PP517 - Relationship Among Suprathreshold ABR Correlates in Noise-Exposed Chinchillas

Pre-clinical studies have shown threshold measures lack sensitivity to selective loss of inner hair cells or their afferent synaptic connections. In contrast, suprathreshold auditory brainstem response (ABR) wave-1 amplitudes are greatly reduced in the presence of selective cochlear pathology, suggesting a reduction in cochlear output, without elevated threshold. However, wave-I amplitudes are variable across patients, limiting its clinical utility. The ABR can be used to assess higher-order auditory abilities by utilizing more complex signals to evoke responses (cABR), like tones-in-noise stimuli and has been suggested as a potential objective measure of cochlear status and functional hearing-in-noise ability.

 

Summary:

Objectives and Rational: Noise-induced hearing loss (NIHL) is the second leading cause of sensorineural hearing loss and is a widespread public health concern. Acute noise exposure is known to cause overt cochlear damage and result in measurable impact on overall hearing sensitivity. However, noise exposure may also result in less evident signs of cochlear damage by inducing deafferentation of inner hair cells (IHC) at the level of the spiral ganglion nerve (SGN) fibers and their dendritic synapses, in the absence of hair cell loss. Pre-clinical studies investigating selective afferent auditory nerve fiber loss, commonly referred to as cochlear synaptopathy, have repeatedly shown temporary threshold shifts (TTS), but no permanent threshold shifts (PTS). These findings demonstrate that noise-induced TTS may indicate permanent degeneration of SGN fibers even if hair cells remain intact. Furthermore, cochlear synaptopathy has been suggested to be a precursor to permanent NIHL and is speculated to contribute to functional, suprathreshold auditory deficits, such as patient reported difficulty understanding speech in complex listening environments yet present with normal pure tone thresholds. To date, our lab has demonstrated that chinchilla auditory brainstem response (ABR) thresholds have shown little to no change following selective IHC loss or synaptopathy, whereas suprathreshold ABR wave-1 amplitudes are typically reduced. Although suprathreshold wave-1 amplitude reductions have been established as the hallmark of synaptopathy in animal models, wave-1 is known to be variable across patients. Given its variability and that it’s use would require clinical baseline measures, this measure is unlikely to have sufficient sensitivity to selective IHC pathology in humans. Thus, the current investigation sought to evaluate ABR correlates using complex, tones-in-noise stimuli (cABR) and its relationship among traditional, transient ABR thresholds and suprathreshold wave-1 amplitudes in chinchillas before and after noise exposure. We hypothesized that noise trauma would result in reduced ABR wave-1 amplitudes and increased cABR wave-1/4 inter-peak latencies in the absence of elevated thresholds.

Methods: Free feeding young adult chinchillas (1-3 years-of-age) were used for this study. Sedated distortion product otoacoustic emissions (DPOAEs) and ABR thresholds were evaluated to assay the status of normal cochlear nonlinearity and as an objective measure of overall hearing ability. Suprathreshold ABR correlates were measured at 90-, 80-, and 70-dB SPL with 1, 2, 4, 8, and 12 kHz tone bursts in quiet and tones embedded in broadband noise of varying intensities with signal-to-noise ratio (SNR) ranging from +10 to -5 dB SPL. Following baseline measures, animals were exposed to an octave-band noise centered at 4 kHz delivered at 93 dB SPL through a speaker positioned above each animal’s enclosure for 24 hours. ABR testing was repeated at 24 hours and 4 weeks post-noise-exposure.

Results and

Conclusions: As expected, DPOAE and ABR thresholds generally showed complete recovery. Suprathreshold transient-evoked ABR wave-1 amplitudes were substantially reduced, consistent with synaptopathy. In contrast, tones-in-noise cABR wave-1/4 latency changes were minimal and may reveal central gain and auditory compensation occurring prior to wave-5. These findings suggest cABR interpeak wave-1/4 latencies may be a sensitive measure for selective IHC-specific pathology.