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Evaluation of Two Types of Drug Treatment with QEEG in Children with ADHD

Abstract Aims The aim of this study is to evalute the effects of methylphenidate and atomoxetine treatments on electroencephalography (EEG) signals in volunteer children diagnosed with Attention Deficit and Hyperactivity Disorder(ADHD). Methods The study contained 40 children all of whom were between the ages of 7 and 17. The participants were classified into two groups as ADHD (n=20), which was in itself divided into two groups as ADHD-MPH (ADHD- Metylphenidate treatment) (n=10) and as ADHD-ATX (ADHD-Atomoxetin treatment) (n=10), and one control group (n=20). Following the first EEG recordings of the ADHD group, long-acting methylphenidate dose was applied to one ADHD group and atomoxetine dose was applied to the other ADHD group. The effect of optimal dosage is about for 4-6 weeks in general. Therefore, the response or lack of response to the treatment was evaluated three months after the beginning of the treatment. After methylphenidate and atomoxetine drug treatment, in order to obtain mean and maximum power values for delta, theta, alpha and beta band, the EEG data were analyzed. Results The EEG power spectrum densities in all the bands yielded similar findings in both methylphenidate and atomoxetine. Although statistically significant frequency values of the electrodes were amplitude and maximally varied, in general, they appeared mostly at both frontal and temporal regions for methylphenidate and atomoxetine. Conclusion Especially, after atomoxetine treatment, Quantitative Electroencephalography (QEEG) rates at frontal area electrodes were found statistically more significant than methylphenidate QEEG rates. What has been researched in this study is not only whether QEEG is likely to support the diagnosis, but whether changes on QEEG by treatment may be related to the severity of ADHD as well.


Introduction
they found some significant effects on ADHD subgroups [4]. It was reported in one other study that there was a deceleration in alpha waves after the application of a single dose of methylphenidate to ADHD subgroups. These findings emphasized that the main frequency of the alpha band may be a determinant index to satisfy methylphenidate response for ADHD [5].
There are studies showing that EEG profiles are significantly normalized by EEG changes and acute atomoxetine treatment resembling the changes caused by psychostimulants (methylphenidate /dexamphetamine) [6][7][8][9]. It was reported in some studies that QEEG profiles of those who responded or not responded to the treatment are declared to have defined the QEEG sub-groups of the children with ADHD [1,7,[10][11][12][13][14][15][16][17][18][19][20][21]. In a study on the investigation of the effects of medical treatment process of the children with cognitive and behavioral disorders accompanying ADHD on EEG, an increase alpha activity in central and parietal regions in cognitive activation conditions is observed. It was shown that there was an increase in the beta activity at the frontal area in those who responded to the treatment and a decrease in the beta activity at the same region in those who did not respond to the treatment.
In addition, in children with ADHD, stimulant medication is determined to have increased beta activity, especially in the frontal areas [22]. DongHoSong et al. determined in their study that methylphenidate caused a significant increase in the alpha band in the right and left frontal and occipital areas; an increase in the beta band in almost all areas except the temporal region; a decrease in the theta band in the occipital and right temporo-parietal regions; a slight decrease in gamma activities in occipital-parietal regions, and an increase in the rate of right frontal and parieto-occipital regions (i.e. theta / beta ratio) [23].
The aim of this study is to investigate the therapeutic properties of long-acting methylphenidate and atomoxetine drugs commonly used in ADHD with EEG signals in conjunction with classical medical evaluation.
It also aims to reveal the advantages and disadvantages of these two drugs relative to each other. Moreover, whether or not the treatment response and the relationship of resistance with EEG signal differences is to be determined by clinical follow-up and scale evaluation can help to guide the clinician in the selection of treatment for EEG signal parameters according to the obtained results.

Subjects and Methods
Fourty volunteer children, directed from the were not included in the study. The control group was one to one matched with the patient group in terms of age and sexuality, and twenty healthy volunteers, evaluated with WISC-R, without mental retardation, were included in the study. The demographic characteristics/ profiles of the participants are given mean age, years of education, and WISC-R mean scores for Following the first EEG recordings of the ADHD group, long-acting methylphenidate dose (OROS MPH) or atomoxetine dose was applied as 0.5 mg / kg / at the beginning of the day. And it was titrated to 1.2 mg / kg / day. The time to achieve optimal dose is about 4-6 weeks in general. Therefore, the response or lack of response to treatment were evaluated three months after the beginning of the treatment. In the literature survey, four artifacts correction methods were mentioned. One of these is the wavelet analysis method.
The wavelet analysis method performs as a filter that can remove artifacts located in frequency bands that overlap with those of the neurological phenomena of interest. It is more advantageous than other methods because of its filter feature based on wavelet transform. Therefore, in this study the wavelet analysis method is chosen to remove artifacts from EEG signals [24][25][26].
After we acquired the raw EEG signal data, all EEG signals are pre-processed using Wavelet analysis. Pre-processing procedures are resampling and windowing of the EEG signal.
During the measurement of EEG signals, other kinds of signals, such as ECG, EMG, 50Hz electrical interference, so called artifacts are also captured by electrodes. Artifacts are undesired signals that can introduce significant changes in neurological signals and ultimately affect the neurological phenomenon [27].
Some types of artifacts increase or decrease EEG band powers (delta, theta, alpha, beta) which leads to mistakes measured in the EEG bands.

Results
The EEG signals from individuals participating in the study were grouped according to frontal, temporal, central, parietal, occipital regions, and the average power for each electrode used to receive brain signals were separately obtained for maximum power and frequency values (delta, theta, alpha and beta bands) at which maximum power were obtained.
The obtained data were subjected to t-test with the control group for statistical analysis in the Matlab program to reveal effective electrodes in four groups including before methylphenidate and atomoxetine use, and after methylphenidate and atomoxetine use, respectively. Figure 2 indicates that the mean power values of the electrodes at the frontal region, delta, theta, alpha, and beta bands were higher than those of other regional electrodes, especially to other regions of the brain, in which the EEG signals were recorded from the individuals with ADHD before methylphenidate use, and mean power values  QEEG rates approximated to the control group decreasing, which is shown in Figure 5( In a study in which the effects of methylphenidate on EEG were investigated, it was reported that theta and alpha levels decreased, but beta activity increased in the frontal region in those who responded well to methylphenidate application, but reversed changes were observed in the EEG of those who responded poorly [33,34]. ii) When the results of EEG analysis after atomoxetine use were evaluated, it was seen that EEG power spectrum densities in Translational Neuroscience  in children with ADHD [34]. The present study may also be consistent with findings in brain imaging studies. For example, decreased blood flow in the frontal regions, decreased metabolic activity, activation differences, and decreased frontal lobe volume were reported for many ADHD patients using neuroimaging studies [35][36][37][38][39].
In this study, QEEG was found statistically significant in the delta/beta ratio of Fz-Cz electrode, and the delta/alpha ratio of