The impact of catechol-O-methyltransferase and dopamine D4 receptor genotypes on neurophysiological markers of performance monitoring
The impact of catechol-O-methyltransferase and dopamine D4 receptor genotypes on neurophysiological markers of performance monitoring
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DOI：
10.1523/jneurosci.4229-07.2007
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发表时间：
2007-12-19
影响因子：
5.3
通讯作者：
Muente, Thomas F.
中科院分区：
文献类型：
--
作者：
Kraemer, Ulrike M.;Cunillera, Toni;Muente, Thomas F.
通过行为监控对行为进行动态调整是人类执行系统的一个核心功能，它是个体间差异的基础。从动物和人类的电生理和神经影像学研究中获得的证据表明，多巴胺能系统对性能监测的调节具有重要意义。在这里，我们研究了影响前额叶皮层多巴胺能功能的两种多态性[儿茶酚-O-甲基转移酶（COMT）Val 108/158 Met和多巴胺D4受体（DRD 4）单核苷酸多态性（SNP）-521]对性能监测的神经生理学相关性的影响。我们应用了一个标准的侧翼任务的修改版本，嵌入停止信号任务，以挖掘所涉及的不同功能，特别是错误监控，冲突检测和抑制过程。与C纯合子相比，DRD 4 T等位基因纯合子的参与者在选择错误和抑制失败后产生了增加的错误相关负性。这与明显的补偿行为有关，反映在更高的错误后减慢。在不相容性N2中没有观察到组差异，表明DRD 4多态性对错误监测过程的不同影响。此外，参与者纯合子的COMT瓦尔等位基因，从而减少前额叶多巴胺能水平，揭示了增加前额叶处理相关的抑制功能，反映在增强的停止信号相关的组件N2和P3 a。这些结果扩展了以前的研究结果，主要是从行为和神经影像学数据多巴胺能基因和执行功能之间的关系，并提出了可能的潜在机制，以前建议这些多巴胺能基因多态性和精神疾病之间的关联精神分裂症或注意缺陷多动障碍。
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.