{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:21:22Z","timestamp":1785410482987,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,8]]},"group-title":"Neuroscience","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["F30DC020916"],"award-info":[{"award-number":["F30DC020916"]}],"id":[{"id":"https:\/\/ror.org\/04mhx6838","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1T32DC016853"],"award-info":[{"award-number":["1T32DC016853"]}],"id":[{"id":"https:\/\/ror.org\/04mhx6838","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1T32DC016853"],"award-info":[{"award-number":["1T32DC016853"]}],"id":[{"id":"https:\/\/ror.org\/04mhx6838","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Aging and noise over-exposure lead to complex mixtures of cochlear degradation that impair the structure and function of outer hair cells, inner hair cells (IHCs), and the cochlear nerve. However, IHC damage and cochlear synaptopathy (CS) remain pathologies \u201chidden\u201d from the audiogram. This study aimed to identify and differentiate the physiological signatures of these two distinct pathologies using promising non-invasive assays: Envelope Following Responses (EFRs), Auditory Brainstem Response (ABRs), Wideband middle-ear reflexes (WB-MEMRs), and Distortion Product Otoacoustic Emissions (DPOAEs). We utilized chinchilla models of carboplatin-induced (CA) IHC damage (N = 4) and temporary threshold shift (TTS) noise-induced CS (N = 4) to compare the physiological signatures of each pathology. While both groups showed unchanged ABR thresholds two weeks after exposure, EFRs, ABR Wave V\/I ratios, and MEMRs showed distinct effects of exposure. Despite non-elevated ABR-derived audiometric thresholds after exposure, both CA and TTS exposure resulted in severe in EFR \u201cpeakiness\u201d, particularly for sharp, short-duty-cycle stimuli and significant elevations in ABR Wave V\/I ratios. However, these findings were less-pronounced in the TTS-exposed animals. WB-MEMR amplitudes were decreased with elevated thresholds in both groups; this effect was more pronounced in the TTS group. Opposite trends in DPOAE amplitudes indicated that while both IHC damage and CS result in similar suprathreshold temporal coding deficits, effects on outer-hair-cell integrity and auditory efferent physiology may differ between the two pathologies. Future work and novel diagnostics should aim to distinguish these specific cochlear pathologies in clinical populations, or at the very least consider their overlap.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>A multi-metric diagnostic approach was used with chinchilla models of inner-hair-cell (IHC) damage and cochlear synaptopathy (CS).<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>IHC damage and synaptopathy both cause suprathreshold deficits \u201chidden\u201d from the audiogram.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>IHC damage results in more severe temporal envelope coding degradation than does synaptopathy.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>A combination of EFR \u201cpeakiness\u201d, ABR Wave V\/I ratio, and Wideband Middle Ear Muscle Reflex (WB-MEMR) appear to be useful measures for profiling IHC damage and CS.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.05.723072","type":"posted-content","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T04:00:22Z","timestamp":1778299222000},"source":"Crossref","is-referenced-by-count":0,"title":["Differentiating the Physiological Signatures of Cochlear Synaptopathy and Inner Hair Cell Damage in a Chinchilla Model"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0623-9536","authenticated-orcid":false,"given":"Andrew","family":"Sivaprakasam","sequence":"first","affiliation":[{"name":"Purdue University, Weldon School of Biomedical Engineering, 206 S Martin Jischke Dr, West Lafayette, IN 47907"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7790-5591","authenticated-orcid":false,"given":"Ivy","family":"Schweinzger","sequence":"additional","affiliation":[{"name":"St. Jude Children\u2019s Research Hospital Rehabilitation Services, 262 Danny Thomas Pl, Memphis, TN 38105,"},{"name":"Purdue University, Department of Speech, Language, and Hearing Sciences 715 Clinic Dr, West Lafayette, IN 47907"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1524-402X","authenticated-orcid":false,"given":"Michael","family":"Heinz","sequence":"additional","affiliation":[{"name":"PhD Purdue University, Department of Speech, Language, and Hearing Sciences Weldon School of Biomedical Engineering, 715 Clinic Drive, West Lafayette, IN USA 47907"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026051206400746000_2026.05.05.723072v1.1","unstructured":"Axe, David R. 2017. \u201cThe Effects of Hair-Cell Specific Dysfunction on Neural Coding in the Auditory Periphery.\u201d PhD Dissertation, Purdue University."},{"key":"2026051206400746000_2026.05.05.723072v1.2","unstructured":"Bates, Douglas , Martin Maechler , Ben Bolker [aut, et al. 2024. 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