Hearing Research 398 (2020) 108094 Contents lists available at ScienceDirect Hearing Research journal homepage: www.elsevier.com/locate/heares Cochlear microphonic latency predicts outer hair cell function in animal models and clinical populations Christofer Bester 1,#,* , Stefan Weder 1,2,3,# , Aaron Collins 1 , Adrian Dragovic 2 , Kate Brody 1 , Amy Hampson 1 , Stephen O’Leary 1,2 1 Otolaryngology, Department of Surgery, University of Melbourne, East Melbourne 3002, Australia 2 Royal Victorian Eye and Ear Hospital, 32 Gisborne St, East Melbourne 3002, Australia 3 Department of Otolaryngology, Head and Neck Surgery, University Hospital Bern, Bern, Switzerland a r t i c l e i n f o Article history: Received 18 February 2020 Revised 29 September 2020 Accepted 9 October 2020 Available online 15 October 2020 Keywords: Cochlear microphonic Auditory nerve neurophonic Electrocochleography Intraoperative monitoring Sensorineural hearing loss a b s t r a c t As recently reported, electrocochleography recorded in cochlear implant recipients showed reduced am- plitude and shorter latency in patients with more severe high-frequency hearing loss compared with those with some residual hearing. As the response is generated primarily by receptor currents in outer hair cells, these variations in amplitude and latency may indicate outer hair cell function after cochlear implantation. We propose that an absence of latency shift when the cochlear microphonic is measured on two adjacent electrodes indicates an absence or dysfunction of outer hair cells between these electrodes. We test this preclinically in noise deafened guinea pigs (2 h of a 124 dB HL, 16–24 kHz narrow-band noise), and clinically, in electrocochleographic recordings made in cochlear implant recipients immedi- ately after implantation. We found that normal hearing guinea pigs showed a progressive increase in latency from basal to apical electrodes. In contrast, guinea pigs with significantly elevated high-frequency hearing thresholds showed no change in cochlear microphonic latency measured on basal electrodes (lo- cated approximately at the 16–24 kHz location in the cochlea).. In the clinical cohort, a significant neg- ative correlation existed between cochlear microphonic latency shifts and hearing thresholds at 1-, 2-, & 4 kHz when tested on electrodes located at the relevant cochlear tonotopic place. This reduction in la- tency shift was such that patients with no measurable hearing also had no detectable latency shift (place assessed by CT scan, r’s of -.70 to -.83). These findings suggest that electrocochleography can be used as a diagnostic tool to detect cochlear regions with functioning hair cells, which may be important for defining cross-over point for electro-acoustic stimulation. © 2020 Published by Elsevier B.V. 1. Introduction Indications for cochlear implantation have expanded to include individuals with substantial residual hearing. In this subset of pa- tients, the goal of modern cochlear implant (CI) is to preserve this hearing during and after surgery, so that electroacoustic stimu- lation can be used. This approach has demonstrated substantial benefits to post-operative outcomes in speech-in-noise reception thresholds and music appreciation (Gantz et al., 2005; Turner et al., 2004). The implant recipients with residual hearing must have some functioning cochlear hair cells. Identifying the cochlear lo- cation of these functioning hair cells may be beneficial for several reasons. First, this would provide an objective measure for setting * Corresponding author. E-mail address: christofer.bester@unimelb.edu.au (C. Bester). # These authors contributed equally to this work. the electric and acoustic frequency allocations in electro-acoustic stimulation, and particularly for identifying dead hair cell regions where acoustic stimulation would not be beneficial (Bonnard et al., 2018). The second advantage would be to facilitate greater preci- sion of diagnosis of hearing loss. This may be of particular ben- efit in paediatric populations where behavioural assessments are challenging and the outcomes of existing objective measurements variable (Vlastarakos et al., 2017). In addition, cochlear implant re- cipients will likely be recipients for future regenerative therapies, and these will require precision diagnostics for patient selection. Lastly, spiral ganglion neurons (SGN) survival is related to hair cell survival, so these areas may relate to those best suited for electri- cal stimulation. Here we address the challenge that, at the present time, there exists no method for the mapping of functioning hair cells in CI recipients. We have recently estimated the cochlear travelling wave from electrocochleography (ECochG), recorded directly from CI recipi- https://doi.org/10.1016/j.heares.2020.108094 0378-5955/© 2020 Published by Elsevier B.V.