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.

ObjectiveCisplatin, a life-saving chemotherapeutic drug, causes ototoxicity. Although sodium thiosulfate is used to prevent ototoxicity in pediatric patients, no other intervention has been approved for clinical use against cisplatin-induced hearing loss. Hence, there is an urgent need to identify drugs that prevent cisplatin ototoxicity. MethodsCBA/J mice were treated with cisplatin (3 mg/kg, i.p., daily for 5 days), and MnTBAP (10 mg/kg, i.p., daily for 8 days) was used to inhibit cisplatin-induced ototoxicity. Auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) were recorded before and after treatment to assess hearing loss, while immunohistochemistry was performed to examine hair cells and spiral ganglion neuron (SGN) loss. ResultsCisplatin treatment elevated the nitrotyrosine levels in hair cells and SGNs and increased the loss of these cells in the middle and basal cochlear regions. A negative correlation was observed between cisplatin-induced changes in the hair cell count or SGN density and nitrotyrosine levels. Cisplatin elevated the hearing thresholds and lowered the DPOAE amplitudes. However, MnTBAP cotreatment prevented the cisplatin-induced changes in the hearing sensitivity and reversed the morphological changes. ConclusionThe otoprotection observed with MnTBAP cotreatment indicates its potential as a therapeutic drug against cisplatin-induced ototoxicity.

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.

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.

The feline auditory cortex is understood to consist of 13 distinct subregions with unique anatomical and functional properties. Differential patterns of SMI-32 immunoreactivity are commonly used to identify the borders between these subregions; however, the detailed description of areal differences that is commonly cited did not include descriptions of the patterns observed along the posterior ectosylvian gyrus. Thus, the current manuscript aims to provide a more complete data set that can used to delineate the dorsal, intermediate, and ventral divisions of the posterior ectosylvian gyrus (auditory cortical regions dPE, iPE, and vPE, respectively) based on SMI-32 reactivity using the same methods and measures. Taken together, the current data and those published previously allow for a standardized approach to identifying all 13 auditory cortical subregions in this essential model of auditory cortical structure and function.

Zfp719 is a zinc finger transcription factor which, when mutated, results in hearing impairment in mice. Its closest human orthologue, OTK18, has been linked to tinnitus in large human cohorts. Here we present our investigation of the electrophysiological, structural and transcriptional phenotypes in Zfp719tm1a mutant mice. Homozygotes have near-normal hearing at two weeks old, but lose sensitivity rapidly between two and three weeks, suggesting that while Zfp719 is not required for development, it is important for maintaining hearing. Heterozygous mice exhibit progressive hearing impairment for high frequencies at older ages. We observed damaged and degenerating outer hair cells from as early as three weeks old in homozygotes. We carried out bulk RNAseq at three ages and found one gene consistently misregulated, a long non-coding RNA specific to mice, Gm15083. A better understanding of the genes regulated by Zfp719 may shed light on genes and proteins important for maintaining hearing in humans.

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.

Auditory confounds have proven to be a major hurdle in the elucidation of veridical neuromodulation effects with transcranial ultrasound stimulation (TUS). Auditory noise masks are an essential method to reduce the audibility of TUS and have shown promise in several studies. Here we describe a novel approach for design, calibration, and psychometric validation of auditory noise masks to reduce the perceptibility of TUS. White noise masks and spectrum-tuned masks matched to a TUS protocol that generates highly salient auditory costimulation (487.5 Hz pulse repetition frequency, 10% duty cycle, 68 W/cm2 pulse-peak average intensity, 500 kHz acoustic frequency) were generated, and dB(A) levels were calibrated with an artificial ear. The masker levels needed to reduce TUS detection performance in a two-interval forced choice task were determined with an adaptive QUEST+ staircase in 20 neurotypical participants. Detection performance of this highly salient TUS protocol was driven to near chance performance (<55%) in 17/20 participants with white-noise and 18/20 participants with spectrum-tuned noise. However, high masker levels approaching safety limits were needed to render TUS inaudible for the majority of participants, indicating the need for formal masker calibration for these TUS settings. Additionally, against expectation the spectrum-tuned masker did not significantly outperform the white-noise masker, suggesting that perceptibility of TUS auditory costimulation does not lawfully follow the sound expected from its pulse envelope and the known spectrum of human hearing.

BackgroundTemporomandibular joint (TMJ) biomechanics can be characterized by mandibular motion, masticatory muscle activity, and bite force generation. When acquired synchronously, these functional variables can serve as model-ready inputs for subject-specific computational analyses of internal joint mechanics. However, existing tools typically measure these signals using separate hardware and software platforms, limiting synchronized acquisition within a clinically practical chairside workflow. MethodsWe developed and technically evaluated a compact multimodal platform for chairside acquisition of TMJ functional data and demonstrated its analytical utility in an illustrative orthognathic surgery application. The platform integrates motion, bite force, muscle activity, acoustic, and event-timing measurements with software for real-time preview, protocol guidance, and synchronized export. We assessed technical performance and chairside feasibility and analyzed representative pre- and postoperative data from an orthognathic surgery patient using kinematic, force-control, and computational modeling workflows. FindingsMotion capture demonstrated submillimeter accuracy, with static and dynamic errors of approximately 0.04 mm and 0.12 mm. Bite force sensors showed excellent linearity (R{superscript 2} = 0.998). Chairside deployment required approximately 15 minutes each for setup and data collection. The illustrative case demonstrated that synchronized chairside data can support preoperative and postoperative kinematic analysis, bite force control capacity assessment, and estimation of TMJ disc stress. InterpretationThe proposed platform enables time-efficient chairside acquisition of synchronized, model-ready multimodal datasets for quantitative TMJ biomechanical assessment. This platform and workflow could support subject-specific biomechanical analysis and future clinical studies of temporomandibular joint function.

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.

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.

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.

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.

PurposeMild therapeutic hypothermia (MTH) preserves cochlear function in animal models and is now entering early-phase human trials for hearing preservation. However, the extent to which the human cochlea can actually be cooled, and the mechanisms underlying MTH, remain unclear, in part because blood perfusion is expected to oppose localized cooling. In this study we evaluated the impact of blood flow on human cochlear temperature exposed to the MTH device using a combined experimental and computational approach. MethodsTemperature measurements were obtained from a human cadaver skull exposed to a commercial MTH device. These data were used to validate a three-dimensional bioheat transfer model incorporating realistic skull anatomy. The validated model was subsequently extended to include physiological blood perfusion in the internal carotid artery; a major heat source located near the cochlea. Finally, the in silico model was further expanded to incorporate the surrounding skin and brain tissues. ResultsIncorporating blood flow in internal carotid artery substantially altered predicted cochlear temperature distributions, highlighting the importance of localized vascular heat transport in the human cochlea during MTH. Although cochlear cooling was attenuated in the presence of perfusion, the therapeutic effects of MTH may not depend solely on the magnitude of local intracochlear temperature reduction. Additional mechanisms, such as reduced facial surface temperature, may also contribute to its efficacy. ConclusionThe validated in silico model provides a physiologically realistic framework for evaluating human cochlear thermal responses, investigating MTH mechanisms, and optimizing temperature-based strategies for hearing preservation.

Background Alveolar bone assessment in periodontal practice relies on radiography and clinical probing, both of which have well-documented limitations in precision. Intraoral high-frequency ultrasonography (US) offers a radiation-free alternative with potential for sub-millimeter resolution, the validity and precision for detecting minute osseous changes have not been established. The purpose of this study was to evaluate the concurrent validity and measurement precision of intraoral US for detecting alveolar bone-level changes in patients undergoing crown lengthening and osseous surgery, thereby enabling its translation to monitor osseous changes in patients with periodontitis. Methods Ten patients (28 tooth sites) undergoing crown lengthening or osseous surgery at a USC Advanced Grad Perio clinic were enrolled in this prospective observational study. Distance from the cementoenamel junction (CEJ) to the Alveolar bone crest (ABC) was measured at pre- and post-operative time points using a 40 MHz handheld intraoral US transducer and, intraoperatively, by standardized clinical photography. Agreement was assessed by Pearson correlation and Bland-Altman analysis. Measurement precision was quantified using the standard error of measurement (SEM) and minimum detectable change (MDC). Results Preoperative agreement between methods was excellent (r = 0.977; Bland-Altman bias = -0.009 mm; 95% limits of agreement [LoA]: +-0.40 mm). Post-operative correlation remained strong (r = 0.912; bias = 0.123 mm; LoA: -0.85 to +1.10 mm). Both methods detected statistically significant post-surgical increases in the ABC-to-CEJ distance (p < 0.001), as anticipated. US demonstrated substantially superior precision: preoperative SEM 0.058 mm with US versus 0.128 mm clinically, yielding MDC values of 0.160 mm (US) versus 0.354 mm (clinical), providing a 2.2-fold precision advantage. Conclusions Intraoral US demonstrated strong concurrent validity with clinical photography and a reproducible precision advantage in detecting alveolar bone-level changes in patients with periodontitis. These findings support its clinical utility as a radiation-free, high-sensitivity bone monitoring tool. Larger longitudinal studies with CBCT validation are warranted.

Cochlear implants (CIs) restore hearing by stimulating auditory neurons to encode amplitude envelopes across frequency bands, providing essential cues for speech recognition. This study investigated how stimulation pulse rate constrains temporal envelope processing and speech cue perception in ten post-lingually deaf CI users by evaluating amplitude modulation (AM) detection thresholds and consonant identification performance across pulse rates. The effects of pulse rate on temporal processing and speech perception were examined using both standard clinical multi-channel strategies and single-channel strategies designed to isolate within-channel envelope representations. Results revealed a significant decline in AM detection and consonant recognition performance at the lowest tested pulse rate of 125 pulses per second (pps), consistent with perceptual constraints on temporal processing at low carrier rates, rather than inadequate envelope sampling. At the highest pulse rate of 4000pps, a non-significant reduction in AM detection was observed which may be consistent with previously reported reductions in amplitude discrimination at high pulse rates. Consonant recognition performance remained stable across clinically relevant pulse rates (250-2000pps), though listener-specific pulse rate effects were observed. Notably, significant correlations were found between single-channel and multi-channel performance in AM detection and consonant recognition tasks. These findings support an important contribution of within-electrode temporal envelope processing to multi-channel speech perception and highlight the clinical relevance of individual variability in pulse rate effects.