2008b, 2010), the opposite was found during a verbal fluency task (Kircher et al. 2009b). Since there were no behavioural SCR7 changes due to genotype during the two firstly mentioned tasks (Krug et al. 2008b, 2010), but verbal fluency decreased with C allele frequency (Kircher et al.

2009), increased BOLD responses were interpreted as a compensatory mechanism. The changes in frontal fiber tract integrity found here might well be the anatomical basis for these functional alterations. While decreases in frontal FA have been described in NRG1 rs35753505 risk type carriers, the overall pattern of changes found in our data set is markedly differed from that of a previously published study on this SNP (Winterer et al. 2008). Inhibitors,research,lifescience,medical Especially increases in FA were not reported. In contrast, the largest cluster in our study was found in the right perihippocampal Inhibitors,research,lifescience,medical region and indicated higher FA in homozygous risk allele carriers. There are several

possible explanations for these differences. First of all, while in the study by Winterer and colleagues homo-and heterozygote C allele carriers were compared to T allele homozygotes for their whole-brain analyses, we here focused on homozygous C and T allele carriers. As neuroanatomical changes Inhibitors,research,lifescience,medical should be most pronounced in homozygotes, this approach may have yielded a higher sensitivity to subtle effects. Adding to this effect, we here used the TBSS algorithm. This method was specifically developed for the analysis Inhibitors,research,lifescience,medical of diffusion imaging data (Smith et al. 2006). Given the methodical problems of conventional VBM-style whole-brain approaches for multisubject FA images with regard to alignment (Simon et al. 2005; Vangberg et al. 2006) and smoothing (Jones et al. 2005), TBSS provides an optimized solution for diffusion data analysis. Previous studies demonstrated that the application of TBSS is especially suitable for imaging genetics Inhibitors,research,lifescience,medical studies, where between-genotype differences often are small and therefore

precise alignment is critical to avoid false positive or false negative findings (Nickl-Jockschat et al. 2012). Especially in a brain region such as the medial temporal lobe, where a variety of gray and white matter structures are located close to each other, misalignment can be a critical problem. Moreover, interindividual variance Sclareol is comparatively high in the neuroanatomy of the medial temporal lobe. The solution of these problems is a largely optimized alignment procedure as provided by TBSS. Consequently, our finding of elevated FA values in the right perihippocampal region might be due to improvements in data processing, in specific by using the TBSS algorithm. Both FA increases and decreases were found in NRG1 rs35753505 risk type carriers. Given that there is still an open discussion on the microstructural correlates of FA, there are several possible scenarios for the link between the genetic variations and diffusion indices.