Dopaminergic encoding of counterfactual information in human striatum

 描述（由申请人提供）：直接受多巴胺系统影响的疾病和障碍（例如，药物成瘾和帕金森病）突出了这些系统在人类行为和认知动机中的重要性。已知多巴胺系统是正常学习、奖励处理和决策的关键组成部分（综述于Montague等人，2004年）。不幸的是，我们目前对人类大脑中多巴胺系统的了解与啮齿动物和非人类灵长类动物中这些系统的大量实验和计算建模相比相对较少。此前，技术限制限制了对人类大脑的直接实验。该提案利用了我们小组最近的技术创新，该技术创新得到了NIH R21机制（CEBRA：R21 DA 024140）的支持，并成功完成了人类大脑中多巴胺释放的第一次亚秒测量。此外，这些测量发生在由学习和奖励处理的计算模型框架的主动决策任务期间（Kishida等人，2011和Kishida等人，审查中）。我们提出了三个具体的目标，其中联合收割机结合我们的技术进步与主动学习任务，旨在探索多巴胺在人类行为中的作用。我们的目标包括三个学习信号，其中实际和反事实的经验将分别在人类纹状体反应中进行检查。拟议的工作将告知多巴胺在奖励/运动相互作用中有争议的作用。这些实验将对患有帕金森病和原发性震颤的人类的多巴胺系统的功能产生前所未有的洞察力。在NIH（R21 DA 024140）的支持下，我们的团队成功开发了一个完整的原型系统，用于对人脑中多巴胺的传递进行电化学测量。通过在决策任务期间获得帕金森病受试者纹状体中的第一个多巴胺测量值，证明了其可行性。这一实质性的初步工作现在已经准备好进行更大规模的研究，对多巴胺系统在帕金森病、原发性震颤以及人类决策和行为中的作用进行具体的假设检验。

 DESCRIPTION (provided by applicant): Diseases and disorders directly affected by dopamine systems (e.g., drug addiction and Parkinson's disease) highlight the importance of these systems in motivated human behavior and cognition. The dopamine system is known to be a critical component of normal learning, reward processing, and decision-making (reviewed in Montague et al., 2004). Unfortunately, our present knowledge of dopamine systems in human brains is relatively sparse compared to the wealth of experimentation and computational modeling on these systems in rodents and non-human primates. Previously, technological constraints have limited direct experimentation in human brains. This proposal capitalizes on our group's recent technological innovation, which was supported by the NIH R21 mechanism - CEBRA: R21DA024140 - and resulted in the successful completion of the first sub-second measurements of dopamine release in a human brain. Furthermore, these measurements took place during an active decision-making task that was framed by computational models of learning and reward processing (Kishida et al., 2011 and Kishida et al., under review). We propose to pursue three specific aims, which combine our technological advance with active learning tasks designed to probe the role of dopamine in human behavior. Our aims incorporate three learning signals, where actual and counterfactual experience will each be examined in human striatal responses. The proposed work will inform on the controversial role for dopamine in reward/movement interactions. The experiments proposed will yield unprecedented insight into the function of the dopamine system in the humans afflicted with Parkinson's disease and Essential Tremor. With the support of the NIH (R21DA024140), our team successfully developed a complete prototype system for making electrochemical measurements of dopamine delivery in the human brain. Feasibility has been demonstrated by obtaining the first dopamine measurements in the striata of subjects with Parkinson's during a decision-making task. This substantial preliminary work is now ready for a larger scale with specific hypothesis testing about the role of dopamine systems in Parkinson's disease, Essential tremor, and human decision-making and behavior.