Gait dysfunction in Parkinson’s disease (PD) is a major source of disability and is often resistant to traditional deep brain stimulation (DBS). Here, we report a novel neuromodulation paradigm, gait-phase-synchronized adaptive DBS (aDBS), that dynamically modulates stimulation amplitude during contralateral leg swing. In five individuals with PD, we identified personalized neural biomarkers of gait phase from cortical and pallidal field potentials and embedded them into a chronically implanted bidirectional neurostimulator. These biomarkers, derived via a data-driven search, enabled real-time detection of swing phase and sub-second modulation of stimulation amplitude. Acute in-clinic testing showed that aDBS significantly reduced gait variability and improved bilateral symmetry compared to clinically optimized continuous DBS. In a double-blinded, multi-day crossover study, gait-phase-synchronized aDBS was well-tolerated, maintained general motor symptom control, and reduced falls and improved other gait metrics. These findings establish the feasibility of biomarker-driven, movement-synchronized neuromodulation and offer a promising strategy to restore dynamic motor control in PD.

D.D.W. consults for Medtronic, Boston Scientific, and Iota Bioscience, and research support from Boston Scientific. P.A.S. receives support from Medtronic and Boston Scientific for fellowship education. K.H.L, J.P.B., J.E.B., S.S, J.H.M., H.F.A., and J.T.C declare no competing interests.

NCT04675398

This study was supported by the Michael J Fox Foundation Grant MNS135499A, the UCSF Burroughs Wellcome Fund Career Award for Medical Scientist, and National Institute of Neurological Disorders and Stroke (NIH/NINDS) 1R01NS130183. This study was also partially supported by UCSF Catalyst Grants. All funding above was obtained by D.D.W. The OpenMind consortium, which provided software to interact with the investigational device and process the raw data, was funded by NINDS U24 NS113637 (to P.A.S).

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