Cerebellar TMS for postural instability in progressive supranuclear palsy

小脑 TMS 治疗进行性核上性麻痹姿势不稳

• 批准号: 10612441
• 负责人: Marian Livingston Dale
• 金额: $ 18.05万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612441
• 关键词: Address; Aftercare; BRAIN initiative; Basal Ganglia; Bradykinesia; Brain; Cerebellar Nuclei; Cerebellum; Clinical; Clinical Investigator; Clinical Trials; Cognitive; Crossover Design; Data; Deep Brain Stimulation; Development; Disease model; Double-blind trial; Early Intervention; Equilibrium; Fluid Balance; Functional Magnetic Resonance Imaging; Funding; Future; Gait; Goals; Human; Image; Impairment; Injury; Intervention; Intervention Studies; Investigation; K-Series Research Career Programs; Laboratories; Lead; Measures; Mentors; Mentorship; Methodology; Methods; Motor; Motor Cortex; Motor output; Movement Disorders; Musculoskeletal Equilibrium; Neural Pathways; Neurologist; Outcome; Outcome Measure; Parkinson Disease; Parkinsonian Disorders; Patients; Pharmaceutical Preparations; Physical therapy; Posture; Progressive Supranuclear Palsy; Protocols documentation; Refractory; Rehabilitation therapy; Research; Research Methodology; Research Personnel; Rest; Risk; Role; Site; Symptoms; Testing; Thalamic structure; Time; Training; Transcranial magnetic stimulation; Translations; United States National Institutes of Health; balance testing; brain circuitry; career; clinical effect; cost; effective therapy; equilibration disorder; falls; functional decline; functional improvement; improved; interest; motor control; neural circuit; neuroregulation; novel therapeutics; posture instability; pressure; prevent; programs; rehabilitation strategy; response; skills; symptom treatment; wearable sensor technology

PROJECT SUMMARY/ABSTRACT This project uses PSP as a model disorder to study early interventions for symptomatic treatment to improve balance and postural instability in parkinsonian disorders. The goal of this research is to develop effective therapies for postural instability and falls in progressive supranuclear palsy (PSP). PSP is a form of parkinsonism classically characterized by early and severe balance deficits, primarily backward postural instability. Injuries related to this debilitating postural instability in PSP, or risk-avoidance aimed at preventing such incidents, limit mobility and physical therapy, which, in turn, leads to a further decline in function. The traditional symptomatic treatments for bradykinesia and rigidity in parkinsonism (dopaminergic medication and stimulation of the basal ganglia circuitry via deep brain stimulation) are not helpful for backward postural instability in PSP, or in advanced Parkinson’s disease. We know that the cerebellum’s normal ability to inhibit and modulate motor output for postural control is diminished in parkinsonian disorders. The objective of this proposal is to investigate the effect of non-invasive repetitive cerebellar transcranial magnetic stimulation (rTMS) on postural instability in progressive supranuclear (PSP). The central hypothesis is that augmenting cerebellar inhibition via cerebellar rTMS will decrease postural instability in patients with PSP by increasing functional connectivity between the cerebellum, thalamus, and primary motor cortex. Aim 1 uses a specialized force plate platform and wearable sensors to evaluate objective posturography measures of postural stability before and after rTMS. Aim 2 identifies changes in cerebellar, thalamic, and motor cortex functional activity before and after resting state fMRI. If successful, this proof-of-concept study for cerebellar neuromodulation in PSP will lead to better rehabilitation strategies, and cerebellar neuromodulation via TMS may also lead to more durable neuromodulation approaches for postural instability, such as cerebellar targeting for future deep brain stimulation paradigms. The candidate for this K23 Career Development Award has a long-term goal of becoming an independent clinical investigator in the field neuromodulation for symptomatic management of balance impairment and of other untreatable aspects of parkinsonism. With the outstanding mentorship of Dr. Fay Horak (quantitative gait and balance research), and co-mentored by Dr. Bill Rooney (fMRI), Dr. Joseph Quinn (clinical trials and PSP), and Dr. Mark George (neuromodulation), a comprehensive training plan for quantitative research methods and fMRI analysis is proposed. In a future RO1, Dr. Dale will pair cerebellar rTMS with rehabilitation programs for postural instability and expand investigations of TMS as a probe of the neural circuitry for motor control in parkinsonism.

项目总结/摘要 该项目使用PSP作为模型障碍，研究早期干预对症治疗，以改善 帕金森病的平衡和姿势不稳定。本研究的目的是开发有效的 治疗进行性核上性麻痹（PSP）的姿势不稳和福尔斯。PSP是一种帕金森症 典型的特征是早期和严重的平衡缺陷，主要是向后姿势不稳定。受伤 与PSP中这种使人衰弱的姿势不稳定有关，或旨在防止此类事件的风险规避， 活动和物理治疗，这反过来又导致功能进一步下降。传统的症状 帕金森综合征中运动迟缓和僵硬的治疗（多巴胺能药物和刺激基底神经元） 通过脑深部电刺激的神经节回路）对PSP中的向后姿势不稳定或晚期 帕金森氏症。我们知道小脑抑制和调节运动输出的正常能力， 在帕金森病中姿势控制减弱。本提案的目的是调查 非侵入性重复小脑经颅磁刺激（rTMS）对姿势不稳定的影响 进行性核上型（PSP）。中心假设是，通过小脑抑制增强小脑抑制， rTMS将通过增加PSP患者的功能连接来减少PSP患者的姿势不稳定。 小脑丘脑和初级运动皮层AIM 1使用专门的测力板平台和可穿戴 传感器来评估rTMS前后姿势稳定性的客观姿势图测量。目的2 确定小脑，丘脑和运动皮质功能活动的变化之前和之后的休息状态功能磁共振成像。 如果成功的话，这项关于PSP小脑神经调节的概念验证研究将带来更好的康复 通过TMS的小脑神经调节也可能导致更持久的神经调节方法 用于姿势不稳定，例如用于未来深部脑刺激范例的小脑靶向。候选 获得K23职业发展奖的长期目标是成为一名独立临床研究者 在神经调节领域，用于平衡障碍和其他不可治疗的 帕金森症的症状在Fay Horak博士的出色指导下（定量步态和平衡 比尔·鲁尼博士（功能磁共振成像），约瑟夫·奎因博士（临床试验和PSP）和马克博士共同指导 乔治（神经调节），定量研究方法和功能磁共振成像分析的综合培训计划 本文提出在未来的RO 1中，Dale博士将把小脑rTMS与姿势不稳定的康复计划配对 并扩大经颅磁刺激作为帕金森病运动控制神经回路探针的研究。