Physiological and Perceptual Assessment of Hearing in Noise in Nonhuman Primates Following Noise-Induced Cochlear Synaptopathy

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PROJECT SUMMARY Hearing in noise is a complex auditory task that is critical for effective communication in the presence of competing sounds. Several neuronal mechanisms and circuits contribute to hearing-in-noise abilities, including neuronal subpopulations that encode suprathreshold signals, neuronal response adaptation, and the middle ear muscle and medial olivocochlear reflexes (MEMR, MOCR). Many patients seeking audiologic care report difficulties hearing in noise, but have normal hearing sensitivity (i.e. `hidden hearing loss'). Cochlear synaptopathy (SYN; the loss of inner hair cell ribbon synapses) is an inner ear pathology thought to contribute to hearing-in-noise deficits, in the absence of hair cell damage and poor hearing thresholds that are more readily identified in the standard audiologic test battery. In rodents, SYN disrupts synaptic signaling, which alters neuronal adaptation and leads to loss of auditory nerve fibers, especially those with high sound-evoked thresholds that encode signals in noise and provide input to the MEMR and MOCR. Since SYN degrades neuronal mechanisms that support hearing-in-noise, SYN may result in concomitant hearing-in-noise deficits. However, few studies have directly assessed the effect of SYN on encoding of signals in noise or perceptual hearing-in-noise abilities. Corroboration of suspected SYN is limited in humans and the relationship between hearing-in-noise abilities and SYN has not been established, leading to translational uncertainty. Our nonhuman primate model of noise-induced SYN is uniquely suited to assess the consequences of SYN on hearing-in-noise and provide a translational bridge between rodent and human research. Complementary physiological and psychophysical measures will be used to assess signal in noise encoding and hearing-in- noise abilities of macaque monkeys before and after noise exposure known to cause SYN. The central hypothesis is that signal encoding and hearing abilities in noise will be impaired following SYN, with greater deficits observed in subjects with greater synapse loss. In Aim 1, encoding of signals in noise will be investigated using variants of traditional noninvasive clinical assays, including auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), MEMRs, and MOCRs, measured with and without ipsilateral and contralateral noise, in order to probe neuronal mechanisms that support in hearing-in-noise. In Aim 2, psychophysical signal detection in noise will be measured under masking conditions that elicit different kinds of neuronal adaptation involved in hearing-in-noise. Within-subject comparisons (pre- vs. post-exposure) and regressions with cochlear histological characterization of synapse loss will assess the relationship between cochlear integrity and auditory function. This multimodal approach to physiologically and perceptually measure hearing-in-noise abilities in nonhuman primates with histologically verified noise-induced SYN could result in novel biomarkers for SYN. Improving the sensitivity of differential diagnosis of hearing disorders such as hidden hearing loss is critically important with the rapid approach of therapeutics for human hearing loss.