Understanding Freezing of Gait Using Brain Signals and Virtual Reality

Leveraging Invasive Recordings and Immersive Virtual Reality to Characterize Freezing of Gait Mechanisms in Parkinson Disease

Freezing of gait - the inability to start or continue walking - is a particularly disabling problem in Parkinson's disease that has few treatment options. This project records human brain activity from deep brain stimulation (DBS) devices during walking and freezing of gait episodes to understand the pathophysiology of freezing of gait. Findings will lay the foundation for the development of new treatment strategies that address this disabling symptom.

The pathophysiology of FOG is poorly understood, likely contributing to disappointing results of novel neuromodulation strategies. The goal of this study is to identify electrophysiological mechanisms of FOG that can serve as biomarkers for novel neuromodulation strategies. Activity in the globus pallidus internus (GPi), the major output nucleus of the basal ganglia, is central to understanding basal ganglia contributions to gait impairment, as it provides insights into activity that downstream locomotor circuits read out from the basal ganglia. The project leverages a state-of-the-art multimodal brain/behavior recording platform and recent advances in sensing deep brain stimulation devices to record neural activity from the human GPi simultaneously with electroencephalography (EEG), motion capture and eye gaze during over-ground walking and FOG episodes in PD patients with and without FOG. To reliably elicit FOG episodes and improve external validity, the investigators implement a novel immersive virtual reality environment to recapitulate real-world scenarios that commonly trigger FOG. With these tools, the proposed studies will determine how gait-related neural oscillations in the beta (12-30 Hz) and theta/alpha (4-12 Hz) bands in the GPi and cortex relate to abnormal gait during continuous walking (Aim 1); the onset and recovery from FOG episodes (Aim 2); and the therapeutic benefits from external cues (Aim 3). This paves the way for multiple innovative neuromodulation strategies that (1) prevent FOG episodes by promoting normal or compensatory gait control during continuous walking and (2) ameliorate severity of FOG episodes by targeting signals associated with FOG onset and recovery. Additionally, it establishes a novel VR paradigm for future precision-medicine approaches to FOG therapeutic development.

Inclusion Criteria:

• Patients meeting the MDS clinical diagnostic criteria for Parkinson's disease who are implanted with a Medtronic Percept DBS Device and SenSight Directional Leads in bilateral globus pallidus internus (GPi).
• Able to walk unassisted indoors
• Age 18 or older
• Half of patients will have disabling freezing of gait as defined by freezing more than once per day by self-report on questions 1 & 2 of the New Freezing of Gait Questionnaire
• The other half of patients will not have freezing of gait as defined by self-report on question 1 of the New Freezing of Gait Questionnaire

Exclusion Criteria:

• Clinical diagnosis of dementia or severe cognitive impairment (MOCA < 21)
• History of stroke, traumatic brain injury, or other neurologic disorders besides Parkinson's disease
• Comorbidities causing severe gait impairments
• Unstable medical condition including cardio-vascular instability in the past 6 months
• Unable or unwilling to comply with the testing protocol