title: Dopamine effects on human error processing depend on catechol-O-methyltransferase VAL158MET genotype.
abstract: Brain dopamine (DA) has been linked to error processing. Because high and low (vs medium) prefrontal cortex (PFC) DA levels may facilitate D2-receptor-related modulations of PFC neural activation patterns, we hypothesized that high and low DA predicts increased error-specific transitions of PFC activity. Male human participants (n = 169) were genotyped for the catechol-O-methyltransferase (COMT) Val158Met polymorphism, associated with low (Val) and medium (Met) PFC DA levels. In addition, DRD2TaqIa and 5-HTTLPR, associated with striatal D(2) receptor density and serotonin uptake, respectively, were assessed. Participants received placebo or a selective DA-D(2) receptor blocker (sulpiride, 200 mg) and performed a Flanker task. EEG was recorded and decomposed into independent brain components (ICs) using independent component analysis. After errors, participants displayed (1) a negative deflection in ICs source-localized to the proximity of the anterior midcingulate cortex [IC-error-related negativity (IC-ERN)], (2) increased midcingulate cortex IC power in the delta/theta frequency range, and (3) slowing in the subsequent trial [posterror slowing (PES)]. Importantly, all, IC-ERN, delta/theta power, and PES were modulated by COMT × Substance interactions such that the Val allele predicted elevated IC-ERN, delta/theta power, and PES after placebo; this association was reversed under sulpiride. Because low doses of sulpiride presumably increase PFC DA levels, the COMT × Substance interaction supports the hypothesis that low (Val, placebo) and high (Met, sulpiride) versus medium (Val, sulpiride; Met, placebo) DA levels elevate reactivity to errors. Consistent with an influence of serotonin on PFC DA, the COMT × Substance interaction was modulated by 5-HTTLPR.
authors: Philipps-Universität Marburg, 35032 Marburg, Germany. erik.mueller@staff.uni-marburg.de
authors: Erik M
authors: EM
authors: Mueller
authors: Scott
authors: S
authors: Makeig
authors: Gerhard
authors: G
authors: Stemmler
authors: Jürgen
authors: J
authors: Hennig
authors: Jan
authors: J
authors: Wacker
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008606:Mental Processes / Q000187:drug effects / Q000502:physiology*; D008715:Methionine / Q000235:genetics*; D009483:Neuropsychological Tests; D010775:Photic Stimulation / Q000379:methods; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology; D013997:Time Factors; D014633:Valine / Q000235:genetics*; D055815:Young Adult
chemical_list: D018492:Dopamine Antagonists; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D013469:Sulpiride; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine; D004298:Dopamine