Reference : Modulating effect of COMT genotype on the brain regions underlying inhibition
Scientific congresses and symposiums : Poster
Social & behavioral sciences, psychology : Neurosciences & behavior
Modulating effect of COMT genotype on the brain regions underlying inhibition
Jaspar, Mathieu mailto [Université de Liège - ULiège > Département de Psychologie : cognition et comportement > Neuropsychologie >]
Grandjean, Julien [Université de Liège - ULiège > Département de Psychologie : cognition et comportement > Neuropsychologie >]
Salmon, Eric mailto [Université de Liège - ULiège > Département des sciences cliniques > Neuroimagerie des troubles de la mémoire et révalid. cogn. >]
Maquet, Pierre mailto [Université de Liège - ULiège > > Centre de recherches du cyclotron >]
Collette, Fabienne mailto [Université de Liège - ULiège > Département de Psychologie : cognition et comportement > Neuropsychologie >]
17th Annual Meeting of the Organization on Human Brain Mapping
du 26 juin 2011 au 30 juin 2011
[en] Inhibition ; COMT ; Brain activation
[en] Introduction
Catechol-O-methytransferase (COMT) is an important enzyme which degrades catecholamines, such dopamine, notably in the prefrontal cortex (Männistö & Kaakkola, 1999). Actually, a transition of guanine to adenine at codon 158 of the COMT gene results in a valine to methionine substitution (Lotta & al., 1995). This phenomenon leads to different COMT genotypes, each associated with a different COMT enzymatic activity (Weinshilboum, & al., 1999). A large number of studies reported an effect of COMT on executive functioning. However, most of them used multi-determined executive tasks (e.g., Barnett & al., 2007). We are interested here to determine the effect of COMT Val158Met genotype on the activity of frontal and parietal areas (Nee & al., 2007; Laird & al., 2005) underlying the specific executive process of inhibition.
In an event-related fMRI experiment, a modified form of the Stroop task was administered to 44 young adults (age range: 18-30) separated into three groups according to their COMT Val158Met genotype: 15 homozygous val/val (VV), 14 homozygous met/met (MM) and 15 heterozygotes val/met (VM) carriers. The Stroop task consisted in the presentation of color words printed in various ink colors (e.g the word blue written in red). Subjects were instructed to name of ink color as fast and accurately as possible by avoiding to read the word. In this version of the Stroop task, three different contexts were created (data not showed here): (1) a congruent context (MC) with a majority of facilitator items (IC), (2) a non-congruent context (MI) with mainly interfering items (II), (3) a neutral context (MN) with mainly neutral items (IN, series of %%% written in different colors).
MRI acquisition, data analysis
Functional MRI time series were acquired on a 3T head-only scanner operated with the standard transmit-receive quadrature head coil. Multislice T2*-weighted functional images were acquired with a gradient-echo echo-planar imaging sequence using axial slice orientation and covering the whole brain (32 slices, FoV = 220x220 mm², voxel size 3.4x3.4x3 mm³, 30% interslice gap, matrix size 64x64x32, TR = 2130 ms, TE = 40 ms, FA = 90°). Structural images were obtained using a high resolution T1-weighted sequence (3D MDEFT [Deichmann & al., (2004)] ; TR = 7.92 ms, TE = 2.4 ms, TI = 910 ms, FA = 15°, FoV = 256 x 224 x 176 mm³, 1 mm isotropic spatial resolution). Preprocessing and statistical analyses were performed with SPM8 (p<.001 uncorrected).
Results Behavioral results indicated the presence of a general interference effect (II – IN items) for reaction time (F(1,41) = 292,44 ; p < 0,001) but no significant difference in interference between the three groups (F(2,41) = 0,27; p = 0,76).
FMRI results revealed that interference effect [(MI_II-MI_IN) + (MC_II-MC_IN) + (MN_II-MN_IN)] observed in our three groups is mainly associated with cerebral activity in frontal and parietal areas. Moreover, group comparisons indicates that this effect is associated with increased medial frontal and precentral gyrus activity in VV and VM groups by comparison with MM group, but also in the superior temporal gyrus and in the thalamus in the VM by comparison to MM . Conversely, no supplementary brain area was observed for the comparison of the MM to the two other groups.
The fronto-parietal brain network associated with interference resolution observed here is consistent with prior reports (Nee & al., 2007; Laird & al., 2005). Moreover, results showed activity in different brain areas according to the COMT genotype. Indeed, a similar behavioral performance is associated to the recruitment of supplementary areas in the carriers of the val allele. This observation, paralleling with the lower COMT enzymatic activity and, thus, the higher cortical dopamine level in met/met individuals, confirms our expectation of a COMT Val158Met genotype modulation of the brain regions underlying inhibition efficiency.
Centre de Recherches du Cyclotron - CRC

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