Wednesday, April 2, 2025
4/2/2025
Neurophysiology of Reward Signaling in Parkinson's Disease - PROJECT SUMMARY Altered reward signaling plays a key role in multiple Parkinson’s disease nonmotor symptoms including depression, apathy, and impulsive and compulsive behaviors. Moreover, therapies for Parkinson’s disease including dopaminergic medication and deep brain stimulation have been associated with both pathologic increases and decreases in reward guided behaviors. Unfortunately, symptoms of altered reward signaling such as depression, apathy, and impulsive and compulsive behaviors lack effective therapies. A better understanding of the neural signaling underlying reward signaling is crucial to developing better treatments for these disorders. This proposal for a mentored clinician scientist research career development award for Dr. Sarah Bick capitalizes on access to human intracranial recordings in neurosurgical procedures to characterize reward signaling neurophysiology in the subthalamic nucleus and dorsolateral prefrontal cortex. Dr. Bick has previously demonstrated that subthalamic nucleus and dorsolateral prefrontal cortex beta power increase during reward and that dorsolateral prefrontal cortex reward related power is associated with depression and apathy. The specific aims of the present study are to 1) characterize neurophysiology correlates of reward signaling in subthalamic nucleus and its connectivity with dorsolateral prefrontal cortex, 2) determine how acute subthalamic nucleus stimulation perturbs reward signaling, and 3) determine how chronic STN stimulation alters reward signaling. Dr. Bick’s long-term goal is to develop improved neuromodulation strategies for cognitive and psychiatric disorders such as Parkinson’s disease nonmotor symptoms. To accomplish this, her objectives during the period of this award are: 1) to develop expertise in advanced computational techniques such as machine learning to apply to neurophysiology analysis, 2) to gain experience with neurophysiology connectivity analysis, and 3) to learn analysis methods for MRI structural connectivity. VUMC is the ideal environment to foster her development into an independent investigator studying the neurophysiology of cognitive and psychiatric processes in order to develop novel neuromodulation techniques. The environment includes a strong team of NIH funded mentors and advisors with expertise in neurophysiology, advanced computational techniques, structural connectivity, engineering, and Parkinson’s disease, a high clinical volume of the patient population needed to recruit study subjects, and strong institutional resources to support career development of physician scientists. The project will thus provide a platform for Dr. Bick to establish preliminary data and critical research skills to launch an independent research career.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).