n = 12; mean 14.5 years) also exhibited hypoactivation in left parietal and fusiform regions but equal activation in all four areas that had exhibited hyperactivation relative to age-matched controls as well. In regions that exhibited atypical activation in the dyslexic group, only the left parietal region exhibited reduced gray matter volume relative to both control groups. Thus, areas of hyperactivation in dyslexia reflected processes related to the level of current reading ability independent of dyslexia. In contrast, areas of hypoactivation in dyslexia reflected functional atypicalities related to dyslexia itself, independent of current reading ability, and related to atypical brain morphology in dyslexia. PMID:17360506
Accumulation of waterborne mercury(II) in specific areas of fish brain
Rouleau, C.; Borg-Neczak, K.; Gottofrey, J.; Tjaelve, H.
The authors used whole-body autoradiography to study the distribution of {sup 203}Hg(II) in the central nervous system of brown (Salmo trutta) and rainbow (Oncorhynchus mykiss) trout. Fish were either exposed to waterborne Hg(II) for 7 and 21 d or they received an intravenous injection of the metal and were sacrificed 1 and 21 d later. Mercury did not accumulate in the brain after intravenous injection, indicating that the blood-brain barrier is impervious to Hg in plasma. In contrast, Hg was accumulated in specific areas of the grain and spinal cord following water exposure. The specificity of the accumulation sites strongly suggests that waterborne Hg was taken up by water-exposed receptor cells of sensory nerves and subsequently transferred toward the brain by axonal transport, a normal physiological process for the transport of organelles and dissolved neuronal constituents along nerve axons. Accumulation of Hg in ventral horn ganglis is probably the result of leaching of metal from blood into muscle followed by uptake in motor plates. Axonal transport allows waterborne inorganic Hg, and possibly other xenobiotics, to circumvent the blood-brain barrier. Considering the importance of complex behavior in the life of fish, and the well-known deleterious effects of mercury on the nervous system, the toxicological significance of this uptake route needs to be assessed.
BRAIN THEORY AND MINIMAL BRAIN DYSFUNCTION * M. S. Gazzaniga
Gazzaniga, Michael
BRAIN THEORY AND MINIMAL BRAIN DYSFUNCTION * M. S. Gazzaniga Department of Graduate Psychology New labeled the diffuse problems of learning disabilities in children as results of minimal brain dysfunction on cerebral functions offered by studying the bisected brain may apply to specific problems seen in some cases
Relation of executive functioning and social communication measures to functional outcomes following traumatic brain injury.
Struchen, Margaret A; Clark, Allison N; Sander, Angelle M; Mills, Monique R; Evans, Gina; Kurtz, Diana
Neuropsychologists are increasingly asked to provide recommendations regarding functional abilities based on test results, particularly within the rehabilitation setting. Yet, the empirical basis for making such recommendations is limited. The current study examines relationships between executive functioning and social communication measures and concurrently measured occupational and social integration outcomes. Participants were 121 individuals with traumatic brain injury (TBI) recruited from participants in a longitudinal study of outcome following TBI who had all received comprehensive brain injury rehabilitation. As part of a larger study designed to evaluate social communication abilities following TBI, participants completed measures of executive functioning, affect perception, perceived communication ability, and functional outcome. After adjusting for age, education, and performance on executive functioning measures, social communication performance accounted for a unique 5.6% of the variance in occupational outcomes and 7.9% of variance in social integration outcomes. Executive functioning performance accounted for a unique 13.3% of the variance in occupational functioning and 16.0% of explained variance in social integration. These results provide evidence of the value of executive functioning and social communication measures in the prediction of functional outcomes. Additionally, such results provide preliminary support for the addition of social communication measures to assessment of TBI in neuropsychological practice. PMID:18525140
The Brain's Orienting Response: An Event-Related Functional Magnetic Resonance Imaging Investigation
Friedman, David; Goldman, Robin; Stern, Yaakov; Brown, Truman R.
An important function of the brain's orienting response is to enable the evaluation of novel, environmental events in order to prepare for potential behavioral action. Here, we assessed the event-related hemodynamic (erfMRI) correlates of this phenomenon using unexpected (i.e., novel) environmental sounds presented within the context of an auditory novelty oddball paradigm. In ERP investigations of the novelty oddball, repetition of the identical novel sound leads to habituation of the novelty P3, an ERP sign of the orienting response. Repetition also leads to an enhancement of a subsequent positivity that appears to reflect semantic analysis of the environmental sounds. In this adaptation for erfMRI recording, frequent tones were intermixed randomly with infrequent target tones and equally infrequent novel, environmental sounds. Subjects responded via speeded button press to targets. To assess habituation, some of the environmental sounds were repeated 2 blocks after their initial presentation. As expected, novel sounds and target tones led to activation of widespread, but somewhat different, neural networks. Contrary to expectation, however, there were no significant areas in which activation was reduced in response to second compared to first presentations of the novel sounds. Conversely, novel sounds relative to target tones engendered activity in the inferior frontal gyrus (BA 45) consistent with semantic analysis of these events. We conclude that a key concomitant of the orienting response is the extraction of meaning, thereby enabling one to determine the significance of the environmental perturbation and take appropriate goal-directed action. PMID:18465750
Molecular contributions to neurovascular unit dysfunctions after brain injuries: lessons for target-specific drug development.
Jullienne, Amandine; Badaut, Jérôme
The revised 'expanded' neurovascular unit (eNVU) is a physiological and functional unit encompassing endothelial cells, pericytes, smooth muscle cells, astrocytes and neurons. Ischemic stroke and traumatic brain injury are acute brain injuries directly affecting the eNVU with secondary damage, such as blood-brain barrier (BBB) disruption, edema formation and hypoperfusion. BBB dysfunctions are observed at an early postinjury time point, and are associated with eNVU activation of proteases, such as tissue plasminogen activator and matrix metalloproteinases. BBB opening is accompanied by edema formation using astrocytic AQP4 as a key protein regulating water movement. Finally, nitric oxide dysfunction plays a dual role in association with BBB injury and dysregulation of cerebral blood flow. These mechanisms are discussed including all targets of eNVU encompassing endothelium, glial cells and neurons, as well as larger blood vessels with smooth muscle. In fact, the feeding blood vessels should also be considered to treat stroke and traumatic brain injury. This review underlines the importance of the eNVU in drug development aimed at improving clinical outcome after stroke and traumatic brain injury. PMID:24489483
High-Level CXCR4 Expression Correlates with Brain-Specific Metastasis of Non-Small Cell Lung Cancer
Gang Chen; Zhou Wang; Xiang-yan Liu; Fan-ying Liu
Background Brain-specific metastasis occurs frequently in lung cancer, and the mechanism is still unclear. The present study was designed\\u000a to investigate the correlation between CXCR4 expression and brain-specific metastasis of non-small cell lung cancer.\\u000a \\u000a \\u000a \\u000a \\u000a Methods The brain metastatic tumors and lung cancer tissues from 32 patients with solitary brain metastasis of non-small cell lung\\u000a cancer (M1 group), who underwent combined surgical treatment
Brain-specific BNIP-2-homology protein Caytaxin relocalises glutaminase to neurite terminals and reduces glutamate levels.
Buschdorf, Jan Paul; Li Chew, Li; Zhang, Bin; Cao, Qiong; Liang, Feng-Yi; Liou, Yih-Cherng; Zhou, Yi Ting; Low, Boon Chuan
Human Cayman ataxia and mouse or rat dystonia are linked to mutations in the genes ATCAY (Atcay) that encode BNIP-H or Caytaxin, a brain-specific member of the BNIP-2 family. To explore its possible role(s) in neuronal function, we used protein precipitation and matrix-assisted laser desorption/ionisation mass spectrometry and identified kidney-type glutaminase (KGA) as a novel partner of BNIP-H. KGA converts glutamine to glutamate, which could serve as an important source of neurotransmitter. Co-immunoprecipitation with specific BNIP-H antibody confirmed that endogenous BNIP-H and KGA form a physiological complex in the brain, whereas binding studies showed that they interact with each other directly. Immunohistochemistry and in situ hybridisation revealed high BNIP-H expression in hippocampus and cerebellum, broadly overlapping with the expression pattern previously reported for KGA. Significantly, BNIP-H expression was activated in differentiating neurons of the embryonic carcinoma cell line P19 whereas its overexpression in rat pheochromocytoma PC12 cells relocalised KGA from the mitochondria to neurite terminals. It also reduced the steady-state levels of glutamate by inhibiting KGA enzyme activity. These results strongly suggest that through binding to KGA, BNIP-H could regulate glutamate synthesis at synapses during neurotransmission. Thus, loss of BNIP-H function could render glutamate excitotoxicity or/and deregulated glutamatergic activation, leading to ataxia, dystonia or other neurological disorders. PMID:16899818
Source-based neurofeedback methods using EEG recordings: training altered brain activity in a functional brain source derived from blind source separation
White, David J.; Congedo, Marco; Ciorciari, Joseph
A developing literature explores the use of neurofeedback in the treatment of a range of clinical conditions, particularly ADHD and epilepsy, whilst neurofeedback also provides an experimental tool for studying the functional significance of endogenous brain activity. A critical component of any neurofeedback method is the underlying physiological signal which forms the basis for the feedback. While the past decade has seen the emergence of fMRI-based protocols training spatially confined BOLD activity, traditional neurofeedback has utilized a small number of electrode sites on the scalp. As scalp EEG at a given electrode site reflects a linear mixture of activity from multiple brain sources and artifacts, efforts to successfully acquire some level of control over the signal may be confounded by these extraneous sources. Further, in the event of successful training, these traditional neurofeedback methods are likely influencing multiple brain regions and processes. The present work describes the use of source-based signal processing methods in EEG neurofeedback. The feasibility and potential utility of such methods were explored in an experiment training increased theta oscillatory activity in a source derived from Blind Source Separation (BSS) of EEG data obtained during completion of a complex cognitive task (spatial navigation). Learned increases in theta activity were observed in two of the four participants to complete 20 sessions of neurofeedback targeting this individually defined functional brain source. Source-based EEG neurofeedback methods using BSS may offer important advantages over traditional neurofeedback, by targeting the desired physiological signal in a more functionally and spatially specific manner. Having provided preliminary evidence of the feasibility of these methods, future work may study a range of clinically and experimentally relevant brain processes where individual brain sources may be targeted by source-based EEG neurofeedback. PMID:25374520
California verbal learning test indicators of Malingered Neurocognitive Dysfunction: sensitivity and specificity in traumatic brain injury.
Curtis, Kelly L; Greve, Kevin W; Bianchini, Kevin J; Brennan, Adrianne
The present study used well-defined traumatic brain injury (TBI) and mixed neurological (other than TBI) and psychiatric samples to examine the specificity and sensitivity to Malingered Neurocognitive Dysfunction (MND) of four individual California Verbal Learning Test (CVLT) variables and eight composite CVLT malingering indicators. Participants were 275 traumatic brain injury and 352 general clinical patients seen for neuropsychological evaluation. The TBI patients were assigned to one of five groups using the Slick, Sherman, and Iverson (1999) criteria: no incentive, incentive only, suspect, and malingering (both Probable MND and Definite MND). Within TBI, persons with the strongest evidence for malingering (Probable and Definite) had the most extreme scores. Good sensitivity (approximately 50%) in the context of excellent specificity (> 95%) was found in the TBI samples. Issues related to the appropriate clinical application of these data are discussed. PMID:16443718
Evolution of human brain functions: the functional structure of human consciousness.
Cloninger, C Robert
The functional structure of self-aware consciousness in human beings is described based on the evolution of human brain functions. Prior work on heritable temperament and character traits is extended to account for the quantum-like and holographic properties (i.e. parts elicit wholes) of self-aware consciousness. Cladistic analysis is used to identify the succession of ancestors leading to human beings. The functional capacities that emerge along this lineage of ancestors are described. The ecological context in which each cladogenesis occurred is described to illustrate the shifting balance of evolution as a complex adaptive system. Comparative neuroanatomy is reviewed to identify the brain structures and networks that emerged coincident with the emergent brain functions. Individual differences in human temperament traits were well developed in the common ancestor shared by reptiles and humans. Neocortical development in mammals proceeded in five major transitions: from early reptiles to early mammals, early primates, simians, early Homo, and modern Homo sapiens. These transitions provide the foundation for human self-awareness related to sexuality, materiality, emotionality, intellectuality, and spirituality, respectively. The functional structure of human self-aware consciousness is concerned with the regulation of five planes of being: sexuality, materiality, emotionality, intellectuality, and spirituality. Each plane elaborates neocortical functions organized around one of the five special senses. The interactions among these five planes gives rise to a 5 x 5 matrix of subplanes, which are functions that coarsely describe the focus of neocortical regulation. Each of these 25 neocortical functions regulates each of five basic motives or drives that can be measured as temperaments or basic emotions related to fear, anger, disgust, surprise, and happiness/sadness. The resulting 5 x 5 x 5 matrix of human characteristics provides a general and testable model of the functional structure of human consciousness that includes personality, physicality, emotionality, cognition, and spirituality in a unified developmental framework. PMID:20001395
Changes in the levels of neural cell specific proteins in the developing rat brain
T. Matsutani; M. Nagayoshi; M. Tamaru; Y. Hirata; K. Kato
The levels of S-100 protein (S-100) and neuron-specific enolase (NSE) in the developing rat brain were determined by a sensitive enzyme immunoassay and the results were compared with those obtained by other methods. Changes with development in the levels of S-100, NSE, and 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), biochemical markers for astroglia, neurons and oligodendroglia respectively, were determined in various
Brain-specific proteins in the occipital cortex of rats housed in enriched and impoverished environments
Ole Steen Jřrgensen; Elisabeth Bock
The occipital cortex was dissected from the brain of rats housed in either enriched or impoverished environment for four weeks. In environmentally enriched rats the weight of occipital cortex was found to be increased 5.7%, compared to environmentally improverished rats, and the amount of protein was increased 6.0%. The amount of six nervous system-specific proteins was measured by crossed immunoelectrophoresis.
A brain-specific microRNA regulates dendritic spine development
Gerhard M. Schratt; Fabian Tuebing; Elizabeth A. Nigh; Christina G. Kane; Mary E. Sabatini; Michael Kiebler; Michael E. Greenberg
MicroRNAs are small, non-coding RNAs that control the translation of target messenger RNAs, thereby regulating critical aspects of plant and animal development. In the mammalian nervous system, the spatiotemporal control of mRNA translation has an important role in synaptic development and plasticity. Although a number of microRNAs have been isolated from the mammalian brain, neither the specific microRNAs that regulate
Specific binding of 3 H-adenosine to rat brain membranes
U. Schwabe; H. Kiffe; C. Puchstein; T. Trost
The binding of 3H-adenosine to rat brain membranes was studied by a microcentrifugation technique. Specific binding of 3H-adenosine was rapid, reversible, saturable and dependent on pH and temperature. Scatchard plots of equilibrium binding data were nonlinear suggesting the existence of two different binding sites for adenosine. The dissociation constants (Kd) were 1.7 µM and 13.6 µM and the maximal number
Imaging local brain function with emission computed tomography
Kuhl, D.E.
Positron emission tomography (PET) using /sup 18/F-fluorodeoxyglucose (FDG) was used to map local cerebral glucose utilization in the study of local cerebral function. This information differs fundamentally from structural assessment by means of computed tomography (CT). In normal human volunteers, the FDG scan was used to determine the cerebral metabolic response to conrolled sensory stimulation and the effects of aging. Cerebral metabolic patterns are distinctive among depressed and demented elderly patients. The FDG scan appears normal in the depressed patient, studded with multiple metabolic defects in patients with multiple infarct dementia, and in the patients with Alzheimer disease, metabolism is particularly reduced in the parietal cortex, but only slightly reduced in the caudate and thalamus. The interictal FDG scan effectively detects hypometabolic brain zones that are sites of onset for seizures in patients with partial epilepsy, even though these zones usually appear normal on CT scans. The future prospects of PET are discussed.
Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity
Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl
Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network—disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses. PMID:24566670
Functional brain changes underlying irritability in premanifest Huntington's disease.
Van den Stock, Jan; De Winter, François-Laurent; Ahmad, Rawaha; Sunaert, Stefan; Van Laere, Koen; Vandenberghe, Wim; Vandenbulcke, Mathieu
The clinical phenotype of Huntington's disease (HD) consists of motor, cognitive and psychiatric symptoms, of which irritability is an important manifestation. Our aim was to identify the functional and structural brain changes that underlie irritability in premanifest HD (preHD). Twenty preHD carriers and 20 gene-negative controls from HD families took part in the study. Although the 5-year probability of disease onset was only 11%, the preHD group showed striatal atrophy and increased clinical irritability ratings. Functional MRI was performed during a mood induction experiment by means of recollection of emotional (angry, sad, and happy) and neutral autobiographical episodes. While there were no significant group differences in the subjective intensity of the emotional experience, the preHD group showed increased anger-selective activation in a distributed network, including the pulvinar, cingulate cortex, and somatosensory association cortex, compared to gene-negative controls. Pulvinar activation during anger experience correlated negatively with putaminal grey matter volume and positively with irritability ratings in the preHD group. In addition, the preHD group showed a decrease in anger-selective activation in the amygdala, which correlated with putaminal and caudate grey matter volume. In conclusion, compared to gene-negative controls, anger experience in preHD is associated with activity changes in a distributed set of regions known to be involved in emotion regulation. Increased activity is related to behavioral and volumetric measures, providing insight in the pathophysiology of early neuropsychiatric symptoms in preHD. Hum Brain Mapp 36:2681-2690, 2015. © 2015 Wiley Periodicals, Inc. PMID:25858294
Delayed convergence between brain network structure and function in rolandic epilepsy
Besseling, René M. H.; Jansen, Jacobus F. A.; Overvliet, Geke M.; van der Kruijs, Sylvie J. M.; Ebus, Saskia C. M.; de Louw, Anton J. A.; Hofman, Paul A. M.; Aldenkamp, Albert P.; Backes, Walter H.
Introduction: Rolandic epilepsy (RE) manifests during a critical phase of brain development, and has been associated with language impairments. Concordant abnormalities in structural and functional connectivity (SC and FC) have been described before. As SC and FC are under mutual influence, the current study investigates abnormalities in the SC-FC synergy in RE. Methods: Twenty-two children with RE (age, mean ± SD: 11.3 ± 2.0 y) and 22 healthy controls (age 10.5 ± 1.6 y) underwent structural, diffusion weighted, and resting-state functional magnetic resonance imaging (MRI) at 3T. The probabilistic anatomical landmarks atlas was used to parcellate the (sub)cortical gray matter. Constrained spherical deconvolution tractography and correlation of time series were used to assess SC and FC, respectively. The SC-FC correlation was assessed as a function of age for the non-zero structural connections over a range of sparsity values (0.01–0.75). A modularity analysis was performed on the mean SC network of the controls to localize potential global effects to subnetworks. SC and FC were also assessed separately using graph analysis. Results: The SC-FC correlation was significantly reduced in children with RE compared to healthy controls, especially for the youngest participants. This effect was most pronounced in a left and a right centro-temporal network, as well as in a medial parietal network. Graph analysis revealed no prominent abnormalities in SC or FC network organization. Conclusion: Since SC and FC converge during normal maturation, our finding of reduced SC-FC correlation illustrates impaired synergy between brain structure and function. More specifically, since this effect was most pronounced in the youngest participants, RE may represent a developmental disorder of delayed brain network maturation. The observed effects seem especially attributable to medial parietal connections, which forms an intermediate between bilateral centro-temporal modules of epileptiform activity, and bear relevance for language function. PMID:25249968
Preferential Detachment During Human Brain Development: Age- and Sex-Specific Structural Connectivity in Diffusion Tensor Imaging (DTI) Data.
Lim, Sol; Han, Cheol E; Uhlhaas, Peter J; Kaiser, Marcus
Human brain maturation is characterized by the prolonged development of structural and functional properties of large-scale networks that extends into adulthood. However, it is not clearly understood which features change and which remain stable over time. Here, we examined structural connectivity based on diffusion tensor imaging (DTI) in 121 participants between 4 and 40 years of age. DTI data were analyzed for small-world parameters, modularity, and the number of fiber tracts at the level of streamlines. First, our findings showed that the number of fiber tracts, small-world topology, and modular organization remained largely stable despite a substantial overall decrease in the number of streamlines with age. Second, this decrease mainly affected fiber tracts that had a large number of streamlines, were short, within modules and within hemispheres; such connections were affected significantly more often than would be expected given their number of occurrences in the network. Third, streamline loss occurred earlier in females than in males. In summary, our findings suggest that core properties of structural brain connectivity, such as the small-world and modular organization, remain stable during brain maturation by focusing streamline loss to specific types of fiber tracts. PMID:24343892
Human brain derived cells respond in a type-specific manner after exposure to urban particulate matter (PM).
Campbell, Arezoo; Daher, Nancy; Solaimani, Parrisa; Mendoza, Kriscelle; Sioutas, Constantinos
Exposure to particulate matter (PM), a component of urban air pollution, may cause adverse effects in the brain. Although the exact mechanisms involved are unknown, both oxidative and inflammatory responses have been reported. Since the main route of exposure to particulate matter is through inhalation, there is a potential for compounds to directly enter the brain and alter normal cellular function. Enhancement in both oxidative stress and neuroinflammatory markers has been observed in neurodegenerative disorders and PM-induced potentiation of these events may accelerate the disease process. The objective of this pilot study was to use normal human brain cells, a model system which has not been previously used, to assess cell-type-specific responses after exposure to ultrafine particles (UFP). Human microglia, neurons, and astrocytes were grown separately or as co-cultures and then exposed to aqueous UFP suspensions. Reactive Oxygen Species (ROS) formation and the proinflammatory cytokine tumor necrosis factor alpha (TNF-?) were measured as markers of oxidative stress or inflammation respectively. Our results revealed that after exposure to 2 ?g/ml of particles, normal human neurons exhibit a decrease in ROS formation and an increase in TNF-?. The observed decrease in ROS formation persisted in the presence of glial cells, which contrasts previous studies done in rodent cells reporting that PM-induced microglial activation modulates neuronal responses. Our study indicates that human CNS cells may respond differently compared to rodent cells and that their use may be more predictive in risk assessment. PMID:24999231
Changes in functional brain networks following sports-related concussion in adolescents.
Virji-Babul, Naznin; Hilderman, Courtney G E; Makan, Nadia; Liu, Aiping; Smith-Forrester, Jenna; Franks, Chris; Wang, Z J
Sports-related concussion is a major public health issue; however, little is known about the underlying changes in functional brain networks in adolescents following injury. Our aim was to use the tools from graph theory to evaluate the changes in brain network properties following concussion in adolescent athletes. We recorded resting state electroencephalography (EEG) in 33 healthy adolescent athletes and 9 adolescent athletes with a clinical diagnosis of subacute concussion. Graph theory analysis was applied to these data to evaluate changes in brain networks. Global and local metrics of the structural properties of the graph were calculated for each group and correlated with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) scores. Brain networks of both groups showed small-world topology with no statistically significant differences in the global metrics; however, significant differences were found in the local metrics. Specifically, in the concussed group, we noted: 1) increased values of betweenness and degree in frontal electrode sites corresponding to the (R) dorsolateral prefrontal cortex and the (R) inferior frontal gyrus and 2) decreased values of degree in the region corresponding to the (R) frontopolar prefrontal cortex. In addition, there was significant negative correlation between degree and hub value, with total symptom score at the electrode site corresponding to the (R) prefrontal cortex. This preliminary report in adolescent athletes shows for the first time that resting-state EEG combined with graph theoretical analysis may provide an objective method of evaluating changes in brain networks following concussion. This approach may be useful in identifying individuals at risk for future injury. PMID:24956041
Immunological Studies of Chicken Brain: Isolation, Purification, and Localization of a Neural Specific Protein CNA-1
James Douglas Redshaw
The differentiation of any cell leads to the synthesis of certain proteins which are responsible for its specific function. In the nervous system this includes such functions as the conductance of action potentials, synaptic transmission and the establishment of specific connections. The developmental biology of proteins unique to the nervous system is therefore of great importance when studying the relationship
Neurovascular coupling: in vivo optical techniques for functional brain imaging
Optical imaging techniques reflect different biochemical processes in the brain, which is closely related with neural activity. Scientists and clinicians employ a variety of optical imaging technologies to visualize and study the relationship between neurons, glial cells and blood vessels. In this paper, we present an overview of the current optical approaches used for the in vivo imaging of neurovascular coupling events in small animal models. These techniques include 2-photon microscopy, laser speckle contrast imaging (LSCI), voltage-sensitive dye imaging (VSDi), functional photoacoustic microscopy (fPAM), functional near-infrared spectroscopy imaging (fNIRS) and multimodal imaging techniques. The basic principles of each technique are described in detail, followed by examples of current applications from cutting-edge studies of cerebral neurovascular coupling functions and metabolic. Moreover, we provide a glimpse of the possible ways in which these techniques might be translated to human studies for clinical investigations of pathophysiology and disease. In vivo optical imaging techniques continue to expand and evolve, allowing us to discover fundamental basis of neurovascular coupling roles in cerebral physiology and pathophysiology. PMID:23631798
Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses.
Iraji, Armin; Benson, Randall R; Welch, Robert D; O'Neil, Brian J; Woodard, John L; Ayaz, Syed Imran; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E Mark; Kou, Zhifeng
Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363
Low mass-specific brain Na+/K+-ATPase activity in elasmobranch compared to teleost fishes: implications for the large brain size of elasmobranchs.
Nilsson, G E; Routley, M H; Renshaw, G M
Elasmobranch fishes have long been noted for having unusually large brains for ectotherms, and therefore may be exceptions to the rule that vertebrates in general devote less than 8% of their resting metabolic rate to the central nervous system. The brain mass of sharks, skates and rays is often several times larger than that of teleost fishes of the same size. Still, the underlying reasons for this have remained unclear. Ion pumping by the Na+/K+-ATPase is the single most energy consuming process in the brain. In this study, Na+/K+-ATPase activity was measured in the brain of four species of elasmobranchs and 11 species of teleosts. While the average brain mass of the elasmobranchs examined was approximately three times that of the teleosts, the mean specific Na+/K+-ATPase activity was only about one-third of that of the teleosts. Thus, the total brain Na+/K+-ATPase activity was similar in elasmobranchs and teleosts. This suggests that the large brain size of elasmobranchs is at least partly related to a low mass-specific rate of brain energy use. PMID:10972129
Graph analysis of functional brain networks: practical issues in translational neuroscience.
De Vico Fallani, Fabrizio; Richiardi, Jonas; Chavez, Mario; Achard, Sophie
The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective, communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires the know-how of all the methodological steps of the pipeline that manipulate the input brain signals and extract the functional network properties. On the other hand, knowledge of the neural phenomenon under study is required to perform physiologically relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes. PMID:25180301
The impact of alcohol dependence on social brain function.
Gizewski, Elke R; Müller, Bernhard W; Scherbaum, Norbert; Lieb, Bodo; Forsting, Michael; Wiltfang, Jens; Leygraf, Norbert; Schiffer, Boris
The impact of alcoholism (ALC) or alcohol dependence on the neural mechanisms underlying cognitive and affective empathy (i.e. the different routes to understanding other people's minds) in schizophrenic patients and non-schizophrenic subjects is still poorly understood. We therefore aimed at determining the extent to which the ability to infer other people's mental states and underlying neural mechanisms were affected by ALC. We examined 48 men, who suffered either from ALC, schizophrenia, both disorders or none of these disorders, using functional magnetic resonance imaging while performing on a mind reading task that involves both cognitive and affective aspects of empathy. Using voxel-based morphometry, we additionally examined whether between-group differences in functional activity were associated with deficits in brain structural integrity. During mental state attribution, all clinical groups as compared with healthy controls exhibited poor performance as well as reduced right-hemispheric insular function with the highest error rate and insular dysfunction seen in the schizophrenic patients without ALC. Accordingly, both behavioral performance and insular functioning revealed schizophrenia × ALC interaction effects. In addition, schizophrenic patients relative to non-schizophrenic subjects (regardless of ALC) exhibited deficits in structural integrity and task-related recruitment of the left ventrolateral prefrontal cortex (vlPFC). Our data suggest that ALC-related impairment in the ability to infer other people's mental states is limited to insular dysfunction and thus deficits in affective empathy. By contrast, mentalizing in schizophrenia (regardless of ALC) may be associated with insular dysfunction as well as a combination of structural and functional deficits in the left vlPFC. PMID:22340281
The discovery of population differences in network community structure: New methods and applications to brain functional networks in schizophrenia
Alexander-Bloch, Aaron; Lambiotte, Renaud; Roberts, Ben; Giedd, Jay; Gogtay, Nitin; Bullmore, Ed
The modular organization of the brain network can vary in two fundamental ways. The amount of interversus intra-modular connections between network nodes can be altered, or the community structure itself can be perturbed, in terms of which nodes belong to which modules (or communities). Alterations have previously been reported in modularity, which is a function of the proportion of intra-modular edges over all modules in the network. For example, we have reported that modularity is decreased in functional brain networks in schizophrenia: There are proportionally more inter-modular edges and fewer intra-modular edges. However, despite numerous and increasing studies of brain modular organization, it is not known how to test for differences in the community structure, i.e., the assignment of regional nodes to specific modules. Here, we introduce a method based on the normalized mutual information between pairs of modular networks to show that the community structure of the brain network is significantly altered in schizophrenia, using resting-state fMRI in 19 participants with childhood-onset schizophrenia and 20 healthy participants. We also develop tools to show which specific nodes (or brain regions) have significantly different modular communities between groups, a subset that includes right insular and perisylvian cortical regions. The methods that we propose are broadly applicable to other experimental contexts, both in neuroimaging and other areas of network science. PMID:22119652
Purification, characterization and developmental expression of a brain-specific chondroitin sulfate proteoglycan, 6B4 proteoglycan\\/phosphacan
N. Maeda; H. Hamanaka; A. Oohira; M. Noda
A large brain-specific chondroitin sulfate proteoglycan, identified with monoclonal antibody 6B4 (6B4 proteoglycan\\/phosphacan), was isolated from rat brain. Soluble proteoglycans in the phosphate-buffered saline extract from 20-day-old rat whole brain were fractionated by anion exchange chromatography and CsCl density gradient centrifugation. 6B4 proteoglycan was further purified by gel filtration and additional ion exchange chromatography. The molecular mass of 6B4 proteoglycan
Functional source separation and hand cortical representation for a brain–computer interface feature extraction
Tecchio, Franca; Porcaro, Camillo; Barbati, Giulia; Zappasodi, Filippo
A brain–computer interface (BCI) can be defined as any system that can track the person's intent which is embedded in his/her brain activity and, from it alone, translate the intention into commands of a computer. Among the brain signal monitoring systems best suited for this challenging task, electroencephalography (EEG) and magnetoencephalography (MEG) are the most realistic, since both are non-invasive, EEG is portable and MEG could provide more specific information that could be later exploited also through EEG signals. The first two BCI steps require set up of the appropriate experimental protocol while recording the brain signal and then to extract interesting features from the recorded cerebral activity. To provide information useful in these BCI stages, our aim is to provide an overview of a new procedure we recently developed, named functional source separation (FSS). As it comes from the blind source separation algorithms, it exploits the most valuable information provided by the electrophysiological techniques, i.e. the waveform signal properties, remaining blind to the biophysical nature of the signal sources. FSS returns the single trial source activity, estimates the time course of a neuronal pool along different experimental states on the basis of a specific functional requirement in a specific time period, and uses the simulated annealing as the optimization procedure allowing the exploit of functional constraints non-differentiable. Moreover, a minor section is included, devoted to information acquired by MEG in stroke patients, to guide BCI applications aiming at sustaining motor behaviour in these patients. Relevant BCI features – spatial and time-frequency properties – are in fact altered by a stroke in the regions devoted to hand control. Moreover, a method to investigate the relationship between sensory and motor hand cortical network activities is described, providing information useful to develop BCI feedback control systems. This review provides a description of the FSS technique, a promising tool for the BCI community for online electrophysiological feature extraction, and offers interesting information to develop BCI applications to sustain hand control in stroke patients. PMID:17331989
Common and specific cognitive deficits in schizophrenia: relationships to function
of the leading causes of disability in the United States (Ormel et al., 2008). Therefore, cognitionCommon and specific cognitive deficits in schizophrenia: relationships to function Julia M in schizophrenia, and to determine the ability of tasks from each battery to predict functional outcome. Subjects
A Model of Functional Brain Connectivity and Background Noise as a Biomarker for Cognitive Phenotypes: Application to Autism
Domínguez, Luis García; Velázquez, José Luis Pérez; Galán, Roberto Fernández
We present an efficient approach to discriminate between typical and atypical brains from macroscopic neural dynamics recorded as magnetoencephalograms (MEG). Our approach is based on the fact that spontaneous brain activity can be accurately described with stochastic dynamics, as a multivariate Ornstein-Uhlenbeck process (mOUP). By fitting the data to a mOUP we obtain: 1) the functional connectivity matrix, corresponding to the drift operator, and 2) the traces of background stochastic activity (noise) driving the brain. We applied this method to investigate functional connectivity and background noise in juvenile patients (n?=?9) with Asperger's syndrome, a form of autism spectrum disorder (ASD), and compared them to age-matched juvenile control subjects (n?=?10). Our analysis reveals significant alterations in both functional brain connectivity and background noise in ASD patients. The dominant connectivity change in ASD relative to control shows enhanced functional excitation from occipital to frontal areas along a parasagittal axis. Background noise in ASD patients is spatially correlated over wide areas, as opposed to control, where areas driven by correlated noise form smaller patches. An analysis of the spatial complexity reveals that it is significantly lower in ASD subjects. Although the detailed physiological mechanisms underlying these alterations cannot be determined from macroscopic brain recordings, we speculate that enhanced occipital-frontal excitation may result from changes in white matter density in ASD, as suggested in previous studies. We also venture that long-range spatial correlations in the background noise may result from less specificity (or more promiscuity) of thalamo-cortical projections. All the calculations involved in our analysis are highly efficient and outperform other algorithms to discriminate typical and atypical brains with a comparable level of accuracy. Altogether our results demonstrate a promising potential of our approach as an efficient biomarker for altered brain dynamics associated with a cognitive phenotype. PMID:23613864
Changes in Connectivity after Visual Cortical Brain Damage Underlie Altered Visual Function
ERIC Educational Resources Information Center
Bridge, Holly; Thomas, Owen; Jbabdi, Saad; Cowey, Alan
The full extent of the brain's ability to compensate for damage or changed experience is yet to be established. One question particularly important for evaluating and understanding rehabilitation following brain damage is whether recovery involves new and aberrant neural connections or whether any change in function is due to the functional…
Functional outcomes and quality of life in patients with brain tumors: A preliminary report
Mark E. Huang; Jennifer E. Wartella; Jeffery S. Kreutzer
Huang ME, Wartella JE, Kreutzer JS. Functional outcomes and quality of life in patients with brain tumors: a preliminary report. Arch Phys Med Rehabil 2001;82:1540-6. Objectives: To determine the relationship between functional outcome and quality of life (QOL) in patients with brain tumors receiving inpatient rehabilitation, and to assess the sensitivity of 4 assessment tools in measuring changes in that
r Human Brain Mapping 00:000000 (2012) r Key Functional Circuitry Altered in Schizophrenia
Feng, Jianfeng
r Human Brain Mapping 00:000000 (2012) r Key Functional Circuitry Altered in Schizophrenia functional and structural changes in the brain in schizophrenia are of most importance, although the main schizophrenia patients, and func- tional connectivity changes were analyzed using resting-state fMRI data from
An independent component analysis based tool for exploring functional connections in the brain
Washington at Seattle, University of
An independent component analysis based tool for exploring functional connections in the brain S. M for investigating functional connectivity in the brain. Independent component analysis (ICA) is used as a measure of voxel similarity which allows the user to find and view statistically independent maps of correlated
Selectionist models of perceptual and motor systems and implications for functionalist theories of brain function
George N. Reeke; Olaf Sporns
Functionalism is at present widely accepted as a working basis for cognitive science and artificial intelligence. This view holds that psychological phenomena can be adequately described in terms of functional processes carried out in the brain, and that these processes can be understood independently of the detailed structure and mode of development of the brain. In the functionalist view, the
Brain–machine interfaces to restore motor function and probe neural circuits
Miguel A. L. Nicolelis
Recent studies have shown that it is possible to create functional, bidirectional, real-time interfaces between living brain tissue and artificial devices. It is reasonable to predict that further research on brain–machine interfaces will lead to the development of a new generation of neuroprosthetic devices aimed at restoring motor functions in severely paralysed patients. In addition, I propose that such interfaces
Mapping Language Function in the Brain: A Review of the Recent Literature.
ERIC Educational Resources Information Center
Crafton, Robert E.; Kido, Elissa
Considers the potential importance of brain study for composition instruction, briefly describes functional imaging techniques, and reviews the findings of recent brain-mapping studies investigating the neurocognitive systems involved in language function. Presents a review of the recent literature and considers the possible implications of this…
From the Left to the Right: How the Brain Compensates Progressive Loss of Language Function
ERIC Educational Resources Information Center
Thiel, Alexander; Habedank, Birgit; Herholz, Karl; Kessler, Josef; Winhuisen, Lutz; Haupt, Walter F.; Heiss, Wolf-Dieter
In normal right-handed subjects language production usually is a function of the left brain hemisphere. Patients with aphasia following brain damage to the left hemisphere have a considerable potential to compensate for the loss of this function. Sometimes, but not always, areas of the right hemisphere which are homologous to language areas of the…
Language-specific dysgraphia in Korean patients with right brain stroke: influence of unilateral spatial neglect.
Jang, Dae-Hyun; Kim, Min-Wook; Park, Kyoung Ha; Lee, Jae Woo
The purpose of the present study was to investigate the relationship between Korean language-specific dysgraphia and unilateral spatial neglect in 31 right brain stroke patients. All patients were tested for writing errors in spontaneous writing, dictation, and copying tests. The dysgraphia was classified into visuospatial omission, visuospatial destruction, syllabic tilting, stroke omission, stroke addition, and stroke tilting. Twenty-three (77.4%) of the 31 patients made dysgraphia and 18 (58.1%) demonstrated unilateral spatial neglect. The visuospatial omission was the most common dysgraphia followed by stroke addition and omission errors. The highest number of errors was made in the copying and the least was in the spontaneous writing test. Patients with unilateral spatial neglect made a significantly higher number of dysgraphia in the copying test than those without. We identified specific dysgraphia features such as a right side space omission and a vertical stroke addition in Korean right brain stroke patients. In conclusion, unilateral spatial neglect influences copy writing system of Korean language in patients with right brain stroke. PMID:25729257
Brain potentials index executive functions during random number generation.
Joppich, Gregor; Däuper, Jan; Dengler, Reinhard; Johannes, Sönke; Rodriguez-Fornells, Antoni; Münte, Thomas F
The generation of random sequences is considered to tax different executive functions. To explore the involvement of these functions further, brain potentials were recorded in 16 healthy young adults while either engaging in random number generation (RNG) by pressing the number keys on a computer keyboard in a random sequence or in ordered number generation (ONG) necessitating key presses in the canonical order. Key presses were paced by an external auditory stimulus to yield either fast (1 press/800 ms) or slow (1 press/1300 ms) sequences in separate runs. Attentional demands of random and ordered tasks were assessed by the introduction of a secondary task (key-press to a target tone). The P3 amplitude to the target tone of this secondary task was reduced during RNG, reflecting the greater consumption of attentional resources during RNG. Moreover, RNG led to a left frontal negativity peaking 140 ms after the onset of the pacing stimulus, whenever the subjects produced a true random response. This negativity could be attributed to the left dorsolateral prefrontal cortex and was absent when numbers were repeated. This negativity was interpreted as an index for the inhibition of habitual responses. Finally, in response locked ERPs a negative component was apparent peaking about 50 ms after the key-press that was more prominent during RNG. Source localization suggested a medial frontal source. This effect was tentatively interpreted as a reflection of the greater monitoring demands during random sequence generation. PMID:15140558
Combining specificity determining and conserved residues improves functional site prediction
Olga V. Kalinina; Mikhail S. Gelfand; Robert B. Russell
BACKGROUND: Predicting the location of functionally important sites from protein sequence and\\/or structure is a long-standing problem in computational biology. Most current approaches make use of sequence conservation, assuming that amino acid residues conserved within a protein family are most likely to be functionally important. Most often these approaches do not consider many residues that act to define specific sub-functions
Brain activation and inhibition after acupuncture at Taichong and Taixi: resting-state functional magnetic resonance imaging.
Zhang, Shao-Qun; Wang, Yan-Jie; Zhang, Ji-Ping; Chen, Jun-Qi; Wu, Chun-Xiao; Li, Zhi-Peng; Chen, Jia-Rong; Ouyang, Huai-Liang; Huang, Yong; Tang, Chun-Zhi
Acupuncture can induce changes in the brain. However, the majority of studies to date have focused on a single acupoint at a time. In the present study, we observed activity changes in the brains of healthy volunteers before and after acupuncture at Taichong (LR3) and Taixi (KI3) using resting-state functional magnetic resonance imaging. Fifteen healthy volunteers underwent resting-state functional magnetic resonance imaging of the brain 15 minutes before acupuncture, then received acupuncture at Taichong and Taixi using the nail-pressing needle insertion method, after which the needle was retained in place for 30 minutes. Fifteen minutes after withdrawal of the needle, the volunteers underwent a further session of resting-state functional magnetic resonance imaging, which revealed that the amplitude of low-frequency fluctuation, a measure of spontaneous neuronal activity, increased mainly in the cerebral occipital lobe and middle occipital gyrus (Brodmann area 18/19), inferior occipital gyrus (Brodmann area 18) and cuneus (Brodmann area 18), but decreased mainly in the gyrus rectus of the frontal lobe (Brodmann area 11), inferior frontal gyrus (Brodmann area 44) and the center of the posterior lobe of the cerebellum. The present findings indicate that acupuncture at Taichong and Taixi specifically promote blood flow and activation in the brain areas related to vision, emotion and cognition, and inhibit brain areas related to emotion, attention, phonological and semantic processing, and memory. PMID:25883630
Brain activation and inhibition after acupuncture at Taichong and Taixi: resting-state functional magnetic resonance imaging
Zhang, Shao-qun; Wang, Yan-jie; Zhang, Ji-ping; Chen, Jun-qi; Wu, Chun-xiao; Li, Zhi-peng; Chen, Jia-rong; Ouyang, Huai-liang; Huang, Yong; Tang, Chun-zhi
Acupuncture can induce changes in the brain. However, the majority of studies to date have focused on a single acupoint at a time. In the present study, we observed activity changes in the brains of healthy volunteers before and after acupuncture at Taichong (LR3) and Taixi (KI3) using resting-state functional magnetic resonance imaging. Fifteen healthy volunteers underwent resting-state functional magnetic resonance imaging of the brain 15 minutes before acupuncture, then received acupuncture at Taichong and Taixi using the nail-pressing needle insertion method, after which the needle was retained in place for 30 minutes. Fifteen minutes after withdrawal of the needle, the volunteers underwent a further session of resting-state functional magnetic resonance imaging, which revealed that the amplitude of low-frequency fluctuation, a measure of spontaneous neuronal activity, increased mainly in the cerebral occipital lobe and middle occipital gyrus (Brodmann area 18/19), inferior occipital gyrus (Brodmann area 18) and cuneus (Brodmann area 18), but decreased mainly in the gyrus rectus of the frontal lobe (Brodmann area 11), inferior frontal gyrus (Brodmann area 44) and the center of the posterior lobe of the cerebellum. The present findings indicate that acupuncture at Taichong and Taixi specifically promote blood flow and activation in the brain areas related to vision, emotion and cognition, and inhibit brain areas related to emotion, attention, phonological and semantic processing, and memory. PMID:25883630
Gene Risk Factors for Age-Related Brain Disorders May Affect Immune System Function
... factors for age-related brain disorders may affect immune system function June 17, 2014 Scientists have discovered gene ... risk factors for age-related neurological disorders to immune system functions, such as inflammation, offers new insights into ...
Use of functional specifications as objective functions in topological optimization of compliant mechanism
G. K. Lau; H. Du; M. K. Lim
Instead of using the concepts of minimum compliance or maximum mutual compliance, alternative formulation, based on functional specification is proposed to solve for topology of compliant mechanism. Among mechanical advantage, geometrical advantage and work ratio, one of the functional specifications is posed as objective function while displacement constraint and material constraint are imposed. The topological design of compliant mechanism is
Control over brain activation and pain learned by using real-time functional MRI
deCharms, R. Christopher; Maeda, Fumiko; Glover, Gary H.; Ludlow, David; Pauly, John M.; Soneji, Deepak; Gabrieli, John D. E.; Mackey, Sean C.
If an individual can learn to directly control activation of localized regions within the brain, this approach might provide control over the neurophysiological mechanisms that mediate behavior and cognition and could potentially provide a different route for treating disease. Control over the endogenous pain modulatory system is a particularly important target because it could enable a unique mechanism for clinical control over pain. Here, we found that by using real-time functional MRI (rtfMRI) to guide training, subjects were able to learn to control activation in the rostral anterior cingulate cortex (rACC), a region putatively involved in pain perception and regulation. When subjects deliberately induced increases or decreases in rACC fMRI activation, there was a corresponding change in the perception of pain caused by an applied noxious thermal stimulus. Control experiments demonstrated that this effect was not observed after similar training conducted without rtfMRI information, or using rtfMRI information derived from a different brain region, or sham rtfMRI information derived previously from a different subject. Chronic pain patients were also trained to control activation in rACC and reported decreases in the ongoing level of chronic pain after training. These findings show that individuals can gain voluntary control over activation in a specific brain region given appropriate training, that voluntary control over activation in rACC leads to control over pain perception, and that these effects were powerful enough to impact severe, chronic clinical pain. PMID:16352728
The effects of sleep deprivation on brain functioning in older adults.
Almklov, Erin L; Drummond, Sean P A; Orff, Henry; Alhassoon, Omar M
Few studies have examined the effects of total sleep deprivation (TSD) on cognitive performance and brain activation using functional MRI (fMRI) in older adults. The current study examines blood oxygen level-dependent (BOLD) activation in older adults and younger adults during the sustained attention (GO) and response inhibition (NOGO) portions of a GO-NOGO cognitive task following 36 hr of total sleep deprivation. No significant performance differences were observed between the groups on the behavioral outcome measures of total hits and false alarms. Neuroimaging results, however, revealed a significant interaction between age-group and sleep-deprivation status. Specifically, older adults showed greater BOLD activation as compared to younger adults after 36 hours total sleep deprivation in brain regions typically associated with attention and inhibitory processes. These results suggest in order for older adults to perform the GO-NOGO task effectively after sleep deprivation, they rely on compensatory recruitment of brain regions that aide in the maintenance of cognitive performance. PMID:24787041
Functional MRI of the vocalization-processing network in the macaque brain
Ortiz-Rios, Michael; Ku?mierek, Pawe?; DeWitt, Iain; Archakov, Denis; Azevedo, Frederico A. C.; Sams, Mikko; Jääskeläinen, Iiro P.; Keliris, Georgios A.; Rauschecker, Josef P.
Using functional magnetic resonance imaging in awake behaving monkeys we investigated how species-specific vocalizations are represented in auditory and auditory-related regions of the macaque brain. We found clusters of active voxels along the ascending auditory pathway that responded to various types of complex sounds: inferior colliculus (IC), medial geniculate nucleus (MGN), auditory core, belt, and parabelt cortex, and other parts of the superior temporal gyrus (STG) and sulcus (STS). Regions sensitive to monkey calls were most prevalent in the anterior STG, but some clusters were also found in frontal and parietal cortex on the basis of comparisons between responses to calls and environmental sounds. Surprisingly, we found that spectrotemporal control sounds derived from the monkey calls ("scrambled calls") also activated the parietal and frontal regions. Taken together, our results demonstrate that species-specific vocalizations in rhesus monkeys activate preferentially the auditory ventral stream, and in particular areas of the antero-lateral belt and parabelt. PMID:25883546
Stimulus-specific induction of an Egr-1 transgene in rat brain.
Slade, J Paul; Man, P-S; Wells, T; Carter, D A
Regulated expression of Egr-1 (Zif268/NGFIA) in a variety of brain networks suggests a diversity of roles in neuronal plasticity. Here, we aimed to determine whether an egr-1 transgene would mediate transcriptional responses to different pharmacological and physiological stimuli in the brain of transgenic rats. Constitutive transgene expression was observed in the cortex, CA1 hippocampal area and pituitary, recapitulating expression of egr-1. Transgene induction was stimulus-specific. Metrazole induced widespread expression in the dentate gyrus, CA2 and CA3 areas, amygdala, and ventromedial nucleus. In contrast, induction following a light stimulus was restricted to the hypothalamic suprachiasmatic and periventricular nuclei. Our studies have provided novel insights into the differential regulation of egr-1, and facilitated approaches to the genetic manipulation of Egr-1-regulated neuronal systems. PMID:11973468
Non-synaptic receptors and transporters involved in brain functions and targets of drug treatment
Vizi, ES; Fekete, A; Karoly, R; Mike, A
Beyond direct synaptic communication, neurons are able to talk to each other without making synapses. They are able to send chemical messages by means of diffusion to target cells via the extracellular space, provided that the target neurons are equipped with high-affinity receptors. While synaptic transmission is responsible for the 'what' of brain function, the 'how' of brain function (mood, attention, level of arousal, general excitability, etc.) is mainly controlled non-synaptically using the extracellular space as communication channel. It is principally the 'how' that can be modulated by medicine. In this paper, we discuss different forms of non-synaptic transmission, localized spillover of synaptic transmitters, local presynaptic modulation and tonic influence of ambient transmitter levels on the activity of vast neuronal populations. We consider different aspects of non-synaptic transmission, such as synaptic–extrasynaptic receptor trafficking, neuron–glia communication and retrograde signalling. We review structural and functional aspects of non-synaptic transmission, including (i) anatomical arrangement of non-synaptic release sites, receptors and transporters, (ii) intravesicular, intra- and extracellular concentrations of neurotransmitters, as well as the spatiotemporal pattern of transmitter diffusion. We propose that an effective general strategy for efficient pharmacological intervention could include the identification of specific non-synaptic targets and the subsequent development of selective pharmacological tools to influence them. PMID:20136842
Functional Cortical Hubs in the Eyes-Closed Resting Human Brain from an Electrophysiological Perspective Using Magnetoencephalography
Jin, Seung-Hyun; Jeong, Woorim; Seol, Jaeho; Kwon, Jiyeon; Chung, Chun Kee
It is not clear whether specific brain areas act as hubs in the eyes-closed (EC) resting state, which is an unconstrained state free from any passive or active tasks. Here, we used electrophysiological magnetoencephalography (MEG) signals to study functional cortical hubs in 88 participants. We identified several multispectral cortical hubs. Although cortical hubs vary slightly with different applied measures and frequency bands, the most consistent hubs were observed in the medial and posterior cingulate cortex, the left dorsolateral superior frontal cortex, and the left pole of the middle temporal cortex. Hubs were characterized as connector nodes integrating EC resting state functional networks. Hubs in the gamma band were more likely to include midline structures. Our results confirm the existence of multispectral cortical cores in EC resting state functional networks based on MEG and imply the existence of optimized functional networks in the resting brain. PMID:23874535
Distribution of vitamin C is tissue specific with early saturation of the brain and adrenal glands following differential oral dose regimens in guinea pigs.
Hasselholt, Stine; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens
Vitamin C (VitC) deficiency is surprisingly common in humans even in developed parts of the world. The micronutrient has several established functions in the brain; however, the consequences of its deficiency are not well characterised. To elucidate the effects of VitC deficiency on the brain, increased knowledge about the distribution of VitC to the brain and within different brain regions after varying dietary concentrations is needed. In the present study, guinea pigs (like humans lacking the ability to synthesise VitC) were randomly divided into six groups (n 10) that received different concentrations of VitC ranging from 100 to 1500 mg/kg feed for 8 weeks, after which VitC concentrations in biological fluids and tissues were measured using HPLC. The distribution of VitC was found to be dynamic and dependent on dietary availability. Brain saturation was region specific, occurred at low dietary doses, and the dose-concentration relationship could be approximated with a three-parameter Hill equation. The correlation between plasma and brain concentrations of VitC was moderate compared with other organs, and during non-scorbutic VitC deficiency, the brain was able to maintain concentrations from about one-quarter to half of sufficient levels depending on the region, whereas concentrations in other tissues decreased to one-sixth or less. The adrenal glands have similar characteristics to the brain. The observed distribution kinetics with a low dietary dose needed for saturation and exceptional retention ability suggest that the brain and adrenal glands are high priority tissues with regard to the distribution of VitC. PMID:25865869
Print-specific multimodal brain activation in kindergarten improves prediction of reading skills in second grade.
Bach, Silvia; Richardson, Ulla; Brandeis, Daniel; Martin, Ernst; Brem, Silvia
Children who are poor readers usually experience troublesome school careers and consequently often suffer from secondary emotional and behavioural problems. Early identification and prediction of later reading problems thus are critical in order to start targeted interventions for those children with an elevated risk for emerging reading problems. In this study, behavioural precursors of reading were assessed in nineteen (aged 6.4 ± 0.3 years) non-reading kindergarteners before training letter-speech sound associations with a computerized game (Graphogame) for eight weeks. The training aimed to introduce the basic principles of letter-speech sound correspondences and to initialize the sensitization of specific brain areas to print. Event-related potentials (ERP) and functional magnetic resonance imaging (fMRI) data were recorded during an explicit word/symbol processing task after the training. Reading skills were assessed two years later in second grade. The focus of this study was on clarifying whether electrophysiological and fMRI data of kindergarten children significantly improve prediction of future reading skills in 2nd grade over behavioural data alone. Based on evidence from previous studies demonstrating the importance of initial print sensitivity in the left occipito-temporal visual word form system (VWFS) for learning to read, the first pronounced difference in processing words compared to symbols in the ERP, an occipito-temporal negativity (N1: 188-281 ms) along with the corresponding functional activation in the left occipito-temporal VWFS were defined as potential predictors. ERP and fMRI data in kindergarteners significantly improved the prediction of reading skills in 2nd grade over behavioural data alone. Together with the behavioural measures they explained up to 88% of the variance. An additional discriminant analysis revealed a remarkably high accuracy in classifying normal (n=11) and poor readers (n=6). Due to the key limitation of the study, i.e. the small group sizes, the results of our prediction analyses should be interpreted with caution and regarded as preliminary despite cross-validation. Nevertheless our results indicate the potential of combining neuroimaging and behavioural measures to improve prediction at an early stage, when literacy skills are acquired and interventions are most beneficial. PMID:23727320
Impact of cross-disorder polygenic risk on frontal brain activation with specific effect of schizophrenia risk.
Whalley, Heather C; Hall, Lynsey; Romaniuk, Liana; Macdonald, Alix; Lawrie, Stephen M; Sussmann, Jessika E; McIntosh, Andrew M
Evidence suggests that there is shared genetic aetiology across the major psychiatric disorders conferred by additive effects of many common variants. Measuring their joint effects on brain function may identify common neural risk mechanisms. We investigated the effects of a cross-disorder polygenic risk score (PGRS), based on additive effects of genetic susceptibility to the five major psychiatric disorders, on brain activation during performance of a language-based executive task. We examined this relationship in healthy individuals with (n=82) and without (n=57) a family history of bipolar disorder to determine whether this effect was additive or interactive dependent on the presence of family history. We demonstrate a significant interaction for polygenic loading×group in left lateral frontal cortex (BA9, BA6). Further examination indicated that this was driven by a significant positive correlation in those without a family history (i.e. healthy unrelated volunteers), with no significant relationships in the familial group. We then examined the effect of the individual diagnoses contributing to the PGRS to determine evidence of disorder-specificity. We found a significant association with the schizophrenia polygenic score only, with no other significant relationships. These findings indicate differences in left lateral frontal brain activation in association with increased cross-disorder PGRS in individuals without a family history of psychiatric illness. Lack of effects in the familial group may reflect epistatic effects, shared environmental influences or effects not captured by the PGRS. The specific relationship with loading for schizophrenia is notably consistent with frontal cortical inefficiency as a circumscribed phenotype of psychotic disorders. PMID:25468172
Measurement of brain function of car driver using functional near-infrared spectroscopy (fNIRS).
Tsunashima, Hitoshi; Yanagisawa, Kazuki
The aim of this study is to propose a method for analyzing measured signal obtained from functional Near-Infrared Spectroscopy (fNIRS), which is applicable for neuroimaging studies for car drivers. We developed a signal processing method by multiresolution analysis (MRA) based on discrete wavelet transform. Statistical group analysis using Z-score is conducted after the extraction of task-related signal using MRA. Brain activities of subjects with different level of mental calculation are measured by fNIRS and fMRI. Results of mental calculation with nine subjects by using fNIRS and fMRI showed that the proposed methods were effective for the evaluation of brain activities due to the task. Finally, the proposed method is applied for evaluating brain function of car driver with and without adaptive cruise control (ACC) system for demonstrating the effectiveness of the proposed method. The results showed that frontal lobe was less active when the subject drove with ACC. PMID:19584938
Multiple functions of endocannabinoid signaling in the brain.
Katona, István; Freund, Tamás F
Despite being regarded as a hippie science for decades, cannabinoid research has finally found its well-deserved position in mainstream neuroscience. A series of groundbreaking discoveries revealed that endocannabinoid molecules are as widespread and important as conventional neurotransmitters such as glutamate or GABA, yet they act in profoundly unconventional ways. We aim to illustrate how uncovering the molecular, anatomical, and physiological characteristics of endocannabinoid signaling has revealed new mechanistic insights into several fundamental phenomena in synaptic physiology. First, we summarize unexpected advances in the molecular complexity of biogenesis and inactivation of the two endocannabinoids, anandamide and 2-arachidonoylglycerol. Then, we show how these new metabolic routes are integrated into well-known intracellular signaling pathways. These endocannabinoid-producing signalosomes operate in phasic and tonic modes, thereby differentially governing homeostatic, short-term, and long-term synaptic plasticity throughout the brain. Finally, we discuss how cell type- and synapse-specific refinement of endocannabinoid signaling may explain the characteristic behavioral effects of cannabinoids. PMID:22524785
Brain Maps on the Go: Functional Imaging During Motor Challenge in Animals
Holschneider, DP; Maarek, J-M I
Brain mapping in the freely-moving animal is useful for studying motor circuits, not only because it avoids the potential confound of sedation or restraints, but because activated brain states may serve to accentuate differences that only manifest partially while a subject is in the resting state. Perfusion or metabolic mapping using autoradiography allows one to examine changes in brain function at the circuit level across the entire brain with a spatial resolution (?100 microns) appropriate for the rat or mouse brain, and a temporal resolution (seconds – minutes) sufficient for capturing acute brain changes. Here we summarize the application of these methods to the functional brain mapping of behaviors involving locomotion of small animals, methods for the three dimensional reconstruction of the brain from autoradiographic sections, voxel based analysis of the whole brain, and generation of maps of the flattened rat cortex. Application of these methods in animal models promises utility in improving our understanding of motor function in the normal brain, and of the effects of neuropathology and treatment interventions such as exercise have on the reorganization of motor circuits. PMID:18554522
Conjugation of functionalized SPIONs with transferrin for targeting and imaging brain glial tumors in rat model.
Jiang, Weili; Xie, Hui; Ghoorah, Devina; Shang, Yalei; Shi, Haojun; Liu, Fang; Yang, Xiangliang; Xu, Haibo
Currently, effective and specific diagnostic imaging of brain glioma is a major challenge. Nanomedicine plays an essential role by delivering the contrast agent in a targeted manner to specific tumor cells, leading to improvement in accurate diagnosis by good visualization and specific demonstration of tumor cells. This study investigated the preparation and characterization of a targeted MR contrast agent, transferrin-conjugated superparamagnetic iron oxide nanoparticles (Tf-SPIONs), for brain glioma detection. MR imaging showed the obvious contrast change of brain glioma before and after administration of Tf-SPIONs in C6 glioma rat model in vivo on T2 weighted imaging. Significant contrast enhancement of brain glioma could still be clearly seen even 48 h post injection, due to the retention of Tf-SPIONs in cytoplasm of tumor cells which was proved by Prussian blue staining. Thus, these results suggest that Tf-SPIONs could be a potential targeting MR contrast agent for the brain glioma. PMID:22615995
Production and Characterization of Monoclonal Antibodies against the ``Brain-Specific'' Proteins 14-3-2 and S-100
Eric A. Haan; Barbara D. Boss; W. Maxwell Cowan
We have raised mouse hybridomas that secrete monoclonal antibodies against bovine brain-specific proteins 14-3-2 and S-100, and we have characterized the antibodies by immunoperoxidase and immunofluorescence methods in sections and in tissue cultures of rat brain. One monoclonal antibody to 14-3-2 (E8.F9) has been found to react strongly with bovine 14-3-2 and with rat neuron-specific enolase in an enzyme-linked immunosorbent
Bilingualism trains specific brain circuits involved in flexible rule selection and application.
Stocco, Andrea; Prat, Chantel S
Bilingual individuals have been shown to outperform monolinguals on a variety of tasks that measure non-linguistic executive functioning, suggesting that some facets of the bilingual experience give rise to generalized improvements in cognitive performance. The current study investigated the hypothesis that such advantage in executive functioning arises from the need to flexibly select and apply rules when speaking multiple languages. Such flexible behavior may strengthen the functioning of the fronto-striatal loops that direct signals to the prefrontal cortex. To test this hypothesis, we compared behavioral and brain data from proficient bilinguals and monolinguals who performed a Rapid Instructed Task Learning paradigm, which requires behaving according to ever-changing rules. Consistent with our hypothesis, bilinguals were faster than monolinguals when executing novel rules, and this improvement was associated with greater modulation of activity in the basal ganglia. The implications of these findings for language and executive function research are discussed herein. PMID:25156160
Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation
Charrier, Cécile; Joshi, Kaumudi; Coutinho-Budd, Jaeda; Kim, Ji-Eun; Lambert, Nelle; de Marchena, Jacqueline; Jin, Wei-Lin; Vanderhaeghen, Pierre; Ghosh, Anirvan; Sassa, Takayuki; Polleux, Franck
Structural genomic variations represent a major driving force of evolution and a burst of large segmental gene duplications occurred in the human lineage during its separation from non-human primates. SRGAP2, a gene recently implicated in neocortical development, has undergone two human-specific duplications. Here we find that both duplications (SRGAP2B and SRGAP2C) are partial and encode a truncated F-BAR domain. SRGAP2C is expressed in the developing and adult human brain and dimerizes with ancestral SRGAP2 to inhibit its function. In the mouse neocortex, SRGAP2 promotes spine maturation and limits spine density. Expression of SRGAP2C phenocopies SRGAP2 deficiency. It underlies sustained radial migration and leads to the emergence of human-specific features, including neoteny during spine maturation and increased density of longer spines. These results suggest that inhibition of SRGAP2 function by its human-specific paralogs has contributed to the evolution of the human neocortex and plays an important role during human brain development. PMID:22559944
Quantitative proteomics analysis of differential protein expression and oxidative modification of specific proteins in the brains of old mice
H. Fai Poon; Radhika A. Vaishnav; Thomas V. Getchell; Marilyn L. Getchell; D. Allan Butterfield
The brain is susceptible to oxidative stress, which is associated with age-related brain dysfunction, because of its high content of peroxidizable unsaturated fatty acids, high oxygen consumption per unit weight, high content of key components for oxidative damage, and the relative scarcity of antioxidant defense systems. Protein oxidation, which results in functional disruption, is not random but appears to be
Mismatch negativity, social cognition, and functional outcomes in patients after traumatic brain injury
Sun, Hui-yan; Li, Qiang; Chen, Xi-ping; Tao, Lu-yang
Mismatch negativity is generated automatically, and is an early monitoring indicator of neuronal integrity impairment and functional abnormality in patients with brain injury, leading to decline of cognitive function. Antipsychotic medication cannot affect mismatch negativity. The present study aimed to explore the relationships of mismatch negativity with neurocognition, daily life and social functional outcomes in patients after brain injury. Twelve patients with traumatic brain injury and 12 healthy controls were recruited in this study. We examined neurocognition with the Wechsler Adult Intelligence Scale-Revised China, and daily and social functional outcomes with the Activity of Daily Living Scale and Social Disability Screening Schedule, respectively. Mismatch negativity was analyzed from electroencephalogram recording. The results showed that mismatch negativity amplitudes decreased in patients with traumatic brain injury compared with healthy controls. Mismatch negativity amplitude was negatively correlated with measurements of neurocognition and positively correlated with functional outcomes in patients after traumatic brain injury. Further, the most significant positive correlations were found between mismatch negativity in the fronto-central region and measures of functional outcomes. The most significant positive correlations were also found between mismatch negativity at the FCz electrode and daily living function. Mismatch negativity amplitudes were extremely positively associated with Social Disability Screening Schedule scores at the Fz electrode in brain injury patients. These experimental findings suggest that mismatch negativity might efficiently reflect functional outcomes in patients after traumatic brain injury. PMID:26170824
Thyroid hormone receptors in brain development and function
Juan Bernal
Thyroid hormones are important during development of the mammalian brain, acting on migration and differentiation of neural cells, synaptogenesis, and myelination. The actions of thyroid hormones are mediated through nuclear thyroid hormone receptors (TRs) and regulation of gene expression. The purpose of this article is to review the role of TRs in brain maturation. In developing humans maternal and fetal
Gender differences in executive functions following traumatic brain injury
Jennifer H. Marwitz; Katrina Lesher; William C. Walker; Tamara Bushnik
The present study used the National Institute on Disability Rehabilitation and Research (NIDRR) funded Traumatic Brain Injury Model Systems (TBIMS) database to examine the effect of gender on presentation of executive dysfunction following traumatic brain injury (TBI) and variables that might impact the course and degree of recovery. The Wisconsin Card Sort Test (WCST) was chosen as a measure of
Commentary: the future of forensic functional brain imaging.
Langleben, Daniel D; Dattilio, Frank M
In "Functional MRI Lie Detection: Too Good to be True?" in this issue of The Journal, Joseph Simpson reviews the merits and the limitations of using fMRI to detect deception. After presenting the gaps in experimental data that stand in the way of translating the laboratory proof of concept to a field application, Simpson surveys the legal, regulatory and ethics concerns facing fMRI, should it emerge as a technologically robust method of lie detection. In our commentary, we update and interpret the data described by Simpson, from the points of view of an experimental scientist and a forensic clinician. We conclude that the current research funding and literature are prematurely skewed toward discussion of existing findings, rather than generation of new fMRI data on deception and related topics such as mind-reading, consciousness, morality, and criminal responsibility. We propose that further progress in brain imaging research may foster the emergence of a new discipline of forensic MRI. PMID:19092068
Astrocytes, Synapses and Brain Function: A Computational Approach
NASA Astrophysics Data System (ADS)
Nadkarni, Suhita
Modulation of synaptic reliability is one of the leading mechanisms involved in long- term potentiation (LTP) and long-term depression (LTD) and therefore has implications in information processing in the brain. A recently discovered mechanism for modulating synaptic reliability critically involves recruitments of astrocytes - star- shaped cells that outnumber the neurons in most parts of the central nervous system. Astrocytes until recently were thought to be subordinate cells merely participating in supporting neuronal functions. New evidence, however, made available by advances in imaging technology has changed the way we envision the role of these cells in synaptic transmission and as modulator of neuronal excitability. We put forward a novel mathematical framework based on the biophysics of the bidirectional neuron-astrocyte interactions that quantitatively accounts for two distinct experimental manifestation of recruitment of astrocytes in synaptic transmission: a) transformation of a low fidelity synapse transforms into a high fidelity synapse and b) enhanced postsynaptic spontaneous currents when astrocytes are activated. Such a framework is not only useful for modeling neuronal dynamics in a realistic environment but also provides a conceptual basis for interpreting experiments. Based on this modeling framework, we explore the role of astrocytes for neuronal network behavior such as synchrony and correlations and compare with experimental data from cultured networks.
CART in the brain of vertebrates: circuits, functions and evolution.
Subhedar, Nishikant K; Nakhate, Kartik T; Upadhya, Manoj A; Kokare, Dadasaheb M
Cocaine- and amphetamine-regulated transcript peptide (CART) with its wide distribution in the brain of mammals has been the focus of considerable research in recent years. Last two decades have witnessed a steady rise in the information on the genes that encode this neuropeptide and regulation of its transcription and translation. CART is highly enriched in the hypothalamic nuclei and its relevance to energy homeostasis and neuroendocrine control has been understood in great details. However, the occurrence of this peptide in a range of diverse circuitries for sensory, motor, vegetative, limbic and higher cortical areas has been confounding. Evidence that CART peptide may have role in addiction, pain, reward, learning and memory, cognition, sleep, reproduction and development, modulation of behavior and regulation of autonomic nervous system are accumulating, but an integration has been missing. A steady stream of papers has been pointing at the therapeutic potentials of CART. The current review is an attempt at piecing together the fragments of available information, and seeks meaning out of the CART elements in their anatomical niche. We try to put together the CART containing neuronal circuitries that have been conclusively demonstrated as well as those which have been proposed, but need confirmation. With a view to finding out the evolutionary antecedents, we visit the CART systems in sub-mammalian vertebrates and seek the answer why the system is shaped the way it is. We enquire into the conservation of the CART system and appreciate its functional diversity across the phyla. PMID:24468550
Simulating 'structure-function' patterns of malignant brain tumors
NASA Astrophysics Data System (ADS)
Mansury, Yuri; Deisboeck, Thomas S.
Rapid growth and extensive tissue infiltration are characteristics of highly malignant neuroepithelial brain tumors. Very little is known, however, about the existence of structure-function relationships in these types of neoplasm. Therefore, using a previously developed two-dimensional agent-based model, we have investigated the emergent patterns of multiple tumor cells that proliferate and migrate on an adaptive grid lattice, driven by a local-search mechanism and guided by the presence of distinct environmental conditions. Numerical results indicate a strong correlation between the fractal dimensions of the tumor surface and the average velocity of the tumor's spatial expansion. In particular, when the so called 'beaten-path advantage' intensifies, i.e., rising 'mechanical rewards' for cells to follow each other along preformed pathways, it results in an increase of the tumor system's fractal dimensions leading to a concomitant acceleration of its spatial expansion. Whereas cell migration is the dominant phenotype responsible for the more extensive branching patterns exhibiting higher fractal dimensions, cell proliferation appears to become more active primarily at lower fracticality associated with stronger mechanical confinements. Implications of these results for experimental and clinical cancer research are discussed.
A cell epigenotype specific model for the correction of brain cellular heterogeneity bias and its application to age, brain region and major depression
Guintivano, Jerry; Aryee, Martin J.; Kaminsky, Zachary A.
Brain cellular heterogeneity may bias cell type specific DNA methylation patterns, influencing findings in psychiatric epigenetic studies. We performed fluorescence activated cell sorting (FACS) of neuronal nuclei and Illumina HM450 DNA methylation profiling in post mortem frontal cortex of 29 major depression and 29 matched controls. We identify genomic features and ontologies enriched for cell type specific epigenetic variation. Using the top cell epigenotype specific (CETS) marks, we generated a publically available R package, "CETS," capable of quantifying neuronal proportions and generating in silico neuronal profiles from DNA methylation data. We demonstrate a significant overlap in major depression DNA methylation associations between FACS separated and CETS model generated neuronal profiles relative to bulk profiles. CETS derived neuronal proportions correlated significantly with age in the frontal cortex and cerebellum and accounted for epigenetic variation between brain regions. CETS based control of cellular heterogeneity will enable more robust hypothesis testing in the brain. PMID:23426267
Crew interface specifications development functions, phase 3A
NASA Technical Reports Server (NTRS)
Carl, J. G.
The findings and data products developed during the crew interface specification study for inflight maintenance and stowage functions are presented. Guidelines are provided for improving the present progress of defining, controlling, and managing the flight crew requirements. The following data products were developed: (1) description of inflight maintenance management process, (2) specifications for inflight maintenance management requirements, and (3) suggested inflight maintenance data processing reports for logistics management.
Computational Detection and Functional Analysis of Human Tissue-Specific A-to-I RNA Editing
Feng, Guihai; Hu, Yaou; Wang, Li; Wang, Yumin
A-to-I RNA editing is a widespread post-transcriptional modification event in vertebrates. It could increase transcriptome and proteome diversity through recoding the genomic information and cross-linking other regulatory events, such as those mediated by alternative splicing, RNAi and microRNA (miRNA). Previous studies indicated that RNA editing can occur in a tissue-specific manner in response to the requirements of the local environment. We set out to systematically detect tissue-specific A-to-I RNA editing sites in 43 human tissues using bioinformatics approaches based on the Fisher's exact test and the Benjamini & Hochberg false discovery rate (FDR) multiple testing correction. Twenty-three sites in total were identified to be tissue-specific. One of them resulted in an altered amino acid residue which may prevent the phosphorylation of PARP-10 and affect its activity. Eight and two tissue-specific A-to-I RNA editing sites were predicted to destroy putative exonic splicing enhancers (ESEs) and exonic splicing silencers (ESSs), respectively. Brain-specific and ovary-specific A-to-I RNA editing sites were further verified by comparing the cDNA sequences with their corresponding genomic templates in multiple cell lines from brain, colon, breast, bone marrow, lymph, liver, ovary and kidney tissue. Our findings help to elucidate the role of A-to-I RNA editing in the regulation of tissue-specific development and function, and the approach utilized here can be broadened to study other types of tissue-specific substitution editing. PMID:21448465
A surgeon specific automatic path planning algorithm for deep brain stimulation
NASA Astrophysics Data System (ADS)
Liu, Yuan; Dawant, Benoit M.; Pallavaram, Srivatsan; Neimat, Joseph S.; Konrad, Peter E.; D'Haese, Pierre-Francois; Datteri, Ryan D.; Landman, Bennett A.; Noble, Jack H.
In deep brain stimulation surgeries, stimulating electrodes are placed at specific targets in the deep brain to treat neurological disorders. Reaching these targets safely requires avoiding critical structures in the brain. Meticulous planning is required to find a safe path from the cortical surface to the intended target. Choosing a trajectory automatically is difficult because there is little consensus among neurosurgeons on what is optimal. Our goals are to design a path planning system that is able to learn the preferences of individual surgeons and, eventually, to standardize the surgical approach using this learned information. In this work, we take the first step towards these goals, which is to develop a trajectory planning approach that is able to effectively mimic individual surgeons and is designed such that parameters, which potentially can be automatically learned, are used to describe an individual surgeon's preferences. To validate the approach, two neurosurgeons were asked to choose between their manual and a computed trajectory, blinded to their identity. The results of this experiment showed that the neurosurgeons preferred the computed trajectory over their own in 10 out of 40 cases. The computed trajectory was judged to be equivalent to the manual one or otherwise acceptable in 27 of the remaining cases. These results demonstrate the potential clinical utility of computer-assisted path planning.
The mouse brain metabolome: region-specific signatures and response to excitotoxic neuronal injury.
Jaeger, Christian; Glaab, Enrico; Michelucci, Alessandro; Binz, Tina M; Koeglsberger, Sandra; Garcia, Pierre; Trezzi, Jean-Pierre; Ghelfi, Jenny; Balling, Rudi; Buttini, Manuel
Neurodegeneration is a multistep process characterized by a multitude of molecular entities and their interactions. Systems analyses, or omics approaches, have become an important tool in characterizing this process. Although RNA and protein profiling made their entry into this field a couple of decades ago, metabolite profiling is a more recent addition. The metabolome represents a large part or all metabolites in a tissue, and gives a snapshot of its physiology. By using gas chromatography coupled to mass spectrometry, we analyzed the metabolic profile of brain regions of the mouse, and found that each region is characterized by its own metabolic signature. We then analyzed the metabolic profile of the mouse brain after excitotoxic injury, a mechanism of neurodegeneration implicated in numerous neurological diseases. More important, we validated our findings by measuring, histologically and molecularly, actual neurodegeneration and glial response. We found that a specific global metabolic signature, best revealed by machine learning algorithms, rather than individual metabolites, was the most robust correlate of neuronal injury and the accompanying gliosis, and this signature could serve as a global biomarker for neurodegeneration. We also observed that brain lesioning induced several metabolites with neuroprotective properties. Our results deepen the understanding of metabolic changes accompanying neurodegeneration in disease models, and could help rapidly evaluate these changes in preclinical drug studies. PMID:25934215
The Autonomic Brain: An Activation Likelihood Estimation Meta-Analysis for Central Processing of Autonomic Function
Meissner, Karin; Bär, Karl-Jürgen; Napadow, Vitaly
The autonomic nervous system (ANS) is of paramount importance for daily life. Its regulatory action on respiratory, cardiovascular, digestive, endocrine, and many other systems is controlled by a number of structures in the CNS. While the majority of these nuclei and cortices have been identified in animal models, neuroimaging studies have recently begun to shed light on central autonomic processing in humans. In this study, we used activation likelihood estimation to conduct a meta-analysis of human neuroimaging experiments evaluating central autonomic processing to localize (1) cortical and subcortical areas involved in autonomic processing, (2) potential subsystems for the sympathetic and parasympathetic divisions of the ANS, and (3) potential subsystems for specific ANS responses to different stimuli/tasks. Across all tasks, we identified a set of consistently activated brain regions, comprising left amygdala, right anterior and left posterior insula and midcingulate cortices that form the core of the central autonomic network. While sympathetic-associated regions predominate in executive- and salience-processing networks, parasympathetic regions predominate in the default mode network. Hence, central processing of autonomic function does not simply involve a monolithic network of brain regions, instead showing elements of task and division specificity. PMID:23785162
The cerebral ventricles, the animal spirits and the dawn of brain localization of function.
Manzoni, T
This paper reviews the early history of brain localization of function. It analyses the doctrines professed in ancient times by philosophers and physicians, who believed that brain functions were carried out in the cerebral ventricles by the psychic pneuma, or animal spirit, a sort of special and light substance endowed with the power to perform sensory, motor and mental activities. This theory, conceived in the Classic Age and called "ventricular-pneumatic doctrine", evolved in the 4th-5th centuries A.D. into the "three-cell theory", according to which each cerebral ventricle was the seat of a specific function, and contained a unique type of spirit with the power to perform that function. The three-cell theory represents the earliest attempt to localize different mind functions in separate brain sites and was held true by Byzantine, Arabian and Western Latin scholars well beyond the Renaissance. The paper is subdivided into an Introduction and eight sections. The first two sections report a brief history of the philosophical and medical doctrines about the pneuma as mediator of all vital functions, the ventricular-pneumatic doctrine elaborated by Galen of Pergamon, and his theory of nerve physiology based on the assumption that the pneuma, set in motion by active brain movements and flowing in the hollow nerves, could transfer sensations from the sense organs to the anterior ventricles, and motor commands from the posterior ventricle to the muscles. The third and fourth sections trace the ways in which these doctrines were transmitted to the Byzantine physicians and then to the Arabs, until they reached the Latin West. Here, throughout the Middle Ages they not only formed the background of medical and natural philosophy, but also influenced Christian theologians. The fifth section is devoted to the ventricular localization of mind faculties, called internal senses by Arabian and Western Latin scholars. Most authors recognized three basic internal senses: imagination, cognition and memory, and generally localized imagination in the anterior ventricle, cognition in the middle and memory in the posterior one, while other scholars adopted complex lists including up to seven faculties, each carried out by a specific type of animal spirit and localized, or sub-localized, in different ventricular sites according to complex topographical patterns. This section reports more than sixty patterns of ventricular localization from various authors (summarized in a Table), the rationale of complex ventricular localization, and the naive interpretations of Medieval physicians and surgeons of the impairment of the internal senses caused by brain disease and trauma. The sixth section deals with the decline of the three-cell theory, which was first challenged in the early 16th century and then drastically revised by several Renaissance and post-Renaissance experimentalists, anatomists and philosophers, although some remnants of the Galenic pneumatic neurophysiology survived in medicine until the 18th century. The penultimate section analyses bibliographical data on the earliest localizationists and shows that, independently of chronological priority, Nemesius of Emesa was the source of the pattern of ventricular localization of function adopted by later Byzantines and by the Arabs, and then transmitted to Latin Western scholars. The last section discusses the legacy of the three-cell theory to later generations of neuroscientists. PMID:9492949
The electrophysiological effects of a brain injury on auditory memory functioning. The QEEG correlates of impaired memory.
Thornton, Kirtley
The effect of a brain injury on the quantitative EEG (QEEG) variables during an auditory memory activation condition was examined with 56 normal subjects and 85 mild traumatic brain-injured (MTBI) subjects. An analysis was conducted on the different response patterns of the two groups, the variables which were correlated with memory performance in the brain-injured group, and the variables which predicted the memory score for the combined two groups (normal and brain injured). The three conditions included the input task, the immediate recall, and the delayed recall task. The consistent effect of a brain injury was a lowering of the connectivity patterns in the beta1 and beta2 frequencies (phase and coherences) and increases predominantly in the relative power of beta1 (13-32Hz), which were correlated with the differences in recall. There is a subtle shift to right hemisphere/right temporal functioning and employment of the higher beta1 and beta2 frequencies (phase and coherence) in the response pattern of the MTBI subject. Memory functioning is predominantly positively correlated with connection activity (phase and coherence) and negatively correlated with beta activation at specific locations. PMID:14591452
Neurocognitive Function of Patients with Brain Metastasis Who Received Either Whole Brain Radiotherapy Plus Stereotactic Radiosurgery or Radiosurgery Alone
Aoyama, Hidefumi [Department of Radiology, Hokkaido University Graduate School of Medicine, Sapporo (Japan)]. E-mail: email@example.com; Tago, Masao [Department of Radiology, University of Tokyo Hospital, Tokyo (Japan); Kato, Norio [Department of Radiology, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Toyoda, Tatsuya [Department of Radiology, Kanto Medical Center Nippon Telegraph and Telephone East Corporation, Tokyo (Japan); Kenjyo, Masahiro [Department of Radiology, Hiroshima University School of Medicine, Hiroshima (Japan); Hirota, Saeko [Department of Radiology, Hyogo Medical Center for Adults, Akashi (Japan); Shioura, Hiroki [Department of Radiology, Izumisano General Hospital, Izumisano (Japan); Inomata, Taisuke [Department of Radiology, Osaka Medical College, Osaka (Japan); Kunieda, Etsuo [Department of Radiology, Keio University School of Medicine, Tokyo (Japan); Hayakawa, Kazushige [Department of Radiology, Kitasato University School of Medicine, Sagamihara (Japan); Nakagawa, Keiichi [Department of Radiology, University of Tokyo Hospital, Tokyo (Japan); Kobashi, Gen [Department of Global Health and Epidemiology, Division of Preventive Medicine, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Shirato, Hiroki [Department of Radiology, Hokkaido University Graduate School of Medicine, Sapporo (Japan)
Purpose: To determine how the omission of whole brain radiotherapy (WBRT) affects the neurocognitive function of patients with one to four brain metastases who have been treated with stereotactic radiosurgery (SRS). Methods and Materials: In a prospective randomized trial between WBRT+SRS and SRS alone for patients with one to four brain metastases, we assessed the neurocognitive function using the Mini-Mental State Examination (MMSE). Of the 132 enrolled patients, MMSE scores were available for 110. Results: In the baseline MMSE analyses, statistically significant differences were observed for total tumor volume, extent of tumor edema, age, and Karnofsky performance status. Of the 92 patients who underwent the follow-up MMSE, 39 had a baseline MMSE score of {<=}27 (17 in the WBRT+SRS group and 22 in the SRS-alone group). Improvements of {>=}3 points in the MMSEs of 9 WBRT+SRS patients and 11 SRS-alone patients (p = 0.85) were observed. Of the 82 patients with a baseline MMSE score of {>=}27 or whose baseline MMSE score was {<=}26 but had improved to {>=}27 after the initial brain treatment, the 12-, 24-, and 36-month actuarial free rate of the 3-point drop in the MMSE was 76.1%, 68.5%, and 14.7% in the WBRT+SRS group and 59.3%, 51.9%, and 51.9% in the SRS-alone group, respectively. The average duration until deterioration was 16.5 months in the WBRT+SRS group and 7.6 months in the SRS-alone group (p = 0.05). Conclusion: The results of the present study have revealed that, for most brain metastatic patients, control of the brain tumor is the most important factor for stabilizing neurocognitive function. However, the long-term adverse effects of WBRT on neurocognitive function might not be negligible.
A novel brain partition highlights the modular skeleton shared by structure and function
Diez, Ibai; Bonifazi, Paolo; Escudero, Ińaki; Mateos, Beatriz; Muńoz, Miguel A.; Stramaglia, Sebastiano; Cortes, Jesus M.
Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent progress in neuroimaging has helped advance our understanding of this important issue, with diffusion images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). Here, we adopt a systems approach, relying on modular hierarchical clustering, to study together SC and rsFC datasets gathered independently from healthy human subjects. Our novel approach allows us to find a common skeleton shared by structure and function from which a new, optimal, brain partition can be extracted. We describe the emerging common structure-function modules (SFMs) in detail and compare them with commonly employed anatomical or functional parcellations. Our results underline the strong correspondence between brain structure and resting-state dynamics as well as the emerging coherent organization of the human brain. PMID:26037235
A novel brain partition highlights the modular skeleton shared by structure and function.
Diez, Ibai; Bonifazi, Paolo; Escudero, Ińaki; Mateos, Beatriz; Muńoz, Miguel A; Stramaglia, Sebastiano; Cortes, Jesus M
Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent progress in neuroimaging has helped advance our understanding of this important issue, with diffusion images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). Here, we adopt a systems approach, relying on modular hierarchical clustering, to study together SC and rsFC datasets gathered independently from healthy human subjects. Our novel approach allows us to find a common skeleton shared by structure and function from which a new, optimal, brain partition can be extracted. We describe the emerging common structure-function modules (SFMs) in detail and compare them with commonly employed anatomical or functional parcellations. Our results underline the strong correspondence between brain structure and resting-state dynamics as well as the emerging coherent organization of the human brain. PMID:26037235
Gene regulatory network analysis reveals differences in site-specific cell fate determination in mammalian brain
Ertaylan, Gökhan; Okawa, Satoshi; Schwamborn, Jens C.; del Sol, Antonio
Neurogenesis—the generation of new neurons—is an ongoing process that persists in the adult mammalian brain of several species, including humans. In this work we analyze two discrete brain regions: the subventricular zone (SVZ) lining the walls of the lateral ventricles; and the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus in mice and shed light on the SVZ and SGZ specific neurogenesis. We propose a computational model that relies on the construction and analysis of region specific gene regulatory networks (GRNs) from the publicly available data on these two regions. Using this model a number of putative factors involved in neuronal stem cell (NSC) identity and maintenance were identified. We also demonstrate potential gender and niche-derived differences based on cell surface and nuclear receptors via Ar, Hif1a, and Nr3c1. We have also conducted cell fate determinant analysis for SVZ NSC populations to Olfactory Bulb interneurons and SGZ NSC populations to the granule cells of the Granular Cell Layer. We report 31 candidate cell fate determinant gene pairs, ready to be validated. We focus on Ar—Pax6 in SVZ and Sox2—Ncor1 in SGZ. Both pairs are expressed and localized in the suggested anatomical structures as shown by in situ hybridization and found to physically interact. Finally, we conclude that there are fundamental differences between SGZ and SVZ neurogenesis. We argue that these regulatory mechanisms are linked to the observed differential neurogenic potential of these regions. The presence of nuclear and cell surface receptors in the region specific regulatory circuits indicate the significance of niche derived extracellular factors, hormones and region specific factors such as the oxygen sensitivity, dictating SGZ and SVZ specific neurogenesis. PMID:25565969
The Molecular Basis for Kinesin Functional Specificity During Mitosis
Welburn, Julie P I
Microtubule-based motor proteins play key roles during mitosis to assemble the bipolar spindle, define the cell division axis, and align and segregate the chromosomes. The majority of mitotic motors are members of the kinesin superfamily. Despite sharing a conserved catalytic core, each kinesin has distinct functions and localization, and is uniquely regulated in time and space. These distinct behaviors and functional specificity are generated by variations in the enzymatic domain as well as the non-conserved regions outside of the kinesin motor domain and the stalk. These flanking regions can directly modulate the properties of the kinesin motor through dimerization or self-interactions, and can associate with extrinsic factors, such as microtubule or DNA binding proteins, to provide additional functional properties. This review discusses the recently identified molecular mechanisms that explain how the control and functional specification of mitotic kinesins is achieved. © 2013 Wiley Periodicals, Inc. PMID:24039047
Neuropsychobiological Evidence for the Functional Presence and Expression of Cannabinoid CB2 Receptors in the Brain
Emmanuel S. Onaivi
For over a decade, until recently, it was thought that marijuana acts by activating brain-type cannabinoid receptors called CB1, and that a second type called CB2 cannabinoid receptor was found only in peripheral tissues. Neuronal CB2 receptors in the brain had been controversial. We reported the discovery and functional presence of CB2 cannabinoid receptors in the mammalian brain that may
FDTD chiral brain tissue model for specific absorption rate determination under radiation from mobile phones at 900 and 1800 MHz
NASA Astrophysics Data System (ADS)
Zamorano, M.; Torres-Silva, H.
A new electrodynamics model formed by chiral bioplasma, which represents the human head inner structure and makes it possible to analyse its behaviour when it is irradiated by a microwave electromagnetic field from cellular phones, is presented. The finite-difference time-domain (FDTD) numeric technique is used, which allows simulation of the electromagnetic fields, deduced with Maxwell's equations, and allows us to simulate the specific absorption rate (SAR). The results show the SAR behaviour as a function of the input power and the chirality factor. In considering the chiral brain tissue in the proposed human head model, the two more important conclusions of our work are the following: (a) the absorption of the electromagnetic fields from cellular phones is stronger, so the SAR coefficient is higher than that using the classical model, when values of the chiral factor are of order of 1; (b) 'inverse skin effect' shows up at 1800 MHz, with respect to a 900 MHz source.
Cannabinoid Receptors CB1 and CB2 Form Functional Heteromers in Brain*
Callén, Lucía; Moreno, Estefanía; Barroso-Chinea, Pedro; Moreno-Delgado, David; Cortés, Antoni; Mallol, Josefa; Casadó, Vicent; Lanciego, José Luis; Franco, Rafael; Lluis, Carmen; Canela, Enric I.; McCormick, Peter J.
Exploring the role of cannabinoid CB2 receptors in the brain, we present evidence of CB2 receptor molecular and functional interaction with cannabinoid CB1 receptors. Using biophysical and biochemical approaches, we discovered that CB2 receptors can form heteromers with CB1 receptors in transfected neuronal cells and in rat brain pineal gland, nucleus accumbens, and globus pallidus. Within CB1-CB2 receptor heteromers expressed in a neuronal cell model, agonist co-activation of CB1 and CB2 receptors resulted in a negative cross-talk in Akt phosphorylation and neurite outgrowth. Moreover, one specific characteristic of CB1-CB2 receptor heteromers consists of both the ability of CB1 receptor antagonists to block the effect of CB2 receptor agonists and, conversely, the ability of CB2 receptor antagonists to block the effect of CB1 receptor agonists, showing a bidirectional cross-antagonism phenomenon. Taken together, these data illuminate the mechanism by which CB2 receptors can negatively modulate CB1 receptor function. PMID:22532560
Spatially Aggregated Multi-Class Pattern Classification in Functional MRI using Optimally Selected Functional Brain Areas
Zheng, Weili; Ackley, Elena S.; Martínez-Ramón, Manel; Posse, Stefan
In previous works, boosting aggregation of classifier outputs from discrete brain areas has been demonstrated to reduce dimensionality, and improve the robustness and accuracy of fMRI classification. However, dimensionality reduction and classification of mixed activation patterns of multiple classes remain challenging. In the present study, the goals were (a) to reduce dimensionality by combining feature reduction at the voxel level and backward elimination of optimally aggregated classifiers at the region level, (b) to compare region selection for spatially aggregated classification using boosting and partial least squares regression methods and (c) to resolve mixed activation patterns using probabilistic prediction of individual tasks. Brain activation maps from interleaved visual, motor, auditory and cognitive tasks were segmented into 144 functional regions. Feature selection reduced the number of feature voxels by more than 50%, leaving 95 regions. The two aggregation approaches further reduced the number of regions to 30, resulting in more than 75% reduction of classification time and misclassification rates of less than 3%. Boosting and partial least squares (PLS) were compared to select the most discriminative and the most task correlated regions, respectively. Successful task prediction in mixed activation patterns was feasible within the first block of task activation in real time fMRI experiments. This methodology is suitable for sparsifying activation patterns in real-time fMRI and for neurofeedback from distributed networks of brain activation. PMID:22902471
From event-related potential to oscillations: genetic diathesis in brain (dys)function and alcohol dependence.
Rangaswamy, Madhavi; Porjesz, Bernice
Recording the brain's electrical activity using electrodes placed on the individual's scalp provides noninvasive sensitive measures of brain function in humans. Regardless of whether an individual receives sensory information or performs higher cognitive processes, the brain regions involved exhibit measurable electrical activity, and by recording this activity with numerous electrodes placed on different areas of the scalp, researchers can determine when and where in the brain information processing occurs. Two general approaches can be used to record these neuroelectric phenomena: The continuous electroencephalogram (EEG) records brain activity when the subject is at rest and not involved in a task. It reflects the sum of the random activity of thousands of neurons that have similar spatial orientation in the brain. This activity typically fluctuates in wave-like patterns, and depending on the frequency of these patterns, one distinguishes different brain waves called ? (frequency of 1 to 3 Hz), ? (frequency of 4 to 7 Hz), ? (frequency of 8 to 12 Hz), ? (frequency of 12 to 28 Hz), and ? (frequency of 28+ Hz) rhythms. Variations in the patterns of these brain waves can indicate the level of consciousness, psychological state, or presence of neurological disorders. Event-related potentials (ERPs) are recorded while the subject is performing a sensory or cognitive task. They reflect the summated activity of network ensembles active during the task and are characterized by a specific pattern called the waveform, which is composed of negative and positive deflections (i.e., waves). For example, a target stimulus detected amidst a series of other nontarget stimuli produces a positive wave around 300 milliseconds after the stimulus. This is known as the P300 or P3 response. PMID:23584866
A Brain-Wide Study of Age-Related Changes in Functional Connectivity.
Geerligs, Linda; Renken, Remco J; Saliasi, Emi; Maurits, Natasha M; Lorist, Monicque M
Aging affects functional connectivity between brain areas, however, a complete picture of how aging affects integration of information within and between functional networks is missing. We used complex network measures, derived from a brain-wide graph, to provide a comprehensive overview of age-related changes in functional connectivity. Functional connectivity in young and older participants was assessed during resting-state fMRI. The results show that aging has a large impact, not only on connectivity within functional networks but also on connectivity between the different functional networks in the brain. Brain networks in the elderly showed decreased modularity (less distinct functional networks) and decreased local efficiency. Connectivity decreased with age within networks supporting higher level cognitive functions, that is, within the default mode, cingulo-opercular and fronto-parietal control networks. Conversely, no changes in connectivity within the somatomotor and visual networks, networks implicated in primary information processing, were observed. Connectivity between these networks even increased with age. A brain-wide analysis approach of functional connectivity in the aging brain thus seems fundamental in understanding how age affects integration of information. PMID:24532319
Striatal astrocytes transdifferentiate into functional mature neurons following ischemic brain injury.
Duan, Chun-Ling; Liu, Chong-Wei; Shen, Shu-Wen; Yu, Zhang; Mo, Jia-Lin; Chen, Xian-Hua; Sun, Feng-Yan
To determine whether reactive astrocytes stimulated by brain injury can transdifferentiate into functional new neurons, we labeled these cells by injecting a glial fibrillary acidic protein (GFAP) targeted enhanced green fluorescence protein plasmid (pGfa2-eGFP plasmid) into the striatum of adult rats immediately following a transient middle cerebral artery occlusion (MCAO) and performed immunolabeling with specific neuronal markers to trace the neural fates of eGFP-expressing (GFP(+) ) reactive astrocytes. The results showed that a portion of striatal GFP(+) astrocytes could transdifferentiate into immature neurons at 1 week after MCAO and mature neurons at 2 weeks as determined by double staining GFP-expressing cells with ?III-tubulin (GFP(+) -Tuj-1(+) ) and microtubule associated protein-2 (GFP(+) -MAP-2(+) ), respectively. GFP(+) neurons further expressed choline acetyltransferase, glutamic acid decarboxylase, dopamine receptor D2-like family proteins, and the N-methyl-d-aspartate receptor subunit R2, indicating that astrocyte-derived neurons could develop into cholinergic or GABAergic neurons and express dopamine and glutamate receptors on their membranes. Electron microscopy analysis indicated that GFP(+) neurons could form synapses with other neurons at 13 weeks after MCAO. Electrophysiological recordings revealed that action potentials and active postsynaptic currents could be recorded in the neuron-like GFP(+) cells but not in the astrocyte-like GFP(+) cells, demonstrating that new GFP(+) neurons possessed the capacity to fire action potentials and receive synaptic inputs. These results demonstrated that striatal astrocyte-derived new neurons participate in the rebuilding of functional neural networks, a fundamental basis for brain repair after injury. These results may lead to new therapeutic strategies for enhancing brain repair after ischemic stroke. GLIA 2015;63:1660-1670. PMID:26031629
Can pharmacological and psychological treatment change brain structure and function in PTSD? A systematic review.
Thomaes, Kathleen; Dorrepaal, Ethy; Draijer, Nel; Jansma, Elise P; Veltman, Dick J; van Balkom, Anton J
While there is evidence of clinical improvement of posttraumatic stress disorder (PTSD) with treatment, its neural underpinnings are insufficiently clear. Moreover, it is unknown whether similar neurophysiological changes occur in PTSD specifically after child abuse, given its enduring nature and the developmental vulnerability of the brain during childhood. We systematically reviewed PTSD treatment effect studies on structural and functional brain changes from PubMed, EMBASE, PsycINFO, PILOTS and the Cochrane Library. We included studies on adults with (partial) PTSD in Randomized Controlled Trials (RCT) or pre-post designs (excluding case studies) on pharmacotherapy and psychotherapy. Risk of bias was evaluated independently by two raters. Brain coordinates and effect sizes were standardized for comparability. We included 15 studies (6 RCTs, 9 pre-post), four of which were on child abuse. Results showed that pharmacotherapy improved structural abnormalities (i.e., increased hippocampus volume) in both adult-trauma and child abuse related PTSD (3 pre-post studies). Functional changes were found to distinguish between groups. Adult-trauma PTSD patients showed decreased amygdala and increased dorsolateral prefrontal activations post-treatment (4 RCTs, 5 pre-post studies). In one RCT, child abuse patients showed no changes in the amygdala, but decreased dorsolateral prefrontal, dorsal anterior cingulate and insula activation post-treatment. In conclusion, pharmacotherapy may reduce structural abnormalities in PTSD, while psychotherapy may decrease amygdala activity and increase prefrontal, dorsal anterior cingulate and hippocampus activations, that may relate to extinction learning and re-appraisal. There is some evidence for a distinct activation pattern in child abuse patients, which clearly awaits further empirical testing. PMID:24321592
Purification and characterization of mu-specific opioid receptor from rat brain
Hasegawa, J.; Cho, T.M.; Ge, B.L.; Loh, H.H.
A mu-specific opioid receptor was purified to apparent homogeneity from rat brain membranes by 6-succinylmorphine affinity chromatography, Ultrogel filtration, wheat germ agglutinin affinity chromatography, and isoelectric focusing. The purified receptor had a molecular weight of 58,000 as determined by polyacrylamide gel electrophoresis, and was judged to be homogeneous by the following criteria: (1) a single band on the SDS gel; and (2) a specific opioid binding activity of 17,720 pmole/mg protein, close to the theoretical value. In addition, the 58,000 molecular weight value agrees closely with that determined by covalently labelling purified receptor with bromoacetyl-/sup 3/H-dihydromorphine or with /sup 125/I-beta-endorphin and dimethyl suberimidate. To their knowledge, this is the first complete purification of an opioid receptor that retains its ability to bind opiates.
The structural-functional connectome and the default mode network of the human brain.
Horn, Andreas; Ostwald, Dirk; Reisert, Marco; Blankenburg, Felix
An emerging field of human brain imaging deals with the characterization of the connectome, a comprehensive global description of structural and functional connectivity within the human brain. However, the question of how functional and structural connectivity are related has not been fully answered yet. Here, we used different methods to estimate the connectivity between each voxel of the cerebral cortex based on functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data in order to obtain observer-independent functional-structural connectomes of the human brain. Probabilistic fiber-tracking and a novel global fiber-tracking technique were used to measure structural connectivity whereas for functional connectivity, full and partial correlations between each voxel pair's fMRI-timecourses were calculated. For every voxel, two vectors consisting of functional and structural connectivity estimates to all other voxels in the cortex were correlated with each other. In this way, voxels structurally and functionally connected to similar regions within the rest of the brain could be identified. Areas forming parts of the 'default mode network' (DMN) showed the highest agreement of structure-function connectivity. Bilateral precuneal and inferior parietal regions were found using all applied techniques, whereas the global tracking algorithm additionally revealed bilateral medial prefrontal cortices and early visual areas. There were no significant differences between the results obtained from full and partial correlations. Our data suggests that the DMN is the functional brain network, which uses the most direct structural connections. Thus, the anatomical profile of the brain seems to shape its functional repertoire and the computation of the whole-brain functional-structural connectome appears to be a valuable method to characterize global brain connectivity within and between populations. PMID:24099851
Is There A Path Beyond BOLD? Molecular Imaging of Brain Function
Koretsky, Alan P.
The dependence of BOLD on neuro-vascular coupling leaves it steps removed from direct monitoring of neural function. MRI based approaches have been developed aimed at reporting more directly on brain function. These include: manganese enhanced MRI as a surrogate for calcium ion influx; agents responsive to calcium concentrations; approaches to measure membrane potential; agents to measure neurotransmittors; and strategies to measure gene expression. This work has led to clever design of molecular imaging tools and many contributions to studies of brain function in animal models. However, a robust approach that has potential to get MRI closer to neurons in the human brain has not yet emerged. PMID:22406355
Astrocytes in sensory circumventricular organs of the rat brain express functional binding sites for endothelin.
Gebke, E; Müller, A R; Pehl, U; Gerstberger, R
Sensory circumventricular organs bordering the anterior third cerebral ventricle, the subfornical organ and the organum vasculosum laminae terminalis, lack blood-brain barrier characteristics and are therefore accessible to circulating peptides like endothelins. Astrocytes of the rat subfornical organ and organum vasculosum laminae terminalis additionally showed immunocytochemical localization of endothelin-1/endothelin-3-like peptides, possibly acting as circumventricular organ-intrinsic modulators. Employing [125I]endothelin-1 as radioligand, quantitative autoradiography demonstrated specific binding sites throughout the rat organum vasculosum laminae terminalis and subfornical organ, and competitive displacement studies revealed expression of both ET(A) and ET(B) receptor subtypes for either circumventricular organ. ET(B) receptor binding prevailed for the whole brain and ET(A) receptors could be labelled in the peripheral vascular system. To characterize endothelin-specific receptors in astrocytes of both circumventricular organs, alterations in the intracellular calcium concentration due to endothelin-1/endothelin-3 stimulation were studied in primary culture of subfornical organ and organum vasculosum laminae terminalis cells obtained from early postnatal rat pups. Endothelin-1 and endothelin-3 induced Ca(2+) transients in 9-13% of either subfornical organ or organum vasculosum laminae terminalis astrocytes, respectively, and some glial cells (subfornical organ: 2%, organum vasculosum laminae terminalis: 5%) responded to both endothelin analogues. The antagonistic action of BQ123 specific for ET(A) receptors (74% of all astrocytes tested), and the pronounced responsiveness to the ET(B) receptor agonist [4Ala]ET-1 (subfornical organ: 27%, organum vasculosum laminae terminalis: 35%) demonstrated glial expression of both endothelin receptor subtypes. Agonist-induced elevations in the intracellular calcium concentration proved to be independent of extracellular Ca(2+). In summary, the results indicate that endothelin(s) interact(s) with circumventricular organ astrocytes. Competitive receptor binding techniques using brain tissue sections as well as a fura-2 loaded primary cell culture system of the subfornical organ and organum vasculosum laminae terminalis demonstrate glial expression of functional ET(A) and ET(B) receptors, with calcium as intracellular messenger emerging primarily from intracellular stores. Endothelin(s) of both circulating and circumventricular organ-intrinsic origin may afferently transfer information important for cardiovascular homeostasis to circumventricular organs serving as "windows to the brain". PMID:10799769
Influenza viruses induce autoantibodies to a brain-specific 37-kDa protein in rabbit.
Laing, P; Knight, J G; Hill, J M; Harris, A G; Oxford, J S; Webster, R G; Markwell, M A; Paul, S M; Pert, C B
Immunization of rabbits with certain H1N1 influenza viruses, including the neurotropic strains NWS/33 and WSN/33 and the New Jersey/76 strain, resulted in the production of autoantibodies to a brain-specific protein of 37 kDa that is present in various species, including humans. Autoantibodies were produced to brain only; various other tissues tested were negative. These antibodies were not elicited by other influenza A or B viruses, including closely related recombinant strains, but were elicited by the isolated hemagglutinin of A/Bellamy/42 strain and by formaldehyde-fixed WSN virus--demonstrating that infection was not essential for the induction of autoantibodies. In histological studies, reaction with anti-viral antisera was specific to gray matter and was confined to sera that recognized the 37-kDa protein. Antibody binding was prominent in regions comprised of neuronal cell bodies in cellular layers of the dentate gyrus, hippocampus, cerebral cortex, and cerebellum and was undetectable in myelin-rich regions, such as the corpus callosum. The 37-kDa protein, therefore, appears to be a neuronal antigen. Antibodies directed against this protein may be involved in the pathogenesis of one or more of the neuropsychiatric disorders that occur after infection with influenza. Images PMID:2467294
Error estimates and specification parameters for functional renormalization
Schnoerr, David [Institute for Theoretical Physics, University of Heidelberg, D-69120 Heidelberg (Germany)] [Institute for Theoretical Physics, University of Heidelberg, D-69120 Heidelberg (Germany); Boettcher, Igor, E-mail: firstname.lastname@example.com [Institute for Theoretical Physics, University of Heidelberg, D-69120 Heidelberg (Germany)] [Institute for Theoretical Physics, University of Heidelberg, D-69120 Heidelberg (Germany); Pawlowski, Jan M. [Institute for Theoretical Physics, University of Heidelberg, D-69120 Heidelberg (Germany) [Institute for Theoretical Physics, University of Heidelberg, D-69120 Heidelberg (Germany); ExtreMe Matter Institute EMMI, GSI Helmholtzzentrum für Schwerionenforschung mbH, D-64291 Darmstadt (Germany); Wetterich, Christof [Institute for Theoretical Physics, University of Heidelberg, D-69120 Heidelberg (Germany)] [Institute for Theoretical Physics, University of Heidelberg, D-69120 Heidelberg (Germany)
We present a strategy for estimating the error of truncated functional flow equations. While the basic functional renormalization group equation is exact, approximated solutions by means of truncations do not only depend on the choice of the retained information, but also on the precise definition of the truncation. Therefore, results depend on specification parameters that can be used to quantify the error of a given truncation. We demonstrate this for the BCS–BEC crossover in ultracold atoms. Within a simple truncation the precise definition of the frequency dependence of the truncated propagator affects the results, indicating a shortcoming of the choice of a frequency independent cutoff function.
TGF?–SMAD signal transduction: molecular specificity and functional flexibility
Bernhard Schmierer; Caroline S. Hill
Ligands of the transforming growth factor-? (TGF?) superfamily of growth factors initiate signal transduction through a bewildering complexity of ligand–receptor interactions. Signalling then converges to nuclear accumulation of transcriptionally active SMAD complexes and gives rise to a plethora of specific functional responses in both embryos and adult organisms. Current research is focused on the mechanisms that regulate SMAD activity to
Sex differences in the brain: The relation between structure and function Geert J. de Vries a,
de Vries, Geert J.
Sex differences in the brain: The relation between structure and function Geert J. de Vries a 2009 Revised 10 March 2009 Accepted 12 March 2009 Keywords: Sex differences Sex similarities hypothesis was proposed, many sex differences have been found in behavior as well as structure of the brain
The Functional Organization of the Brain of the Cuttlefish Sepia officinalis
B. B. Boycott
The functional organization of the brain of Sepia has been investigated by electrical stimulation. As a result several new divisions of the brain have been made. The pedal ganglion has been shown to consist of four parts: (1) the anterior chromatophore lobes innervating the skin and muscles of the anterior part of the head and arms; (2) the anterior pedal
Scientists Probe Immune System's Role in Brain Function and Neurological Disease
Boulanger, Lisa
Scientists Probe Immune System's Role in Brain Function and Neurological Disease Bridget M. Kuehn E MERGING EVIDENCE SUGGESTS that proteins associated with the immune system may play additional roles protects the brain from the immune system by acting as a bar- ricade to its components, scientists have
Hypertension and the Brain: Vulnerability of the Prefrontal Regions and Executive Functions
Naftali Raz; Karen M. Rodrigue; James D. Acker
Untreated hypertension negatively affects brain anatomy and cognitive functions, but the effects of medically treated hypertension are unclear. The authors compared 40 middle-age and older adults diagnosed with essential hypertension to demographically matched normotensive peers. Volumes of 7 brain regions and deep and periventricular white-matter hyperintensities (WMH) were measured on magnetic resonance imaging scans. Performance in 4 cognitive domains (perseveration,
Investigation of the large-scale functional brain networks modulated by acupuncture
Tian, Jie
Investigation of the large-scale functional brain networks modulated by acupuncture Yuanyuan Fenga effects of acupuncture. Considering that acupuncture can induce long-lasting effects, several researchers have begun to pay attention to the sustained effects of acupuncture on the resting brain. Most
Image-Derived Input Function for Human Brain Using High Resolution PET Imaging with [11
Shen, Jun
Image-Derived Input Function for Human Brain Using High Resolution PET Imaging with [11 C was to test seven previously published image-input methods in state-of-the-art high resolution PET brain images. Images were obtained with a High Resolution Research Tomograph plus a resolution
Understanding the potency of stressful early life experiences on brain and body function
Bruce S. McEwen
Early life experiences have powerful effects on the brain and body lasting throughout the entire life span and influencing brain function, behavior, and the risk for a number of systemic and mental disorders. Animal models of early life adversity are providing mechanistic insights, including glimpses into the fascinating world that is now called "epigenetics" as well as the role of
The social brain in adolescence: Evidence from functional magnetic resonance imaging and behavioural studies
Stephanie Burnett; Catherine Sebastian; Kathrin Cohen Kadosh; Sarah-Jayne Blakemore
Social cognition is the collection of cognitive processes required to understand and interact with others. The term 'social brain' refers to the network of brain regions that underlies these processes. Recent evidence suggests that a number of social cognitive functions continue to develop during adolescence, resulting in age differences in tasks that assess cognitive domains including face processing, mental state
Individual Differences in General Intelligence Correlate with Brain Function during Nonreasoning Tasks.
ERIC Educational Resources Information Center
Haier, Richard J.; White, Nathan S.; Alkire, Michael T.
Administered Raven's Advanced Progressive Matrices to 22 adults and measured cerebral glucose activity as subjects viewed videos on 2 occasions. Data provide evidence that individual differences in intelligence correlate with brain function even when the brain is engaged in non-reasoning tasks. (SLD)
Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat
T. M Madsen; P. E. G Kristjansen; T. G Bolwig; G Wörtwein
The generation of new neurons in the adult mammalian brain has been documented in numerous recent reports. Studies undertaken so far indicate that adult hippocampal neurogenesis is related in a number of ways to hippocampal function.Here, we report that subjecting adult rats to fractionated brain irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At
Horticultural Therapy has Beneficial Effects on Brain Functions in Cerebrovascular Diseases
Yuko Mizuno-Matsumoto; Syoji Kobashi; Yutaka Hata; Osamu Ishikawa; Fusayo Asano
Horticultural therapy (HT) is gaining attention as a form of rehabilitations in medical fields especially such as occupational therapy and nursing care, although its effectiveness has not been proven yet. This paper uses a strictly medical point of view to assess whether or not HT is effective for improvement of functional activities in the brains of brain-damaged patients. Five patients
Structural and functional brain development and its relation to cognitive development
B. J. Casey; Jay N. Giedd; Kathleen M. Thomas
Despite significant gains in the fields of pediatric neuroimaging and developmental neurobiology, surprisingly little is known about the developing human brain or the neural bases of cognitive development. This paper addresses MRI studies of structural and functional changes in the developing human brain and their relation to changes in cognitive processes over the first few decades of human life. Based
MRI Study on the Functional and Spatial Consistency of Resting State-Related Independent Components of the Brain Network
Jeong, Bumseok; Kim, Ji-Woong
Objective Resting-state networks (RSNs), including the default mode network (DMN), have been considered as markers of brain status such as consciousness, developmental change, and treatment effects. The consistency of functional connectivity among RSNs has not been fully explored, especially among resting-state-related independent components (RSICs). Materials and Methods This resting-state fMRI study addressed the consistency of functional connectivity among RSICs as well as their spatial consistency between 'at day 1' and 'after 4 weeks' in 13 healthy volunteers. Results We found that most RSICs, especially the DMN, are reproducible across time, whereas some RSICs were variable in either their spatial characteristics or their functional connectivity. Relatively low spatial consistency was found in the basal ganglia, a parietal region of left frontoparietal network, and the supplementary motor area. The functional connectivity between two independent components, the bilateral angular/supramarginal gyri/intraparietal lobule and bilateral middle temporal/occipital gyri, was decreased across time regardless of the correlation analysis method employed, (Pearson's or partial correlation). Conclusion RSICs showing variable consistency are different between spatial characteristics and functional connectivity. To understand the brain as a dynamic network, we recommend further investigation of both changes in the activation of specific regions and the modulation of functional connectivity in the brain network. PMID:22563263
Microglia function during brain development: New insights from animal models.
Bilimoria, Parizad M; Stevens, Beth
The role of microglia in healthy brains is just beginning to receive notice. Recent studies have revealed that these phagocytic cells control the patterning and wiring of the developing central nervous system (CNS) by regulating, amongst many other processes, programmed cell death, activity-dependent synaptic pruning and synapse maturation. Microglia also play important roles in the mature brain and have demonstrated effects on behavior. Converging evidence from human and mouse studies together raise questions as to the role of microglia in disorders of brain development such as autism and, schizophrenia. In this review, we summarize a number of major findings regarding the role of microglia in brain development and highlight some key questions and avenues for future study. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. PMID:25463024
Emergence of Functional Specificity in Balanced Networks with Synaptic Plasticity
Sadeh, Sadra; Clopath, Claudia; Rotter, Stefan
In rodent visual cortex, synaptic connections between orientation-selective neurons are unspecific at the time of eye opening, and become to some degree functionally specific only later during development. An explanation for this two-stage process was proposed in terms of Hebbian plasticity based on visual experience that would eventually enhance connections between neurons with similar response features. For this to work, however, two conditions must be satisfied: First, orientation selective neuronal responses must exist before specific recurrent synaptic connections can be established. Second, Hebbian learning must be compatible with the recurrent network dynamics contributing to orientation selectivity, and the resulting specific connectivity must remain stable for unspecific background activity. Previous studies have mainly focused on very simple models, where the receptive fields of neurons were essentially determined by feedforward mechanisms, and where the recurrent network was small, lacking the complex recurrent dynamics of large-scale networks of excitatory and inhibitory neurons. Here we studied the emergence of functionally specific connectivity in large-scale recurrent networks with synaptic plasticity. Our results show that balanced random networks, which already exhibit highly selective responses at eye opening, can develop feature-specific connectivity if appropriate rules of synaptic plasticity are invoked within and between excitatory and inhibitory populations. If these conditions are met, the initial orientation selectivity guides the process of Hebbian learning and, as a result, functionally specific and a surplus of bidirectional connections emerge. Our results thus demonstrate the cooperation of synaptic plasticity and recurrent dynamics in large-scale functional networks with realistic receptive fields, highlight the role of inhibition as a critical element in this process, and paves the road for further computational studies of sensory processing in neocortical network models equipped with synaptic plasticity. PMID:26090844
Obesity Increases Cerebrocortical Reactive Oxygen Species And Impairs Brain Function
Freeman, Linnea R.; Zhang, Le; Nair, Anand; Dasuri, Kalavathi; Francis, Joseph; Fernandez-Kim, Sun-Ok; Bruce-Keller, Annadora J.; Keller, Jeffrey N.
Nearly two-thirds of the population in the United States is overweight or obese, and this unprecedented level of obesity will undoubtedly have a profound impact on overall health, although little is currently known about the effects of obesity on the brain. The objective of the current study was to investigate cerebral oxidative stress and cognitive decline in the context of diet-induced obesity (DIO). We demonstrate for the first time that DIO induces higher levels of reactive oxygen species (ROS) in the brain, and promotes cognitive impairment. Importantly, we also demonstrate for the first time in these studies that both body weight and adiposity are tightly correlated with the level of ROS. Interestingly, ROS were not correlated with cognitive decline in this model. Alterations in the antioxidant/detoxification Nrf2 pathway, superoxide dismutase, and catalase were not significantly altered in response to DIO. A significant impairment in glutathione peroxidase was observed in response to DIO. Taken together, these data demonstrate for the first time that DIO increases the level of total and individual ROS in the brain, and highlight a direct relationship between the amount of adiposity and the level of oxidative stress within the brain. These data have important implications for understanding the negative effects of obesity on the brain, and are vital to understanding the role of oxidative stress in mediating the effects of obesity on the brain. PMID:23116605
Functionalized Carbon Nanotubes in the Brain: Cellular Internalization and Neuroinflammatory Responses
Bates, Katie; Al-Jamal, Khuloud T.; Gaillard, Claire; Prato, Maurizio; Bianco, Alberto; Pizzorusso, Tommaso; Kostarelos, Kostas
The potential use of functionalized carbon nanotubes (f-CNTs) for drug and gene delivery to the central nervous system (CNS) and as neural substrates makes the understanding of their in vivo interactions with the neural tissue essential. The aim of this study was to investigate the interactions between chemically functionalized multi-walled carbon nanotubes (f-MWNTs) and the neural tissue following cortical stereotactic administration. Two different f-MWNT constructs were used in these studies: shortened (by oxidation) amino-functionalized MWNT (oxMWNT-NH3+) and amino-functionalized MWNT (MWNT-NH3+). Parenchymal distribution of the stereotactically injected f-MWNTs was assessed by histological examination. Both f-MWNT were uptaken by different types of neural tissue cells (microglia, astrocytes and neurons), however different patterns of cellular internalization were observed between the nanotubes. Furthermore, immunohistochemical staining for specific markers of glial cell activation (GFAP and CD11b) was performed and secretion of inflammatory cytokines was investigated using real-time PCR (qRT-PCR). Injections of both f-MWNT constructs led to a local and transient induction of inflammatory cytokines at early time points. Oxidation of nanotubes seemed to induce significant levels of GFAP and CD11b over-expression in areas peripheral to the f-MWNT injection site. These results highlight the importance of nanotube functionalization on their interaction with brain tissue that is deemed critical for the development nanotube-based vector systems for CNS applications. PMID:24260521
Functional brain imaging in 14 patients with dissociative amnesia reveals right inferolateral prefrontal hypometabolism.
Brand, Matthias; Eggers, Carsten; Reinhold, Nadine; Fujiwara, Esther; Kessler, Josef; Heiss, Wolf-Dieter; Markowitsch, Hans J
Dissociative amnesia is a condition usually characterized by severely impaired retrograde memory functioning in the absence of structural brain damage. Recent case studies nevertheless found functional brain changes in patients suffering from autobiographical-episodic memory loss in the cause of dissociative amnesia. Functional changes were demonstrated in both resting state and memory retrieval conditions. In addition, some but not all cases also showed other neuropsychological impairments beyond retrograde memory deficits. However, there is no group study available that examined potential functional brain abnormalities and accompanying neuropsychological deteriorations in larger samples of patients with dissociative retrograde amnesia. We report functional imaging and neuropsychological data acquired in 14 patients with dissociative amnesia following stressful or traumatic events. All patients suffered from autobiographical memory loss. In addition, approximately half of the patients had deficits in anterograde memory and executive functioning. Accompanying functional brain changes were measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). Regional glucose utilization of the patients was compared with that of 19 healthy subjects, matched for age and gender. We found significantly decreased glucose utilization in the right inferolateral prefrontal cortex in the patients. Hypometabolism in this brain region, known to be involved in retrieval of autobiographical memories and self-referential processing, may be a functional brain correlate of dissociative amnesia. PMID:19783409
Time-varying functional network information extracted from brief instances of spontaneous brain activity
Liu, Xiao; Duyn, Jeff H.
Recent functional magnetic resonance imaging studies have shown that the brain is remarkably active even in the absence of overt behavior, and this activity occurs in spatial patterns that are reproducible across subjects and follow the brain's established functional subdivision. Investigating the distribution of these spatial patterns is an active area of research with the goal of obtaining a better understanding of the neural networks underlying brain function. One intriguing aspect of spontaneous activity is an apparent nonstationarity, or variability of interaction between brain regions. It was recently proposed that spontaneous brain activity may be dominated by brief traces of activity, possibly originating from a neuronal avalanching phenomenon. Such traces may involve different subregions in a network at different times, potentially reflecting functionally relevant relationships that are not captured with conventional data analysis. To investigate this, we examined publicly available functional magnetic resonance imaging data with a dedicated analysis method and found indications that functional networks inferred from conventional correlation analysis may indeed be driven by activity at only a few critical time points. Subsequent analysis of the activity at these critical time points revealed multiple spatial patterns, each distinctly different from the established functional networks. The spatial distribution of these patterns suggests a potential functional relevance. PMID:23440216
Large-scale functional brain network changes in taxi drivers: evidence from resting-state fMRI.
Wang, Lubin; Liu, Qiang; Shen, Hui; Li, Hong; Hu, Dewen
Driving a car in the environment is a complex behavior that involves cognitive processing of visual information to generate the proper motor outputs and action controls. Previous neuroimaging studies have used virtual simulation to identify the brain areas that are associated with various driving-related tasks. Few studies, however, have focused on the specific patterns of functional organization in the driver's brain. The aim of this study was to assess differences in the resting-state networks (RSNs) of the brains of drivers and nondrivers. Forty healthy subjects (20 licensed taxi drivers, 20 nondrivers) underwent an 8-min resting-state functional MRI acquisition. Using independent component analysis, three sensory (primary and extrastriate visual, sensorimotor) RSNs and four cognitive (anterior and posterior default mode, left and right frontoparietal) RSNs were retrieved from the data. We then examined the group differences in the intrinsic brain activity of each RSN and in the functional network connectivity (FNC) between the RSNs. We found that the drivers had reduced intrinsic brain activity in the visual RSNs and reduced FNC between the sensory RSNs compared with the nondrivers. The major finding of this study, however, was that the FNC between the cognitive and sensory RSNs became more positively or less negatively correlated in the drivers relative to that in the nondrivers. Notably, the strength of the FNC between the left frontoparietal and primary visual RSNs was positively correlated with the number of taxi-driving years. Our findings may provide new insight into how the brain supports driving behavior. PMID:25338709
Induced specific immunological unresponsiveness & conditioned behavioral reflexes, in functional isomorphism-meditation and conditioned specific unresponsiveness.
Freed, S
Detailed functional isomorphism had been observed (Freed, 1984) between induced (conditioned) immunogenicity and classical conditioned defensive reflexes, possibly as evolutionary adaptation against danger at micro and macro levels respectively. Similarly, functional isomorphism is postulated between conditioned specific tolerogenicity of the immunotolerance system and behavioral reflexes. Isomorphism requires that sensory signals elaborated with intrinsic (unconditioned) behavioral tolerogens as carriers do not subsequently combine classically with unconditioned aversive stimuli and evoke conditioned defensive responses. Unconditioned behavioral tolerogenic carriers were identified with behavioral (physiological) activities of Oriental meditation. Confirmation of conditioned behavioral tolerogenicity appeared in the unresponsiveness of Yogi mediators to sensory stimuli as reflected in unchanged alpha rhythms of their encephalograms. Conditioned behavioral specific unresponsiveness maintains the "quiet" of meditation and mediates the experience of Zen mediators, namely, sharpened, clearer perceptions and unresponsiveness to aversive components of current conditioned signals ordinarily reactivating residues of affect. Conditioned behavioral specific unresponsiveness has survival value. PMID:2656566
Establishing, versus Maintaining, Brain Function: A Neuro-computational Model of Cortical Reorganization after Injury to the Immature Brain
Varier, Sreedevi; Forsyth, Rob; 10.1017/S1355617711000993
The effect of age at injury on outcome after acquired brain injury (ABI) has been the subject of much debate. Many argue that young brains are relatively tolerant of injury. A contrasting viewpoint due to Hebb argues that greater system integrity may be required for the initial establishment of a function than for preservation of an already-established function. A neuro-computational model of cortical map formation was adapted to examine effects of focal and distributed injury at various stages of development. This neural network model requires a period of training during which it self-organizes to establish cortical maps. Injuries were simulated by lesioning the model at various stages of this process and network function was monitored as "development" progressed to completion. Lesion effects are greater for larger, earlier, and distributed (multifocal) lesions. The mature system is relatively robust, particularly to focal injury. Activities in recovering systems injured at an early stage show changes that e...
A multimodal approach for determining brain networks by jointly modeling functional and structural connectivity.
Xue, Wenqiong; Bowman, F DuBois; Pileggi, Anthony V; Mayer, Andrew R
Recent innovations in neuroimaging technology have provided opportunities for researchers to investigate connectivity in the human brain by examining the anatomical circuitry as well as functional relationships between brain regions. Existing statistical approaches for connectivity generally examine resting-state or task-related functional connectivity (FC) between brain regions or separately examine structural linkages. As a means to determine brain networks, we present a unified Bayesian framework for analyzing FC utilizing the knowledge of associated structural connections, which extends an approach by Patel et al. (2006a) that considers only functional data. We introduce an FC measure that rests upon assessments of functional coherence between regional brain activity identified from functional magnetic resonance imaging (fMRI) data. Our structural connectivity (SC) information is drawn from diffusion tensor imaging (DTI) data, which is used to quantify probabilities of SC between brain regions. We formulate a prior distribution for FC that depends upon the probability of SC between brain regions, with this dependence adhering to structural-functional links revealed by our fMRI and DTI data. We further characterize the functional hierarchy of functionally connected brain regions by defining an ascendancy measure that compares the marginal probabilities of elevated activity between regions. In addition, we describe topological properties of the network, which is composed of connected region pairs, by performing graph theoretic analyses. We demonstrate the use of our Bayesian model using fMRI and DTI data from a study of auditory processing. We further illustrate the advantages of our method by comparisons to methods that only incorporate functional information. PMID:25750621
CONEUR-1155; NO. OF PAGES 12 Please cite this article in press as: Barrett LF, Satpute AB. Large-scale brain networks in affective and social neuroscience: towards an integrative functional architecture of the brain, Curr Opin
Barrett, Lisa Feldman
to distinct brain net- works. Understanding the functions of the human brain in psychological terms requires-scale brain networks in affective and social neuroscience: towards an integrative functional architecture of the brain, Curr Opin Neurobiol (2013), http://dx.doi.org/10.1016/j.conb.2012.12.012 Large-scale brain
Small-World Brain Network and Dynamic Functional Distribution in Patients with Subcortical Vascular Cognitive Impairment.
Yu, Yongqiang; Zhou, Xia; Wang, Haibao; Hu, Xiaopeng; Zhu, Xiaoqun; Xu, Liyan; Zhang, Chao; Sun, Zhongwu
To investigate the topological properties of the functional connectivity and their relationships with cognition impairment in subcortical vascular cognitive impairment (SVCI) patients, resting-state fMRI and graph theory approaches were employed in 23 SVCI patients and 20 healthy controls. Functional connectivity between 90 brain regions was estimated using bivariate correlation analysis and thresholded to construct a set of undirected graphs. Moreover, all of them were subjected to a battery of cognitive assessment, and the correlations between graph metrics and cognitive performance were further analyzed. Our results are as follows: functional brain networks of both SVCI patients and controls showed small-world attributes over a range of thresholds(0.15?sparsity?0.40). However, global topological organization of the functional brain networks in SVCI was significantly disrupted, as indicated by reduced global and local efficiency, clustering coefficients and increased characteristic path lengths relative to normal subjects. The decreased activity areas in SVCI predominantly targeted in the frontal-temporal lobes, while subcortical regions showed increased topological properties, which are suspected to compensate for the inefficiency of the functional network. We also demonstrated that altered brain network properties in SVCI are closely correlated with general cognitive and praxis dysfunction. The disruption of whole-brain topological organization of the functional connectome provides insight into the functional changes in the human brain in SVCI. PMID:26132397
Small-World Brain Network and Dynamic Functional Distribution in Patients with Subcortical Vascular Cognitive Impairment
Yu, Yongqiang; Zhou, Xia; Wang, Haibao; Hu, Xiaopeng; Zhu, Xiaoqun; Xu, Liyan; Zhang, Chao; Sun, Zhongwu
To investigate the topological properties of the functional connectivity and their relationships with cognition impairment in subcortical vascular cognitive impairment (SVCI) patients, resting-state fMRI and graph theory approaches were employed in 23 SVCI patients and 20 healthy controls. Functional connectivity between 90 brain regions was estimated using bivariate correlation analysis and thresholded to construct a set of undirected graphs. Moreover, all of them were subjected to a battery of cognitive assessment, and the correlations between graph metrics and cognitive performance were further analyzed. Our results are as follows: functional brain networks of both SVCI patients and controls showed small-world attributes over a range of thresholds(0.15?sparsity?0.40). However, global topological organization of the functional brain networks in SVCI was significantly disrupted, as indicated by reduced global and local efficiency, clustering coefficients and increased characteristic path lengths relative to normal subjects. The decreased activity areas in SVCI predominantly targeted in the frontal-temporal lobes, while subcortical regions showed increased topological properties, which are suspected to compensate for the inefficiency of the functional network. We also demonstrated that altered brain network properties in SVCI are closely correlated with general cognitive and praxis dysfunction. The disruption of whole-brain topological organization of the functional connectome provides insight into the functional changes in the human brain in SVCI. PMID:26132397
Evidence for sex-specific selection in brain: a case study of the nine-spined stickleback.
Herczeg, G; Välimäki, K; Gonda, A; Merilä, J
Theory predicts that the sex making greater investments into reproductive behaviours demands higher cognitive ability, and as a consequence, larger brains or brain parts. Further, the resulting sexual dimorphism can differ between populations adapted to different environments, or among individuals developing under different environmental conditions. In the nine-spine stickleback (Pungitius pungitius), males perform nest building, courtship, territory defence and parental care, whereas females perform mate choice and produce eggs. Also, predation-adapted marine and competition-adapted pond populations have diverged in a series of ecologically relevant traits, including the level of phenotypic plasticity. Here, we studied sexual dimorphism in brain size and architecture in nine-spined stickleback from marine and pond populations reared in a factorial experiment with predation and food treatments in a common garden experiment. Males had relatively larger brains, larger telencephala, cerebella and hypothalami (6-16% divergence) than females, irrespective of habitat. Females tended to have larger bulbi olfactorii than males (13%) in the high food treatment, whereas no such difference was found in the low food treatment. The strong sexual dimorphism in brain architecture implies that the different reproductive allocation strategies (behaviour vs. egg production) select for different investments into the costly brains between males and females. The lack of habitat dependence in brain sexual dimorphism suggests that the sex-specific selection forces on brains differ only negligibly between habitats. Although significance of the observed sex-specific brain plasticity in the size of bulbus olfactorius remains unclear, it demonstrates the potential for sex-specific neural plasticity. PMID:24898271
The Conundrum of Functional Brain Networks: Small-World Efficiency or Fractal Modularity
Gallos, Lazaros K.; Sigman, Mariano; Makse, Hernán A.
The human brain has been studied at multiple scales, from neurons, circuits, areas with well-defined anatomical and functional boundaries, to large-scale functional networks which mediate coherent cognition. In a recent work, we addressed the problem of the hierarchical organization in the brain through network analysis. Our analysis identified functional brain modules of fractal structure that were inter-connected in a small-world topology. Here, we provide more details on the use of network science tools to elaborate on this behavior. We indicate the importance of using percolation theory to highlight the modular character of the functional brain network. These modules present a fractal, self-similar topology, identified through fractal network methods. When we lower the threshold of correlations to include weaker ties, the network as a whole assumes a small-world character. These weak ties are organized precisely as predicted by theory maximizing information transfer with minimal wiring costs. PMID:22586406
Categories and functional units: An infinite hierarchical model for brain activations
Lashkari, Danial
We present a model that describes the structure in the responses of different brain areas to a set of stimuli in terms of stimulus categories (clusters of stimuli) and functional units (clusters of voxels). We assume that ...
Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans
Technology Transfer Automated Retrieval System (TEKTRAN)
Objective: In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during carbohydrate ingestion suggest that glucose may regulate HT signaling but are potentially confoun...
Functional Magnetic Resonance Imaging of Rats with Experimental Autoimmune Encephalomyelitis Reveals Brain Cortex Remodelling
Tambalo, Stefano; Peruzzotti-Jametti, Luca; Rigolio, Roberta; Fiorini, Silvia; Bontempi, Pietro; Mallucci, Giulia; Balzarotti, Beatrice; Marmiroli, Paola; Sbarbati, Andrea; Cavaletti, Guido; Pluchino, Stefano; Marzola, Pasquina
reorganization and its brain structural/pathological correlates in Dark Agouti rats with experimental autoimmune encephalomyelitis (EAE), a widely accepted preclinical model of chronic MS. Morphological and functional MRI (fMRI) were performed before disease...
A Probabilistic Model of Functional Brain Connectivity Network for Discovering Novel Biomarkers
Bian, Jiang; Xie, Mengjun; Topaloglu, Umit; Cisler, Josh M.
Graph theoretical analyses of functional brain connectivity networks have been limited to a static view of brain activities over the entire timeseries. In this paper, we propose a new probabilistic model of the functional brain connectivity network, the strong-edge model, which incorporates the temporal fluctuation of neurodynamics. We also introduce a systematic approach to identifying biomarkers based on network characteristics that quantitatively describe the organization of the brain network. The evaluation results of the proposed strong-edge network model is quite promising. The biomarkers derived from the strong-edge model have achieved much higher prediction accuracy of 89% (ROCAUC: 0.96) in distinguishing depression subjects from healthy controls in comparison with the conventional network model (accuracy: 76%, ROC-AUC: 0.87). These novel biomarkers have the high potential of being applied clinically in diagnosing neurological and psychiatric brain diseases with noninvasive neuroimaging technologies. PMID:24303289
Brain temperature fluctuation: a reflection of functional neural activation.
Kiyatkin, Eugene A; Brown, P Leon; Wise, Roy A
Although it is known that relatively large increases in local brain temperature can occur during behaviour and in response to various novel, stressful and emotionally arousing environmental stimuli, the source of this heat is not clearly established. To clarify this issue, we monitored the temperature in three brain structures (dorsal and ventral striatum, cerebellum) and in arterial blood at the level of the abdominal aorta in freely moving rats exposed to several environmental challenges ranging from traditional stressors to simple sensory stimuli (cage change, tail pinch, exposure to another male rat, a female rat, a mouse or an unexpected sound). We found that brain temperature was consistently higher than arterial blood temperature, and that brain temperature increased prior to, and to a greater extent than, the increase in blood temperature evoked by each test challenge. Thus, the local metabolic consequences of widely correlated neural activity appear to be the primary source of increases in brain temperature and a driving force behind the associated changes in body temperature. PMID:12153543
Brain structural connectivity increases concurrent with functional improvement: evidence from diffusion tensor MRI in children with cerebral palsy during therapy.
Englander, Zoë A; Sun, Jessica; Laura Case; Mikati, Mohamad A; Kurtzberg, Joanne; Song, Allen W
Cerebral Palsy (CP) refers to a heterogeneous group of permanent but non-progressive movement disorders caused by injury to the developing fetal or infant brain (Bax et al., 2005). Because of its serious long-term consequences, effective interventions that can help improve motor function, independence, and quality of life are critically needed. Our ongoing longitudinal clinical trial to treat children with CP is specifically designed to meet this challenge. To maximize the potential for functional improvement, all children in this trial received autologous cord blood transfusions (with order randomized with a placebo administration over 2 years) in conjunction with more standard physical and occupational therapies. As a part of this trial, magnetic resonance imaging (MRI) is used to improve our understanding of how these interventions affect brain development, and to develop biomarkers of treatment efficacy. In this report, diffusion tensor imaging (DTI) and subsequent brain connectome analyses were performed in a subset of children enrolled in the clinical trial (n = 17), who all exhibited positive but varying degrees of functional improvement over the first 2-year period of the study. Strong correlations between increases in white matter (WM) connectivity and functional improvement were demonstrated; however no significant relationships between either of these factors with the age of the child at time of enrollment were identified. Thus, our data indicate that increases in brain connectivity reflect improved functional abilities in children with CP. In future work, this potential biomarker can be used to help differentiate the underlying mechanisms of functional improvement, as well as to identify treatments that can best facilitate functional improvement upon un-blinding of the timing of autologous cord blood transfusions at the completion of this study. PMID:25610796
Functions of Huntingtin in Germ Layer Specification and Organogenesis
Nguyen, Giang D.; Molero, Aldrin E.; Gokhan, Solen; Mehler, Mark F.
Huntington's disease (HD) is a neurodegenerative disease caused by abnormal polyglutamine expansion in the huntingtin protein (Htt). Although both Htt and the HD pathogenic mutation (mHtt) are implicated in early developmental events, their individual involvement has not been adequately explored. In order to better define the developmental functions and pathological consequences of the normal and mutant proteins, respectively, we employed embryonic stem cell (ESC) expansion, differentiation and induction experiments using huntingtin knock-out (KO) and mutant huntingtin knock-in (Q111) mouse ESC lines. In KO ESCs, we observed impairments in the spontaneous specification and survival of ectodermal and mesodermal lineages during embryoid body formation and under inductive conditions using retinoic acid and Wnt3A, respectively. Ablation of BAX improves cell survival, but failed to correct defects in germ layer specification. In addition, we observed ensuing impairments in the specification and maturation of neural, hepatic, pancreatic and cardiomyocyte lineages. These developmental deficits occurred in concert with alterations in Notch, Hes1 and STAT3 signaling pathways. Moreover, in Q111 ESCs, we observed differential developmental stage-specific alterations in lineage specification and maturation. We also observed changes in Notch/STAT3 expression and activation. Our observations underscore essential roles of Htt in the specification of ectoderm, endoderm and mesoderm, in the specification of neural and non-neural organ-specific lineages, as well as cell survival during early embryogenesis. Remarkably, these developmental events are differentially deregulated by mHtt, raising the possibility that HD-associated early developmental impairments may contribute not only to region-specific neurodegeneration, but also to non-neural co-morbidities. PMID:23967334
Reduced brain insulin-like growth factor I function during aging
Alexandre Pastoris Muller; Ana M. Fernandez; Clarissa Haas; Eduardo Zimmer; Luis Valmor Portela; Ignacio Torres-Aleman
Peripheral insulin-like growth factor I (IGF-I) function progressively deteriorates with age. However, whereas deterioration of IGF-I function in the aged brain seems probable, it has not been directly addressed yet. Because serum IGF-I can enter into the brain through the cerebrospinal fluid (CSF), we examined this route of entrance in aged mice. To distinguish endogenous murine IGF-I from exogenously applied
Local brain atrophy accounts for functional activity differences in normal aging
Grégoria Kalpouzos; Jonas Persson; Lars Nyberg
Functional brain imaging studies of normal aging typically show age-related under- and overactivations during episodic memory tasks. Older individuals also undergo nonuniform gray matter volume (GMv) loss. Thus, age differences in functional brain activity could at least in part result from local atrophy. We conducted a series of voxel-based blood oxygen level-dependent (BOLD)-GMv analyses to highlight whether age-related under- and
Erythropoietin promotes neurovascular remodeling and long-term functional recovery in rats following traumatic brain injury
Ruizhuo Ning; Ye Xiong; Asim Mahmood; Yanlu Zhang; Yuling Meng; Changsheng Qu; Michael Chopp
Erythropoietin (EPO) improves functional recovery after traumatic brain injury (TBI). This study was designed to investigate long-term (3months) effects of EPO on brain remodeling and functional recovery in rats after TBI. Young male Wistar rats were subjected to unilateral controlled cortical impact injury. TBI rats were divided into the following groups: (1) saline group (n=7); (2) EPO-6h group (n=8); and
Functional connectivity in the mouse brain imaged by B-mode photoacoustic microscopy
NASA Astrophysics Data System (ADS)
Nasiriavanaki, Mohammadreza; Xing, Wenxin; Xia, Jun; Wang, Lihong V.
The increasing use of mouse models for human brain disease studies, coupled with the fact that existing functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing acoustic-resolution photoacoustic microscopy (AR-PAM), we imaged spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images were acquired noninvasively in B-scan mode with a fast frame rate, a large field of view, and a high spatial resolution. At a location relative to the bregma 0, correlations were investigated inter-hemispherically between bilaterally homologous regions, as well as intra-hemispherically within the same functional regions. The functional connectivity in different functional regions was studied. The locations of these regions agreed well with the Paxinos mouse brain atlas. The functional connectivity map obtained in this study can then be used in the investigation of brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy. Our experiments show that photoacoustic microscopy is capable to detect connectivities between different functional regions in B-scan mode, promising a powerful functional imaging modality for future brain research.
The use of functional and effective connectivity techniques to understand the developing brain.
Goldenberg, Diane; Galván, Adriana
Developmental neuroscience, the study of the processes that shape and reshape the maturing brain, is a growing field still in its nascent stages. The developmental application of functional and effective connectivity techniques, which are tools that measure the interactions between elements of the brain, has revealed insight to the developing brain as a complex system. However, this insight is granted in discrete windows of consecutive time. The current review uses dynamic systems theory as a conceptual framework to understand how functional and effective connectivity tools may be used in conjunction to capture the dynamic process of change that occurs with development. PMID:25770766
Brain activity during simulated deception: an event-related functional magnetic resonance study.
Langleben, D D; Schroeder, L; Maldjian, J A; Gur, R C; McDonald, S; Ragland, J D; O'Brien, C P; Childress, A R
TheGuilty Knowledge Test (GKT) has been used extensively to model deception. An association between the brain evoked response potentials and lying on the GKT suggests that deception may be associated with changes in other measures of brain activity such as regional blood flow that could be anatomically localized with event-related functional magnetic resonance imaging (fMRI). Blood oxygenation level-dependent fMRI contrasts between deceptive and truthful responses were measured with a 4 Tesla scanner in 18 participants performing the GKT and analyzed using statistical parametric mapping. Increased activity in the anterior cingulate cortex (ACC), the superior frontal gyrus (SFG), and the left premotor, motor, and anterior parietal cortex was specifically associated with deceptive responses. The results indicate that: (a) cognitive differences between deception and truth have neural correlates detectable by fMRI, (b) inhibition of the truthful response may be a basic component of intentional deception, and (c) ACC and SFG are components of the basic neural circuitry for deception. PMID:11848716
Structure, expression, and function of kynurenine aminotransferases in human and rodent brains
Han, Qian; Cai, Tao; Tagle, Danilo A.
Kynurenine aminotransferases (KATs) catalyze the synthesis of kynurenic acid (KYNA), an endogenous antagonist of N-methyl-d-aspartate and alpha 7-nicotinic acetylcholine receptors. Abnormal KYNA levels in human brains are implicated in the pathophysiology of schizophrenia, Alzheimer's disease, and other neurological disorders. Four KATs have been reported in mammalian brains, KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1, KAT II/aminoadipate aminotransferase, KAT III/cysteine conjugate beta-lyase 2, and KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase. KAT II has a striking tertiary structure in N-terminal part and forms a new subgroup in fold type I aminotransferases, which has been classified as subgroup I?. Knowledge regarding KATs is vast and complex; therefore, this review is focused on recent important progress of their gene characterization, physiological and biochemical function, and structural properties. The biochemical differences of four KATs, specific enzyme activity assays, and the structural insights into the mechanism of catalysis and inhibition of these enzymes are discussed. PMID:19826765
How does morality work in the brain? A functional and structural perspective of moral behavior.
Pascual, Leo; Rodrigues, Paulo; Gallardo-Pujol, David
Neural underpinnings of morality are not yet well understood. Researchers in moral neuroscience have tried to find specific structures and processes that shed light on how morality works. Here, we review the main brain areas that have been associated with morality at both structural and functional levels and speculate about how it can be studied. Orbital and ventromedial prefrontal cortices are implicated in emotionally-driven moral decisions, while dorsolateral prefrontal cortex appears to moderate its response. These competing processes may be mediated by the anterior cingulate cortex. Parietal and temporal structures play important roles in the attribution of others' beliefs and intentions. The insular cortex is engaged during empathic processes. Other regions seem to play a more complementary role in morality. Morality is supported not by a single brain circuitry or structure, but by several circuits overlapping with other complex processes. The identification of the core features of morality and moral-related processes is needed. Neuroscience can provide meaningful insights in order to delineate the boundaries of morality in conjunction with moral psychology. PMID:24062650
Inhibition of Monocyte Adhesion to Brain-Derived Endothelial Cells by Dual Functional RNA Chimeras
Hu, Jing; Xiao, Feng; Hao, Xin; Bai, Shuhua; Hao, Jiukuan
Because adhesion of leukocytes to endothelial cells is the first step of vascular-neuronal inflammation, inhibition of adhesion and recruitment of leukocytes to vascular endothelial cells will have a beneficial effect on neuroinflammatory diseases. In this study, we used the pRNA of bacteriophage phi29 DNA packaging motor to construct a novel RNA nanoparticle for specific targeting to transferrin receptor (TfR) on the murine brain-derived endothelial cells (bEND5) to deliver ICAM-1 siRNA. This RNA nanoparticle (FRS-NPs) contained a FB4 aptamer targeting to TfR and a siRNA moiety for silencing the intercellular adhesion molecule-1 (ICAM-1). Our data indicated that this RNA nanoparticle was delivered into murine brain-derived endothelial cells. Furthermore, the siRNA was released from the FRS-NPs in the cells and knocked down ICAM-1 expression in the TNF-?–stimulated cells and in the cells under oxygen-glucose deprivation/reoxygenation (OGD/R) condition. The functional end points of the study indicated that FRS-NPs significantly inhibited monocyte adhesion to the bEND5 cells induced by TNF-? and OGD/R. In conclusion, our approach using RNA nanotechnology for siRNA delivery could be potentially applied for inhibition of inflammation in ischemic stroke and other neuroinflammatory diseases, or diseases affecting endothelium of vasculature. PMID:25368913
Functional analyses of genetic pathways controlling petal specification in poppy.
Drea, Sinéad; Hileman, Lena C; de Martino, Gemma; Irish, Vivian F
MADS-box genes are crucial regulators of floral development, yet how their functions have evolved to control different aspects of floral patterning is unclear. To understand the extent to which MADS-box gene functions are conserved or have diversified in different angiosperm lineages, we have exploited the capability for functional analyses in a new model system, Papaver somniferum (opium poppy). P. somniferum is a member of the order Ranunculales, and so represents a clade that is evolutionarily distant from those containing traditional model systems such as Arabidopsis, Petunia, maize or rice. We have identified and characterized the roles of several candidate MADS-box genes in petal specification in poppy. In Arabidopsis, the APETALA3 (AP3) MADS-box gene is required for both petal and stamen identity specification. By contrast, we show that the AP3 lineage has undergone gene duplication and subfunctionalization in poppy, with one gene copy required for petal development and the other responsible for stamen development. These differences in gene function are due to differences both in expression patterns and co-factor interactions. Furthermore, the genetic hierarchy controlling petal development in poppy has diverged as compared with that of Arabidopsis. As these are the first functional analyses of AP3 genes in this evolutionarily divergent clade, our results provide new information on the similarities and differences in petal developmental programs across angiosperms. Based on these observations, we discuss a model for how the petal developmental program has evolved. PMID:17959716
A CamKIIalpha iCre BAC allows brain-specific gene inactivation.
Casanova, E; Fehsenfeld, S; Mantamadiotis, T; Lemberger, T; Greiner, E; Stewart, A F; Schütz, G
We describe the generation of transgenic mouse lines expressing the Cre recombinase enzyme in brain under control of the CamKIIalpha gene present in a BAC expression vector. The CamKIIalpha BAC transgene gave a faithful expression pattern resembling the pattern of the endogenous CamKIIalpha gene. Specifically, high levels of CamKIIalpha Cre were detected in hippocampus, cortex, and amygdala, and lower levels were detected in striatum, thalamus, and hypothalamus. As expected, no expression was detected in the cerebellum or outside of the brain. The expression level of the BAC CamKIIalpha driven Cre was shown to be copy number dependent. To test the activity of the Cre recombinase, the transgenic mice were crossed with mice harbouring the CREB (cAMP response element binding protein) allele with the 10th exon flanked by two loxP sites, and recombination was monitored by the disappearance of the CREB protein. Finally, evaluation of the developmental postnatal expression of the CamKIIalpha Cre BAC revealed the expression of the Cre recombinase as early as P3. PMID:11668676
Tissue specificity in the nuclear envelope supports its functional complexity
de las Heras, Jose I; Meinke, Peter; Batrakou, Dzmitry G; Srsen, Vlastimil; Zuleger, Nikolaj; Kerr, Alastair RW; Schirmer, Eric C
Nuclear envelope links to inherited disease gave the conundrum of how mutations in near-ubiquitous proteins can yield many distinct pathologies, each focused in different tissues. One conundrum-resolving hypothesis is that tissue-specific partner proteins mediate these pathologies. Such partner proteins may have now been identified with recent proteome studies determining nuclear envelope composition in different tissues. These studies revealed that the majority of the total nuclear envelope proteins are tissue restricted in their expression. Moreover, functions have been found for a number these tissue-restricted nuclear envelope proteins that fit with mechanisms proposed to explain how the nuclear envelope could mediate disease, including defects in mechanical stability, cell cycle regulation, signaling, genome organization, gene expression, nucleocytoplasmic transport, and differentiation. The wide range of functions to which these proteins contribute is consistent with not only their involvement in tissue-specific nuclear envelope disease pathologies, but also tissue evolution. PMID:24213376
Adult-specific functions of animal microRNAs
Sun, Kailiang; Lai, Eric C.
microRNAs (miRNAs) are ~22 nucleotide (nt) RNAs that coordinate vast regulatory networks in animals, and thereby influence myriad processes. This review examines evidence that miRNAs play continuous roles in adults, in ways that are separable from developmental control. Adult-specific activities for miRNAs have been described in a variety of stem cell populations, in the context of neural function and cardiovascular biology, in metabolism and physiology, and during cancer. In addition to reviewing recent results, we also discuss methods for studying miRNA activities specifically in adults and evaluate their relative strengths and weaknesses. A fuller understanding of continuous functions of miRNAs in adults has bearing on efforts and opportunities to manipulate miRNAs for therapeutic purposes. PMID:23817310
Specific peptide for functionalization of GaN
NASA Astrophysics Data System (ADS)
Estephan, E.; Larroque, C.; Cloitre, T.; Cuisinier, F. J. G.; Gergely, C.
Nanobiotechnology aims to exploit biomolecular recognition and self-assembly capabilities for integrating advanced materials into medicine and biology. However frequent problems are encountered at the interface of substrate-biological molecule, as the direct physical adsorption of biological molecules is dependent of unpredictable non-specific interactions with the surface, often causing their denaturation. Therefore, a proper functionalization of the substrate should avoid a loss of biological activity. In this work we address the functionalization of the semiconductor GaN (0001) for biosensing applications. The basic interest of using III-V class semiconductors is their good light emitting properties and a fair chemical stability that allows various applications of these materials. The technology chosen to elaborate GaN-specific peptides is the combinatorial phage-display method, a biological screening procedure based on affinity selection. An M13 bacteriophage library has been used to screen 10 10 different peptides against the GaN (0001) surface to finally isolate one specific peptide. The preferential attachment of the biotinylated selected peptide onto the GaN (0001), in close proximity to a surface of different chemical and structural composition has been demonstrated by fluorescence microscopy. Further physicochemical studies have been initiated to evaluate the semiconductor-peptide interface and understand the details in the specific recognition of peptides for semiconductor substrates. Fourier Transform Infrared spectroscopy in Attenuated Total Reflection mode (FTIR-ATR) has been employed to prove the presence of peptides on the surface. Our Atomic Force Microscopy (AFM) studies on the morphology of the GaN surface after functionalization revealed a total surface coverage by a very thin, homogeneous peptide layer. Due to its good biocompatibility, functionalized GaN devices might evolve in a new class of implantable biosensors for medical applications.
Bottom up modeling of the connectome: Linking structure and function in the resting brain and their changes in aging
Deco, Gustavo
aspects and understand how dynamics and structure interact to form functional brain net- works in task connectivity patterns, and given support to the view that the brain works at a critical point at the edgeReview Bottom up modeling of the connectome: Linking structure and function in the resting brain
Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors
NASA Astrophysics Data System (ADS)
Chen, Robert J.; Bangsaruntip, Sarunya; Drouvalakis, Katerina A.; Wong Shi Kam, Nadine; Shim, Moonsub; Li, Yiming; Kim, Woong; Utz, Paul J.; Dai, Hongjie
Novel nanomaterials for bioassay applications represent a rapidly progressing field of nanotechnology and nanobiotechnology. Here, we present an exploration of single-walled carbon nanotubes as a platform for investigating surface-protein and protein-protein binding and developing highly specific electronic biomolecule detectors. Nonspecific binding on nanotubes, a phenomenon found with a wide range of proteins, is overcome by immobilization of polyethylene oxide chains. A general approach is then advanced to enable the selective recognition and binding of target proteins by conjugation of their specific receptors to polyethylene oxide-functionalized nanotubes. This scheme, combined with the sensitivity of nanotube electronic devices, enables highly specific electronic sensors for detecting clinically important biomolecules such as antibodies associated with human autoimmune diseases.
Functional brain activation to emotional and nonemotional faces in healthy children: Evidence for developmentally
for developmentally undifferentiated amygdala function during the school-age period David Pagliaccio & Joan L. Luby of the amygdala's functional role in humans consistently noted that the amygdala is significantly involvedFunctional brain activation to emotional and nonemotional faces in healthy children: Evidence
Perfusion-based high-resolution functional imaging in the human brain at 7 Tesla
Josef Pfeuffer; Gregor Adriany; Amir Shmuel; Essa Yacoub; Pierre-Francois Van De Moortele; Xiaoping Hu; Kamil Ugurbil
Perfusion-based MRI measures cerebral blood flow (CBF) at the capillary level and can be used for functional studies based on the tight spatial coupling between brain activity and blood flow. Obtaining functional CBF maps with high spatial resolution is a major challenge because the CBF signal is intrinsically low and the SNR is critical. In the present work, CBF-based functional
Impairment of Glymphatic Pathway Function Promotes Tau Pathology after Traumatic Brain Injury
Chen, Michael J.; Plog, Benjamin A.; Zeppenfeld, Douglas M.; Soltero, Melissa; Yang, Lijun; Singh, Itender; Deane, Rashid; Nedergaard, Maiken
Traumatic brain injury (TBI) is an established risk factor for the early development of dementia, including Alzheimer's disease, and the post-traumatic brain frequently exhibits neurofibrillary tangles comprised of aggregates of the protein tau. We have recently defined a brain-wide network of paravascular channels, termed the "glymphatic" pathway, along which CSF moves into and through the brain parenchyma, facilitating the clearance of interstitial solutes, including amyloid-?, from the brain. Here we demonstrate in mice that extracellular tau is cleared from the brain along these paravascular pathways. After TBI, glymphatic pathway function was reduced by ?60%, with this impairment persisting for at least 1 month post injury. Genetic knock-out of the gene encoding the astroglial water channel aquaporin-4, which is importantly involved in paravascular interstitial solute clearance, exacerbated glymphatic pathway dysfunction after TBI and promoted the development of neurofibrillary pathology and neurodegeneration in the post-traumatic brain. These findings suggest that chronic impairment of glymphatic pathway function after TBI may be a key factor that renders the post-traumatic brain vulnerable to tau aggregation and the onset of neurodegeneration. PMID:25471560
Dietary resistant starch improves selected brain and behavioral functions in adult and aged rodents.
Zhou, June; Keenan, Michael J; Fernandez-Kim, Sun Ok; Pistell, Paul J; Ingram, Donald K; Li, Bing; Raggio, Anne M; Shen, Li; Zhang, Hanjie; McCutcheon, Kathleen L; Tulley, Richard T; Blackman, Marc R; Keller, Jeffrey N; Martin, Roy J
Resistant starch (RS) is a dietary fiber that exerts multiple beneficial effects. The current study explored the effects of dietary RS on selected brain and behavioral functions in adult and aged rodents. Because glucokinase (GK) expression in hypothalamic arcuate nucleus and area postrema of the brainstem is important for brain glucose sensing, GK mRNA was measured by brain nuclei microdissection and PCR. Adult RS-fed rats had a higher GK mRNA than controls in both brain nuclei, an indicator of improved brain glucose sensing. Next, we tested whether dietary RS improve selected behaviors in aged mice. RS-fed aged mice exhibited (i) an increased eating responses to fasting, a behavioral indicator of improvement in aged brain glucose sensing; (ii) a longer latency to fall from an accelerating rotarod, a behavioral indicator of improved motor coordination; and (iii) a higher serum active glucagon-like peptide-1 (GLP-1). Then, GLP-1 receptor null (GLP-1RKO) mice were used to test the role of GLP-1 in brain glucose sensing, and they exhibited impaired eating responses to fasting. We conclude that in rodents (i) dietary RS improves two important indicators of brain function: glucose sensing and motor coordination, and (ii) GLP-1 is important in the optimal feeding response to a fast. PMID:23818307
Call for startup project applications `brain function and dysfunction' The University Research Profile Area Brain Function and Dysfunction over the Lifespan invites
Galis, Frietson
Call for startup project applications `brain function and dysfunction' The University Research startup projects. This is the first call with a submission deadline on November 1, 2010. Three projects will be selected. A second and third call will follow in 2011 and 2012. The goal of these startup projects
Hintz et al, Real-time neonatal optical functional brain imaging 335 J. Perinat. Med. Bedside functional imaging of the premature infant brain
Hintz et al, Real-time neonatal optical functional brain imaging 335 J. Perinat. Med. Bedside Biomedical Optics Group, Division of Neonatal and Developmental Medicine, Stanford University School, these modalities are not feasible in many intensive care situations due to the problems and hazards of moving
Diagnosing and managing functional visual complications after brain injury
Christine L. Allison; Helen Gabriel; Darrell Schlange
BackgroundBrain injury caused by an arteriovenous malformation (AVM) hemorrhage is an uncommon occurrence in a teenager. An AVM is a congenital anomaly of unknown etiology, often described as a tangle of arteries and veins that may vary in length and width leading to a loss of capillary bed. The vessels can break down with time and cause hemorrhage or aneurysm.
The blood–brain barrier and immune function and dysfunction
William A. Banks; Michelle A. Erickson
The blood–brain barrier (BBB) is the monocellular interface that divides the peripheral circulation from direct contact with the central nervous system (CNS). This interface consists of several parallel barriers that include most notably the capillary bed of the CNS and the choroid plexus. These barriers at one level create the dichotomy between the circulating factors of the immune system and
N -Acetylaspartate in the Vertebrate Brain: Metabolism and Function
Morris H. Baslow
N-Acetyl-l-aspartate (NAA) is an amino acid that is present in the vertebrate brain. Its concentration is one of the highest of all free amino acids and, although NAA is synthesized and stored primarily in neurons, it cannot be hydrolyzed in these cells. Furthermore, neuronal NAA is dynamic and turns over more than once each day by virtue of its continuous
Noninvasive Functional Imaging of Human Brain Using Light
David A. Benaron; Susan R. Hintz; Arno Villringer; David Boas; Andreas Kleinschmidt; Jens Frahm; Christina Hirth; Hellmuth Obrig; John C. van Houten; Eben L. Kermit; Wai-Fung Cheong; David K. Stevenson
Analysis of photon transit time for low-power light passing into the head, and through both skull and brain, of human subjects allowed for tomographic imaging of cerebral hemoglobin oxygenation based on photon diffusion theory. In healthy adults, imaging of changes in hemoglobin saturation during hand movement revealed focal, contralateral increases in motor cortex oxygenation with spatial agreement to activation maps
Toward Technical Understanding. Part 1: Brain Structure and Function.
ERIC Educational Resources Information Center
Haile, J. M.
Argues that there are many kinds of understanding and many ways to reach these different understandings. Suggests that this is the reason why articulating general rules that can consistently lead to understanding is difficult. Discusses the relationship between brain structure and learning. (DDR)
Critical Periods of Brain Growth and Cognitive Function in Children
ERIC Educational Resources Information Center
Gale, Catharine R.; O'Callaghan, Finbar J.; Godfrey, Keith M.; Law, Catherine M.; Martyn, Christopher N.
There is evidence that IQ tends to be higher in those who were heavier at birth or who grew taller in childhood and adolescence. Although these findings imply that growth in both foetal and postnatal life influences cognitive performance, little is known about the relative importance of brain growth during different periods of development. We…
Abstract: Voltage sensitive Ca2+ channels in brain functions
Gruen, Sonja
to restore the resting Ca2+ level. We use various tools for analysis of the mutants to define the brain link, sleep stability, and pathogenesis of absence seizures. We are interested in trying to understand how+ channels. Science 302:117-119 Lee J et al. (2004). Lack of delta waves and sleep disturbances during NREM
EEG Oscillatory States: Universality, Uniqueness and Specificity across Healthy-Normal, Altered and Pathological Brain Conditions
Fingelkurts, Alexander A.; Fingelkurts, Andrew A.
For the first time the dynamic repertoires and oscillatory types of local EEG states in 13 diverse conditions (examined over 9 studies) that covered healthy-normal, altered and pathological brain states were quantified within the same methodological and conceptual framework. EEG oscillatory states were assessed by the probability-classification analysis of short-term EEG spectral patterns. The results demonstrated that brain activity consists of a limited repertoire of local EEG states in any of the examined conditions. The size of the state repertoires was associated with changes in cognition and vigilance or neuropsychopathologic conditions. Additionally universal, optional and unique EEG states across 13 diverse conditions were observed. It was demonstrated also that EEG oscillations which constituted EEG states were characteristic for different groups of conditions in accordance to oscillations' functional significance. The results suggested that (a) there is a limit in the number of local states available to the cortex and many ways in which these local states can rearrange themselves and still produce the same global state and (b) EEG individuality is determined by varying proportions of universal, optional and unique oscillatory states. The results enriched our understanding about dynamic microstructure of EEG-signal. PMID:24505292
EEG oscillatory states: universality, uniqueness and specificity across healthy-normal, altered and pathological brain conditions.
Fingelkurts, Alexander A; Fingelkurts, Andrew A
For the first time the dynamic repertoires and oscillatory types of local EEG states in 13 diverse conditions (examined over 9 studies) that covered healthy-normal, altered and pathological brain states were quantified within the same methodological and conceptual framework. EEG oscillatory states were assessed by the probability-classification analysis of short-term EEG spectral patterns. The results demonstrated that brain activity consists of a limited repertoire of local EEG states in any of the examined conditions. The size of the state repertoires was associated with changes in cognition and vigilance or neuropsychopathologic conditions. Additionally universal, optional and unique EEG states across 13 diverse conditions were observed. It was demonstrated also that EEG oscillations which constituted EEG states were characteristic for different groups of conditions in accordance to oscillations' functional significance. The results suggested that (a) there is a limit in the number of local states available to the cortex and many ways in which these local states can rearrange themselves and still produce the same global state and (b) EEG individuality is determined by varying proportions of universal, optional and unique oscillatory states. The results enriched our understanding about dynamic microstructure of EEG-signal. PMID:24505292
Brain Systems for Probabilistic and Dynamic Prediction: Computational Specificity and Integration
O'Reilly, Jill X.; Jbabdi, Saad; Rushworth, Matthew F. S.; Behrens, Timothy E. J.
A computational approach to functional specialization suggests that brain systems can be characterized in terms of the types of computations they perform, rather than their sensory or behavioral domains. We contrasted the neural systems associated with two computationally distinct forms of predictive model: a reinforcement-learning model of the environment obtained through experience with discrete events, and continuous dynamic forward modeling. By manipulating the precision with which each type of prediction could be used, we caused participants to shift computational strategies within a single spatial prediction task. Hence (using fMRI) we showed that activity in two brain systems (typically associated with reward learning and motor control) could be dissociated in terms of the forms of computations that were performed there, even when both systems were used to make parallel predictions of the same event. A region in parietal cortex, which was sensitive to the divergence between the predictions of the models and anatomically connected to both computational networks, is proposed to mediate integration of the two predictive modes to produce a single behavioral output. PMID:24086106
ABL Tyrosine Kinases: Evolution of Function, Regulation, and Specificity
NSDL National Science Digital Library
John Colicelli (David Geffen School of Medicine at UCLA; Molecular Biology Institute and Jonsson Comprehensive Cancer Center REV)
ABL-family proteins couple a highly regulated tyrosine kinase domain with an actin-binding and -bundling domain to carry out a set of unique and essential functions. The ABL genes are among the earliest identifiable genes encoding tyrosine kinases, and they show remarkable sequence conservation. Gene duplication produced two vertebrate ABL paralogs with specialized properties. ABL1 evolved nuclear localization signals and a DNA binding domain to mediate damage repair functions. ABL2 developed additional binding domains for actin and microtubules, extending its cytoskeletal remodeling functions. This Review surveys the recent literature and available databases with a focus on ABL evolution and the mechanisms regulating ABL's catalytic activity and substrate specificity. This Review contains 7 figures, 2 tables, and 248 references. A better understanding of these properties could facilitate the design of new treatments for malignancies driven by ABL fusion proteins.
Structure and Function of the Phosphothreonine-Specific FHA Domain
NSDL National Science Digital Library
Anjali Mahajan (Ohio State University; Biophysics Program REV)
The forkhead-associated (FHA) domain is a signaling domain present in various proteins from prokaryotes and eukaryotes. It interacts with other proteins on the basis of its ability to specifically recognize phosphothreonine residues. Proteins that contain the FHA domain play important functional roles in such processes as protein kinase signaling, cell cycle regulation, and DNA damage response. It is now evident that interference with the binding capabilities of these domains can elicit abnormal cellular responses. Detailed structural analyses have led to an understanding of the structural bases of the biological functions of the FHA domain. Information about this structure-function relationship will be useful in understanding the signaling mechanisms that involve FHA domains and, potentially, in the design of therapeutics.
Highlighting the Structure-Function Relationship of the Brain with the Ising Model and Graph Theory
Das, T. K.; Abeyasinghe, P. M.; Crone, J. S.; Sosnowski, A.; Laureys, S.; Owen, A. M.; Soddu, A.
With the advent of neuroimaging techniques, it becomes feasible to explore the structure-function relationships in the brain. When the brain is not involved in any cognitive task or stimulated by any external output, it preserves important activities which follow well-defined spatial distribution patterns. Understanding the self-organization of the brain from its anatomical structure, it has been recently suggested to model the observed functional pattern from the structure of white matter fiber bundles. Different models which study synchronization (e.g., the Kuramoto model) or global dynamics (e.g., the Ising model) have shown success in capturing fundamental properties of the brain. In particular, these models can explain the competition between modularity and specialization and the need for integration in the brain. Graphing the functional and structural brain organization supports the model and can also highlight the strategy used to process and organize large amount of information traveling between the different modules. How the flow of information can be prevented or partially destroyed in pathological states, like in severe brain injured patients with disorders of consciousness or by pharmacological induction like in anaesthesia, will also help us to better understand how global or integrated behavior can emerge from local and modular interactions. PMID:25276772
Cannabis Use and Memory Brain Function in Adolescent Boys: A Cross-Sectional Multicenter Functional Magnetic Resonance Imaging Study
ERIC Educational Resources Information Center
Jager, Gerry; Block, Robert I.; Luijten, Maartje; Ramsey, Nick F.
Objective: Early-onset cannabis use has been associated with later use/abuse, mental health problems (psychosis, depression), and abnormal development of cognition and brain function. During adolescence, ongoing neurodevelopmental maturation and experience shape the neural circuitry underlying complex cognitive functions such as memory and…
Role for glutathione peroxidase-4 in brain development and neuronal apoptosis: Specific induction of enzyme expression in reactive astrocytes following brain injury
Nicolai E. Savaskan; Astrid Borchert; Anja U. Bräuer; Hartmut Kuhn
Glutathione peroxidase-4 (GPx4) is a multifunctional selenoprotein expressed as mitochondrial, cytosolic, or nuclear isoforms. As a catalytically active enzyme it has been implicated in antioxidative defense, but during sperm development it functions as a structural protein. GPx4 null mice die in utero at midgestation and knockdown of GPx4 during embryogenesis disturbs brain development. To explore the cerebral function of GPx4
Handedness- and brain size-related efficiency differences in small-world brain networks: a resting-state functional magnetic resonance imaging study.
Li, Meiling; Wang, Junping; Liu, Feng; Chen, Heng; Lu, Fengmei; Wu, Guorong; Yu, Chunshui; Chen, Huafu
The human brain has been described as a complex network, which integrates information with high efficiency. However, the relationships between the efficiency of human brain functional networks and handedness and brain size remain unclear. Twenty-one left-handed and 32 right-handed healthy subjects underwent a resting-state functional magnetic resonance imaging scan. The whole brain functional networks were constructed by thresholding Pearson correlation matrices of 90 cortical and subcortical regions. Graph theory-based methods were employed to further analyze their topological properties. As expected, all participants demonstrated small-world topology, suggesting a highly efficient topological structure. Furthermore, we found that smaller brains showed higher local efficiency, whereas larger brains showed higher global efficiency, reflecting a suitable efficiency balance between local specialization and global integration of brain functional activity. Compared with right-handers, significant alterations in nodal efficiency were revealed in left-handers, involving the anterior and median cingulate gyrus, middle temporal gyrus, angular gyrus, and amygdala. Our findings indicated that the functional network organization in the human brain was associated with handedness and brain size. PMID:25535788
Functional brain connectivity from EEG in epilepsy: seizure prediction and epileptogenic focus localization.
van Mierlo, Pieter; Papadopoulou, Margarita; Carrette, Evelien; Boon, Paul; Vandenberghe, Stefaan; Vonck, Kristl; Marinazzo, Daniele
Today, neuroimaging techniques are frequently used to investigate the integration of functionally specialized brain regions in a network. Functional connectivity, which quantifies the statistical dependencies among the dynamics of simultaneously recorded signals, allows to infer the dynamical interactions of segregated brain regions. In this review we discuss how the functional connectivity patterns obtained from intracranial and scalp electroencephalographic (EEG) recordings reveal information about the dynamics of the epileptic brain and can be used to predict upcoming seizures and to localize the seizure onset zone. The added value of extracting information that is not visibly identifiable in the EEG data using functional connectivity analysis is stressed. Despite the fact that many studies have showed promising results, we must conclude that functional connectivity analysis has not made its way into clinical practice yet. PMID:25014528
Functional optoacoustic neuro-tomography (FONT) for whole-brain monitoring of calcium indicators
Sela, Gali; Deán-Ben, X Luís; Kneipp, Moritz; Ntziachristos, Vasilis; Shoham, Shy; Westmeyer, Gil G; Razansky, Daniel
Non-invasive observation of spatiotemporal neural activity of large neural populations distributed over entire brains is a longstanding goal of neuroscience. We developed a real-time volumetric and multispectral optoacoustic tomography platform for imaging of neural activation deep in scattering brains. The system can record 100 volumetric frames per second across a 200mm3 field of view and spatial resolutions below 70um. Experiments performed in immobilized and freely swimming larvae and in adult zebrafish brains demonstrate, for the first time, the fundamental ability to optoacoustically track neural calcium dynamics in animals labeled with genetically encoded calcium indicator GCaMP5G, while overcoming the longstanding penetration barrier of optical imaging in scattering brains. The newly developed platform offers unprecedented capabilities for functional whole-brain observations of fast calcium dynamics; in combination with optoacoustics' well-established capacity in resolving vascular hemodynamics, it co...
Brain Region-Specific Activity Patterns after Recent or Remote Memory Retrieval of Auditory Conditioned Fear
ERIC Educational Resources Information Center
Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee
Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or…
Resting State Brain Function Analysis Using Concurrent BOLD in ASL Perfusion fMRI
Zhu, Senhua; Fang, Zhuo; Hu, Siyuan; Wang, Ze; Rao, Hengyi
The past decade has seen astounding discoveries about resting-state brain activity patterns in normal brain as well as their alterations in brain diseases. While the vast majority of resting-state studies are based on the blood-oxygen-level-dependent (BOLD) functional MRI (fMRI), arterial spin labeling (ASL) perfusion fMRI can simultaneously capture BOLD and cerebral blood flow (CBF) signals, providing a unique opportunity for assessing resting brain functions with concurrent BOLD (ccBOLD) and CBF signals. Before taking that benefit, it is necessary to validate the utility of ccBOLD signal for resting-state analysis using conventional BOLD (cvBOLD) signal acquired without ASL modulations. To address this technical issue, resting cvBOLD and ASL perfusion MRI were acquired from a large cohort (n?=?89) of healthy subjects. Four widely used resting-state brain function analyses were conducted and compared between the two types of BOLD signal, including the posterior cingulate cortex (PCC) seed-based functional connectivity (FC) analysis, independent component analysis (ICA), analysis of amplitude of low frequency fluctuation (ALFF), and analysis of regional homogeneity (ReHo). Consistent default mode network (DMN) as well as other resting-state networks (RSNs) were observed from cvBOLD and ccBOLD using PCC-FC analysis and ICA. ALFF from both modalities were the same for most of brain regions but were different in peripheral regions suffering from the susceptibility gradients induced signal drop. ReHo showed difference in many brain regions, likely reflecting the SNR and resolution differences between the two BOLD modalities. The DMN and auditory networks showed highest CBF values among all RSNs. These results demonstrated the feasibility of ASL perfusion MRI for assessing resting brain functions using its concurrent BOLD in addition to CBF signal, which provides a potentially useful way to maximize the utility of ASL perfusion MRI. PMID:23750275
Intrinsic Functional Brain Architecture Derived from Graph Theoretical Analysis in the Human Fetus
Thomason, Moriah E.; Brown, Jesse A.; Dassanayake, Maya T.; Shastri, Rupal; Marusak, Hilary A.; Hernandez-Andrade, Edgar; Yeo, Lami; Mody, Swati; Berman, Susan; Hassan, Sonia S.; Romero, Roberto
The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI) data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA), our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks) and older (GA?31 weeks) fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed. PMID:24788455
Specific Resting-State Brain Networks in Mesial Temporal Lobe Epilepsy
Maneshi, Mona; Vahdat, Shahabeddin; Fahoum, Firas; Grova, Christophe; Gotman, Jean
We studied with functional magnetic resonance imaging (fMRI) differences in resting-state networks between patients with mesial temporal lobe epilepsy (MTLE) and healthy subjects. To avoid any a priori hypothesis, we use a data-driven analysis assessing differences between groups independently of structures involved. Shared and specific independent component analysis (SSICA) is an exploratory method based on independent component analysis, which performs between-group network comparison. It extracts and classifies components (networks) in those common between groups and those specific to one group. Resting fMRI data were collected from 10 healthy subjects and 10 MTLE patients. SSICA was applied multiple times with altered initializations and different numbers of specific components. This resulted in many components specific to patients and to controls. Spatial clustering identified the reliable resting-state networks among all specific components in each group. For each reliable specific network, power spectrum analysis was performed on reconstructed time-series to estimate connectivity in each group and differences between groups. Two reliable networks, corresponding to statistically significant clusters robustly detected with clustering were labeled as specific to MTLE and one as specific to the control group. The most reliable MTLE network included hippocampus and amygdala bilaterally. The other MTLE network included the postcentral gyri and temporal poles. The control-specific network included bilateral precuneus, anterior cingulate, thalamus, and parahippocampal gyrus. Results indicated that the two MTLE networks show increased connectivity in patients, whereas the control-specific network shows decreased connectivity in patients. Our findings complement results from seed-based connectivity analysis (1). The pattern of changes in connectivity between mesial temporal lobe structures and other areas may help us understand the cognitive impairments often reported in patients with MTLE. PMID:25071712
Systematic analysis of transcription-level effects of neurodegenerative diseases on human brain metabolism by a newly reconstructed brain-specific metabolic network
Sertba?, Mustafa; Ülgen, Kutlu; Çak?r, Tunahan
Network-oriented analysis is essential to identify those parts of a cell affected by a given perturbation. The effect of neurodegenerative perturbations in the form of diseases of brain metabolism was investigated by using a newly reconstructed brain-specific metabolic network. The developed stoichiometric model correctly represents healthy brain metabolism, and includes 630 metabolic reactions in and between astrocytes and neurons, which are controlled by 570 genes. The integration of transcriptome data of six neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia) with the model was performed to identify reporter features specific and common for these diseases, which revealed metabolites and pathways around which the most significant changes occur. The identified metabolites are potential biomarkers for the pathology of the related diseases. Our model indicated perturbations in oxidative stress, energy metabolism including TCA cycle and lipid metabolism as well as several amino acid related pathways, in agreement with the role of these pathways in the studied diseases. The computational prediction of transcription factors that commonly regulate the reporter metabolites was achieved through binding-site analysis. Literature support for the identified transcription factors such as USF1, SP1 and those from FOX families are known from the literature to have regulatory roles in the identified reporter metabolic pathways as well as in the neurodegenerative diseases. In essence, the reconstructed brain model enables the elucidation of effects of a perturbation on brain metabolism and the illumination of possible machineries in which a specific metabolite or pathway acts as a regulatory spot for cellular reorganization. PMID:25061554
Functional imaging of the brain by infrared radiation (thermoencephaloscopy)
Igor A. Shevelev
A technique for thermal imaging of the animal and human brain cortex using an infrared optical system is described. Thermoencephaloscopy (TES) is based on improved thermovision and image processing techniques and allows two-dimensional, contact-free, dynamic and non-invasive recording of background and evoked cortical activity through an unopened skull. Activated (heated) and deactivated (cooled) zones of the cerebral cortex are revealed.
Functional Magnetic Resonance-Guided Brain Tumor Resection
Peter D. Kim; Charles L. Truwit; Walter A. Hall
\\u000a The ultimate goal of brain tumor surgery is maximum tumor removal without the development of a new neurologic deficit. This\\u000a is especially true in the treatment of intraparenchymal tumors such as gliomas and metastatic lesions. In the treatment of\\u000a glioblastoma multiforme (GBM), for example, gross total resection (GTR) has been demonstrated in a number of studies to be\\u000a one of
Temporal and Functional Relationship of Brain Maturation and Behavioural Development
H. R. GÜttinger; K. W. Kafitz; S. Stocker-Buschina
\\u000a The song system is a model for studying the influence of steroids on the development of brain and behaviour [4, 14, 19]. It consists of anatomically discrete nuclei, that are sexually dimorphic and target regions for steroids [1, 7, chapter\\u000a by Lipp and Wolfer, present volume]. The main descending pathway for motor control of song production (Fig. 1) includes the
Chronology and chronicity of altered resting-state functional connectivity after traumatic brain injury.
Venkatesan, Umesh M; Dennis, Nancy A; Hillary, Frank G
Whereas traumatic brain injury (TBI) results in widespread disruption of neural networks, changes in regional resting-state functional connectivity patterns after insult remain unclear. Specifically, little is known about the chronology of emergent connectivity alterations and whether they persist after a critical recovery window. We used resting-state functional magnetic resonance imaging and seed-voxel correlational analyses in both cross-sectional and longitudinal designs to probe intrinsic connectivity patterns involving the posterior cingulate cortex (PCC) and hippocampi, regions shown to be important in the default mode network (DMN) and vulnerable to neuropathology. A total of 22 participants in the chronic stage of moderate-to-severe TBI and 18 healthy controls were included for cross-sectional study. Longitudinal analyses included 13 individuals in the TBI group for whom data approximately 3 months after injury (subacute) were available. Overall, results indicated dissociable connectivity trajectories of the PCC and hippocampi during recovery from TBI, with PCC alterations characterized by early hypersynchrony with the anterior DMN that is gradually reduced, and hippocampal changes marked by increasing synchrony with proximal cortex and subcortex. The PCC also showed increasing antiphase synchrony with posterior attentional regions, and the hippocampi showed decreasing antiphase synchrony with frontal attentional regions. Antiphase synchrony of the hippocampus and dorsolateral prefrontal cortex at the subacute stage of TBI was positively associated with attentional performance on neuropsychological tests at both the subacute and chronic stages. Our findings highlight the heterogeneity of regional whole-brain connectivity changes after TBI, and suggest that residual connectivity alterations exist in the clinically stable phase of TBI. Parallels between the chronicity of the observed effects and findings in neurodegenerative disease are discussed in the context of potential long-term outcomes of TBI. PMID:24955788
Automatic brain response to facial emotion as a function of implicitly and explicitly measured extraversion.
Suslow, T; Kugel, H; Reber, H; Bauer, J; Dannlowski, U; Kersting, A; Arolt, V; Heindel, W; Ohrmann, P; Egloff, B
Extraversion/introversion is a basic dimension of personality that describes individual differences in social behavior and sensory sensitivity. Previous neuroimaging research exclusively relied on self reports for assessing personality traits. In recent years, implicit measures of personality have been developed that aim at assessing the implicit self-concept of personality and complement self report instruments which are thought to measure aspects of the explicit self-concept of personality. In the present study functional magnetic resonance imaging was used to examine automatic brain reactivity to facial expression as a function of both implicitly and explicitly measured extraversion in 30 healthy women. Sad, happy, and neutral faces were presented for 33 ms masked by neutral faces beside a no face control condition. Subjects evaluated the briefly shown neutral mask faces. The Implicit Association Test (IAT) and the NEO Five-Factor Inventory (NEO-FFI) were applied as measures of extraversion which were not correlated in our sample. IAT extraversion was negatively correlated with automatic reactivity of the caudate head, thalamus, and inferior frontal cortex to sad faces. NEO-FFI extraversion was negatively correlated with response of the inferior frontal cortex and putamen to sad faces. For masked happy faces, an inverse correlation of the IAT effect for extraversion with activation of the caudate head and superior parietal lobule was observed. NEO-FFI extraversion was inversely correlated with the response of the thalamus to happy faces. Neither NEO-FFI extraversion nor IAT effect were significantly related to brain response to masked neutral faces (compared to the no face condition). Taken together, a specific heightened responsivity of the fronto-striatal-thalamic circuit to facial emotions which are arousing stimuli might underlie introverts' preference for avoiding social interactions. Research on the neurobiology of extraversion could benefit from the application of implicit in addition to explicit measurement instruments when automatic neural responses are investigated. PMID:20144695
Distinct Pools of Non-Glycolytic Substrates Differentiate Brain Regions and Prime Region-Specific Responses of Mitochondria
Platt, Virginia; Budworth, Helen; Canaria, Christie A.; McMurray, Cynthia T.
Many hereditary diseases are characterized by region-specific toxicity, despite the fact that disease-linked proteins are generally ubiquitously expressed. The underlying basis of the region-specific vulnerability remains enigmatic. Here, we evaluate the fundamental features of mitochondrial and glucose metabolism in synaptosomes from four brain regions in basal and stressed states. Although the brain has an absolute need for glucose in vivo, we find that synaptosomes prefer to respire on non-glycolytic substrates, even when glucose is present. Moreover, glucose is metabolized differently in each brain region, resulting in region-specific "signature" pools of non-glycolytic substrates. The use of non-glycolytic resources increases and dominates during energy crisis, and triggers a marked region-specific metabolic response. We envision that disease-linked proteins confer stress on all relevant brain cells, but region-specific susceptibility stems from metabolism of non-glycolytic substrates, which limits how and to what extent neurons respond to the stress. PMID:23874783
Computational deconvolution of genome wide expression data from Parkinson's and Huntington's disease brain tissues using population-specific expression analysis
Capurro, Alberto; Bodea, Liviu-Gabriel; Schaefer, Patrick; Luthi-Carter, Ruth; Perreau, Victoria M.
The characterization of molecular changes in diseased tissues gives insight into pathophysiological mechanisms and is important for therapeutic development. Genome-wide gene expression analysis has proven valuable for identifying biological processes in neurodegenerative diseases using post mortem human brain tissue and numerous datasets are publically available. However, many studies utilize heterogeneous tissue samples consisting of multiple cell types, all of which contribute to global gene expression values, confounding biological interpretation of the data. In particular, changes in numbers of neuronal and glial cells occurring in neurodegeneration confound transcriptomic analyses, particularly in human brain tissues where sample availability and controls are limited. To identify cell specific gene expression changes in neurodegenerative disease, we have applied our recently published computational deconvolution method, population specific expression analysis (PSEA). PSEA estimates cell-type-specific expression values using reference expression measures, which in the case of brain tissue comprises mRNAs with cell-type-specific expression in neurons, astrocytes, oligodendrocytes and microglia. As an exercise in PSEA implementation and hypothesis development regarding neurodegenerative diseases, we applied PSEA to Parkinson's and Huntington's disease (PD, HD) datasets. Genes identified as differentially expressed in substantia nigra pars compacta neurons by PSEA were validated using external laser capture microdissection data. Network analysis and Annotation Clustering (DAVID) identified molecular processes implicated by differential gene expression in specific cell types. The results of these analyses provided new insights into the implementation of PSEA in brain tissues and additional refinement of molecular signatures in human HD and PD. PMID:25620908
Multiloop Integral System Test (MIST): MIST Facility Functional Specification
Habib, T F; Koksal, C G; Moskal, T E; Rush, G C; Gloudemans, J R [Babcock and Wilcox Co. (USA)
The Multiloop Integral System Test (MIST) is part of a multiphase program started in 1983 to address small-break loss-of-coolant accidents (SBLOCAs) specific to Babcock and Wilcox designed plants. MIST is sponsored by the US Nuclear Regulatory Commission, the Babcock Wilcox Owners Group, the Electric Power Research Institute, and Babcock and Wilcox. The unique features of the Babcock and Wilcox design, specifically the hot leg U-bends and steam generators, prevented the use of existing integral system data or existing integral facilities to address the thermal-hydraulic SBLOCA questions. MIST was specifically designed and constructed for this program, and an existing facility -- the Once Through Integral System (OTIS) -- was also used. Data from MIST and OTIS are used to benchmark the adequacy of system codes, such as RELAP5 and TRAC, for predicting abnormal plant transients. The MIST Functional Specification documents as-built design features, dimensions, instrumentation, and test approach. It also presents the scaling basis for the facility and serves to define the scope of work for the facility design and construction. 13 refs., 112 figs., 38 tabs.
Resting-state functional connectivity imaging of the mouse brain using photoacoustic tomography
NASA Astrophysics Data System (ADS)
Nasiriavanaki, Mohammadreza; Xia, Jun; Wan, Hanlin; Bauer, Adam Q.; Culver, Joseph P.; Wang, Lihong V.
Resting-state functional connectivity (RSFC) imaging is an emerging neuroimaging approach that aims to identify spontaneous cerebral hemodynamic fluctuations and their associated functional connections. Clinical studies have demonstrated that RSFC is altered in brain disorders such as stroke, Alzheimer's, autism, and epilepsy. However, conventional neuroimaging modalities cannot easily be applied to mice, the most widely used model species for human brain disease studies. For instance, functional magnetic resonance imaging (fMRI) of mice requires a very high magnetic field to obtain a sufficient signal-to-noise ratio and spatial resolution. Functional connectivity mapping with optical intrinsic signal imaging (fcOIS) is an alternative method. Due to the diffusion of light in tissue, the spatial resolution of fcOIS is limited, and experiments have been performed using an exposed skull preparation. In this study, we show for the first time, the use of photoacoustic computed tomography (PACT) to noninvasively image resting-state functional connectivity in the mouse brain, with a large field of view and a high spatial resolution. Bilateral correlations were observed in eight regions, as well as several subregions. These findings agreed well with the Paxinos mouse brain atlas. This study showed that PACT is a promising, non-invasive modality for small-animal functional brain imaging.
Spatial specificity of chromophore assisted laser inactivation of protein function.
Linden, K G; Liao, J C; Jay, D G
Chromophore assisted laser inactivation (CALI) is a new technique that selectively inactivates proteins of interest to elucidate their in vivo functions. This method has application to a wide array of biological questions. An understanding of aspects of the mechanism of CALI is required for its judicious application. A critical concern for CALI is its spatial specificity because nonspecific inactivation of neighboring unbound proteins by CALI is a possibility. We show here that CALI is very dependent on the distance between the chromophore and the protein such that there is no significant effect beyond 60 A. CALI using antibodies can inactivate other proteins through a complex but its efficacy decreases approximately fourfold for each intervening protein. These data imply that CALI is spatially specific and damage to neighboring proteins is unlikely. PMID:1581504
Evaluation of cerebral function using iomazenil SPECT for patients with traumatic brain injury.
Shibata, Yasushi; Endo, Kiyoshi
Traumatic brain injuries demonstrate various symptoms, including the disturbance of higher brain function, which is not visualized as a morphological lesion on magnetic resonance (MR) imaging. We examined the use of iomazenil single photon emission computed tomography (SPECT) for patients with traumatic brain injury and evaluated its diagnostic value. The study population included patients who were admitted to our hospital for traumatic brain injuries. All patients survived and were discharged from our hospital. MR imaging and iomazenil SPECT were examined during the acute and/or chronic phases. MR images were acquired using a 1.5-T clinical instrument. The T1- and T2-weighted and fluid-attenuated inversion recovery (FLAIR) axial images were evaluated. SPECT images were acquired using a multi-detector SPECT machine 3 h after the intravenous injection of 740 MBq of iomazenil. Axial, statistically analyzed images and stereotactic extraction estimation images were reconstructed and evaluated statistically based on the Z-score for each cerebral cortex. Iomazenil SPECT showed various lesions that were not demonstrated by MR imaging. Some clinical symptoms correlated with the iomazenil SPECT findings. Iomazenil SPECT is thus considered to be valuable for evaluating both brain lesions and the brain function after traumatic brain injury. PMID:23564143
Endogenous brain erythropoietin is a potent sex-specific respiratory stimulant in adult and newborn mice.
Ballot, Orlane; Joseph, Vincent; Soliz, Jorge
We tested the hypothesis that endogenous brain Epo is a respiratory stimulant. Adult (3 mo) and newborn (10 days) male and female mice received an intracisternal (cisterna magna) injection of soluble Epo receptor (sEpoR; competes with EpoR to bind Epo; 50 ?g/ml) or vehicle (0.1% BSA in PBS). Twenty-four hours after injection, we used whole body plethysmography to record minute ventilation (V?e) tidal volume (VT), respiratory frequency (fR), O2 consumption (V?o2), and CO2 production (V?co2) under normoxia and progressive exposure to hypoxia (12-10-6% O2; 10 min each). In adult male and female mice sEpoR decreased normoxic V?e (-25%), due to a decrease of VT in males and fR in females. Moreover, sEpoR injection decreased the ventilatory response to 12% O2, assessed as V?e/V?o2 or V?e/V?co2, in male but not in female mice. In newborn male and female mice sEpoR decreased V?e (-37% in males, -59% in females) and VT (-38% in males, -47% in females) in normoxia and fR in females. During hypoxia, sEpoR decreased V?e/V?o2 and V?e/V?co2 in mice of both sexes. Upon extreme hypoxia (6% O2), the newborn mice treated with sEpoR showed respiratory depression, signs of asphyxia (gasping) and a high mortality rate in males and females. We concluded that endogenous brain Epo is a potent respiratory stimulant under normoxia and hypoxia in adult and newborn mice. Because sex-specific effects are different in newborn male and female, sex steroids secreted at different ages mice appear to modulate the effects of Epo on respiratory regulation in normoxia and in response to hypoxia. PMID:25792712
Individual Differences in Brain Structure and Resting Brain Function Underlie Cognitive Styles: Evidence from the Embedded Figures Test
Hao, Xin; Wang, Kangcheng; Li, Wenfu; Yang, Wenjing; Wei, Dongtao; Qiu, Jiang; Zhang, Qinglin
Cognitive styles can be characterized as individual differences in the way people perceive, think, solve problems, learn, and relate to others. Field dependence/independence (FDI) is an important and widely studied dimension of cognitive styles. Although functional imaging studies have investigated the brain activation of FDI cognitive styles, the combined structural and functional correlates with individual differences in a large sample have never been investigated. In the present study, we investigated the neural correlates of individual differences in FDI cognitive styles by analyzing the correlations between Embedded Figures Test (EFT) score and structural neuroimaging data [regional gray matter volume (rGMV) was assessed using voxel-based morphometry (VBM)] / functional neuroimaging data [resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF)] throughout the whole brain. Results showed that the increased rGMV in the left inferior parietal lobule (IPL) was associated with the EFT score, which might be the structural basis of effective local processing. Additionally, a significant positive correlation between ALFF and EFT score was found in the fronto-parietal network, including the left inferior parietal lobule (IPL) and the medial prefrontal cortex (mPFC). We speculated that the left IPL might be associated with superior feature identification, and mPFC might be related to cognitive inhibition of global processing bias. These results suggested that the underlying neuroanatomical and functional bases were linked to the individual differences in FDI cognitive styles and emphasized the important contribution of superior local processing ability and cognitive inhibition to field-independent style. PMID:24348991