In mammals, a 2-hr exposure to an octave-band noise (OBN) at 100 to 108 dB SPL induces loss of synaptic ribbons between inner hair cells and auditory nerve fibers with high thresholds of response (hiT neurons), that encode high-intensity sounds. Here, we tackle the challenge of diagnosing this synaptopathy by a noninvasive functional audiological test, ultimately in humans, despite the expected absence of auditory-threshold elevation and of clear electrophysiological abnormality, hiT neuron contributions being hidden by those of more sensitive and robust neurons.
The noise-induced synaptopathy was replicated in mice (at 94, 97, and 100 dB SPL; n = 7, 7, and 8, respectively, against 8 unexposed controls), without long-lasting auditory-threshold elevation despite a twofold decrease in ribbon-synapse number for the 100-dB OBN exposure. Auditory brainstem responses (ABRs) were collected using a simultaneous broadband noise masker just able to erase the ABR response to a 60-dB tone burst. Tone burst intensity was then increased up to 100 dB SPL for eliciting reemerging ABRs (R-ABRs), dependent on hiT neurons as more sensitive neurons are masked.
In most ears exposed to 97-dB-SPL and all ears exposed to 100-dB-SPL OBN, contrary to controls, R-ABRs from the overexposed region have vanished, whereas standard ABR distributions widely overlap.
R-ABRs afford an individual noninvasive marker of normal-auditory-threshold cochlear synaptopathy. A simple modification of standard ABRs would allow hidden auditory synaptopathy to be searched in a patient.