Biomarkers of cochlear synaptopathy and their relation to suprathreshold hearing disorders in humans with sensorineural hearing loss

耳蜗突触病的生物标志物及其与感音神经性听力损失人类阈上听力障碍的关系

• 批准号: 10641773
• 负责人: Stéphane Maison
• 金额: $ 57.82万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-02 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10641773
• 关键词: Accounting; Acoustic Nerve; Adult; Affective; Animal Model; Animals; Auditory; Auditory system; Behavioral; Biological Assay; Biological Markers; Brain Stem; Cell Death; Cell physiology; Central Nervous System; Characteristics; Chronic; Cochlea; Development; Diagnosis; Disease; Electrocochleographies; Environment; Frequencies; Future; Grant; Hair Cells; Hearing; Hearing Aids; Hearing Tests; Hearing problem; Histopathology; Human; Hyperactivity; Hyperacusis; Hypersensitivity; Impairment; Inner Hair Cells; Labyrinth; Light; Location; Loudness; Maintenance; Maps; Measures; Medial; Meniere' s Disease; Nerve Degeneration; Nerve Fibers; Neurologic Symptoms; Noise; Outcome; Outcome Measure; Outer Hair Cells; Participant; Patient Recruitments; Patients; Pattern; Performance; Peripheral; Physiological; Population; Presbycusis; Prevalence; Psychoacoustics; Psychophysics; Questionnaires; Reflex action; Regression Analysis; Reporting; Research; Residual state; Role; Secondary to; Sensorineural Hearing Loss; Sensory; Series; Severities; Speech; Speech Intelligibility; Statistical Models; Subjective Tinnitus; Synapses; Temporal bone structure; Testing; Therapeutic; Time; Tinnitus; Traction; Vertigo; Visual; analog; auditory processing; biomarker identification; candidate identification; cellular pathology; cochlear synaptopathy; cognitive function; ear muscle; hearing impairment; middle ear; neural; normal aging; normal hearing; otoacoustic emission; outcome prediction; public health relevance; repaired; response; sex; sound; therapy design

Project 3 Summary – Abstract Difficulty understanding speech in noisy backgrounds, reduced sound-level tolerance and tinnitus are the most common complaints associated with noise- and age-related hearing loss. Parsing the sensory vs. neural contributions to these impairments gained new traction from animal studies showing that hair cell death (and the threshold shift it produces) is often preceded by loss of hair cell synapses with auditory nerve fibers. This cochlear neural degeneration (CND) degrades auditory processing and may contribute to difficulties understanding speech, especially in noisy environments, but has little effect on thresholds in quiet until it becomes extreme. CND could also be a major contributor to the genesis of tinnitus and hyperacusis, via an induction of central-gain adjustment secondary to the loss of auditory input to the central nervous system. Over the last grant period, we showed correlations between inferred measures of CND and word- recognition performance in difficult listening environments among normal-hearing listeners. Over the next five years, we broaden our focus to include those with threshold shifts. In Aim 1 we study high-tone hearing-loss, because temporal bone studies show that CND will be worse, despite normal thresholds in the speech- frequency region. In Aim 2 we study the flat hearing loss in late-stage Ménière's, because CND may be particularly severe in this disorder. In both, we test the correlation of the word-score outcomes with a battery of physiological measures chosen to probe the early stages of auditory processing, i.e. distortion product otoacoustic emissions and high-frequency audiometry to evaluate OHC function, threshold-in-noise tests and pitch-masking tasks to identify cochlear dead regions, and electrocochleography (including stacked ABRs), envelope-following responses to rectangular envelopes and middle-ear-muscle reflexes to probe for CND and assess its severity as a function of cochlear location. A medial olivocochlear reflex assay will evaluate the potential for hyperresponsivity of brainstem circuits. In Aim 3, we test if CND is a major elicitor of tinnitus and hyperacusis by assessing the relationships between our physiological estimates of CND, word-identification tasks, and several psychophysical measures of tinnitus and sound level tolerance. In concert with Project 4, which will further examine the same subjects, we will directly probe the relation between estimated CND and central manifestations of neural hyperactivity, perceptual hypersensitivity and behavioral hyperreactivity. The successful completion of these Aims will determine if, and to what extent, markers consistent with CND are associated with the speech intelligibility deficits observed in patients with SNHL and will clarify the association between biomarkers of peripheral neural deficits with psychophysical measures of tinnitus and sound-level intolerance. Given progress in the repair of noise-induced cochlear neural degeneration in animal models, reliable markers of CND in humans are needed to identify candidates for future therapeutics and to track the efficacy of any treatments designed to rebuild a damaged inner ear.

项目3摘要-摘要