Abstract
Background: Cochlear synaptopathy is defined as the loss of synapses between inner hair cells and auditory nerve fibers. It is well established in animal models following noise exposure and aging. In humans, direct histopathologic confirmation is not feasible; therefore, synaptopathy must be inferred from electrophysiologic and behavioral proxies, contributing to variability in findings across populations.
Objective: To synthesize translational evidence for cochlear synaptopathy and to evaluate the validity of electrophysiologic markers, including auditory brainstem responses, electrocochleography, envelope following responses, and middle‑ear muscle reflex measures.
Methods: A PRISMA‑informed narrative review of peer‑reviewed studies indexed in MEDLINE, Scopus, and Embase was conducted. Animal, human temporal bone, and human in vivo investigations were organized thematically and tabulated to compare exposure categories, electrophysiologic measures, and clinical outcomes.
Results: Animal and temporal bone studies consistently demonstrate synaptic loss accompanied by reduced suprathreshold neural output despite preserved thresholds. Human findings are more heterogeneous. High‑risk groups, including individuals with military or occupational noise exposure and older adults, frequently show reduced neural responses as signs of cochlear synaptopathy, whereas younger normal‑hearing cohorts often show null results unless stress‑test paradigms or complex electrophysiologic batteries are employed.
Conclusion: Cochlear synaptopathy is a biologically established neural lesion in animals but remains a probabilistic diagnosis in humans. Convergent abnormalities across multiple electrophysiologic measures enhance detection relative to single metrics and may inform future clinical trials targeting synaptic repair.