Abstract
OBJECTIVES: Cochlear synaptopathy, caused by the destruction of synaptic connections due to aging, noise exposure, and ototoxic agents, is defined as auditory dysfunction despite the normal hearing threshold, specifically in challenging situations. One of the main obstacles in synaptopathy studies and the integration and generalization of research findings is the need for a valid diagnostic test. Although the issue of identifying synaptopathy has received considerable critical attention, little agreement is available on a valid and efficient diagnostic method for cochlear synaptopathy. MATERIAL & METHODS: A critical review was conducted on previous animal and human studies addressing cochlear synaptopathy, with particular emphasis on the paired-click paradigm and I' wave electrophysiological assessments. Subsequently, pertinent physiological and biophysical models elucidating excitatory postsynaptic potentials at the inner hair cell ribbon synapse were analyzed. Finally, the feasibility and limitations of I' wave recording were theoretically evaluated, with recommendations for future validation studies. RESULTS: A review of the existing evidence and analysis of biophysical modeling data indicate that the I' wave in the auditory brainstem response, particularly when using the paired-click paradigm, represents the excitatory postsynaptic potential (EPSP) generated at the inner hair cell ribbon synapse. CONCLUSION: The present hypothesis attempts to bring forward a non-invasive tool that can investigate synaptic function. It sheds new light on future studies in cochlear synaptopathy by suggesting the I' wave as its biomarker.