Physiology of Vestibular Compensation

前庭代偿生理学

基本信息

批准号：
10436209
负责人：
Kathleen E Cullen
金额：
$ 51.62万
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 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10436209
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

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.

项目概要该研究计划有两个目标。首先，我们试图通过以下方式理解神经机制：大脑适应前庭（内耳平衡）输入的变化。第二，我们力求进步开发前庭假体/植入物，这是一种高度创新的治疗方法，有潜力改善前庭丧失后因视力不平衡和不稳定而致残的人的生活质量感觉。仅在美国，就有大约 150,000 名成年人患有眩晕和不稳定症状每年由于急性单侧前庭功能丧失，而大约 65,000 人患有慢性失衡和视力不稳定，典型的严重双侧感觉丧失，尽管现有治疗仍无法解决。前庭神经输入的突然、永久性丧失会导致失衡，由于前庭神经的破坏而导致视觉模糊。前庭眼反射（VOR），以及由于前庭脊髓反射破坏而导致的姿势不稳定。这些症状之后通常会出现令人印象深刻但不完全的恢复。在上一个资助期间，我们在定义调解这些重要途径的补偿动态方面取得了巨大进展反射。此外，我们还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，我们将建立在这一坚实的基础上通过 3 个协同目标取得进展。针对目标 1 的实验将确定中枢前庭如何神经元适应持续假体刺激的开始、随后刺激的停止，以及运动调节刺激。我们预测适应主要涉及以下两个方面之一的变化平行路径，以及减少传入放电同步和/或添加一致的前庭外自我运动提示将进一步改善反应。目标 2 实验将检查中枢神经元如何处理自然行为期间的假体前庭输入，例如聚散、主动目光转移和 VOR 抑制，这些都需要编码非前庭感觉和传出感觉的神经元信号的上下文特定整合命令。这些实验将把我们的研究扩展到反射途径之外，并提供这两个系统以及神经元层面的洞察，了解中枢神经系统 (CNS) 如何在复杂的过程中优化性能日常生活中的典型行为。针对目标 3 的实验将表征中枢前庭神经元在旨在减少 VOR 的新颖训练模式中适应自然和假肢刺激不对称。结合起来，这些针对警觉的非人类灵长类动物的研究将加深对中枢神经系统如何适应前庭输入的变化；推进潜在革命性治疗方法的开发内耳功能；并阐明细胞水平学习背后的神经机制如何用于优化因前庭感觉丧失而致残的个体的康复。

项目成果

期刊论文数量（134）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（1）

Context-independent encoding of passive and active self-motion in vestibular afferent fibers during locomotion in primates.

灵长类动物运动过程中前庭传入纤维中被动和主动自我运动的上下文无关编码。

DOI：
发表时间：
2022-01-10
期刊：
影响因子：
16.6
作者：
Mackrous, Isabelle;Carriot, Jérome;Cullen, Kathleen E
通讯作者：
Cullen, Kathleen E

Function of bidirectional sensitivity in the otolith organs established by transcription factor Emx2.

转录因子 Emx2 建立的耳石器官双向敏感性功能。

DOI：
发表时间：
2022-10-24
期刊：
影响因子：
16.6
作者：
Ji, Young Rae;Tona, Yosuke;Wafa, Talah;Christman, Matthew E;Tourney, Edward D;Jiang, Tao;Ohta, Sho;Cheng, Hui;Fitzgerald, Tracy;Fritzsch, Bernd;Jones, Sherri M;Cullen, Kathleen E;Wu, Doris K
通讯作者：
Wu, Doris K

Vestibular Contributions to Primate Neck Postural Muscle Activity during Natural Motion.

自然运动期间前庭对灵长类动物颈部姿势肌肉活动的贡献。

DOI：
发表时间：
2023-03-29
期刊：
影响因子：
0
作者：
Mildren, Robyn L;Cullen, Kathleen E
通讯作者：
Cullen, Kathleen E

Nystagmus induced by circular head shaking in normal human subjects.

正常人因圆形摇头引起的眼球震颤。

DOI：
发表时间：
1999-01
期刊：
影响因子：
2
作者：
Haslwanter, T;Minor, L B
通讯作者：
Minor, L B

Responses of irregularly discharging chinchilla semicircular canal vestibular-nerve afferents during high-frequency head rotations.

高频头部旋转期间龙猫半规管前庭神经传入的不规则放电反应。

DOI：
发表时间：
2005-05
期刊：
影响因子：
0
作者：
Hullar, Timothy E;Della Santina, Charles C;Hirvonen, Timo;Lasker, David M;Carey, John P;Minor, Lloyd B
通讯作者：
Minor, Lloyd B