Refractoriness-Based Masking Yields Threshold-Specific Human Auditory Nerve Responses

Distinct auditory nerve (AN) fiber populations with varying thresholds and vulnerabilities to synaptopathy are observable in animal models, but standard non-invasive human measures lack the resolution to differentiate these groups of fibers. This fundamental limitation hinders the translation of findings in animals to human auditory pathologies. To overcome this, we developed a novel refractoriness-masking paradigm to non-invasively isolate threshold-specific AN fiber responses in humans. By presenting rapid click trains with cumulatively rising levels (45 to 105 dB peSPL) at a 250-microsecond inter-click interval, we sequentially masked lower-threshold fibers. Using a tympanic membrane electrode, we recorded compound action potentials (CAPs) in adults with normal hearing and isolated threshold-specific responses via waveform subtraction. Our results demonstrated that the isolated CAPs exhibited decreased latencies with increasing levels and a non-linear amplitude growth, plateauing at 90 dB peSPL before sharply increasing at 105 dB peSPL. This pattern reflects the sequential recruitment of AN fiber that were not effectively recruited by the preceding clicks. Validate conditions, in which the final two clicks had equal levels, produced substantially smaller CAPs, consistent with response suppression by refractoriness. Overall, this paradigm establishes a human measurement approach for characterizing level-threshold-dependent AN responses, providing a potential way to better investigate different AN pathologies, such as cochlear synaptopathy or auditory neuropathy.