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

• 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
• 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' 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' 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

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.

项目总结/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PD治疗的一个组成部分，特别是固定自行车 被认为是PD患者的理想运动方式。我们开创性的双人自行车研究 是第一个在人类PD患者中使用强迫运动（FE）的人，并证明了30%的改善， 临床评级相比，自愿运动（VE）在一个自我选择的速度。FE是一种高强度模式 有氧运动起源于PD动物模型，其中运动的自主踩踏率（节奏） 它是增强的，但不是替代的。有氧运动，包括FE，已被证明是一种潜在的疾病- 修改干预;然而，为了真正检查疾病修改，作用机制必须 被评价。基底神经节内运动回路的超同步性与主要运动体征相关 如PD患者的运动迟缓、震颤和僵硬。最近使用FE进行的动物研究评价了 局部场电位（LFP）从初级运动皮层（M1），并报告了衰减的神经 与改善的运动功能相关的β（13- 35 Hz）频带中的超同步。到现在为止， 来自基底神经节的神经活动已被分离用于动物模型或高度侵入性的人类研究 其中深部脑刺激器（DBS）导线已经被外部化。近年来，DBS技术的进步， 人类首次允许直接记录来自丘脑底核（subthalamic nucleus，缩写为丘脑底核）的神经活动。 植入Medtronic Percept DBS系统的个体的基底神经节。该项目旨在记录 PD患者在FE和VE两种模式下的脑电活动。我们的基本 假设是高强度运动减少了大脑皮层超同步性， 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 FE和VE在停止服用抗帕金森病药物的情况下进行固定周期的运动。双侧神经活动 将连续记录大约130分钟（运动前、FE或VE期间 和运动后）在两个不同的日子。MDS-GRESS III运动检查和上肢握力 跟踪范例将用于确定运动对运动的反应。虽然我们期望在 在FE和VE的单次发作之后，β带活动的性能和衰减，假设 由于较高的循环节奏导致更大的β衰减，FE将获得更好的上级结果。