ORIGINS OF PHYSIOLOGICAL MEASUREMENTS FROM THE EAR

耳朵生理测量的起源

• 批准号: 9008886
• 负责人: Jeffery Lichtenhan
• 金额: $ 32.41万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9008886
• 关键词: Ablation; Acoustic Nerve; Acoustics; Action Potentials; Acute; Address; Amplifiers; Animal Model; Auditory; Auditory Evoked Potentials; Auditory Physiology; Basic Science; Cells; Characteristics; Chronic; Clinical; Cochlea; Complication; Ear; Early treatment; Edema; Eligibility Determination; Endolymphatic Hydrops; Endolymphatic duct; Frequencies; Functional disorder; Health; Hearing; Human; Injection of therapeutic agent; Knowledge; Learning; Left; Length; Liquid substance; Low Frequency Deafness; Measurement; Measures; Mechanics; Meniere' s Disease; Methods; Neonatal; Noise; Nurseries; Pathology; Pharmacologic Substance; Physiological; Physiology; Process; Sensorineural Hearing Loss; Sensory; Speech; Staging; Stimulus; Symptoms; Techniques; Temporal bone structure; Testing; Uncertainty; Vasopressins; Work; base; clinical Diagnosis; clinical application; design; electrical measurement; hearing impairment; improved; insight; interest; novel strategies; novel therapeutics; otoacoustic emission; prevent; response

Acoustic and electrical measurements from normal and diseased ears have many uses but their origins are not fully understood. This work proposes to identify the origin of several objective auditory responses in ears with and without hearing loss. Transient-evoked otoacoustic emissions (TEOAEs) are widely used to screen for hearing loss in neonatal well-baby nurseries. Stimulus frequency otoacoustic emissions (SFOAEs) are widely used as a non-invasive measurement to study cochlear mechanics. Despite progress, there is controversy on where in the cochlea TEOAEs and SFOAEs originate. Aims 1 & 2 will definitively identify the origin along the cochlea of TEOAEs and SFOAEs. Our novel approach is to progressively ablate responses along the cochlear length by slowly injecting ototoxic pharmaceuticals into the cochlear apex. This will provide what no other method has been able to do: remove emission contributions from an OAE’s characteristic frequency (CF) place without removing any OAE components that originate far basal (an octave or more higher) of the CF place. The work of Aim 1 & 2 will improve the interpretation of TEOAE-based screening protocols, and advance the understanding of SFOAEs and what they tell us about cochlear tuning and the cochlear amplifier. Aim 3 will study low-frequency sensorineural hearing loss in ears with endolymphatic hydrops. Low-frequency sensorineural hearing loss and endolymphatic hydrops are hallmarks of Ménière’s disease that is the focus of high scientific and clinical interest. Our approach uses a new technique that provides an objective measure of low-frequency hearing: the Auditory Nerve Overlapped Waveform (ANOW). ANOW overcomes the longstanding obstacle that conventional electrophysiologic measurements (e.g. otoacoustic emissions and compound action potentials) do not work adequately below ~1 kHz where hearing loss in Ménière’s disease occurs. ANOW can detect dysfunction from acute cochlear fluid manipulations that is not detected by conventional measurements, suggesting that ANOW can detect the earliest stages of chronic endolymphatic hydrops. Aim 3 will use ANOW to identify early stages of dysfunction from endolymphatic hydrops before the pathology progresses and can be detected with conventional measures. The proposed studies will expand the knowledge of the origins of physiologic measurements of otoacoustic emissions and hearing loss that is needed to advance basic science studies of cochlear mechanics and clinical diagnosis of hearing loss.

正常耳朵和解散的耳朵的声学和电测量都有很多用途，但它们的起源不是 完全理解。这项工作提出的建议，以确定耳朵中几种客观听觉反应的起源 并且没有听力损失。瞬态诱发的耳声排放（TEOAE）被广泛用于筛选 新生儿良好的苗圃的听力损失。刺激频率耳声排放（SFOAE）广泛 用作研究人工耳蜗的非侵入性测量。尽管进步了，但仍有争议 在耳蜗Teoaes和Sfoaes中的位置。目标1和2将确定沿着 Teoaes和Sfoaes的耳蜗。我们的新方法是逐渐浪费沿着耳蜗的反应 长度通过将耳毒性药物缓慢注入人工耳蜗顶点。这将提供没有其他的东西 方法已经能够做到：从OAE的特征频率（CF）位置删除排放贡献 不删除CF位置的任何基础（八度或更高）的OAE组件。 AIM 1和2的工作将改善对基于TEOAE的筛选协议的解释，并提高 了解SFOAES及其对人工耳蜗调整和耳蜗放大器的了解。目标3意志 研究内淋巴水滴的耳朵的低频感官听力损失。低频 感官听力损失和内淋巴水滴是梅尼尔氏病的标志，这是 高科学和临床兴趣。我们的方法使用一种新技术，可提供客观的测量 低频听力：听觉神经重叠波形（Anow）。 Anow克服了长期的 常规电生理测量的障碍（例如，耳声排放和 复合动作电位）在梅尼氏病的听力损失的情况下不能充分起作用〜1 kHz 发生。 Anow可以检测到未检测到的急性人工耳蜗操作的功能障碍 常规测量结果，表明Anow可以检测到慢性内淋巴的最早阶段 水力局。 AIM 3将使用ANOW来识别内聚合水力化的功能障碍的早期阶段 病理进展，可以通过常规措施检测到。拟议的研究将扩大 了解耳声排放和听力损失的生理测量的起源 需要推进耳蜗机械和听力损失的临床诊断的基础科学研究。