The auditory cortex integrates sensory and contextual inputs in emotion and fear driven situations that can be consolidated over learning. Somatostatin-expressing (SST+) interneurons play a key role in inhibitory modulation of sensory processing, yet their long-range inputs remain poorly characterised. We performed rabies-based retrograde monosynaptic tracing to compare the specific inputs to SST+ interneurons with the general input connectome of neurons in the mouse auditory cortex. Overall, inputs were similar, with the majority of presynaptic neurons originating from the ipsilateral auditory cortex, medial geniculate body and other sensory areas. However, SST+ interneurons received significantly more inputs from limbic regions, including the hippocampus and amygdala, than other auditory neurons. Our results show preferential targeting of SST+ interneurons in auditory cortex by regions involved in emotion and memory. These connections may be involved in auditory learning and state-dependent gating of auditory responses.
Objectives This study examined whether automatic change detection to within-stimulus gaps, indexed by the deviant-related response (DRN), varies with gap duration and the temporal position of the gap within a long-duration sound, and whether these effects differ between children and adults. Methods Fifteen typically developing children (8–12 years) and fifteen adults (23-37 years) completed passive EEG recordings using a multi-deviant sequence in which standards and deviants alternated. All stimuli were 500-ms broadband-noise bursts. Deviants contained a silent gap of 10 or 30 ms inserted at 15, 50, 100, 200, 300, or 400 ms after stimulus onset. DRNs were derived from deviant–standard difference waves, and the presence of a DRN was evaluated using confidence interval procedures. In a separate behavioural task, participants performed active gap detection, and sensitivity was quantified using d′. Results In both groups, DRN amplitude increased with gap duration and decreased as the gap onset time was delayed. Reliable DRNs were absent at the latest gap position (400 ms) in both groups. In adults, a small DRN was evident at 300 ms, whereas in children, DRNs were not reliably elicited by gaps at 200 ms or later. Behavioural sensitivity was high overall but lower in children than in adults, and did not correlate with DRN amplitude. Conclusions Automatic detection of within-stimulus gaps is constrained by the timing of the change, and this temporal constraint appears to be more pronounced in children. The dissociation between DRN outcomes and behavioural performance suggests that active detection may be supported by mechanisms beyond those indexed by the passive DRN.
Objective In general, the neural origins of the ‘acoustic change complex’ (ACC) are attributed to the auditory cortex, based on measurements performed on the brain response to the ‘onset’ of a sound, rather than a ‘change’ response per se. Aims: (1) to produce ACC topographical maps via high-density electroencephalography (EEG) multi-electrode arrays to visualise brain activity across the entire scalp; (2) to perform source localization specifically on the ACC. Design ACC responses were recorded via 128 channel EEG from 18 normal hearing adults. Sound stimulus: 1 kHz pure tone containing a 10% frequency change, 3000 ms pre-transition duration. ‘Onset’ and ‘ACC’ topographical maps were generated. Source localization was performed using MNE-Python and a standard linearly constrained minimum variance (LCMV) beamforming method. Results Classic P1-N1-P2 waveforms were observed for both the onset response and ACC by plotting voltage against time. The sound onset elicited a faster response than the sound change. ACC topographical maps resembled those of the onset response; P1, N1 and P2 peaks were identified, and central electrodes gave robust responses. ACC and onset response source time courses revealed bilateral localization of the N1 peaks in the auditory cortex. Conclusions Topographical maps represent a useful means to explore the fidelity and temporal dynamics of the ACC. Results confirmed that neural origins of the ACC reside bilaterally in the auditory cortex. Interestingly, source localization of the ACC showed a similar spatial distribution to the onset response, suggesting similar neural generators, although further research is required for deeper clarification.
INTRODUCTION:Environmental noise is recognised by the World Health Organization and the European Environment Agency as a major environmental risk factor. However, the biophysical mechanisms linking acoustic exposure to cochlear mechanical and neural responses remain incompletely characterised. OBJECTIVE:This preliminary study organises established cochlear modelling approaches within a multiscale computational framework to examine how environmental sound levels are translated into passive mechanical responses and simulated neural activity. METHODS:Passive in silico simulations were performed using three complementary computational modules: (i) a one-dimensional transmission-line model of longitudinal cochlear mechanics; (ii) a three-dimensional finite-difference time-domain model incorporating cochlear-fluid propagation and fluid-basilar-membrane coupling; and (iii) a perceptual post-processing pipeline based on equivalent rectangular bandwidth filtering, inner hair cell transduction, and stochastic auditory-nerve activity. Acoustic inputs included synthetic and environmental signals calibrated between 30 and 85 dB SPL. Both mechanical models were implemented under passive linear assumptions and did not include outer-hair-cell-mediated amplification, compressive nonlinearity, or level-dependent active tuning. RESULTS:Higher acoustic input levels produced greater basilar membrane displacement in the 1D and 3D mechanical models, increased pressure magnitude in the three-dimensional fluid domain, and greater simulated neural activity and burstiness in the perceptual module. In the passive 1D model, increasing the input from 30 to 85 dB SPL produced an approximately 55 dB increase in basilar membrane displacement level while the normalised frequency-position ridge geometry remained essentially unchanged, consistent with proportional linear scaling. The derived characteristic-frequency and Q10 distributions reproduced the expected longitudinal tonotopic gradient within the frequency range reliably resolved by the simulations, although their extension into the most apical region was limited by the 200 Hz lower-frequency boundary and the peak-identification criteria. The Environmental Auditory Risk Index was used as an exploratory, model-derived composite indicator for integrating the mechanical and simulated neural outputs evaluated in the study. CONCLUSION:The proposed framework provides a controlled computational representation of how environmental acoustic inputs are translated into passive cochlear mechanics and simulated neural activity across complementary modelling domains. The results should not be interpreted as evidence of active cochlear amplification, physiological injury, or clinically validated auditory risk. Incorporation of nonlinear outer hair cell mechanics, extension of the low-frequency simulation range, sensitivity analysis, and experimental or clinical validation will be required before the framework or its derived indicators can support predictive applications.
During the development of the mammalian cochlea, Notch signaling induces prosensory cell formation and later directs the differentiation of prosensory progenitor cells into hair cells and supporting cells. Previous studies have demonstrated that ectopic activation of Notch signaling in the early embryonic cochlea results in the formation of ectopic sensory patches in non-sensory regions; however, the ability to respond to Notch signaling declines with age and is lost after embryonic day (E) 13.5. Here, we observed that Notch activation at birth induced ectopic sensory patches in the mouse cochlea. These ectopic patches produced hair cell-like cells that express some proteins found in mature hair cells. Ectopic sensory patches result from hyperplasia of non-sensory cells throughout the cochlear duct that reentered the cell cycle and produced foci of prosensory competent cells. Within the organ of Corti, cells remained quiescent, however, cellular patterning was altered leading to differentiation of outer sulcus cells into supporting cell-like cells and altering the identity of pillar cells. We further investigated different levels of activated Notch signaling using a doxycycline-inducible system and found that the competence of the neonatal cochlea to induce prosensory markers, such as Sox2, correlates with the level of Notch activation, whereby higher levels of Notch signaling induced ectopic Sox2 expression. Because this conflicted with previous reports, we investigated the mechanism underlying prosensory reactivation in our experiments and found that the loss of one copy of Sox10 resulting from our use of Sox10rtTA/+ knock-in mice facilitated prosensory competence, and that higher levels of Notch activation increased the penetrance of the phenotype. Our results demonstrate that the interaction between Notch signaling and SOX10 is important for the regulation of cellular identity in the developing inner ear.
Auditory processing deficits are a prominent early feature of Alzheimer's disease (AD), yet whether they reflect generalized cognitive slowing or domain-specific neural degradation remains unclear. This study combined a categorical perception paradigm with high-temporal-resolution electroencephalography (EEG) to evaluate neural responses to distinct combinations of acoustic cues, rapid temporal dynamics (consonants) versus stable spectral configurations (lexical tones), across a continuum of healthy aging, mild cognitive impairment (MCI), and AD. Rather than a monolithic functional loss, behavioral analysis revealed a differential vulnerability: while psychomotor slowing was global, categorical precision collapsed specifically for rapid consonant cues but remained remarkably resilient for tones. Neurophysiologically, this divergence was underpinned by a distinct trajectory transitioning from successful compensatory hyper-activation in normal aging to a state of inefficient hyper-activation in clinical cohorts, characterized by sustained P300 amplitudes but severe temporal processing delays. Crucially, we demonstrated the clinical utility of these domain-specific electrophysiological signatures using a fivefold cross-validated machine learning approach. Advanced classification algorithms, notably the gradient boosting machine (GBM), distinguished participants with MCI from cognitively normal older adults with an area under the receiver operating characteristic curve (AUC) of 0.836. These findings reframe auditory deficits in dementia as a nuanced erosion of specific neural codes and highlight the efficacy of interpretable, EEG-based neurocomputational tools for the early clinical screening of pre-dementia states.
Hearing loss is one of the most common age-related health conditions and is associated with a number of adverse psychological, physical, and social outcomes. Chronic under-stimulation, due to reduced auditory input from the ear is hypothesised to result in cascading neural consequences, including atrophy in auditory and associated cortices. One key factor known to protect healthy brain ageing is exercise, potentially by providing an alternative source of stimulation and environmental enrichment. As such, we tested whether engaging with physical activity moderates the association between hearing loss and neural atrophy. Structural equation modelling from a large cohort of middle-aged and older adults sourced from the UK-Biobank (N = 28 994) replicated previous findings that hearing loss is associated with reduced grey matter volume in the frontal lobe, temporal lobe, and subcortical nuclei. The potential deleterious effect of hearing loss was reduced across all brain areas in adults who spent more time engaging in physical activity. Socioeconomic status was not a significant mediator of the hearing loss-brain volume association. Promoting physical activity through social prescribing may be effective in protecting healthy brain ageing in older adults with hearing loss. Further research should extend this population neuroscience approach with experimental interventions to assess practical implications for population health.
Hyperacusis describes the condition in which mid-level sounds are perceived as uncomfortably loud. This study assessed 36 listeners (mean age = 25.75 years) with low noise-exposure history (Noise Exposure Structured Interview, NESI) and no tinnitus, to investigate the association between assessed hyperacusis scores (Hyperacusis Questionnaire, HQ), measured uncomfortable loudness levels (ULLs), and speech intelligibility in noise (Matrix Speech test). Thresholds were ≤ 20 dB HL, for the standard audiometric signal frequencies (0.25-8 kHz). ULLs were measured for signal frequencies of 0.5-, 2-, and 4-kHz. Extended high-frequency (EHF) audiometric thresholds were also measured for signal frequencies up to 16 kHz. Cluster analysis identified three groups based on EHF audiometric threshold and slope. The cluster EHF thresholds for the three groups were 5.2 dB HL (LOW-hf), 18.3 dB HL (MED-hf), and 45.7 dB HL (HIGH-hf). Results indicated that the MED-hf group exhibited significantly higher HQ scores compared to the HQ scores associated with LOW-hf and HIGH-hf groups. Also, elevated EHF thresholds were generally unrelated to speech-in-noise intelligibility scores, and there was no significant relationship between HQ and NESI scores. For young listeners with relatively low noise exposure, normal or mildly-elevated EHF thresholds (8-16 kHz) may be associated with mid-range HQ scores.
Music plays an important role in many people’s lives. While the effects of hearing loss on speech are well studied, its impact on music perception is less understood. To address this gap, the current study utilized polyphonic female vocal passages in an enumeration and a voice-tracking task to investigate how normal-hearing (NH) and hearing-impaired (HI) listeners with mild to moderate sensorineural hearing loss perceive individual voices in polyphonic music. We hypothesized that hearing loss would hinder listeners’ ability to distinguish voices in music due to impaired frequency selectivity, but that inharmonicity, introduced separately into each voice, would impact HI listeners less, due to their potentially reduced sensitivity to inharmonicity and pitch. Results indicated that NH listeners outperformed HI listeners in the enumeration task, but that performance in the voice-tracking task was not significantly different between groups. Although inharmonicity degraded performance across tasks, particularly in the enumeration task, HI listeners were less affected than NH listeners, at least at higher voice numbers. Exploratory analyses showed modest influences of age and musicianship on HI listeners’ performance in the enumeration task and provide promising avenues for future research. Overall, these findings point toward a task-dependent effect of hearing loss on music perception, impacting dense auditory scenes more severely, while leaving some ability to track a cued voice within polyphonic music. Taken together, these results may help inform future research exploring targeted interventions to support music listening for HI listeners.
Age-related hearing loss is associated with lower cognitive performance in later life, but the behavioral pathways linking these domains remain unclear. Phonological working memory, as assessed by nonword repetition, depends on both auditory input quality and availability of cognitive resources and may represent a candidate pathway linking hearing and cognition. This study examined whether hearing sensitivity and global cognitive performance are independently associated with nonword repetition and whether nonword repetition accounts for part of their association. One hundred twenty adults aged 55-80 years completed pure-tone audiometry, a standardized nonword repetition task, and the Montreal Cognitive Assessment (MoCA). Associations among hearing sensitivity, nonword repetition, and global cognitive performance were examined using regression and mediation analyses controlling for age, sex, and education. Poorer hearing sensitivity and poorer cognitive performance were each independently associated with reduced nonword repetition accuracy, with hearing sensitivity showing a stronger association. Both factors explained unique variance in performance, with additive (non-interactive) effects. Mediation analyses indicated that nonword repetition accounted for part of the association between hearing sensitivity and global cognitive performance. The results showed that nonword repetition is a task that is independently associated with hearing sensitivity and global cognition in older adults. The findings support a framework in which degraded auditory input imposes primary constraints on phonological processing, with cognitive resources providing limited compensation. Nonword repetition may offer a useful behavioral measure for assessing combined auditory and cognitive variability in adults in mid-to-late life.
This study investigated the effects of noise and reverberation on recognition of Dutch digits-in-noise (DIN) test triplets. The findings demonstrate that the STIDIN, an adaptation to the standard speech transmission index (STI), provides a reliable, low‑error predictor of DIN test performance in conditions with noise and/or reverberation when only a single speech recognition threshold (SRT) measurement in noise is completed. To achieve this, twenty-four normal-hearing (NH) adults completed adaptive SRT measurements in noise-only, reverberation-only and combined noise and reverberation conditions using unprocessed (UP), low-pass filtered (LPF) and cochlear implant vocoded (CIvoc) speech materials. Standard STI values differed across conditions and overestimated the detrimental effect of reverberation on recognition. The STIDIN, derived from the magnitude cross power spectrum (mCPS) of reverberated DIN test triplets and unprocessed triplets, was applicable for T60 reverberation times up to 12 s. STIDIN values remained constant across conditions, showing no significant main effect of condition for any of the unprocessed and processed speech materials. The results show that when an SRTn measurement in noise-only is obtained using DIN test triplets (i.e., the clinical standard), the STIDIN can be used to predict the SRT in other listening conditions with noise and reverberation. The root‑mean‑square error between measured and predicted SRTs was 0.92 dB, and 95 % of predictions deviated <1.7 dB from the measured values in conditions with noise and/or reverberation.
Adult and pediatric cochlear implant (CI) users differ in age, duration of deafness, and etiology, yet cochlear nerve (CN) response properties have not been systematically compared between these populations. To address this gap, this study examined electrically evoked compound action potentials (eCAPs) in pediatric and postlingually deafened adult CI users. Seven eCAP-derived indices were evaluated, including threshold, amplitude at the maximum comfortable level, overall and maximal slopes of the amplitude growth function (AGF), absolute and relative refractory periods (t0 and τ), and the local electrode-neuron interface (ENI) index. Sixty-four adult and 56 pediatric users of Cochlear™ Nucleus® CI devices were tested. eCAP AGFs and refractory recovery functions (RRFs) were measured at three to seven electrodes along the array. AGF slopes were quantified using linear regression and the window method, while t0 and τ were derived by fitting RRFs with exponential decay functions. Local ENI index was calculated using a machine-learning model incorporating several eCAP measurements. Linear mixed-effects models revealed both shared and distinct patterns of CN responsiveness between pediatric and adult CI users. Pediatric users demonstrated lower eCAP thresholds than adults when pooled across electrode locations. Adults exhibited shallower AGF slopes at basal electrodes than middle and apical electrodes. RRF-derived indices revealed shorter refractory periods in adults, likely influenced by group differences in maximum comfortable stimulation levels. Across both groups, several eCAP measures showed poorer responses at middle electrode locations relative to apical and/or basal sites. Future studies incorporating additional eCAP metrics may further clarify group differences in CN health and function.
OBJECTIVE:This study evaluated subcortical auditory and peripheral vestibular pathway alterations in normal-hearing individuals with unilateral subjective somatic tinnitus, isolating cross-modal electrophysiological relationships using an intra-subject, internally controlled paradigm. METHODS:Twenty-four participants (aged 17-61 years) with unilateral subjective somatic tinnitus and symmetric normal hearing thresholds (≤15 dB HL across 0.125-8 kHz) underwent auditory brainstem response (ABR), cervical vestibular evoked myogenic potential (cVEMP), and ocular VEMP (oVEMP) testing. Mathematically normalized Interaural Asymmetry Indices (AI) isolated side-specific neural imbalances. RESULTS:Conventional audiological profiles, middle ear compliance, and absolute ABR parameters (waves I-V) displayed interaural symmetry (p > .05). Conversely, absolute oVEMP evaluations demonstrated a statistically significant reduction in P1-N1 peak-to-peak amplitudes within the tinnitus-affected ears (M = 4.23 µV, SD = 2.98) relative to the healthy contralateral ears (M = 5.76 µV, SD = 4.72, p = .014), while absolute cVEMP parameters remained balanced (p = .396). Correlation analysis of normalized indices revealed a strong positive relationship between cVEMP AI and ABR wave V AI (r(22) = .555, p = .005). Multiple linear regression modeling showed that combined vestibulocollic (cVEMP) and vestibulo-ocular (oVEMP) neural asymmetries significantly predicted upper-brainstem auditory asymmetry at the level of the inferior colliculus, F(2, 21) = 8.66, p = .002, accounting for 45.2% of the variance in ABR wave V asymmetry (R2 = .452). Tinnitus chronicity showed an exploratory positive correlation with cVEMP AI (r(22) = .456, unadjusted p = .025; did not survive FDR correction). CONCLUSION:Unilateral subjective somatic tinnitus appears to involve tract-specific subcortical electrophysiological asymmetries. We discuss these side-specific differences within a chronological reorganization framework. While acute ascending vestibulo-ocular suppression marks the initial gating failure, a progressively deepening descending vestibulocollic imbalance is strongly associated with upper auditory brainstem asymmetry. These outcomes validate combined VEMP indices as objective biomarkers and provide a neurophysiological rationale for future interventional trials to test whether early targeted bimodal neuromodulation can effectively reset subcortical hyperactivity before persistent neuroplastic consolidation.
Objective This study examined if the amplitude growth function (AGF) of the electrically evoked compound action potential (ECAP) can objectively predict the perceptual loudness growth function (LGF) in cochlear implant (CI) users. Methods ECAP AGFs were measured in 16 CI users across all active electrodes using the MED-EL AutoART fine-grain procedure. Perceptual LGFs were obtained with psychophysical loudness scaling at stimulation rates between 150 and 1200 pulses per second (pps). A third experiment collected ECAP and LGF data simultaneously at 80 pps. Both physiological and perceptual functions were normalized to their dynamic ranges, and a power-law transformation was fitted to model the transformation between ECAP amplitude and perceived loudness. The effects of stimulation rate and electrode position on the model parameters were examined statistically, and the model’s predictive accuracy was assessed using a goodness-of-fit (R²) analysis. Results Loudness growth functions showed a systematic rate dependency: shifting from compressive at 80 pps to expansive at 1200 pps. Electrode-specific effects were less pronounced. The power-law exponent increased significantly with stimulation rate (p < 10⁻¹⁵), indicating steeper loudness growth at higher rates. The transformation model was remarkably accurate predicting perceptual loudness: 66% of fits yielded R²>0.8 and 45% >0.9, demonstrating strong correspondence between physiological and perceptual growth functions. Conclusions A strong, systematic relationship exists between ECAP AGFs and perceptual loudness growth across stimulation rates in CI users. Modeling loudness growth from ECAP data provides a viable path toward objective, physiology-based individualization of compression functions in future CI fittings.
