The Michael J. Fox Foundation for Parkinson's Research

The Michael J. Fox Foundation for Parkinson's Research is using its 2020 distribution to fund:

PROJECT TITLE: Using adaptive deep brain stimulation for gait re-training in Parkinson’s Disease

Investigator/Author: Doris Wang, MD, PhD (PI); Philip Starr, MD, PhD (co-PI), Simon Little, MBBS, PhD (co-PI); Coralie de Hemptinne (co-PI)

Objective: Patients undergoing deep brain stimulation (DBS) surgery for treatment of their PD will be implanted with an electrode spanning the striatum and the conventional therapeutic target (the pallidum). This electrode will be connected to a specialized DBS device that can record neural signals in addition to providing therapeutic stimulation. We will record brain activities from the striatum and pallidum while patients engage in a task where they learn a sequence of steps. We will then test whether stimulation of the striatum during different parts of walking can improve learning of these step sequences.

Background: Our hypothesis is that electrical stimulation of the pallidum during different phases of the walking cycle can enhance the walking functions in patients with PD.

Methods/Design: Patients undergoing deep brain stimulation (DBS) surgery for treatment of their PD will be implanted with an electrode spanning the striatum and the conventional therapeutic target (the pallidum). This electrode will be connected to a specialized DBS device that can record neural signals in addition to providing therapeutic stimulation. We will record brain activities from the striatum and pallidum while patients engage in a task where they learn a sequence of steps. We will then test whether stimulation of the striatum during different parts of walking can improve learning of these step sequences.  

Relevance to Diagnosis/Treatment of Parkinson’s Disease: This study will allow us to define and test individualized stimulation parameters to improve the effect of gait rehabilitation in patients with Parkinson’s disease. This novel strategy has the potential to address the critical need for improving gait in Parkinson’s disease.

Positive results from this study will allow us to test these novel individualized stimulation strategies in a larger clinical trial to measure gait improvements over traditional DBS therapy. Eventually, we hope to make these novel stimulation strategies standard of care for treating gait disturbances in PD.

October 2021 Project Update:

Human locomotion is a complex task requiring rhythmic control of muscle activity and postural adjustments to the environment. Currently, the neural dynamics underlying locomotion are poorly understood. Here we recorded neural activity using a bidirectional neural stimulator (Summit RC+S) in Parkinson’s disease individuals while they are walking overground. We found gait related changes in the neural signal. In most cases, the changes coincided when one of the heels strikes the ground. However, some recordings showed changes coinciding with toe lift off as the leg swings forward. Classification algorithms used to determine left from right heel strikes were built and achieved a median accuracy of 60% with some models achieving near perfect accuracy at 93%. The pipeline developed for this analysis will be used in the adaptive deep brain stimulation study. As of July, we have received both FDA IDE and UCSF IRB approval. Two potential study candidates have been contacted. One has declined, and the other was excluded for medical reasons. While we continue to recruit for the adaptive stimulation study, we will be collecting gait data in other patients implanted with the RC+S device at UCSF.