TY - JOUR
T1 - COMT genotype predicts BOLD signal and noise characteristics in prefrontal circuits
AU - Winterer, Georg
AU - Musso, Francesco
AU - Vucurevic, Goran
AU - Stoeter, Peter
AU - Konrad, Andreas
AU - Seker, Berna
AU - Gallinat, Juergen
AU - Dahmen, Norbert
AU - Weinberger, Daniel R.
PY - 2006/10/1
Y1 - 2006/10/1
N2 - Objective: Prefrontal dopamine (DA) is catabolized by the COMT (catechol-O-methyltransferase) enzyme. Literature suggests that the Val/Met single nucleotide polymorphism (SNP) in the COMT gene predicts executive cognition in humans with Val carriers showing poorer performance due to less available synaptic DA. Recent fMRI studies are thought to agree with these studies having demonstrated prefrontal hyperactivation during n-back and attention-requiring tasks. This was interpreted as "less efficient" processing due to impaired signal-to-noise ratio (SNR) of neuronal activity. However, electrophysiological studies of neuronal SNR in primates and humans imply that prefrontal cortex should show a diminished prefrontal BOLD response in Val carriers. In the present study, we addressed the question of whether the prefrontal SNR of the BOLD response is decreased in Val carriers using a visual oddball task and an approach to analysis of fMRI data that maximizes noise characterization. Methods: We investigated N = 17 homozygous Met carriers compared with N = 24 Val carriers matched for age, sex, education, IQ, reaction time (variability) and head motion. Event-related fMRI was conducted presenting 160 visual stimuli (40 targets, checkerboard reversal). Subjects had to respond as quickly as possible to targets by button press. In the fMRI GLM [y(t) = β * x(t) + c + e(t)] analysis, voxel-by-voxel 'activation' [y(t)] as well as residual noise variance [e(t) = σ2] were calculated using a conservative full-width half maximum (FWHM = 6 mm). Results: As compared to Val carriers, we observed a stronger and more extended BOLD responses in homozygous Met carriers in left supplementary motor area (SMA) extending to ACC and dorsolateral prefrontal cortex. Vice versa, increased levels of noise were seen in Val carriers surrounding the peak activation maximum. Discussion: In line with our expectations from prior electrophysiological studies, we observed a diminished BOLD response and increased noise in Val carriers. This suggests that the DA stabilizes cortical microcircuits by sharpening the signal and suppressing surrounding noise.
AB - Objective: Prefrontal dopamine (DA) is catabolized by the COMT (catechol-O-methyltransferase) enzyme. Literature suggests that the Val/Met single nucleotide polymorphism (SNP) in the COMT gene predicts executive cognition in humans with Val carriers showing poorer performance due to less available synaptic DA. Recent fMRI studies are thought to agree with these studies having demonstrated prefrontal hyperactivation during n-back and attention-requiring tasks. This was interpreted as "less efficient" processing due to impaired signal-to-noise ratio (SNR) of neuronal activity. However, electrophysiological studies of neuronal SNR in primates and humans imply that prefrontal cortex should show a diminished prefrontal BOLD response in Val carriers. In the present study, we addressed the question of whether the prefrontal SNR of the BOLD response is decreased in Val carriers using a visual oddball task and an approach to analysis of fMRI data that maximizes noise characterization. Methods: We investigated N = 17 homozygous Met carriers compared with N = 24 Val carriers matched for age, sex, education, IQ, reaction time (variability) and head motion. Event-related fMRI was conducted presenting 160 visual stimuli (40 targets, checkerboard reversal). Subjects had to respond as quickly as possible to targets by button press. In the fMRI GLM [y(t) = β * x(t) + c + e(t)] analysis, voxel-by-voxel 'activation' [y(t)] as well as residual noise variance [e(t) = σ2] were calculated using a conservative full-width half maximum (FWHM = 6 mm). Results: As compared to Val carriers, we observed a stronger and more extended BOLD responses in homozygous Met carriers in left supplementary motor area (SMA) extending to ACC and dorsolateral prefrontal cortex. Vice versa, increased levels of noise were seen in Val carriers surrounding the peak activation maximum. Discussion: In line with our expectations from prior electrophysiological studies, we observed a diminished BOLD response and increased noise in Val carriers. This suggests that the DA stabilizes cortical microcircuits by sharpening the signal and suppressing surrounding noise.
KW - Attention
KW - COMT
KW - Dopamine
KW - Prefrontal
KW - fMRI
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UR - http://www.scopus.com/inward/citedby.url?scp=33748294193&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2006.05.058
DO - 10.1016/j.neuroimage.2006.05.058
M3 - Article
C2 - 16884927
AN - SCOPUS:33748294193
SN - 1053-8119
VL - 32
SP - 1722
EP - 1732
JO - NeuroImage
JF - NeuroImage
IS - 4
ER -