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

Jaspar, Mathieu; Genon, Sarah; Muto, Vincenzo; Meyer, C; Manard, Marine; Dideberg, Vinciane; Salmon, Eric; Maquet, Pierre; Collette, Fabienne

doi:10.1016/j.cortex.2013.06.003

Cited by 28 publications

(19 citation statements)

References 54 publications

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“…Indeed, independently of any genetic considerations, the interfering component of the Sternberg probe recency task (Sternberg, 1966) was previously found to be associated with left PFC activity (mainly in the left IFG; Badre & Wagner, 2005;Burgess & Braver, 2010;D'Esposito et al, 1999;Jonides et al, 1998;Mecklinger et al, 2003;Nelson et al, 2003;Postle & Brush, 2004). Activation in a similar region was also observed in studies considering the impact of COMT genotype on updating and inhibitory functions, with Met allele carriers showing lesser recruitment of the left prefrontal cortex for the same level of performance (Bertolino et al, 2008;Caldu et al, 2007;Egan et al, 2001;Jaspar et al, 2014a;Jaspar et al, 2014b;Mattay et al, 2003). Together, these elements led us to hypothesize that VV homozygous people should recruit the bilateral PFC more extensively in response to interference during the probe recency task.…”

Section: Aim Of the Study And A Priori Hypothesesmentioning

confidence: 56%

“…In others words, only proactive control processes would be dependent of the midbrain dopaminergic system. Finally, our previous results had shown that VV homozygous individuals increased frontal activity related to interference during reactive control processes (Jaspar et al, 2014a;Jaspar et al, 2014b). However, as genotype-related discrepancies during reactive control were localized in the right inferior frontal operculum, an area not classically related to interference resolution in the Sternberg probe recency task (Burgess & Braver, 2010;D'Esposito et al, 1999;Jonides et al, 1998), we did not expect to observe group differences during this condition.…”

Section: Aim Of the Study And A Priori Hypothesesmentioning

confidence: 64%

“…Thus, it seems plausible that over-or under-representation of that genotype in a group of participants (particularly with small sample sizes) is likely to modify the results obtained. In that context, we had previously observed that different patterns of brain activity were obtained on a Stroop task depending on whether or not COMT genotype is controlled for (Grandjean et al, 2012;Jaspar et al, 2014a).…”

Section: How Can We Explain the Brain-related Absence Of Interferencementioning

confidence: 99%

“…Back to the COMT Val 158 Met polymorphism and according to the DMC model, Met allele carriers' individuals should benefit from their higher level of DA within the PFC when the context requires a sustained brain activity. In that sense, we recently reported that, in MM individuals, proactive control processes during an inhibitory task were linked to decreased sustained brain activity in the left MFG and increased activity in the anterior cingulate cortex (ACC) (Jaspar et al, 2014a).…”

Section: Introductionmentioning

confidence: 99%

“…In a recent study (Jaspar et al, 2014a), we also explored the effects of COMT genotypes on various kinds of cognitive control using an inhibitory task (the Stroop task; Stroop, 1935). Cognitive control refers to the ability to flexibly adjust behaviour depending on situational demands and changes in the environment.…”

Section: Introductionmentioning

confidence: 99%

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Modulating effect of COMT Val158Met polymorphism on interference resolution during a working memory task

Jaspar

Dideberg

Maquet

et al. 2015

Brain and Cognition

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Jaspar M., Dideberg V., Bours V. Maquet P., Collette F. (2015). Modulating Effect of COMT Val 158 Met Polymorphism on Interference Resolution during a Working Memory Task. Brain and Cognition (In press)2 Abstract Genetic variability related to the catechol-O-methyltransferase (COMT) gene has received increasing attention in the last 15 years, in particular as a potential modulator of the neural substrates underlying inhibitory processes and updating in working memory (WM). In an event-related functional magnetic resonance imaging (fMRI) study, we administered a modified version of the Sternberg probe recency task (Sternberg, 1966) to 43 young healthy volunteers, varying the level of interference across successive items. The task was divided into two parts (high vs. low interference) to induce either proactive or reactive control processes. The participants were separated into three groups according to their COMT Val 158 Met genotype [Val/Val (VV); Val/Met (VM); Met/Met (MM)]. The general aim of the study was to determine whether COMT polymorphism has a modulating effect on the neural substrates of interference resolution during WM processing. Results indicate that interfering trials were associated with greater involvement of frontal cortices (bilateral medial frontal gyrus, left precentral and superior frontal gyri, right inferior frontal gyrus) in VV homozygous subjects (by comparison to Met allele carriers) only in the proactive condition of the task. In addition, analysis of peristimulus haemodynamic responses (PSTH) revealed that the genotype-related difference observed in the left SFG was specifically driven by a larger increase in activity from the storage to the recognition phase of the interfering trials in VV homozygous subjects. These results confirm the impact of COMT genotype on inhibitory processes during a WM task, with an advantage for Met allele carriers. Interestingly, this impact on frontal areas is present only when the level of interference is high, and especially during the transition from storage to recognition in the left superior frontal gyrus.Keywords: COMT gene -Working memory -fMRI -Cognitive control 3 IntroductionIn the last two decades, several lines of evidence have suggested that the neurotransmitter dopamine (DA) plays an important role in cognitive functions associated with prefrontal activity (Braver & Cohen, 1999;Cropley et al., 2006;Mattay et al., 2002). The study of the influence of DA on cognition in healthy populations appears particularly relevant given the long hypothesized role of DA in schizophrenia (Carlsson et al., 2000), a pathology that is well known to be associated with cognitive impairments (in particular in the executive domain). In that general context, genetic variability related to the catechol-Omethyltransferase (COMT) gene has received increasing attention as a potential modulator of executive functioning (Witte & Flöel, 2012). The human COMT gene codes for the major enzyme involved in the metabolic degradation of released DA. This gene, located on the lon...

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Section: Aim Of the Study And A Priori Hypothesesmentioning

confidence: 56%

Section: Aim Of the Study And A Priori Hypothesesmentioning

confidence: 64%

Section: How Can We Explain the Brain-related Absence Of Interferencementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Modulating effect of COMT Val158Met polymorphism on interference resolution during a working memory task

Jaspar

Dideberg

Maquet

et al. 2015

Brain and Cognition

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Dissociations of cognitive inhibition, response inhibition, and emotional interference: Voxelwise ALE meta‐analyses of fMRI studies

Hung

Gaillard

Yarmak

et al. 2018

Human Brain Mapping

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111

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Inhibitory control is the stopping of a mental process with or without intention, conceptualized as mental suppression of competing information because of limited cognitive capacity. Inhibitory control dysfunction is a core characteristic of many major psychiatric disorders. Inhibition is generally thought to involve the prefrontal cortex; however, a single inhibitory mechanism is insufficient for interpreting the heterogeneous nature of human cognition. It remains unclear whether different dimensions of inhibitory processes-specifically cognitive inhibition, response inhibition, and emotional interference-rely on dissociated neural systems. We conducted systematic meta-analyses of fMRI studies in the BrainMap database supplemented by PubMed using whole-brain activation likelihood estimation. A total of 66 study experiments including 1,447 participants and 987 foci revealed that while the left anterior insula was concordant in all inhibitory dimensions, cognitive inhibition reliably activated specific dorsal frontal inhibitory system, engaging dorsal anterior cingulate, dorsolateral prefrontal cortex, and parietal areas, whereas emotional interference reliably implicated a ventral inhibitory system, involving the ventral surface of the inferior frontal gyrus and the amygdala. Response inhibition showed concordant clusters in the fronto-striatal system, including the dorsal anterior cingulate region and extended supplementary motor areas, the dorsal and ventral lateral prefrontal cortex, basal ganglia, midbrain regions, and parietal regions. We provide an empirically derived dimensional model of inhibition characterizing neural systems underlying different aspects of inhibitory mechanisms. This study offers a fundamental framework to advance current understanding of inhibition and provides new insights for future clinical research into disorders with different types of inhibition-related dysfunctions.

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Effects of tolcapone and bromocriptine on cognitive stability and flexibility

et al. 2018

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RationaleThe prefrontal cortex (PFC) and basal ganglia (BG) have been associated with cognitive stability and cognitive flexibility, respectively. We hypothesized that increasing PFC dopamine tone by administering tolcapone (a catechol-O-methyltransferase (COMT) inhibitor) to human subjects should promote stability; conversely, increasing BG dopamine tone by administering bromocriptine (a D2 receptor agonist) should promote flexibility.ObjectiveWe assessed these hypotheses by administering tolcapone, bromocriptine, and a placebo to healthy subjects who performed a saccadic eye movement task requiring stability and flexibility.MethodsWe used a randomized, double-blind, within-subject design that was counterbalanced across drug administration sessions. In each session, subjects were cued to prepare for a pro-saccade (look towards a visual stimulus) or anti-saccade (look away) on every trial. On 60% of the trials, subjects were instructed to switch the response already in preparation. We hypothesized that flexibility would be required on switch trials, whereas stability would be required on non-switch trials. The primary measure of performance was efficiency (the percentage correct divided by reaction time for each trial type).ResultsSubjects were significantly less efficient across all trial types under tolcapone, and there were no significant effects of bromocriptine. After grouping subjects based on Val158Met COMT polymorphism, we found that Met/Met and Val/Met subjects (greater PFC dopamine) were less efficient compared to Val/Val subjects.ConclusionsOptimal behavior was based on obeying the environmental stimuli, and we found reduced efficiency with greater PFC dopamine tone. We suggest that greater PFC dopamine interfered with the ability to flexibly follow the environment.

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

Cited by 28 publications

References 54 publications

Modulating effect of COMT Val158Met polymorphism on interference resolution during a working memory task

Modulating effect of COMT Val158Met polymorphism on interference resolution during a working memory task

Dissociations of cognitive inhibition, response inhibition, and emotional interference: Voxelwise ALE meta‐analyses of fMRI studies

Effects of tolcapone and bromocriptine on cognitive stability and flexibility

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