Marine Manard

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

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.

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

BackgroundResearch 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.ResultsRepeated 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).ConclusionsThis 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.

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

Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val(158)Met) has received increasing attention as a possible modulator of executive functioning and its neural correlates. However, this attention has generally centered 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 2 main non-executive determinants of the Stroop effect). The Stroop task was administered during functional magnetic resonance imaging scanning to 3 groups of 15 young adults divided according to their COMT Val(158)Met 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 in homozygous VV individuals than in Met allele carriers. In addition, the VV group exhibited stronger positive functional connectivity between these 2 brain regions and stronger negative connectivity between the right IFop and left lingual gyrus. These results confirm the impact of COMT genotype on frontal functions. They also strongly suggest that differences in frontal activity influence posterior brain regions related to a non-executive component of the task. Particularly, 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.

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

HighlightsWe administered the Stroop test to young and older subjects during fMRI acquisitions.We examined BOLD signal changes linked to reactive and proactive cognitive control.Aging differentially affects neural networks associated with both kind of control.Very similar changes to those observed in young people with low brain dopamine level.Prefrontal dopamine availability may be a brain modulator of cognitive control. 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 < 0.05) 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.

Decreased Synaptic Density in Early Alzheimer’s Disease Assessed with [18F]UCB-H-PET

Background:Hypertension and Type 2 diabetes are cardiovascular disease risk factors (CVD-RFs) associated with pathological aging, including Alzheimer’s disease (AD) and vascular dementia. Mid-life hypertension and diabetes predict late-life white matter alterations including white matter hyperintensities (WMH) associated with dementia. Further, evidence suggests that theseCVD-RFsmay exert their impact as early as the third or fourth decade of life in affected individuals. Hypertension and diabetes are two of the most prevalent CVDRFs in minority populations, and rates of treatment-related control in these populations lag behind those of non-Hispanic Whites. Work is needed to detect white matter vulnerability associated with CVDRFs before overt damage occurs. Given that myelin degradation is thought to contribute to white matter damage, we focused this study on multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) as it relates to CVD-RFs in an ethnically diverse sample of older adults. Methods: Forty-six non-demented/ non-depressed participants (mean age1⁄466.4 years; 56% female; equal % Black/Hispanic/non-Hispanic White) underwent 3TMRI. mcDESPOT quantified ‘restricted’ water trapped within the lipid bilayers of myelin sheath, providing a measure of myelin water fraction (MWF). Regardless of medication status, systolic blood pressure (SBP) was determined via two readings separated by 5-minute intervals; blood glucose was measured by fasting levels of hemoglobin A1c. Separate age-adjusted linear regressions investigated the associations betweenSBPandA1conwhole-brainMWF.Analyseswere fully corrected for multiple comparisons and utilized threshold-free cluster enhancement. Results:Higher SBP was associated with lower MWF within deepwhitematter and parietal regions (p<.05), whereas greater A1c was associated with lower MWF in deep white matter and more temporal regions (p<.05; see Figure 1a). Similar associations were noted in a subset of fifteen Hispanics at increased risk for uncontrolled CVD-RFs (see Figure 1b). Conclusions:Higher levels of SBP and A1c are associated with decreased myelin integrity in a sample of older, ethnically diverse adults. These results suggest that mcDESPOT may be a useful tool to detect the adverse effects of CVD-RFs onwhitematter integrity in and around areas ofWMH in older non-demented/nondepressed adults.