Vestibular Precision: Physiology and Pathophysiology

这项建议的目的是通过量化行为的变异性来研究前庭的精确性。 由外周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转换并由大脑、前庭- 即使在提供相同刺激时，介导的行为反应也不同。在本提案中，我们重点关注 前庭精度在人类受试者，并调查其来源，其对行为的影响，以及其退化 当外周受损时及其潜在的可塑性。具体而言，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 使用增强或消除眼睛运动的新颖运动组合的前庭眼反射（VOR） 反应，这将使我们能够确定在感官中产生的噪音的分布和大小 （耳道、耳石）通路和眼神经通路中。我们假设正常人会表现出 噪音呈双峰分布，以感觉或运动为主，而感觉较多的受试者 噪声将表现出反映该特性的其它行为特性（例如，较高感知 阈值）;以及B）我们将从VOR的试验-试验变化中分析前庭噪声，并将VOR 动态与贝叶斯模型使用测定的噪声预测的动态。我们预测VOR的变化 跨受试者、年龄和刺激幅度的动态将与噪声的贝叶斯处理一致。 将仔细控制潜在的混杂因素，包括注意力、疲劳和非前庭线索。 SA 2：外周损伤后前庭精确性-病理生理学：A）我们将检查 当一条前庭神经受损（前庭神经鞘瘤，VS）时发生的前庭精确性， 在受损神经被手术切除后， 由受损神经产生的病理性噪音的证据，因此有助于预测临床结果， 神经被切开。我们假设，由于VS引起的信号可靠性变化可追溯到 由于传入纤维的损失和由受损的神经元产生的异常噪音引起的冗余减少， 前庭神经和神经切除术后精度的变化将与结果测量相关， 表征患者残疾;和B）我们将检查前庭精确度在眼内的可塑性 和感知领域，其目标是确定是否可以提高精度。使用新的训练 提供具有挑战性的信号提取任务的方法，我们假设受试者将提高他们的 前庭精度的训练任务。作为次要结果指标，我们将确定是否训练一个 行为推广到未经训练的行为，以及患者的症状是否受到精度提高的影响。

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.