Abstract
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, movementsynchronized neuromodulation and offer a promising strategy to restore dynamic motor control in PD.