The Role of Dopamine Reward Mechanisms in Motor Control

描述(由申请人提供)： 这个有指导的项目的主要目标是为成瘾患者的脑功能成像职业生涯做好准备。培训计划的目的是增强候选人的知识：(1)成瘾的神经生物学，(2)临床驱动的成瘾模型，(3)成瘾评估的临床和行为方法。第二个目标是训练候选人与神经激活相关的血流动力学反应的模型，特别是当这种反应在功能磁共振成像(FMRI)信号中表现出来的时候。次级培训目标将支持候选人将正电子发射断层扫描信号计算模型的工作扩展到功能磁共振成像数据。这项研究计划旨在使用计算建模和功能神经成像来检查人类的期望、回报和运动控制之间的关系。在运动研究中，多巴胺作为奖赏和期望的调节器的作用将是这些研究的核心组织概念。通过了解多巴胺在正常情况下对认知和运动行为的影响，人们可以更好地了解成瘾性精神运动兴奋剂是如何改变运动反应的，这种兴奋剂促进了多巴胺的释放。因此，候选人将接受关于多巴胺在奖赏和成瘾中的作用的教学和实验室培训。该研究提案确定了支持训练计划的四个主要推动力：(1)实施与运动控制有关的多巴胺奖励机制的计算模型；(2)利用功能磁共振成像识别并分离与奖励机制和运动控制有关的激活模式；(3)实施一种方法，使大脑功能的计算模型能够提供类似fMR1的结果；(4)支持收集飞行员数据，用于设计未来对甲基苯丙胺使用者和对照组的期望和奖励的功能神经解剖学研究。这项提案中概述的研究将提供设计和分析功能磁共振成像和运动学数据的培训，以及调查成瘾的临床方法。建模部分将有助于更好地理解在人类中观察到的分布式功能大脑系统与主要从动物研究中获得的神经生理学数据之间的关系。这项研究和培训将通过建立控制组和成瘾患者在奖赏方面的功能激活差异，为未来成瘾个体奖赏机制的工作奠定基础。

DESCRIPTION (provided by applicant): The primary goal of this mentored project is to prepare the candidate for a career in functional brain imaging of addicted patients. The purpose of the training plan is to enhance the candidate's knowledge of: (1) the neurobiology of addiction, (2) clinically driven models of addiction, and (3) clinical and behavioral methods of addiction assessment. A secondary goal is to train the candidate in models of the hemodynamic response associated with neural activation, especially as this response is manifested in functional magnetic resonance imaging (fMRI) signals. The secondary training goal will support the extension of the candidate's work in computational models of positron emission tomography signals to fMRI data. The research plan aims to examine the relationships among expectation, reward, and motor control in humans using both computational modeling and functional neuroimaging. The role of dopamine as a modulator of reward and expectation in motor studies will be a core organizing-concept for these studies. By understanding dopamine's influence upon cognitive and motor behavior under normal circumstances, one can gain a better understanding of how addictive psychomotor stimulants, which enhance dopamine's release, alter motor response. Thus the candidate will receive both didactic and laboratory training in the role of dopamine in reward and addiction. The research proposal identifies four main thrusts to support the training plan: (1) implement a computational model of dopamine reward mechanisms as they relate to motor control; (2) identify and dissociate activation patterns as they relate to reward mechanisms and motor control using fMRI; (3) implement a methodology by which computational models of brain function can provide fMRl-like results; (4) support the collection of pilot data to be used to design a future study of the functional neuroanatomy of expectation and reward in methamphetamine users and controls. The research outlined in this proposal will provide training in the design and analysis of fMRI and kinematic data, and clinical methods to investigate addiction. The modeling component will lead to better understanding of the relationship between distributed functional brain systems observed in humans and neurophysiological data obtained primarily from animal studies. This research and training will form the foundation for future work in reward mechanisms of addicted individuals by establishing functional activation differences between control subjects and addicted patients with respect to reward.