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 在我们实验室较早的研究中使用了干扰音(ITS)和矢量差分析之间的对照 各种实验条件确定了大失真产物耳声发射(DPOAEs) 表现为强烈增强和/或抑制的成分可能来自位于以下区域 在f2基音基础上的几个八度。拟议中的沙土鼠实验主要集中在识别一种 耳蜗细观力学中解释这种基础DPOAE存在的物理机制 组件。具体地说，下面描述的研究旨在表明基本组件是 由最近描述的定位于外毛细胞(OHC)的非线性振动热点(VHS)产生 区域。与BM不同，这些OHC/VHS在测量BF以下的许多倍频程上是非线性的，并且 能够产生比其对应的BM振动大得多的物理运动。方法 将使用非侵入性光学相干层析成像(OCT)，它能够测量各种不同的振动 Corti器官的亚组分，以及耳壳内扭曲的同步记录 产品(IDP)和耳道DPOAEs。通过这种方式，OHC/VHS将广泛地与非扩增 假设分布式非线性是基本产生的DPOAE分量的来源，因此， 为它们的产生提供了直接的物理机制。简而言之，Aim 1利用OCT来描述国内流离失所者的特征 从BM和OHC/VHS区域同时作为原音电平和f2/f1比的函数 原音在顶部超过OCT测量位置的最佳频率(BF)。傅立叶 将对来自BM和OHC/VHS的振动进行转换，以从中提取IDPs 子组件。接下来，将使用ITS和短暂的噪声过度曝光来线性化非放大 同时测量耳道DPOAEs时OHC/VHSs的非线性。向量减法将是 用于隔离假定负责生成基本DPOAE组件的组件。 在目标2中，将采用速尿给药暂时消除OHC/VHS和BM国内流离失所者， 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，捐款 从BM峰值可以分离出宽带非线性。同样，基本的IDP和DPOAE组件 将上述干预前后的这些指标进行向量减法提取。这个 这些实验的预期结果将阐明OHC/VHS在什么情况下产生国内流离失所者和 它们在多大程度上对通常记录在耳道中的DPOEs有贡献。如果建议的 通过为基本DPOAE的产生提供直接物理机制，实验是成功的， 数十年的DPOAE产生的理论模型将需要重大的修改和临床DP图 可以通过用IT去除混杂的基本DPOAE组件来改进。 -- 第1条