Cochlear synaptopathy can result from various insults, including acoustic trauma, aging, ototoxicity, or chronic conductive hearing loss. For example, moderate noise exposure in mice can destroy up to ∼50% of synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) without affecting outer hair cells (OHCs) or thresholds, because the synaptopathy occurs first in high-threshold ANFs. However, the fiber loss likely impairs temporal processing and hearing-in-noise, a classic complaint of those with sensorineural hearing loss. Non-human primates appear to be less vulnerable to noise-induced hair-cell loss than rodents, but their susceptibility to synaptopathy has not been studied. Because establishing a non-human primate model may be important in the development of diagnostics and therapeutics, we examined cochlear innervation and the damaging effects of acoustic overexposure in young adult rhesus macaques. Anesthetized animals were exposed bilaterally to narrow-band noise centered at 2 kHz at various sound-pressure levels for 4 hrs. Cochlear function was assayed for up to 8 weeks following exposure via auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs). A moderate loss of synaptic connections (mean of 12-27% in the basal half of the cochlea) followed temporary threshold shifts (TTS), despite minimal hair-cell loss. A dramatic loss of synapses (mean of 50-75% in the basal half of the cochlea) was seen on IHCs surviving noise exposures that produced permanent threshold shifts (PTS) and widespread hair-cell loss. Higher noise levels were required to produce PTS in macaques compared to rodents, suggesting that primates are less vulnerable to hair-cell loss. However, the phenomenon of noise-induced cochlear synaptopathy in primates is similar to that seen in rodents.

This report explores the consequences of acoustic overexposures on hearing in noisy environments for two macaque monkeys trained to perform a reaction time detection task using a Go/No-Go lever release paradigm. Behavioral and non-invasive physiological assessments were obtained before and after narrowband noise exposure. Physiological measurements showed elevated auditory brainstem response (ABR) thresholds and absent distortion product otoacoustic emissions (DPOAEs) post-exposure relative to pre-exposure. Audiograms revealed frequency specific increases in tone detection thresholds, with the greatest increases at the exposure band frequency and higher. Masked detection was affected in a similar frequency specific manner: threshold shift rates (change of masked threshold per dB increase in noise level) were lower than pre-exposure values at frequencies higher than the exposure band. Detection thresholds in sinusoidally amplitude modulated (SAM) noise post-exposure showed no difference from those in unmodulated noise, whereas pre-exposure masked detection thresholds were lower in the presence of SAM noise compared to unmodulated noise. These frequency-dependent results were correlated with cochlear histopathological changes in monkeys that underwent similar noise exposure. These results reveal that behavioral and physiological effects of noise exposure in macaques are similar to those seen in humans and provide preliminary information on the relationship between noise exposure, cochlear pathology and perceptual changes in hearing within individual subjects.

Temporal envelope fluctuations are abundant in nature and are critical for perception of complex sounds. While psychophysical sinusoidal amplitude modulation (SAM) processing studies have characterized the perception of SAM, and neurophysiological studies report a subcortical transformation from temporal to rate-based code, no studies have characterized this transformation in unanesthetized animals or in nonhuman primates. To address this, we recorded single-unit responses and compared derived neurometric measures in the cochlear nucleus (CN) and inferior colliculus (IC) to psychometric measures of modulation frequency (MF) discrimination in macaques. IC and CN neurons often exhibited tuned responses to SAM in their rate and spike-timing. Neurometric thresholds spanned a large range (2-200 Hz Δ MF). The lowest 40% of IC thresholds were less than or equal to psychometric thresholds, regardless of which code was used, while CN thresholds were greater than psychometric thresholds. Discrimination at 10-20 Hz could be explained by indiscriminately pooling 30 units in either structure, while discrimination at higher MFs was best explained by more selective pooling. This suggests that pooled brainstem activity was sufficient for AM discrimination. Psychometric and neurometric thresholds decreased as a function of stimulus duration, but IC and CN thresholds were greater and more variable than behavior at durations less than 500 ms. This slower subcortical temporal integration compared to behavior was consistent with a drift diffusion model which reproduced individual differences in performance and can constrain future neurophysiological studies of temporal integration. These measures provide an account of AM perception at the neurophysiological, computational, and behavioral levels.