Influence of COMT Genotype on Antero-Posterior Cortical Functional Connectivity Underlying Interference Resolution

Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val158Met) has received increasing attention as a possible modulator of executive functioning and its neural correlates. However, this attention has generally centred on the prefrontal cortices because of the well-known direct impact of COMT enzyme on these cerebral regions. In this study, we were interested in the modulating effect of COMT genotype on anterior and posterior brain areas underlying interference resolution during a Stroop task. More specifically, we were interested in the functional connectivity between the right inferior frontal operculum (IFop), an area frequently associated with inhibitory efficiency, and posterior brain regions involved in reading/naming processes (the two main non-executive determinants of the Stroop effect). The Stroop task was administered during fMRI scanning to three groups of 15 young adults divided according to their COMT Val158Met genotype [Val/Val (VV), Val/Met (VM) and Met/Met (MM)]. Results indicate greater activity in the right IFop and the left middle temporal gyrus (MTG) in homozygous VV individuals than in Met allele carriers. In addition, the VV group exhibited stronger positive functional connectivity between these two brain regions and stronger negative connectivity between the right IFop and left lingual gyrus. These results confirm the impact of COMT genotype on frontal function. They also strongly suggest that differences in frontal activity influence posterior brain regions related to a non-executive component of the task. Especially, changes in functional connectivity between anterior and posterior brain areas might correspond to compensatory processes for performing the task efficiently when the available dopamine level is low.