The nonlinear cochlear amplifier, driven by outer hair cells, underlies the remarkable sensitivity and frequency selectivity of the mammalian auditory system. Stimulus frequency otoacoustic emissions (SFOAEs) provide a noninvasive window into these active cochlear processes, yet the relationship between emission gain and delay across stimulus levels remains incompletely understood. This study examined the level dependence of SFOAEs in normal-hearing human listeners to characterize cochlear nonlinear response properties. We tested how emission gain and delay vary with stimulus level and estimated the frequency of the apical–basal transition associated with the breakdown of the approximate local scaling symmetry. SFOAEs were recorded from a cohort of normal-hearing participants (n = 20; females = 13) across a range of stimulus levels. A time-frequency filtering approach was applied to isolate single-reflection components and improve signal-to-noise ratio, yielding stable and unbiased estimates of emission level and phase-gradient delay. The relationships between stimulus level, gain, and delay were analyzed and normalized using a general relation derived from the fundamental physical properties of linear two-dimensional cochlear model. The results confirm the nonlinear dependence of SFOAE level and delay on stimulus level. However, when the variations in gain and delay were compared to the predictions of a linear and a nonlinear 2D cochlear model, the discrepancy with the linear model predictions was evident. Measurements also revealed no stimulus-level dependence of the apical–basal transition frequency, consistent with a fixed apical cochlear region associated with the breakdown of the approximate scaling symmetry. The relative decoupling between gain and delay indicates that changes in cochlear amplification do not produce proportionate changes in emission timing, revealing constraints on the relationship between amplification and phase behavior in human cochlear responses. These findings indicate that SFOAE delay may remain informative about cochlear tuning, but nonlinear cochlear models could be constrained by the observed decoupling between gain and delay.
Kv3.1 channels are high-voltage-activated potassium channels that facilitate high-frequency firing in auditory brainstem neurons. Fusiform neurons in the dorsal cochlear nucleus (DCN) can fire rapid trains of action potentials and express Kv3.1 channels. Their ability to fire high-frequency action potential trains increases after hearing onset at postnatal day 14. Simultaneously, the action potentials become shorter and faster. We tested whether Kv3.1 channels drive the developmental maturation of action potentials in DCN fusiform neurons. We used Swiss female mice from postnatal day 8 to 25 and divided them into pre-hearing (< P14) and post-hearing (> P14). We measured Kv currents and action potentials in whole-cell patch-clamp. Tetraethylammonium (TEA) was applied at a concentration of 1–5 mM to block Kv3 channels, and we detected the expression of Kv3.1b channel subunits by immunocytochemistry. We found increased Kv3.1b subunit expression in the DCN after hearing onset, suggesting that this subunit could be responsible for the electrophysiological changes in post-hearing fusiform neurons. TEA-sensitive high-threshold currents were a significant component of voltage-dependent potassium currents in both pre- and post-hearing fusiform neurons, with similar magnitudes in both groups. However, blocking Kv3 currents with 1–5 mM TEA broadens action potential waveforms in neurons from both groups while maintaining the developmental differences between groups. On the other hand, TEA was more effective at reducing the firing of post-hearing neurons. We conclude that the rise in Kv3.1b channel expression in DCN fusiform neurons after hearing does not account for the shorter, faster action potentials observed at that time, but could contribute to their ability to fire action potentials at high frequencies.
In the central nervous system, Ca2⁺ signaling plays a pivotal role in various cellular processes, including neuronal development and maturation. Disruption of Ca2⁺ homeostasis impairs auditory circuit formation, compromising auditory processing and behavior. Here, we aimed to investigate systematically the development of Ca2⁺ signaling in neurons of the medial nucleus of the trapezoid body (MNTB), a brainstem nucleus critical for sound localization. Using Ca2⁺ imaging in brain slices from mice genetically expressing the Ca2⁺ indicator GCaMP in glycinergic cells, we studied Ca2⁺ signaling in MNTB neurons from mice of either sex at three developmental milestone stages, in response to both bath-applied agonists of various neurotransmitter receptors and synaptic activation of glutamatergic afferents. Prior to hearing onset at postnatal 7 days (P7), robust Ca2⁺ responses were evoked in MNTB neurons upon activation of glutamate receptors (NMDARs, AMPARs, and group I (Gp-I) mGluRs by 200 μM NMDA, 100 μM AMPA, and 200 μM 3,5-DHPG, respectively), whereas after hearing onset (P14 and P21), responses induced by NMDA and 3,5-DHPG declined markedly while AMPA-induced responses remained relatively strong. Ca2⁺ responses upon application of GABA (100 μM) and glycine (200 μM) were detected in neonatal mice, diminished in a few days after birth, and almost completely disappeared by P7. Whole-cell patch-clamp recordings showed that stimulation of excitatory afferents evoked action potentials across all ages with no differences in firing frequency up to 100 Hz, but Ca2⁺ responses varied in a stimulus intensity- and frequency-dependent manner and exhibited developmental downregulation. Ca2⁺ signaling induced by activation of the major transmitter receptors in MNTB neurons is highly developmentally down-regulated.
Simultaneous hearing and balance restoration through combined cochlear-vestibular implants (CVIs) offers a promising treatment for patients with dual sensory deficits. However, the effects of electrical stimulation on neighboring neural structures in the inner ear remain poorly understood. In this study, we present a detailed computational model of the human inner ear that simulates electrical stimulation of cochlear and vestibular nerves under clinically relevant conditions. The model integrates high-resolution micro-CT-based geometry, anisotropic tissue conductivities, and myelinated fiber models to predict neural activation patterns across a wide range of clinically relevant stimulation parameters. Simulation results suggest that vestibular stimulation at clinically relevant amplitudes can influence cochlear nerve activation thresholds, particularly in basal cochlear regions. Conversely, cochlear stimulation had a comparatively weaker effect on vestibular activation. Interleaved stimulation with short interstimulus intervals (smaller 100 s) resulted in increased excitability in the non-targeted nerve population, suggesting the potential for undesired cross-talk effects. Pulse waveform characteristics, including phase duration and symmetry, further modulated the degree of crosstalk observed. This model allows for comprehensive evaluation of scenarios that cannot be tested in humans due to ethical, practical, or technical limitations. As a result, it provides a valuable tool for exploring new combined simulation scenarios and may aid the development of newly designed implants.
To evaluate the safety and tolerability and exploratory efficacy of OTO-413, an intratympanic-administered, sustained release formulation of brain-derived neurotrophic factor (BDNF) in a thermoreversible gel, in participants with speech-in-noise hearing difficulties. This was a single dose, dose-ascending, randomized, double-blind, Placebo-controlled Phase 1/2 study conducted at 7 enrolling clinical sites in the U.S. 110 participants (56
Platinum-based chemotherapy is widely used in cancer care but carries a substantial risk of cochleotoxicity and vestibulotoxicity. This study aimed to characterize early (3-month) and long-term (1-year) auditory and vestibular effects of platinum derivatives in adults, with the goal of improving monitoring strategies. A total of 110 adults (34–81 years; 63 female) received cisplatin (n = 73), carboplatin (n = 22), or sequential cisplatin followed by carboplatin (ciscarbo; n = 15). Assessments at baseline, 3 months, and 1 year included conventional and extended high-frequency (EHF) audiometry, distortion product otoacoustic emissions (DPOAEs), speech perception, auditory brainstem response (ABR), and envelope following response (EFR). Vestibular testing comprised vHIT and cVEMP. Ototoxicity was classified using ASHA (1994) and graded with TUNE. Linear mixed models assessed treatment- and time-related changes. Cisplatin induced significant threshold shifts across the audiogram, including low, mid, high, and extended high frequencies, with progression up to 1 year. Low- and mid-frequency thresholds remained largely stable in the carboplatin group, while the ciscarbo group showed early mid- and EHF deterioration. EHF thresholds increased across all groups. ASHA-defined ototoxicity was present in 73.5
The history of hearing aids is rife with examples of deaf invention, “sonic skills,” and other expertise on the parts of deaf and hard of hearing people—whether they were celebrated figures like Thomas Edison, forgotten deaf scientists and engineers, or lay experts. This article, a contribution to the roundtable from the field of history of science, examines correspondence about hearing aids in the Edison archives to argue that Edison and his deaf interlocutors have much to tell us about deaf acoustics: the innovations or insights offered by deaf and hard of hearing people that have contributed to the suite of scientific approaches to sound (i.e., acoustics) including engineering, architecture, physiology, and psychology.
PurposeDistortion product otoacoustic emission (DPOAE) magnitudes measured in the ear canal in response to a range of primary stimulus levels as growth functions (GFs) may be useful for assessing cochlear non-linearity, predicting behavioral audiometric thresholds, estimating loudness perception, and differentiating types of cochlear pathology. A variety of stimulation schemes have been proposed, and GF shapes differ depending on the stimulation scheme used. A clearer understanding of the relationships between stimuli, GFs, cochlear non-linearities, and cochlear health is important for maximizing the diagnostic potential of DPOAEs.MethodsLatent growth modeling, a technique within the structural equation modeling framework, can provide insight into the relationships between observed (e.g., GFs) and unobserved latent variables (e.g., cochlear non-linearities). We describe a latent growth model for characterizing GFs with a generalized logistic function representing the latent non-linearity, coupled with a generalized linear regression model appropriate for fitting GFs with varying signal-to-noise ratios (SNRs). The model was applied to GF data from twelve young adult ears (9 female, 3 male). The resulting fits inferred the shape of the underlying non-linearity and also quantified standard GF characteristics such as slope, threshold, and inflection points.ResultsData from participants, along with Monte Carlo simulations, demonstrate that this fitting method performs well under low SNR conditions and accurately predicts DPOAE magnitudes at low stimulus levels.ConclusionThis report establishes a robust method for characterizing GFs, supporting the long-term goal of applying the method in future studies of the relationships between acoustic stimuli, GFs, cochlear non-linearities, and cochlear health.
Older adults with profound hearing loss can derive substantial benefit from cochlear implants (CIs), yet outcomes are more variable than in younger recipients. Degeneration of spiral ganglion neurons (SGNs) is a major determinant of CI performance, and age-related hearing loss (ARHL) is accompanied by subtype-specific SGN alterations. However, how these changes shape electrically evoked neural responses remains unclear. This study examined the effects of age-related changes in SGN packing density and subtype composition on electrically evoked compound action potentials (ECAPs), with particular emphasis on interphase gap (IPG) sensitivity. A cochlear implant model was established in 17 male C57BL/6 J mice across three age groups: 6–8-weeks, 6 months, and 12 months. ECAPs were quantified using absolute measures, including amplitude, slope, dynamic range, 50
We employ the Hamiltonian Monte Carlo (HMC) algorithm to estimate model parameters and quantify their uncertainties in a fractional-order lumped-element model of the human ear in a Bayesian inference framework. The model, originally developed by Naghibolhosseini and Long (2018), incorporates fractional-order elements to capture viscoelastic memory effects in ear tissues that otherwise cannot adequately be represented via conventional integer-order models. Using previously optimized model parameters to construct informative priors, we perform Bayesian parameter estimation via the No-U-Turn Sampler (NUTS) implementation. From the inferred posterior distributions, we compute the model’s outer-middle ear gain (OMEG) and validate predictions against experimental OMEG derived from DPOAE measurements. Additionally, we compare stapes velocity transfer functions and ear canal pressure gain with established experimental and computational literature. HMC sampling yields well-convergent posterior distributions for all parameters, centered near original optimized values with uncertainty quantified through credible intervals. The posterior predictive OMEG frequency response closely matches the experimental OMEG measurements. Interestingly, the Bayesian-derived parameter sets correctly exhibit stapes velocity resonances near 1 kHz and ear canal pressure gain peaks between 2.5 and 4 kHz, with amplification ranging from 4 to 12 dB, consistent with cadaveric experimental measurements and existing computational models. The model demonstrates a minimal intersubject variability while capturing realistic biological variations within experimentally reported ranges. The present Bayesian HMC simulation approach then provides a robust uncertainty quantification for fractional-order ear model parameter inference, maintaining physiologically consistent predictions across multiple validation datasets. Hence, the proposed framework enhances the model’s credibility by establishing a firm foundation for further developing probabilistic diagnostic tools for hearing assessment in the future.
The UmboMic is a recently developed middle ear microphone that functions by detecting the sound-induced motion of the umbo [1]. To prepare for a live animal study of the in vivo performance of the UmboMic, we developed the surgical implantation and fixation system in cadaveric sheep ears. Temporal bones from seven female sheep were prepared for implantation of the UmboMic system. Fixation hardware for sheep was designed to secure the UmboMic sensor in position so that the sensing tip contacted the umbo in the middle-ear cavity and the non-sensing tail end was secured to the surrounding mastoid bone. First, pre-surgical micro-CT scans of the temporal bones and open-source software were used to simulate surgical drilling, and to virtually plan and fit the UmboMic fixation system. Then, in physical sheep temporal bones, sound-induced umbo motion was measured with a laser Doppler vibrometer as a preliminary step. After surgical implantation of the UmboMic system, the position of the UmboMic sensor was evaluated with microscopic visualization and post-surgical micro-CT. Implanted UmboMic sensor function in response to acoustic frequency sweeps to the external ear canal was measured in two specimens. Measurements of sheep temporal bone anatomical dimensions with micro-CT showed that the facial recess featured a mean maximum height of 2.36 mm, length of 12.2 mm, and depth from outer opening surface of facial recess to the umbo of 11.1 mm. The amplitude of umbo motion prior to UmboMic implantation was consistent with that previously reported by [2], with a displacement of 14 nm/Pa up to a frequency of 5.5 kHz, followed by a gradual drop-off. When bench tested and implanted in sheep temporal bones, the UmboMic sensitivity was as predicted from [1], 1–2 fC/nm. When implanted in sheep cadaveric ears, UmboMic performance was similar to previous measurements in fresh human cadaveric temporal bones. The method of simulating surgical drilling using micro-CT and simple open-source software is economical and broadly applicable in understanding the 3D biological anatomy and implantable device design and customization. The UmboMic implantation in cadaveric sheep ears was possible, and this study represents a step towards planned live animal studies.
Purpose Tinnitus and hearing loss are the most prevalent service-related auditory disabilities among American veterans. Previous studies have examined gray matter or white matter alterations in tinnitus and hearing loss relative to healthy controls, but typically in isolation, and none of them have focused specifically on a military-affiliated population. Methods We employed voxel-based morphometry to assess gray matter differences and diffusion tensor imaging to evaluate white matter integrity in tinnitus and/or hearing loss compared to controls in a sample of 68 military-affiliated adults (56 men, 10 women, two identifying as 'other' gender). Additionally, we conducted an exploratory, hypothesis-generating effect size analysis to describe the magnitude of group differences. Results Combined tinnitus and hearing loss was associated with decreased gray matter volume in the thalamus. White matter integrity was reduced in the forceps minor, right superior longitudinal fasciculus, and left inferior longitudinal fasciculus. Hearing loss alone was associated with white matter orientation changes in the right anterior thalamic radiation, left supe-rior longitudinal fasciculus, and right corticospinal tract. Larger effect sizes were noted in white matter comparisons across tinnitus, hearing loss, and combined conditions, suggesting that white matter differences may be of greater magnitude than gray matter alterations. Conclusion These findings advance the understanding of the neural correlates of tinnitus and hearing loss in the military population, an understudied group with a high prevalence of tinnitus and hearing loss. They also present preliminary effect size estimates that may inform future studies on the neural correlates of tinnitus and hearing loss, indicating a larger overall magnitude in white matter and more subtle contributions from gray matter.
Ménière’s disease presents with endolymphatic hydrops and disproportionately poor word-recognition compared to other forms of sensorineural hearing loss, yet the underlying patterns of cochlear degeneration are not well defined. This study aimed to characterize cochlear pathology in Ménières, compare it to age-matched controls and clinically unaffected contralateral ears, and evaluate how hydrops severity and clinical endotypes relate to tissue degeneration. We analyzed 97 human cochleas, including 43 Ménière’s ears, 10 contralateral (clinically unaffected) ears, and 44 age-matched controls. Quantitative histopathology assessed survival of hair cells, spiral ganglion cells, auditory-nerve peripheral axons, stria vascularis, and spiral ligament fibrocytes, along with the degree of endolymphatic hydrops. We also examined the effects of disease duration and endolymphatic sac phenotype (hypoplastic vs degenerative). Ménière’s ears displayed consistent cochlear hydrops and more severe saccular hydrops. They showed roughly half the normal complement of cochlear hair cells but only 25
MYO7A is involved in several forms of deafness in humans and mice, and in this study we aimed to investigate if the hearing loss could be reversed after its onset. A knockdown allele of Myo7a in the mouse, Myo7atm1a, was characterised by recording ABR thresholds at ages from 4 weeks to 6 months old and measuring the amount of hair cell degeneration at 4 weeks old. Scanning electron microscopy was used to assess the condition of stereocilia bundles. A tamoxifen-inducible Flp recombinase was used to activate expression of Myo7a in Myo7atm1a/tm1a homozygotes at 4 weeks old by excising the transcription disruption cassette in the tm1a allele allowing expression of the Myo7a gene, and ABRs were recorded before and after activation of the gene. Myo7atm1a was found to be a recessive allele causing reduced transcription and early onset profound deafness. Some hair cell loss was found at 4 weeks old, and scanning electron microscopy showed Myo7atm1a severely affects stereocilia morphology and organisation. Activation of Myo7a expression at 4 weeks old results in very small improvements in ABR thresholds of Myo7atm1a/tm1a mice at 12 and 18 kHz at 6 and 8 weeks old but there were no responses to sound by 14 weeks old. It is likely to be challenging to reverse hearing loss due to very early developmental defects of stereocilia organisation.
Understanding speech in noisy environments is a major challenge for millions, a problem that conventional hearing aids often exacerbate by amplifying all sounds indiscriminately. Auditory Attention Decoding (AAD) offers a revolutionary alternative: a brain-computer interface that decodes a listener’s attentional focus from their neural signals to selectively enhance the desired sound source. For over a decade, research has demonstrated the scientific feasibility of attention decoding, yet the field has faced a critical barrier in translating this promise into a real-time system that provides a demonstrable perceptual benefit in real-world listening conditions. This perspective charts the journey of AAD, from its foundational neuroscientific discoveries to the current engineering hurdles that must be overcome for real-world deployment. We outline the key remaining challenges, including the need to define user-centric metrics for success, develop practical and power-efficient wearable sensors, design low-latency and computationally efficient decoding algorithms, and ensure robust performance in complex, naturalistic scenes. By addressing these questions, the field can move beyond passive amplification and create the next generation of assistive technology: one that listens with the brain to restore or augment the hearing experience, making it fully aligned with the user’s intent.
PurposeFluid flow and transport of therapeutic agents and pathogenic bacteria into the cochlea has been challenging to study due to its small size and location within bone. We here take advantage of recent non-invasive Computed Tomography (CT) imaging to infer transport parameters in a 1-dimensional advection-diffusion model of the cochlear aqueduct using a Bayesian approach.MethodsSix male C56BL/6 mice injected with the small molecule tracer iohexol in cisterna magna were scanned every 5 min for 30 min in CT under anesthesia. Using the CT data to set boundary conditions, we solve the advection-diffusion equation for given advection and spatially varying diffusion parameters. The CT data is modeled as normally distributed around the model-predicted concentration. We specify priors for the model unknown parameters and infer their posterior distributions using Bayes' formula and the CUQIpy library. The statistical approach is validated using synthetic data.ResultsThe evolution of the concentration of tracer in the cochlear aqueduct is well predicted by the advection-diffusion model using inferred parameters. Though diffusion of the small CT tracer varies along the aqueduct, it is usually near the free diffusion and therefore not likely to be influenced much by membranes or flow. Advection is inferred near zero in most cases. We show how to use these results to calculate transport through the cochlear aqueduct for other animals and molecules.ConclusionFree diffusion dominates transport of small molecules in the cochlear aqueduct, which can therefore be effectively approximated using simple 1-dimensional (advection-)diffusion formulas.
Despite significant advances in our understanding of human hearing and assistive hearing technologies, the benefits of hearing loss compensation continue to vary widely across individuals. A central challenge is the complexity and heterogeneity of hearing loss, whose perceptual consequences often extend far beyond reduced sensitivity. Conventional strategies rely on signal processing algorithms—such as spatial filtering, noise reduction, and dynamic range compression—to improve audibility and enhance target signals. These components are usually optimized in isolation, yet their combined effects may interfere with one another and therefore do not necessarily yield an overall benefit. More recently, machine learning techniques have been used to further improve the performance of individual components. To tailor compensation strategies to specific acoustic environments or listeners, various steering mechanisms have also been proposed, guided by acoustic cues, audiovisual input, or listener attention. While these approaches show promise, a consistent and objective computational target for optimization has yet to be established. As an alternative, auditory model-based strategies, increasingly combined with machine learning, have emerged. These approaches aim to minimize the discrepancy between simulated auditory representations of normal and impaired hearing, thereby providing a physiologically motivated optimization goal. Although both categories of strategies offer considerable potential, achieving effective compensation under real-time, real-world conditions remains a major challenge. This paper reviews opportunities and limitations of these approaches for individualized hearing aid compensation.
Efferent modulation of vertebrate auditory organs has been known since the early twentieth century, mediated by cholinergic brainstem neurons. In mammals, medial olivocochlear neurons release acetylcholine (ACh) to inhibit outer hair cells to reduce cochlear sensitivity and tuning through an unusual mechanism of nicotinic inhibition, employing unique α9α10-containing AChRs (nAChRs). This synaptic mechanism and orthologous nAChRs, are conserved among vertebrate hair cells. Genetic modification of α9α10-containing nAChRs has cemented the role of efferent feedback in protection against noise-induced hearing loss in mice. Virally-mediated introduction of gain-of-function nAChRs reduces the impact of acoustic trauma in wildtype mice, encouraging development of cholinergic gene therapy for clinical application.
Purpose We describe a novel paradigm for evoking and measuring middle ear muscle reflex (MEMR), in which a train of broadband clicks act as probes, while a broadband noise elicitor is continuously swept in both ascending and descending sound levels. A new measure, total change, incorporates both magnitude and phase to quantify MEMR in a way that promotes meaningful averaging across a wide range of sound levels and frequencies. The aims of the study were to assess the retest reliability of the new swept-elicitor MEMR paradigm, to compare results with those obtained using traditional discrete-elicitor stimuli, and to preliminarily examine correlations with speech-in-noise performance.MethodsMEMR was measured in 38 young, normal-hearing participants (24 female, 14 male) using both the novel swept paradigm and a more conventional paradigm with elicitor noises that were discretely varied in level. Key measures of MEMR dynamics were obtained from the swept elicitor paradigm, including maximum total change, onset and offset thresholds, hysteresis, and reflex delay. Intraclass correlation coefficients (ICCs) were used to assess repeatability, and robust linear regression was used to examine correlations with QuickSIN performance.ResultsThe swept MEMR paradigm demonstrated excellent repeatability, with ICC values exceeding 0.90 for all extracted measures. MEMR thresholds from the swept elicitor correlated moderately with speech-in-noise performance.ConclusionsOur new MEMR paradigm provides fast, repeatable measurements. Several measures of MEMR dynamics can be obtained, improving upon traditional measurement approaches. Results suggest a possible link between MEMR dynamics and speech-in-noise performance.
