Patients with advanced Parkinson's can be treated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). This affords a unique opportunity to record from this nucleus and stimulate it in a controlled manner. Previous work has shown that activity in the STN is modulated in a rhythmic pattern when Parkinson's patients perform stepping movements, raising the question whether the STN is involved in the dynamic control of stepping. To answer this question, we tested whether an alternating stimulation pattern resembling the stepping-related modulation of activity in the STN could entrain patients' stepping movements as evidence of the STN's involvement in stepping control. Group analyses of 10 Parkinson's patients (one female) showed that alternating stimulation significantly entrained stepping rhythms. We found a remarkably consistent alignment between the stepping and stimulation cycle when the stimulation speed was close to the stepping speed in the five patients that demonstrated significant individual entrainment to the stimulation cycle. Our study suggests that the STN is causally involved in dynamic control of step timing and motivates further exploration of this biomimetic stimulation pattern as a potential basis for the development of DBS strategies to ameliorate gait impairments.

SIGNIFICANCE STATEMENT We tested whether the subthalamic nucleus (STN) in humans is causally involved in controlling stepping movements. To this end, we studied patients with Parkinson's disease who have undergone therapeutic deep brain stimulation (DBS), as in these individuals we can stimulate the STNs in a controlled manner. We developed an alternating pattern of stimulation that mimics the pattern of activity modulation recorded in this nucleus during stepping. The alternating DBS (altDBS) could entrain patients' stepping rhythm, suggesting a causal role of the STN in dynamic gait control. This type of stimulation may potentially form the basis for improved DBS strategies for gait.

晚期帕金森氏症患者可通过丘脑底核（STN）的深部脑刺激（DBS）进行治疗。这提供了一个独特的机会来记录该核并以受控方式对其进行刺激。先前的研究表明，当帕金森氏病患者执行踩踏运动时，STN中的活动会以有节奏的方式进行调节，这引发了一个问题，即STN是否参与踩踏的动态控制。为了回答这个问题，我们测试了类似于STN中步进相关活动调节的交替刺激模式是否可以带动患者的步进运动，以此作为STN参与步进控制的证据。对10名帕金森氏病患者（一名女性）进行的小组分析显示，交替刺激显着增强了脚步节奏。当五名患者的刺激速度接近步进速度时，我们发现步进和刺激周期之间存在非常一致的一致性，这五名患者表现出明显的个人夹带刺激周期。我们的研究表明，STN因果关系参与步距计时的动态控制，并促使人们进一步探索这种仿生刺激模式，以此作为开发DBS策略以改善步态障碍的潜在基础。

意义声明我们测试了人的丘脑底核（STN）是否与控制踏步运动有因果关系。为此，我们研究了接受过治疗性深部脑刺激（DBS）的帕金森氏病患者，因为在这些个体中，我们可以以受控方式刺激STN。我们开发了一种交替刺激模式，模仿了步进过程中此核中记录的活动调节模式。交替DBS（altDBS）可能会带动患者的步进节奏，表明STN在动态步态控制中起因果作用。这种刺激可能会构成改善步态DBS策略的基础。