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Primary Neural Degeneration after Cochlear Implantation: Histological and Electrophysiological Evidence from a Mouse Model
Journal article   Peer reviewed

Primary Neural Degeneration after Cochlear Implantation: Histological and Electrophysiological Evidence from a Mouse Model

Pei-Zhe Wu, Rachel Scheperle, Brian Mostaert, Robert D Gay, Ya Lang Enke, M Charles Liberman, Alexander D Claussen and Marlan R Hansen
The Journal of neuroscience, Vol.46(22), e0301262026
06/03/2026
DOI: 10.1523/JNEUROSCI.0301-26.2026
PMCID: PMC13233907
PMID: 42049515

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Abstract

Patients undergoing hearing-preservation cochlear implantation (HPCI) often retain low-frequency thresholds initially, yet many develop progressive loss of residual hearing and variable speech performance. The biological basis of this delayed functional decline remains unclear. Here we show that HPCI at the basal turn induces primary neural degeneration at the cochlear apex-a region anatomically remote from the electrode array and functionally important for low-frequency hearing and speech discrimination. Using a mouse model of HPCI (all male), we systematically quantified longitudinal electrophysiological and histopathological changes up to 16 weeks after implantation. Although low-frequency thresholds were preserved and remained stable, suprathreshold ABR wave I amplitudes progressively declined. Correspondingly, afferent synapses were progressively reduced across the cochlea, with synapse loss exceeding inner hair cell loss by 7.1-fold at the cochlear apex, demonstrating neural degeneration independent of inner hair cell death. Cochlear nerve fiber loss followed synapse loss and was consistent with progressive neural disconnection. Notably, apical synapse survival was best predicted by the slope of the wave I amplitude-level function, directly linking CI-induced primary neural degeneration to suprathreshold electrophysiological decline. Together, these findings demonstrate that HPCI can induce primary neural degeneration at the cochlear apex, providing a mechanistic explanation for the delayed loss of residual acoustic hearing and for functional deficits not captured by audiometric threshold measures. We demonstrate that hearing-preservation cochlear implantation induces primary neural degeneration at the cochlear apex, a region anatomically remote from the electrode array and essential for low-frequency hearing and speech recognition. Using a longitudinal mouse model, we show that afferent synapse and cochlear nerve fiber loss progresses across the cochlea and markedly exceeds inner hair cell loss at the apex. This degeneration occurs despite preserved low-frequency thresholds and is best predicted by suprathreshold ABR wave I measures, revealing neural dysfunction not detected by standard audiometry. These findings challenge the prevailing assumption that apical cochlear structures remain intact after basal electrode insertion.
 cochlear implant delayed loss of residual hearing hearing-preservation cochlear implant primary neural degeneration synaptopathy

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