Study Rationale: People with Parkinson's disease (PD) have long been known to display remarkable motor abilities under special circumstances, such as situations that involve strong emotions or stress, a phenomenon known as paradoxical kinesia. In addition, placebos can be surprisingly effective in treating the motor signs of the disease. We hypothesize that a specific neuroanatomical circuit within the basal ganglia, a brain region that controls movement, supports paradoxical kinesia and the placebo effect. We plan to define this network and investigate its functional organization.
Hypothesis: We hypothesize that a specific neural circuit supports paradoxical kinesia and the placebo effect.
Study Design: We will use cutting-edge techniques to reveal the two distinct brain circuits that enable the basal ganglia to influence the control of voluntary movement in primates. Next, we will record the electrical and chemical activity of basal ganglia neurons in the most appropriate preclinical model of PD. In addition, we will determine the molecular signatures of basal ganglia neurons that are affected by the disease and those that are left intact. Finally, we will image neural activity in people with PD to determine the full range of strategies that could be used to improve basal ganglia function.
Impact on Diagnosis/Treatment of Parkinson’s disease: Our results could reshape paradigms for therapeutic development and attempts to influence PD progression. Importantly, our results have the potential to identify and recruit basal ganglia circuits that are untouched by the disease to promote recovery of more normal motor function.
Next Steps for Development: The results from this project could be translated directly into new treatments for people with PD. Our research could lead to new targets for deep-brain stimulation (DBS) and more accurate placement of DBS electrodes.