Deep brain stimulation (DBS) is a widely used therapy for Parkinson’s disease (PD) but lacks dynamic responsiveness to changing clinical and neural states. Feedback control might improve therapeutic effectiveness, but the optimal control strategy and additional benefits of ‘adaptive’ neurostimulation are unclear. Here we present the results of a blinded randomized cross-over pilot trial aimed at determining the neural correlates of specific motor signs in individuals with PD and the feasibility of using these signals to drive adaptive DBS. Four male patients with PD were recruited from a population undergoing DBS implantation for motor fluctuations, with each patient receiving adaptive DBS and continuous DBS. We identified stimulation-entrained gamma oscillations in the subthalamic nucleus or motor cortex as optimal markers of high versus low dopaminergic states and their associated residual motor signs in all four patients. We then demonstrated improved motor symptoms and quality of life with adaptive compared to clinically optimized standard stimulation. The results of this pilot trial highlight the promise of personalized adaptive neurostimulation in PD based on data-driven selection of neural signals. Furthermore, these findings provide the foundation for further larger clinical trials to evaluate the efficacy of personalized adaptive neurostimulation in PD and other neurological disorders. ClinicalTrials.gov registration: NCT03582891.

深部脑刺激 （DBS） 是一种广泛使用的帕金森病 （PD） 疗法，但缺乏对不断变化的临床和神经状态的动态响应。反馈控制可能会提高治疗效果，但最佳控制策略和 “适应性 ”神经刺激的额外好处尚不清楚。在这里，我们介绍了一项盲法随机交叉试点试验的结果，该试验旨在确定 PD 个体特定运动体征的神经相关性以及使用这些信号驱动自适应 DBS 的可行性。从接受 DBS 植入运动波动的人群中招募了 4 名男性 PD 患者，每位患者接受适应性 DBS 和连续 DBS。我们确定了丘脑底核或运动皮层中夹带的 γ 振荡是所有 4 例患者高多巴胺能状态与低多巴胺能状态及其相关残余运动体征的最佳标志物。然后，我们证明与临床优化的标准刺激相比，适应性刺激改善了运动症状和生活质量。这项试点试验的结果突出了基于数据驱动的神经信号选择在 PD 中个性化适应性神经刺激的前景。此外，这些发现为进一步更大规模的临床试验提供了基础，以评估个性化适应性神经刺激对 PD 和其他神经系统疾病的疗效。ClinicalTrials.gov 注册：NCT03582891。