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

基本信息

项目摘要

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.
项目概要/摘要 该项目使用 PSP 作为模型疾病来研究对症治疗的早期干预措施,以改善 本研究的目标是开发有效的帕金森病的平衡和姿势不稳定的方法。 治疗进行性核上性麻痹 (PSP) 中的姿势不稳和跌倒是帕金森病的一种形式。 典型的特征是早期和严重的平衡缺陷,主要是向后的姿势不稳定。 与 PSP 中这种使人衰弱的姿势不稳定性有关,或旨在防止此类事件的风险规避,限制 活动和物理治疗,这反过来又导致传统症状的功能进一步下降。 治疗帕金森病的运动迟缓和强直(多巴胺能药物和刺激基底神经节) 通过深部脑刺激的神经节电路)对于 PSP 或高级患者的向后姿势不稳定没有帮助 我们知道小脑抑制和调节运动输出的正常能力。 帕金森病的姿势控制能力减弱。该提案的目的是研究其影响。 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(PSP)的中心假设是通过小脑增强小脑抑制。 rTMS 将通过增加 PSP 患者之间的功能连接来减少 PSP 患者的姿势不稳定性。 Aim 1 使用专门的测力板平台和可穿戴设备。 传感器用于评估 rTMS Aim 2 前后姿势稳定性的客观姿势测量。 识别静息状态功能磁共振成像前后小脑、丘脑和运动皮层功能活动的变化。 如果成功,这项 PSP 小脑神经调节的概念验证研究将带来更好的康复 策略和通过 TMS 进行的小脑神经调节也可能导致更持久的神经调节方法 用于姿势不稳定性,例如未来深部脑刺激范例的小脑靶向。 获得这个K23职业发展奖的长期目标是成为一名独立的临床研究者 用于平衡障碍和其他无法治疗的症状管理的现场神经调节 在 Fay Horak 博士的出色指导下(定量步态和平衡) 研究),并由 Bill Rooney 博士(fMRI)、Joseph Quinn 博士(临床试验和 PSP)和 Mark 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 建议在未来的 RO1 中,Dale 博士将小脑 rTMS 与姿势不稳定的康复计划结合起来。 并扩大 TMS 作为帕金森病运动控制神经回路探针的研究。

项目成果

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Marian Livingston Dale其他文献

Marian Livingston Dale的其他文献

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{{ truncateString('Marian Livingston Dale', 18)}}的其他基金

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:
    10447428
  • 财政年份:
    2022
  • 资助金额:
    $ 18.05万
  • 项目类别:

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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
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