Effect of Inner Hair Cell Loss and Afferent Damage on Functional Hearing

摘要

ABSTRACT Audiometry, or threshold testing at frequencies essential for speech understanding, is the most common and universally accepted metric for hearing health. However, it is becoming clear from animal studies that there can be significant inner ear damage that is undetected by threshold measures and among hearing impaired individuals there can be substantial variability in functional metrics of hearing such as hearing in noise even across individuals with similar thresholds and no evidence of retrocochlear pathology. These findings have generated tremendous interest in “hidden hearing loss” characterized by inner ear damage that is undetected by threshold measures. There is now speculation that loss of afferent synapses may underlie hearing-in-noise deficits, hyperacusis, and tinnitus. However, what is the evidence for functional deficits and where do these deficits begin? Surprisingly, there is no current evidence of any significant functional deficits associated with synaptopathy in animals and there is no compelling evidence in humans. Thus, it is essential to determine the critical boundaries for when functional deficits associated with hidden hearing loss begin. Establishing the relationship between specific patterns of cochlear damage such as loss of inner hair cells (IHC) or synapses and the corresponding functional deficits undetected by thresholds are critical in understanding risk factors, early detection, and intervention for early onset or undetected hearing loss. The overall aims of this proposal is to evaluate functional hearing impairment in an animal model with degradation of afferent synapses using noise-exposure or selective ototoxic loss of inner hair cells in the absence of corresponding threshold elevations. Specifically, what is the effect of this “hidden” but significant cochlear pathology on hearing-in-noise, intensity discrimination, forward masking, tinnitus and physiological correlates of functional hearing? When do these deficits begin? When completed, this work will explicitly define the functional deficits encompassed within “hidden hearing losses” induced by noise exposure or carboplatin. These data will provide the evidence urgently needed to guide potential changes to auditory monitoring plans recommended as best practice in hearing conservation programs, enhance site of lesion diagnosis, and reveal hidden functional deficit targets for rehabilitative purposes.