Vestibular Precision: Physiology and Pathophysiology

前庭精确度：生理学和病理生理学

• 批准号: 10651646
• 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/10651646
• 关键词: Ablation; Acoustic Neuroma; Affect; Age; Attention; Bayesian Modeling; Bayesian Prediction; Behavior; Behavioral; Biological Assay; Brain; Characteristics; Clinical; Compensation; Cues; Data; Dizziness; Ear; Environment; Excision; Exposure to; Eye Movements; Fatigue; Fiber; Functional disorder; Goals; Head; Learning; Lesion; Measurement; Measures; Mediating; Methods; Modality; 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; behavioral response; disability; experience; human subject; improved; nerve damage; neural; novel; oculomotor; otoconia; predict clinical outcome; 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.

该提案的目标是通过量化行为的变异性来研究前庭精度 由周围和中枢前庭系统固有的神经噪声引起的反应。因为 神经噪声污染了由耳朵传导并由大脑、前庭处理的信号 即使提供相同的刺激，介导的行为反应也会有所不同。在这个提案中，我们重点关注 人类受试者的前庭精确度并调查其来源、对行为的影响及其退化 当外围受损时及其潜在的可塑性。具体来说，我们将调查： SA 1：正常受试者的前庭精度 – 生理学：A) 我们将测量角度和线性 前庭眼反射 (VOR) 使用新颖的运动组合来增强或取消眼球运动 响应，这将使我们能够确定感官中产生的噪声的分布和大小 （耳管、耳石）通路和动眼神经通路。我们假设正常受试者会表现出 噪声的双峰分布，以感觉或运动为主，并且具有更多感觉的受试者 噪音将表现出反映该特征的其他行为特征（例如，更高的感知 阈值）； B) 我们将分析 VOR 中试验变化的前庭噪声，并比较 VOR 与使用所分析的噪声的贝叶斯模型预测的动态进行比较。我们预测 VOR 的变化 受试者之间的动态、年龄和刺激幅度将与噪声的贝叶斯处理一致。 潜在的混杂因素将得到仔细控制，包括注意力、疲劳和非前庭线索。 SA 2：外周损伤后前庭精度 – 病理生理学：A) 我们将检查 当一根前庭神经受损（前庭神经鞘瘤，VS）时发生的前庭精确度 在通过手术切除受损神经后，我们将研究精确测量是否可以提供 受损神经产生的病理噪音的证据，因此有助于预测临床结果 神经被切断。我们假设 VS 导致的信号可靠性变化可追溯到 由于传入纤维损失和受损产生的异常噪音而导致的冗余减少 前庭神经和神经切除术后精度的变化将与结果测量相关联 描述患者残疾的特征； B）我们将检查动眼神经前庭精度的可塑性 和感知领域，以确定是否可以提高精度。使用新颖的训练 提供具有挑战性的信号提取任务的方法，我们假设受试者会提高他们的能力 训练任务的前庭精确度。作为次要结果衡量标准，我们将确定培训是否 如果患者的症状受到精度提高的影响，则行为会推广到未经训练的行为。