Pub Date : 2025-01-14DOI: 10.1007/s10162-024-00971-0
Aleksandra Ivanovic, Jeffrey Tao Cheng, Margaux Schmeltz, Wilhelm Wimmer, Christian M Schlepuetz, Aaron K Remenschneider, Anne Bonnin, Lukas Anschuetz
Purpose: There are challenges in understanding the biomechanics of the human middle ear, and established methods for studying this system show significant limitations. In this study, we evaluate a novel dynamic imaging technique based on synchrotron X-ray microtomography designed to assess the biomechanical properties of the human middle ear by comparing it to laser-Doppler vibrometry (LDV).
Methods: We examined three fresh-frozen temporal bones (TB), two donated by white males and one by a Black female, using dynamic synchrotron-based X-ray microtomography for 256 and 512 Hz, stimulated at 110 dB and 120 dB sound pressure level (SPL). In addition, we performed measurements on these TBs using 1D LDV, a well-established method.
Results: The normalized displacement values (µm/Pa) at the umbo and the posterior crus of the stapes are consistent or within 5-10 dB differences between all LDV and dynamic microtomography measurements and previously reported literature references. In general, the overall behavior is similar between the two measurement techniques.
Conclusion: In conclusion, our results demonstrate the suitability of dynamic synchrotron-based X-ray microtomography in studying the middle ear's biomechanics. However, this study shows that better standardization regarding acoustic stimulation and measurement points is needed to better compare the two measurement techniques.
{"title":"Dynamic X-ray Microtomography vs. Laser-Doppler Vibrometry: A Comparative Study.","authors":"Aleksandra Ivanovic, Jeffrey Tao Cheng, Margaux Schmeltz, Wilhelm Wimmer, Christian M Schlepuetz, Aaron K Remenschneider, Anne Bonnin, Lukas Anschuetz","doi":"10.1007/s10162-024-00971-0","DOIUrl":"https://doi.org/10.1007/s10162-024-00971-0","url":null,"abstract":"<p><strong>Purpose: </strong>There are challenges in understanding the biomechanics of the human middle ear, and established methods for studying this system show significant limitations. In this study, we evaluate a novel dynamic imaging technique based on synchrotron X-ray microtomography designed to assess the biomechanical properties of the human middle ear by comparing it to laser-Doppler vibrometry (LDV).</p><p><strong>Methods: </strong>We examined three fresh-frozen temporal bones (TB), two donated by white males and one by a Black female, using dynamic synchrotron-based X-ray microtomography for 256 and 512 Hz, stimulated at 110 dB and 120 dB sound pressure level (SPL). In addition, we performed measurements on these TBs using 1D LDV, a well-established method.</p><p><strong>Results: </strong>The normalized displacement values (µm/Pa) at the umbo and the posterior crus of the stapes are consistent or within 5-10 dB differences between all LDV and dynamic microtomography measurements and previously reported literature references. In general, the overall behavior is similar between the two measurement techniques.</p><p><strong>Conclusion: </strong>In conclusion, our results demonstrate the suitability of dynamic synchrotron-based X-ray microtomography in studying the middle ear's biomechanics. However, this study shows that better standardization regarding acoustic stimulation and measurement points is needed to better compare the two measurement techniques.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985771","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}
Pub Date : 2025-01-08DOI: 10.1007/s10162-024-00972-z
Tommy Peng, Charlotte Garcia, Mica Haneman, Maureen J Shader, Robert P Carlyon, Colette M McKay
Purpose: Variations in neural survival along the cochlear implant electrode array leads to off-place listening, resulting in poorer speech understanding outcomes for recipients. Therefore, it is important to develop and compare clinically viable tests to identify these patient-specific intra-cochlear neural differences.
Methods: Nineteen experienced cochlear implant recipients (9 males and 10 females) were recruited for this study. We estimated the neural health along the electrode array for a group of experienced adult implant recipients using two methods: the difference between psychophysical detection thresholds in bipolar vs. monopolar mode and the panoramic electrically evoked compound action potential method (PECAP). We hypothesised that: neural health estimated using both methods at single electrodes will be correlated at the participant level and the group level; and participants with larger variations in neural health along the electrode array will have poorer speech outcomes.
Results: At the individual level, the two neural measures correlated significantly across electrodes (p < 0.05) for 5 out of 15 participants. At the group level, we observed a weak but significant across-electrode correlation (R2 = 0.111, p < 0.001). While a larger variation in neural measures estimated from psychophysical thresholds was associated with lower phoneme speech scores (R2 = 0.499, p < 0.01), no significant association was found between variations in PECAP's neural health estimates and phoneme speech scores (R2 = 0.082, p = 0.366).
Conclusion: Our evidence suggests that both methods likely quantify a shared underlying neural basis, hypothesised to be the neural health along the cochlear implant array. The differences between the two measures may be attributed to differences in stimulus rate or loudness used to elicit responses and/or the influence of factors arising more centrally than the auditory nerve.
{"title":"Comparing Patient-Specific Variations in Intra-Cochlear Neural Health Estimated Using Psychophysical Thresholds and Panoramic Electrically Evoked Compound Action Potentials (PECAPs).","authors":"Tommy Peng, Charlotte Garcia, Mica Haneman, Maureen J Shader, Robert P Carlyon, Colette M McKay","doi":"10.1007/s10162-024-00972-z","DOIUrl":"https://doi.org/10.1007/s10162-024-00972-z","url":null,"abstract":"<p><strong>Purpose: </strong>Variations in neural survival along the cochlear implant electrode array leads to off-place listening, resulting in poorer speech understanding outcomes for recipients. Therefore, it is important to develop and compare clinically viable tests to identify these patient-specific intra-cochlear neural differences.</p><p><strong>Methods: </strong>Nineteen experienced cochlear implant recipients (9 males and 10 females) were recruited for this study. We estimated the neural health along the electrode array for a group of experienced adult implant recipients using two methods: the difference between psychophysical detection thresholds in bipolar vs. monopolar mode and the panoramic electrically evoked compound action potential method (PECAP). We hypothesised that: neural health estimated using both methods at single electrodes will be correlated at the participant level and the group level; and participants with larger variations in neural health along the electrode array will have poorer speech outcomes.</p><p><strong>Results: </strong>At the individual level, the two neural measures correlated significantly across electrodes (p < 0.05) for 5 out of 15 participants. At the group level, we observed a weak but significant across-electrode correlation (R<sup>2</sup> = 0.111, p < 0.001). While a larger variation in neural measures estimated from psychophysical thresholds was associated with lower phoneme speech scores (R<sup>2</sup> = 0.499, p < 0.01), no significant association was found between variations in PECAP's neural health estimates and phoneme speech scores (R<sup>2</sup> = 0.082, p = 0.366).</p><p><strong>Conclusion: </strong>Our evidence suggests that both methods likely quantify a shared underlying neural basis, hypothesised to be the neural health along the cochlear implant array. The differences between the two measures may be attributed to differences in stimulus rate or loudness used to elicit responses and/or the influence of factors arising more centrally than the auditory nerve.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959051","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}
Pub Date : 2024-12-16DOI: 10.1007/s10162-024-00970-1
Ekaterina A Yukhnovich, Kai Alter, William Sedley
Due to the heterogeneous causes, symptoms and associated comorbidities with tinnitus, there remains an unmet need for a clear biomarker of tinnitus presence. Previous research has suggested a "final pathway" of tinnitus presence, which occurs regardless of the specific mechanisms that resulted in alterations of auditory predictions and, eventually, tinnitus perception. Predictive inference mechanisms have been proposed as the possible basis for this final unifying pathway. A commonly used measure of prediction violation is mismatch negativity (MMN), an electrical potential generated in response to most stimuli that violate an established regularity. This narrative review discusses 16 studies comparing MMN between tinnitus and non-tinnitus groups. Methods varied considerably, including type of deviant, type of paradigm and carrier frequency. A minority of studies matched groups for age, sex and hearing, with few measuring hyperacusis. Frequency deviants were the most widely studied; at frequencies remote from tinnitus, MMN was consistently smaller in tinnitus groups, though hyperacusis or altered distress or attention could not be ruled out as explanatory factors. Few studies have used tinnitus-related frequencies; these showed larger MMN to upward frequency deviants above the tinnitus frequency, and larger MMN to upward intensity deviants at or close to the tinnitus frequency. However, the latter appears a correlate of hyperacusis rather than tinnitus, and tinnitus groups without hyperacusis instead show larger MMN to downward intensity deviants than controls. Other factors that affect MMN amplitudes included age, attention, and the specific characteristics of the range of stimuli across a particular experiment paradigm. As such, MMN cannot presently be considered a specific biomarker of tinnitus, but showed potential to objectively characterise a number of auditory processing traits relevant to tinnitus and hyperacusis.
{"title":"What Do Mismatch Negativity (MMN) Responses Tell Us About Tinnitus?","authors":"Ekaterina A Yukhnovich, Kai Alter, William Sedley","doi":"10.1007/s10162-024-00970-1","DOIUrl":"https://doi.org/10.1007/s10162-024-00970-1","url":null,"abstract":"<p><p>Due to the heterogeneous causes, symptoms and associated comorbidities with tinnitus, there remains an unmet need for a clear biomarker of tinnitus presence. Previous research has suggested a \"final pathway\" of tinnitus presence, which occurs regardless of the specific mechanisms that resulted in alterations of auditory predictions and, eventually, tinnitus perception. Predictive inference mechanisms have been proposed as the possible basis for this final unifying pathway. A commonly used measure of prediction violation is mismatch negativity (MMN), an electrical potential generated in response to most stimuli that violate an established regularity. This narrative review discusses 16 studies comparing MMN between tinnitus and non-tinnitus groups. Methods varied considerably, including type of deviant, type of paradigm and carrier frequency. A minority of studies matched groups for age, sex and hearing, with few measuring hyperacusis. Frequency deviants were the most widely studied; at frequencies remote from tinnitus, MMN was consistently smaller in tinnitus groups, though hyperacusis or altered distress or attention could not be ruled out as explanatory factors. Few studies have used tinnitus-related frequencies; these showed larger MMN to upward frequency deviants above the tinnitus frequency, and larger MMN to upward intensity deviants at or close to the tinnitus frequency. However, the latter appears a correlate of hyperacusis rather than tinnitus, and tinnitus groups without hyperacusis instead show larger MMN to downward intensity deviants than controls. Other factors that affect MMN amplitudes included age, attention, and the specific characteristics of the range of stimuli across a particular experiment paradigm. As such, MMN cannot presently be considered a specific biomarker of tinnitus, but showed potential to objectively characterise a number of auditory processing traits relevant to tinnitus and hyperacusis.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840519","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}
Pub Date : 2024-12-01Epub Date: 2024-10-08DOI: 10.1007/s10162-024-00964-z
Paul B Manis
{"title":"Eric Daniel Young.","authors":"Paul B Manis","doi":"10.1007/s10162-024-00964-z","DOIUrl":"10.1007/s10162-024-00964-z","url":null,"abstract":"","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"527-530"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395592","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}
Pub Date : 2024-12-01Epub Date: 2024-11-07DOI: 10.1007/s10162-024-00968-9
Yiwei Xia, George Samaras, Julien Meaud
Purpose: A theoretical framework based on coherent reflection and filter theory predicts that the phase-gradient delays of stimulus frequency otoacoustic emissions (SFOAEs) are correlated with tuning sharpness in the mammalian cochlea. In this paper, we use a computational model of the cochlea to test this theory and to evaluate how SFOAE phase-gradient delays may be used to estimate the sharpness of cochlear tuning.
Methods: This study is based on a physiologically motivated model which has been previously shown to predict key aspects of cochlear micromechanics. Cochlear roughness is introduced to model the reflection mechanism which underlies SFOAE generation. We then examine how varying the values of key model parameters or of the sound pressure level of the stimulus affects the relation between cochlear tuning and SFOAE delays. Finally, we quantify the ability of model simulations of SFOAE phase-gradient delays to provide reliable estimates of the tuning sharpness of the model.
Results: We find that variations of model parameters that cause significant broadening of basilar membrane (BM) tuning typically give rise to a sizeable reduction in SFOAE phase-gradient delays. However, some changes in model parameters may cause a significant broadening of BM tuning with only a moderate decrease in SFOAE delays. SFOAE delays can be used to estimate the tuning sharpness of the model with reasonable accuracy only in cases where broadening of cochlear tuning is associated with a significant reduction in SFOAE delays.
Conclusion: The numerical results provide key insights about the correlations between cochlear tuning and SFOAE delays.
{"title":"Evaluating the Correlation Between Stimulus Frequency Otoacoustic Emission Group Delays and Tuning Sharpness in a Cochlear Model.","authors":"Yiwei Xia, George Samaras, Julien Meaud","doi":"10.1007/s10162-024-00968-9","DOIUrl":"10.1007/s10162-024-00968-9","url":null,"abstract":"<p><strong>Purpose: </strong>A theoretical framework based on coherent reflection and filter theory predicts that the phase-gradient delays of stimulus frequency otoacoustic emissions (SFOAEs) are correlated with tuning sharpness in the mammalian cochlea. In this paper, we use a computational model of the cochlea to test this theory and to evaluate how SFOAE phase-gradient delays may be used to estimate the sharpness of cochlear tuning.</p><p><strong>Methods: </strong>This study is based on a physiologically motivated model which has been previously shown to predict key aspects of cochlear micromechanics. Cochlear roughness is introduced to model the reflection mechanism which underlies SFOAE generation. We then examine how varying the values of key model parameters or of the sound pressure level of the stimulus affects the relation between cochlear tuning and SFOAE delays. Finally, we quantify the ability of model simulations of SFOAE phase-gradient delays to provide reliable estimates of the tuning sharpness of the model.</p><p><strong>Results: </strong>We find that variations of model parameters that cause significant broadening of basilar membrane (BM) tuning typically give rise to a sizeable reduction in SFOAE phase-gradient delays. However, some changes in model parameters may cause a significant broadening of BM tuning with only a moderate decrease in SFOAE delays. SFOAE delays can be used to estimate the tuning sharpness of the model with reasonable accuracy only in cases where broadening of cochlear tuning is associated with a significant reduction in SFOAE delays.</p><p><strong>Conclusion: </strong>The numerical results provide key insights about the correlations between cochlear tuning and SFOAE delays.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"575-589"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606490","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}
Pub Date : 2024-12-01Epub Date: 2024-10-16DOI: 10.1007/s10162-024-00966-x
Charlotte Garcia, Charlotte Morse-Fortier, François Guérit, Scott Hislop, Tobias Goehring, Robert P Carlyon, Julie G Arenberg
Purpose: For some cochlear implants (CIs), it is possible to focus electrical stimulation by partially returning current from the active electrode to nearby, intra-cochlear electrodes (partial tripolar (pTP) stimulation). Another method achieves the opposite: "blurring" by stimulating multiple electrodes simultaneously. The Panoramic ECAP (PECAP) method provides a platform to investigate their effects in detail by measuring electrically evoked compound action potentials and estimating current spread and neural responsiveness along the length of the CI electrode array. We investigate how sharpening and broadening the electrical current spread are reflected in PECAP estimates.
Methods: PECAP measurements were recorded at most comfortable level in 12 ears of Advanced Bionics CI users. Focused thresholds were also determined. For the electrodes with the highest and lowest focused thresholds, additional PECAP measurements were recorded while stimulating in pTP mode and in "blurred" mode with 3 or 5 adjacent electrodes simultaneously stimulated. Current spread and neural responsiveness were then estimated along the electrode array using PECAP.
Results: PECAP revealed increased current spread estimates across participants for blurred stimulation of the targeted electrodes towards the apex of the cochlea. Variable results for pTP stimulation were found, with two of eight ears appearing to drive a small group-level effect of increased current spread.
Conclusion: When stimulating multiple electrodes simultaneously, PECAP detected localized increases in current spread towards the apex (but not the base) of the cochlea. pTP stimulation showed mixed effects on PECAP current spread estimates. These findings are in line with behavioral speech perception studies and have implications for cochlear implant optimization.
{"title":"Investigating the Effect of Blurring and Focusing Current in Cochlear Implant Users with the Panoramic ECAP Method.","authors":"Charlotte Garcia, Charlotte Morse-Fortier, François Guérit, Scott Hislop, Tobias Goehring, Robert P Carlyon, Julie G Arenberg","doi":"10.1007/s10162-024-00966-x","DOIUrl":"10.1007/s10162-024-00966-x","url":null,"abstract":"<p><strong>Purpose: </strong>For some cochlear implants (CIs), it is possible to focus electrical stimulation by partially returning current from the active electrode to nearby, intra-cochlear electrodes (partial tripolar (pTP) stimulation). Another method achieves the opposite: \"blurring\" by stimulating multiple electrodes simultaneously. The Panoramic ECAP (PECAP) method provides a platform to investigate their effects in detail by measuring electrically evoked compound action potentials and estimating current spread and neural responsiveness along the length of the CI electrode array. We investigate how sharpening and broadening the electrical current spread are reflected in PECAP estimates.</p><p><strong>Methods: </strong>PECAP measurements were recorded at most comfortable level in 12 ears of Advanced Bionics CI users. Focused thresholds were also determined. For the electrodes with the highest and lowest focused thresholds, additional PECAP measurements were recorded while stimulating in pTP mode and in \"blurred\" mode with 3 or 5 adjacent electrodes simultaneously stimulated. Current spread and neural responsiveness were then estimated along the electrode array using PECAP.</p><p><strong>Results: </strong>PECAP revealed increased current spread estimates across participants for blurred stimulation of the targeted electrodes towards the apex of the cochlea. Variable results for pTP stimulation were found, with two of eight ears appearing to drive a small group-level effect of increased current spread.</p><p><strong>Conclusion: </strong>When stimulating multiple electrodes simultaneously, PECAP detected localized increases in current spread towards the apex (but not the base) of the cochlea. pTP stimulation showed mixed effects on PECAP current spread estimates. These findings are in line with behavioral speech perception studies and have implications for cochlear implant optimization.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"591-609"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482028","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}
Pub Date : 2024-12-01Epub Date: 2024-10-21DOI: 10.1007/s10162-024-00967-w
Ashley Scott Patterson, Joseph Dugdale, Alaa Koleilat, Anna Krauss, Gabriel A Hernandez-Herrera, Jasmine G Wallace, Cassidy Petree, Gaurav K Varshney, Lisa A Schimmenti
Purpose: Vital dyes allow the visualization of cells in vivo without causing tissue damage, making them a useful tool for studying lateral line and inner ear hair cells in living zebrafish and other vertebrates. FM1-43, YO-PRO-1, and DASPEI are three vital dyes commonly used for hair cell visualization. While it has been established that FM1-43 enters hair cells of zebrafish and other organisms through the mechanoelectrical transduction (MET) channel, the mechanism of entry into hair cells for YO-PRO-1 and DASPEI has not been established despite widespread use. We hypothesize that YO-PRO-1 and DASPEI entry into zebrafish hair cells is MET channel uptake dependent similar to FM1-43.
Methods: To test this hypothesis, we used both genetic and pharmacologic means to block MET channel function. Genetic based MET channel assays were conducted with two different mechanotransduction defective zebrafish lines, specifically the myo7aa-/- loss of function mutant tc320b (p.Y846X) and cdh23-/- loss of function mutant (c.570-571del). Pharmacologic assays were performed with Gadolinium(III) Chloride (Gad(III)), a compound that can temporarily block mechanotransduction activity.
Results: Five-day post fertilization (5dpf) myo7aa-/- and cdh23-/- larvae incubated with FM1-43, YO-PRO-1, and DASPEI all showed nearly absent uptake of each vital dye. Treatment of wildtype zebrafish larvae with Gad(III) significantly reduces uptake of FM1-43, YO-PRO-1, and DASPEI vital dyes.
Conclusion: These results indicate that YO-PRO-1 and DASPEI entry into zebrafish hair cells is MET channel dependent similar to FM1-43. This knowledge expands the repertoire of vital dyes that can be used to assess mechanotransduction and MET channel function in zebrafish and other vertebrate models of hair cell function.
目的:活力染料可使活体细胞可视化而不会造成组织损伤,是研究活体斑马鱼和其他脊椎动物侧线和内耳毛细胞的有用工具。FM1-43、YO-PRO-1 和 DASPEI 是常用于观察毛细胞的三种重要染料。虽然已经确定 FM1-43 通过机械电转导(MET)通道进入斑马鱼和其他生物的毛细胞,但 YO-PRO-1 和 DASPEI 进入毛细胞的机制尚未确定,尽管它们已被广泛使用。我们假设 YO-PRO-1 和 DASPEI 进入斑马鱼毛细胞与 FM1-43 类似,都依赖于 MET 通道的摄取:为了验证这一假设,我们采用了基因和药物方法来阻断 MET 通道的功能。我们用两种不同的机械传导缺陷斑马鱼品系,特别是 myo7aa-/- 功能缺失突变体 tc320b(p.Y846X)和 cdh23-/- 功能缺失突变体(c.570-571del)进行了基于基因的 MET 通道检测。用氯化钆(III)(Gad(III))进行了药理学检测,该化合物可暂时阻断机械传导活性:结果:受精后五天(5dpf)的myo7aa-/-和cdh23-/-幼体在与FM1-43、YO-PRO-1和DASPEI一起孵育时,对每种重要染料的吸收都几乎为零。用 Gad(III)处理野生型斑马鱼幼体可显著减少对 FM1-43、YO-PRO-1 和 DASPEI 生命染料的吸收:这些结果表明,YO-PRO-1 和 DASPEI 进入斑马鱼毛细胞与 FM1-43 类似,都依赖于 MET 通道。这一知识扩展了可用于评估斑马鱼和其他脊椎动物毛细胞功能模型中机械传导和 MET 通道功能的重要染料的范围。
{"title":"Vital Dye Uptake of YO-PRO-1 and DASPEI Depends Upon Mechanoelectrical Transduction Function in Zebrafish Hair Cells.","authors":"Ashley Scott Patterson, Joseph Dugdale, Alaa Koleilat, Anna Krauss, Gabriel A Hernandez-Herrera, Jasmine G Wallace, Cassidy Petree, Gaurav K Varshney, Lisa A Schimmenti","doi":"10.1007/s10162-024-00967-w","DOIUrl":"10.1007/s10162-024-00967-w","url":null,"abstract":"<p><strong>Purpose: </strong>Vital dyes allow the visualization of cells in vivo without causing tissue damage, making them a useful tool for studying lateral line and inner ear hair cells in living zebrafish and other vertebrates. FM1-43, YO-PRO-1, and DASPEI are three vital dyes commonly used for hair cell visualization. While it has been established that FM1-43 enters hair cells of zebrafish and other organisms through the mechanoelectrical transduction (MET) channel, the mechanism of entry into hair cells for YO-PRO-1 and DASPEI has not been established despite widespread use. We hypothesize that YO-PRO-1 and DASPEI entry into zebrafish hair cells is MET channel uptake dependent similar to FM1-43.</p><p><strong>Methods: </strong>To test this hypothesis, we used both genetic and pharmacologic means to block MET channel function. Genetic based MET channel assays were conducted with two different mechanotransduction defective zebrafish lines, specifically the myo7aa<sup>-/-</sup> loss of function mutant tc320b (p.Y846X) and cdh23<sup>-/-</sup> loss of function mutant (c.570-571del). Pharmacologic assays were performed with Gadolinium(III) Chloride (Gad(III)), a compound that can temporarily block mechanotransduction activity.</p><p><strong>Results: </strong>Five-day post fertilization (5dpf) myo7aa<sup>-/-</sup> and cdh23<sup>-/-</sup> larvae incubated with FM1-43, YO-PRO-1, and DASPEI all showed nearly absent uptake of each vital dye. Treatment of wildtype zebrafish larvae with Gad(III) significantly reduces uptake of FM1-43, YO-PRO-1, and DASPEI vital dyes.</p><p><strong>Conclusion: </strong>These results indicate that YO-PRO-1 and DASPEI entry into zebrafish hair cells is MET channel dependent similar to FM1-43. This knowledge expands the repertoire of vital dyes that can be used to assess mechanotransduction and MET channel function in zebrafish and other vertebrate models of hair cell function.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"531-543"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482029","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}
Pub Date : 2024-12-01Epub Date: 2024-10-24DOI: 10.1007/s10162-024-00965-y
Alberto Recio-Spinoso, John S Oghalai, Mario A Ruggero
Purpose: The goal of this research was to record sound-evoked vibrations in the organ of Corti at the apex of the intact cochlea of the chinchilla, an animal with a frequency hearing range similar to that of humans.
Methods: Twelve adult anesthetized chinchillas of either sex were used. Measurements of sound-evoked vibrations of the intact organ of Corti (OoC) were performed using optical coherence tomography (OCT). Acoustic stimuli consisted of single tones of 1-s duration. OoC vibrations were recorded using a Telesto Spectral Domain OCT system (Thorlabs GmbH, Germany) and ThorImage® OCT version 5.4.2 (Thorlabs GmbH, Germany). Further analysis of the output of the ThorImage software was performed by ad hoc programs written using Matlab® R2020b.
Results: Recordings were performed at several OoC sites extending from the Hensen's cell region to the vicinity of the basilar membrane (BM). The measurement angle between the optical axis of the OCT system and the BM was approximately 45°. Under that experimental condition, delays among the different OoC locations indicate that BM motion occurs earlier than at other sites. At all OoC sites, sound-evoked vibrations grow nonlinearly with stimulus level at compressive rates. The sharpness of tuning of OoC vibrations increases with stimulus level and death. Iso-velocity curves as a function of frequency are well-tuned around 500 Hz and closely resemble threshold tuning curves of chinchilla auditory-nerve fibers with similar characteristic frequencies.
Conclusions: The nonlinear processing of sounds at the apex of the chinchilla cochlea differs significantly from the processing of sounds at the base of the cochlea in the same species.
{"title":"Tuning and Timing of Organ of Corti Vibrations at the Apex of the Intact Chinchilla Cochlea.","authors":"Alberto Recio-Spinoso, John S Oghalai, Mario A Ruggero","doi":"10.1007/s10162-024-00965-y","DOIUrl":"10.1007/s10162-024-00965-y","url":null,"abstract":"<p><strong>Purpose: </strong>The goal of this research was to record sound-evoked vibrations in the organ of Corti at the apex of the intact cochlea of the chinchilla, an animal with a frequency hearing range similar to that of humans.</p><p><strong>Methods: </strong>Twelve adult anesthetized chinchillas of either sex were used. Measurements of sound-evoked vibrations of the intact organ of Corti (OoC) were performed using optical coherence tomography (OCT). Acoustic stimuli consisted of single tones of 1-s duration. OoC vibrations were recorded using a Telesto Spectral Domain OCT system (Thorlabs GmbH, Germany) and ThorImage® OCT version 5.4.2 (Thorlabs GmbH, Germany). Further analysis of the output of the ThorImage software was performed by ad hoc programs written using Matlab® R2020b.</p><p><strong>Results: </strong>Recordings were performed at several OoC sites extending from the Hensen's cell region to the vicinity of the basilar membrane (BM). The measurement angle between the optical axis of the OCT system and the BM was approximately 45°. Under that experimental condition, delays among the different OoC locations indicate that BM motion occurs earlier than at other sites. At all OoC sites, sound-evoked vibrations grow nonlinearly with stimulus level at compressive rates. The sharpness of tuning of OoC vibrations increases with stimulus level and death. Iso-velocity curves as a function of frequency are well-tuned around 500 Hz and closely resemble threshold tuning curves of chinchilla auditory-nerve fibers with similar characteristic frequencies.</p><p><strong>Conclusions: </strong>The nonlinear processing of sounds at the apex of the chinchilla cochlea differs significantly from the processing of sounds at the base of the cochlea in the same species.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"545-562"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513849","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}
Pub Date : 2024-11-27DOI: 10.1007/s10162-024-00969-8
Courtney Coburn Glavin, Sumitrajit Dhar
Otoacoustic emissions (OAEs) are low-level signals generated from active processes related to outer hair cell transduction in the cochlea. In current clinical applications, OAEs are typically used to detect the presence or absence of hearing loss. However, their potential extends far beyond hearing screenings. Dr. Glenis Long realized this unfulfilled potential decades ago. She subsequently devoted a large portion of her storied scientific career to understanding OAEs and cochlear mechanics, particularly at the intersection of OAEs and perceptual measures. One specific application of OAEs that has yet to be translated from research laboratories to the clinic is using them to non-invasively characterize cochlear nonlinearity-a hallmark feature of a healthy cochlea-across a wide dynamic range. This can be done by measuring OAEs across input levels to obtain an OAE growth, or input-output (I/O), function. In this review, we describe distortion product OAE (DPOAE) growth and its relation to cochlear nonlinearity and mechanics. We then review biological and measurement factors that are known to influence OAE growth and finish with a discussion of potential applications. Throughout the review, we emphasize Dr. Long's many contributions to the field.
{"title":"The Ins and Outs of Distortion Product Otoacoustic Emission Growth: A Review.","authors":"Courtney Coburn Glavin, Sumitrajit Dhar","doi":"10.1007/s10162-024-00969-8","DOIUrl":"https://doi.org/10.1007/s10162-024-00969-8","url":null,"abstract":"<p><p>Otoacoustic emissions (OAEs) are low-level signals generated from active processes related to outer hair cell transduction in the cochlea. In current clinical applications, OAEs are typically used to detect the presence or absence of hearing loss. However, their potential extends far beyond hearing screenings. Dr. Glenis Long realized this unfulfilled potential decades ago. She subsequently devoted a large portion of her storied scientific career to understanding OAEs and cochlear mechanics, particularly at the intersection of OAEs and perceptual measures. One specific application of OAEs that has yet to be translated from research laboratories to the clinic is using them to non-invasively characterize cochlear nonlinearity-a hallmark feature of a healthy cochlea-across a wide dynamic range. This can be done by measuring OAEs across input levels to obtain an OAE growth, or input-output (I/O), function. In this review, we describe distortion product OAE (DPOAE) growth and its relation to cochlear nonlinearity and mechanics. We then review biological and measurement factors that are known to influence OAE growth and finish with a discussion of potential applications. Throughout the review, we emphasize Dr. Long's many contributions to the field.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735079","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}
Pub Date : 2024-10-01Epub Date: 2024-08-13DOI: 10.1007/s10162-024-00960-3
Tobias Kleinjung, Nicole Peter, Martin Schecklmann, Berthold Langguth
Tinnitus, the perception of sound without an external source, affects 15% of the population, with 2.4% experiencing significant distress. In this review, we summarize the current state of knowledge about tinnitus management with a particular focus on the translation into clinical practice. In the first section, we analyze shortcomings, knowledge gaps, and challenges in the field of tinnitus research. Then, we highlight the relevance of the diagnostic process to account for tinnitus heterogeneity and to identify all relevant aspects of the tinnitus in an individual patient, such as etiological aspects, pathophysiological mechanisms, factors that contribute most to suffering, and comorbidities. In the next section, we review available treatment options, including counselling, cognitive-behavioral therapy (CBT), hearing aids and cochlear implants for patients with a relevant hearing loss, sound generators, novel auditory stimulation approaches, tinnitus retraining therapy (TRT), pharmacological treatment, neurofeedback, brain stimulation, bimodal stimulation, Internet- and app-based digital approaches, and alternative treatment approaches. The evidence for the effectiveness of the various treatment interventions varies considerably. We also discuss differences in current respective guideline recommendations and close with a discussion of how current pathophysiological knowledge, latest scientific evidence, and patient perspectives can be translated in patient-centered care.
{"title":"The Current State of Tinnitus Diagnosis and Treatment: a Multidisciplinary Expert Perspective.","authors":"Tobias Kleinjung, Nicole Peter, Martin Schecklmann, Berthold Langguth","doi":"10.1007/s10162-024-00960-3","DOIUrl":"10.1007/s10162-024-00960-3","url":null,"abstract":"<p><p>Tinnitus, the perception of sound without an external source, affects 15% of the population, with 2.4% experiencing significant distress. In this review, we summarize the current state of knowledge about tinnitus management with a particular focus on the translation into clinical practice. In the first section, we analyze shortcomings, knowledge gaps, and challenges in the field of tinnitus research. Then, we highlight the relevance of the diagnostic process to account for tinnitus heterogeneity and to identify all relevant aspects of the tinnitus in an individual patient, such as etiological aspects, pathophysiological mechanisms, factors that contribute most to suffering, and comorbidities. In the next section, we review available treatment options, including counselling, cognitive-behavioral therapy (CBT), hearing aids and cochlear implants for patients with a relevant hearing loss, sound generators, novel auditory stimulation approaches, tinnitus retraining therapy (TRT), pharmacological treatment, neurofeedback, brain stimulation, bimodal stimulation, Internet- and app-based digital approaches, and alternative treatment approaches. The evidence for the effectiveness of the various treatment interventions varies considerably. We also discuss differences in current respective guideline recommendations and close with a discussion of how current pathophysiological knowledge, latest scientific evidence, and patient perspectives can be translated in patient-centered care.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"413-425"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977385","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}