{"title":"Transient Receptor Potential (TRP) Channels in Cochlear Function: Looking Beyond Mechanotransduction.","authors":"Trinh Nguyen, Dwight E Bergles","doi":"10.1007/s10162-024-00954-1","DOIUrl":"10.1007/s10162-024-00954-1","url":null,"abstract":"<p><p>Transient receptor potential (TRP) channels play key roles in sensory biology as transducers of various stimuli. Although these ion channels are expressed in the cochlea, their functions remain poorly understood. Recent studies by Vélez-Ortega and colleagues indicate that their expression by non-sensory supporting cells helps limit damage from acoustic trauma.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"409-412"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461103","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":"Enhanced Place Specificity of the Parallel Auditory Brainstem Response: An Electrophysiological Study.","authors":"Thomas J Stoll, Ross K Maddox","doi":"10.1007/s10162-024-00959-w","DOIUrl":"10.1007/s10162-024-00959-w","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates the effect of parallel stimulus presentation on the place specificity of the auditory brainstem response (ABR) in human listeners. Frequency-specific stimuli do not guarantee a response from the place on the cochlea corresponding only to that characteristic frequency - especially for brief and high-level stimuli. Adding masking noise yields responses that are more place specific, and our prior modeling study has suggested similar effects when multiple frequency-specific stimuli are presented in parallel. We tested this hypothesis experimentally here, comparing the place specificity of responses to serial and parallel stimuli at two stimulus frequencies and three stimulus rates.</p><p><strong>Methods: </strong>Parallel ABR (pABR) stimuli were presented alongside high-pass filtered noise with a varied cutoff frequency. Serial presentation was also tested by isolating and presenting single-frequency stimulus trains from the pABR ensemble. Latencies of the ABRs were examined to assess place specificity of responses. Response bands were derived by subtracting responses from different high-pass noise conditions. The response amplitude from each derived response band was then used to determine how much individual frequency regions of the auditory system were contributing to the overall response.</p><p><strong>Results: </strong>We found that parallel presentation improves place specificity of ABRs for the lower stimulus frequency and at higher stimulus rates. At a higher stimulus frequency, serial and parallel presentations were equally place specific.</p><p><strong>Conclusion: </strong>Parallel presentation can provide more place-specific responses than serial for lower stimulus frequencies. The improvement increases with higher stimulus rates and is in addition to the pABR's primary benefit of faster test times.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"477-489"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010023","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":"Conditions Underlying the Appearance of Spontaneous Otoacoustic Emissions in Mammals.","authors":"Geoffrey A Manley","doi":"10.1007/s10162-024-00950-5","DOIUrl":"10.1007/s10162-024-00950-5","url":null,"abstract":"<p><p>Across the wide range of land vertebrate species, spontaneous otoacoustic emissions (SOAE) are common, but not always found. The reasons for the differences between species of the various groups in their emission patterns are often not well understood, particularly within mammals. This review examines the question as to what determines in mammals whether SOAE are emitted or not, and suggests that the coupling between hair-cell regions diminishes when the space constant of frequency distribution becomes larger. The reduced coupling is assumed to result in a greater likelihood of SOAE being emitted.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"303-311"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961241","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":"Correction: Something in Our Ears Is Oscillating, but What? A Modeller's View of Efforts to Model Spontaneous Emissions.","authors":"Hero P Wit, Andrew Bell","doi":"10.1007/s10162-024-00951-4","DOIUrl":"10.1007/s10162-024-00951-4","url":null,"abstract":"","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"407"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072377","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":"Something in Our Ears Is Oscillating, but What? A Modeller's View of Efforts to Model Spontaneous Emissions.","authors":"Hero P Wit, Andrew Bell","doi":"10.1007/s10162-024-00940-7","DOIUrl":"10.1007/s10162-024-00940-7","url":null,"abstract":"<p><p>When David Kemp discovered \"spontaneous ear noise\" in 1978, it opened up a whole new perspective on how the cochlea works. The continuous tonal sound emerging from most healthy human ears, now called spontaneous otoacoustic emissions or SOAEs, was an unmistakable sign that our hearing organ must be considered an active detector, not just a passive microphone, just as Thomas Gold had speculated some 30 years earlier. Clearly, something is oscillating as a byproduct of that sensitive inbuilt detector, but what exactly is it? Here, we give a chronological account of efforts to model SOAEs as some form of oscillator, and at intervals, we illustrate key concepts with numerical simulations. We find that after many decades there is still no consensus, and the debate extends to whether the oscillator is local, confined to discrete local sources on the basilar membrane, or global, in which an assembly of micro-mechanical elements and basilar membrane sections, coupled by inner ear fluid, interact over a wide region. It is also undecided whether the cochlear oscillator is best described in terms of the well-known Van der Pol oscillator or the less familiar Duffing or Hopf oscillators. We find that irregularities play a key role in generating the emissions. This paper is not a systematic review of SOAEs and their properties but more a historical survey of the way in which various oscillator configurations have been applied to modelling human ears. The conclusion is that the difference between the local and global approaches is not clear-cut, and they are probably not mutually exclusive concepts. Nevertheless, when one sees how closely human SOAEs can be matched to certain arrangements of oscillators, Gold would no doubt say we are on the right track.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"313-328"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874231","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}
Ishan Sunilkumar Bhatt, Juan Antonio Raygoza Garay, Srividya Grama Bhagavan, Valerie Ingalls, Raquel Dias, Ali Torkamani
{"title":"Polygenic Risk Score-Based Association Analysis Identifies Genetic Comorbidities Associated with Age-Related Hearing Difficulty in Two Independent Samples.","authors":"Ishan Sunilkumar Bhatt, Juan Antonio Raygoza Garay, Srividya Grama Bhagavan, Valerie Ingalls, Raquel Dias, Ali Torkamani","doi":"10.1007/s10162-024-00947-0","DOIUrl":"10.1007/s10162-024-00947-0","url":null,"abstract":"<p><strong>Purpose: </strong>Age-related hearing loss is the most common form of permanent hearing loss that is associated with various health traits, including Alzheimer's disease, cognitive decline, and depression. The present study aims to identify genetic comorbidities of age-related hearing loss. Past genome-wide association studies identified multiple genomic loci involved in common adult-onset health traits. Polygenic risk scores (PRS) could summarize the polygenic inheritance and quantify the genetic susceptibility of complex traits independent of trait expression. The present study conducted a PRS-based association analysis of age-related hearing difficulty in the UK Biobank sample (N = 425,240), followed by a replication analysis using hearing thresholds (HTs) and distortion-product otoacoustic emissions (DPOAEs) in 242 young adults with self-reported normal hearing. We hypothesized that young adults with genetic comorbidities associated with age-related hearing difficulty would exhibit subclinical decline in HTs and DPOAEs in both ears.</p><p><strong>Methods: </strong>A total of 111,243 participants reported age-related hearing difficulty in the UK Biobank sample (> 40 years). The PRS models were derived from the polygenic risk score catalog to obtain 2627 PRS predictors across the health spectrum. HTs (0.25-16 kHz) and DPOAEs (1-16 kHz, L1/L2 = 65/55 dB SPL, F2/F1 = 1.22) were measured on 242 young adults. Saliva-derived DNA samples were subjected to low-pass whole genome sequencing, followed by genome-wide imputation and PRS calculation. The logistic regression analyses were performed to identify PRS predictors of age-related hearing difficulty in the UK Biobank cohort. The linear mixed model analyses were performed to identify PRS predictors of HTs and DPOAEs.</p><p><strong>Results: </strong>The PRS-based association analysis identified 977 PRS predictors across the health spectrum associated with age-related hearing difficulty. Hearing difficulty and hearing aid use PRS predictors revealed the strongest association with the age-related hearing difficulty phenotype. Youth with a higher genetic predisposition to hearing difficulty revealed a subclinical elevation in HTs and a decline in DPOAEs in both ears. PRS predictors associated with age-related hearing difficulty were enriched for mental health, lifestyle, metabolic, sleep, reproductive, digestive, respiratory, hematopoietic, and immune traits. Fifty PRS predictors belonging to various trait categories were replicated for HTs and DPOAEs in both ears.</p><p><strong>Conclusion: </strong>The study identified genetic comorbidities associated with age-related hearing loss across the health spectrum. Youth with a high genetic predisposition to age-related hearing difficulty and other related complex traits could exhibit sub-clinical decline in HTs and DPOAEs decades before clinically meaningful age-related hearing loss is observed. We posit that effective communication of genetic risk","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"387-406"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089079","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}
Aseem Jain, Dianela Perdomo, Nimesh Nagururu, Jintong Alice Li, Bryan K Ward, Amanda M Lauer, Francis X Creighton
{"title":"SVPath: A Deep Learning Tool for Analysis of Stria Vascularis from Histology Slides.","authors":"Aseem Jain, Dianela Perdomo, Nimesh Nagururu, Jintong Alice Li, Bryan K Ward, Amanda M Lauer, Francis X Creighton","doi":"10.1007/s10162-024-00948-z","DOIUrl":"10.1007/s10162-024-00948-z","url":null,"abstract":"<p><strong>Introduction: </strong>The stria vascularis (SV) may have a significant role in various otologic pathologies. Currently, researchers manually segment and analyze the stria vascularis to measure structural atrophy. Our group developed a tool, SVPath, that uses deep learning to extract and analyze the stria vascularis and its associated capillary bed from whole temporal bone histopathology slides (TBS).</p><p><strong>Methods: </strong>This study used an internal dataset of 203 digitized hematoxylin and eosin-stained sections from a normal macaque ear and a separate external validation set of 10 sections from another normal macaque ear. SVPath employed deep learning methods YOLOv8 and nnUnet to detect and segment the SV features from TBS, respectively. The results from this process were analyzed with the SV Analysis Tool (SVAT) to measure SV capillaries and features related to SV morphology, including width, area, and cell count. Once the model was developed, both YOLOv8 and nnUnet were validated on external and internal datasets.</p><p><strong>Results: </strong>YOLOv8 implementation achieved over 90% accuracy for cochlea and SV detection. nnUnet SV segmentation achieved a DICE score of 0.84-0.95; the capillary bed DICE score was 0.75-0.88. SVAT was applied to compare both the ears used in the study. There was no statistical difference in SV width, SV area, and average area of capillary between the two ears. There was a statistical difference between the two ears for the cell count per SV.</p><p><strong>Conclusion: </strong>The proposed method accurately and efficiently analyzes the SV from temporal histopathology bone slides, creating a platform for researchers to understand the function of the SV further.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"1-8"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961275","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":"Optimal Scale-Invariant Wavelet Representation and Filtering of Human Otoacoustic Emissions.","authors":"Arturo Moleti","doi":"10.1007/s10162-024-00943-4","DOIUrl":"10.1007/s10162-024-00943-4","url":null,"abstract":"<p><p>Otoacoustic emissions (OAEs) are generated in the cochlea and recorded in the ear canal either as a time domain waveform or as a collection of complex responses to tones in the frequency domain (Probst et al. J Account Soc Am 89:2027-2067, 1991). They are typically represented either in their original acquisition domain or in its Fourier-conjugated domain. Round-trip excursions to the conjugated domain are often used to perform filtering operations in the computationally simplest way, exploiting the convolution theorem. OAE signals consist of the superposition of backward waves generated in different cochlear regions by different generation mechanisms, over a wide frequency range. The cochlear scaling symmetry (cochlear physics is the same at all frequency scales), which approximately holds in the human cochlea, leaves its fingerprints in the mathematical properties of OAE signals. According to a generally accepted taxonomy (Sher and Guinan Jr, J Acoust Soc Am 105:782-798, 1999), OAEs are generated either by wave-fixed sources, moving with frequency according with the cochlear scaling (as in nonlinear distortion) or by place-fixed sources (as in coherent reflection by roughness). If scaling symmetry holds, the two generation mechanisms yield OAEs with different phase gradient delay: almost null for wave-fixed sources, and long (and scaling as 1/f) for place-fixed sources. Thus, the most effective representation of OAE signals is often that respecting the cochlear scale-invariance, such as the time-frequency domain representation provided by the wavelet transform. In the time-frequency domain, the elaborate spectra or waveforms yielded by the superposition of OAE components from different generation mechanisms assume a much clearer 2-D pattern, with each component localized in a specific and predictable region. The wavelet representation of OAE signals is optimal both for visualization purposes and for designing filters that effectively separate different OAE components, improving both the specificity and the sensitivity of OAE-based applications. Indeed, different OAE components have different physiological meanings, and filtering dramatically improves the signal-to-noise ratio.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"329-340"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094528","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}
Yan Lu, Yi Jiang, Fangfang Wang, Hao Wu, Yunfeng Hua
{"title":"Electron Microscopic Mapping of Mitochondrial Morphology in the Cochlear Nerve Fibers.","authors":"Yan Lu, Yi Jiang, Fangfang Wang, Hao Wu, Yunfeng Hua","doi":"10.1007/s10162-024-00957-y","DOIUrl":"10.1007/s10162-024-00957-y","url":null,"abstract":"<p><p>To enable nervous system function, neurons are powered in a use-dependent manner by mitochondria undergoing morphological-functional adaptation. In a well-studied model system-the mammalian cochlea, auditory nerve fibers (ANFs) display distinct electrophysiological properties, which is essential for collectively sampling acoustic information of a large dynamic range. How exactly the associated mitochondrial networks are deployed in functionally differentiated ANFs remains scarcely interrogated. Here, we leverage volume electron microscopy and machine-learning-assisted image analysis to phenotype mitochondrial morphology and distribution along ANFs of full-length in the mouse cochlea inner spiral bundle. This reveals greater variance in mitochondrial size with increased ANF habenula to terminal path length. Particularly, we analyzed the ANF terminal-residing mitochondria, which are critical for local calcium uptake during sustained afferent activities. Our results suggest that terminal-specific enrichment of mitochondria, in addition to terminal size and overall mitochondrial abundance of the ANF, correlates with heterogenous mitochondrial contents of the terminal.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"341-354"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473064","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}
Shawn S Goodman, Shannon M Lefler, Choongheon Lee, John J Guinan, Jeffery T Lichtenhan
{"title":"The Origin Along the Cochlea of Otoacoustic Emissions Evoked by Mid-Frequency Tone Pips.","authors":"Shawn S Goodman, Shannon M Lefler, Choongheon Lee, John J Guinan, Jeffery T Lichtenhan","doi":"10.1007/s10162-024-00955-0","DOIUrl":"10.1007/s10162-024-00955-0","url":null,"abstract":"<p><strong>Purpose: </strong>Tone-pip-evoked otoacoustic emissions (PEOAEs) are transient-evoked otoacoustic emissions (OAEs) that are hypothesized to originate from reflection of energy near the best-frequency (BF) cochlear place of the stimulus frequency. However, individual PEOAEs have energy with a wide range of delays. We sought to determine whether some PEOAE energy is consistent with having been generated far from BF.</p><p><strong>Methods: </strong>PEOAEs from 35 and 47 dB SPL tone pips were obtained by removing pip-stimulus energy by subtracting the ear-canal sound pressure from scaled-down 59 dB SPL tone pips (which evoke relatively small OAEs). PEOAE delays were measured at each peak in the PEOAE absolute-value waveforms. While measuring PEOAEs and auditory-nerve compound action potentials (CAPs), amplification was blocked sequentially from apex to base by cochlear salicylate perfusion. The perfusion time when a CAP was reduced identified when the perfusion reached the tone-pip BF place. The perfusion times when each PEOAE peak was reduced identified where along the cochlea it received cochlear amplification. PEOAEs and CAPs were measured simultaneously using one pip frequency in each ear (1.4 to 4 kHz across 16 ears).</p><p><strong>Results: </strong>Most PEOAE peaks received amplification primarily between the BF place and 1-2 octaves basal of the BF place. PEOAE peaks with short delays received amplification basal of BF place. PEOAE peaks with longer delays sometimes received amplification apical of BF place, consistent with previous stimulus-frequency-OAE results.</p><p><strong>Conclusion: </strong>PEOAEs provide information about cochlear amplification primarily within ~ 1.5 octave of the tone-pip BF place, not about regions > 3 octaves basal of BF.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"363-376"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473065","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}