Wednesday, April 2, 2025
4/2/2025
Consequences of chronic noise exposure in nonhuman primates - ABSTRACT Noise-induced hearing loss (NIHL, including clinically measurable audiometric threshold shifts) affects over 25 million adults, with the primary cause being exposure to occupational or other loud environmental sound. However, many noise-exposed individuals report difficulty hearing in noisy environments without clinically significant threshold increases. Animal model studies have revealed potential mechanisms of noise induced hearing difficulties (NIHD) and their accompanying psychophysical and physiological changes, including a candidate mechanism (with evidence from rodent models and emerging support from the macaque model) for clinically normal hearing with difficulty in noisy environments: cochlear synapse loss. However, animal models typically use single exposure protocols to create cochlear pathology, which are unlike the chronic noise exposures leading to NIHL in humans, who experience smaller, repeated daily noise doses that result in NIHL. Data from our macaque model of NIHL (having noise susceptibility similar to humans) suggests that the single exposure noise levels needed to induce NIHL and cochlear synapse loss are much higher than sound levels typically experienced by humans occupationally or recreationally. Nonetheless, preliminary data in macaques show that single noise exposures that cause temporary threshold shifts (TTS) result in cochlear synapse loss 2- months post exposure but not at 10-months post-exposure, and auditory processing deficits. This project will expand these early observations to more realistic chronic noise exposures similar to those experienced by workers. We propose psychophysical, physiological, and histological studies 1) to establish a timeline for the development of sustained auditory processing deficits and cochlear pathology in macaques chronically exposed to noise, and 2) to define behavioral and electrophysiological assays that detect changes in hearing that develop prior to permanent threshold shifts (PTS). Our hypothesis is that chronic noise exposures (8 hours a day, 5 days a week) cause a sequence of non-transient NIHD that progress to PTS. Specifically, we predict that chronic noise exposures will cause psychophysical changes (Aim 1): the earliest deficits will be in spatial and temporal processing, followed by deficits in processing signals in noise, followed by audiometric deficits (PTS). Physiological changes (Aim 2) will parallel psychophysical changes: earliest deficits will be in middle ear muscle reflex (MEMR) and measures of binaural and temporal processing, followed by deficits in distortion product otoacoustic emission (DPOAE) amplitudes and masked auditory brainstem responses (ABR), followed by deficits in DPOAEs and ABR thresholds. These deficits will be paralleled by cochlear pathology: early, non-transient cochlear synapse loss, followed by outer hair cell loss, followed by a combination of outer and inner hair cell loss (Aim 3). The results of these studies will reveal sensitive markers of early auditory damage with realistic noise exposures, and the sequence of cochlear pathology. Study results will be used to develop reliable, clinically viable early indicators of NIHL and enhance hearing loss prevention program outcomes.
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