Resolving the Paradox of Hearing Complaints with a Normal Audiogram: Differential Diagnosis and Perceptual Impacts of Cochlear Deafferentation

用正常听力图解决听力投诉的悖论：耳蜗传入神经阻滞的鉴别诊断和知觉影响

• 批准号: 10596630
• 负责人: Naomi Bramhall
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596630
• 关键词: Acoustic Nerve; Algorithms; Animal Model; Audiology; Auditory; Auditory Brainstem Responses; Auditory Threshold; Auditory system; Cell physiology; Clinical; Clinical assessments; Cochlea; Cognitive deficits; Complex; Consensus; Data; Deafferentation procedure; Diagnosis; Differential Diagnosis; Ear; Environment; Etiology; Future; Health; Hearing; Hearing Aids; Hearing Tests; Hearing problem; Hyperacusis; Inner Hair Cells; Least-Squares Analysis; Lesion; Location; Loudness; Measurement; Measures; Natural regeneration; Nature; Nerve Fibers; Noise; Outcome; Outer Hair Cells; Patients; Peripheral; Persons; Pharmacotherapy; Physiological; Population Heterogeneity; Publishing; Recommendation; Recording of previous events; Reference Values; Reflex action; Reporting; Research; Risk; Sampling; Site; Speech; Speech Perception; Stimulus; Synapses; Testing; Tinnitus; Traumatic Brain Injury; Treatment outcome; Veterans; Weight; cell injury; clinical candidate; clinical practice; cognitive load; ear muscle; high risk population; individual patient; innovation; middle ear; military service; noise exposure; normal hearing; otoacoustic emission; patient population; prevent; repaired; research clinical testing; response; sex; sound; therapy development

Approximately 10% of Veterans with hearing complaints have clinically normal audiograms. Unfortunately, treatment options for these patients are limited and the outcomes are variable, resulting in a lack of consensus on how to manage these patients. Loss of the cochlear synapses between inner hair cells and afferent auditory nerve fibers can co-occur with normal hearing thresholds and may account for these perceptual complaints. However, subclinical outer hair cell (OHC) damage or central auditory deficits, such as those arising from traumatic brain injury, could lead to similar problems. The variability in treatment outcomes may be due to the heterogeneous nature of the underlying damage, which cannot be determined using existing clinical tests. The best treatment approach may depend on the specific type of damage. Although OHC function can be assessed with otoacoustic emissions (OAEs), current audiological testing cannot differentiate between peripheral deafferentation and damage to the central auditory system. However, several physiological measures are sensitive to deafferentation in animal models. These include the auditory brainstem response (ABR), the envelope following response (EFR), and the middle ear muscle reflex (MEMR). Our published and preliminary data show that ABR, EFR, and MEMR measurements are reduced in magnitude among young Veterans who report high levels of noise exposure during their military service compared to non-Veterans with limited noise exposure, consistent with animal models of noise-induced deafferentation. In addition, our data indicates that reductions in these measurements are associated with auditory perceptual deficits such as tinnitus and increased cognitive load (i.e., listening effort) during complex speech perception. The overall objective of this proposal is to develop a clinical test for deafferentation and determine the perceptual impacts of this condition. Our central hypothesis is that patients with deafferentation can be identified by comparing their physiological measurements to those from a normative sample with a low risk of deafferentation and that patients with abnormal measurements will have auditory perceptual deficits (tinnitus, hyperacusis, and difficulty with complex speech perception, including increased listening effort). We plan to test our hypothesis by pursuing three specific aims: 1) Identify normative ranges for ABR, EFR, and MEMR measurements, statistically adjusted for sex and OHC function, that can be used to identify patients likely to have significant cochlear deafferentation; 2) Compare ABR, EFR, and MEMR measurements in terms of their ability to differentiate between groups with low vs. high deafferentation risk; and 3) Characterize the relationship between abnormal physiological measurements and auditory perceptual deficits. This approach is innovative because it 1) allows for identification of deafferentation in individual patients; 2) incorporates OHC function, through OAE measurements, into the normative ranges; 3) investigates the best combination of test measures/stimuli for identifying deafferentation, including the use of new EFR and MEMR measurements; and 4) assesses increased listening effort during complex speech perception as a possible consequence of deafferentation. The proposed research is significant because there is currently no clinical test for deafferentation and the perceptual consequences of deafferentation are unclear, preventing the development of treatment options. This study is expected to result in 1) identification of physiological test measures and stimulus parameters, with normative ranges, that we can recommend for clinical assessment of cochlear deafferentation and 2) clarification of the perceptual impacts of deafferentation. Clinical recommendations for diagnosing deafferentation will have immediate impacts on clinical practice by allowing audiologists to test for deafferentation. A clinical test for deafferentation in combination with measurement of OHC function using OAEs will allow for differential diagnosis of peripheral auditory damage. Future research can then focus on treatments for specific peripheral sites of lesion (e.g., individualized hearing aid algorithms based on the degree of OHC damage and deafferentation or drug treatments for synapse repair or regeneration).

大约 10% 有听力问题的退伍军人的听力图临床正常。很遗憾， 这些患者的治疗选择有限，结果也各不相同，导致缺乏共识 关于如何管理这些患者。内毛细胞和传入听觉之间的耳蜗突触丧失 神经纤维可以与正常的听力阈值同时出现，并且可以解释这些知觉不适。 然而，亚临床外毛细胞 (OHC) 损伤或中枢听觉缺陷，例如由以下原因引起的损伤： 外伤性脑损伤，可能会导致类似的问题。治疗结果的差异可能是由于 潜在损伤的异质性，无法使用现有的临床来确定 测试。最佳治疗方法可能取决于具体的损伤类型。尽管 OHC 功能可以 通过耳声发射 (OAE) 进行评估，当前的听力测试无法区分 外周传入神经阻滞和中枢听觉系统损伤。然而，一些生理措施 在动物模型中对传入神经阻滞敏感。这些包括听觉脑干反应（ABR）、 包络跟随反应（EFR）和中耳肌肉反射（MEMR）。我们已发布的和初步的 数据显示，年轻退伍军人的 ABR、EFR 和 MEMR 测量值均下降 报告称，与噪音有限的非退伍军人相比，他们在服兵役期间接触的噪音水平较高 暴露，与噪声引起的传入神经阻滞的动物模型一致。此外，我们的数据表明 这些测量值的减少与听觉感知缺陷有关，例如耳鸣和增加 复杂语音感知期间的认知负荷（即听力努力）。该提案的总体目标是 开发传入神经阻滞的临床测试并确定这种情况的知觉影响。我们的中央 假设可以通过比较生理测量来识别传入神经阻滞的患者 对于那些来自正常样本的患者来说，传入神经阻滞风险较低，并且患有异常的患者 测量结果会出现听觉感知缺陷（耳鸣、听觉过敏和复杂言语困难） 感知，包括增加倾听的努力）。我们计划通过追求三个具体目标来检验我们的假设： 1) 确定 ABR、EFR 和 MEMR 测量的标准范围，并根据性别和 OHC 进行统计调整 功能，可用于识别可能患有严重耳蜗传入神经阻滞的患者； 2）比较 ABR、EFR 和 MEMR 测量能够区分低组和高组 传入阻滞风险； 3) 表征异常生理测量值与 听觉感知缺陷。这种方法具有创新性，因为它 1) 可以识别传入神经阻滞 个别患者； 2）通过OAE测量将OHC功能纳入规范范围； 3） 研究用于识别传入神经阻滞的测试措施/刺激的最佳组合，包括使用 新的 EFR 和 MEMR 测量； 4) 评估在复杂演讲期间增加的听力努力 知觉是传入神经阻滞的可能结果。拟议的研究意义重大，因为 目前还没有针对传入神经阻滞的临床测试，并且传入阻滞的知觉后果尚不清楚， 阻碍治疗方案的发展。这项研究预计将导致 1) 识别 我们可以推荐用于临床的生理测试测量和刺激参数（具有规范范围） 评估耳蜗传入神经阻滞；2) 澄清传入阻滞的知觉影响。临床 诊断传入神经阻滞的建议将对临床实践产生直接影响 听力学家测试传入神经阻滞。结合测量的传入神经阻滞的临床测试 使用 OAE 的 OHC 功能将允许对周围听觉损伤进行鉴别诊断。未来的研究可以 然后专注于针对特定外围病变部位的治疗（例如，基于助听器算法的个性化助听器） OHC 损伤和传入神经阻滞的程度或突触修复或再生的药物治疗）。