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: 10424840
• 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/10424840
• 关键词: Acoustic Nerve; Algorithms; Animal Model; 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; Lead; 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; base; 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; Acoustic Nerve; Algorithms; Animal Model; 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; Lead; 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; base; 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％的有听力投诉的退伍军人具有临床正常的听力图。很遗憾， 这些患者的治疗选择有限，结果是可变的，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共同发生，并可能解释这些感知投诉。 但是，亚临床外毛细胞（OHC）损伤或中央听觉缺陷，例如由 创伤性脑损伤可能导致类似的问题。治疗结果的差异可能是由于 潜在损害的异质性质，无法使用现有临床确定 测试。最好的治疗方法可能取决于特定的损害类型。虽然OHC功能可以是 通过耳声发射（OAE）评估，当前的听力学测试无法区分 中央听觉系统的外围剥离和损坏。但是，几种生理措施 对动物模型中的脱素敏感。这些包括听觉脑干响应（ABR）， 响应后的包膜（EFR）和中耳肌肉反射（MEMR）。我们出版和初步 数据表明，ABR，EFR和MEMR测量值降低了 与噪音有限的非退伍军人相比，举报在服兵役期间的噪音暴露高度 暴露，与噪声诱导的脱落的动物模型一致。此外，我们的数据表明 这些测量值的减少与听觉感知缺陷（如耳鸣）有关，并增加 在复杂的语音感知过程中，认知负载（即听力工作）。该提议的总体目标是 为了开发临床测试以进行剥离并确定这种情况的感知影响。我们的中心 假设是可以通过比较其生理测量来鉴定出脱离的患者 对于那些具有较低风险且异常患者的规范样本的人 测量结果将具有听觉感知缺陷（耳鸣，超声波和复杂语音困难 感知，包括增加听力工作）。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测量的规范范围，对性别和OHC进行了统计调整 功能，可用于识别可能具有明显的人工耳蜗的患者； 2）比较 ABR，EFR和MEMR测量的能力在低与高的群体之间区分了它们的能力 停用风险； 3）表征异常的生理测量与 听觉感知缺陷。这种方法具有创新性，因为它1）允许识别脱依 在个别患者中； 2）通过OAE测量将OHC函数纳入规范范围； 3） 研究测试措施/刺激的最佳组合，用于识别剥离，包括使用 新的EFR和MEMR测量； 4）评估复杂语音期间的听力增加 感知是剥夺的可能结果。拟议的研究很重要，因为有 目前，尚不清楚临床测试的临床测试和脱附的感知后果尚不清楚，而是 防止治疗选择的发展。预计这项研究将导致1）鉴定 生理测试措施和具有规范范围的刺激参数，我们可以推荐用于临床 评估人工耳蜗的脱落和2）阐明了脱落的感知影响。临床 通过允许的建议，诊断诊断不诊断的建议将对临床实践产生立即影响 听力学家测试剥离。临床测试，用于脱离，并结合测量 使用OAE的OHC功能将允许诊断外周听觉损害。未来的研究可以 然后专注于病变特定外围部位的治疗（例如，基于个性化的助听器算法 关于OHC损坏，脱离或药物治疗的程度，用于突触修复或再生）。