Both the COMT Val158Met single-nucleotide polymorphism and sex-dependent differences influence response inhibition

Abstract

Reactive and proactive controls of actions are cognitive abilities that allow one to deal with a continuously changing environment by adjusting already programmed actions. They also set forthcoming actions by evaluating the outcome of the previous ones. Earlier studies highlighted sex-related differences in the strategies and in the pattern of brain activation during cognitive tasks involving reactive and proactive control. To further identify sex-dependent characteristics in the cognitive control of actions, in this study, we have assessed whether/how differences in performance are modulated by the COMT Val158Met single-nucleotide polymorphism (SNP), a genetic factor known to influence the functionality of the dopaminergic system—in particular, at the level of the prefrontal cortex. Two groups of male and female participants were sorted according to their genotype (Val/Val, Val/Met, and Met/Met) and tested in a stop signal task, a consolidated tool for measuring executive control in experimental and clinical settings. In each group of participants, we estimated both a measure of the capacity to react to unexpected events and the ability to monitor their performance. The between-group comparison of these measures indicated a poorer ability of male individuals and Val/Val subjects in error-monitoring. These observations suggest that sex differences in inhibitory control could be influenced by the efficiency of COMT and that other sex-specific factors have to be considered. Understanding the inter-group variability of behavioral and physiological correlates of cognitive control could provide more accurate diagnostic tools for predicting the incidence and/or the development of pathologies, like ADHD, or deviant behaviors, such as drug or alcohol abuse.

Visual salience of the stop signal affects the neuronal dynamics of controlled inhibition

“…Figure 1a shows the schema of the general task employed, which is a modified version of the reaching countermanding task 21 , 45 , 47 , 65 , 90 , 91 , characterized by the presentation of two types of trials, randomly intermixed: no-signal trials and stop-signal trials (see Table 1 ).…”

Corticocortical Systems Underlying High-Order Motor Control

“…The distributed system for inhibitory control of action must be elaborate and flexible enough to subserve different action contexts, individual differences and genetic variations (Mione et al, 2015). The cerebral cortex contains several types of pyramidal cells in layers II-III and V-VI, and their characteristics depend on the cortical layer, area, and species (van Aerde and Feldmeyer, 2015;Gilman et al, 2017;Luebke, 2017).…”

Peer Review #2 of "No association of COMT with insight problem solving in Chinese college students (v0.1)"

“…Because the insight phenomenon, like other complex traits, might be highly polygenic and influenced by thousands of genetic variants with small individual effects (Gratten et al 2014;Manolio et al 2009;Robinson et al 2014), it is important for future studies to validate these results in larger samples. Second, the imbalanced gender ratio in our sample may bias the results of gender-dependent analysis (Mione et al 2015). Although COMT is well known to be sexually dimorphic (Chen et al 2004;Tunbridge et al 2007), gender-dependent effect was not observed in this study.…”

“…Moreover, since COMT enzyme activity is influenced by gender (Chen et al 2004), many studies have also shown a gender-dependent effect of COMT. For example, Mione et al (2015) and White et al (2014) reported a gender-dependent effect of COMT on inhibitory control and related brain activity. Elton et al (2017) demonstrated that COMT exerted a genderdependent effect on resting brain functional connectivity and brain activity during decisionmaking task.…”