Physiology of Vestibular Compensation

前庭代偿生理学

基本信息

批准号：
10212365
负责人：
Kathleen E Cullen
金额：
$ 52.21万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-09-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10212365
关键词：
Acute Address Adult Advanced Development Animals Artificial Implants Automobile Driving Behavior Bilateral Bionics Brain CNS processing Chronic Clinical Clinical Trials Complex Cues Devices Disabled Persons Ensure Equilibrium Esthesia Excision Exhibits Financial compensation Foundations Funding Goals Head Human Implant Infection Investigation Ischemia Labyrinth Learning Life Long-Term Depression Macaca mulatta Mediating Modeling Monkeys Motion Motor Movement Neuraxis Neuronal Plasticity Neurons Neurosciences Pathologic Nystagmus Pathway interactions Patients Performance Physiologic pulse Physiology Process Prosthesis Protocols documentation Publications Pulse Rates Quality of life Ramp Recovery Reflex action Regimen Research Research Project Grants Research Project Summaries Risk Rotation Sensory Sensory Process Side Signal Transduction Solid Speed Spinal Symptoms Synapses System Technology Testing Training Trauma United States Vertigo Vestibular Labyrinth Vestibular Nerve Vestibular loss Vestibular nucleus structure Vision Visual base binaural hearing clinical care design evidence base experimental study first-in-human gaze hearing impairment human subject implantation improved innovation insight motor learning multimodality neural circuit neuromechanism neurophysiology neurotransmission nonhuman primate novel posture instability programs rehabilitation paradigm response restoration sample fixation sensory input sensory integration signal processing spinal pathway spinal reflex translational impact tumor vestibular pathway vestibular prosthesis vestibular reflex vestibulo-ocular reflex

Acute Address Adult Advanced Development Animals Artificial Implants Automobile Driving Behavior Bilateral Bionics Brain CNS processing Chronic Clinical Clinical Trials Complex Cues Devices Disabled Persons Ensure Equilibrium Esthesia Excision Exhibits Financial compensation Foundations Funding Goals Head Human Implant Infection Investigation Ischemia Labyrinth Learning Life Long-Term Depression Macaca mulatta Mediating Modeling Monkeys Motion Motor Movement Neuraxis Neuronal Plasticity Neurons Neurosciences Pathologic Nystagmus Pathway interactions Patients Performance Physiologic pulse Physiology Process Prosthesis Protocols documentation Publications Pulse Rates Quality of life Ramp Recovery Reflex action Regimen Research Research Project Grants Research Project Summaries Risk Rotation Sensory Sensory Process Side Signal Transduction Solid Speed Spinal Symptoms Synapses System Technology Testing Training Trauma United States Vertigo Vestibular Labyrinth Vestibular Nerve Vestibular loss Vestibular nucleus structure Vision Visual base binaural hearing clinical care design evidence base experimental study first-in-human gaze hearing impairment human subject implantation improved innovation insight motor learning multimodality neural circuit neuromechanism neurophysiology neurotransmission nonhuman primate novel posture instability programs rehabilitation paradigm response restoration sample fixation sensory input sensory integration signal processing spinal pathway spinal reflex translational impact tumor vestibular pathway vestibular prosthesis vestibular reflex vestibulo-ocular reflex

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项目摘要

Project Summary This research program is motivated by two goals. First, we seek to understand the neural mechanisms by which the brain adapts to changes in vestibular (inner ear balance) input. Second, we seek to advance development of a vestibular prosthesis/implant, a highly innovative treatment approach with potential to improve quality of life for individuals disabled by disequilibrium and unsteady vision after loss of vestibular sensation. In the United States alone, about 150,000 adults suffer disabling vertigo and unsteadiness each year due to acute unilateral loss of vestibular function, while about 65,000 suffer chronic imbalance and unsteady vision typical of severe bilateral sensory loss that fails to resolve despite existing treatments. Sudden, permanent loss of vestibular nerve input causes disequilibrium, visual blurring due to disruption of the vestibulo-ocular reflex (VOR), and postural instability due to disruption of vestibulo-spinal reflexes. These symptoms are usually followed by impressive but incomplete recovery. During the previous funding period, we made excellent progress toward defining the dynamics of compensation in pathways that mediate these vital reflexes. In addition, we established how these pathways respond acutely to activation of a multichannel vestibular prosthesis (MVP). In the proposed research program, we will build upon this solid foundation of progress through 3 synergistic aims. Experiments addressing Aim 1 will determine how central vestibular neurons adapt to the onset of constant prosthetic stimulation, to subsequent cessation of stimulation, and to motion-modulated stimulation. We predict that adaptation predominantly involves changes in one of two parallel paths, and that reduction of afferent discharge synchrony and/or addition of congruent extra-vestibular self-motion cues will further improve responses. Aim 2 experiments will examine how central neurons process prosthetic vestibular input during natural behaviors such as vergence, active gaze shifts and VOR suppression, which all require context-specific integration of neuronal signals encoding non-vestibular senses and efferent commands. These experiments will extend our investigation beyond reflex pathways and provide both systems and neuronal-level insight into how the central nervous system (CNS) optimizes performance during complex behaviors typical of daily life. Experiments addressing Aim 3 will characterize central vestibular neuron adaptation to natural and prosthetic stimulation during a novel training paradigm designed to reduce VOR asymmetry. Combined, these studies in alert nonhuman primates will enhance understanding of how the CNS adapts to changes in vestibular input; advance development of a potentially revolutionary treatment for loss of inner ear function; and clarify how neuronal mechanisms that underlie learning at a cellular level can be leveraged to optimize recovery of individuals disabled by loss of vestibular sensation.

项目摘要该研究计划是由两个目标激励的。首先，我们试图通过大脑适应前庭（内耳平衡）输入的变化。其次，我们试图进步开发前庭假体/植入物，一种高度创新的治疗方法，有可能通过失去前庭后的不平衡和不稳定的视力来改善残疾人的生活质量感觉。仅在美国，大约有15万名成年人遭受残疾的眩晕和不稳定由于前庭功能的急性单侧损失而导致的一年，而大约65,000次遭受了慢性失衡和不稳定的视力典型的严重双边感觉丧失，尽管有现有治疗，但仍无法解决。突然的，永久的前庭神经输入导致不平衡，视觉上的模糊。前庭反射（VOR）和由于脊柱反射的破坏而导致的姿势不稳定。这些症状通常是令人印象深刻但恢复不完全的。在上一个资金期间，我们在定义介导这些重要的途径中的补偿动力方面取得了良好的进步反射。此外，我们确定了这些途径如何对多通道的激活做出敏锐的反应前庭假体（MVP）。在拟议的研究计划中，我们将建立在这个坚实的基础上通过3个协同目标进展。针对AIM 1的实验将决定中央前庭神经元适应恒定的假体刺激的发作，随后停止刺激以及运动调节刺激。我们预测，适应性主要涉及两个之一的变化平行路径，并减少传入排放同步和/或添加一致的外牙自我运动提示将进一步改善反应。 AIM 2实验将检查中央神经元如何过程自然行为期间的假肢前庭输入，例如gergence，主动凝视和抑制，所有这些都需要对编码非vestibular感觉和传出的神经元信号的特定于上下文集成命令。这些实验将把我们的调查扩展到反射途径，并提供两个系统神经元水平洞察中枢神经系统（CNS）如何优化复合物的性能日常生活的典型行为。针对AIM 3的实验将表征中央前庭神经元在新型训练范式中适应自然和假肢刺激，旨在减少VOR 不对称。合并后，在警报非人类灵长类动物中的这些研究将增强对CNS的理解适应前庭输入的变化；提前开发了潜在革命性的治疗方法内耳功能；并阐明在细胞水平学习基础的神经元机制如何通过损失前庭感觉来优化残疾人的恢复。