Progressive resistance exercise and dystonia pathophysiology.

渐进性阻力运动和肌张力障碍病理生理学。

• 批准号: 10445435
• 负责人: Aparna Wagle Shukla
• 金额: $ 52.18万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10445435
• 关键词: Activities of Daily Living; Advisory Committees; Alzheimer' s Disease; Base Pairing; Behavioral; Blinded; Botulinum Toxins; Brain; Brain region; Cervical; Cervical Dystonia; Clinical; Clinical Research; Clinical Trials; Cognition; Control Groups; Data; Deep Brain Stimulation; Dose; Dystonia; Enrollment; Exercise; Exercise Therapy; Fatigue; Focal Dystonias; Functional Magnetic Resonance Imaging; Functional disorder; Gait; Goals; Injections; Intervention; Involuntary Movements; Measures; Mediating; Medical; Monitor; Moods; Motor; Motor Evoked Potentials; Movement; Movement Disorders; Muscle; Muscle Contraction; Muscle relaxation phase; Operative Surgical Procedures; Oral; Outcome; Outcome Study; Oxygen; Pain; Parkinson Disease; Participant; Patients; Pharmaceutical Preparations; Pharmacology; Physical Function; Physiological; Pilot Projects; Posture; Protocols documentation; Quality of life; Randomized; Range of motion exercise; Relaxation; Rest; Role; Seeds; Shoulder; Signal Transduction; Sleep; Smooth Muscle; Stretching; Symptoms; Techniques; Testing; Therapeutic; Training; Training Programs; Transcranial magnetic stimulation; Treatment outcome; base; brain circuitry; effective therapy; exercise program; exercise regimen; functional disability; grasp; improved; improved functioning; motor control; motor symptom; muscle strength; nervous system disorder; network dysfunction; non-motor symptom; novel; physical therapist; programs; resistance exercise; response; standard of care; strength training; symptomatic improvement; trend

PROJECT ABSTRACT Dystonia is a debilitating movement disorder characterized by involuntary muscle contractions with abnormal and repetitive movements, postures, or both. The current treatments for dystonia, consisting of oral medications, botulinum toxin injections, and deep brain stimulation surgery, fail to improve symptoms in more than a third of patients despite optimal management. The improvements are often unpredictable. Recent studies found exercise therapy primarily involving muscle stretching, muscle relaxation, and range of motion exercises, when added to optimal medical management, further improved symptoms of focal cervical dystonia. But the clinical outcomes were noted to be variable and modest. These studies did not investigate the pathophysiological underpinnings that could explain the variability of treatment outcomes. They did not include progressive resistance training that has the potential to induce central brain changes. The main goal of this proposal is to investigate the brain adaptation effects for progressive resistance exercise-focused cervical and shoulder training (PERFECT) in patients with focal cervical dystonia, which is the most common form of dystonia. We will use functional MRI (fMRI) and transcranial magnetic stimulation (TMS) techniques for understanding the pathophysiological underpinnings. We will randomize patients into PERFECT plus standard-of-care (SOC) group and SOC alone group. Participants in the PERFECT + SOC group will perform personal-trainer-guided exercises twice a week for six months. Participants in the SOC group will continue receiving standard pharmacological therapies at stable doses, and they will not exercise. We will use fMRI and TMS techniques to examine brain effects. We hypothesize that the PERFECT program in focal cervical dystonia will improve the functioning of dystonia circuitries involving the sensorimotor cortex. In Aim 1, we will determine the brain adaptation changes in response to PERFECT at six months compared to baseline with fMRI. We will record seed-based functional connectivity and bold oxygen level-dependent signal in the sensorimotor network. In Aim 2, we will determine the brain adaptation changes in response to PERFECT at six months compared to baseline with TMS. We will use a TMS-based paired associative stimulation protocol to measure sensorimotor plasticity and compare. We will monitor the TMS-based resting motor threshold; motor evoked potential, intracortical inhibition, and intracortical facilitation as additional measures. In Aim 3, we will determine whether the brain adaptation response relates to clinical and functional change. We will assess with blinded dystonia ratings, cognition and mood measures, muscle strength, physical functioning capacity. The outcomes of this proposal will (1) test whether a 6-month long resistance exercise is viable, (2) identify physiological brain markers that are responsive to effects of resistance exercise and are specific to dystonia circuitries, (3) provide essential data to for planning a large scale clinical trial.

项目摘要 肌张力障碍是一种使人衰弱的运动障碍，其特征是不自主的肌肉收缩， 和重复的动作、姿势或两者。目前肌张力障碍的治疗，包括口服 药物治疗，肉毒杆菌毒素注射和深部脑刺激手术，未能改善更多的症状， 超过三分之一的病人，尽管管理得当。这些改进往往是不可预测的。最近 研究发现，运动疗法主要包括肌肉拉伸、肌肉放松和运动范围 运动，当添加到最佳的医疗管理，进一步改善症状的局灶性颈部肌张力障碍。 但临床结果是可变的和适度的。这些研究没有调查 病理生理学基础，可以解释治疗结果的变异性。他们没有 包括渐进式阻力训练，有可能引起中枢脑变化。的主要目标 本研究旨在探讨渐进式抗阻运动对颈椎病患者的脑适应性影响。 和肩部训练（PERFECT）的患者局灶性颈肌张力障碍，这是最常见的形式， 肌张力障碍我们将使用功能性MRI（fMRI）和经颅磁刺激（TMS）技术， 了解病理生理学基础。我们将患者随机分配至PERFECT plus 标准治疗（SOC）组和SOC单独组。PERFECT + SOC组的参与者将执行 私人教练指导下的锻炼，每周两次，为期六个月。SOC组的参与者将继续 接受稳定剂量的标准药物治疗，他们不会运动。我们将使用功能性磁共振成像， 经颅磁刺激技术来检查大脑的影响。我们假设局灶性颈肌张力障碍的PERFECT程序 将改善涉及感觉运动皮层的肌张力障碍电路的功能。在目标1中，我们 与基线相比，确定6个月时对PERFECT的大脑适应性变化， 功能磁共振成像。我们将记录基于种子的功能连接和粗体氧水平依赖性信号， 感觉运动网络在目标2中，我们将确定大脑对PERFECT的适应性变化， 与TMS基线相比6个月。我们将使用基于TMS的配对联想刺激协议， 测量感觉运动可塑性并进行比较。我们将监测基于TMS的静息运动阈值;运动 诱发电位、皮质内抑制和皮质内易化作为附加测量。在目标3中，我们 确定大脑适应反应是否与临床和功能变化有关。我们将与 盲性肌张力障碍评级、认知和情绪测量、肌肉力量、身体功能能力。的 该建议的结果将（1）测试6个月的抗阻训练是否可行，（2）确定 对抗阻运动的影响有反应并对肌张力障碍有特异性的生理脑标记物 电路，（3）为计划大规模临床试验提供必要的数据。