The Impact of Catechol-O-Methyltransferase and Dopamine D4 Receptor Genotypes on Neurophysiological Markers of Performance Monitoring

Abstract

Dynamic adaptations of one's behavior by means of performance monitoring are a central function of the human executive system, that underlies considerable interindividual variation. Converging evidence from electrophysiological and neuroimaging studies in both animals and humans hints at the importance of the dopaminergic system for the regulation of performance monitoring. Here, we studied the impact of two polymorphisms affecting dopaminergic functioning in the prefrontal cortex [catechol-O-methyltransferase (COMT) Val108/158Met and dopamine D4 receptor (DRD4) single-nucleotide polymorphism (SNP)-521] on neurophysiological correlates of performance monitoring. We applied a modified version of a standard flanker task with an embedded stop-signal task to tap into the different functions involved, particularly error monitoring, conflict detection and inhibitory processes. Participants homozygous for the DRD4 T allele produced an increased error-related negativity after both choice errors and failed inhibitions compared with C-homozygotes. This was associated with pronounced compensatory behavior reflected in higher post-error slowing. No group differences were seen in the incompatibility N2, suggesting distinct effects of the DRD4 polymorphism on error monitoring processes. Additionally, participants homozygous for the COMT Val allele, with a thereby diminished prefrontal dopaminergic level, revealed increased prefrontal processing related to inhibitory functions, reflected in the enhanced stop-signal-related components N2 and P3a. The results extend previous findings from mainly behavioral and neuroimaging data on the relationship between dopaminergic genes and executive functions and present possible underlying mechanisms for the previously suggested association between these dopaminergic polymorphisms and psychiatric disorders as schizophrenia or attention deficit hyperactivity disorder.

Acute effects of cocaine on the neurobiology of cognitive control

“…This conclusion is supported by recent functional MRI and electrophysiological evidence linking the brain's error response to genetic markers of dopamine function ( Frank et al 2007;Klein et al 2007;Krämer et al 2007). Additionally, patients with Parkinson's disease show reduced ACC responses to errors that are partly moderated by dopaminergic medication (Frank et al 2004).…”

Neural Markers of Errors as Endophenotypes in Neuropsychiatric Disorders

“…In Val allele carriers increased ERN (Osinsky et al, 2012) or a trend to an increased ERN (Kramer et al, 2007), no effect on the ERN but increased Pe in Met homozygotes .…”

“…The DRD4 -521C allele has been associated with schizophrenia (Okuyama et al, 1999;Xing et al, 2003;Allen et al, 2008) and healthy individuals homozygous for the C allele showed a decreased ERN and decreased post-error slowing compared to T homozygotes (Kramer et al, 2007).…”

“…While COMT Val 158 Met primarily affects DA availability in the prefrontal cortex (Egan et al, 2001;Craddock et al, 2006b), it may also have downstream effects on midbrain DA . Studies of error processing have yielded inconsistent findings, showing an increased amplitude of the ERN in Val allele carriers (Osinsky et al, 2012), only a trend-level enhancement of the ERN in Val compared to Met homozygotes (Kramer et al, 2007), and no effect of COMT Val 158 Met on the ERN but an increased Pe in Met homozygotes compared to Val carriers .…”

The Role of the BDNF Val66Met Polymorphism for the Synchronization of Error-Specific Neural Networks

“…The influence of genetic factors on error processing and response monitoring functions has frequently been studied in the past (Klein et al, 2007;Krämer et al, 2007;Beste et al, 2010a). Until now, no study examined the role of neurotrophins for these im- portant cognitive functions.…”