TY - JOUR
T1 - Cumulative Dopamine Genetic Score predicts behavioral and electrophysiological correlates of response inhibition via interactions with task demand
AU - Enge, Soeren
AU - Sach, Mareike
AU - Reif, Andreas
AU - Lesch, Klaus-Peter
AU - Miller, Robert
AU - Fleischhauer, Monika
N1 - Funding Information:
The authors thank Inge Reck, Carola Gagel, and Nicole Döring for their technical assistance in DNA sample processing and genotyping. AR was supported by the European Community's Horizon 2020 Programme (H2020/2014-2020) under Grant Nos. 643051 (MiND) and 667302 (CoCA). This work was partly supported by the German Research Foundation (DFG, SFB 940/2).
Funding Information:
The authors thank Inge Reck, Carola Gagel, and Nicole D?ring for their technical assistance in DNA sample processing and genotyping. AR was supported by the European Community's Horizon 2020 Programme (H2020/2014-2020) under Grant Nos. 643051 (MiND) and 667302 (CoCA). This work was partly supported by the German Research Foundation (DFG, SFB 940/2). All data and materials are available upon request. Please contact the first author ([email protected]) or the senior author ([email protected]). The study was not preregistered.
Publisher Copyright:
© 2019, The Author(s).
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Genetic score
KW - Dopamine
KW - Response inhibition
KW - ERP
KW - NoGo-P3
KW - DEFICIT HYPERACTIVITY DISORDER
KW - GO/NO-GO TASKS
KW - O-METHYLTRANSFERASE COMT
KW - WORKING-MEMORY
KW - TRANSPORTER AVAILABILITY
KW - PREFRONTAL CORTEX
KW - 7-REPEAT ALLELE
KW - RECEPTOR GENE
KW - NEURAL BASIS
KW - COGNITIVE FLEXIBILITY
U2 - 10.3758/s13415-019-00752-w
DO - 10.3758/s13415-019-00752-w
M3 - Article
C2 - 31802408
SN - 1530-7026
VL - 20
SP - 59
EP - 75
JO - Cognitive, Affective, & Behavioral Neuroscience
JF - Cognitive, Affective, & Behavioral Neuroscience
IS - 1
ER -