Neurophysiology of locomotor adaptation and freezing of gait in Parkinson's Disease

Freezing of gait (FoG) is a common symptom in Parkinson’s disease (PD), characterized by a sudden reduction in forward stepping movement, leading to falls and reduced quality of life. The combination of FoG and difficulties in adapting walking patterns to different situations further increases the risk of falls in PD, highlighting a critical need for improved understanding and strategies to alleviate these gait impairments. This project aims to understand the neural mechanisms underlying locomotor adaptation deficits in PD with FoG. We will study neural activity in the globus pallidus internus (GPi), the major basal ganglia output center, using novel deep brain stimulation (DBS) technology with recording capabilities during treadmill walking in PD. We posit that abnormal neural oscillations in the GPi disrupts the regulation of human walking, and we hypothesize that an increase in 13-30 Hz oscillatory activity may lead to locomotor adaptation deficits in PD with FoG. The proposed studies will include 60 PD patients implanted with GPi-DBS, 20 of whom will have the Medtronic Percept PC capable of recording local field potential (LFPs). Locomotor adaptation will be studied using a split-belt treadmill paradigm, consisting of baseline (1:1 speed ratio), split-belt adaptation (2:1) and post-adaptation (1:1) walking. The experiments will be performed under DBS ON and DBS OFF conditions. We will capture joint kinematics and electromyography (EMG) to characterize locomotor adaptation deficits and various types of FoG manifestation. GPi LFP recordings will be aligned with motion capture and EMG data. Aim 1 will identify GPi LFP oscillations related to locomotor adaptation deficits and FoG in PD. Aim 2 will determine whether GPi-DBS facilitates split- belt walking adaptation in PD. This work has theoretical and translational significance because the outcomes will provide new scientific knowledge regarding the role of pallidal neural activity in human walking adaptation, and identify new strategies to mitigate locomotor adaptation deficits associated with FoG in PD. Project Number: 1R21AG088600-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Julia Choi | Institution: UNIVERSITY OF FLORIDA, GAINESVILLE, FL | Award Amount: $405,045 | Activity Code: R21 | Study Section: Musculoskeletal Rehabilitation Sciences Study Section[MRS] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R21AG08860001A1