Trends in Hearing

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.

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.

Bilateral cochlear implantation (BCI) can improve spatial hearing in adults with bilateral hearing loss, but the early development of spatial hearing following sequential BCI remains poorly understood. This prospective longitudinal study investigated changes in spatial hearing experience in 23 adults undergoing sequential BCI, assessed before and at ~1, 3, and 8 months after bilateral implantation under two conditions: spontaneous and restrained head movements. Using a motion-tracking system combined with virtual reality, sound localization was assessed through absolute and signed errors, along with self-reported localization confidence and listening effort. Subjective spatial hearing was also assessed using the Speech, Spatial and Qualities of Hearing Scale (SSQ). Localization performance improved by 1 month after bilateral implantation, as evidenced by a reduction of absolute error and in the bias toward the first-implanted ear. Participants reported greater localization confidence and lower listening effort at 1 month, although these changes were not consistently maintained at later follow-ups. SSQ scores showed improved spatial hearing at 1 month, speech perception at 3 months, and sound clarity and discriminability at 8 months. Compared with head-restrained condition, accuracy and confidence improved when spontaneous head rotations were allowed. The temporal trajectories of localization bias, confidence, and effort were modulated by the duration of experience with the first CI. These findings indicate that changes in spatial hearing can emerge soon after second CI activation. They further highlight the contribution of spontaneous head movements and previous CI experience, and support the use of complementary measures to monitor the early development of bilateral listening.

Predicting when an event will occur is key to perceiving and evaluating dynamic sensory inputs, such as speech. The utility of temporal predictions hinges on perceptual timing precision (PTP), the sensitivity to deviations between actual and predicted sound onset times. Past work suggests that PTP is primarily determined by acoustic properties of target sounds, regardless of the acoustics of preceding sound cues. In contrast, in four experiments, we discover that PTP is best when context and target sound spectra and temporal envelopes match, with only minor effects of individual sound acoustics. This ability to utilize contextual continuity improved with musical aptitude. Theoretical modeling showed that spectrally tuned oscillatory entrainment to sound onsets and offsets is necessary to account for our results. In sum, the precision of temporal predictions is defined not by the acoustics of individual sounds but by the continuity of spectral and temporal content within a sound stream.

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.

The relationship between neural processes supporting perception, deviance processing, and post-perceptual task demands during auditory processing is not well understood. We used multitone masking and a no-report inattentional deafness paradigm to dissociate neural correlates of auditory perceptual awareness, deviance processing, and task demands. Evoked responses to physically identical target-tone pairs were recorded across three phases differing only in task instructions. In Phase A, human participants remained nave to (and thus unaware of) the target tones. In Phase B, participants were informed about (and thus aware of) the target tones. In Phase C, participants remained aware of the target tones and judged the duration of the silent gap between them, rendering them task-relevant. When participants were aware of them, target tones elicited an auditory awareness negativity and an increased positivity in the P3 window), with larger responses when target tones were additionally task-relevant. Furthermore, though largest in Phase C, deviant stimuli elicited a mismatch negativity across all task conditions, while a significant P3 to deviants was only observed in Phase C. Thus, early and late responses can be independently modulated by awareness, deviance, and task-relevance, indicating that they do not necessarily rely on shared neural mechanisms despite overlapping spatiotemporal profiles.

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.

Computational models of the middle ear are typically developed within the linear range of the middle ear's response, which corresponds to typical sounds in daily life. Understanding middle-ear biomechanics under high-intensity sounds is also important for assessing potential auditory damage under adverse conditions. In this study, a finite-element (FE) model of the human middle ear plus the external ear canal is presented, employing a first-order Ogden hyperelastic material formulation and time-domain nonlinear analysis to capture nonlinear deformation of soft tissues and the resulting middle-ear response. The model was analyzed using pure-tone pressure excitations applied at the ear canal entrance over the 80 Hz to 8 kHz frequency range and 110 to 180 dB sound pressure levels (SPL). The ear canal pressure near the tympanic membrane (TM) and full-field three-dimensional response of the middle ear structures were examined. Across the investigated frequency range, the simulated middle-ear motion exhibited a transition from predominantly piston-like behavior at low frequencies, up to 1 kHz, to increasingly intricate multi-modal and multi-directional vibration patterns at higher frequencies. Nonlinear behaviors became increasingly significant at high frequencies and high stimulus levels, including compressive/expansive pressure-displacement relationships, waveform distortions, and the emergence of non-harmonic spectral components. The model developed in this study provides a computational framework for studying nonlinear sound transmission through the middle ear and its implications for high-intensity acoustic exposure. The findings contribute to a better understanding of middle-ear mechanics under adverse conditions and support future investigations of acoustic trauma and hearing protection strategies.

Purpose: Stimulability testing involves the evaluation of multiple aspects of a patient's behavior, but the results are most frequently consolidated into a single domain (i.e., "stimulable"). The current study performs preliminary content, construct, concurrent, and predictive validation for the Multidimensional Stimulability Profile for Voice (MSP-V), a rating scale designed to measure multiple domains during stimulability testing (Degree of Change, Rapidity of Change, Generalization, Patient-rated Voice Quality, Patient-rated Voice Feel, and an overall rating of Stimulability Level). Methods: 78 patients with voice disorders (24 functional, 15 structural, 39 neurological) were administered the MSP-V by five speech-language pathologists (SLPs). Content validity was evaluated via the Content Validity Index (CVI) completed by nine voice-specialized SLPs. Construct validity was evaluated via exploratory factor analysis. Concurrent validity was assessed by determining whether MSP-V domains scaled in the expected direction compared to categorical stimulability ratings (e.g., "Highly stimulable" vs. "Stimulable"). Predictive validity was assessed by examining the relationship between MSP-V domains and voice disorder diagnosis, return to voice therapy, and patient-reported practice outside of therapy. Results: The CVI reached the critical value for clinician-rated and patient-rated domains. Two distinct factors were identified during EFA, one consisting of clinician-rated domains and the other of patient-rated domains. All MSP-V domains showed the expected directional relationships as categorical stimulability ratings. No domains differed significantly between disorder etiologies. The Rapidity of Change and Stimulability Level domains both significantly predicted return for voice therapy, where participants who rated lower on each domain were more likely to return to for voice therapy. No domains were predictive of patient-reported practice. Conclusions: The MSP-V is a clinically feasible tool with emerging content, construct, concurrent, and predictive validity that could be used to provide increased clarity and precision in stimulability testing documentation for research and practice.

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.

Neural tracking of speech is a well-established phenomenon in neuroscience. However, for speech signals with a fixed structure, significant correlations between speech envelopes and neurophysiological representations occur even for unheard sentences. We exploit a structured speech-in-noise matrix hearing test (Oldenburger Sentence Test, OLSA) to systematically quantify the relationship between acoustic sentence similarity and neural tracking. Simultaneous magnetoencephalography (MEG) and 76-channel electroencephalography (EEG) data, including 16 channels positioned directly around the ears (ear-EEG), were recorded from 21 young adults with normal hearing during the presentation of clean-speech audiobooks and OLSA sentences at six signal-to-noise ratios. A linear decoder trained on audiobooks reconstructed OLSA sentence envelopes. Reconstruction accuracies were compared using a linear mixed model across heard (matched) and unheard (mismatched) sentences of varying acoustic similarity. Significant reconstruction accuracies were achieved across MEG, EEG, and ear-EEG for both matched and mismatched sentences. For mismatched sentences, these accuracies gradually increased with their acoustic similarity to the heard speech data. The high similarity between sentences, which is especially prominent in matrix tests, can cause significant spurious tracking for mismatched stimuli. This effect can reach levels comparable to those of matched sentences and can be mistaken for true neural tracking. Robust neural tracking across modalities further supported the established viability of ear-EEG compared to whole-head systems.

Objective: Kabuki syndrome type 2 (KS2) is a rare X-linked disorder caused by pathogenic variants in KDM6A and is frequently associated with hearing impairment. Because auditory phenotypes include sensorineural, conductive, and mixed hearing loss, we examined whether Kdm6a deficiency directly impairs cochlear morphology or auditory function in mice. Methods: We generated Nestin-Cre; Kdm6a conditional mutants and a germline-derived global Kdm6a deletion model using Sox2-Cre-mediated germline recombination. Auditory function and cochlear morphology were assessed by auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and histological analyses. Results: Whole-body hemizygous or homozygous Kdm6a deletion resulted in embryonic lethality. Analyses therefore focused on Nestin-Cre; Kdm6aflox/Y males and females carrying a germline-derived heterozygous Kdm6a deletion. In Nestin-Cre mutants, ABR thresholds, wave I amplitudes and latencies, and DPOAE measures at 8, 16, and 32 kHz were comparable with littermate controls at 4 and 8 weeks. In heterozygous deletion females, ABR thresholds, wave I amplitudes and latencies at 4-64 kHz and DPOAE measures at 8, 16, and 32 kHz were comparable with male and female wild-type controls. No overt cochlear pathology was observed in either model. Conclusion: Kdm6a deficiency in the viable mouse models examined did not produce overt cochlear pathology or baseline auditory dysfunction. These findings suggest that partial Kdm6a loss alone is insufficient to produce a robust primary cochlear phenotype in young mice and highlight the potential contributions of non-cochlear, developmental, central, and later-onset mechanisms to hearing impairment in KS2. Clinically, these findings support careful evaluation for potentially treatable middle-ear disease.

Severe hearing impairment affects approximately 5% of the global population, with a prevalence projected to increase over the coming decades. Cochlear implant devices pose a neuroprosthetic treatment option to allow sound perception and speech comprehension. However, users are limited in the spectrum of auditory information they can regain because electrical stimulation of the auditory nerve generates a broad spread of current and limits the transmission of sound frequency information. Recently, optogenetic stimulation of the cochlear nerve has emerged as a promising alternative for hearing restoration. Because light can be precisely confined in space, optogenetic stimulation of the cochlea permits to activate auditory neurons within smaller tonotopic regions, thereby improving the encoding of sound frequencies compared to electrical stimulation. However, this approach is limited in terms of dynamic range and ability to follow rapidly varying inputs, thus preventing faithful transmission of auditory information. Here, we developed an alternative approach targeting directly sensory inner hair cells with optogenetics. We demonstrate that this approach decreases the amount of light energy necessary to evoke auditory responses. Direct stimulation of hair cells increases the dynamic range of intensities encoded by neurons in subcortical auditory areas and improves the temporal fidelity of optogenetic responses. Finally, a biophysical model of the auditory system suggests that preserving the synapses between inner hair cells and auditory neurons greatly improves the encoding performance of an optical cochlear implant. Together, our results suggest that targeting sensory inner hair cells is a promising approach for hearing restoration through an optical implant.

Hearing loss and deafness as a result of hair cell loss cannot be restored due to the incapacity of spontaneous regeneration of these cells. Compounds that manipulate key signaling pathways can potentially regenerate cochlear hair cells. In order to test different compounds that promote hair cell regeneration in vitro models can be used. Three-dimensional cultures have allowed the expansion and experimentation of human and mouse inner ear organoids. This is mainly performed in the embryonic or the early postnatal developmental stage. However, since the majority of patients with hearing loss are adult, it is crucial to understand the adult inner ear regenerative capacity. Here, we evaluated progenitor cell markers in the adult human and mouse inner ear and the generation, expansion and differentiation of cochlear organoids derived from the adult human and mouse inner ear. Cochlear and vestibular sensory epithelium from adult humans; and from adult and aged mice express the progenitor markers SOX2 and LGR5; and can generate organoids in vitro. By optimizing the culture conditions, organoids derived from the cochlea and vestibular organ from adult human and adult and aged mouse differentiated to Myosin 7A positive cells. This indicates that the adult inner ear has regenerative capacity. These findings are encouraging for future regenerative therapies to cure hair cell-related hearing loss and deafness.

Efficient processing of complex acoustic signals within noisy environments is a fundamental challenge for the auditory system. This study investigates the cortical representation of structured noise and vocalizations embedded in it using widefield calcium imaging with the high-speed Calcium indicator jGCaMP8m in the mouse auditory cortex. The spectrotemporal statistics of the structured noise were controllable, including its temporal variance and cross-frequency correlations. We find that structured noise invokes spatially and temporally complex neural responses across the auditory cortex that reflect the spectrotemporal properties of the noise. We identified partially distinct noise response components: noise onset responses showed stronger overlap with primary than secondary areas, while later suppression components did not show a significant primary-secondary bias. Vocalization-evoked responses were significantly attenuated in the presence of noise compared to silent contexts, exhibiting reduced onset magnitude and altered adaptation dynamics. Using decoding we find the neural representation of vocalizations to become more discriminable with longer preceding noise exposure. Furthermore, structured noise cochleograms could be reconstructed from neural population activity, with performance depending on stimulus statistics, tending to be higher in primary than secondary auditory cortex while remaining substantial across both. These findings suggest that the mouse auditory cortex represents acoustic targets in noise through context-dependent and spatially distributed population activity, shaped by both the statistical structure and temporal history of the acoustic background.

Efficient motion perception requires integrating immediate sensory evidence with internal representations shaped by experience. This influence of recent history can produce serial dependence effects (SDEs), in which current judgments are biased toward or away from the source of previous information. We examined SDEs in auditory, visual, and cued audiovisual motion-direction discrimination using aggregate psychometric measures and trial-level generalized linear mixed-effects models (GLMMs), which estimated the independent contributions of the previous stimulus direction and the participant's previous response. Participants completed unisensory (n=57) and cued audiovisual (n=48) motion-discrimination tasks. Aggregate analyses indicated attractive SDEs in auditory conditions, repulsive SDEs in visual conditions, and no net SDE in the audiovisual-cued condition. Trial-level modeling revealed a more nuanced structure: previous stimulus direction produced repulsive effects in both unisensory conditions, with previous visual direction influencing judgments across all conditions containing visual motion, whereas previous response produced attractive effects only when visual information was task-relevant. In the audiovisual-cued condition, the absence of a net psychometric shift was consistent with the opposing influences of an attractive response-history effect and a repulsive visual stimulus-history effect rather than an absence of serial dependence. These findings suggest that serial dependence in motion perception reflects dissociable and concurrently operating processes, including a predominantly visual, adaptation-like stimulus-history effect and a task-dependent, decision-related response-history effect.

Perception combines incoming sensory evidence with priors learned from preceding input. One example is the central tendency effect in which stimulus estimates regress towards a prior based on the mean of the stimulus distribution. Whether such priors are specific to each modality or shared across modalities remains unresolved. Here, we examined this question using speed perception in the visual, auditory and tactile modalities and used central tendency as a behavioral probe. By giving each modality its own speed range, clear predictions emerge when modalities are interleaved: if priors are modality specific, each modality should maintain its own central tendency bias whereas a supramodal prior would exhibit a different mean based on the pooled set of speeds. Moreover, a supra-modal prior should exhibit precision weighting, with the more reliable cue receiving more weight. For vision and touch, speed estimates converged when interleaved: both modalities shifted but the less reliable one shifted more, consistent with a precision-weighted supramodal prior. For vision and audition, the priors remained largely distinct: audition (the less reliable modality) showed a partial shift but did not converge on the precision weighted, supramodal mean. This was not explained by the large audiovisual reliability difference: it persisted when visual precision was reduced. These results show that in the motion domain, visual and tactile signals can combine crossmodally, but auditory and visual signals do not. Supramodal processing of motion therefore depends on which senses are involved and is likely explained by the lack of an early spatial mapping in audition.

When asked to discriminate between two stimuli that differ along some dimension, such as intensity, frequency, or orientation, humans exhibit a smallest stimulus difference, or threshold, below which discrimination becomes impossible. These limits on perceptual sensitivity have traditionally been explained by internal noise. Contemporary theories instead link perceptual sensitivity to efficient coding of the natural environment but have not been comprehensively tested. Here, we measured the psychoacoustic sensitivity of a computational model optimized for everyday sound localization and recognition tasks. We used linear classifiers operating on the model's learned representations to estimate 1632 thresholds spanning the perceptual dimensions of sound. These model-derived thresholds closely matched thresholds measured behaviorally in humans on the same test battery. The results show that many classical psychophysical phenomena emerge from representations optimized for natural behavior and suggest that discrimination thresholds are determined by linear separability in these optimized representations, rather than intrinsic neural noise.

Free recall of naturalistic stimuli, such as films and stories, reveals what people remember and how they organize it. Scoring such recall requires matching each recalled utterance to the encoded stimulus, and doing this manually often makes large studies impractical. Existing automated methods mostly return similarity or aggregate scores rather than explicit matches between recalled and stimulus content. Here we introduce an open-source, model-agnostic pipeline that uses a large language model (LLM) to divide the stimulus and the recall into information units and to match units between the two texts. The output is a table of unit-to-unit matches with accuracy labels, from which standard analysis scripts compute recall measures. We validated the pipeline with four LLMs (Claude Sonnet 4.5, GPT 5.4, Gemini 2.5 Pro, and Gemini 2.5 Flash) on three datasets. On typed recall of four short stories, agreement between each model and two trained raters ({phi} = .73-.79) was close to the agreement between the raters themselves ({phi} = .77). A second run reproduced each model's matches ({phi} = .91-.97) more closely than the raters agreed with each other. On spoken recall of 10 films, every model attributed recall to the correct film with high agreement. On uncorrected speech-to-text recall of a television episode, agreement varied more across models. The median cost was under $1 per participant for every model. These results suggest that the pipeline can serve as a reliable, low-cost alternative to manual scoring of free recall.

PurposeDuring speech planning, the brain predicts the auditory consequences of its movements and modulates the auditory system--a process called pre-speech auditory modulation (PSAM). We investigated the link between PSAM and behavioral error correction and determined how aging influences these mechanisms. MethodsSeventeen young adults (18-32 years) and 13 older adults (50-85 years) performed a speaking task involving auditory feedback perturbations and a silent reading control. We measured electrophysiological responses (N1/P2) to auditory probes during speech planning and correlated these modulations with the magnitude of participants subsequent behavioral corrective responses. ResultsBoth groups showed significant modulation of N1 and P2. However, N1 modulation correlated with corrective responses only in young adults. Older adults showed reduced behavioral corrections and smaller, delayed P2 components. Despite these age-related behavioral differences and the loss of the modulation-correction correlation, older adults maintained modulation magnitudes comparable to those of younger adults. ConclusionsN1 modulation serves as a neural index of the brains predictive processes during speech planning. Aging appears to selectively disrupt the integration of these signals into motor output rather than the internal generation of the predictions themselves.