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.

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.

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.

Acoustic cues such as pitch and spatial location allow listeners to attend to a target speaker and ignore competing talkers, aiding speech recognition in background noise. Diminished ability to utilize acoustic cues for speech stream segregation may thus contribute to older adults' challenges hearing in noise. Adults aged 18-74 completed a speech-in-speech identification task with three conditions containing 1) only pitch cues (fundamental frequency), 2) only spatial cues (interaural time differences; ITDs), and 3) both pitch and spatial cues for segregating a target talker from competing talkers. Hearing thresholds at standard and extended high frequencies (EHFs), auditory brainstem responses (ABRs), and digit span scores were acquired to examine the influence of sensory and cognitive factors on use of each acoustic cue for speech-in-speech recognition. Significant differences were observed between cue condition scores indicating that use of the available cue(s) drove performance. ABR metrics were not a significant predictor but digit span scores significantly predicted scores on all three cue conditions. Working memory abilities therefore set a baseline for participants' speech-in-speech recognition regardless of the acoustic content. Hearing thresholds at standard frequencies significantly predicted scores on the Pitch condition. EHF hearing thresholds better predicted Spatial and Both Cue condition performance, suggesting that EHF thresholds represent auditory processing important for coding ITDs. Age group analysis revealed that older adults (aged 40+) performed significantly more poorly on all cue conditions of the speech-in-speech recognition task relative to younger adults. Age-related changes in auditory sensory processing may therefore impair older adults' speech-in-noise perception by reducing their ability to use acoustic cues for segregating target and competing speech.

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.

How sensory information is processed over time is often conceptualized as a process of temporal integration. Recently, auditory temporal integration has received renewed attention as a potential assay of hidden hearing loss caused by cochlear synaptopathy in rodent and avian studies. How these results relate to human hearing is in question due to a lack of studies in primates, and, more generally, the neural basis of auditory temporal integration is unclear, as most subcortical studies of it have been conducted under anesthesia. We have recently introduced a nonhuman primate (NHP) model which can address translational questions about auditory temporal integration and hidden hearing loss. Thus, in this study, we utilized single-unit recordings and compared derived neurometric measures to psychometric measures of temporal integration in normal hearing NHPs performing a tone-in-noise detection task. We then assessed psychometric measures of temporal integration in NHPs before and after noise exposure. In normal hearing NHPs, cochlear nucleus and inferior colliculus (IC) integration rates were significantly greater than psychometric rates. However, in noise only, [~]25% of IC neurons exhibited similar integration rates to behavior. After noise exposure, psychometric integration was disrupted for brief stimuli presented in quiet, but not in noise. The dynamic range of the psychometric function reliably increased, months after recovery from the noise-induced temporary threshold shift (TTS). Together, these data identify a subcortical neural substrate for temporal integration in noisy environments and suggest that behavioral assays of temporal integration may serve as sensitive indicators of subclinical hearing loss.

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.

Auditory brainstem responses (ABRs) are a core part of objective functional evaluations of hearing sensitivity and subcortical auditory transmission. Manual assessments of ABR waveforms are still a primary means by which thresholds and peak amplitudes and latencies are measured, which is time-consuming and prone to user variability. Automated methods have offered promising alternatives for ABR classification, but they have sometimes been limited in accuracy or robustness. Here, we developed and tested a supervised convolutional neural network (CNN) based ABR peak classifier that works across sound levels and sound frequencies that can be run quickly on a personal computer using single or dual-channel ABR inputs. For ABR peaks I, III, IV, and V, the classifier achieved over 95% accuracy. High accuracy was maintained even after noise-exposure causing temporary or permanent threshold shifts, and over 90% of peaks were within 0.041 ms (1 sample) of the manually identified peak. Only a few hundred samples were needed to train the network, making it widely amenable to smaller data studies or where the number of subjects or sessions may be low.

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.

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.

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.

Standard demographic models of age-related hearing loss (presbycusis) predominantly utilize symmetric functions, such as log-normal distributions for age-binned thresholds and 4-parameter logistic curves for prevalence estimates. While these models capture early-to-moderate degradation effectively, they structurally struggle to characterize the heavy tails associated with severe clinical impairment. In this study, we present a statistical critique using a secondary analysis of the historical Medical Research Council (MRC) National Study of Hearing (1980-1986) dataset. By applying Generalized Extreme Value (GEV) distribution theory, we demonstrate that as severity increases, the underlying statistical geometry of hearing loss shifts. The asymmetric, heavy-tailed GEV distribution provides a parsimonious description of severe impairment, requiring fewer parameters than standard symmetric models. However, we explicitly acknowledge that utilizing static population data to infer progression introduces an ecological fallacy. Furthermore, the dataset's historical nature embeds unquantified generational cohort effects. We conclude that while extreme value statistics offer a compelling mathematical framework for modeling the variance of severe presbycusis, true longitudinal datasets are required to isolate physiological degradation from historical cohort variance.

Background: Speech-in-noise (SIN) perception is a difficult everyday listening task that becomes more difficult with age. Neural tracking of target speech is associated with successful speech perception in clean and noise-degraded listening environments. How aging impacts neural tracking of speech and relates to behavioral decrements in older adults' SIN perception remains unclear. To address these questions, we measured neural speech tracking during a continuous SIN perception task in younger and older adults via multichannel EEG. Method: Participants (n=83) monitored a continuous stream of syllables (~4.5 Hz) presented in quiet and noise conditions during EEG recordings. We assessed neural phase-locking value (PLV) to the acoustic speech envelope to investigate interactions between aging, hearing loss, and stimulus noise on neural synchronization to speech. Results: Compared to younger adults, older adults demonstrated less behavioral sensitivity to noise effects than young adults and had higher overall PLV to target speech. Older adults also showed greater noise-related degradations in neural speech processing relative to younger listeners. Age remained a strong predictor of behavioral responses to speech even after controlling for hearing loss. Covarying for hearing loss removed most age-related effects on neural PLV. Conclusion: Older adults demonstrate overexaggerated neural tracking to ongoing speech presented in quiet and greater noise-related reductions in neurobehavioral speech processing than young adults. Our results support the decline-compensation hypothesis, corroborate unusually large speech envelope encoding in older listeners, and suggest more robust neural synchronization to the speech signal is not always perceptually advantageous.

ObjectivesOutcomes following cochlear implantation vary substantially across adult recipients, and the cognitive and perceptual factors contributing to this variability are not fully understood. This poses a challenge for developing strategies to improve cochlear implant outcomes, as such approaches require a clearer understanding of the mechanisms underlying individual listening difficulties. In this study, we investigated auditory cognitive measures in cochlear implant (CI) users to further elucidate the origins of this variability. DesignThirty-seven adult cochlear implant users completed measures of auditory cognition, comprising auditory working memory (AWM) and sound segregation ability, measured using an auditory figure-ground task (AFG), as well as measures of peripheral temporal and spectral processing, comprising the temporal modulation detection threshold (TMDT) and spectral ripple discrimination threshold (SRDT). Speech perception outcomes were assessed using word-in-noise (WIN) and sentence-in-noise (SIN) tasks. Separate multiple linear regression models evaluated the unique contribution of the auditory cognition measures to WIN and SIN performance, after accounting for the peripheral measures. ResultsBoth regression models explained a substantial proportion of variance in speech-in-noise outcomes (WIN: adjusted R{superscript 2} = 0.55; SIN: adjusted R{superscript 2}=0.57, both p < 0.001). For WIN performance, AFG and AWM were significant predictors. A similar pattern was found for SIN performance, where lower AWM ability and poorer AFG segregation were linked to poorer sentence listening in noise. No significant effects of spectral ripple discrimination or temporal modulation detection were observed in either model, even though both were significantly correlated with WIN performance. ConclusionsThese findings indicate that auditory working memory and sound segregation ability are robust predictors of speech-in-noise outcomes in adult cochlear implant users, across both word- and sentence-level measures. Together, the results may help explain why speech-in-noise outcomes remain highly variable among CI users, even when basic sensory encoding abilities are taken into account. Incorporating measures of auditory working memory and fundamental sound segregation may therefore improve outcome prediction and help in developing more individualised rehabilitation strategies.

Objective: This study investigated whether plosive consonants carry a perceptual loudness weighting that significantly exceeds that of non-plosive consonants when judged by hearing-impaired listeners. Design: A prospective loudness matching experiment utilizing the method of adjustment. Study Sample: 19 consenting native English speakers (Mean age: 61.4, SD: 16.4) with bilateral mild to moderate high-frequency sensorineural hearing loss, indicative of presbycusis. Stimuli: 13 vowel-consonant-vowel (VCV) nonsense syllables, exclusively utilizing the flanking vowel /u/. Results: Descriptive analysis revealed a strong time-order effect influencing loudness judgments for 7 of the 13 VCV test stimuli. Statistical testing showed no significant didference (P = 0.94) between the relative amplitudes corresponding to the point of equal loudness for plosive-containing versus non-plosive-containing VCV stimuli. However, 6 individual VCV stimuli, containing consonants from 4 separate manners of articulation, produced significant loudness matching data (P < 0.01). Conclusions: The results falsify the hypothesis that plosives, analyzed collectively as a class, possess a heavier perceptual loudness weighting than non-plosive consonants. While 6 individual VCV stimuli indicated potential individual consonantal loudness weightings, these findings must be interpreted cautiously due to the restriction to a single vowel context and the presence of procedural time-order biases.

Objective: Impaired understanding of noisy or degraded speech is a central feature of listening difficulties (LiD), but the possible causes of these symptoms are wide-ranging. Accordingly, recent research underscores the need to study these deficits using a test battery approach. Event-related potentials are useful objective metrics for studying LiD, but probing function across the speech processing hierarchy using traditional protocols is sequential and unrealistic in clinical settings. The novel chirped speech (Cheech) method combines natural speech with acoustic chirps to overcome these limitations. This study examines its utility for profiling childhood LiD. Methods: Twenty-eight children (15 typically developing, 13 with LiD), aged 8-17 years old, listened to a 17-minute Cheech story and detected a target word within the story via button press while EEG data were collected from 53 scalp sites. Results: Cheech successfully evoked responses from the auditory brainstem response through to the brain's language centers, as reflected by the N400 effect. Unlike TD children, those with LiD demonstrated N400 effects with atypical distributions that favored frontal rather than the typical parietal sites. A trend towards a delayed and reduced amplitude Wave V was also observed. Conclusions: Hierarchical examination of speech processing using Cheech primarily implicates altered language processing as a contributing factor to LiD, with the frontal topography of the N400 effect for those with LiD potentially suggesting a greater reliance on deliberate memory retrieval during the speech perception task. Significance: LiD could arise due to auditory and/or cognitive factors. The present results demonstrate the feasibility of objective, parallel measurement across this hierarchy and point to impaired language processing as a possible mechanism.

The inflammatory foreign body response that follows cochlear implantation produces intracochlear fibrosis, neo-ossification, and elevated electrode impedances that can compromise implant performance. Dexamethasone-eluting cochlear implants reduce this response, but the durability of their anti-inflammatory effect over long implantation intervals has not been established. Using a murine model of chronic cochlear implantation in CX3CR1+/eGFP Thy1+/eYFP dual-reporter mice, we compared dexamethasone-eluting and standard mouse cochlear implants at 224 and 336 days post-implantation. Density of CX3CR1+ macrophages, MHCII+CX3CR1+ antigen-presenting macrophages, -SMA+ fibrosis, and neo-ossification were quantified in the scala tympani, Rosenthal canal, and lateral wall of the basal turn. Standard implants produced persistent macrophage and antigen-presenting macrophage infiltration, accompanied by an -SMA+ fibrotic response and neo-ossification. Dexamethasone-eluting implants suppressed macrophage infiltration in all three regions out to 336 days and reduced fibrosis at 224 days. In the subset of cochleae with electrode array translocation, dexamethasone-eluting implants attenuated macrophage infiltration and confined the fibrotic and osseous response to the site of translocation, whereas standard implants produced a widespread response. A reduction in immune cell density was also observed in the contralateral, unimplanted cochleae of animals implanted with dexamethasone-eluting implants, suggesting a wider component to the drug's effect. Dexamethasone-eluting cochlear implants therefore provide sustained, long-term suppression of the cochlear foreign body response in mice, supporting their continued translation toward clinical application. This effect was associated with continued low-level dexamethasone elution out to 336 days post-implantation; further work is needed to assess the durability of this effect at the conclusion of drug elution.

Intrinsic lateral olivocochlear (iLOC) neurons provide vital brainstem efferent feedback to the cochlea in order to modulate hearing sensitivity through synapses onto type-I spiral ganglion neurons. During ageing or mutations affecting hair cell transduction in mice, efferent neurons rewire to form direct axo-somatic synapses onto inner hair cells (IHCs), recapitulating a synaptic configuration typically only restricted to the immature cochlea. Whether this rewiring reflects a compensatory mechanism or some form of attempted repair, or how iLOC biophysics change throughout ageing and this rewiring process, is not known. We utilised whole-cell patch-clamp electrophysiology to investigate iLOC activity and their underlying biophysics across the wild-type mouse lifespan. We show that iLOC neurons undergo a progressive increase in excitability with post-natal development and ageing, producing more spikes for a given stimulus. This intrinsic excitability shift was driven by the developmental decline in the A-type Kv4 mediated potassium current and increase in Kv2 mediated current. In ageing animals, and distinct from post-natal development, further increased firing rates were supported by an increased size of the fast-activating Kv3 current. Spontaneous bursting activity remained present in ageing iLOC neurons, and no reversion to an immature biophysics profile was evident. Interestingly, despite robustly eliciting efferent rewiring of IHCs, an accelerated ageing-like re-innervation genetic model did not recreate the biophysical changes in the iLOC neurons that reflected the ageing system. This work reveals distinct processes occurring within the iLOC feedback system, and shows that age-related enhancements of SGN resting activity are not triggered by deficits in IHC transduction.

PurposeThe neural representation of pitch and timbre in complex sounds has previously been studied using synthetic, controlled stimuli to investigate underlying encoding mechanisms. These studies provide information about how single attributes of sound are represented in the inferior colliculus (IC), a critical hub of the auditory pathway where neurons are sensitive to stimulus periodicity and spectral shape, giving rise to representations of pitch and timbre, respectively. However, there is a gap in understanding how natural sounds with both pitch and timbre attributes, such as instrument sounds, are represented in the IC. MethodsIn this study, extracellular recordings were made in the IC of awake rabbits in response to natural instrument stimuli varying in fundamental frequency (F0) to determine how instrument identity (timbre) and F0 (pitch) are represented in IC neurons. ResultsUsing decoding models for instrument identification, we found that instrument identity was redundantly encoded in a population of neurons with diverse rate and timing characteristics. F0 identification using decoding models trained on single-neuron rate responses was poor, but the population of rate responses contained enough information to identify F0 reliably. F0 information was also encoded in single-neuron temporal responses up to 196 Hz. F0 identification from a population of temporal responses was accurate up to approximately 900 Hz, but accuracy decreased at high F0s. For the task in which F0 was identified based on responses to both oboe and bassoon stimuli that had overlapping F0s, performance decreased compared to F0 identification based on responses to a single instrument. ConclusionThis result supports the hypothesis that pitch and timbre information are encoded jointly in the IC.