Individualized Profiles of Sensorineural Hearing Loss from Non-Invasive Biomarkers of Peripheral Pathology

周围病理学非侵入性生物标志物的感音神经性听力损失个体化概况

• 批准号: 10827155
• 负责人: Samantha Nicole Hauser
• 金额: $ 9.21万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10827155
• 关键词: Acoustic Nerve; Address; Affect; Age; American; Anatomy; Animal Model; Animals; Atrophic; Audiology; Auditory; Auditory Brainstem Responses; Auditory Threshold; Autopsy; Biological Assay; Biological Markers; Caring; Categories; Chinchilla (genus); Clinic; Clinical; Cochlea; Cochlear Nerve; Communication; Complement; Complex; Complex Mixtures; Data; Data Set; Development; Diagnostic; Diagnostic tests; Economics; Environment; Foundations; Functional disorder; Gentamicins; Goals; Health; Healthcare; Hearing; Hearing Tests; Histologic; Histology; Human; Individual; Individual Differences; Infrastructure; Inner Hair Cells; Intervention; Link; Measures; Modeling; Nerve Degeneration; Noise; Outcome; Outer Hair Cells; Pathology; Perception; Performance; Peripheral; Persons; Pharmacologic Substance; Physiological; Population; Recording of previous events; Reflex action; Reporting; Research; Risk Factors; Sampling; Sensorineural Hearing Loss; Site; Societies; Speech; Speech Perception; Stria Vascularis; Temporal bone structure; Testing; Training; Translations; Work; career; clinical training; cochlear synaptopathy; design; diagnostic signature; diagnostic tool; ear muscle; hearing impairment; hearing loss treatment; human data; improved; insight; middle ear; minimally invasive; neural; noise exposure; noise perception; noninvasive diagnosis; normal hearing; personalized diagnostics; personalized medicine; pre-clinical; predictive modeling; response; social; sound; speech in noise; synergism

ABSTRACT The audiogram is the cornerstone of clinical hearing assessment, but individual differences in speech perception, especially in noisy environments, cannot be explained by audibility alone. People with normal hearing thresholds often complain of difficulty understanding speech-in-noise, and listeners with sensorineural hearing loss (SNHL) show significant variability in speech perception, even when audibility is restored. Animal models of SNHL and temporal bone histology suggest that peripheral pathology missed by the audiogram may explain some of this variance. Outer hair cell (OHC) dysfunction elevates hearing thresholds, but inner hair cell (IHC) and auditory nerve (AN) dysfunction may be hidden from the audiogram despite their impact on neural encoding of sound. The presence of specific cochlear pathologies and their relative contribution to perception, however, cannot be directly tested in humans. Instead, non-invasive biomarkers of pathology are used. Though diagnostics have been developed for identifying hidden pathologies in people with normal hearing, an individual metric is unlikely to be enough when SNHL results from a combination of peripheral dysfunctions. To address this gap, we use a battery of non-invasive diagnostic tools to determine a biomarker profile for individual subjects and assess its relationship to cochlear anatomy and speech-in-noise perception when there are varying degrees of OHC and non-OHC dysfunctions. This proposal tests our central hypothesis that identifying subtypes of SNHL from integration of biomarkers sensitive to both OHC and non-OHC pathologies significantly improves prediction of suprathreshold hearing over the audiogram alone. Using a cross-species approach, three synergistic specific aims test our hypothesis. First, we assess the differences in biomarker profiles of two chinchilla models of distinct SNHL subtypes, OHC-only hearing loss and complex SNHL (e.g., a combination of OHC, IHC, and AN dysfunction), to measure the effect of non-OHC pathologies when they co-occur with OHC dysfunction. Second, we measure physiological biomarker profiles in humans with SNHL and test whether they better predict speech understanding than the audiogram. Third, using our coordinated physiological test battery as a link between species, we make predictions about the underlying cochlear pathology distributions in humans with complex SNHL based on our histology from chinchillas with known exposures. Whether our hypotheses are supported or refuted, this cross-species dataset will advance our understanding of the factors important for everyday communication and establish a quantitative framework for developing more detailed diagnostic profiles. Greater diagnostic precision that recognizes the multifactorial physiological underpinnings of SNHL will support personalization of hearing healthcare and treatment, especially pharmaceutical interventions for hearing loss. Additionally, the quantitative, cross-species, and professional training received through completion of these aims complements my clinical training in audiology and will be foundational to my career as a translational auditory neuroscientist.

抽象的 听力图是临床听力评估的基石，但言语感知的个体差异， 尤其是在嘈杂的环境中，不能仅用可听度来解释。听力阈值正常的人 经常抱怨难以理解噪声中的语音，以及患有感音神经性听力损失 (SNHL) 的听众 即使恢复了可听度，语音感知也表现出显着的变化。 SNHL动物模型和 颞骨组织学表明，听力图遗漏的周围病理学可能可以解释其中的一些原因 方差。外毛细胞 (OHC) 功能障碍会提高听力阈值，但内毛细胞 (IHC) 和听觉阈值会升高 尽管神经（AN）功能障碍对声音的神经编码有影响，但听力图可能会隐藏它们。 然而，特定耳蜗病变的存在及其对感知的相对贡献不能被确定。 直接在人体上进行测试。相反，使用非侵入性的病理生物标志物。尽管诊断有 开发用于识别听力正常的人中隐藏的病症，单个指标不太可能 当 SNHL 是由外周功能障碍联合引起时，就足够了。为了解决这个差距，我们使用 一系列非侵入性诊断工具，用于确定个体受试者的生物标志物概况并评估其 当存在不同程度的 OHC 时，与耳蜗解剖结构和噪声中言语感知的关系 非 OHC 功能障碍。该提案检验了我们的中心假设，即从以下来源识别 SNHL 亚型： 对 OHC 和非 OHC 病理敏感的生物标志物的整合显着提高了预测 仅通过听力图进行超阈听力。使用跨物种方法，三种协同特定 目的是检验我们的假设。首先，我们评估了两种不同特征的龙猫模型的生物标志物谱差异。 SNHL 亚型、仅 OHC 听力损失和复杂 SNHL（例如 OHC、IHC 和 AN 的组合） 功能障碍），以测量非 OHC 病理与 OHC 功能障碍同时发生时的影响。第二， 我们测量了 SNHL 人类的生理生物标志物概况，并测试它们是否能更好地预测言语 比听力图更能理解。第三，使用我们协调的生理测试电池作为之间的联系 物种，我们对具有复杂特征的人类潜在的耳蜗病理分布进行预测 SNHL 基于已知暴露的龙猫的组织学。我们的假设是否得到支持或 反驳说，这个跨物种数据集将促进我们对日常生活中重要因素的理解 沟通并建立定量框架以开发更详细的诊断资料。更大 识别 SNHL 多因素生理基础的诊断精度将支持 听力保健和治疗的个性化，特别是针对听力损失的药物干预。 此外，通过完成这些目标而获得的定量、跨物种和专业培训 补充了我在听力学方面的临床培训，并将为我作为翻译听觉师的职业生涯奠定基础 神经科学家。