Neural mechanisms of sound activation of vestibular system

描述(由申请人提供)：申请的总体目标是通过严格检查前庭对临床VEMP刺激的传入反应，为人类VEMP测试(前庭诱发肌源性电位)提供神经基础。自从1992年发现颈部肌肉的肌源性电位以来，VEMP的出版和临床应用迅速增长。世界各地的研究人员已经使用VEMP来表征与衰老和各种外周和中枢性前庭疾病相关的前庭缺陷，包括图利奥/上管裂综合征、前庭神经炎、梅尼埃病和肿瘤。这项申请的动机是两个基本事实。首先，需要对VEMP检测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，耳道和耳石传入对VEMP刺激有反应。由于颈部肌肉接受来自耳道和耳石的输入，我们的结果对目前对VEMP测试的解释提出了质疑，并质疑在各种实验和临床条件下，哪些前庭器官负责VEMP反应-这些知识对于区分VEMP测试的临床设计和临床结果的解释非常重要。在应用中，我们将检查单个单位前庭传入反应的识别器官的空气传导(目标1)和骨传导的声音刺激(目标2)，这是临床上使用。我们将确定某些声音刺激是否优先激活特定的前庭末梢器官。我们的初步结果支持这一观点，并表明一定强度和频率的声音刺激优先激活耳石而不是耳道。建议的实验结果将导致最佳的VEMP测试方案和解释性指南。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递有关。我们将通过构建声音激活前庭末端器官的3D生物力学模型来检验这一假说。

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.