Evaluation of Targeted Plasticity Therapy as a Treatment for Motor Dysfunction in Parkinson’s Disease

Objective/Rationale:             

Deterioration of motor function is a debilitating symptom of Parkinson’s disease (PD). We have recently developed a novel method that utilizes stimulation of the vagus nerve delivered during rehabilitative training to improve motor function after various types of brain injury. Vagus nerve stimulation (VNS) enhances plasticity, or the ability to change, within neural circuitry that controls movement. We propose to evaluate whether VNS paired with rehabilitative training can improve motor function in pre-clinical models of PD.

Project Description:             

Pre-clinical models will be trained to perform a behavioral task that measures forelimb movement speed. Once they are proficient at the task, each model will receive an injection of 6-OHDA to cause dopaminergic cell loss and impair function of the trained forelimb. Models will undergo implantation of a stimulating cuff around the vagus nerve and be separated into balanced groups. One group will undergo rehabilitative training alone. The second group will undergo identical rehabilitative training, but will also receive stimulation of the vagus nerve paired with training. A third group will undergo identical rehabilitative training, but will receive VNS two hours after the completion of training. For all groups, rehabilitative training will continue for six weeks. We will measure multiple parameters describing forelimb performance throughout the course of testing.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:                     

VNS holds significant promise for treating disease. It is currently FDA-approved for the treatment of epilepsy and depression, and we are testing the therapy for tinnitus and stroke recovery. VNS paired with physical rehabilitation may be sufficient to reorganize neural circuitry controlling movement and restore motor function. If VNS paired with rehabilitative training does result in motor improvements, then a similar implementation may be useful in PD patients.

Anticipated Outcome:          

We expect that VNS paired with rehabilitative training will result in enhanced recovery of forelimb function compared to rehabilitative training alone. Additionally, based on our previous findings, we expect the VNS delivered outside of rehabilitative training sessions will be ineffective at restoring motor function. The outcome of this study will provide initial evidence characterizing the efficacy of VNS with rehabilitation training as a potential therapy for restoring motor function in PD patients.