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Inherent limitations of tractography for accurate connectivity maps.

youth. These individuals were compared with a control cohort of athletes with similar ages and educational levels who had never sustained a concussion. Each individual was administered an exhaustive neuropsychological test battery to identify neurocognitive dysfunction. Patients then underwent magnetic resonance imaging examinations, includingDTI, determinations of fractional anisotropy, andmean, radial, and axial diffusivity. Using these data, the authors carried out a novel computational technique called tract-based spatial statistics. This technique allows the correlation between white matter integrity metrics and neurocognitive measurements via the performance of statistics on every voxel from a 3-dimensional network of coregistered fiber tracts from every study participant. What these authors discovered is concerning but not shocking. Neuropsychological testing revealed that the cohort of retired athletes, many years removed from their concussions, demonstrated cognitive dysfunction in the domains of memory and executive functioning compared with the control subjects. It is notable that this is a population of individuals having suffered only amean of 2 known concussions as discerned by a standardized concussion questionnaire. Conventional magnetic resonance imaging identified typical alterations in the brain tissue usually associated with aging and did not reveal significant differences between groups. Structural imaging analysis revealed that the older concussed athletes demonstrated significantly enlarged lateral ventricles compared with control subjects. This was statistically correlated with delayed recall and recognition testing. There were no meaningful differences in gray matter between the 2 cohorts.However, this was not the case for white matter. Tract-based spatial statistics identified widespread abnormalities in the aging, previously concussed brains compared with the controls (Figure). Numerous areas of the brain, including the interhemispheric fibers of the corpus callosum, the anterior limb of the internal capsule, the corona radiate involving the corticospinal tracts, and the superior and inferior longitudinal fasciculi, all demonstrated DTI evidence of damage. A regression analysis was performed to correlate these findings with the abnormal results of the neuropsychological testing batteries. Importantly, extensive correlations were identified. For example, dysfunction of visual episodic memory function correlated with abnormal DTI metrics and predicted delayed recall on the Taylor Complex Figure Test. Disruption of the anterior body and genu of the corpus callosum was associated with disturbances in episodic memory. Injury to left hemispheric tracts was associated with dysfunction in sequential motor learning in the contralateral hand. No similar structurefunction relationships were identified in the control cohort. As the authors indicate, this is the first study of its kind to demonstrate persistent white matter abnormalities in clinically normal, aged, retired athletes. This research has profound implications for the worlds of amateur and professional athletics. First, although a questionnaire administered years after an injury has the potential to underestimate the incidence of concussions, the low incidence in the concussed cohort suggests that even a single concussion can lead to lifelong consequences and may work in concert with the negative effects of normal aging on cognitive function. Moreover, sequelae of such injuries is now detectable on both imaging and neurocognitive testing. Such knowledge calls into question any participation in sports in which concussion is common. Now that we are identifying these structure-function relationships in concussed athletes, what will the culpability be of athletic organizing bodies and professional leagues for the consequences of these injuries going forward? Previously, there was deniability for these matters. Demonstration of the power of DTI techniques to uncover white matter injuries begs the question as to when such techniques will be applied on a routine clinical basis for athletes. Data such as these are already affecting the billiondollar sports industry and will change the current sports landscape as we know it from the youth level to the professional level.