The Role of Dopamine Reward Mechanisms in Motor Control

描述（由申请人提供）： 这个指导项目的主要目标是为成瘾患者的功能性脑成像职业生涯做好准备。培训计划的目的是提高候选人的知识：（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。 第二个目标是在与神经激活相关的血液动力学反应模型中训练候选人，特别是当这种反应表现在功能性磁共振成像（fMRI）信号中时。 第二个训练目标将支持候选人在正电子发射断层扫描信号到功能磁共振成像数据的计算模型方面的工作的扩展。 该研究计划旨在使用计算建模和功能神经成像来研究人类的期望，奖励和运动控制之间的关系。 多巴胺在运动研究中作为奖赏和期望调节剂的作用将成为这些研究的核心组织概念。 通过了解正常情况下多巴胺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兴奋剂如何增强多巴胺的释放，改变运动反应。 因此，候选人将接受关于多巴胺在奖励和成瘾中的作用的教学和实验室培训。 该研究计划确定了四个主要目标来支持训练计划：（1）实现多巴胺奖励机制的计算模型，因为它们与运动控制有关;（2）使用fMRI识别和分离激活模式，因为它们与奖励机制和运动控制有关;（3）实现一种方法，通过该方法，大脑功能的计算模型可以提供类似fMRI的结果;（4）支持收集试点数据，用于设计未来的甲基苯丙胺使用者和对照者的期望和奖励功能神经解剖学研究。 该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，以及研究成瘾的临床方法。 建模组件将导致更好地理解在人类中观察到的分布式功能性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受试者和成瘾患者之间关于奖励的功能激活差异，为成瘾个体奖励机制的未来工作奠定基础。

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.