Jaro-Journal of the Association for Research in Otolaryngology最新文献

{"title":"Weighting of Spectral and Temporal Cues with n-of-m Cochlear Implant Strategies Depends on Voice Pitch.","authors":"Floris Rotteveel, Bert Maat, Chris J James, Damir Kovačić, Lina A J Reiss, Deniz Başkent, Etienne Gaudrain","doi":"10.1007/s10162-026-01073-9","DOIUrl":"https://doi.org/10.1007/s10162-026-01073-9","url":null,"abstract":"<p><strong>Purpose: </strong>The relative contributions of spectral and temporal cues to voice pitch perception in cochlear implant (CI) users remain unclear. This study aimed to directly quantify these contributions in dynamic speech stimuli with clinical n-of-m processors.</p><p><strong>Methods: </strong>Fundamental frequency (F0) discrimination was measured using consonant-vowel triplets in two experiments. Sixteen (eight female) postlingually deaf adult CI users with n-of-m strategies participated in experiment 1 (F0 range 76-242 Hz). Five (three female) also participated in experiment 2 (F0 range 242-768 Hz). Stimuli were presented acoustically or via direct stimulation. For the latter, pulse patterns were recorded in advance using the participants' own settings and modified to suppress temporal or spectral cues.</p><p><strong>Results: </strong>In experiment 1, temporal suppression drastically decreased F0 discrimination. Spectral suppression decreased the F0 discrimination of only some participants, while spectral and temporal suppression combined decreased performance further. Conversely, in experiment 2, spectral suppression caused a drop in F0 discrimination while temporal suppression had no effect. Analysis of the unaltered stimuli showed that with increasing F0, temporal cues decreased and spectral cues increased in availability.</p><p><strong>Conclusion: </strong>The novel prerecording and streaming method effectively combines realistic stimulation patterns with precise control at the pulse level. Our results indicate that in voice pitch discrimination, postlingually deafened adult CI users rely predominantly on the most available cue, which depends on the F0. Temporal cues dominate when discriminating F0s within the typical male to female voice range, while spectral cues tend to dominate within the typical female to child voice range.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On Balancing Sharpness of Excitation Patterns, Loudness, and Potential Effects on Speech Perception with Cochlear-Implant Current-Focussing Strategies.","authors":"François Guérit, Robert P Carlyon","doi":"10.1007/s10162-026-01076-6","DOIUrl":"https://doi.org/10.1007/s10162-026-01076-6","url":null,"abstract":"<p><strong>Purpose: </strong>Cochlear implant (CI) users struggle to understand speech under noisy conditions. This has long been attributed to channel interactions: a given neuron not only responds to electrical stimulation from the closest electrode but also is sensitive to stimulation from electrodes located further away. Shaping the stimulation voltage into a very sharp profile (e.g. using tripolar instead of the more common monopolar stimulation) has been proposed as a solution, only with limited success. We argue this is due to several factors: the strong correlation between envelopes of adjacent CI channels with speech sounds, the necessity to recruit enough neurons for sufficient loudness, and, at loud levels, the similarity between monopolar and sharp stimulation output voltages at locations that are at least 3-4 electrodes away from a given stimulation electrode.</p><p><strong>Methods: </strong>We describe a \"Hilltop\" method to effectively reduce the voltage more than 3-4 electrodes away from a given electrode, while keeping the same percept of place pitch as with monopolar stimulation. We assess this method psychophysically in human CI users (N = 7 males, 9 females) and with computational modelling.</p><p><strong>Results: </strong>Based on computational modelling and on psychophysical measures of charge summation, we show that the voltage difference between monopolar and Hilltop stimulation persists at the level of the spiral ganglion neurons.</p><p><strong>Conclusions: </strong>The results warrant investigations with more complex, multichannel stimuli. We also describe possible limitations of this strategy, including the presence of sidelobes of opposite effective polarity in some participants, and suggest ways to mitigate their effects.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Development of the Surgical Implantation and Fixation of an Implanted Middle Ear Microphone, the \"UmboMic,\" in Cadaveric Sheep.","authors":"Isadora C Comens, Chaoqun Zhou, Dan L Nguyen, Emma F Wawrzynek, John Z Zhang, Ioannis Kymissis, D Bradley Welling, Jeffrey H Lang, Hideko Heidi Nakajima, Elizabeth S Olson","doi":"10.1007/s10162-026-01072-w","DOIUrl":"10.1007/s10162-026-01072-w","url":null,"abstract":"","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"861"},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Model for Synthesizing Auditory Brainstem Responses to Assess Neuronal Alterations in Aging and Autistic Animal Models.","authors":"Ben-Zheng Li, Shani Poleg, Matthew Ridenour, Daniel Tollin, Tim Lei, Achim Klug","doi":"10.1007/s10162-026-01060-0","DOIUrl":"10.1007/s10162-026-01060-0","url":null,"abstract":"<p><strong>Purpose: </strong>The auditory brainstem response (ABR) is a widely used objective electrophysiology measure for non-invasively assessing auditory function and neural activity in the auditory brainstem, but its ability to reflect detailed neuronal processing is limited due to the averaging nature of the electroencephalogram-type recordings.</p><p><strong>Method: </strong>This study addresses this limitation by developing a computational model of the auditory brainstem, which is capable of synthesizing ABR traces based on a large, population scale neural extrapolation of a spiking neuronal network of auditory brainstem circuitry. The model was able to recapitulate alterations in ABR waveform morphology that have been shown to be present in two medical conditions: animal models of autism and aging. Moreover, in both conditions, the ABR alterations are caused by known, distinct changes in auditory brainstem physiology, and the model could recapitulate these changes.</p><p><strong>Results: </strong>In the autism model, the simulation revealed myelin deficits and hyperexcitability, which caused a decreased wave III amplitude and a prolonged wave III-V interval, consistent with experimentally recorded ABRs in Fmr1-KO mice (Fmr1-KO: N = 19, 9 females; B6: N = 10, 3 females). For the aging condition (old: N = 23, 11 females, P750 to P1167; young: N = 39, 13 females, P60 to P109), the model recapitulated ABRs recorded in aged gerbils and indicated a reduction in activity in the medial nucleus of the trapezoid body (MNTB), a finding validated by confocal imaging data.</p><p><strong>Conclusion: </strong>These results demonstrate not only the model's accuracy but also its ability to link features of ABR morphology with underlying neuronal properties and suggest follow-up physiological experiments.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"771-784"},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Calcium Signaling in Postsynaptic Neurons of the Medial Nucleus of the Trapezoid Body in the Mouse.","authors":"Tasmuna T Tanmy, Huimei Wang, Yong Lu","doi":"10.1007/s10162-026-01066-8","DOIUrl":"10.1007/s10162-026-01066-8","url":null,"abstract":"<p><strong>Purpose: </strong>In the central nervous system, Ca²⁺ signaling plays a pivotal role in various cellular processes, including neuronal development and maturation. Disruption of Ca²⁺ homeostasis impairs auditory circuit formation, compromising auditory processing and behavior. Here, we aimed to investigate systematically the development of Ca²⁺ signaling in neurons of the medial nucleus of the trapezoid body (MNTB), a brainstem nucleus critical for sound localization.</p><p><strong>Methods: </strong>Using Ca²⁺ imaging in brain slices from mice genetically expressing the Ca²⁺ indicator GCaMP in glycinergic cells, we studied Ca²⁺ signaling in MNTB neurons from mice of either sex at three developmental milestone stages, in response to both bath-applied agonists of various neurotransmitter receptors and synaptic activation of glutamatergic afferents.</p><p><strong>Results: </strong>Prior to hearing onset at postnatal 7 days (P7), robust Ca²⁺ responses were evoked in MNTB neurons upon activation of glutamate receptors (NMDARs, AMPARs, and group I (Gp-I) mGluRs by 200 μM NMDA, 100 μM AMPA, and 200 μM 3,5-DHPG, respectively), whereas after hearing onset (P14 and P21), responses induced by NMDA and 3,5-DHPG declined markedly while AMPA-induced responses remained relatively strong. Ca²⁺ responses upon application of GABA (100 μM) and glycine (200 μM) were detected in neonatal mice, diminished in a few days after birth, and almost completely disappeared by P7. Whole-cell patch-clamp recordings showed that stimulation of excitatory afferents evoked action potentials across all ages with no differences in firing frequency up to 100 Hz, but Ca²⁺ responses varied in a stimulus intensity- and frequency-dependent manner and exhibited developmental downregulation.</p><p><strong>Conclusion: </strong>Ca²⁺ signaling induced by activation of the major transmitter receptors in MNTB neurons is highly developmentally down-regulated.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"735-752"},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single Intratympanic Injection of Proprietary Brain-Derived Neurotrophic Factor (OTO-413) in Subjects with Speech-in-Noise Hearing Impairment: a Randomized, Dose Escalating, Double-Blind, Placebo-Controlled Phase 1/2 Study.","authors":"Alan C Foster, Jeffery J Anderson, David R Moore, Morgan Oktela Fuentes, Yiwei Wang, Peter G Volsky, K Paul Boyev, Victoria A Sanchez","doi":"10.1007/s10162-026-01061-z","DOIUrl":"10.1007/s10162-026-01061-z","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the safety and tolerability and exploratory efficacy of OTO-413, an intratympanic-administered, sustained release formulation of brain-derived neurotrophic factor (BDNF) in a thermoreversible gel, in participants with speech-in-noise hearing difficulties.</p><p><strong>Methods: </strong>This was a single dose, dose-ascending, randomized, double-blind, Placebo-controlled Phase 1/2 study conducted at 7 enrolling clinical sites in the U.S. 110 participants (56% female) enrolled had self-reported speech-in-noise (SIN) difficulties that were confirmed by a SIN test and were randomized to OTO-413 or Placebo. OTO-413 dose range was escalated from 0.01 mg to 1.5 mg within 7 Cohorts. Safety evaluations included monitoring for treatment-emergent adverse events, physical and audiological examinations, and monitoring for plasma BDNF and anti-BDNF antibodies. Exploratory efficacy outcomes included three SIN tests with the Digits-in-Noise Test (DIN), Words in Noise Test (WIN), and the American English Matrix Test (AEMT) and self-reported Patient Global Impression of Change (PGIC).</p><p><strong>Results: </strong>There were no study drug-related serious adverse events, and no audiometric safety concerns at any OTO-413 dose. Plasma levels of BDNF were comparable to endogenous levels of BDNF and anti-BDNF antibodies were not detected. An exploratory responder analysis indicated a numerical advantage for OTO-413 versus placebo over the three months of observation. Improvement was particularly evident with the WIN at the 0.3 mg dose. No improvement in PGIC was noted.</p><p><strong>Conclusion: </strong>This exploratory study demonstrated that a single intratympanic injection of OTO-413 was safe and well tolerated and provided evidence for a SIN hearing treatment benefit of 0.3 mg OTO-413.</p><p><strong>Trial registration: </strong>NCT04129775.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"843-859"},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Audiological and Vestibular Follow-up in Adult Cancer Patients Receiving Platinum-Based Chemotherapy.","authors":"Heleen Van Der Biest, Sarah Verhulst, Hannah Keppler, Leen Maes, Frederic Acke, Michael Saerens, Eline Naert, Sylvie Rottey, Ingeborg Dhooge","doi":"10.1007/s10162-026-01062-y","DOIUrl":"10.1007/s10162-026-01062-y","url":null,"abstract":"<p><strong>Purpose: </strong>Platinum-based chemotherapy is widely used in cancer care but carries a substantial risk of cochleotoxicity and vestibulotoxicity. This study aimed to characterize early (3-month) and long-term (1-year) auditory and vestibular effects of platinum derivatives in adults, with the goal of improving monitoring strategies.</p><p><strong>Methods: </strong>A total of 110 adults (34-81 years; 63 female) received cisplatin (n = 73), carboplatin (n = 22), or sequential cisplatin followed by carboplatin (ciscarbo; n = 15). Assessments at baseline, 3 months, and 1 year included conventional and extended high-frequency (EHF) audiometry, distortion product otoacoustic emissions (DPOAEs), speech perception, auditory brainstem response (ABR), and envelope following response (EFR). Vestibular testing comprised vHIT and cVEMP. Ototoxicity was classified using ASHA (1994) and graded with TUNE. Linear mixed models assessed treatment- and time-related changes.</p><p><strong>Results: </strong>Cisplatin induced significant threshold shifts across the audiogram, including low, mid, high, and extended high frequencies, with progression up to 1 year. Low- and mid-frequency thresholds remained largely stable in the carboplatin group, while the ciscarbo group showed early mid- and EHF deterioration. EHF thresholds increased across all groups. ASHA-defined ototoxicity was present in 73.5% at 3 months and > 90% at 1 year. DPOAEs revealed early, progressive OHC dysfunction, and ABR and EFR indicated neural involvement, particularly after cisplatin. Speech perception remained stable, and no significant vestibular deficits were detected.</p><p><strong>Conclusion: </strong>Cisplatin induces broad, progressive cochleotoxicity, while carboplatin produces milder, delayed effects. EHF audiometry, DPOAEs, and electrophysiological measures enhance early detection. Combining behavioral and objective markers with standardized grading supports comprehensive ototoxicity monitoring.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"823-842"},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148439193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Time-Domain Model for the Generation of Spontaneous Otoacoustic Emissions in Resonant Cavities.","authors":"Hero P Wit","doi":"10.1007/s10162-026-01063-x","DOIUrl":"10.1007/s10162-026-01063-x","url":null,"abstract":"<p><p>A long-standing question in hearing science is whether spontaneous otoacoustic emissions (SOAEs) arise from a specific active site on the basilar membrane-they have a local origin-or whether they derive from distributed active elements working together in a resonant cavity-a global picture. This paper uses numerical modelling to investigate the difference between local and global activity in the ear. The cochlea is modelled as a graded array of discrete oscillators, each of fixed natural frequency and coupled only by the surrounding fluid. We examine what happens when the damping parameters of the system are varied in particular ways. Do the continuous oscillations that emerge at the middle ear carry the tell-tale frequency of a specific oscillator-pointing to a local origin-or is the oscillation one that arose from the global activity of multiple interacting oscillators? The basic oscillating element considered here is made up of two feedback-coupled masses, a general arrangement first proposed by Neely and Kim. An important parameter is the amount of undamping of the element, such that high undamping (low damping) energizes the system and tends to generate spontaneous oscillations. We use the time-domain state-space formalism to describe the interacting system of oscillating elements. We find that the entire system can be made local or global depending on the size and distribution of the undamping parameters. Thus, if a single element is made to continuously oscillate by increasing its undamping, a spontaneous otoacoustic emission (SOAE) will emerge at the oscillator's natural frequency-it can be considered to have a local origin. On the other hand, if all the elements are provided with sufficient undamping, an SOAE can again emerge even though each individual element remains below its oscillation threshold-the conclusion being that the oscillation now arises from global coupling. In this manner, our numerical modelling shows that even when undamping is supplied irregularly all along the array (but not enough to make any individual element continuously oscillate), one or more SOAEs can still be produced. When such a system is examined, we see an underlying pattern of standing waves, but even so, we see no clear evidence of a more or less regular process for the reflection of waves from irregularities at the apical side of a resonant cavity-which is what the generally accepted global model of SOAE generation by coherent reflection calls for.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"785-804"},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148426569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Biophysical Model for Simultaneous Cochlear and Vestibular Nerve Stimulation: Insights into Neural Activation and Crosstalk in Inner Ear Implants.","authors":"Björn Vey, Michael Handler, Rudolf Glueckert, Rami Saba, Carolyn Garnham, Daniel Baumgarten","doi":"10.1007/s10162-026-01065-9","DOIUrl":"10.1007/s10162-026-01065-9","url":null,"abstract":"<p><strong>Purpose: </strong>Simultaneous hearing and balance restoration through combined cochlear-vestibular implants (CVIs) offers a promising treatment for patients with dual sensory deficits. However, the effects of electrical stimulation on neighboring neural structures in the inner ear remain poorly understood.</p><p><strong>Methods: </strong>In this study, we present a detailed computational model of the human inner ear that simulates electrical stimulation of cochlear and vestibular nerves under clinically relevant conditions. The model integrates high-resolution micro-CT-based geometry, anisotropic tissue conductivities, and myelinated fiber models to predict neural activation patterns across a wide range of clinically relevant stimulation parameters.</p><p><strong>Results: </strong>Simulation results suggest that vestibular stimulation at clinically relevant amplitudes can influence cochlear nerve activation thresholds, particularly in basal cochlear regions. Conversely, cochlear stimulation had a comparatively weaker effect on vestibular activation. Interleaved stimulation with short interstimulus intervals (smaller 100 <math><mi>μ</mi></math> s) resulted in increased excitability in the non-targeted nerve population, suggesting the potential for undesired cross-talk effects. Pulse waveform characteristics, including phase duration and symmetry, further modulated the degree of crosstalk observed.</p><p><strong>Conclusion: </strong>This model allows for comprehensive evaluation of scenarios that cannot be tested in humans due to ethical, practical, or technical limitations. As a result, it provides a valuable tool for exploring new combined simulation scenarios and may aid the development of newly designed implants.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"805-822"},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148586000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing and Optimizing Tissue Clearing Protocols for Cochlear Immunostaining and 3D Reconstruction by Light-Sheet Microscopy.","authors":"Franziska M K Becker, Gina Dunkel, Martina Giampetraglia, Bettina Weigelin, Ellen Reisinger","doi":"10.1007/s10162-026-01068-6","DOIUrl":"10.1007/s10162-026-01068-6","url":null,"abstract":"<p><strong>Purpose: </strong>Current standard methods for immunohistochemical analysis of the inner ear rely on cryosectioning of the intact cochlea or dissection of the organ of Corti. Cryosections provide only limited structural information and do not allow quantification of hair cell numbers per basilar membrane length, whereas dissections require substantial technical expertise and often result in damage to the basal cochlear turns. Tissue clearing has largely overcome these limitations and has been widely applied to organs such as the brain, heart, liver, and kidney. However, despite several reports describing cochlear clearing, a systematic comparison of diverse methods is lacking.</p><p><strong>Methods: </strong>Here, we present a comparative evaluation of five established clearing protocols applied to the mouse cochlea, including three organic solvent-based (applied to n = 10 cochleae each) and two aqueous-based approaches (n = 4/8).</p><p><strong>Results: </strong>Among these, iDISCO/cDISCO (i/cDISCO) and ethyl cinnamate (ECi) provided superior tissue transparency, morphological preservation, and immunofluorescence staining quality. In contrast, PEGASOS resulted in reduced transparency and occasional wave-like distortion of hair cell rows, probably due to uneven tissue shrinkage. ScaleS and FRUIT exhibited limited clearing performance and variable staining results. Based on these findings, we optimized the two best-performing protocols to enable cochlear clearing within only five days, using inexpensive and minimally toxic reagents.</p><p><strong>Conclusion: </strong>The resulting fastDISCO and fastECi protocols achieved clearing and immunolabeling quality comparable to their full-length counterparts while preserving tissue morphology (applied to n = 17/20 cochleae). These rapid clearing protocols support reproducible 3D light-sheet microscopy of immunostained cochleae and enable automated cell segmentation and quantitative analysis of distinct cell types, including the inner and outer hair cells.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"715-733"},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}