Role of Organ of Corti Outer Hair Cell/Vibration Hot Spots in Distortion Product Otoacoustic Emission Generation

柯蒂氏器外毛细胞/振动热点在失真产物耳声发射产生中的作用

• 批准号: 10354021
• 负责人: Wei Dong
• 金额: $ 18.31万
• 依托单位: LOMA LINDA VETERANS ASSN RESEARCH & EDUC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10354021
• 关键词: Accounting; Address; Affect; Apical; Basilar Membrane; Clinical; Cochlea; Data; Exhibits; External auditory canal; Fourier Transform; Frequencies; Furosemide; Generations; Gerbils; Hearing; Hot Spot; Injections; Intervention; Laboratories; Laboratory Animal Models; Laboratory Animals; Link; Literature; Location; Measurement; Measures; Mechanics; Methods; Modification; Motion; Noise; Optical Coherence Tomography; Organ of Corti; Oryctolagus cuniculus; Outcome; Outer Hair Cell of the Organ of the Corti; Outer Hair Cells; Process; Property; Recovery; Research; Role; Site; Source; Stimulus; Theoretical model; Time; data acquisition; design; experimental study; improved; otoacoustic emission; response; vector; vibration

PROJECT SUMMARY/ABSTRACT Earlier research in our laboratory using interference tones (ITs) and vector-difference analyses between control and various experimental conditions established that large distortion product otoacoustic emissions (DPOAEs) components evidenced by strong enhancement and/or suppression, can arise from regions located up to several octaves basal to the f2 primary-tone. The proposed experiments in gerbils are focused on identifying a physical mechanism in cochlear micromechanics that explains the existence of such basal DPOAE components. Specifically, the studies described below are aimed at showing that basal components are produced by recently described nonlinear vibration hotspots (VHSs) that localize to the outer hair cell (OHC) region. These OHC/VHSs, unlike the BM, are nonlinear over many octaves below the measurement BF, and are capable of generating physical motions significantly larger than their counterpart BM vibrations. Methods will utilize noninvasive optical coherence tomography (OCT) that is capable of measuring vibrations of various subcomponents of the organ of Corti, along with the simultaneous recordings of intracochlear distortion products (iDPs) and ear-canal DPOAEs. In this manner, OHC/VHSs will be linked to the nonamplifying widely distributed nonlinearity hypothesized to be the source of basally generated DPOAE components, thus, providing a direct physical mechanism for their generation. Briefly, Aim 1 utilizes OCT to characterize iDPs from the BM and OHC/VHS regions simultaneously as a function of primary-tone levels and f2/f1 ratios as the primary-tones are stepped apically past the best frequency (BF) of the OCT-measurement location. Fourier transforms of the vibrations from the BM and the OHC/VHSs will be performed to extract iDPs from these subcomponents. Next, ITs and brief noise overexposures will be used to linearize the nonamplifying nonlinearity of the OHC/VHSs while simultaneously measuring ear-canal DPOAEs. Vector subtraction will be used to isolate components that are hypothesized to be responsible for generating basal DPOAE components. In Aim 2, furosemide administration will be employed to temporarily eliminate OHC/VHSs and BM iDPs, thereby interfering with both the broadly distributed OHC/VHS nonlinearity and the BM amplifying peak nonlinearity, which have been shown to exhibit different recovery-time courses. In this manner, contributions from the BM peak and broadband nonlinearities can be separated. Again, basal iDP and DPOAE components will be extracted by vector subtraction of these measures before and after the above interventions. The expected outcomes of these experiments will clarify under what circumstances OHC/VHSs produce iDPs and to what extent they contribute to the DPOAEs commonly recorded in the ear canal. If the proposed experiments are successful, by providing a direct physical mechanism for the generation of basal DPOAEs, decades of theoretical models of DPOAE generation will require significant modification and clinical DP-grams can be improved by removing the confounding basal DPOAE components with an IT.     1

项目摘要/摘要 使用干扰色调（ITS）和矢量差异分析在我们实验室中的早期研究 各种实验条件确定了大型失真产物耳声排放（DPOAES） 强大的增强和/或抑制所证明的组成部分可能是由位于 F2主音调的几个八度。沙鼠中提出的实验侧重于识别 人工耳蜗微力学中的物理机制，解释了这种基本DPOAE的存在 组件。特别是，以下所述的研究旨在表明基本组成部分是 由最近描述的非线性振动热点（VHSS）产生的，该热点位于外毛细胞（OHC） 地区。这些OHC/VHSS与BM不同，在测量BF以下的许多八度上是非线性的，并且 能够产生比其对应的BM振动大得多的物理运动。方法 将利用能够测量各种振动的非侵入性光学相干断层扫描（OCT） Corti器官的子组成，以及对等方内失真的简单记录 产品（IDP）和耳式DPOAE。这样，OHC/VHSS将被链接到非扩增的链接 因此，分布式非线性假设是基本生成的DPOAE组分的来源，因此 为其世代提供直接的物理机制。简而言之，AIM 1利用OCT来表征IDP 从BM和OHC/VHS区域仅作为主要色调水平和F2/F1比的函数 主要色调是超过Oct-测量位置的最佳频率（BF）。傅立叶 将执行从BM和OHC/VHSS的振动转换以从这些中提取IDP 子组件。接下来，它的短暂噪声过度曝光将用于线性化非扩增 OHC/VHSS的非线性同时测量耳朵dpoaes。向量减法将是 用于隔离该组件的组件是为了产生基本的DPOAE组件。 在AIM 2中，将雇用速尿剂给药以暂时消除OHC/VHSS和BM IDP， 从而干扰广泛分布的OHC/VHS非线性和BM扩增峰 非线性，已证明可以暴露不同的恢复时间课程。以这种方式贡献 从BM峰和宽带非线性可以分开。同样，基本IDP和DPOAE组件 将在上述干预措施之前和之后通过矢量减法提取。这 这些实验的预期结果将在什么情况下阐明OHC/VHSS产生的IDP和 它们在多大程度上有助于耳道中通常记录的DPOAE。如果提议 实验是成功的，通过提供直接生成基本DPOAE的物理机制， DPOAE生成的几十年理论模型将需要重大修改和临床DP-Grams 可以通过将混淆的基本DPOAE组件与IT删除，可以改善。   1