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

项目概要/摘要 我们实验室的早期研究使用干扰音 (IT) 和控制之间的矢量差异分析 和建立的各种实验条件，大失真产物耳声发射（DPOAE） 通过强烈增强和/或抑制证明的成分，可以来自位于以下区域： f2 主音的几个八度音阶。拟议的沙鼠实验重点是确定 耳蜗微力学中的物理机制解释了这种基础 DPOAE 的存在 成分。具体来说，下面描述的研究旨在表明基本成分是 由最近描述的位于外毛细胞 (OHC) 的非线性振动热点 (VHS) 产生 地区。这些 OHC/VHS 与 BM 不同，在低于测量值 BF 的许多倍频程内呈非线性，并且 能够产生比对应的 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） 柯蒂氏器的子组件，以及耳蜗内畸变的同步记录 产品 (iDP) 和耳道 DPOAE。通过这种方式，OHC/VHS 将广泛链接到非放大 假设分布非线性是基本生成的 DPOAE 分量的来源，因此， 为它们的产生提供直接的物理机制。简而言之，目标 1 利用 OCT 来表征 iDP 同时来自 BM 和 OHC/VHS 区域，作为主音电平和 f2/f1 比率的函数 主音从顶部逐步超过 OCT 测量位置的最佳频率 (BF)。傅立叶 将执行来自 BM 和 OHC/VHS 的振动转换，以从这些中提取 iDP 子组件。接下来，IT 和短暂的噪声过度暴露将用于线性化非放大 OHC/VHS 的非线性，同时测量耳道 DPOAE。向量减法将是 用于分离假设负责生成基础 DPOAE 成分的成分。 在目标 2 中，将使用呋塞米暂时消除 OHC/VHS 和 BM iDP， 从而干扰广泛分布的 OHC/VHS 非线性和 BM 放大峰值 非线性，已被证明表现出不同的恢复时间过程。通过这种方式，贡献 可以将 BM 峰值和宽带非线性分开。同样，基础 iDP 和 DPOAE 组件 将通过上述干预之前和之后这些措施的向量减法来提取。这 这些实验的预期结果将阐明 OHC/VHS 在什么情况下产生 iDP 和 它们对耳道中通常记录的 DPOAE 的贡献程度。如果建议 实验取得了成功，为基础 DPOAE 的生成提供了直接的物理机制， 数十年的 DPOAE 生成理论模型将需要重大修改和临床 DP-gram 可以通过消除与 IT 混淆的基础 DPOAE 组件来改进。     1