Dopamine Effects on Mesocorticolimbic Function in Parkinson Disease

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DESCRIPTION (provided by applicant): Dopamine (DA) therapy used for the treatment of Parkinson Disease (PD) consists of Levodopa and Dopamine receptor Agonist (DAA) medications. In approximately 15-20% of PD patients, a behavioral syndrome known as Impulsive Compulsive Behavior (ICB) can arise. These behaviors are characterized by an increased and compulsive participation in certain behaviors, such as sex, eating, gambling, shopping, and hobbies. DAA use, more so than Levodopa, is associated with this disorder. DAAs preferentially target D2-like receptors (D2/D3 Dopamine receptors), which are expressed in greater number in the mesolimbic and neocortical areas. These behaviors are thus thought to result from alterations to mesocorticolimbic function. It is still unclear why certain patients are susceptible to the development of ICB, what specific alterations to reward-based decision- making underlie the emergence of the disorder, what neuropathological mechanisms in mesocorticolimbic regions account for this vulnerability, and how DA therapy triggers the expression of these behaviors. This proposal details a training and career development plan that will enable the candidate to develop expertise in the use of cognitive science and DA neuroimaging tools in order develop improved treatments for patients with neurodegenerative disorders. This work is a direct extension of the candidate's clinical training and postdoctoral area of research. The Specific Aims of the proposal are: (1) To characterize the elements of reward-motivated decision-making that underlie Impulsive Compulsive Behaviors in Parkinson Disease patients, and (2) To examine D2-like receptors in Parkinson Disease patients with and without Impulsive Compulsive Behaviors. The career training proposal complements the research aims by focusing on developing expertise in cognitive science and neuroimaging. These aims are enhanced by an interdisciplinary mentorship structure with Neurology, Psychology and Neuroradiology, thus providing important expertise in the study of DA function and biology. Also, the opportunities for clinical research are further enhanced by the large clinical population of PD patients at the candidate's institution. Through a combination of specialized classroom learning, external learning opportunities, and utilization of the research environment opportunities, the candidate will translate this expertise into improved treatment and prognosis of patients with PD. Future studies will therefore focus on optimizing cognitive performance in PD patients, providing a basis for improved individualized therapy for patients with PD.