Parallel Age-Related Cochlear Neural Degeneration and Cortical Gain Adaptation in Normal-Hearing Humans

Accumulating evidence indicates that aging is associated with degeneration of neural components in the cochlea even before elevated hearing thresholds indicate hearing loss. Yet, it remains uncertain how such "hidden" hearing loss might shape brain responses to sound. Age-related cochlear decline has been associated with hyperactivity in central auditory pathways, but similar hyperactivity could also arise with age-related brain changes in inhibitory neurotransmission, regardless of peripheral status. Here, we collected an extensive physiological assay of cochlear neural health in an age-diverse cohort of human participants of both sexes (N = 105, ages 18-77). Despite clinically normal hearing, the assay indicated pronounced age-related cochlear neural degeneration, including reduced electrocochleographic responses to high-level clicks from the cochlear nerve (ABR wave I) as well as reduced brainstem frequency-following responses to 326 Hz tone carriers. ABR wave V did not show the same age-related reduction, indicating a response gain specific to transient stimulation between the cochlea and auditory brainstem. In the auditory cortex, aging was associated with enhanced transient evoked responses and diminished repetition suppression. Older adults showed pronounced N1-P2 components to individual sound onsets in regular tone sequences at faster repetition rates (2 Hz), where younger adults showed more steady-state-like potentials with little P2 deflection. However, these cortical functional changes were not significantly correlated with measures of cochlear neural degeneration. This suggests primary brain aging may be a significant contributor to auditory cortical hyperactivity and altered gain adaptation, progressing in parallel with peripheral neural degeneration.