Cumulative Dopamine Genetic Score predicts behavioral and electrophysiological correlates of response inhibition via interactions with task demand

Soeren Enge*, Mareike Sach, Andreas Reif, Klaus-Peter Lesch, Robert Miller, Monika Fleischhauer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)

Abstract

Functional genetic polymorphisms in the brain dopamine (DA) system have been suggested to underlie individual differences in response inhibition, namely the suppression of a prepotent or inappropriate action. However, findings on associations between single DA polymorphisms and inhibitory control often are mixed, partly due to their small effect sizes. In the present study, a cumulative genetic score (CGS) was used: alleles previously associated with both impulsive behavior and lower baseline DA level, precisely the DRD4 Exon III 7-repeat, DAT1 VNTR 10-repeat and the COMT 158val allele, each added a point to the DA-CGS. Participants (N = 128) completed a Go/No-Go task varying in difficulty and EEG recordings were made with focus on the NoGo-P3, an ERP that reflects inhibitory response processes. We found a higher DA-CGS (lower basal/tonic DA level) to be associated with better performance (lower %FA and more adaptive responding) in the very demanding/rapid than in the less demanding/rapid condition, whereas the reverse pattern was true for individuals with a lower DA-CGS. A similar interaction pattern of DA-CGS and task condition was found for NoGo-P3 amplitude. In line with assumptions of distinct optimum DA levels for different cognitive demands, a DA-CGS-dependent variation of tonic DA levels could have modulated the balance between cognitive stability and flexibility, thereby affecting the optimal DA level required for the specific task condition. Moreover, a task demand-dependent phasic DA release might have added to the DA-CGS-related basal/tonic DA levels, thereby additionally affecting the balance between flexibility and stability, in turn influencing performance and NoGo-P3.

Original languageEnglish
Pages (from-to)59-75
Number of pages17
JournalCognitive, Affective, & Behavioral Neuroscience
Volume20
Issue number1
Early online date4 Dec 2019
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Genetic score
  • Dopamine
  • Response inhibition
  • ERP
  • NoGo-P3
  • DEFICIT HYPERACTIVITY DISORDER
  • GO/NO-GO TASKS
  • O-METHYLTRANSFERASE COMT
  • WORKING-MEMORY
  • TRANSPORTER AVAILABILITY
  • PREFRONTAL CORTEX
  • 7-REPEAT ALLELE
  • RECEPTOR GENE
  • NEURAL BASIS
  • COGNITIVE FLEXIBILITY

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