Investigating subthreshold vestibular stimulation as a strategy for rehabilitation in individuals with bilateral vestibular hypofunction

1项目概要/摘要 2双侧前庭功能减退（BVH）的个体，前庭对自我运动线索的反应降低， 3、经常没有明确的原因。持续的脱敏状态会产生弹跳的症状， 4视力不稳定、头晕、不平衡和福尔斯;这些症状共同导致 5生活质量然而，尽管BVH对生活质量、医疗保健支出和福尔斯有相当大的影响， 针对BVH患者的特定需求量身定制的6种干预措施，而不是单侧病变患者， 七是要发展。本提案的目的是研究一种新的改善前庭功能的策略。 8在BVH个体中起作用。神经系统具有强大的能力来调节神经活动， 9.面对不断变化的环境或内部条件。当暴露于弱的感官刺激（例如，慢 10运动的头部），一种特殊类型的神经可塑性，“稳态可塑性”，已被证明增加 图11所示为相关神经元对后续运动刺激的反应。在这个项目中，我们的目标是确定， 12种这样的机制，由亚阈值的时间段（即，低幅度）运动，可以用作潜在的 13策略驱动损伤前庭系统的可塑性。具体而言，在诊断为BVH的个体中， 我们将（1）测量在阈下运动之后对自我运动线索的敏感性的变化 15刺激（目的1），（2）表征反复暴露于阈下刺激后前庭功能的变化 16运动刺激（目标2），以及（3）确定添加阈下运动“引物”是否可以改善运动刺激（目标2）。 前庭眼反射（VOR）适应（Aim 3A）和平衡训练（Aim 3B）的17个结局。我们假设 18认为，使用阈下刺激，继发于其驱动前庭可塑性变化的能力 19系统，将导致对自我运动线索的敏感性增加，以及前庭功能的积极变化 20（例如，凝视稳定性、平衡）。根据拟议研究项目的主题， 我的长期职业目标是建立一个研究实验室，专注于开发创新的治疗方法， 22前庭功能障碍。为实现这一目标，拟议的职业发展计划侧重于获得 设计，实施，监测和分析临床试验结果所需的23项技能和知识 24康复科学;更具体地说，这包括（1）更好地了解 25项前庭可塑性/学习的神经生理学原理，（2）学习最先进的技术， 分析VOR的行为，以及（3）学习用于适配VOR的增益的当前方法。的 培训计划的27个指导阶段将在俄亥俄州州立大学的丹尼尔梅菲尔德博士的实验室进行。 28与项目的转化性质相一致，导师团队将由临床科学家和 29名基础前庭科学家，无论是在俄亥俄州（丹尼尔梅菲尔德，博士和凯文克尔伯，医学博士）和外部 30个机构（Michael Schubert，PT，PhD和Soroush Sadeghi Ghandehari，MD，PhD）。 31 32 33 34 35

1 Project Summary/Abstract 2 In individuals with bilateral vestibular hypofunction (BVH), vestibular responses to self-motion cues are reduced 3 bilaterally, often without a defined cause. The persistent state of desensitization yields symptoms of bouncing or 4 unstable vision, dizziness, imbalance, and falls; collectively, these symptoms lead to a substantial reduction in 5 quality of life. However, despite the sizeable impact of BVH on quality of life, health care expenditures, and falls, 6 interventions tailored to the specific needs of patients with BVH, as opposed to patients with unilateral lesions, 7 have yet to be developed. The objective of this proposal is to investigate a novel strategy for improving vestibular 8 function in individuals with BVH. The nervous system possesses a robust capacity to regulate neural activity in 9 the face of changing environmental or internal conditions. When exposed to a weak sensory stimulus (e.g., slow 10 movements of the head), a specific type of neural plasticity, “homeostatic plasticity”, has been shown to increase 11 the responsiveness of the involved neurons to subsequent motion stimuli. In this project, we aim to determine if 12 such mechanisms, prompted by periods of subthreshold (i.e., low amplitude) motion, may serve as a potential 13 strategy for driving plasticity in the lesioned vestibular system. Specifically, in individuals diagnosed with BVH 14 we will (1) measure changes in sensitivity to self-motion cues immediately following a subthreshold motion 15 stimulus (Aim 1), (2) characterize changes in vestibular function after repeated exposure to a subthreshold 16 motion stimulus (Aim 2), and (3) determine if the addition of a subthreshold motion “primer” can improve the 17 outcomes of vestibulo-ocular reflex (VOR) adaptation (Aim 3A) and balance training (Aim 3B). We hypothesize 18 that the use of a subthreshold stimulus, secondary to its capacity to drive plastic changes in the vestibular 19 system, will lead to an increased sensitivity to self-motion cues, as well as positive changes in vestibular function 20 (e.g., gaze stability, balance), in patients with BVH. In accordance with the topic of the proposed research project, 21 my long-term career goal is to establish a research lab that focuses on developing innovative treatments for 22 vestibular dysfunction. To achieve this goal, the proposed career development plan focuses on acquiring the 23 skills and knowledge required to design, implement, monitor, and analyze the results of clinical trials in the 24 rehabilitation sciences; more specifically, this includes (1) gaining a better understanding of the 25 neurophysiological principles underlying vestibular plasticity/learning, (2) learning state-of-the-art techniques for 26 analyzing the behavior of the VOR, and (3) learning current methods for adapting the gain of the VOR. The 27 mentored phase of the training plan will take place at Ohio State University in the lab of Dr. Daniel Merfeld, PhD. 28 Consistent with the translational nature of the project, the mentorship team will consist of clinician-scientists and 29 basic vestibular scientists, both at Ohio State (Daniel Merfeld, PhD & Kevin Kerber, MD) and at external 30 institutions (Michael Schubert, PT, PhD, and Soroush Sadeghi Ghandehari, MD, PhD). 31 32 33 34 35