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Introduction. Non-invasive neuromodulation via transcranial direct current stimulation (tDCS) is a promising method for modulating plasticity. For the first time multichannel tDCS was used to investigate a larger number of children and young adolescents. Previous studies suggest that tDCS affects cognitive functions. It is assumed that the inferior frontal gyrus (IFG) has an important role in the process of response inhibition. Therefore, multichannel tDCS might has potential as therapy option for neurodevelopmental diseases such as attention deficit hyperactivity disorder (ADHD). The present study addressed the question whether tDCS could modulate this function. In addition, the study intended to investigate the most effective timing and tolerance of stimulation. Methods. The study was approved by the Ethic Committee of the Faculty of Medicine of Kiel university. 29 healthy participants (10-17 years old, mean age: 14,2 years, SD 2,14) were included in the analysis in a double-blinded and sham-controlled crossover study. The Flanker-task was used as target-task so that reaction time and accuracy were focused in the evaluation. Stimulation was scheduled prior (offline) or during (online) target task. After that the participants completed the n-back-task and the CPT-task as non-target-tasks. Resting state EEG was recorded before and after stimulation. Additionally, task related EEG was performed to expose changes at the neurophysiological level. For multichannel 2 mA tDCS over the right IFG we used a 6-channel solution (3.14 cm2 circular electrodes, positioned at F8 (1000 µA), FC6 (999 µA), P7 (−377 µA), T8 (−422 µA), C6 (−577 µA) and FPZ (−623 µA), filled with EEG electrode gel). Current was ramped up for 30 seconds at the beginning and the end in sham as well in verum stimulation. A linear mixed model was used for statistical evaluation. Results. There were only a few participants showing side effects such as itching, burning or fatigue. In a total of 112 sessions there were eight cases of adverse events such as headache. Our preliminary results at the behavioural level show no significant differences (p > 0.05) between tDCS and sham stimulation. There were no significant effects on accuracy or reaction time between online or offline stimulation neither. Conclusion. Our results show that tDCS was tolerated well by the participants. Based on preliminary results we could not confirm that tDCS could modulate the rIFG because response inhibition was not affected significantly. Further analysis could find out about possible reasons for our results such as ceiling effects. Analysis of resting EEG prior and after stimulation as well as task related EEG might yield neurophysiological explanation for the absence of behavioural improvement outcomes. The results provide a basis for future studies such as investigations of ADHD patients and might offer a compatible therapy option.

Large, longitudinal, multi-center MR neuroimaging studies require comprehensive quality assurance (QA) protocols for assessing the general quality of the compiled data, indicating potential malfunctions in the scanning equipment, and evaluating inter-site differences that need to be accounted for in subsequent analyses. We describe the implementation of a QA protocol for functional magnet resonance imaging (fMRI) data based on the regular measurement of an MRI phantom and an extensive variety of currently published QA statistics. The protocol is implemented in the MACS (Marburg-Münster Affective Disorders Cohort Study, http://for2107.de/), a two-center research consortium studying the neurobiological foundations of affective disorders. Between February 2015 and October 2016, 1214 phantom measurements have been acquired using a standard fMRI protocol. Using 444 healthy control subjects which have been measured between 2014 and 2016 in the cohort, we investigate the extent of between-site differences in contrast to the dependence on subject-specific covariates (age and sex) for structural MRI, fMRI, and diffusion tensor imaging (DTI) data. We show that most of the presented QA statistics differ severely not only between the two scanners used for the cohort but also between experimental settings (e.g. hardware and software changes), demonstrate that some of these statistics depend on external variables (e.g. time of day, temperature), highlight their strong dependence on proper handling of the MRI phantom, and show how the use of a phantom holder may balance this dependence. Site effects, however, do not only exist for the phantom data, but also for human MRI data. Using T1-weighted structural images, we show that total intracranial (TIV), grey matter (GMV), and white matter (WMV) volumes significantly differ between the MR scanners, showing large effect sizes. Voxel-based morphometry (VBM) analyses show that these structural differences observed between scanners are most pronounced in the bilateral basal ganglia, thalamus, and posterior regions. Using DTI data, we also show that fractional anisotropy (FA) differs between sites in almost all regions assessed. When pooling data from multiple centers, our data show that it is a necessity to account not only for inter-site differences but also for hardware and software changes of the scanning equipment. Also, the strong dependence of the QA statistics on the reliable placement of the MRI phantom shows that the use of a phantom holder is recommended to reduce the variance of the QA statistics and thus to increase the probability of detecting potential scanner malfunctions.

Several rare mutations in the melanocortin-4 receptor gene (MC4R) predispose to obesity. For the most common missense variant V103I (rs2229616), however, the previously reported similar carrier frequencies in obese and nonobese individuals are in line with in vitro studies, which have not shown a functional implication of this variant. In the present study, we initially performed a transmission/disequilibrium test on 520 trios with obesity, and we observed a lower transmission rate of the I103 allele (P = .017), which was an unexpected finding. Therefore, we initiated two large case-control studies (N = 2,334 and N = 661) and combined the data with those from 12 published studies, for a total of 7,713 individuals. The resulting meta-analysis provides evidence for a negative association of the I103 allele with obesity (odds ratio 0.69; 95% confidence interval 0.50-0.96; P = .03), mainly comprising samples of European origin. Additional screening of four other ethnic groups showed comparable I103 carrier frequencies well below 10%. Genomic sequencing of the MC4R gene revealed three polymorphisms in the noncoding region that displayed strong linkage disequilibrium with V103I. In our functional in vitro assays, the variant was indistinguishable from the wild-type allele, as was the result in previous studies. This report on an SNP/haplotype that is negatively associated with obesity expands the successful application of meta-analysis of modest effects in common diseases to a variant with a carrier frequency well below 10%. The respective protective effect against obesity implies that variation in the MC4R gene entails both loss and gain of function.