The impact of exercise on subthalamic nucleus neural activity in Parkinson's disease

项目摘要/摘要 帕金森氏病(PD)是增长最快的神经系统疾病，甚至超过了阿尔茨海默病。 有氧运动被普遍认为是帕金森病治疗中不可或缺的一部分，尤其是静态自行车 已经被认为是帕金森氏症患者的理想锻炼方式。我们开创性的双人自行车研究 是第一个在人类帕金森病患者中使用强迫运动(FE)的人，并证明在 临床评分与自选率的自愿锻炼(VE)的比较。铁是一种高强度的模式 有氧运动起源于帕金森病动物模型，在该动物模型中，运动的自愿性踏板速度(节奏) 是增强的，但不是替换的。有氧运动，包括FE，已经显示出作为一种疾病的潜力-- 修改干预措施；然而，为了真正检查疾病修改，作用机制必须 被评估。基底节内运动回路的超同步性与主要运动体征有关 如帕金森病患者的运动迟缓、震颤和僵硬。最近使用FE进行的动物研究评估 初级运动皮质(M1)的局部场电位(LFP)，并报告神经衰减 贝塔(13-35赫兹)频段的超同步性与运动功能的改善有关。到目前为止， 基底节的神经活动已被分离到动物模型或高度侵入性的人类研究中。 大脑深部刺激器(DBS)的导线已经外部化。近年来，DBS技术在中国的进展 人类首次允许从丘脑底核(STN)直接记录神经活动。 植入美敦力Percept DBS系统的个体的基底节。该项目旨在记录 帕金森病患者在FE和VE两种模式下STN的神经活动。我们的基础 假说是，高强度运动降低了STN的超同步性，从而促进了皮层-基底 神经节丘脑皮质回路功能，从而改善运动后的运动功能。 15名之前使用Percept系统接受过DBS手术的PwPD将完成一次 在停用抗帕金森病药物的同时，进行固定周期的FE和VE锻炼。双侧神经活动 将连续记录STN的总时间约130分钟(运动前、FE或VE期间 和运动后)在两个单独的日子。MDS-UPDRS III运动测试与上肢握力 跟踪范式将被用来确定运动对运动的反应。虽然我们希望在以下方面有所改进 在单次FE和VE之后，β频段活动的性能和衰减，假设 由于更高的骑行节奏导致更大的贝塔衰减，FE将体验到更好的结果。

PROJECT SUMMARY/ABSTRACT Parkinson’s disease (PD) is the fastest growing neurological disease, outpacing even Alzheimer’s disease. Aerobic exercise is universally accepted as an integral part of PD treatment, and stationary cycling in particular has been suggested to be an ideal exercise modality for people with PD. Our seminal tandem cycling study was the first to utilize forced exercise (FE) in human PD patients and demonstrate a 30% improvement in clinical ratings compared to voluntary exercise (VE) at a self-selected rate. FE is a mode of high intensity aerobic exercise originating in animal models of PD in which the voluntary pedaling rate (cadence) of exercise is augmented, but not replaced. Aerobic exercise, including FE, has demonstrated potential as a disease- modifying intervention; however, in order to truly examine disease-modification, the mechanism of action must be evaluated. Hypersynchrony of motor circuits within the basal ganglia is associated with cardinal motor signs such as bradykinesia, tremor, and rigidity in individuals with PD. Recent animal studies using FE evaluated local field potentials (LFP) from the primary motor cortex (M1) and reported an attenuation of neural hypersynchrony in the beta (13-35Hz) frequency band associated with improved motor function. Until now, neural activity from the basal ganglia has been isolated to animal models or highly invasive human studies where the deep brain stimulator (DBS) wires have been externalized. Recently, advances in DBS technology in humans allows, for the first time, direct neural activity recording from the subthalamic nucleus (STN) of the basal ganglia in individuals implanted with the Medtronic Percept DBS system. This project aims to record neural activity from the STN during two modes, FE and VE, in individuals with PD. Our underlying hypothesis is that high intensity exercise reduces STN hypersynchrony which facilitates cortico-basal ganglia thalamocortical circuit functionality thereby improving motor function following exercise. Fifteen PwPD who have previously undergone DBS surgery utilizing the Percept system will complete a single FE and VE exercise session on a stationary cycle while off antiparkinsonian medication. Bilateral neural activity of the STN will be continuously recorded for approximately 130 minutes total (pre-exercise, during FE or VE and post-exercise) on two separate days. The MDS-UPDRS III Motor Exam and an upper extremity grip force tracking paradigm will be used to determine motor response to exercise. While we expect improvements in performance and attenuation in beta band activity following a single bout of FE and VE, it is hypothesized that FE will experience superior results due to the higher cycling cadence resulting in greater beta attenuation.