Primary Neural Degeneration in the Human Cochlea: Evidence for Hidden Hearing Loss in the Aging Ear

Neuroscience. 2019 May 21;407:8-20. doi: 10.1016/j.neuroscience.2018.07.053. Epub 2018 Aug 10.


The noise-induced and age-related loss of synaptic connections between auditory-nerve fibers and cochlear hair cells is well-established from histopathology in several mammalian species; however, its prevalence in humans, as inferred from electrophysiological measures, remains controversial. Here we look for cochlear neuropathy in a temporal-bone study of "normal-aging" humans, using autopsy material from 20 subjects aged 0-89 yrs, with no history of otologic disease. Cochleas were immunostained to allow accurate quantification of surviving hair cells in the organ Corti and peripheral axons of auditory-nerve fibers. Mean loss of outer hair cells was 30-40% throughout the audiometric frequency range (0.25-8.0 kHz) in subjects over 60 yrs, with even greater losses at both apical (low-frequency) and basal (high-frequency) ends. In contrast, mean inner hair cell loss across audiometric frequencies was rarely >15%, at any age. Neural loss greatly exceeded inner hair cell loss, with 7/11 subjects over 60 yrs showing >60% loss of peripheral axons re the youngest subjects, and with the age-related slope of axonal loss outstripping the age-related loss of inner hair cells by almost 3:1. The results suggest that a large number of auditory neurons in the aging ear are disconnected from their hair cell targets. This primary neural degeneration would not affect the audiogram, but likely contributes to age-related hearing impairment, especially in noisy environments. Thus, therapies designed to regrow peripheral axons could provide clinically meaningful improvement in the aged ear.

Keywords: aging; cochlear neuropathy; hidden hearing loss; human temporal bone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Auditory Threshold / physiology
  • Cochlea / pathology
  • Cochlea / physiopathology*
  • Deafness / physiopathology*
  • Evoked Potentials, Auditory, Brain Stem / physiology
  • Female
  • Hair Cells, Auditory, Inner / pathology
  • Hair Cells, Auditory, Inner / physiology
  • Hearing Loss, Sensorineural / pathology
  • Hearing Loss, Sensorineural / physiopathology*
  • Hearing Tests / methods
  • Humans
  • Male
  • Middle Aged
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology*
  • Noise
  • Presbycusis / pathology
  • Presbycusis / physiopathology