Modulating effect of COMT genotype on the brain regions underlying proactive control process during inhibition

Abstract

Introduction: Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val(158)Met polymorphism) has received increasing attention as a possible modulator of cognitive control functions.

Methods: In an event-related functional magnetic resonance imaging (fMRI) study, a modified version of the Stroop task was administered to three groups of 15 young adults according to their COMT Val(158)Met genotype [Val/Val (VV), Val/Met (VM) and Met/Met (MM)]. Based on the theory of dual mechanisms of control (Braver et al., 2007), the Stroop task has been built to induce proactive or reactive control processes according to the task context.

Results: Behavioral results did not show any significant group differences for reaction times but Val allele carriers individuals are less accurate in the processing of incongruent items. fMRI results revealed that proactive control is specifically associated with increased activity in the anterior cingulate cortex (ACC) in carriers of the Met allele, while increased activity is observed in the middle frontal gyrus (MFG) in carriers of the Val allele.

Conclusion: These observations, in keeping with a higher cortical dopamine level in MM individuals, support the hypothesis of a COMT Val(158)Met genotype modulation of the brain regions underlying proactive control, especially in frontal areas as suggested by Braver et al.

Keywords: COMT gene; Cognitive control; Inhibition; Stroop task; fMRI.