The Potential biomarker in Assessing Cochlear Synaptopathy: Evidence from Animal and Human Studies
09-12, 17:30–18:00 (Europe/Istanbul), Audiology 2

<p>Cochlear synaptopathy, characterized by damage to the synapses between inner hair cells (IHCs) and auditory nerve fibers, has emerged as a key contributor to auditory dysfunctions such as hidden hearing loss, tinnitus, and hyperacusis, often in the absence of elevated auditory thresholds. Despite the significant neurodegenerative consequences, conventional diagnostic methods lack sufficient sensitivity and specificity to detect synaptic dysfunction in living human subjects. Here, we introduce and validate the hypothesis that the I' potential—an early-latency component in the auditory brainstem response (ABR)—can serve as a sensitive, non-invasive biomarker for IHC ribbon synapse integrity.</p> <p>The mammalian auditory system relies on the precise and rapid transmission of acoustic information, a process orchestrated by specialized ribbon synapses of the IHCs. These synapses convert graded receptor potentials, induced by hair bundle displacement, into neurotransmitter release, enabling the fine temporal coding required for accurate sound localization and speech perception. Given their unique ultrastructure, IHC ribbon synapses are particularly susceptible to insults such as acoustic overexposure, ototoxic drugs, and aging—factors implicated in cochlear synaptopathy. Notably, substantial synaptic loss can occur without detectable changes in the pure-tone audiogram, complicating early diagnosis.</p> <p>To address the need for an accessible, reliable diagnostic tool, we explored the utility of the I' potential within the ABR using the paired-click paradigm. We first tested this hypothesis in a guinea pig model, correlating I' amplitude changes with histological assessments of ribbon synapse integrity following induced synaptopathy. Subsequently, the paradigm was applied to a cohort of young, normal-hearing adults. ABRs were recorded with standard clinical equipment, and mean I' amplitudes were quantified. Our animal model data revealed that reductions in the I' amplitude were strongly associated with synaptic ribbon loss, confirming that I' reflects synaptic integrity. In human participants, the I' potential was readily observable in ABRs elicited by the paired-click protocol, and its amplitude and presence were quantifiable across individuals with normal audiometric thresholds. These findings establish the practicality and feasibility of the I' potential as a cross-species measure of auditory synaptic function. The clinical implications of using the I' potential as a diagnostic biomarker are substantial. Unlike conventional ABR wave I amplitude or otoacoustic emissions—which may be affected by extraneous factors or lack specificity for synaptic dysfunction—the I' potential targets synaptic EPSPs, providing a more direct insight into ribbon synapse status. Clinically, diminished or absent I' amplitude may herald early cochlear synaptopathy in individuals reporting difficulty with speech-in-noise perception, even in the context of normal hearing thresholds.</p> <p>Given its rapid, non-invasive, and cost-effective nature, the I' potential via the paired-click ABR could be integrated into routine clinical assessment, aiding in early detection, risk stratification, and selection of patients for targeted interventions or clinical trials. Moreover, establishing normative data on I' amplitude and latency across demographic variables will facilitate broader adoption and standardization. Our findings from both animal and human studies demonstrate that the I' potential, elicited by the paired-click ABR paradigm, is a promising biomarker for cochlear synaptopathy.</p>
<p>This proposal aims to evaluate the I’ potential as a sensitive, non-invasive biomarker for detecting cochlear synaptopathy in humans. Currently, no clinical tool can directly assess synaptic dysfunction at the level of inner hair cell ribbon synapses in living individuals. By validating the I’ potential, this study seeks to address this critical diagnostic gap and enable early identification of synaptopathy, which conventional audiological methods cannot achieve.</p>
Co-Chair Co-Chair
Nilüfer Bal
Session Chair Session Chair
Pelin Kocdor
Speaker Speaker
Akram Pourbakht
Akram Pourbakht
<p>Dr. Akram Pourbakht is an MD and PhD in the field of audiology, born in Tehran, Iran. She earned her MD degree from a national university in Iran. Dr. Pourbakht pursued her graduate studies at the University of Tokyo, where she investigated protection against noise-induced hearing loss. Her passion for the field led her to obtain a Ph.D. in Audiology.</p> <p>Currently, she is a faculty member at the Iran University of Medical Sciences and serves as the Head of the Directory Board in Audiology. Her work has been published in various peer-reviewed journals, where she has explored topics such as tinnitus, auditory processing disorders, synaptopathy, and the efficacy of different rehabilitative interventions.</p>
Pelin Kocdor
<p>Dr. Pelin Koçdor, MD, PhD Associate Professor of Otolaryngology – Head and Neck Surgery Başkent University, Istanbul, Türkiye</p> <p>Dr. Pelin Koçdor is an otologist and neurotologist with a strong foundation in both clinical surgery and neuroscience research. She currently serves as an Associate Professor at Başkent University, where she specializes in otology, lateral skull base surgery, cochlear implantation, and complex vestibular disorders.</p> <p>She completed her PhD in Neuroscience at Koç University with a focus on migraine, CGRP signaling, and hearing loss—bridging molecular neurobiology with clinical otology. Dr. Koçdor has completed fellowships in otology and neurotology at the Paparella Ear Head and Neck Institute and the University of North Carolina at Chapel Hill.</p> <p>Her research interests include vestibular migraine, Ménière’s disease, autoimmune inner ear disease, and the role of neuroinflammation in otologic conditions. She is a recipient of the Politzer Society Gold Medal (2022) and has been supported by TUBITAK and the Capita Foundation for her auditory research.</p> <p>Dr. Koçdor is a member of the American Neurotology Society, the Politzer Society, and the Turkish ENT Society, and is certified by both the Turkish and European Boards in Otolaryngology.</p>
This speaker also appears in:
Nilüfer Bal
<p>Nilüfer Bal is an Ass. Prof. lecturer at Marmara University's School of Medicine, Department of Audiology. She completed a BSC degree in audiology at Gazi University (2008) and a doctorate (PhD) in audiology at Marmara University (2021). She worked as an expert audiologist in the private sector and as a lecturer at several universities. She is the author and reviewer of several articles in scientific journals. Her research interests include ERPs, the effects of noise, auditory maturation, auditory and vestibular neurophysiology, and clinical audiology.</p>
This speaker also appears in: