Comparing physiological signatures of synaptopathic noise exposure and carboplatin-induced inner-hair-cell...

Aging and noise over-exposure lead to complex mixtures of cochlear degradation that impair the structure and function of outer hair cells (OHCs), inner hair cells (IHCs), and the cochlear nerve. However, IHC damage and cochlear synaptopathy (CS) remain pathologies "hidden" from the audiogram. This study aimed to compare and contrast the physiological signatures of these two popular and distinct exposure paradigms using promising non-invasive assays: Envelope Following Responses (EFRs), Auditory Brainstem Response (ABRs), Wideband Middle-Ear Muscle Reflexes (WB-MEMRs), and Distortion Product Otoacoustic Emissions (DPOAEs). We utilized chinchilla models of carboplatin exposure (CA) (N = 4) and temporary threshold shift (TTS) noise-induced CS (N = 4) to compare the physiological signatures of each type of exposure. While both groups showed unchanged ABR thresholds two weeks after exposure, EFRs, ABR Wave 5/1 ratios, and MEMRs showed distinct effects of exposure. CA and TTS exposures showed differences in the pattern and degree of decreased EFR "peakiness" across different stimulus modulation types (e.g., sinusoidal vs. rectangular). Significant elevations in ABR Wave 5/1 ratios were less-pronounced in the TTS-exposed animals. Reduced WB-MEMR amplitudes and increased WB-MEMR thresholds occurred in both groups, although this effect was more pronounced for TTS. Opposite trends in DPOAE amplitudes suggest that effects on OHC integrity and auditory efferent physiology may differ between the two exposure types and their induced pathologies. Overall, these results suggest a combination of EFR "peakiness", ABR Wave 5/1 ratio, and WB-MEMR may be useful for profiling IHC dysfunction and CS as potentially distinct forms of hidden hearing loss.