Study Rationale:
People with Parkinson's disease have long been known to display remarkable motor abilities under special circumstances such as smooth walking with certain visual or auditory cues. This phenomenon is called paradoxical kinesia. In addition, placebos can be surprisingly effective in treating the motor signs of the disease. We hypothesize that a specific neuroanatomical substrate supports paradoxical kinesia and the placebo effect. We plan to define this substrate 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 best animal model of Parkinson’s disease. 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 human subjects affected by the disease 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 re-shape paradigms for therapeutic development and attempts to influence disease progression. Importantly, our results have the potential to use 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 patients. Our research could lead to new targets for deep brain stimulation (DBS) and more accurate placement of DBS electrodes.