Journal of the Association for Research in Otolaryngology 2024-09-13

Otoacoustic Estimate of Astronauts’ Intracranial Pressure Changes During Spaceflight

A Moleti,T Minniti,Y Sharma,A Russo,A Civiero,MP Orlando,R MacGregor,M Lucertini,A D'Amico,G Pennazza,M Santonico,A Zompanti,A Crisafi,M Deffacis,R Sapone,G Mascetti,M Vadrucci,G Valentini,D Castagnolo,T Botti,L Cerini,F Sanjust,R Sisto

Publication date 13-09-2024


Purpose To investigate the potential correlation between prolonged exposure to microgravity on the International Space Station and increased intracranial fluid pressure, which is considered a risk factor for the astronauts’ vision, and to explore the feasibility of using distortion product otoacoustic emissions as a non-invasive in-flight monitor for intracranial pressure changes. Methods Distortion product otoacoustic emission phase measurements were taken from both ears of five astronauts pre-flight, in-flight, and post-flight. These measurements served as indirect indicators of intracranial pressure changes, given their high sensitivity to middle ear transmission alterations. The baseline pre-flight ground measurements were taken in the seated upright position. Results In-flight measurements revealed a significant systematic increase in otoacoustic phase, indicating elevated intracranial pressure during spaceflight compared to seated upright pre-flight ground baseline. Noteworthy, in two astronauts, strong agreement was also observed between the time course of the phase changes measured in the two ears during and after the mission. Reproducibility and stability of the probe placement in the ear canal were recognized as a critical issue. Conclusions The study suggests that distortion product otoacoustic emissions hold promise as a non-invasive tool for monitoring intracranial pressure changes in astronauts during space missions. Pre-flight measurements in different body postures and probe fitting strategies based on the individual ear morphology are needed to validate and refine this approach.

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Enhanced Place Specificity of the Parallel Auditory Brainstem Response: An Electrophysiological Study

TJ Stoll,RK Maddox

Publication date 20-08-2024


Purpose 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. Methods 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. Results 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. Conclusion 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.

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DNA Methylation Patterns Associated with Tinnitus in Young Adults—A Pilot Study

IS Bhatt,JAR Garay,A Torkamani,R Dias

Publication date 15-08-2024


Purpose Tinnitus, the perception of sound without any external sound source, is a prevalent hearing health concern. Mounting evidence suggests that a confluence of genetic, environmental, and lifestyle factors can influence the pathogenesis of tinnitus. We hypothesized that alteration in DNA methylation, an epigenetic modification that occurs at cytosines of cytosine-phosphate-guanine (CpG) dinucleotide sites, where a methyl group from S-adenyl methionine gets transferred to the fifth carbon of the cytosine, could contribute to tinnitus. DNA methylation patterns are tissue-specific, but the tissues involved in tinnitus are not easily accessible in humans. This pilot study used saliva as a surrogate tissue to identify differentially methylated CpG regions (DMRs) associated with tinnitus. The study was conducted on healthy young adults reporting bilateral continuous chronic tinnitus to limit the influence of age-related confounding factors and health-related comorbidities. Methods The present study evaluated the genome-wide methylation levels from saliva-derived DNA samples from 24 healthy young adults with bilateral continuous chronic tinnitus (> 1 year) and 24 age, sex, and ethnicity-matched controls with no tinnitus. Genome-wide DNA methylation was evaluated for > 850,000 CpG sites using the Infinium Human Methylation EPIC Bead Chip. The association analysis used the Bumphunter algorithm on 23 cases and 20 controls meeting the quality control standards. The methylation level was expressed as the area under the curve of CpG sites within DMRs.
The FDR-adjusted p-value threshold of 0.05 was used to identify statistically significant DMRs associated with tinnitus. Results We obtained 25 differentially methylated regions (DMRs) associated with tinnitus. Genes within or in the proximity of the hypermethylated DMRs related to tinnitus included LCLAT1, RUNX1, RUFY1, NUDT12, TTC23, SLC43A2, C4orf27 (STPG2), and EFCAB4B. Genes within or in the proximity of hypomethylated DMRs associated with tinnitus included HLA-DPB2, PM20D1, TMEM18, SNTG2, MUC4, MIR886, MIR596, TXNRD1, EID3, SDHAP3, HLA-DPB2, LASS3 (CERS3), C10orf11 (LRMDA), HLA-DQB1, NADK, SZRD1, MFAP2, NUP210L, TPM3, INTS9, and SLC2A14. The burden of genetic variation could explain the differences in the methylation levels for DMRs involving HLA-DPB2, HLA-DQB1, and MUC4, indicating the need for replication in large independent cohorts. Conclusion Consistent with the literature on comorbidities associated with tinnitus, we identified genes within or close to DMRs involved in auditory functions, chemical dependency, cardiovascular diseases, psychiatric conditions, immune disorders, and metabolic syndromes. These results indicate that epigenetic mechanisms could influence tinnitus, and saliva can be a good surrogate for identifying the epigenetic underpinnings of tinnitus in humans. Further research with a larger sample size is needed to identify epigenetic biomarkers and investigate their influence on the phenotypic expression of tinnitus.

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The Current State of Tinnitus Diagnosis and Treatment: a Multidisciplinary Expert Perspective

T Kleinjung,N Peter,M Schecklmann,B Langguth

Publication date 13-08-2024


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.

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Correction: Something in Our Ears Is Oscillating, but What? A Modeller’s View of Efforts to Model Spontaneous Emissions

HP Wit,A Bell

Publication date 01-08-2024


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The Origin Along the Cochlea of Otoacoustic Emissions Evoked by Mid-Frequency Tone Pips

SS Goodman,SM Lefler,C Lee,JJ Guinan,JT Lichtenhan

Publication date 01-08-2024


Purpose 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. Methods 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 k Hz across 16 ears). Results 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. Conclusion 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.

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Optimal Scale-Invariant Wavelet Representation and Filtering of Human Otoacoustic Emissions

A Moleti

Publication date 01-08-2024


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.

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SVPath: A Deep Learning Tool for Analysis of Stria Vascularis from Histology Slides

A Jain,D Perdomo,N Nagururu,JA Li,BK Ward,AM Lauer,FX Creighton

Publication date 01-08-2024


Introduction 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). Methods 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 nn Unet 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 nn Unet were validated on external and internal datasets. Results YOLOv8 implementation achieved over 90% accuracy for cochlea and SV detection. nn Unet 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. Conclusion 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.

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Conditions Underlying the Appearance of Spontaneous Otoacoustic Emissions in Mammals

GA Manley

Publication date 01-08-2024


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.

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The Rapid Decline in Interaural-Time-Difference Sensitivity for Pure Tones Can Be Explained by Peripheral Filtering

MJ Goupell,GC Stecker,BT Williams,A Bilokon,DJ Tollin

Publication date 01-08-2024


Purpose The interaural time difference (ITD) is a primary horizontal-plane sound localization cue computed in the auditory brainstem. ITDs are accessible in the temporal fine structure of pure tones with a frequency of no higher than about 1400 Hz. How listeners’ ITD sensitivity transitions from very best sensitivity near 700 Hz to impossible to detect within 1 octave currently lacks a fully compelling physiological explanation. Here, it was hypothesized that the rapid decline in ITD sensitivity is dictated not by a central neural limitation but by initial peripheral sound encoding, specifically, the low-frequency (apical) portion of the cochlear excitation pattern produced by a pure tone. Methods ITD sensitivity was measured in 16 normal-hearing listeners as a joint function of frequency (900–1500 Hz) and level (10–50 dB sensation level). Results Performance decreased with increasing frequency and decreasing sound level. The slope of performance decline was 90 dB/octave, consistent with the low-frequency slope of the cochlear excitation pattern. Conclusion Fine-structure ITD sensitivity near 1400 Hz may be conveyed primarily by “off-frequency” activation of neurons tuned to lower frequencies near 700 Hz. Physiologically, this could be realized by having neurons sensitive to fine-structure ITD up to only about 700 Hz. A more extreme model would have only a single narrow channel near 700 Hz that conveys fine-structure ITDs. Such a model is a major simplification and departure from the classic formulation of the binaural display, which consists of a matrix of neurons tuned to a wide range of relevant frequencies and ITDs.

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Polygenic Risk Score-Based Association Analysis Identifies Genetic Comorbidities Associated with Age-Related Hearing Difficulty in Two Independent Samples

IS Bhatt,JA Raygoza Garay,SG Bhagavan,V Ingalls,R Dias,A Torkamani

Publication date 01-08-2024


Purpose 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. Methods 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 k Hz) and DPOAEs (1–16 k Hz, 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. Results 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. Conclusion 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, promoting a healthy lifestyle, and reducing exposure to environmental risk factors at younger ages could help prevent or delay the onset of age-related hearing difficulty at older ages.

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Asymmetry in the Perception of Electrical Chirps Presented to Cochlear Implant Listeners

A Šodan,S Meunier,V Péan,JP Lavieille,S Roman,O Macherey

Publication date 01-08-2024


Introduction Although a broadband acoustic click is physically the shortest duration sound we can hear, its peripheral neural representation is not as short because of cochlear filtering. The traveling wave imposes frequency-dependent delays to the sound waveform so that in response to a click, apical nerve fibers, coding for low frequencies, are excited several milliseconds after basal fibers, coding for high frequencies. Nevertheless, a click sounds like a click and these across-fiber delays are not perceived. This suggests that they may be compensated by the central auditory system, rendering our perception consistent with the external world. This explanation is difficult to evaluate in normal-hearing listeners because the contributions of peripheral and central auditory processing cannot easily be disentangled. Here, we test this hypothesis in cochlear implant listeners for whom cochlear mechanics is bypassed. Method Eight cochlear implant users ranked in perceived duration 12 electrical chirps of various physical durations and spanning the cochlea in the apex-to-base or base-to-apex direction (Exp. 1). Late-latency cortical potentials were also recorded in response to a subset of these chirps (Exp. 2). Results We show that an electrical chirp spanning the cochlea from base-to-apex is perceived as shorter than the same chirp spanning the cochlea in the opposite direction despite having the same physical duration. Cortical potentials also provide neural correlates of this asymmetry in perception. Conclusion These results demonstrate that the central auditory system processes frequency sweeps differently depending on the direction of the frequency change and that this processing difference is not simply the result of peripheral filtering.

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Electron Microscopic Mapping of Mitochondrial Morphology in the Cochlear Nerve Fibers

Y Lu,Y Jiang,F Wang,H Wu,Y Hua

Publication date 01-08-2024


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.

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Something in Our Ears Is Oscillating, but What? A Modeller’s View of Efforts to Model Spontaneous Emissions

HP Wit,A Bell

Publication date 01-08-2024


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.

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Correction: Transient Receptor Potential (TRP) Channels in Cochlear Function: Looking Beyond Mechanotransduction

T Nguyen,DE Bergles

Publication date 15-07-2024


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Experimental Study of Needle Insertion into Gerbil Tympanic Membrane

H Mohammadi,A Ebrahimian,N Maftoon

Publication date 11-07-2024


The perforation characteristics and fracture-related mechanical properties of the tympanic membrane (TM) greatly affect surgical procedures like myringotomy and tympanostomy performed on the middle ear. We analyzed the most important features of the gerbil TM perforation using an experimental approach that was based on force measurement during a 2-cycle needle insertion/extraction process. Fracture energy, friction energy, strain energy, and hysteresis loss were taken into consideration for the analysis of the different stages of needle insertion and extraction. The results demonstrated that (1) although the TM shows viscoelastic behavior, the contribution of hysteresis loss was negligible compared to other irreversible dissipated energy components (i.e., fracture energy and friction energy). (2) The TM puncture force did not substantially change during the first hours after animal death, but interestingly, it increased after 1 week due to the drying effects of soft tissue. (3) The needle geometry affected the crack length and the most important features of the force-displacement plot for the needle insertion process (puncture force, puncture displacement, and jump-in force) increased with increasing needle diameter, whereas the insertion velocity only changed the puncture and jump-in forces (both increased with increasing insertion velocity) and did not have a noticeable effect on the puncture displacement. (4) The fracture toughness of the gerbil TM was almost independent of the needle geometry and was found to be around 0.33 \(\pm\) 0.10 kJ/m2.

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Human Olivocochlear Effects: A Statistical Detection Approach Applied to the Cochlear Microphonic Evoked by Swept Tones

SS Goodman,S Haysley,SG Jennings

Publication date 01-07-2024


The human medial olivocochlear (MOC) reflex was assessed by observing the effects of contralateral acoustic stimulation (CAS) on the cochlear microphonic (CM) across a range of probe frequencies. A frequency-swept probe tone (125–4757 Hz, 90 dB SPL) was presented in two directions (up sweep and down sweep) to normal-hearing young adults. This study assessed MOC effects on the CM in individual participants using a statistical approach that calculated minimum detectable changes in magnitude and phase based on CM signal-to-noise ratio (SNR). Significant increases in CM magnitude, typically 1–2 dB in size, were observed for most participants from 354 to 1414 Hz, where the size and consistency of these effects depended on participant, probe frequency, sweep direction, and SNR. CAS-related phase lags were also observed, consistent with CM-based MOC studies in laboratory animals. Observed effects on CM magnitude and phase were in the opposite directions of reported effects on otoacoustic emissions (OAEs). OAEs are sensitive to changes in the motility of outer hair cells located near the peak region of the traveling wave, while the effects of CAS on the CM likely originate from MOC-related changes in the conductance of outer hair cells located in the basal tail of the traveling wave. Thus, MOC effects on the CM are complementary to those observed for OAEs.

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Transient Receptor Potential (TRP) Channels in Cochlear Function: Looking Beyond Mechanotransduction

T Nguyen,DE Bergles

Publication date 26-06-2024


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.

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Tinnitus: Clinical Insights in Its Pathophysiology-A Perspective

B Langguth,D de Ridder,W Schlee,T Kleinjung

Publication date 01-06-2024


Tinnitus, the perception of sound without a corresponding external sound source, and tinnitus disorder, which is tinnitus with associated suffering, present a multifaceted clinical challenge due to its heterogeneity and its incompletely understood pathophysiology and especially due to the limited therapeutic options. In this narrative review, we give an overview on various clinical aspects of tinnitus including its heterogeneity, contributing factors, comorbidities and therapeutic pathways with a specific emphasis on the implications for its pathophysiology and future research directions. Tinnitus exhibits high perceptual variability between affected individuals (heterogeneity) and within affected individuals (temporal variability). Hearing loss emerges as predominant risk factor and the perceived pitch corresponds to areas of hearing loss, supporting the compensatory response theory. Whereas most people who have tinnitus can live a normal life, in 10–20% tinnitus interferes severely with quality of life. These patients suffer frequently from comorbidities such as anxiety, depression or insomnia, acting as both risk factors and consequences. Accordingly, neuroimaging studies demonstrate shared brain networks between tinnitus and stress-related disorders shedding light on the intricate interplay of mental health and tinnitus. The challenge lies in deciphering causative relationships and shared pathophysiological mechanisms. Stress, external sounds, time of day, head movements, distraction, and sleep quality can impact tinnitus perception. Understanding these factors provides insights into the interplay with autonomic, sensory, motor, and cognitive processes. Counselling and cognitive-behavioural therapy demonstrate efficacy in reducing suffering, supporting the involvement of stress and anxiety-related networks. Hearing improvement, especially through cochlear implants, reduces tinnitus and thus indirectly validates the compensatory nature of tinnitus. Brain stimulation techniques can modulate the suffering of tinnitus, presumably by alteration of stress-related brain networks. Continued research is crucial for unravelling the complexities of tinnitus. Progress in management hinges on decoding diverse manifestations, identifying treatment-responsive subtypes, and advancing targeted therapeutic approaches.

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Hampshire Sheep as a Large-Animal Model for Cochlear Implantation

NA Waring,A Chern,BJ Vilarello,YS Cheng,C Zhou,JH Lang,ES Olson,HH Nakajima

Publication date 01-06-2024


Background Sheep have been proposed as a large-animal model for studying cochlear implantation. However, prior sheep studies report that the facial nerve (FN) obscures the round window membrane (RWM), requiring FN sacrifice or a retrofacial opening to access the middle-ear cavity posterior to the FN for cochlear implantation. We investigated surgical access to the RWM in Hampshire sheep compared to Suffolk-Dorset sheep and the feasibility of Hampshire sheep for cochlear implantation via a facial recess approach. Methods Sixteen temporal bones from cadaveric sheep heads (ten Hampshire and six Suffolk-Dorset) were dissected to gain surgical access to the RWM via an extended facial recess approach. RWM visibility was graded using St. Thomas’ Hospital (STH) classification. Cochlear implant (CI) electrode array insertion was performed in two Hampshire specimens. Micro-CT scans were obtained for each temporal bone, with confirmation of appropriate electrode array placement and segmentation of the inner ear structures. Results Visibility of the RWM on average was 83% in Hampshire specimens and 59% in Suffolk-Dorset specimens (p = 0.0262). Hampshire RWM visibility was Type I (100% visibility) for three specimens and Type IIa (> 50% visibility) for seven specimens. Suffolk-Dorset RWM visibility was Type IIa for four specimens and Type IIb (< 50% visibility) for two specimens. FN appeared to course more anterolaterally in Suffolk-Dorset specimens. Micro-CT confirmed appropriate CI electrode array placement in the scala tympani without apparent basilar membrane rupture. Conclusions Hampshire sheep appear to be a suitable large-animal model for CI electrode insertion via an extended facial recess approach without sacrificing the FN. In this small sample, Hampshire specimens had improved RWM visibility compared to Suffolk-Dorset. Thus, Hampshire sheep may be superior to other breeds for ease of cochlear implantation, with FN and facial recess anatomy more similar to humans.

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