Louie Kenneth H, Balakid Jannine P, Bath Jessica E, Song Seongmi, Fekri Azgomi Hamid, Marks Jacob H, Choi Julia T, Starr Philip A, Wang Doris D
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Department of Physical Therapy and Rehabilitation Sciences, University of California, San Francisco, San Francisco, CA, USA.
medRxiv. 2025 Aug 21:2025.08.19.25333759. doi: 10.1101/2025.08.19.25333759.
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.
帕金森病（PD）中的步态功能障碍是致残的主要原因，并且通常对传统的深部脑刺激（DBS）有抵抗性。在此，我们报告一种新型神经调节范式，即步态相位同步自适应DBS（aDBS），它在对侧腿部摆动期间动态调节刺激幅度。在五名帕金森病患者中，我们从皮质和苍白球场电位中识别出步态相位的个性化神经生物标志物，并将它们嵌入到长期植入的双向神经刺激器中。这些通过数据驱动搜索得出的生物标志物能够实时检测摆动相位并对刺激幅度进行亚秒级调节。急性临床测试表明，与临床优化的连续DBS相比，aDBS显著降低了步态变异性并改善了双侧对称性。在一项双盲、多天交叉研究中，步态相位同步aDBS耐受性良好，维持了对一般运动症状的控制，并减少了跌倒次数，改善了其他步态指标。这些发现确立了生物标志物驱动、运动同步神经调节的可行性，并为恢复帕金森病患者的动态运动控制提供了一种有前景的策略。
