MRC Brain Network Dynamics Unit, University of Oxford, Oxford OX1 3TH, United Kingdom
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, United Kingdom.
J Neurosci. 2020 Nov 11;40(46):8964-8972. doi: 10.1523/JNEUROSCI.1767-20.2020. Epub 2020 Oct 21.
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. 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.
患有晚期帕金森病的患者可以通过丘脑底核(STN)的深部脑刺激(DBS)进行治疗。这为从该核记录和以受控方式刺激它提供了独特的机会。以前的工作表明,当帕金森病患者进行踏步运动时,STN 的活动以节律模式进行调制,这提出了 STN 是否参与踏步运动的动态控制的问题。为了回答这个问题,我们测试了一种类似于 STN 活动与踏步相关的调制的交替刺激模式是否可以使患者的踏步运动同步,作为 STN 参与踏步控制的证据。对 10 名帕金森病患者(一名女性)的组分析表明,交替刺激显着同步踏步节律。当刺激速度接近在对刺激周期有显著个体同步作用的五名患者中的踏步速度时,我们发现踏步和刺激周期之间存在惊人的一致对准。我们的研究表明,STN 因果关系地参与了步时的动态控制,并促使进一步探索这种仿生刺激模式作为改善步态障碍的 DBS 策略的潜在基础。我们测试了人类的丘脑底核(STN)是否因果关系地参与控制踏步运动。为此,我们研究了接受治疗性深部脑刺激(DBS)的帕金森病患者,因为在这些个体中,我们可以以受控的方式刺激 STN。我们开发了一种交替刺激模式,模仿在踏步期间记录的该核中的活动调制模式。交替 DBS(altDBS)可以使患者的踏步节奏同步,这表明 STN 在动态步态控制中起因果作用。这种类型的刺激可能有可能成为改善步态的 DBS 策略的基础。