The Role of Dopamine Reward Mechanisms in Motor Control

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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.