Journal of the Association for Research in Otolaryngology

Aging and noise over-exposure lead to complex mixtures of cochlear degradation that impair the structure and function of outer hair cells, inner hair cells (IHCs), and the cochlear nerve. However, IHC damage and cochlear synaptopathy (CS) remain pathologies "hidden" from the audiogram. This study aimed to identify and differentiate the physiological signatures of these two distinct pathologies using promising non-invasive assays: Envelope Following Responses (EFRs), Auditory Brainstem Response (ABRs), Wideband middle-ear reflexes (WB-MEMRs), and Distortion Product Otoacoustic Emissions (DPOAEs). We utilized chinchilla models of carboplatin-induced (CA) IHC damage (N = 4) and temporary threshold shift (TTS) noise-induced CS (N = 4) to compare the physiological signatures of each pathology. While both groups showed unchanged ABR thresholds two weeks after exposure, EFRs, ABR Wave V/I ratios, and MEMRs showed distinct effects of exposure. Despite non-elevated ABR-derived audiometric thresholds after exposure, both CA and TTS exposure resulted in severe in EFR "peakiness", particularly for sharp, short-duty-cycle stimuli and significant elevations in ABR Wave V/I ratios. However, these findings were less-pronounced in the TTS-exposed animals. WB-MEMR amplitudes were decreased with elevated thresholds in both groups; this effect was more pronounced in the TTS group. Opposite trends in DPOAE amplitudes indicated that while both IHC damage and CS result in similar suprathreshold temporal coding deficits, effects on outer-hair-cell integrity and auditory efferent physiology may differ between the two pathologies. Future work and novel diagnostics should aim to distinguish these specific cochlear pathologies in clinical populations, or at the very least consider their overlap. HighlightsO_LIA multi-metric diagnostic approach was used with chinchilla models of inner-hair-cell (IHC) damage and cochlear synaptopathy (CS). C_LIO_LIIHC damage and synaptopathy both cause suprathreshold deficits "hidden" from the audiogram. C_LIO_LIIHC damage results in more severe temporal envelope coding degradation than does synaptopathy. C_LIO_LIA combination of EFR "peakiness", ABR Wave V/I ratio, and Wideband Middle Ear Muscle Reflex (WB-MEMR) appear to be useful measures for profiling IHC damage and CS. C_LI

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.

Mammalian hearing depends on the active amplification of sound-evoked waves as they travel along the basilar membrane within the cochlea. This amplification is mediated by the outer hair cells (OHCs), which generate force to enhance the vibrations of the surrounding structures. While OHCs at a given location only amplify basilar membrane motion for a narrow frequency range, recent measurements show that the amplification of motions deeper within the organ of Corti is much more broadband. However, the extent to which this broadband amplification influences the motions that are most relevant to inner hair cell stimulation - i.e., at the organs apical surface - remains uncertain. Here, optical coherence tomography was used to demonstrate that OHCs nonlinearly amplify the motions near the top of the organ of Corti, including at the reticular lamina and tectorial membrane, over a wide frequency range in the mouse cochlear apex. Responses at all frequencies were physiologically vulnerable and grew compressively with stimulus level. Low-frequency responses also exhibited non-monotonic features that were due to interference between amplified motion and the underlying traveling wave. The data suggest that broadband amplification of motions at the top of the organ of Corti likely explains certain phenomena observed in auditory nerve responses.

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.

The early-onset, high-frequency hearing loss phenotype of CD-1 mice is rescued by the A88V mutation of the connexin 30 gap-junctional protein, despite a reduced endocochlear potential (EP), which drives cochlear hair cell receptor potentials. The mutation enables organ of Corti (OoC) extracellular receptor potentials to be similar in size to those of sensitive-hearing CBA/J mice, presumably through increased OoC resistance, despite smaller intracellular outer hair cell (OHC) receptor potentials. Low-frequency hearing in CD-1Cx30A88V/A88V mice is impaired, compared with those of CBA/J and wild-type CD-1 mice. To investigate the cellular basis of OoC resistance increase and EP decrease, we made in situ electrophysiological measurements from Deiters cells (DCs) in the OoC of homozygous CD-1Cx30A88V/A88V mice. DCs contribute to the OHC cytoskeletal scaffold and cochlear K+ recycling, and are interconnected by syncytial junctions comprising connexins 30 and 26. Measurements from CD-1Cx30A88V/A88V mice were compared with those from wild-type CD-1 mice, with sensitive hearing below 12 kHz, and from the CBA/J strain. Syncytial junctional-coupling between DCs of CD-1Cx30A88V/A88V mice was weaker, input resistance greater, potassium current expression was modified, and voltage-sensitive activation was shifted to more negative values compared to those of CD-1 and CBA/J mice. Inactivating potassium currents dominate in DCs of CBA/J and CD-1Cx30A88V/A88V mice with excellent high-frequency hearing, and sustained currents dominate in DCs of CD-1 mice with early-onset hearing loss. These findings are discussed in relation to maintenance of OoC electrochemistry, rescue of early-onset hearing loss, impaired low-frequency hearing in CD-1Cx30A88V/A88V mice, and the basis of high-frequency hearing.

The peripheral auditory system of dolphins comprises specialised bony, fatty, vascular, and neural structures adapted for underwater hearing and diving physiology. These include the external ear canal, acoustic fat bodies, sinuses, and associated neurovascular networks, which together support sound conduction, protection, and possibly sensory functions. Despite advances in gross anatomical description, the detailed integration of these tissues, particularly the innervation, neurovascular organisation, and their functional implications, remains poorly understood. Previous studies have described the presence of sensory nerve formations and vascular plexuses, but their arrangement, connectivity, and relation to each other are unresolved. Here, we combine macroscopic dissection, DICE-{micro}CT, histology, and high-resolution confocal microscopy to characterise several neurovascular and sensory components of the dolphin peripheral auditory system in several delphinid species. Macroscopic dissection and DICE-{micro}CT revealed the traditional acoustic fat body distribution with detailed morphology of the posterolateral extension that is not well-known. The cranial nerve distribution, and specifically the mandibular nerve branching patterns, are described in detail. Confocal microscopy uncovered a stratified neurovascular plexus around the external ear canal with a complex sensory system comprising lamellar corpuscles, Merkel cell-neurite complexes, and intraepithelial nerve fibres. Notably, the lamellar corpuscles formed a continuous, three-dimensional neural network with frequent merging and splitting of axonal bundles, shared perineuria, and vascular integration, features not observed in previous studies. Our findings demonstrate that the dolphin external ear canal and surrounding structures form a sophisticated, multimodal somatosensory organ, integrating structural, vascular, and neural specialisations likely adapted for proprioceptive mechanosensation in the aquatic environment. This study provides insights into the integration of the various components of the peripheral hearing apparatus. Future studies integrating anatomical, electrophysiological, and biomechanical approaches are needed to fully elucidate these adaptations.

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.

Generation of otic progenitors from pluripotent stem cells requires precise timed regulation of signalling pathways, including bone morphogenetic protein 4 (BMP4). Because endogenous levels of BMP4 varie between cell lines, the optimal concentration of exogenous BMP4 must be determined individually to achieve efficient otic differentiation. Three different human induced pluripotent stem cell lines (hiPSCs) underwent ectodermal differentiation to early otic induction stages in the presence of various concentrations of BMP4 (0-5 ng/ml). Differentiation outcomes were assessed by immunofluorescence staining, and quantitative gene expression analysis. Raman microscopy was used to characterize biochemical differences between hiPSC differentiated cultures exposed to different BMP4 concentration. We observed distinct ectodermal fate were after 8 days of in vitro differentiation depending on BMP4 concentration, including neural, non-neural/otic ectoderm and surface epidermal fates. The proportion of PAX2-otic progenitors varied substantially between cell lines and culture conditions, ranging from approximately 9% to 77%. Raman spectroscopy revealed concentration dependent spectral differences and enabled discrimination between differentiating condition within individual hiPSC lines. Analysis of Raman spectral features indicated differences in nucleic acid, lipid, protein, and collagen associated signatures across culture conditions and cell lines. These findings demonstrate that Raman microscopy provides a non-destructive, label-free method for monitoring molecular changes associated with early otic differentiation. By complementing conventional molecular and immunocytochemical analyses, Raman spectroscopy offers a valuable tool for optimizing BMP4-mediated otic induction protocols and improving the reproducibility of stem cell-based strategies for inner ear research and regenerative medicine.

The vestibular system is critical for early motor development, yet the respective roles of its two subsystems, the semicircular canals and otolith organs, remain poorly defined. Here we analyse 411 children with comprehensive vestibular assessment to determine whether a functional hierarchy underlies their contributions to the acquisition of four postural and motor milestones during the first two years of life. Using Type III ANOVA to account for the frequent co-occurrence of canal and otolith dysfunction, we show that canal areflexia is associated with a 7.0-month delay in independent walking, three times larger than the otolith effect. Canal function is the only component reaching significance after Bonferroni correction across four milestones. Canal function alone predicts walking delay (>18 months) with an area under the curve of 0.83. Canal areflexia carries a positive predictive value of 80.2% for walking delay, while normal canal function effectively rules out a walking delay of vestibular origin (negative predictive value 93.5%). These findings establish a functional hierarchy of vestibular contributions to motor development and identify canal function as a powerful developmental biomarker.

The middle ear muscle reflex (MEMR) and medial olivocochlear reflex (MOCR) are increasingly studied for their role in suprathreshold auditory processing. However, recording these reflexes in humans is potentially complicated by age-related (sub)clinical hearing loss and co-activation. This study investigates (1) the influence of age-related (sub)clinical hearing loss, (2) methodological differences between conventional and wideband MEMR techniques, and (3) how MEMR activation contaminates MOCR recordings. Three test groups were included: young normal-hearing adults, middle-aged normal-hearing adults, and middle-aged adults with audiometric hearing loss. Cochlear status and neural encoding was assessed using distortion-product otoacoustic emissions (DPOAEs) and envelope following responses (EFRs). MEMR recordings were compared using conventional tonal stimuli and wideband stimuli. MOCR was recorded at elicitor levels of 60 and 75 dB to evaluate MEMR co-activation. MEMR was related to age, suggesting sensitivity to subclinical cochlear damage. Wideband stimuli were beneficial as elicitor (noise vs. tone), while changing the probe stimuli added no significant benefit (click vs. tone). MOCR strength did not correlate with age-related subclinical hearing, suggesting that MOCR measurements may reflect efferent function relatively independently of afferent sensorineural status in audiometric normal hearing subjects. However, reliable recordings were challenging in participants with audiometric hearing loss due to poor OAE baselines. MEMR co-activation was detectable in the click response and could alter MOCR-induced suppression. These findings suggest that, in cases of normal hearing thresholds, MEMR amplitude may be a marker of subclinical cochlear damage and MOCR measurements may more specifically reflect efferent function. Clinical measurements can be improved using broadband stimuli, accounting for outer-hair-cell damage, and defining criteria for reflex co-activation.

Modern cochlear implants (CIs) use pulsatile stimulation to restore hearing for individuals with severe hearing loss. CIs provide robust speech recognition in quiet but poorly represent temporal fine structure (TFS), needed for challenging listening situations. Analog stimulation preserves the acoustic waveform and may better encode TFS, yet it has not been evaluated combined with modern current-focusing strategies. We compared neural responses in the inferior colliculus (IC) evoked by CI stimuli consisting of 100 pulses/s biphasic pulse trains and 100 cycles/s sinusoidal analog stimulation with monopolar, bipolar, and tripolar electrode configurations in urethane-anesthetized guinea pigs. Following cochlear implantation, multiunit activity was recorded from the tonotopic axis of the central nucleus of the IC using 16-channel silicon probes. Detection thresholds, spread of excitation, vector strength, sustained response percentage, and temporal response properties were quantified. Analog stimulation consistently evoked significantly lower activation thresholds than pulsatile stimulation while maintaining comparable or sometimes narrower spatial selectivity across stimulation modes. In contrast, analog stimulation generated lower vector strength, larger tonic response components, and a pronounced level-dependent polarity effect. At low stimulus levels, responses were dominated by the cathodic phase of the sinusoidal waveform, whereas increasing stimulus level responses were elicited by both phases, producing synchronization at twice the stimulus frequency. These findings demonstrate that stimulation waveform strongly influences temporal coding while having relatively little effect on the spatial distribution of neural activation. These results provide a physiological basis for reexamining analog stimulation as an alternative strategy for cochlear implant sound coding.

Pure tone audiometry (PTA) remains the clinical standard for evaluating hearing ability, yet individuals with similar audiometric profiles often exhibit substantial variability in their capacity to understand speech in everyday listening environments. Growing evidence suggests this variance is related to contributions from cognitive ability and auditory processing that standard threshold measures do not capture. To investigate how PTA, cognitive factors, and demographics such as age jointly predict real-world speech perception, 116 veteran adults 20-70 years old spanning a range of normal to moderate sensorineural hearing losses completed a spatial auditory attention task. Target color words were embedded within naturalistic short-story narratives presented under two conditions: a mono-talker speech-in-quiet (SIQ) condition and a dual-talker speech-in-noise (SIN) condition with a spatially separated competing narrative. Behavioral performance was quantified via color word hit accuracy, reaction time, and comprehension question accuracy. Participants also completed pure tone audiometry, the Montreal Cognitive Assessment (MoCA), and the Speech, Spatial and Qualities of Hearing Scale (SSQ12). Mixed-effects regression models were used to evaluate the contributions of PTA, age, cognitive ability, and self-reported hearing difficulty (SSQ12) to task performance across conditions. Results demonstrate a complex interplay between age, PTA, MoCA, and/or listening condition (SIQ vs. SIN) in predicting identification accuracy, reaction time, and comprehension. Age and condition significantly predicted hit accuracy and reaction time, with older participants showing improved accuracy in quiet but declining accuracy and slower responses in noise. PTA did not emerge as a significant main effect predictor but interacted with cognitive ability and condition to modulate performance, in some cases exhibiting a paradoxical inverse relationship with accuracy dependent on MoCA score. MoCA scores significantly predicted comprehension across conditions, and SIN hit accuracy was positively correlated with SSQ12 scores, validating the task against participants real-world listening experiences. These findings highlight the importance of incorporating cognitive screening and ecologically valid speech perception tasks into audiological assessment to better identify individuals at risk for functional hearing impairment in complex listening environments.

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.

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.

Subjective tinnitus is the most common auditory phantom perception in the absence of an acoustic stimulus yet there is no cure nor widely effective treatment to date. Previously, we suggested that sleep may contribute to tinnitus development after a triggering event, such as noise overexposure (NOE). Here, we investigated the effect of natural sleep on tinnitus development following NOE in mice. One group of mice was kept awake for 6 hours immediately after NOE, whereas a control group could sleep ad libitum. Tinnitus and hearing loss were assessed before and after NOE by determining gap prepulse inhibition of the acoustic startle reflex (GPIAS) and by recording auditory brainstem responses (ABRs). Only mice that were allowed to sleep in the first six hours after NOE developed a significant change in the GPIAS ratio one week after NOE, indicative of tinnitus. Habituation to the startle stimulus was largely similar between both groups, except that at eight weeks after NOE, when GPIAS ratio had returned to baseline levels in both groups, the sleep deprived group showed less habituation to the startle stimulus. Notably, animals in neither group showed significantly elevated ABR thresholds after NOE, yet the control group showed signs of elevated evoked activity in the auditory brainstem one week after NOE. These findings demonstrate that sleep early after noise overexposure may amplify subsequent tinnitus development. Our results suggest that sleep represents a temporal window that may be harnessed for potential modulation or mitigation of noise-induced hearing loss and tinnitus-related impairments.

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.

Gene therapy may provide a way to restore inner ear function to deaf and dizzy patients. The mouse is a crucial model system for functional genomics because of the numerous genetic models for hearing loss and inner ear dysfunction. Using an advance generation, E1-/E3-/E2b-(preterminal protein-/polymerase-) Type 5 Adenovirus, we investigated several routes of virus microinjection to determine which were most reproducible in targeting the endolymphatic fluid compartment of the cochlea. We found that when adenovirus is injected via the round window, transduced cells are found only adjacent to the scala tympani and not in the organ of Corti, suggesting that Adenovirus is unable to penetrate the basilar membrane or bony wall of the modiolus. Delivery to the cochlea via the semicircular canals is also inefficient. In contrast, our new method, via a stylomastoid foramen cochleostomy, increases the likelihood of adenovirus gene transfer to the scala media including cells in the organ of Corti and stria vascularis while preserving some hearing. The ability to target delivery of virus and other therapeutic reagents to specific inner ear fluid compartments will facilitate in vivo testing of candidate molecules implicated in multiple aspects of inner ear physiology and regeneration.

PurposeThis research sought to develop a low-cognitive-load speech-in-noise test based on consonant confusions with the potential for assessing hearing-aid benefit. MethodsVowel-consonant-vowel (VCV) stimuli with added speech-shaped noise were presented as a closed-set consonant identification task. Initially, consonant-confusion matrices were used to select, from a larger set of consonants and vowel contexts, a set of ten consonants and associated signal-to-noise ratios (SNR) that were sensitive to hearing loss. The sensitivity of the qVCV test to hearing loss was validated by comparing predicted pure-tone average (PTA) hearing thresholds with their audiometric PTA. Clinical viability of the qVCV test was assessed by comparisons to the QuickSIN test. Hearing-aid benefit was assessed by comparing test scores in unaided and aided conditions. ResultsThe consonants most sensitive to hearing loss were /b d g t k v z s [esh] n/ in the vowel context /[a]/. A cross-validated prediction of PTA had a mean-absolute error of 5.7 dB. The repeatability of qVCV at 50 trials was equivalent to the QuickSIN average of two lists. Hearing-aid benefit was quantified as a decibel reduction in hearing loss. ConclusionsqVCV and QuickSIN performed similarly when test times are equated. The advantages of qVCV include lower cognitive demand, fewer learning effects, and automated scoring. PTA predicted by qVCV which greatly exceeds audiometric PTA may indicate either cognitive deficits or cochlear neural degeneration. The qVCV quantification of hearing-aid benefit may have clinical value.

Tinnitus is commonly associated with hearing loss, yet it can also occur in individuals with clinically normal audiometric thresholds. This dissociation has led to the hypothesis that hidden sensorineural hearing loss underlies tinnitus in audiometrically normal-hearing individuals. However, identifying such subclinical deficits non-invasively is challenging because audiometric measures are influenced by age-related changes and interactions among sensorineural processes. In this study, we disentangled the contributions of tinnitus, age, and hearing status to sensorineural encoding and speech perception. We included 113 participants, divided into age- and hearing-status-matched groups with and without tinnitus, and assessed them using otoacoustic emissions, auditory evoked potentials, auditory reflex measurements, and behavioral tasks of speech perception. This design enabled a rigorous evaluation of whether hidden sensorineural deficits underlie tinnitus. Age and hearing status had substantial effects on objective measures of sensorineural function, whereas tinnitus-related effects were subtle and age specific. Young adults with tinnitus and normal audiometric thresholds exhibited enhanced auditory brainstem responses, elevated envelope following responses, and better vowel discrimination. In contrast, middle-aged adults with tinnitus showed no such enhancements and demonstrated poorer speech-in-noise performance. Correlation analyses revealed a tinnitus-related shift toward greater reliance on central auditory processing, compared with the predominantly peripheral associations observed in controls. The middle ear muscle reflex was unaffected by tinnitus but was correlated with hyperacusis-related parameters. Together, these findings suggest distinct tinnitus-related auditory profiles across the lifespan: neural enhancement and improved vowel discrimination in young adults, versus degraded sensorineural encoding and reduced speech intelligibility in middle-aged adults. Significance StatementTinnitus affects a significant portion of the population, yet its underlying origins are still unclear. While hearing loss is a common cause, individuals with tinnitus may also have normal hearing thresholds. This suggests that subtle sensorineural damage may also play a role. This study critically investigates tinnitus-, age-, and hearing-related sensorineural encoding using non-invasive electrophysiological measures, auditory reflexes, and speech perception tasks in carefully matched participant groups. The study reveals distinct tinnitus-related auditory profiles throughout the lifespan; including enhanced sensorineural processing in young adults and degraded encoding with impaired speech perception in middle-aged adults. These findings provide critical insight into the mechanisms underlying tinnitus and offer objective markers for future research on tinnitus diagnosis and treatment

ObjectivesObjective and ecologically valid measures of speech processing can complement conventional audiologic assessments. Phoneme-related potentials (PRPs), derived by averaging listeners electroencephalography (EEG) responses time-locked to phonemes in continuous speech, have emerged as a promising approach for capturing cortical processing of speech in naturalistic listening conditions. Importantly, PRPs reveal speech perception challenges even when conventional audiograms are clinically normal, positioning them as a promising neural marker for suprathreshold listening difficulties that standard audiometry often misses. As a critical step toward clinical translation, this study examined the extent to which PRP-derived measures remain stable across real-world contexts relevant to clinical implementation, including monaural versus binaural presentation, stimulus intensity level, and repeated testing sessions. The study also assessed cortical tracking of lower-level speech acoustics to determine whether the PRP findings could be attributed to acoustic processing. DesignEEG was recorded from 18 young adults with normal hearing as they listened to audiobook speech presented monaurally or binaurally at 60 or 75 dB across two sessions separated by approximately one week. Neural differentiation of phoneme manner-of-articulation classes (vowels, nasals/approximants, fricatives, and stops) in PRPs was quantified using two measures: an F-statistic reflecting between-manner relative to within-manner variability, and classification accuracy from a machine-learning model trained to predict manner class from PRPs. Temporal response function modeling assessed neural tracking of continuous acoustic envelope and onset features of the audiobook speech. ResultsNeither PRP-derived measure of manner differentiation showed significant effects of session, presentation modality, intensity level, or their interactions. Intraclass correlation analyses further indicated moderate-to-good reliability across all three factors. In contrast, neural tracking of the acoustic envelope and acoustic onsets was stronger under binaural than monaural presentation, with binaural presentation eliciting more pronounced cortical responses to the envelope. ConclusionsPRP-derived measures remained relatively stable across modest procedural variations that are common in clinical testing contexts, positioning PRPs as a potent objective index of naturalistic speech processing. This stability may reflect cortical processing of abstract, linguistically relevant speech categories and suggest that PRPs provide complementary information beyond audiologic assessments of peripheral auditory functions and EEG measures that primarily capture lower-level acoustic processing.