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

运动对帕金森病丘脑底核神经活动的影响

基本信息

批准号：
10538708
负责人：
JAY L. ALBERTS
金额：
$ 20.13万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10538708
关键词：
Aerobic Exercise Affect Alzheimer&apos s Disease Animal Model Animals Antiparkinson Agents Basal Ganglia Bilateral Blinded Bradykinesia Brain Clinical Deep Brain Stimulation Development Disease Disease Management Disease Progression Dopamine Elderly Electrodes Exercise Exercise Physiology Exhibits Frequencies Human Implant Individual Intervention Long-Term Effects Modification Motor Motor Cortex Movement Disorder Society Unified Parkinson&apos s Disease Rating Scale Multi-Institutional Clinical Trial Neurons Neurosciences Operative Surgical Procedures Parkinson Disease Pathway interactions Patients Pattern Performance Persons Pharmaceutical Preparations Recommendation Records Reporting Rest Seminal Stream Structure Structure of subthalamic nucleus Symptoms System Technology Time Tremor Upper Extremity Work attenuation clinical outcome measures deep brain stimulator exercise intensity experience grasp insight mode of exercise motor function improvement motor symptom nervous system disorder neural patterning relating to nervous system response simulation

项目摘要

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.

项目概要/摘要帕金森病 (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的一个组成部分，尤其是固定自行车我们的开创性串联自行车研究被认为是帕金森病患者的理想锻炼方式。是第一个在人类 PD 患者中使用强迫运动 (FE) 的公司，并证明其改善了 30% 与自行选择速率的自愿运动 (VE) 相比，临床评级是一种高强度模式。有氧运动起源于 PD 动物模型，其中运动的自愿踩踏频率（节奏）有氧运动（包括 FE）已被增强，但并未被取代，已被证明具有作为一种疾病的潜力。改变干预措施；然而，为了真正检查疾病改变，作用机制必须基底神经节内运动回路的超同步性与主要运动体征相关。例如最近使用 FE 评估的动物研究显示帕金森病患者的运动迟缓、震颤和僵硬。来自初级运动皮层 (M1) 的局部场电位 (LFP) 并报告了神经衰减 β（13-35Hz）频段的超同步与改善的运动功能相关。基底神经节的神经活动已被分离到动物模型或高度侵入性的人体研究中最近，深部脑刺激器（DBS）线已被外部化，DBS 技术取得了进展。人类首次允许从丘脑底核（STN）直接记录神经活动该项目旨在记录植入 Medtronic Percept DBS 基础系统的个体的神经节。 PD 患者在 FE 和 VE 两种模式下 STN 的神经活动。假设是高强度运动会降低 STN 超同步性，从而促进皮质基底节神经节丘脑皮质回路功能改善，从而改善运动后的运动功能。之前使用 Percept 系统接受过 DBS 手术的 15 名残疾人士将完成一项单次手术 FE 和 VE 在停止抗帕金森病药物的情况下进行固定循环锻炼。 STN 的记录将持续记录总计约 130 分钟（运动前、FE 或 VE 期间）和运动后）分别进行两天的 MDS-UPDRS III 运动检查和上肢握力测试。跟踪范式将用于确定对运动的运动反应，同时我们预计会有所改进。在单次 FE 和 VE 后，β 频段活动的表现和衰减，据赛跑由于更高的骑行节奏导致更大的 beta 衰减，FE 将获得优异的结果。