Journal of the Association for Research in Otolaryngology

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.

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.

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.

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.

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.

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.

Several types of cues contribute to speech recognition in multi-talker environments. In this study, we investigated how talker head-orientation related (THOR) cues and extended high- frequency (EHF; >8kHz) cues affect speech-in-speech recognition for both female and male speech. We examined the THOR benefit associated with a non-facing masker talker head orientation (relative to a facing orientation) as a function of masker talker facing angle. The target talker always faced the listener, whereas co-located maskers were tested with eight different masker head angles, ranging from 0{degrees} (facing the listener) to facing 180{degrees} away. Two filtering conditions were tested: full- band and low-pass filtered at 8 kHz. A THOR benefit was observed at masker head angles greater than 45{degrees}, increasing from 2 dB to 8 dB between angles of 67.5{degrees} and 180{degrees}. This benefit was reduced for low-pass filtered speech. Access to EHF cues improved performance, but only for masker head angles >22.5{degrees}. There was no significant relationship between 16-kHz pure-tone thresholds and performance for young, normal-hearing listeners with good EHF hearing. These findings indicate that listeners benefit from non-facing masker talker head orientations >45{degrees} when the target talker is facing the listener, with greater benefit for larger head angles.

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.

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.

The human bony labyrinth has attracted increasing interest because of its taxonomic, evolutionary, and functional significance. Although sexual dimorphism has been reported in several aspects of the temporal bone, the extent to which sex, age, size, and allometry contribute to labyrinth shape variation remains poorly understood. Here, we investigated patterns of sexual shape variation in the human bony labyrinth using three-dimensional geometric morphometrics in a sample of 98 archaeological individuals from South America with known genomic sex. Centroid size and allometric effects were assessed in a subset of 90 individuals with comparable metric scaling. In addition to analysing the complete labyrinth, the cochlea and semicircular canals were examined separately to evaluate region-specific patterns of sexual shape variation. Principal Component Analysis showed extensive overlap between females and males, and overall labyrinth shape did not differ significantly between sexes. Males exhibited significantly larger labyrinths than females, and centroid size explained a small but significant proportion of overall shape variation. Regional analyses showed no evidence of significant sexual shape differences in the cochlea or in any individual semicircular canal when analysed separately. In contrast, the combined semicircular canal system exhibited subtle but significant sexual shape variation independent of centroid size, whereas morphological disparity did not differ between sexes. The geometric comparison of the female and male consensus configurations further showed that sexual shape variation was regionally heterogeneous. Whereas the cochlea exhibited a pattern of localized changes with low directional coherence, the semicircular canals displayed more coordinated regional shape changes. The male consensus also exhibited slightly higher canal circularity across all three semicircular canals, particularly the posterior canal, while differences in canal-plane orientation remained minimal. These findings demonstrate that sexual shape variation in the human bony labyrinth is subtle and anatomically partitioned among its components. Although significant sex differences in centroid size were detected across most anatomical regions, overall labyrinth shape and cochlear morphology were primarily influenced by allometry, whereas significant sex-related shape differences were detected only when the semicircular canals were considered as an integrated anatomical system. These findings demonstrate that sexual dimorphism in the human bony labyrinth is subtle but regionally heterogeneous, with the cochlea and semicircular canals exhibiting distinct patterns of shape variation, suggesting that these structures are influenced by different developmental, functional, and evolutionary processes.

Since model dose-response is critical when assessing caries lesion development over time, this study evaluated the influence of fluoride dose and treatment duration on caries progression in a rat caries model. Streptococcus mutans-infected Sprague-Dawley rats were treated with deionized water, 226 ppm F-, or 2,260 ppm F- twice daily for 3, 4, or 5 weeks. Caries lesions were assessed using Larson's modification of the Keyes scoring system and complemented by micro-computed tomography (microCT). Intraoral fluoride availability, serum and bone fluoride concentrations and microbial counts were also determined. Fluoride reduced caries severity in a dose- and time-dependent manner. While early enamel lesions were detected in all groups, extensive dentine lesions increased over time, in a dose-dependent manner, in the control and 226 ppm F- groups, and were not observed in the 2,260 ppm F- group after 5 weeks. Intraoral and bone fluoride availability increased significantly with fluoride concentration and treatment duration, whereas serum fluoride levels reflected fluoride dose instead of treatment duration. MicroCT-derived enamel volume correlated negatively with both total and extensive caries scores, supporting its utility as an objective measure of lesion severity. In conclusion, extending model length from 3 to 5 weeks increased the severity of caries lesions in a dose-dependent manner. Fluoride intraoral availability and bone fluoride also demonstrated a dose and time-dependent response.

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.

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.

Natural-sound research requires stimulus sets that combine acoustic standardization with detailed behavioural characterization. We present 1,377 two-second sounds representing 240 expert-defined source--action classes. We call this database "MaMa Sounds", as it resulted from the collaborative effort of two academic teams in Maastricht and Marseille. The sounds were manually curated, segmented, sampled at 16 kHz, and labelled with a noun identifying the source and a verb identifying the action. We release deidentified trial-level identification and familiarity data together with multiple per-sound norms (e.g., identification accuracy, confidence and agreement; familiarity), along with overall norms derived with principal component analysis. Noun, verb, and joint noun--verb norms are provided as direct means and medians with the number of contributing observations. This battery preserves process-specific information, while two principal-component scores provide compact overall behavioural-identifiability measures derived from response ease, semantic correspondence, agreement, and familiarity. The repository also contains deterministic response-cleaning code, participant and reference Word2Vec representations, and code reproducing the public sound-level tables. The resource supports stimulus selection, matching, and continuous modelling in auditory cognition and neuroscience.

While movement variability is a natural element of human expression, in sign languages it may affect mutual understanding, learning, and potential overuse injury. Sign language variability is not well-understood in part because quantitative analytical methods are yet to be clearly defined. Hence the aim of this study was to assess intra-subject reliability across repeated sessions for three signers, to identify features sensitive to experience-related differences in motor control consistency, and to establish movement consistency metrics for treating sign language kinematic differences as linguistically meaningful. Three signers were assigned to three different proficiency levels of sign language: Deaf (D), proficient (P), and student (S). Sign production variables were evaluated using intraclass correlation coefficients (ICCs) and coefficients of variation(CVs).Most kinematic features showed good to excellent ICCs such as duration, path length, signing space volume, and average and peak velocity. Some EMG features such as mean forearm amplitudes and co-contraction also showed good to excellent ICCs. These data can be used to improve the scientific investigation of sign languages, improve educational resources, and establish baseline thresholds to inform ergonomic or scheduling guidelines for interpreters.

The availability of hearing aids that can connect wirelessly to smartphone technologies via Bluetooth has grown exponentially in recent years. However, there is limited evidence assessing the benefits of user-adjustability afforded by these devices. This study aimed to assess the benefits of smartphone-connected hearing aids and an accompanying application (or app) in new and existing hearing aid users. In this single-centre, prospective, observational study, 44 adult hearing aid users (14 new and 30 existing) were recruited. Participants were fitted bilaterally with smartphone-connected hearing aids that could be adjusted by the user via an app. Self-reported outcome measures were collected at fitting and after seven-weeks of using the device in everyday life. For both new and existing hearing aid users, significant improvements in social participation, hearing-related fatigue, and hearing aid benefit and satisfaction were found. For existing hearing aid users, all outcomes were significantly better for the smartphone-connected hearing aids plus app in comparison to their existing hearing aids that did not connect to a smartphone, all with moderate-to-large clinical effect sizes (d> .6). User-controllability via the app was identified as the key benefit, and most participants (68%) reported that the app met their needs 'extremely' or 'very well'. These results suggest that, when used in conjunction with an app, smartphone-connected hearing aids can improve hearing outcomes due to greater user-controllability to improve listening. Thus, smartphone-connected hearing aids have the potential to facilitate patient-centred care, empowering the individual to successfully manage their hearing loss.

Introduction Deafness is the most common human sensory deficit. Cochlear implantation is the primary intervention for severe-to-profound deafness. Currently, over 7000 people have bilateral cochlear implants (CIs) in the United Kingdom (UK), most of whom are children. Patient feedback suggests that for children with bilateral CIs, everyday communication is challenging and tiring, with extra effort required to integrate information from two ears, especially in noise, and that current rehabilitation techniques are not engaging, or appropriate to their lifestyles. To address these issues, researchers developed the Both EARS (BEARS) training package comprised of three virtual reality games to improve sound localization and listening in noise. Objectives This protocol describes the design and methodology of a multi-center phase III randomized controlled trial (RCT) to evaluate whether use of the BEARS training package alongside usual care compared to only receiving usual care improves speech-in-noise perception, hearing experiences, vocabulary and quality of life and reduces listening effort in children and young people (aged 8 -16 years (inclusive) with bilateral CIs. Methods This RCT is currently underway in 16 clinical CI departments in National Health Service or university hospitals across the UK. The intervention involves 3 months of spatial-listening training delivered via the BEARS training package in addition to any routine rehabilitation. The control is usual care (routine rehabilitation clinical care pathway). The primary outcome is the difference between the intervention groups in speech-in-noise perception score at 3 months derived from the spatial speech in noise (SSiN-VA) test. Recruitment closes at the end of the day on 31st July 2026, and end of data collection is 31st October 2026. Data analyses will be reported by 31st March 2026. Significance This is the largest known trial of children and young people with bilateral CIs. It will generate high-quality evidence on speech-in-noise outcomes and inform training interventions to improve spatial listening. Trial registration ClinicalTrials.gov registration: NCT05808543; UKs clinical study registry (ISRCTN92454702)

Intelligible speech disrupts selective auditory attention more than an unintelligible stream. However, low-level acoustic features of intelligible speech are relatively similar to target speech, confounding results. While controlling acoustic similarity and limiting energetic masking, we examined how masker intelligibility affects behavior and electroencephalography (EEG). Normal hearing listeners detected color words within a target stream of randomly timed words while ignoring an ongoing masker. Maskers were either spoken by the same or a different talker and comprised either isochronous sequences of intelligible words or temporally scrambled versions. Scrambled maskers either lacked broadband energy changes over time (Experiment 1) or were amplitude modulated to have the same energy profiles as intelligible, isochronous maskers (Experiment 2). In both experiments, scrambled maskers yielded better performance than intelligible maskers. For intelligible maskers, performance was better for different compared to identical talkers. EEG responses paralleled behavior: target-evoked onset responses were larger for scrambled than for intelligible maskers, particularly for identical talkers. Later target recognition responses were larger for color than other target words but unaffected by masker type or talker. Even when low-level acoustic features were carefully matched, intelligible maskers impaired auditory attention and reduced target-evoked neural responses more than scrambled maskers, implicating early sensory filtering.

Objective. A deep learning (DL) model was used to convert smartphone videos of a complete arch implant cast into 3D scans. The aim of current study was to determine if a custom scan body (SB) with geometric features and coating would outperform regular PEEK stock SB in this DL scenario. The DL-derived scan outcomes were compared with those obtained from a conventional splinted open-tray impression and from photogrammetry. Materials and Methods. A maxillary edentulous model with six implants and multi-unit abutment analogs was scanned using four protocols: conventional splinted open-tray impression (CO), photogrammetry (PG; Icam4D), DL using stock SBs (DLS) and DL using custom SBs (DLC). Each protocol was repeated for 10 times. The DL scans were produced from smartphone videos with a high-fidelity, multi-view 3D construction AI model (Neuralangelo). The custom designed SB incorporated geometric features and was fabricated via 3D printing followed by a spray coating. Accuracy (trueness and precision) was assessed using three measurements: Root Mean Square (RMS), linear deviation, and angular deviation. Results. DLC outperformed DLS in both trueness and precision regarding RMS and linear measurements (p<0.001). CO and PG demonstrated the highest RMS and linear trueness, with no significant difference between them (RMS: p=0.93; linear: p=0.663). PG achieved the best precision across RMS, linear and angular measurements. Conclusion. The optimised SB significantly improves the accuracy of DL-based approach for full-arch implant scan comparing to regular PEEK stock scan bodies. While early stage, neural surface reconstruction has potential as a viable option for full-arch implant rehabilitation.

Cochlear hair cell (HC) loss is a leading cause of hearing loss in humans. HCs can be generated from adjacent supporting cells (SCs); however, this regenerative capacity is lost after the onset of hearing. Using Emx2Cre Zbtb20 knockout mice, we show that ZBTB20 deficiency delays cell-cycle exit, differentiation, and maturation of cochlear SCs. Transcriptomic analysis of postnatal cochlear sensory epithelia indicates that ZBTB20 loss postpones the downregulation of progenitor genes, including Sox11 and Hmga2, and delays activation of a maturation-specific gene program. Additionally, experiments with cochlear organoid and organotypic explant models, reveal that prolonged, and to a lesser extent acute, ZBTB20 loss increases the mitotic and HC-regenerative potential of cochlear SCs. Transcriptomic profiling shows that acute ZBTB20 loss upregulates the midkine receptor Ptprz1, and further studies show that exogenous midkine, similar to ZBTB20 loss, promotes cell-cycle reentry and proliferation in cochlear organoid cultures.