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Currently there are no clinical diagnostic tools to detect human cochlear deafferentation in vivo. Preclinical studies using a combination of electrophysiological and post-mortem histological methods clearly demonstrate cochlear deafferentation including myelination loss, mitochondrial damages in spiral ganglion neurons (SGNs), and synaptic loss between inner hair cells and SGNs. Since clinical diagnosis of human cochlear deafferentation cannot include post-mortem histological quantification, various attempts based on functional measurements have been made to detect cochlear deafferentation. So far, those efforts have led to inconclusive results. Two major obstacles to the development of in vivo clinical diagnostics include a lack of standardized methods to validate new approaches and characterize the normative range of repeated measurements. In this overview, we examine strategies from previous studies to detect cochlear deafferentation from electrocochleography and auditory brainstem responses. We then summarize possible approaches to improve these non-invasive functional methods for detecting cochlear deafferentation with a focus on cochlear synaptopathy. We identify conceptual approaches that should be tested to associate unique electrophysiological features with cochlear deafferentation.<\/jats:p>","DOI":"10.1121\/10.0010317","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T11:23:20Z","timestamp":1650626600000},"page":"2802-2808","update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Optimizing non-invasive functional markers for cochlear deafferentation based on electrocochleography and auditory brainstem responses"],"prefix":"10.1121","volume":"151","author":[{"given":"Kelly C.","family":"Harris","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Head & Neck Surgery, Medical University of South Carolina 1 , 135 Rutledge Avenue, MSC 550, Charleston, South Carolina 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxin","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Northeast Ohio Medical University 2 , Rootstown, Ohio 44272, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"231","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"key":"2023080317460863400_c1","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/0378-5955(91)90012-X","article-title":"Electrically evoked auditory brainstem response: Refractory properties and strength-duration functions","volume":"51","year":"1991","journal-title":"Hear Res."},{"key":"2023080317460863400_c2","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1097\/AUD.0000000000000001","article-title":"Predicting hearing thresholds in occupational noise-induced hearing loss by auditory steady state responses","volume":"35","year":"2014","journal-title":"Ear Hear."},{"key":"2023080317460863400_c4","doi-asserted-by":"publisher","first-page":"851500","DOI":"10.3389\/fncel.2022.851500","article-title":"Detecting cochlear synaptopathy through curvature quantification of the auditory brainstem response","volume":"16","year":"2022","journal-title":"Front. 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