Hearing Research

Sensorineural hearing loss can result from different pathologies, but the primary diagnostic method is a threshold-based audiogram, which is insensitive to some forms of cochlear dysfunction. Individuals may experience difficulty understanding speech in noise despite normal audiometric thresholds. Because most cochlear insults damage both inner (IHCs) and outer hair cells (OHCs), the contribution of IHC dysfunction to auditory-nerve coding has been difficult to isolate. We used the IHC-selective ototoxicity of carboplatin in chinchillas to examine how IHC dysfunction, with preserved OHC function, affects temporal-envelope coding in auditory-nerve fibers (ANFs). Carboplatin produced 10 to 20% IHC loss with stereocilia damage in surviving IHCs, while OHC-dependent measures such as DPOAEs and ANF thresholds were unchanged. Suprathreshold ABR wave 1 was reduced, whereas wave 5 was preserved, suggesting central compensation. Both spontaneous and driven firing rates decreased following exposure. Mean vector strength to amplitude-modulated tones was unchanged, but response variability increased. Neurometric analysis and mutual information showed degraded AM detection in carboplatin-exposed fibers, an effect accounted for by reduced driven rate (i.e., normalizing spike counts across groups removed the group difference). Background noise degraded AM coding similarly in both groups. Pooled-neurometric modeling showed that population redundancy compensated for impaired fibers in quiet, but not in noise, where carboplatin-exposed pools remained worse. These findings indicate that IHC dysfunction degrades envelope coding by reducing neural output rather than by altering temporal synchrony. This study suggests IHC dysfunction is a phenotype consistent with "hidden hearing loss" (but distinct from cochlear synaptopathy), and motivates suprathreshold clinical assays.

The inferior colliculus (IC) is a major midbrain convergence site critical for processing complex sounds and undergoes fundamental changes with age-related hearing loss (ARHL). Local field potentials (LFPs) represent pre-synaptic integration of excitatory and inhibitory signals in local neural populations. Here, we assessed age-related changes in sound-evoked IC LFPs in the CBA/CaJ mouse model of ARHL across the tonotopic axis. We recorded from 495 sites across four age groups (young: 4-6 months; middle: 8-14 months; old: 24-25 months; oldest old: 27-31 months), examining LFP responses from dorsal (low-frequency), medial (mid-frequency), and ventral (high-frequency) IC regions. Analysis of the onset depolarization (N1 component) in response to broadband noise bursts revealed significant age-related hyperexcitability in medial and dorsal regions, with oldest old animals showing enhanced responses while ventral regions were unaffected. Amplitude-intensity functions demonstrated significant age x level interactions across all regions, with oldest old animals exhibiting level-dependent hyperexcitability most pronounced at suprathreshold intensities. Time-frequency analysis of LFP spectral content (30-100 Hz) revealed a crossover pattern across medial and dorsal regions, with oldest old animals showing reduced power at low-to-moderate stimulus levels but enhanced power at high stimulus levels. Ventral regions showed a low-level reduction without suprathreshold enhancement. These findings reveal paradoxical enhancement of neural activity in the aging IC, with the most pronounced changes in dorsal and medial regions rather than ventral regions most affected by peripheral hearing loss, suggesting that central hyperexcitability depends on residual afferent drive and implicating region-specific alterations in excitatory-inhibitory balance underlying central presbycusis.

Purpose: Otoacoustic emissions (OAEs) are used to assess outer hair cell (OHC) function. Clinical interpretation of OAE responses, however, is often limited to a present/absent binary since both physiological factors and measurement variability affect the measured OAE amplitude. Prior work showed elevated OAE responses in sedated compared to awake chinchillas, pointing to the potential influence of the medial olivocochlear (MOC) efferents on amplitudes, but this finding is inconsistent across species and OAE type. Here, we aimed to further investigate the effect of anesthesia on distortion- and reflection-type emissions in chinchillas using swept stimuli and more reliable calibration methods. Methods: Swept distortion-product (DP) and stimulus-frequency (SF) OAEs were measured in chinchillas with and without ketamine/xylazine sedation. Stimuli were presented using in-ear forward pressure level calibrations. DPOAE and SFOAE amplitudes and estimated Qerb from SFOAE group delays were compared across the two conditions. Results: We found that low-frequency DPOAE amplitudes were elevated when animals were sedated. The difference in SFOAE amplitudes was more variable across animals but appeared mildly reduced in sedated animals. Qerb estimates were slightly higher in sedated animals at some frequencies. The effect of sedation was not different across sexes. Conclusion: Taken together, these findings suggest that sedation impacts OAE measurements in chinchillas. MOC modulation could account for the present findings and differences across species. For diagnostic precision, OAE responses should be considered in the context of not only intrinsic OHC function but also extrinsic physiological processes that can modulate OHCs.

Cochlear implant (CI) candidates with residual low frequency hearing increasingly receive hearing preserving electrode arrays to enable electric acoustic stimulation (EAS). However, assessing very low frequency hearing in newborns and young children remains difficult. Previous work has shown that acoustic stimulation can mask electrically evoked auditory percepts when stimulation sites are spatially separated. Whether such masking also occurs when electric stimulation is delivered near the round window (RW), prior to cochlear insertion, remains unclear. This study investigated ipsilateral acoustic masking of electric stimulation delivered at apical, basal, and near RW sites in 12 EAS users with residual low frequency hearing implanted with short or partially inserted electrode arrays. Using a psychophysical paradigm, threshold elevations of electric pulse trains were measured during simultaneous acoustic stimulation. Electric stimulation was applied at extra cochlear RW locations and intra cochlear basal and apical electrodes, while stimulation parameters were systematically varied. Electric stimulation near the RW reliably evoked auditory percepts without side effects, though optimal stimulation parameters and masking strength varied across participants. Strong acoustic masking was consistently observed for apical stimulation, whereas weaker but measurable masking occurred for basal and RW stimulation. A cochlear lumped parameter model indicated that approximately 5% of current delivered at the RW can reach apical regions, explaining the observed masking by low frequency acoustic tones. Masking strength correlated with residual hearing for apical stimulation only. These findings indicate that acoustic masking of apical electric stimulation, which correlated with residual hearing, holds potential as a diagnostic tool for assessing low frequency hearing post operatively. The detection of masking during both RW and basal stimulation represents a promising result, indicating that these stimulation paradigms can produce quantifiable effects. Given the considerable variability observed among participants, further investigation is required to establish the extent to which masking measures reflect residual hearing or hearing loss. Nonetheless, these results provide novel insight into auditory perception and side effects associated with basal and extra cochlear electric stimulation, informing future efforts to optimize this approach for low-frequency hearing assessment.

Introduction: Auditory brainstem responses (ABRs) are routinely used to assess neural timing and function along the auditory pathway. In older adults, however, peripheral hearing loss, central auditory dysfunction, and broader structural changes in the brain may converge to shape the recorded response. Because ABR waves arise from multiple overlapping neural sources, how their electrophysiological features map onto specific auditory pathway structures in vivo remains poorly understood. Here, we examined the associations between cortical and subcortical gray matter volumes and the latencies and amplitudes of click evoked ABR Waves I and V in older adults. Methods: We evaluated 88 adults aged > 65 years from the Auditory and Dementia Study (ANDES) cohort. Click evoked ABRs were recorded at 80 dB nHL, and the latencies and amplitudes of Waves I and V were measured. High resolution 3T structural MRI data were processed using voxel based morphometry and standardized anatomical masks to estimate bilateral gray matter volumes of the cochlear nucleus, superior olivary complex, inferior colliculus, medial geniculate nucleus, and auditory cortex. Associations were assessed using partial correlations adjusted for age, pure tone hearing thresholds, and intracranial volume, as well as multivariate linear regression models. Results: ABR latencies, rather than amplitudes, showed significant associations with regional gray matter volumes. After adjustment for age, hearing thresholds, and intracranial volume, larger superior olivary complex volume was associated with shorter Wave I latency ({rho}partial = -0.305, p = 0.005), whereas larger medial geniculate nucleus and auditory cortex volumes were associated with shorter Wave V latency ({rho}partial = -0.265, p = 0.014 and {rho}partial = -0.404, p < 0.001, respectively). In multivariate models, superior olivary complex volume remained associated with Wave I latency ({beta} = -0.310, p = 0.007). Medial geniculate nucleus volume was initially associated with Wave V latency ({beta} = -0.247, p = 0.038); however, this relationship was attenuated once auditory cortex volume was included in the model ({beta} = -0.350, p = 0.002), which emerged as the dominant predictor. Inferior colliculus volume was not significantly associated with Wave V latency or amplitude. Conclusions: In older adults, ABR latencies showed selective associations with regional gray matter volumes, whereas amplitudes did not. These associations extended beyond the structures traditionally considered the main generators of Waves I and V, suggesting that interindividual variation in ABR latency may reflect distributed anatomical variation across the auditory pathway rather than a strict one-wave-one-generator correspondence.

Aging has profound effects on sensory systems, such that older adults can report problems in hearing despite having normal audiometric thresholds. While it is known that older listeners have poorer temporal processing than younger listeners, there is limited understanding of how these deficits interact with effects of sound level, in particular when they are above conversational level (e.g., > 65 dB SPL). Here we wanted to investigate the link between temporal processing and sound level as a function of age in normal-hearing listeners. Using a forward-masking paradigm, auditory brainstem responses (ABRs) and behavioral detection thresholds were measured at different masker levels. It was found that with increasing age and masker sound level, the Wave V amplitudes of older listeners decreased and directly correlated with behavioral detection thresholds of the probe stimulus in the forward-masking paradigm. These results elucidate the fundamental effects of aging on temporal processing and its interactions with sound level in the central auditory system. The results of this study have clinical implications for the concept of normal hearing in the aging population and how older listeners may struggle in different listening environments that are not captured by simple audiometry. Further delineating the important effects of aging will pave the way for earlier clinical diagnosis of hearing disorders and personalized treatments for different forms of age-related hearing loss.

Noise exposure can produce lasting auditory dysfunction in the absence of permanent threshold shifts or hair cell loss, yet the functional consequences of temporary threshold shift (TTS) remain poorly defined in translational models. We assessed auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) in rhesus macaques (n = 13) at 2 and 9-10 months following a single moderate noise exposure that induced TTS. Previous histological analyses of these macaques showed no significant loss of hair cells or ribbon synapses but revealed persistent broadening of inner and outer hair cell ribbon-volume distributions. After exposure, DPOAE amplitudes and thresholds and ABR thresholds returned to pre-exposure values and showed low-frequency enhancement at later time points. Suprathreshold click- and tone-evoked ABR amplitudes were largely preserved or enhanced after exposure, consistent with compensatory gain. In contrast, macaque-specific chirp-evoked ABRs showed modest amplitude reductions and latency prolongation across waves, indicating altered neural synchrony at standard stimulus presentation rates, but with variable time courses. More temporally demanding paradigms revealed persistent impairments. ABRs to faster click rates and shorter paired-click intervals showed reduced adaptability in response amplitude and timing after normalization, with deficits persisting through 9-10 months. Increased inner hair cell ribbon-volume variability was more consistently associated with temporal response measures, including latency, paired-click recovery, and rate adaptation, than with amplitude-based ABR measures. Together, these findings reveal a lasting dissociation between response magnitude and fidelity after TTS: suprathreshold responses may be preserved or enhanced, while neural synchrony and temporal adaptability remain impaired. Increased presynaptic ribbon volume variability may serve as a structural marker of synaptic remodeling accompanying hidden auditory dysfunction, rather than as a direct determinant of suprathreshold response magnitude. Temporally demanding ABR paradigms may supplement threshold-based diagnostics for detecting persistent noise-induced auditory dysfunction.

Tinnitus is commonly associated with psychosocial stress. However, it is unclear whether stress alone is sufficient to induce neural alterations resulting in tinnitus. In this study, we investigated the causal role of stress in tinnitus generation by experimentally isolating stress exposure as the sole independent variable in a well-established Mongolian gerbil model. Animals were subjected to repeated, inescapable electric foot shocks over three weeks to create a chronic, repeated stress paradigm. Behavioural, endocrine and histological measures were combined to assess tinnitus perception, stress system activation and cochlear synaptopathy. Repeated stress exposure reliably activated the endocrine stress response, as indicated by transient increases in serum cortisol following specific stress sessions. Basal cortisol levels returned to baseline values after the stress period. Behavioural assessment using gap-prepulse inhibition of the acoustic startle reflex revealed only isolated cases of behavioural signs of tinnitus, which occurred at a frequency consistent with false-positive detection and were evenly distributed between stress-exposed and control animals. Histological analyses revealed that ribbon synapse counts were preserved across the cochlea, with no evidence of stress-induced synaptopathy. No systematic relationships were observed between endocrine activation, behavioural outcomes and the number of inner hair cell ribbon synapses. Taken together, these findings suggest that, in the absence of acoustic trauma, repeated chronic stress is not sufficient to induce tinnitus or inner hair cell synaptopathy. These results argue against a primary causal role of stress alone in tinnitus generation and instead support models in which stress modulates symptom expression or perceptual salience in the context of pre-existing auditory dysfunction.

As part of cochlear innate immunity, cochlear resident macrophages regulate different aspects of tissue maturation, cochlear homeostasis, and injury response. Cochlear resident macrophages exhibit dynamic changes in morphology, distribution, and abundance after cochlear injury. However, in the absence of pathology, regulation of cochlear innate immunity is poorly understood. Since loss of cochlear outer hair cells (OHCs) are indicators of cochlear pathology, we hypothesize that cochlear innate immunity might be sensitive to changes in OHC function. Calcium homeostasis in OHCs is necessary for auditory function, and its dysregulation is associated with hearing loss. However, it is unknown if changes in OHC Ca2+ homeostasis are sufficient to alter cochlear innate immunity. Here, we investigate alterations in cochlear innate immunity in a mouse model lacking oncomodulin (OCM), an OHC-specific calcium buffer. Our study focused on the osseous spiral lamina (OSL), a region adjacent to cochlear hair cells. At 1 month, wild-type (WT) mice and Ocm knockout (KO) mice have similar hearing thresholds and no evidence of cochlear damage. However, in KO mice, OSL resident macrophages show increased density, altered morphology, and increased spatial segregation closer to the sensory epithelium. Despite these changes in OSL resident macrophages, cytokine profiling revealed no remarkable differences. At 5 months, Ocm KO mice show a progressive hearing loss with a frequency dependent loss of OHCs and inner hair cell ribbon synapses, but the density of OSL macrophages remained unchanged. Prior to hearing onset, there was no significant difference in immune cell numbers between Ocm WT and KO mice. These findings suggest that cochlear innate immunity is sensitive to OHC calcium buffering following hearing onset.

Background: Auditory Brainstem Responses (ABRs) are objective and highly standardized evoked potentials, but their clinical interpretation still largely depends on expert visual assessment. Most automated ABR approaches focus on signal detection, threshold estimation, or waveform recognition, whereas the diagnostic reasoning linking ABR features to clinically meaningful categories remains insufficiently formalized. Methods: We developed a theoretical, rule-based framework for ABR classification. Nine clinically relevant descriptors were defined: amplitudes of waves I, III, and V; latencies of waves I, III, and V; the I/V amplitude ratio; and the I-V and III-V interpeak intervals. The complete theoretical combinatorial space was generated and progressively reduced using rules that accounted for non-applicable descriptors, algebraic consistency, and neurobiological plausibility. Two expert raters independently labeled valid configurations and compared with language-model-assisted and logic-based rule systems. Agreement was assessed using percentage concordance and Cohen's k;. Descriptor importance was explored using Random Forest analysis. Results: The initial space of 5,832 possible ABR configurations was reduced to 343 valid configurations. Expert raters showed high agreement, with 84.55% concordance and Cohen's k = 0.620. Agreement between expert classifications and language-model-assisted rules was lower, whereas logic-based rules showed higher agreement with both raters and were retained as the final proposed rule set. The diagnostic space was highly asymmetric, with NORM, PPSHA, and PPC occupying narrow regions, and PB and MIXED representing broader diagnostic domains. Wave I amplitude was the most influential descriptor across classification agents. Conclusions: This work provides an interpretable framework for ABR classification by transforming a broad theoretical combinatorial space into a constrained diagnostic domain. This proof-of-concept study supports the feasibility of modelling ABR interpretation as a structured diagnostic space grounded in auditory neurobiology, providing a reproducible foundation for future clinical validation and semi-automated decision-support tools.

Standard hearing tests miss cochlear neural degeneration (CND), the loss of synapses between inner hair cells and auditory nerve fibers that may underlie unexplained hearing difficulty in roughly one in ten adults. Envelope following responses (EFRs) can index this neural loss noninvasively, but conventional protocols are too slow for clinical use. We tested a dynamic amplitude-modulated (dAM) EFR that sweeps the full modulation spectrum in a single brief stimulus. In Mongolian gerbils with histologically verified CND, dAM EFRs revealed selective deficits at fast modulation rates without threshold elevation. A machine-learning classifier distinguished young from middle-aged animals with high accuracy; additionally, its most informative feature, power near 400-500 Hz, tracked synapse counts, indicating a readout of cochlear neural health rather than age. Applied without retraining to 56 human listeners, the gerbil-trained classifier separated age groups above chance. dAM EFRs thus offer a rapid, objective and clinically viable marker of CND.

Speech perception ability in a cocktail party environment is highly variable, even for people with clinically healthy hearing. The mechanisms of these differences are poorly understood. A possible reason for these differences could be due to the neural mechanisms of auditory attention. This investigation aims to quantify how well a person is able to neurally entrain to a continuous narrative using a temporal response function (TRF), then evaluate if that TRF measure is correlated with an individual's performance on a selective attention and narrative comprehension task. This was accomplished using a cohort of twenty-five young and healthy listeners who completed speech-in-noise (SIN) perception tasks while their neural activity was recorded with EEG. This EEG data and regressors (speech envelope and gammatone spectrogram) of an auditory stimulus was used to train TRF models. TRF cross validation correlation coefficients were then used in multiple regression models to predict a participant's SIN performance. Task performance had a significant positive relationship with the neural entrainment to an attended stimulus and a negative relationship with the neural entrainment to an unattended stimulus. This was observed with both the selective attention and narrative comprehension measures. The difference of the attended and unattended correlation coefficients were also significantly related to increased task performance. These measures could be a potential biomarker to predict an individual's speech perception in a noisy environment.

Aminoglycoside antibiotics such as kanamycin induce sensorineural hearing loss by killing hair cells, resulting in secondary degeneration of spiral ganglion neurons (SGNs). Previous studies show that anti-inflammatory agents reduce SGN death, implicating a causal role of the immune response. This is consistent with observations of increased numbers of macrophages and lymphocytes, including T and NK cells, in the spiral ganglion after exposure to aminoglycosides. Here, we directly test the role of T cells and other lymphocytes in SGN degeneration in kanamycin-deafened rats. Homozygous RNU nude rats that lack T cells - but retain NK and B cells- show neurodegeneration similar to rats with a normal T cell complement, indicating that T cells are not necessary for neurodegeneration. Homozygous SRG rats lacking all lymphocytes (i.e., T, B, and NK cell-deficient), exhibit remarkable regional variation in the pattern of spiral ganglion degeneration post-deafening. In the basal half of the ganglion, SGN degeneration is significantly reduced in deafened SRG rats, implying a role for lymphocytes, presumably NK cells of the innate immune system, in SGN death. In the apical half of the deafened ganglion, SGN degeneration is not significantly affected by the lack of all lymphocytes, implying a role for other cellular mechanisms.

Difficulty perceiving speech in noise is the primary complaint of patients seeking hearing healthcare, even absent overt losses in audiometric thresholds. Yet current clinical practice largely focuses on sensory function while ignoring the potentially outsized effects of executive function on everyday suprathreshold listening. Speech perception in noise depends on the dynamic interplay between the fidelity of sensory coding along the auditory pathway and higher-order top-down cognitive processes that support goal-directed listening, both of which can independently change across the lifespan. Here we examined how two subcomponents of executive function, working memory and inhibitory control, vary across the adult lifespan and contribute to speech-in-noise performance. Two hundred participants aged 18 to 73 with normal hearing thresholds were tested on a validated online auditory psychophysics platform. Working memory was assessed with an n-back task and inhibitory control with an auditory Stroop task. Participants then performed two speech-in-noise tasks: a modified rhyme test emphasizing sensory coding through energetic masking at the cochlea, and a matrix sentence task emphasizing executive function through informational masking. Age significantly affected performance on both tasks. Aging was associated with reduced inhibitory control (increased Stroop cost) but no significant effect on working memory. Regression analyses revealed that both working memory and inhibitory control predicted performance on the informational masking task, whereas only inhibitory control predicted performance on the energetic masking task. These findings underscore the critical role of executive function in everyday suprathreshold listening and support including cognitive measures in clinical assessments of hearing difficulties.

Distinct auditory nerve (AN) fiber populations with varying thresholds and vulnerabilities to synaptopathy are observable in animal models, but standard non-invasive human measures lack the resolution to differentiate these groups of fibers. This fundamental limitation hinders the translation of findings in animals to human auditory pathologies. To overcome this, we developed a novel refractoriness-masking paradigm to non-invasively isolate threshold-specific AN fiber responses in humans. By presenting rapid click trains with cumulatively rising levels (45 to 105 dB peSPL) at a 250-microsecond inter-click interval, we sequentially masked lower-threshold fibers. Using a tympanic membrane electrode, we recorded compound action potentials (CAPs) in adults with normal hearing and isolated threshold-specific responses via waveform subtraction. Our results demonstrated that the isolated CAPs exhibited decreased latencies with increasing levels and a non-linear amplitude growth, plateauing at 90 dB peSPL before sharply increasing at 105 dB peSPL. This pattern reflects the sequential recruitment of AN fiber that were not effectively recruited by the preceding clicks. Validate conditions, in which the final two clicks had equal levels, produced substantially smaller CAPs, consistent with response suppression by refractoriness. Overall, this paradigm establishes a human measurement approach for characterizing level-threshold-dependent AN responses, providing a potential way to better investigate different AN pathologies, such as cochlear synaptopathy or auditory neuropathy.

BackgroundHearing aids and cochlear implants (CIs) are the primary interventions for sensorineural hearing loss, restoring auditory function through amplification and intracochlear electrical stimulation, respectively. For those with residual low-frequency hearing, the combined electric-acoustic stimulation (EAS) has demonstrated superior speech perception, particularly in noisy environments, compared to either modality. However, CI surgery carries inherent risks, including postoperative hearing loss, which undermines EAS benefits and limits future rehabilitation options. To overcome these limitations, we propose a non-invasive alternative: extracochlear electric and acoustic stimulation (EEAS), delivering electrical stimulation via transcutaneous electrodes without surgery. Here, we present a first systematic investigation of non-invasive extracochlear electrical stimulation using ear canal electrode montages, evaluating its feasibility, perceptual effects, and key parameters across diverse hearing statuses. MethodsWe conducted a controlled, within-subject study with 15 participants: 5 with normal hearing (NH), 5 with high-frequency hearing loss (HI), and 5 with severe-to-profound deafness (PL). We used charge-balanced sinusoidal stimuli (125-4000 Hz) applied via an ear canal electrode and four return electrode montages, including contralateral ear canal, contralateral mastoid, ipsilateral mastoid, and forehead electrodes. Participants rated auditory sensations, including loudness, sound quality, and lateralization, as well as side effects on separate 0-10 scales, with current intensity increased up to 2 mA/cm{superscript 2}. Thresholds and perceptual responses were analyzed across frequencies, electrode configurations, and hearing groups. ResultsReliable auditory percepts were elicited across all groups. NH participants reported pure-tone sensations, whereas HI and PL participants perceived broadband, noise-like sounds. Loudness decreased with increasing frequency, particularly for HI and PL, with minimal responses in the high-frequency range. The current threshold increased with stimulation frequency, whereas the threshold expressed as charge per phase remained constant, suggesting that charge per phase primarily determines neural activation, whereas current amplitude is more closely associated with the intensity of auditory and side effect perception. Contralateral montages produced significantly higher loudness ratings than ipsilateral or forehead configurations. The forehead montage was poorly tolerated, leading to early termination due to discomforting side effects. Sound lateralization was predominantly central or bilateral with contralateral setups, while ipsilateral and forehead configurations yielded ipsilateral perceptions. ConclusionsNon-invasive extracochlear electrical stimulation via ear canal electrodes is feasible and perceptually effective across a spectrum of hearing statuses. Perceptive outcomes are strongly influenced by electrode montage and residual hearing, with evidence of electrophonic excitation in NH individuals and electroneural activation in HI and PL participants. Contralateral mastoid electrode configurations offer the optimal balance of perceptual strength, tolerability, and spatial localization. These findings establish a critical foundation for the development of EEAS devices, demonstrating that non-invasive electrical stimulation can generate meaningful auditory percepts, paving the way for safe, accessible, and integrated hearing rehabilitation solutions. This work informs future EEAS developments and advances the path toward clinically viable, non-invasive cochlear stimulation.

The pure-tone audiogram remains the cornerstone of hearing assessment, yet it captures only part of the functional consequences of cochlear damage. Most phenotyping schemes rely solely on the audiogram, which cannot detect hidden suprathreshold dysfunction when thresholds are normal. How best to represent audiological data - as discrete phenotypes or as a continuous space - remains unresolved. Using a retrospective database from the Copenhagen Hearing and Balance Centre, Rigshospitalet (Denmark; 1995-2022; 251986 ear-session units from 81883 adults with normal or sensorineural audiograms), we compared linear (PCA) and non-linear (UMAP) embeddings of the audiogram alone and with word recognition in quiet (WRSmax-Q). Here we show that a linear embedding suffices for the audiogram, but a non-linear one becomes advantageous once suprathreshold measures are added. PCA compressed the audiogram onto two interpretable axes, overall level and slope, explaining 91.5% of the variance, with ears forming a continuous cloud that published reference schemes tiled into overlapping regions. For the audiogram alone, UMAP recovered the same organisation. WRSmax-Q varied widely among ears with similar audiograms; adding it left the PCA unchanged but reorganised the UMAP. A synthetic experiment illustrated this: ears with identical audiograms but different WRSmax-Q separated under UMAP, not PCA. Combining thresholds with WRSmax-Q, UMAP yielded a continuous representation - a prototype Hearing Loss Map - where each ear's position reflects threshold and suprathreshold measures. Representing hearing loss as a location in a continuous space rather than as discrete categories may better reflect its graded nature, with clinical relevance for individual patients.

Difficulties understanding speech in noise remain a common complaint even among listeners with normal hearing sensitivity, highlighting the need for objective, more effective measures of real-world listening. The goal of this study was to validate the use of a novel, chirped-speech (Cheech) stimulus - continuous, naturally-spoken speech fused with chirps designed to elicit robust auditory evoked potentials - to characterize relationships between speech recognition, listening effort, and auditory neural encoding. Twenty-five normal-hearing adults completed a sentence-recognition task using both original (unmodified) and Cheech-modified AzBio sentence lists in quiet, +3 dB, and -3 dB signal-to-noise ratio (SNR) conditions while neural responses from the brainstem through cortex were recorded simultaneously. Speech recognition remained near ceiling in quiet but declined with decreasing SNR for both original and Cheech stimuli. Compared with clean speech, Cheech-modified speech showed slightly poorer recognition performance as SNR decreased and somewhat higher perceived effort overall. Yet, Cheech was highly effective at evoking auditory responses from the brainstem (auditory brainstem response, ABR) through the cortex (including middle- and late-latency responses, MLR and LLR) even with <5 minutes listening time per condition. Neural responses showed reduced amplitudes and prolonged latencies as SNR decreased. In general, ABR latencies and wave I amplitudes were associated with speech-in-noise recognition performance, whereas cortical responses (MLR Na, Nb, and LLR P1) were associated with subjective workload. These findings show that Cheech-modified speech preserves intelligibility while yielding robust, multilevel neural recordings during sentence perception, offering a promising approach to examine hierarchical auditory processing under ecologically relevant speech-in-noise conditions.

Hearing aid users commonly report listening-related fatigue, which may contribute to disengagement from demanding listening situations and negative psychosocial outcomes. Hearing rehabilitation currently lacks strategies to mitigate listening fatigue, partly because fatigue build-up and its consequences are difficult to measure beyond self-report. This study investigated whether value-based listening decisions and associated frontal cortical activity are modulated by fatigue. Thirty hearing aid users completed a one-hour listening paradigm while cortical hemodynamic activity was measured using functional near-infrared spectroscopy (fNIRS). On each trial, participants decided whether to engage in listening or rest based on an offer defined by expected task difficulty and reward, and rated their momentary fatigue. Fatigue ratings increased over time, and unsuccessful listening trials were associated with larger subsequent increases in fatigue, suggesting that performance contributed to changes in self-reported fatigue. Listen-versus-rest decisions followed the expected effort-reward trade-off, with participants more likely to accept offers that provided higher rewards and lower listening demands. Over the course of the experiment, participants became less likely to accept listening offers; however, neither time on task nor subjective fatigue altered the weighting of reward and difficulty. In contrast, frontal cortical activation during evaluation of accepted offers increased over time for high-difficulty offers with low or medium rewards. Follow-up analyses indicated that frontal oxygenation and listening decisions were more strongly associated with time on task than with subjective fatigue ratings. Together, these findings suggest that behavioral and neural measures obtained before listening capture fatigue-related processes beyond self-report, providing a basis for identifying and potentially addressing fatigue in hearing rehabilitation.

Many individuals experience problems that are undetected by standard hearing tests, such as persistent tinnitus and difficulties understanding speech in background noise. Here, we report evidence of altered neural gain in young adults with self-reported listening problems despite exceptional hearing thresholds. Individuals reporting persistent tinnitus (the daily percept of sound in the absence of an external source) exhibited elevated thresholds of the middle ear muscle reflex, suggestive of altered gain in brainstem reflexive circuits, and reduced cortical responses to auditory spatial cues conveyed in the temporal fine structure of low-frequency sounds. Moreover, in both groups, greater self-reported speech-in-noise difficulties were associated with higher magnitude cortical responses, particularly at the highest stimulus intensity, consistent with elevated neural gain. Using a conceptual model, we demonstrate how damage to high-threshold auditory nerve fibres innervating cochlear nuclei can account for reduced activity of binaural neurons sensitive to the temporal fine structure of low-frequency sounds, generating a compensatory increase in neural gain in higher brain centres that impacts listening in complex environments.