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，甚至超过阿尔茨海默氏病。 有氧运动被普遍接受为PD治疗的组成部分，尤其是固定骑行 人们被认为是PD患者的理想运动方式。我们的第二个串联自行车研究 是第一个在人类PD患者中使用强制运动（FE）的人，并证明了30％的提高 与自愿运动（VE）相比，临床评级以自选择的速度。 FE是一种高强度的模式 有氧运动起源于PD动物模型，其中锻炼的自愿踩踏率（节奏） 被增强，但没有被替换。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；但是，为了真正检查疾病调整，作用机理必须 进行评估。基底神经节内电动电路的高度同步与基本电机标志有关 例如Bradykinesia，Tremor和PD患者的僵化。最近使用FE评估的动物研究 一级运动皮层（M1）的局部田间电势（LFP），并报告了神经的衰减 与改善运动功能相关的Beta（13-35Hz）频带中的高度同步。到目前为止， 基底神经节的神经活动已分离为动物模型或高度侵入性的人类研究 深脑刺激器（DB）电线已被外部化。最近，DBS技术的进步 人类首次允许直接从丘脑核核（STN）记录的神经活动 植入Medtronic感知DBS系统的个体中的基底神经节。该项目旨在记录 PD患者的两种模式中的STN的神经活动。我们的基础 假设是，高强度运动减少了STN超同步，该功能是Cortico-Basal的设施 神经节丘脑皮层电路功能，从而改善运动后运动功能。 以前使用感知系统进行了DBS手术的15个PWPD将完成一个单一的PWPD 在反帕金森氏药物中，在固定周期进行了FE和VE运动。双侧神经活动 STN的总记录将总计约130分钟（预运动期间，FE或VE 和运动后）在两天之间。 MDS-UPDRS III运动检查和上肢抓地力 跟踪范例将用于确定运动的运动响应。虽然我们期望有所改善 在一次FE和VE之后，Beta带活动的性能和衰减，假设是 由于较高的循环节奏会导致更大的β衰减，FE将会获得较高的结果。