Pub Date : 2026-03-01Epub Date: 2025-12-17DOI: 10.1016/j.heares.2025.109509
Christoph Müller, Nico Bilic, Matthias Bornitz, Marcus Neudert, Thomas Zahnert, Martin Koch
Intraoperative assessment of ossicular chain mobility remains challenging in reconstructive middle-ear surgery because conventional palpation is subjective. To better predict the postoperative air–bone gap (ABG) and guide decisions on whether revision surgery may be beneficial for hearing restoration, a more refined intraoperative assessment that differentiates the degree of ossicular chain mobility reduction is required. In this ex vivo study, we evaluated whether quasi-static stiffness measurements can predict sound transmission.
Twelve human cadaveric temporal bones were mounted on a robotic setup in which a force-sensing needle robotically executed a standardized palpation sequence along a predefined trajectory, enabling calculation of direction-specific stiffness metrics. Stepwise artificial stiffening of the annular ligament, the stapes superstructure and the surrounding anatomical spaces of the tympanic cavity with thin layers of UV-curable resin produced graded sound transmission losses across up to five increments (for a total of ≈20–30 dB). The derived stiffness metrics tracked this decline only partially and anisotropically, with changes corresponding to <10 dB equivalents in specific probing directions. Nevertheless, binomial generalized linear models identified stiffness thresholds that discriminated among clinically relevant ABG categories (<10 dB, 10–20 dB, >20 dB). Similar trends were observed in three additional specimens with an opened incudostapedial joint. These finding demonstrate that quantitative force measurements or simplified surgical tools fitted to specific force thresholds could potentially provide surgeons with an intraoperative evaluation support tool.
{"title":"Relationship of sound transmission and ossicular chain mobility: investigations for the development of an intraoperative predictive surgical tool using a robotic approach","authors":"Christoph Müller, Nico Bilic, Matthias Bornitz, Marcus Neudert, Thomas Zahnert, Martin Koch","doi":"10.1016/j.heares.2025.109509","DOIUrl":"10.1016/j.heares.2025.109509","url":null,"abstract":"<div><div>Intraoperative assessment of ossicular chain mobility remains challenging in reconstructive middle-ear surgery because conventional palpation is subjective. To better predict the postoperative air–bone gap (ABG) and guide decisions on whether revision surgery may be beneficial for hearing restoration, a more refined intraoperative assessment that differentiates the degree of ossicular chain mobility reduction is required. In this ex vivo study, we evaluated whether quasi-static stiffness measurements can predict sound transmission.</div><div>Twelve human cadaveric temporal bones were mounted on a robotic setup in which a force-sensing needle robotically executed a standardized palpation sequence along a predefined trajectory, enabling calculation of direction-specific stiffness metrics. Stepwise artificial stiffening of the annular ligament, the stapes superstructure and the surrounding anatomical spaces of the tympanic cavity with thin layers of UV-curable resin produced graded sound transmission losses across up to five increments (for a total of ≈20–30 dB). The derived stiffness metrics tracked this decline only partially and anisotropically, with changes corresponding to <10 dB equivalents in specific probing directions. Nevertheless, binomial generalized linear models identified stiffness thresholds that discriminated among clinically relevant ABG categories (<10 dB, 10–20 dB, >20 dB). Similar trends were observed in three additional specimens with an opened incudostapedial joint. These finding demonstrate that quantitative force measurements or simplified surgical tools fitted to specific force thresholds could potentially provide surgeons with an intraoperative evaluation support tool.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"473 ","pages":"Article 109509"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-10DOI: 10.1016/j.heares.2026.109572
Evangelia Tserga , Ivan A. Lopez , Barbara Canlon
Circadian rhythms are fundamental for maintaining physiological homeostasis, influencing processes such as sleep-wake cycles, metabolism, and hormonal regulation. The suprachiasmatic nucleus (SCN), the primary pacemaker in the brain, is necessary to maintain behavioral circadian rhythms and to synchronize peripheral clocks throughout the body in mammals. The vestibular system, responsible for balance and spatial orientation, has been implicated in circadian regulation, yet its intrinsic clock machinery remains unexplored. Previous studies suggest vestibular input influences circadian rhythms, as evidenced by altered locomotor activity and temperature control in animals with vestibular dysfunction. Additionally, vestibular disorders in humans display time-dependent patterns, further supporting a vestibular-circadian interaction. Our study investigates the presence of an autonomous circadian clock in the peripheral vestibular organs (semicircular canals SCC, saccule, utricle and vestibular ganglia) by assessing core clock gene and protein expression in vestibular structures of mice and humans. Using PERIOD2::LUCIFERASE (PER2::LUC) bioluminescence assays from mouse tissues, we observed self-sustained oscillations in SCC, saccule, and utricle, with differential amplitudes and phase relationships. RNA scope (Bmal1) confirmed the rhythmic expression in the peripheral vestibular organ from mice, corroborating their functional circadian regulation. Furthermore, we explored the impact of cisplatin, a chemotherapeutic agent, on vestibular clock rhythms. Cisplatin administration disrupts PER2 oscillations in vestibular explants in a time-dependent manner, mirroring the cochlear findings where the day or night timing of drug delivery modulates drug response. Our findings provide the first direct evidence of a clock within the peripheral vestibular organ of rodents and humans, highlighting its potential role in modulating vestibular function and responses to pharmacological interventions. These findings suggest that vestibular disorders may follow a daily pattern, which could help explain why symptoms worsen or improve at different times of the day. This could lead to better treatment strategies for millions of people affected by vestibular dysfunction. Demonstrating that the chemotherapy drug cisplatin disrupts vestibular rhythms in a time-dependent manner, suggests that administering drugs at the right time of day could minimize side effects like dizziness and nausea while maximizing effectiveness. These results underscore the importance of considering circadian timing in vestibular research and therapeutic strategies.
{"title":"Circadian control of the peripheral vestibular organs in rodents and humans","authors":"Evangelia Tserga , Ivan A. Lopez , Barbara Canlon","doi":"10.1016/j.heares.2026.109572","DOIUrl":"10.1016/j.heares.2026.109572","url":null,"abstract":"<div><div>Circadian rhythms are fundamental for maintaining physiological homeostasis, influencing processes such as sleep-wake cycles, metabolism, and hormonal regulation. The suprachiasmatic nucleus (SCN), the primary pacemaker in the brain, is necessary to maintain behavioral circadian rhythms and to synchronize peripheral clocks throughout the body in mammals. The vestibular system, responsible for balance and spatial orientation, has been implicated in circadian regulation, yet its intrinsic clock machinery remains unexplored. Previous studies suggest vestibular input influences circadian rhythms, as evidenced by altered locomotor activity and temperature control in animals with vestibular dysfunction. Additionally, vestibular disorders in humans display time-dependent patterns, further supporting a vestibular-circadian interaction. Our study investigates the presence of an autonomous circadian clock in the peripheral vestibular organs (semicircular canals SCC, saccule, utricle and vestibular ganglia) by assessing core clock gene and protein expression in vestibular structures of mice and humans. Using PERIOD2::LUCIFERASE (PER2::LUC) bioluminescence assays from mouse tissues, we observed self-sustained oscillations in SCC, saccule, and utricle, with differential amplitudes and phase relationships. RNA scope (<em>Bmal1</em>) confirmed the rhythmic expression in the peripheral vestibular organ from mice, corroborating their functional circadian regulation. Furthermore, we explored the impact of cisplatin, a chemotherapeutic agent, on vestibular clock rhythms. Cisplatin administration disrupts PER2 oscillations in vestibular explants in a time-dependent manner, mirroring the cochlear findings where the day or night timing of drug delivery modulates drug response. Our findings provide the first direct evidence of a clock within the peripheral vestibular organ of rodents and humans, highlighting its potential role in modulating vestibular function and responses to pharmacological interventions. These findings suggest that vestibular disorders may follow a daily pattern, which could help explain why symptoms worsen or improve at different times of the day. This could lead to better treatment strategies for millions of people affected by vestibular dysfunction. Demonstrating that the chemotherapy drug cisplatin disrupts vestibular rhythms in a time-dependent manner, suggests that administering drugs at the right time of day could minimize side effects like dizziness and nausea while maximizing effectiveness. These results underscore the importance of considering circadian timing in vestibular research and therapeutic strategies.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"473 ","pages":"Article 109572"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-18DOI: 10.1016/j.heares.2026.109575
John J. Guinan Jr. , Hui Nam
The auditory-nerve initial peak (ANIP) is the earliest response from moderate-to-high-level clicks in cat auditory-nerve type-1 fibers with characteristic frequencies (CFs) <3 kHz. ANIP is inhibited by medial-olivocochlear-efferent stimulation, and is suppressed when low-frequency (50 Hz) “bias” tones place the outer-hair-cell (OHC) mechano-electric-transduction (MET) function into low-slope, saturating edges. These properties show that ANIP emanates from OHC motility. Unexpectedly, the bias-tone phase that produces the most suppression (the major-suppression phase, MSP) is opposite for ANIP versus for low-level click or tone responses. We present data showing this difference, plus this hypothesis for its origin: Low-level responses take several cycles to build up and their gain is set by the local MET-function slope; their MSP is when the bias tone quasi-statically deflects the MET operating point to its nearest low-slope, saturation edge. In contrast, ANIP is the first half-cycle response from higher-level clicks, and requires OHC stereocilia deflection only in one direction. When a bias tone places the OHC-MET operating point at its nearest saturating edge, a rarefaction-click’s unidirectional initial stereocilia deflection is away from this saturation, enabling a large traverse of the MET-function high-slope, high-gain region. The bias-tone level necessary to reach criterion suppression was higher for ANIP than for low-level clicks, which indicates that ANIP suppression occurred more basal where BM stiffness is higher. We hypothesize that ANIP is driven by apically-directed transverse motion of cortilymph and nearby organ-of-Corti-core tissue, i.e., is separate from the traveling-wave. Waxing-and-waning click responses also show that traveling waves are not simple, unitary waves.
听觉神经初始峰值(ANIP)是猫听觉神经1型纤维在中高强度咔哒声中最早的反应,其特征频率为CFs。
{"title":"Bias-tone suppression of the auditory-nerve initial-peak (ANIP) response supports the hypothesis that ANIP is driven by cortilymph-organ-of-Corti-core longitudinal motion","authors":"John J. Guinan Jr. , Hui Nam","doi":"10.1016/j.heares.2026.109575","DOIUrl":"10.1016/j.heares.2026.109575","url":null,"abstract":"<div><div>The auditory-nerve initial peak (ANIP) is the earliest response from moderate-to-high-level clicks in cat auditory-nerve type-1 fibers with characteristic frequencies (CFs) <3 kHz. ANIP is inhibited by medial-olivocochlear-efferent stimulation, and is suppressed when low-frequency (50 Hz) “bias” tones place the outer-hair-cell (OHC) mechano-electric-transduction (MET) function into low-slope, saturating edges. These properties show that ANIP emanates from OHC motility. Unexpectedly, the bias-tone phase that produces the most suppression (the major-suppression phase, MSP) is opposite for ANIP versus for low-level click or tone responses. We present data showing this difference, plus this hypothesis for its origin: Low-level responses take several cycles to build up and their gain is set by the local MET-function slope; their MSP is when the bias tone quasi-statically deflects the MET operating point to its nearest low-slope, saturation edge. In contrast, ANIP is the first half-cycle response from higher-level clicks, and requires OHC stereocilia deflection only in one direction. When a bias tone places the OHC-MET operating point at its nearest saturating edge, a rarefaction-click’s unidirectional initial stereocilia deflection is <em>away from</em> this saturation, enabling a large traverse of the MET-function high-slope, high-gain region. The bias-tone level necessary to reach criterion suppression was higher for ANIP than for low-level clicks, which indicates that ANIP suppression occurred more basal where BM stiffness is higher. We hypothesize that ANIP is driven by apically-directed transverse motion of cortilymph and nearby organ-of-Corti-core tissue, i.e., is separate from the traveling-wave. Waxing-and-waning click responses also show that traveling waves are not simple, unitary waves.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"473 ","pages":"Article 109575"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-20DOI: 10.1016/j.heares.2026.109578
Jing Qian , Minghui Xiao , Jijun Guo , Danyan Cao , Xuehua Wu , Xiufeng Lu , Linyan Shu , Hairu Yang , Taihua Long , Aichu Yang
Noise-induced hearing loss represents a significant global occupational health issue. Understanding the recovery patterns of temporary threshold shift (TTS) is crucial for early intervention. This longitudinal study enrolled 140 occupational noise-exposed workers and conducted serial audiological assessments over one week to characterize multi-frequency TTS recovery trajectories and explore influencing factors. The results showed that the highest prevalence of TTS occurred at 6 kHz (81.4%), followed by 4 kHz (72.1%). Recovery was frequency-dependent: low-frequency hearing thresholds (0.5-1 kHz) returned to baseline within 72.2 h in more than 85% of participants, while recovery at high frequencies (4-6 kHz) was comparatively slower. Longer occupational noise exposure (>10 years), male, and higher noise level (≥85 dB(A)) were each associated with delayed recovery. Notably, although more than 80% of participants showed substantial hearing recovery within 72.2 h, complete recovery across all frequencies required up to one week, this suggests that the current mandated 48-h pre-audiometry rest period may be insufficient to assess full auditory recovery. We recommend extending this rest period to 72 h, with a follow-up confirmatory test one week after exposure, to provide a more evidence-based approach for occupational hearing protection protocols.
{"title":"Recovery patterns and influencing factors of temporary threshold shifts in occupational noise-exposed workers","authors":"Jing Qian , Minghui Xiao , Jijun Guo , Danyan Cao , Xuehua Wu , Xiufeng Lu , Linyan Shu , Hairu Yang , Taihua Long , Aichu Yang","doi":"10.1016/j.heares.2026.109578","DOIUrl":"10.1016/j.heares.2026.109578","url":null,"abstract":"<div><div>Noise-induced hearing loss represents a significant global occupational health issue. Understanding the recovery patterns of temporary threshold shift (TTS) is crucial for early intervention. This longitudinal study enrolled 140 occupational noise-exposed workers and conducted serial audiological assessments over one week to characterize multi-frequency TTS recovery trajectories and explore influencing factors. The results showed that the highest prevalence of TTS occurred at 6 kHz (81.4%), followed by 4 kHz (72.1%). Recovery was frequency-dependent: low-frequency hearing thresholds (0.5-1 kHz) returned to baseline within 72.2 h in more than 85% of participants, while recovery at high frequencies (4-6 kHz) was comparatively slower. Longer occupational noise exposure (>10 years), male, and higher noise level (≥85 dB(A)) were each associated with delayed recovery. Notably, although more than 80% of participants showed substantial hearing recovery within 72.2 h, complete recovery across all frequencies required up to one week, this suggests that the current mandated 48-h pre-audiometry rest period may be insufficient to assess full auditory recovery. We recommend extending this rest period to 72 h, with a follow-up confirmatory test one week after exposure, to provide a more evidence-based approach for occupational hearing protection protocols.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"473 ","pages":"Article 109578"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-10DOI: 10.1016/j.heares.2026.109571
Marlies Geys , Leanne Sijgers , Timona Leandra Oesch , Patrick Boyle , Josef Chalupper , Alexander Huber , Flurin Pfiffner
This study compared outcomes of two electrophysiological measures, electrocochleography (ECochG) and panoramic electrically-evoked compound action potential (PECAP), and two psychophysical measures, temporal and electrode discrimination test (TED) and spectrotemporal two-octave bandpass modulation test (STM), in cochlear implant (CI) listeners. The aim was to investigate whether tonotopic regions showing poorer performance on the acoustic STM test also exhibit reduced peripheral integrity (ECochG and PECAP) or diminished modulation encoding abilities at the electrode level (TED). Twenty-seven Advanced Bionics CI candidates were prospectively enrolled prior to CI surgery. ECochG and PECAP recordings were obtained from all intracochlear electrodes intraoperatively and three months post-implantation, respectively. TED was measured via direct electrode stimulation six months post-implantation, and the STM test was conducted with CI-processed acoustic stimulation one year after surgery. All measures were obtained or averaged across four tonotopic regions. After adjusting for region-specific CI-processing differences, linear mixed model analyses showed significantly poorer STM performance in the worst-performing region compared with the other three regions (p < 0.001). TED values were also significantly worse in this region (p < 0.01), whereas ECochG and PECAP values did not differ significantly between the worst region on the STM test and the remaining regions. These findings demonstrate that while electrophysiological and psychophysical measures each provide valuable, spatially specific information, they capture distinct physiological and perceptual aspects of auditory processing. This highlights the need to investigating which measure, or combination of measures, can best guide individualized CI programming adjustments by identifying suboptimal performing tonotopic regions.
{"title":"Toward individualized cochlear implant programming: Relating electrophysiological and psychophysical indicators of tonotopic region performance","authors":"Marlies Geys , Leanne Sijgers , Timona Leandra Oesch , Patrick Boyle , Josef Chalupper , Alexander Huber , Flurin Pfiffner","doi":"10.1016/j.heares.2026.109571","DOIUrl":"10.1016/j.heares.2026.109571","url":null,"abstract":"<div><div>This study compared outcomes of two electrophysiological measures, electrocochleography (ECochG) and panoramic electrically-evoked compound action potential (PECAP), and two psychophysical measures, temporal and electrode discrimination test (TED) and spectrotemporal two-octave bandpass modulation test (STM), in cochlear implant (CI) listeners. The aim was to investigate whether tonotopic regions showing poorer performance on the acoustic STM test also exhibit reduced peripheral integrity (ECochG and PECAP) or diminished modulation encoding abilities at the electrode level (TED). Twenty-seven Advanced Bionics CI candidates were prospectively enrolled prior to CI surgery. ECochG and PECAP recordings were obtained from all intracochlear electrodes intraoperatively and three months post-implantation, respectively. TED was measured via direct electrode stimulation six months post-implantation, and the STM test was conducted with CI-processed acoustic stimulation one year after surgery. All measures were obtained or averaged across four tonotopic regions. After adjusting for region-specific CI-processing differences, linear mixed model analyses showed significantly poorer STM performance in the worst-performing region compared with the other three regions (<em>p</em> < 0.001). TED values were also significantly worse in this region (<em>p</em> < 0.01), whereas ECochG and PECAP values did not differ significantly between the worst region on the STM test and the remaining regions. These findings demonstrate that while electrophysiological and psychophysical measures each provide valuable, spatially specific information, they capture distinct physiological and perceptual aspects of auditory processing. This highlights the need to investigating which measure, or combination of measures, can best guide individualized CI programming adjustments by identifying suboptimal performing tonotopic regions.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"473 ","pages":"Article 109571"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-28DOI: 10.1016/j.heares.2026.109549
Breann Krygsman, Alisa Pitre, Sebastien Paquette
Hyperacusis and sound sensitivity are complex phenomena influenced by both auditory and psychological factors. This study investigated the relationship between hearing thresholds, perceptual ratings of natural sounds, attitudes toward noise, and sex-based differences in a sample of healthy young adults. Fifty participants underwent pure-tone audiometry, completed a psychoacoustic test assessing hyperacusis (sound sensitivity), and filled out self-report questionnaires including the Youth Attitudes to Noise Scale (YANS) and the Beliefs About Hearing Protection and Hearing Loss (BAHPHL). Contrary to expectations, greater sound sensitivity was associated with lower hearing thresholds (indicating minimal hearing loss) in the low-frequency range. This suggests that preserved low-frequency hearing may contribute to auditory discomfort. Questionnaire data revealed that individuals with higher sound sensitivity also held more negative beliefs about noise and hearing protection, highlighting the role of cognitive and affective factors. No significant sex differences were found, though prior research suggests biological distinctions may still influence auditory processing. These findings underscore the importance of considering both perceptual and psychological dimensions in understanding hyperacusis.
{"title":"Psychoacoustic and cognitive predictors of sound sensitivity in healthy young adults","authors":"Breann Krygsman, Alisa Pitre, Sebastien Paquette","doi":"10.1016/j.heares.2026.109549","DOIUrl":"10.1016/j.heares.2026.109549","url":null,"abstract":"<div><div>Hyperacusis and sound sensitivity are complex phenomena influenced by both auditory and psychological factors. This study investigated the relationship between hearing thresholds, perceptual ratings of natural sounds, attitudes toward noise, and sex-based differences in a sample of healthy young adults. Fifty participants underwent pure-tone audiometry, completed a psychoacoustic test assessing hyperacusis (sound sensitivity), and filled out self-report questionnaires including the Youth Attitudes to Noise Scale (YANS) and the Beliefs About Hearing Protection and Hearing Loss (BAHPHL). Contrary to expectations, greater sound sensitivity was associated with lower hearing thresholds (indicating minimal hearing loss) in the low-frequency range. This suggests that preserved low-frequency hearing may contribute to auditory discomfort. Questionnaire data revealed that individuals with higher sound sensitivity also held more negative beliefs about noise and hearing protection, highlighting the role of cognitive and affective factors. No significant sex differences were found, though prior research suggests biological distinctions may still influence auditory processing. These findings underscore the importance of considering both perceptual and psychological dimensions in understanding hyperacusis.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"472 ","pages":"Article 109549"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146136979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-04DOI: 10.1016/j.heares.2026.109563
Hanbo Seng , Guodong Hong , Le Wang , Yunhao Wu , Peipei Li , Tiancheng Zhang , Yuan Zhang , Xiaolong Fu , Fanglei Ye
Cochlear hair cells are critical sensory receptors for auditory function, and exposure to high-intensity noise can lead to irreversible hearing loss. However, the mechanisms underlying noise-induced hearing loss (NIHL) are poorly understood, and effective therapeutic strategies have yet to be developed. In this study, berberrubine (BB) was found to protect HEI-OC1 cells and hair cells of cochlear explants from hydrogen peroxide (H2O2)-induced damage. Furthermore, BB pretreatment protected against cochlear damage and preserved hearing in a mouse model of NIHL. Structural analysis using hematoxylin–eosin and immunofluorescence staining showed that BB pretreatment effectively protected structures such as the ribbon synapses of hair cells and the stria vascularis. In addition, BB pretreatment significantly reduced 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) levels in the cochlear hair cells following noise exposure. RNA-sequencing analyses revealed that the protective effect of BB against NIHL involved the downregulation of Traf2 and Traf6 in the MAPK signaling pathway, leading to reduced p38 phosphorylation and accumulation of the downstream stress biomarker Chop. This reduced reactive oxygen species (ROS) generation and inflammation in the cochlea of mice following noise exposure, thereby alleviating NIHL-related cochlear damage and protecting hearing function. In summary, our findings indicate that BB is an effective agent against NIHL, acting through regulation of the p38 MAPK signaling pathway to reduce ROS generation and inflammation in the cochlea, which may represent a novel preventive strategy.
{"title":"Berberrubine protects against noise-induced cochlear damage and hearing loss by inhibiting the p38 MAPK signaling pathway","authors":"Hanbo Seng , Guodong Hong , Le Wang , Yunhao Wu , Peipei Li , Tiancheng Zhang , Yuan Zhang , Xiaolong Fu , Fanglei Ye","doi":"10.1016/j.heares.2026.109563","DOIUrl":"10.1016/j.heares.2026.109563","url":null,"abstract":"<div><div>Cochlear hair cells are critical sensory receptors for auditory function, and exposure to high-intensity noise can lead to irreversible hearing loss. However, the mechanisms underlying noise-induced hearing loss (NIHL) are poorly understood, and effective therapeutic strategies have yet to be developed. In this study, berberrubine (BB) was found to protect HEI-OC1 cells and hair cells of cochlear explants from hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced damage. Furthermore, BB pretreatment protected against cochlear damage and preserved hearing in a mouse model of NIHL. Structural analysis using hematoxylin–eosin and immunofluorescence staining showed that BB pretreatment effectively protected structures such as the ribbon synapses of hair cells and the stria vascularis. In addition, BB pretreatment significantly reduced 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) levels in the cochlear hair cells following noise exposure. RNA-sequencing analyses revealed that the protective effect of BB against NIHL involved the downregulation of <em>Traf2</em> and <em>Traf6</em> in the MAPK signaling pathway, leading to reduced p38 phosphorylation and accumulation of the downstream stress biomarker Chop. This reduced reactive oxygen species (ROS) generation and inflammation in the cochlea of mice following noise exposure, thereby alleviating NIHL-related cochlear damage and protecting hearing function. In summary, our findings indicate that BB is an effective agent against NIHL, acting through regulation of the p38 MAPK signaling pathway to reduce ROS generation and inflammation in the cochlea, which may represent a novel preventive strategy.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"472 ","pages":"Article 109563"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-29DOI: 10.1016/j.heares.2026.109548
Sean Lang , John J. Galvin III , Isaac Cooley , Natalia Stupak , David M. Landsberger
Despite the poor sound quality provided by cochlear implants (CIs), single-sided deaf (SSD) CI users prefer to listen to music with the acoustic hearing (AH) and CI ears together rather than with the AH ear alone. The source of this binaural benefit remains unclear. In the present study, sound quality ratings were collected in SSD CI users for music excerpts from different genres (pop, rock, and classical). A novel vocoder-to-the-CI (VCI) approach was used to control the spectral and temporal information delivered to the CI ear. Custom sine-wave vocoders were designed for each participant according to the frequency allocation in their clinical map. Sound quality ratings were collected with CI-only, AH-only, and CI+AH listening. CI+AH ratings were significantly higher than AH-only ratings when unprocessed stimuli or vocoded stimuli with spectro-temporal information were delivered to the CI ear. There were no significant differences among CI+AH ratings for the unprocessed stimuli, vocoded stimuli with spectro-temporal information, and vocoded stimuli with greatly reduced temporal cues, suggesting that the binaural benefit was largely driven by similar spectral information across ears. Effects of genre were minimal. CI+AH ratings for unprocessed music were significantly correlated with CI-only ratings (r = 0.57, p < 0.001), with the slope (0.97) suggesting that the binaural benefit was largely additive between the AH and CI ears. VCI appears to be a fruitful approach to control the spectral and temporal information delivered to the CI ear without directly manipulating CI users’ clinical processors.
尽管人工耳蜗(CIs)提供的音质较差,但单侧耳聋(SSD) CI用户更喜欢用声学听力(AH)和CI耳朵一起听音乐,而不是单独使用AH耳朵。这种双耳益处的来源尚不清楚。在本研究中,我们收集了SSD CI用户对不同类型音乐(流行、摇滚和古典)的音质评分。提出了一种新的声码器-声码器(VCI)方法来控制传递到声码器耳的频谱和时间信息。根据临床图谱中的频率分配,为每位参与者设计定制的正弦波声码器。通过仅CI、仅AH和CI+AH收听收集音质评分。当将未经处理的刺激或带有光谱时间信息的声音编码刺激传递到CI耳时,CI+AH评分明显高于AH评分。未处理的刺激、带有光谱-时间信息的声编码刺激和时间线索大大减少的声编码刺激的CI+AH评分无显著差异,表明双耳获益主要是由双耳间相似的频谱信息驱动的。体裁的影响很小。未处理音乐的CI+AH评分与仅CI评分显著相关(r = 0.57, p < 0.001),斜率(0.97)表明双耳收益在很大程度上是AH和CI耳朵之间的相加性。VCI似乎是一种有效的方法来控制传递到CI耳的频谱和时间信息,而无需直接操纵CI用户的临床处理器。
{"title":"Using vocoders to the implanted ear to investigate the binaural benefit for music sound quality in single-sided deaf cochlear implant users","authors":"Sean Lang , John J. Galvin III , Isaac Cooley , Natalia Stupak , David M. Landsberger","doi":"10.1016/j.heares.2026.109548","DOIUrl":"10.1016/j.heares.2026.109548","url":null,"abstract":"<div><div>Despite the poor sound quality provided by cochlear implants (CIs), single-sided deaf (SSD) CI users prefer to listen to music with the acoustic hearing (AH) and CI ears together rather than with the AH ear alone. The source of this binaural benefit remains unclear. In the present study, sound quality ratings were collected in SSD CI users for music excerpts from different genres (pop, rock, and classical). A novel vocoder-to-the-CI (VCI) approach was used to control the spectral and temporal information delivered to the CI ear. Custom sine-wave vocoders were designed for each participant according to the frequency allocation in their clinical map. Sound quality ratings were collected with CI-only, AH-only, and CI+AH listening. CI+AH ratings were significantly higher than AH-only ratings when unprocessed stimuli or vocoded stimuli with spectro-temporal information were delivered to the CI ear. There were no significant differences among CI+AH ratings for the unprocessed stimuli, vocoded stimuli with spectro-temporal information, and vocoded stimuli with greatly reduced temporal cues, suggesting that the binaural benefit was largely driven by similar spectral information across ears. Effects of genre were minimal. CI+AH ratings for unprocessed music were significantly correlated with CI-only ratings (<em>r</em> = 0.57, <em>p</em> < 0.001), with the slope (0.97) suggesting that the binaural benefit was largely additive between the AH and CI ears. VCI appears to be a fruitful approach to control the spectral and temporal information delivered to the CI ear without directly manipulating CI users’ clinical processors.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"472 ","pages":"Article 109548"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Age-related hearing loss (ARHL), the most prevalent sensory disorder worldwide, arises primarily from cochlear hair cells (HCs) degeneration due to aging. Although the molecular mechanisms driving HC senescence are increasingly understood, effective treatments for ARHL remain lacking. This study explores the therapeutic potential role of Pre-B cell leukemia homeobox 1 (Pbx1), a transcription factor involved in inner ear development and pluripotency, in mitigating ARHL. Our results reveal a striking age-dependent reduction in PBX1 expression within mouse cochlear HCs. Using D-galactose (D-gal)/lipopolysaccharide (LPS)-induced aging models in OC-1 cells and cultured cochlear explants, we demonstrated that lentiviral and adeno-associated virus (AAV)-mediated Pbx1 overexpression significantly suppresses senescent markers and preserves HC integrity. Remarkably, in vivo delivery of Pbx1 by AAV improved auditory function and preserved HC structure and function in ARHL mouse model. These results establish Pbx1 as a key mediator of HC aging and a promising therapeutic target for ARHL. Our findings demonstrate that AAV-mediated Pbx1 overexpression represents a potential therapeutic approach to prevent ARHL progression, paving the way for future clinical management of this prevalent sensory disorder.
{"title":"Pbx1 overexpression delays cochlear hair cells degeneration in an accelerated aging mouse model","authors":"Ruihan Zhu , Gaogan Jia , Yiming Shen , Xian Gao , Yunjie Li , Hua Jiang , Hui Chai , Mingyu Xia","doi":"10.1016/j.heares.2026.109546","DOIUrl":"10.1016/j.heares.2026.109546","url":null,"abstract":"<div><div>Age-related hearing loss (ARHL), the most prevalent sensory disorder worldwide, arises primarily from cochlear hair cells (HCs) degeneration due to aging. Although the molecular mechanisms driving HC senescence are increasingly understood<em>,</em> effective treatments for ARHL remain lacking<em>.</em> This study explores the therapeutic potential role of Pre-B cell leukemia homeobox 1 (<em>Pbx1</em>), a transcription factor involved in inner ear development and pluripotency, in mitigating ARHL. Our results reveal a striking age-dependent reduction in PBX1 expression within mouse cochlear HCs. Using D-galactose (D-gal)/lipopolysaccharide (LPS)-induced aging models in OC-1 cells and cultured cochlear explants, we demonstrated that lentiviral and adeno-associated virus (AAV)-mediated <em>Pbx1</em> overexpression significantly suppresses senescent markers and preserves HC integrity. Remarkably, in vivo delivery of <em>Pbx1</em> by AAV improved auditory function and preserved HC structure and function in ARHL mouse model. These results establish <em>Pbx1</em> as a key mediator of HC aging and a promising therapeutic target for ARHL. Our findings demonstrate that AAV-mediated <em>Pbx1</em> overexpression represents a potential therapeutic approach to prevent ARHL progression, paving the way for future clinical management of this prevalent sensory disorder.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"472 ","pages":"Article 109546"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-14DOI: 10.1016/j.heares.2026.109574
Charanjeet Kaur , Pei-Zhe Wu , Jennifer T. O’Malley , M. Charles Liberman
Patients with Ménière’s disease show lower word scores than those with other types of sensorineural hearing loss [Grant et al., 2022, Sci. Reports 12(1):8929]. We hypothesized that cochlear neural degeneration is a key driver of these differences among patients with similar audiograms. Here, we quantified histopathology in human cochleas with hearing loss from several etiologies and assessed the contribution of each cell type to word scores in a multivariable regression. We studied Ménière’s cases (n = 44), contralateral (unaffected) ears of Ménière’s cases (n = 10), age-matched normal-aging controls (n = 44), cases with platinum ototoxicity (cisplatin/carboplatin; n = 10), or aminoglycoside ototoxicity (n = 13), and age-matched controls for this (younger) group of ototoxic cases (n = 15). We quantified fractional survival of inner (IHC) and outer (OHC) hair cells, auditory-nerve (AN) peripheral axons, spiral ganglion cells (SGCs) and the stria. Ménière’s ears showed the lowest survival of IHCs (<50 %), OHCs (<30 %), AN peripheral axons (<30 %), and stria (<60 %), as well as the worst mean thresholds (75.4 dB HL) and word scores (36.68 %). Pairwise correlations showed the strongest word-score associations with IHC survival in the apical half (R² = 0.404) and with AN axons in both apical (R² = 0.329) and basal (R² = 0.324) halves of the cochlea. Despite the massive loss of AN peripheral axons, SGC loss re age-matched controls was minimal. In a multivariable regression including all histological variables and thresholds (0.5–4 kHz), AN peripheral axons were the only significant histological predictor of word score. The survival of most SGCs helps explains why most Ménière’s patients nevertheless perform well with cochlear implants.
{"title":"Cochlear neural degeneration is key to the variation in word scores among people with similar thresholds","authors":"Charanjeet Kaur , Pei-Zhe Wu , Jennifer T. O’Malley , M. Charles Liberman","doi":"10.1016/j.heares.2026.109574","DOIUrl":"10.1016/j.heares.2026.109574","url":null,"abstract":"<div><div>Patients with Ménière’s disease show lower word scores than those with other types of sensorineural hearing loss [Grant et al., 2022, Sci. Reports 12(1):8929]. We hypothesized that cochlear neural degeneration is a key driver of these differences among patients with similar audiograms. Here, we quantified histopathology in human cochleas with hearing loss from several etiologies and assessed the contribution of each cell type to word scores in a multivariable regression. We studied Ménière’s cases (<em>n</em> = 44), contralateral (unaffected) ears of Ménière’s cases (<em>n</em> = 10), age-matched normal-aging controls (<em>n</em> = 44), cases with platinum ototoxicity (cisplatin/carboplatin; <em>n</em> = 10), or aminoglycoside ototoxicity (<em>n</em> = 13), and age-matched controls for this (younger) group of ototoxic cases (<em>n</em> = 15). We quantified fractional survival of inner (IHC) and outer (OHC) hair cells, auditory-nerve (AN) peripheral axons, spiral ganglion cells (SGCs) and the stria. Ménière’s ears showed the lowest survival of IHCs (<50 %), OHCs (<30 %), AN peripheral axons (<30 %), and stria (<60 %), as well as the worst mean thresholds (75.4 dB HL) and word scores (36.68 %). Pairwise correlations showed the strongest word-score associations with IHC survival in the apical half (R² = 0.404) and with AN axons in both apical (R² = 0.329) and basal (R² = 0.324) halves of the cochlea. Despite the massive loss of AN peripheral axons, SGC loss <em>re</em> age-matched controls was minimal. In a multivariable regression including all histological variables and thresholds (0.5–4 kHz), AN peripheral axons were the only significant histological predictor of word score. The survival of most SGCs helps explains why most Ménière’s patients nevertheless perform well with cochlear implants.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"473 ","pages":"Article 109574"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}