PROJECT SUMMARY/ ABSTRACT The long-term goal of this project is to understand the cortical-basal ganglia network activities that are involved with human gait control, and reveal the abnormalities in this circuit that underlie gait disorders in patients with Parkinson’s disease (PD). Human gait is a complex motor task that requires the flexible coordination of both cortical and subcortical structures within the brain. However, the neural encoding for gait initiation, continuous rhythmic walking, and gait adaptation is largely unknown due largely to methodological constraints. Decoding the neural control of gait is not only important for understanding a fundamental human behavior, but is also important for developing novel neuromodulation paradigms to treat gait problems in PD. We propose to study the neurophysiology of human gait control by capturing simultaneous local field potentials from bilateral motor cortex and globus pallidus interna (GPi) of ten PD patients implanted with bidirectional sensing and stimulating devices. We plan to decode the cortical and pallidal neural activities that underlie effective and abnormal gait initiation, continuous walking, and gait modification under different medication states and stimulation cycles in the naturalistic environment in addition to the laboratory setting. Our working model is that continuous gait is generated by rhythmic low frequency fluctuations—theta (4-8Hz), alpha (8-12Hz), and beta oscillations (13-30Hz) in the GPi and does not require much cortical input except periodic beta desynchronization required to disinhibit the motor cortex. Motor cortical involvement is greater during gait initiation and gait adaptation, where top-down cortical command is necessary to modify basal ganglia activities to maintain postural balance. We theorize that in PD, where increased beta synchrony throughout the motor system is associated with an akinetic state, gait impairments are caused by this excessive cortical-pallidal synchronization and disrupt the dynamic and transient synchronization required for normal gait. To test this hypothesis, we will study gait initiation (Aim 1) in the laboratory setting under different medication and stimulation conditions, continuous locomotion (Aim 2) both in the laboratory setting and in the home setting to capture dynamic changes of gait in the naturalistic setting, and a visually guided gait adaptation task (Aim 3) under different medication and stimulation conditions in the laboratory. The impact of this study will be 1) perform the first chronic network analysis of human gait using cortical and pallidal recordings, 2) investigate the human brain activities underlying walking in the natural environment, and 3) provide a conceptual framework for understanding the mechanism of supraspinal network control of gait and pathophysiology of gait impairments in PD.