Vestibular Precision: Physiology and Pathophysiology

前庭精确度：生理学和病理生理学

• 批准号: 10434014
• 负责人: Faisal Karmali
• 金额: $ 43.65万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10434014
• 关键词: Ablation; Acoustic Neuroma; Affect; Age; Attention; Bayesian Modeling; Bayesian Prediction; Behavior; Behavioral; Biological Assay; Brain; Characteristics; Clinical; Cues; Data; Dizziness; Ear; Environment; Excision; Exposure to; Eye Movements; Fatigue; Fiber; Functional disorder; Goals; Head; Immersion; Learning; Lesion; Measurement; Measures; Mediating; Methods; Morbidity - disease rate; Motion; Motor; Motor Pathways; Nerve; Noise; Operative Surgical Procedures; Outcome; Outcome Measure; Pathologic; Pathway interactions; Patient Education; Patients; Perception; Peripheral; Physiology; Play; Population; Postoperative Period; Predictive Value; Process; Research; Residual state; Role; Rotation; Sensory; Signal Transduction; Source; Stimulus; Symptoms; System; Testing; Theoretical model; Time; Training; Translations; Validation; Variant; Vestibular Nerve; Visual; Work; base; behavioral response; disability; experience; human subject; improved; nerve damage; novel; oculomotor; otoconia; predict clinical outcome; relating to nervous system; response; secondary outcome; sensor; symptomatology; tumor; vestibulo-ocular reflex

The goal of this proposal is to investigate vestibular precision by quantifying the variability in behavioral responses that result from the neural noise inherent to the peripheral and central vestibular systems. Because neural noise contaminates the signals that are transduced by the ear and processed by the brain, vestibular- mediated behavioral responses vary even when identical stimuli are provided. In this proposal, we focus on vestibular precision in human subjects and investigate its sources, its effects on behavior, and its degradation when the periphery is damaged and its potential plasticity. Specifically, we will investigate: SA 1: Vestibular precision in normal subjects – physiology: A) We will measure the angular and linear vestibulo-ocular reflex (VOR) using novel motion combinations that reinforce or cancel eye movement responses, which will allow us to determine the distribution and magnitude of noise produced in the sensory (canal, otolith) pathways and in the oculomotor pathway. We hypothesize that normal subjects will demonstrate a bimodal distribution of noise with either sensory or motor predominance, and that subjects with more sensory noise will demonstrate other behavioral characteristics that reflect this characteristic (e.g., higher perceptual thresholds); and B) We will assay vestibular noise from trial-trial variations in the VOR and will compare VOR dynamics with those predicted by a Bayesian model using the assayed noise. We predict variations in VOR dynamics across subjects, age and stimulus amplitudes will be consistent with Bayesian processing of noise. Potential confounding factors will be carefully controlled, including attention, fatigue, and non-vestibular cues. SA 2: Vestibular precision after peripheral damage – pathophysiology: A) We will examine the changes in vestibular precision that occur when one vestibular nerve is damaged (by a vestibular schwannoma, VS) and after the damaged nerve is surgically sectioned, and will investigate if precision measurements can provide evidence of pathologic noise produced by the damaged nerve and therefore help predict clinical outcome when the nerve is sectioned. We hypothesize that changes in signal reliability due to the VS will be traceable to both the reduced redundancy caused by loss of afferent fibers and to aberrant noise generated by the damaged vestibular nerve and that changes in precision after neurectomy will correlate the outcome measures that characterize patient disability; and B) We will examine the plasticity of vestibular precision in the oculomotor and perceptual realms with the goal of determining if precision can be improved. Using novel training approaches that provide challenging signal extraction tasks, we hypothesize that subjects will improve their vestibular precision on the trained task. As secondary outcome measures, we will determine if training one behavior generalizes to the non-trained behavior and if patient’s symptoms are affected by improved precision.

这项建议的目标是通过量化行为的变异性来调查前庭的精确度。 由外周和中央前庭系统固有的神经噪声引起的反应。因为 神经噪音污染了由耳朵传递并由大脑处理的信号，前庭- 即使提供了相同的刺激，中介的行为反应也不同。在这份提案中，我们重点关注 研究受试者前庭精确度的来源、对行为的影响及其退化 当外周受到破坏时，其潜在的可塑性。具体来说，我们将调查： SA 1：正常受试者的前庭精确度-生理学：A)我们将测量角度和直线 前庭-眼反射(VOR)使用新的运动组合来加强或取消眼睛运动 反应，这将使我们能够确定在感官产生的噪音的分布和大小 (耳道、耳石)通路和动眼神经通路。我们假设正常的受试者会证明 具有感觉或运动优势的噪声的双峰分布，并且受试者具有更多的感觉 噪声将表现出反映该特征的其他行为特征(例如，更高的知觉 阈值)；和B)我们将从VOR的试验-试验变化中分析前庭噪声，并将VOR进行比较 动力学与使用检测的噪声的贝叶斯模型预测的动力学一致。我们预测VOR会发生变化 受试者、年龄和刺激幅度的动态变化将与噪声的贝叶斯处理一致。 潜在的混杂因素将被仔细控制，包括注意力、疲劳和非前庭暗示。 SA 2：外周损伤后前庭的精确度-病理生理学：A)我们将检查 当一条前庭神经受损时(前庭神经鞘瘤，VS)发生的前庭精确度 在对受损的神经进行手术切除后，将调查精确的测量是否可以提供 损伤神经产生病理性噪音的证据，因此有助于预测临床结果 神经被切开了。我们假设，由于VS导致的信号可靠性的变化将可追溯到两者 由于传入纤维的丢失和由损坏产生的异常噪声而导致的冗余减少 前庭神经和神经切除后精确度的变化将与以下结果指标相关 描述患者的残疾；以及B)我们将检查前庭运动的精确度的可塑性 以及感知领域，目标是确定是否可以提高精度。使用新的培训 提供具有挑战性的信号提取任务的方法，我们假设受试者将提高他们的 前庭对训练任务的精确度。作为次要结果衡量标准，我们将确定是否培训一名 行为概括为未经训练的行为，以及患者的症状是否受到改进的精确度的影响。