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

peer reviewedIntroduction. Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val158Met polymorphism) has received increasing attention as a possible modulator of cognitive control functions. Methods. In an event-related fMRI study, a modified version of the Stroop task was administered to three groups of 15 young adults according to their COMT Val158Met 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 Val158Met genotype modulation of the brain regions underlying proactive control, especially in frontal areas as suggested by Braver et al

In vivo imaging of synaptic loss in Alzheimer’s disease with [18F]UCB-H Positron Emission Tomography

IUAP - Interuniversity Attraction Poles Programme (IUAP 7/11); ARC - Actions de recherche concertées (ARC 12/17-01); Special Research Funds classical grant 2016 (Faculty of Medicine, University of Liege, Belgium), FRS-FNR

Influence du polymorphisme nucléotidique COMT sur la mémoire de travail et son vieillissement

L’objectif de cette revue est de synthétiser les connaissances sur l’influence du polymorphisme nucléotidique Catéchol-O-Méthyltransférase (COMT) val108/158met sur la diminution des capacités de mémoire de travail (et plus particulièrement de ses aspects exécutifs) associée à l’avancée en âge. Par son implication dans les processus de dégradation de la dopamine, notamment au niveau préfrontal, ce polymorphisme semble avoir un rôle central dans l’efficacité de la mise en œuvre de processus exécutifs. En effet, plusieurs études suggèrent un avantage phénotypique de l’allèle met du polymorphisme COMT lors de tâches exécutives requérant une stabilité des représentations cognitives. Etant donné les modifications cérébrales observées avec l’âge au niveau frontal, le polymorphisme COMT semble constituer une piste pertinente pour comprendre les altérations cognitives liées à l’âge. En effet, suite à la diminution d’efficacité du système dopaminergique, les personnes âgées présentent des déficits de mémoire de travail plus ou moins importants selon leur génotype pour le polymorphisme COMT. De plus, l’activité cérébrale associée à la réalisation de ces tâches va également varier en fonction de ce polymorphisme. Ces résultats soulignent l’intérêt d’intégrer les approches de génétique comportementale et de neuroimagerie génétique afin d’approfondir notre compréhension du vieillissement cognitif

Age-related decline in cognitive control: the role of fluid intelligence and processing speed

Background Research on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items. Results Repeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities). Conclusions This study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment

The influence of COMT on the neural substrates of short-term memory in normal aging

Working memory dopaminergic modulation is generally expressed in healthy aging by an advantage for carriers of the Met allele at behavioral and brain activity levels. However, most tasks used did not allow to easily disentangle the contribution of maintenance and manipulation processes. We explored the effect of COMT genotype on the maintenance process using a Sternberg memory task varying the amount of information presented, in young and older homozygous carriers for the Val and Met alleles of the COMT gene. Although no clear behavioral difference was observed between groups, patterns of cerebral activity indicate difficulties for Met older individuals to maintain stable representations. These results will be discussed in terms of dopaminergic contribution to stability/flexibility of cognitive processes during aging

The neural bases of proactive and reactive control processes in normal aging

Introduction. Research on cognitive control suggests an age-related decline in proactive control abilities (anticipatory control), whereas reactive control (following conflict detection) seems to remain intact. As proactive and reactive control abilities are associated with specific brain networks, this study investigated age-related effects on the neural substrates associated with each kind of control. Methods. In an event-related fMRI study, a modified version of the Stroop task was administered to groups of 20 young and 20 older healthy adults. Based on the theory of dual mechanisms of control, the Stroop task has been built to induce proactive or reactive control depending on task context. Results. Behavioral results (p < .05) indicated faster processing of interfering items in the mostly incongruent (MI) than the mostly congruent (MC) context in both young and older participants. fMRI results showed that reactive control is associated with increased activity in left frontal areas for older participants. For proactive control, decreased activity in the bilateral anterior cingulate cortex was associated with more activity in the right middle frontal gyrus in the older than the younger group. Conclusion. These observations support the hypothesis that aging affects the neural networks associated with reactive and proactive cognitive control differentially. These age-related changes are very similar to those observed in young adults with low dopamine availability, suggesting that a general mechanism (prefrontal dopamine availability) may modulate brain networks associated with various kinds of cognitive control

Vieillissement non pathologique des fonctions exécutives : influence du polymorphisme nucléotidique Val108/158Met du gène COMT

Introduction. According to the Dual-State Theory of prefrontal cortex dopamine, Val/Val polymorphism of the COMT gene would favor better flexibility abilities, whereas Met/Met carriers would favor better stability abilities. These genotypic effects should be magnified in older people, as a decrease in cognitive resources increases the influence of individual genetic differences on cognitive performance. Therefore, the aim of the study is to investigate the influence of the COMT Val108/158Met nucleotide polymorphism on executive functions in normal aging. Method. We assessed the executive processes of inhibition, shifting, and updating thanks to many different tasks in groups of young (n = 55) and aged participants (n = 45) carrying one of the three polymorphisms of the COMT gene (Val/Val, Val/Met, Met/Met). T-tests between our two groups (Young versus Aged) but also a 6 (Group: Young-Met/Met, Young-Val/Met, Young-Val/Val, Old-Met/Met, Old-Val/Met, and Old-Val/Val) X 3 (Executive functioning: Inhibition, Shifting, and Updating) repeated measure ANOVA with Executive functioning as within-subject factor (p < .05) were carried out. Results. Young and old participants significantly differed on the three executive functions. The comparison of genotypic groups showed no significant differences in young or older participants respectively. Interestingly, the Old-Val/Val group showed a lower performance than the young one on inhibition tasks. Discussion. As expected, we found an age effect on all the executive functions. The significant difference between the Young-Val/Val and the Old-Val/Val groups on inhibition suggests an age-related decrease in abilities requiring a stability component in individuals possessing a less favoring genotype for this component