Evaluating Human Cochlear Aging Using Otoacoustic Emissions (OAEs)

项目摘要/摘要 年龄相关性听力损失(ARHL)在美国影响着数百万人，并与 毁灭性的健康和经济后果。与年龄相关的听觉功能障碍的主要部位是耳蜗部。 耳蜗老化早在生命的第四个十年就开始了，并源于多种原因。因此，很早 鉴别诊断将是当前和未来老年性耳蜗病治疗成功的关键 功能障碍。然而，目前的临床工具对听觉老化的早期迹象非常不敏感。 外围设备。我们的长期目标是使用耳声发射(OAE)来填补这一临床空白。这个项目需要 通过填补目前阻碍OAE履行其职责的知识中的关键空白，逐步实现这一目标 潜在的诊断能力。我们通过使用OAE系统地探索老化的耳蜗来做到这一点，重点是 未被充分开发的耳蜗基，是年龄相关性衰退的开始，也是高频编码的地方。 我们的中心假设是，新陈代谢下降和不规则增加(即，由于 耳蜗基底部的随机组织退化)是耳蜗老化的最早迹象，而这些迹象 发生在使用目前的临床测量方法(即行为测听)可以检测到之前。我们将对此进行测试 通过追求三个特定目标来研究不同年龄被认为正常的耳朵的耳蜗功能的假设 按照传统的衡量标准。在目标1中，我们将描述年龄如何影响两种类型的OAE的生长 (失真和反射)通过人类听觉的最高频率(20千赫)。这种双排放方法 已被证明在阐明与年龄相关的耳蜗性衰退的机制方面很有希望，但尚未被使用 通过耳蜗基底部来描述衰老的特征。在目标2中，我们将评估老龄化对世代的影响 同一地区的两种类型的OAE。了解耳声发射沿耳蜗区的位置，以及它们是否 受到耳蜗基底区的影响(我们假设耳蜗基底区在衰老的早期阶段会下降)是至关重要的 用于解释老化的OAE模式和识别耳蜗性ARHL的病因。在《目标3》中，我们将 研究耳声发射产生区域、知觉调谐和年龄之间的关系。一个关键问题是 是否可以使用传统上不使用的感知测量来检测耳蜗老化的早期迹象 临床(例如，心理物理调谐)。我们将系统地探讨耳蜗调谐之间的关系。 从失真和反射获得的估计OAEs和心理物理调谐估计，并探讨如何 这些关系会随着年龄的增长而变化。了解这一点对于确定耳蜗后滤过是否 在老化的耳朵中具有重要意义，并用于确定耳声发射是否可用于评估老龄耳朵的耳蜗调谐。 总而言之，这项工作将探索耳声发射在检测与年龄相关的早期耳蜗中的应用 并有助于阐明推动这些耳蜗变化的生物物理机制。

PROJECT SUMMARY/ABSTRACT Age-related hearing loss (ARHL) affects millions of individuals in the U.S. and is associated with devastating health and economic outcomes. A primary site of age-related auditory dysfunction is the cochlea. Cochlear aging begins as early as the fourth decade of life and stems from multiple etiologies. Therefore, early and differential diagnosis will be key for the success of current and future treatments for age-related cochlear dysfunction. However, current clinical tools are remarkably insensitive to early signs of aging in the auditory periphery. Our long-term goal is to fill this clinical void using otoacoustic emissions (OAEs). This project takes steps towards that goal by filling in critical gaps in knowledge that currently prevent OAEs from fulfilling their diagnostic potential. We do this by systematically exploring the aging cochlea using OAEs, with a focus on the underexplored cochlear base where age-related decline begins and where high frequencies are encoded. Our central hypothesis is that metabolic decline and increased irregularities (i.e., “roughness” due to random tissue degradation) in the cochlear base are the earliest signs of cochlear aging, and that these signs occur before they are detectable using current clinical measures (i.e., behavioral audiometry). We will test this hypothesis by pursuing three specific aims that explore cochlear function in ears of varying ages deemed normal by traditional measures. In Aim 1, we will characterize how age impacts the growth of two types of OAEs (distortion and reflection) through the highest frequency of human hearing (20 kHz). This dual-emission approach has proven promising in illuminating the mechanisms of age-related cochlear decline but has not yet been used to characterize aging through the cochlear base. In Aim 2, we will assess the influence of aging on the generation region of the same two types of OAEs. Understanding where OAEs arise along the cochlear partition and if they are impacted by basal regions of the cochlea (which we hypothesize decline in an early stage of aging) is crucial for both interpreting aging OAE patterns and for discerning the etiology of cochlear ARHL. In Aim 3, we will examine the relationship between the generation region of OAEs, perceptual tuning, and age. A key question is whether early signs of cochlear aging are detectable using perceptual measures not traditionally used in the clinic (e.g., psychophysical tuning). We will systematically probe the relationship between cochlear tuning estimates derived from distortion and reflection OAEs and psychophysical estimates of tuning and explore how these relationships change with age. Understanding this will be crucial for determining if retrocochlear filtering is significant in the aging ear, and for determining if OAEs may be used to assess cochlear tuning in aged ears. Collectively, this work will explore the use of otoacoustic emissions in detecting early age-related cochlear decline and help elucidate the biophysical mechanisms driving these cochlear changes.