Age-related myelin deficits in the auditory brain stem contribute to cocktail-party deficits

Age-related hearing loss consists of both peripheral and central components and is an increasing global health concern. While peripheral hearing loss is well understood, central hearing loss- age-related changes in the central auditory pathways resulting in a listener's inability to process sound correctly -remains poorly understood. In this study, we focus on the pathway from the cochlear nucleus to the medial nucleus of the trapezoid body (MNTB), which depends on heavily myelinated axons for microsecond-level temporal precision required for sound localization. Using a combination of auditory brainstem response recordings (ABR), advanced light and electron microscopy, and behavioral testing with prepulse inhibition of the acoustic startle response (PPI) we identified a correlation between oligodendrocyte loss, abnormal myelination in MNTB afferents, altered ABR wave III morphology indicating MNTB dysfunction, and deficits in spatial hearing behaviors in aging Mongolian gerbils. These findings provide a mechanistic explanation of how demyelination contributes to age-related dysfunction in the auditory brainstem's sound localization pathway.