Aversive motivation and cognitive control

 描述(由申请者提供)：调整行为和认知以满足不断变化的环境需求是优化福祉的关键。以前的研究已经发现，神经调节剂多巴胺在调节认知灵活性方面发挥着重要作用，特别是它对纹状体的影响，即灵活更新工作记忆和相关目标的内容的能力。纹状体多巴胺系统的变异性与认知灵活性的改变有关，事实上，包括注意力缺陷障碍、帕金森病、精神分裂症和药物成瘾在内的各种神经精神障碍的特征都是多巴胺能神经传递和认知控制的异常。重要的是，欲望动机和厌恶动机被认为分别阶段性地增加和减少纹状体中多巴胺的释放，从而增加了动机背景可能以不同方式影响认知控制过程的可能性。近期 研究表明，奖励动机提高了认知灵活性，但仅限于纹状体多巴胺基线水平较高的个人。考察厌恶动机对认知控制的影响的研究要有限得多；在一项研究中，惩罚的威胁与工作记忆内容的更新减少有关，这表明厌恶动机可能会使个人偏离认知灵活性，转向认知稳定性。然而，到目前为止，还没有工作明确地研究基线多巴胺系统功能在调节厌恶动机对认知控制过程或支持它们的额纹状体回路的影响中所起的作用。通过利用已知的影响纹状体多巴胺系统的基因变异，并使用有针对性的精神药理学干预，拟议的fMRI实验试图通过检测纹状体多巴胺变异对面对厌恶动机时大脑激活模式和认知灵活性的影响来填补这一空白。这项研究的第二个目的是描述缰核在调节厌恶动机环境对认知控制过程的影响中的作用。缰核是上皮层的一个小区域，最近被发现参与抑制纹状体DA的释放以应对潜在的惩罚；如果厌恶动机导致纹状体DA的抑制影响支持认知灵活性的前额纹状体回路，缰核可能提供动机和认知控制之间的关键联系。总之，这项拟议的研究将扩大我们对神经生物学机制的了解，这些机制可能会导致动机和认知之间的关系中的个体差异。此外，这项工作的结果可能有助于我们理解以DA神经传递异常为特征的神经精神障碍中的认知控制异常，以及治疗性和非法药物使用对认知控制方面的影响。

 DESCRIPTION (provided by applicant): Adapting behavior and cognition to meet changing environmental demands is critical for optimizing wellbeing. Previous research has identified an important role for the neuromodulator dopamine, particularly with respect to its effects on the striatum, in regulating cognitive flexibility, that is, the ability to flexibly update the contentsof working memory and relevant goals. Variability in the striatal dopamine system has been associated with alterations in cognitive flexibility, and indeed, a variety of neuropsychiatric disorders including attentional deficit disorder, Parkinson's disease, schizophrenia, and drug addiction are characterized by abnormalities in both dopaminergic neurotransmission and cognitive control. Importantly, both appetitive and aversive motivation are thought to phasically increase and decrease, respectively, the release of dopamine into the striatum, thus raising the possibility that motivational context may differentially impact cognitive control processes. Recent work has demonstrated that reward motivation increases cognitive flexibility, but only in individuals with higher baseline levels of striatal dopamine. Research examining the impact of aversive motivation on cognitive control has been much more limited; in one study, threat of punishment was associated with reduced updating of working memory content, suggesting that aversive motivation may bias individuals away from cognitive flexibility and toward cognitive stability. However, to date, no work has explicitly examined the role of baseline dopamine system function in mediating the influence of aversive motivation on cognitive control processes or the frontostriatal circuitry that supports them. By exploiting genetic variants known to impact the striatal dopamine system, and using a targeted psychopharmacological intervention, the proposed fMRI experiment seeks to fill this gap by examining the effect of striatal dopamine variability on patterns of brain activation and cognitive flexibility in the face of aversive motivation. A second aim of the proposed research is to characterize the role of the habenula in moderating the impact of an aversive motivational context on cognitive control processes. The habenula is a small region of the epithalamus that has recently been implicated in inhibiting striatal DA release in response to potential punishment; if inhibition of striatal DA resulting fro aversive motivation impacts the frontostriatal circuitry supporting cognitive flexibility, the habenula may provide a critical linkage between motivation and cognitive control. Together, the proposed research will expand our knowledge of the neurobiological mechanisms that may contribute to individual differences in the relation between motivation and cognition. Further, results of this work may inform our understanding of cognitive control abnormalities in neuropsychiatric disorders characterized by aberrant DA neurotransmission and of the impact of both therapeutic and illicit drug use on aspects of cognitive control.