Neural mechanisms of sound activation of vestibular system

描述（由申请人提供）：本申请的总体目标是通过严格检查对临床VEMP刺激的前庭传入反应，为人体VEMP测试（前庭诱发肌源性电位）提供神经基础。自1992年发现颈部肌肉肌源性电位以来，VEMP的出版物和临床应用迅速增长。世界各地的研究者已经使用VEMP来表征与衰老和各种外周和中枢前庭病变相关的前庭缺陷，包括Tullio/上级管裂开综合征、前庭神经炎、梅尼埃病和肿瘤。申请的动机是两个基本事实。首先，需要对VEMP测试的神经基础进行严格的动物基础科学研究。其次，我们的研究清楚地表明，耳道以及耳石传入响应VEMP刺激。由于颈部肌肉接受输入的运河和耳石，我们的研究结果提出了怀疑目前的解释VEMP测试，并呼吁质疑前庭器官负责VEMP反应在各种实验和临床条件下的知识重要的临床设计的歧视VEMP测试和解释的临床结果。在应用程序中，我们将检查单个单位前庭传入反应，从确定的器官，以空气传导（目标1）和骨传导的声音刺激（目标2），是临床使用。我们将确定某些声音刺激是否优先激活特定的前庭终末器官。我们的初步结果支持这一观点，并表明，具有一定强度和频率的声音刺激优先激活耳石与运河。从拟议的实验结果将导致最佳的VEMP测试协议和解释准则。器官选择性的基础被假设为生物力学-即，与声能如何通过迷宫传输有关。我们将通过构建前庭终末器官声音激活的3D生物力学模型来检验这一假设。 公共卫生相关性：声音诱发的前庭肌源性电位（VEMPs）已成为临床上一种常用的前庭功能检测方法，但我们并不清楚前庭器官是如何被声音激活的。从这项研究中获得的知识将有助于理解前庭终末器官的声音激活，并为开发和解释人类VEMP测试提供见解。

DESCRIPTION (provided by applicant): The overall objective of the application is to provide the neural basis for human VEMP testing (vestibular evoked myogenic potentials) by rigorously examining vestibular afferent responses to clinical VEMP stimuli. Since the discovery of cervical neck muscle myogenic potentials in 1992, there has been a rapid growth of VEMP publications and clinical use. Investigators worldwide have used the VEMPs to characterize vestibular deficiencies related to aging and a variety of peripheral and central vestibulopathies, including Tullio/superior canal dehiscence syndrome, vestibular neuritis, Meniere's disease and tumors. The application is motivated by two basic facts. First, there is a need of rigorous animal basic science research on the neural basis for VEMP testing. Second, our studies clearly demonstrated that the canal as well as otolith afferents responded to VEMP stimuli. Since neck muscles receive inputs from both the canals and the otoliths, our results cast doubt on the current interpretation of VEMP testing, and call into question which vestibular organs are responsible for VEMP responses under various experimental and clinical conditions-knowledge important for clinical design of discriminating VEMP tests and interpretation of clinical results. In the application, we will examine single unit vestibular afferent responses from identified organs to air-conducted (Aim 1) and bone-conducted sound stimuli (Aim 2) that are used clinically. We will determine if certain sound stimuli preferentially activate specific vestibular end organs. Our preliminary results support this idea and have shown that sound stimuli with certain intensity and frequency preferentially activate the otoliths vs. the canals. The results from the proposed experiments would lead to optimal VEMP testing protocols and interpretive guidelines. The basis of the organ selectivity is hypothesized to be biomechanical- i.e., related to how acoustic energy is transmitted through the labyrinth. We will examine the hypothesis by constructing a 3D biomechanical model of sound activation of the vestibular end organs. PUBLIC HEALTH RELEVANCE: Sound-evoked vestibular myogenic potentials (VEMPs) are becoming a common clinical test of vestibular function, yet we really do not know how the vestibular organs are activated by sound. The knowledge obtained from the study will contribute to understanding sound activation of vestibular end organs and provide insights into developing and interpreting human VEMP tests.