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The Journal of Neuroscience, December 19, 2007, 27(51):14190-14198; doi:10.1523/JNEUROSCI.4229-07.2007

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

Ulrike M. Krämer,¹ Toni Cunillera,² Estela Càmara,^1,3 Josep Marco-Pallarés,¹ David Cucurell,² Wido Nager,^1,3 Peter Bauer,⁴ Rebecca Schüle,⁵ Ludger Schöls,⁵ Antoni Rodriguez-Fornells,^2,6 and Thomas F. Münte¹

¹Department of Neuropsychology, Otto-von-Guericke-University, 39106 Magdeburg, Germany, ²Department Psicologia Bàsica, University of Barcelona, 08035 Barcelona, Spain, ³Medical University of Hannover, 30163 Hannover, Germany, ⁴Medical Genetics, University of Tübingen, 72074 Tübingen, Germany, ⁵Hertie-Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany, and ⁶Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain

Correspondence should be addressed to Thomas F. Münte, Department of Neuropsychology, Otto-von-Guericke-University, Universitätsplatz 2, 39106 Magdeburg, Germany. Email: thomas.muente{at}med.ovgu.de

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.

Key words: executive functions; COMT; DRD4; error-related negativity; inhibition; dopamine

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Received Sept. 14, 2007; revised Nov. 10, 2007; accepted Nov. 12, 2007.

Correspondence should be addressed to Thomas F. Münte, Department of Neuropsychology, Otto-von-Guericke-University, Universitätsplatz 2, 39106 Magdeburg, Germany. Email: thomas.muente{at}med.ovgu.de

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