Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.05.136184v1?rss=1 Authors: Vasilkov, V., Garrett, M., Mauermann, M., Verhulst, S. Abstract: Auditory de-afferentation, a permanent reduction in the number of inner-hair-cells and auditory-nerve synapses due to cochlear synaptopathy or damage, can reliably be quantified using temporal bone histology and immunostaining. There is, however, an urgent need for non-invasive markers of synaptopathy to study its perceptual consequences in live humans and to develop effective therapeutic interventions. While animal studies have identified candidate auditory-evoked-potential (AEP) based markers for synaptopathy, their interpretation in humans has suffered from translational issues related to neural generator differences, unknown hearing-damage histopathologies or measurement sensitivity. To render AEP-based markers of synaptopathy more robust and differential to the synaptopathy aspect of sensorineural hearing loss, we followed a combined computational and experimental approach. Starting from the known characteristics of auditory-nerve physiology, we optimized the stimulus envelope for envelope-following-responses (EFRs) to optimally and synchronously stimulate the available auditory-nerve population and consequently generate a strong AEP. We additionally used model simulations to explore which stimuli evoked a response which was sensitive to synaptopathy, while being insensitive to possible co-existing outer-hair-cell pathologies. We compared the model-predicted trends to AEPs recorded in younger and older listeners (N=44, 24f) who either had normal or impaired audiograms. We conclude that optimal stimulation paradigms for EFR-based quantification of synaptopathy should have sharply rising envelope shapes, a minimal plateau duration of 1.7-2.1 ms for a 120 Hz modulation rate, and inter-peak intervals which contain near-zero amplitudes. From our recorded conditions, the optimal EFR-evoking stimulus had a rectangular envelope shape with a 25% duty cycle and a 95% modulation depth. Copy rights belong to original authors. Visit the link for more info