Krämer Ulrike M, Cunillera Toni, Càmara Estela, Marco-Pallarés Josep, Cucurell David, Nager Wido, Bauer Peter, Schüle Rebecca, Schöls Ludger, Rodriguez-Fornells Antoni, Münte Thomas F
Department of Neuropsychology, Otto-von-Guericke-University, 39106 Magdeburg, Germany.
J Neurosci. 2007 Dec 19;27(51):14190-8. doi: 10.1523/JNEUROSCI.4229-07.2007.
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.
通过绩效监测对自身行为进行动态调整是人类执行系统的核心功能，该系统存在相当大的个体差异。来自动物和人类的电生理及神经影像学研究的越来越多的证据表明，多巴胺能系统对绩效监测的调节具有重要意义。在此，我们研究了影响前额叶皮质多巴胺能功能的两种多态性[儿茶酚-O-甲基转移酶（COMT）Val108/158Met和多巴胺D4受体（DRD4）单核苷酸多态性（SNP）-521]对绩效监测神经生理相关性的影响。我们应用了一个经过修改的标准侧翼任务，其中嵌入了停止信号任务，以探究所涉及的不同功能，特别是错误监测、冲突检测和抑制过程。与C纯合子相比，DRD4 T等位基因纯合的参与者在选择错误和抑制失败后产生的错误相关负波增加。这与错误后明显的补偿行为有关，表现为更高的错误后减缓。在不相容性N2中未观察到组间差异，表明DRD4多态性对错误监测过程有独特影响。此外，COMT Val等位基因纯合的参与者，其前额叶多巴胺能水平因此降低，显示出与抑制功能相关的前额叶加工增加，表现为增强的停止信号相关成分N2和P3a。这些结果扩展了先前主要来自行为和神经影像学数据的关于多巴胺能基因与执行功能之间关系的研究发现，并为先前提出的这些多巴胺能多态性与精神疾病如精神分裂症或注意力缺陷多动障碍之间的关联提供了可能的潜在机制。
