Hearing Research

Information about eye movements is necessary for linking auditory and visual information across space. Recent work has suggested that such signals are incorporated into processing at the level of the ear itself (Gruters, Murphy et al. 2018). Here we report confirmation that the eye movement signals that reach the ear can produce perceptual consequences, via a case report of an unusual participant with tensor tympani myoclonus who hears sounds when she moves her eyes. The sounds she hears could be recorded with a microphone in the ear in which she hears them (left), and occurred for large leftward eye movements to extreme orbital positions of the eyes. The sounds elicited by this participants eye movements were reminiscent of eye movement-related eardrum oscillations (EMREOs, (Gruters, Murphy et al. 2018, Brohl and Kayser 2023, King, Lovich et al. 2023, Lovich, King et al. 2023, Lovich, King et al. 2023, Abbasi, King et al. 2025, Sotero Silva, Kayser et al. 2025, King and Groh 2026, Leon, Ramos et al. 2026, Sotero Silva, Brohl et al. 2026)), but were larger and longer lasting than classical EMREOs, helping to explain why they were audible to her. Overall, the observations from this patient help establish that (a) eye movement-related signals specifically reach the tensor tympani muscle and that (b) when there is an abnormality involving that muscle, such signals can lead to actual audible percepts. Given that the tensor tympani contributes to the regulation of sound transmission in the middle ear, these findings support that eye movement signals reaching the ear have functional consequences for auditory perception. The findings also expand the types of medical conditions that produce gaze-evoked tinnitus, to date most commonly observed in connection with acoustic neuromas.

Introduction: Auditory brainstem response (ABR) is a standard objective method for estimating hearing threshold, especially in patients who cannot reliably participate in behavioral audiometry. However, ABR interpretation is usually performed by an expert. This study evaluated whether two general-purpose artificial intelligence (AI) multimodal large language model (LLM) chatbots, ChatGPT and Qwen, can accurately estimate ABR hearing thresholds from ABR waveform images. The accuracy was measured by comparisons with the judgements of 3 expert audiologists. Methods: A total of 500 images each containing several ABR waveforms recorded at different stimulus intensities were analyzed. Three expert audiologists established the reference auditory thresholds based on visual identification of wave V at the lowest stimulus intensity, with the most frequent judgment among the three used as the reference. Each waveform image was independently submitted to ChatGPT (version 5.1) and Qwen (version 3Max) using the same standardized prompt and without additional clinical context. Agreement with the expert thresholds was assessed as mean errors and correlations. Sensitivity and specificity for detecting hearing loss (>20 dB nHL) were also calculated. In cases where the AI and expert thresholds nominally matched, corresponding latency measures were also compared. Results: Auditory thresholds derived from both LLMs correlated strongly with expert opinion, with Pearson r = 0.954 for ChatGPT and r = 0.958 for Qwen. ChatGPT showed a mean error of +5.5 dB and Qwen showed a mean error of -2.7 dB. Exact nominal agreement with expert values was achieved in 34.6% of ChatGPT estimates and 35.6% of Qwen estimates; agreement within +/-10 dB was observed in 75.6% and 80.0% of cases, respectively. For hearing-loss classification, ChatGPT achieved 100% sensitivity but low specificity (20.4%), whereas Qwen showed a more balanced profile with 91.6% sensitivity and 67.5% specificity. Curiously, estimates of wave V latency were markedly poor for both LLMs, with systematic underestimation and weak correlations with the expert judgements. Conclusion: ChatGPT and Qwen demonstrated a moderate ability to estimate ABR thresholds from waveform images, although their performance was not good enough for independent clinical use. Both models captured general patterns of hearing loss severity, but there was systematic bias, limited specificity and sensitivity balance, and poor latency estimation. General-purpose multimodal LLMs may have potential as assistive or preliminary tools, but clinically reliable ABR interpretation will likely require specialized, domain-trained AI systems with expert oversight.

Eye movement-related eardrum oscillations (EMREOs) appear to consist of a pulse of oscillation occurring in conjunction with saccades. However, this apparent pulse could occur either because there is an increase in energy at that frequency at the time of saccades (a true pulse), or because there is saccade-related phase resetting of ongoing energy at that frequency band, thus appearing like a pulse when averaged in the time domain across many trials. Here we conducted a spectral analysis at the individual trial level in humans performing a visually guided saccade task to determine whether the power at the EMREO frequency (30-45 Hz) is higher during saccades than during steady fixation. We found both an increase in sound power in the EMREO frequency band associated with saccades, i.e. sound pulses at the individual trial level, as well as, phase resetting at saccade onset/offset. While both factors contribute to the apparently pulse-like EMREO signal, phase resetting appears to be more prevalent across participants. The prevalence of phase resetting has implications for the underlying mechanism(s) producing EMREOs as well as functional consequences for how the ear might respond to incoming sound in an eye-position dependent fashion.

Conductive hearing loss (CHL) with a normal otoscopic exam can be difficult to diagnose because routine clinical measures such as audiometric air-bone gaps (ABGs) can identify a conductive component but often cannot distinguish among specific underlying mechanical pathologies (e.g., stapes fixation versus superior canal dehiscence, which may produce similar audiograms). Wideband tympanometry (WBT) is a fast, noninvasive test that can provide additional mechanical information across a broad range of frequencies (200 Hz to 8 kHz). However, WBT metrics are influenced by variations in ear canal geometry and probe placement and can be challenging to interpret clinically. In this study, we extend prior WBT absorbance-based classification work by estimating the middle ear input impedance at the tympanic membrane (ZME), a WBT-derived metric intended to reduce ear canal effects. To estimate ZME, we fit an analog circuit model of the ear canal, middle ear, and inner ear to raw WBT data collected at tympanometric peak pressure (TPP). Data from 27 normal ears, 32 ears with superior canal dehiscence, and 38 ears with stapes fixation were analyzed. A multinomial logistic regression classifier was trained using principal component analysis (retaining 90% variance) and stratified 5-fold cross-validation with regularization. We compared feature sets based on ABGs alone, ABGs combined with absorbance, and ABGs combined with the magnitude of ZME. The combination of ABGs and the magnitude of ZME produced the best performance, achieving an overall accuracy of 85.6% compared to 80.4% for ABGs alone and 78.4% for ABGs combined with absorbance. These results suggest that incorporating model-derived middle ear impedance features with standard audiometric measures (ABGs) can improve automated pathology classification for stapes fixation and superior canal dehiscence.

The rat vestibular system plays a critical role in anti-gravity responses such as the tail-lift reflex and the air-righting reflex. In a previous study in male rats, we obtained evidence that these two reflexes depend on the function of non-identical populations of vestibular sensory hair cells (HC). Here, we caused graded lesions in the vestibular system of female rats by exposing the animals to several different doses of an ototoxic chemical, 3,3-iminodipropionitrile (IDPN). After exposure, we assessed the anti-gravity responses of the rats and then assessed the loss of type I HC (HCI) and type II HC (HCII) in the central and peripheral regions of the crista, utricle and saccule. As expected, we recorded a dose-dependent loss of vestibular function and loss of HCs. The relationship between hair cell loss and functional loss was examined using non-linear models fitted by orthogonal distance regression. The results indicated that both the tail-lift reflex and the air-righting reflexes mostly depend on HCI function. However, a different dependency was found on the epithelium triggering the reflex: while the tail-lift response is sensitive to loss of crista and/or utricle HCIs, the air-righting response rather depends on utricular and/or saccular integrity.

Objectives: Patients with Cystic fibrosis (CF) often receive aminoglycosides (AGs) to manage recurrent pulmonary infections, placing them at risk for ototoxicity. Chronic AG use can lead to complex cochlear damage affecting inner and outer hair cells, the stria vascularis, and spiral ganglion neurons. The greatest damage is typically in the basal cochlear region, which encodes high-frequency hearing, with additional involvement of more apical regions. While extended-high-frequency (EHF) hearing loss (EHFHL; 9-16 kHz) is often the earliest sign of AG ototoxicity, speech in noise (SiN) effects are rarely studied. Our overall hypothesis is that SiN perception difficulties in individuals with CF, treated with AGs, are related to combined cochlear and neural damage, primarily in the EHF range but also in the standard frequency (SF; 0.25-8 kHz) range. Three mechanisms that contribute to SiN perception were evaluated in children and young adults: 1) a primary effect of reduced EHF sensitivity, measured by pure-tone audiometry (PTA) and transient-evoked otoacoustic emissions (TEOAEs); 2) a secondary effect of subclinical damage in the SF range, measured by PTA and TEOAEs; and 3) additional neural effects, measured by middle ear muscle reflex (MEMR) threshold (afferent) and growth functions (efferent).Design:A total of 185 participants were enrolled; 101 individuals with CF treated with intravenous AGs and 84 age and sex-matched Controls without hearing concerns or CF. Assessments included EHF and SF PTA; the Bamford-Kowal-Bench (BKB)-SIN test for SiN perception; double-evoked TEOAEs with chirp stimuli from 0.71 to 14.7 kHz; and ipsilateral and contralateral wideband MEMR thresholds and growth functions using broadband stimuli. Results: Reduced sensitivity at EHFs (PTA, TEOAEs) was not associated with impaired SiN perception in the CF group. SF hearing, regardless of EHF status, was the primary predictor of SiN performance in the CF group. Increased MEMR growth was also significantly associated with poorer SiN in the CF group. Conclusions: In CF, impaired SiN perception was primarily predicted by SF hearing impairment, with additional involvement of the efferent auditory pathway through increased MEMR growth. These results build on prior evidence for efferent neural effects due to ototoxic exposures, supporting both sensory (afferent) and neural (efferent) mechanisms that contribute to listening difficulties in CF. Thus, preventive and intervention strategies should consider these combined mechanisms in people with AG ototoxicity to address their SiN problems.

Vestibular schwannomas (VS) cause vestibular function loss by mechanisms still poorly understood. We evaluated the vestibulo-ocular reflex by the video-assisted Head Impulse Test (vHIT) in patients with planned tumour resection by a trans-labyrinthine approach. The vestibular sensory epithelia were collected and processed by immunofluorescent labelling for confocal microscopy analysis of sensory hair cell subtypes (type I, HCI, and type II, HCII), calyx endings of the pure-calyx afferents, and the calyceal junction normally found between HCI and the calyx (n=23). Comparing Normofunction and Hypofunction patients, we concluded that worse vestibular function associates with decreased HCI and HCII counts in the sensory epithelia and with increased proportion of damaged calyces. A decrease in the number of HCI and calyx endings of the pure-calyx afferents was recorded to associate with age increase. Partial least squares regression (PLSR) models indicated that VS and age had independent, additive effects on vestibular function. Correlation analyses indicated that lower vHIT gains associate with lower numbers of HCI and increased percentages of damaged calyces. These data support the hypothesis that the deleterious effect of VS on vestibular function is mediated, at least in part, by its damaging impact on the vestibular sensory epithelium. They also provide further evidence for the dependency of the vestibulo-ocular reflex on HCI function and for the calyceal junction pathology as a common response of the sensory epithelium to HC stress.

Functional near infrared spectroscopy (fNIRS) is increasingly used in hearing and communication research, with advantages such as robustness to movement artifacts, improved spatial resolution, and flexibility of contexts in which it can be applied. At the same time, the field is progressively moving towards more continuous, naturalistic listening paradigms resulting in the widespread adoption of speech tracking analyses such as temporal response functions (TRFs) in electroencephalography (EEG) and magnetoencephalography (MEG) studies. However, it remains unclear whether these analyses can be applied to slower haemodynamic signals measured by fNIRS. In the present study, we investigated whether a TRF framework can similarly be applied to fNIRS data recorded during continuous speech perception. Eight participants listened to speech simultaneously while fNIRS signals were acquired in a hyperscanning setup. Speech features were regressed onto the haemodynamic responses to test the feasibility and interpretability of fNIRS-based TRFs. Prediction correlations between observed and modelled fNIRS signals across speech features were higher than those typically reported for EEG- and comparable to those reported for MEG-TRF studies. Moreover, these correlations did not overlap with a null distribution generated from triallJmismatched fNIRS data, confirming statistical significance and were slightly greater than those obtained from a conventional GLM approach. Our findings support that TRF estimation method can yield meaningful and statistically significant responses from fNIRS data. HighlightsO_LITRF modelling can be meaningfully applied to fNIRS data acquired during speech listening tasks. C_LIO_LIPrediction correlations between actual and modelled fNIRS signals were above chance level, with values comparable to previous EEG/MEG studies. C_LIO_LITRFs explained more fNIRS variance than a conventional GLM approach. C_LI

Cochlear implant (CI) users typically experience difficulties perceiving musical harmony due to a restricted spectro-temporal resolution at the electrode-nerve interface, resulting in limited pitch perception. We investigated how stimulus parameters affect discrimination of complex-tone triads (three-voice chords), aiming to identify conditions that maximize perceptual sensitivity. Six post-lingually deafened CI listeners completed a same/different task with harmonic complex tones, while spectral complexity, voice(s) containing a pitch change, and temporal synchrony (simultaneous vs. sequential triad presentation) were manipulated. CI listeners discriminated harmonically relevant one-semitone pitch changes within triads when spectral complexity was reduced to three or five components per voice, with significantly better performance for three-component compared to nine-component tones. Sensitivity was observed for pitch changes in the high voice or in both high and low voices, but not for changes in only the low voice. Single-voice sensitivity predicted simultaneous-triad sensitivity when controlling for spectral complexity and voice with pitch change. Contrary to expectations, sequential triad presentation did not improve discrimination. An analysis of processor pulse patterns suggests that difference-frequency cues encoded in the temporal envelope rather than place-of-excitation cues underlie perceptual triad sensitivity. These findings support reducing spectral complexity to enhance chord discrimination for CI users based on temporal cues.

In a loudness-matching paradigm, a reduction in the loudness of sounds with bandwidths less than one-half octave compared to a tone of equal sound pressure level has been observed previously for five-tone complexes at 60 dB SPL centered at 1 kHz. Here, this loudness-reduction phenomenon is explored using band-limited noise across wide ranges of frequency and level. Additionally, these measurements are simulated by a model of loudness judgement based on neural ensemble averaging (NEA), which serves as a proxy for central auditory signal processing. Multi-frequency equal-loudness contours (ELC) were measured for each of the adult participants (N=100) with pure-tone average (PTA) thresholds that ranged from normal to moderate hearing loss using a categorical-loudness-scaling (CLS) paradigm. Presentation level and center frequency of the test stimuli were determined on each trial according to a Bayesian adaptive algorithm, which enabled multi-frequency ELC estimation within about five minutes of testing. Three separate test conditions differed by stimulus type: (1) pure-tone, (2) quarter-octave noise and (3) octave noise. For comparison, loudness judgements for all three stimulus types were also simulated by the NEA model, which comprised a nonlinear, active, time-domain cochlear model with an appended stage of neural spike generation. Mid-bandwidth loudness reduction was observed to be greatest at moderate stimulus levels and frequencies near 1 kHz. This feature was approximated by the NEA model, which suggests involvement of an early stage of the central auditory system in the formation of loudness judgements.

Numerical abilities are widespread in the animal kingdom and are not exclusive to humans. Domestic chicks (Gallus gallus) have been shown to discriminate numerosities spontaneously, but prior research has focused exclusively on the visual modality. Whether chicks can discriminate numerical information in the auditory domain remains unknown, despite evidence that they can perceive other auditory features such as tone and rhythm. In this study, we investigated spontaneous numerical discrimination in the auditory modality in naive domestic chicks. In Experiment 1, newly-hatched chicks were tested for their ability to discriminate between two auditory sequences differing in numerosity (4 vs. 12 identical sounds), with and without controlling for continuous variables such as duration and total sound amount. Experiment 2 examined chicks filial imprinting responses to familiar or unfamiliar numerosities. Experiment 3 controlled for potential spontaneous preferences for a single longer sound versus a shorter one. Our results showed a preference for the 12-sound sequence only when duration and total sound amount were not matched. When these continuous variables were controlled, no spontaneous numerical preference emerged. Experiment 2 revealed an overall preference for the 12-sound sequence regardless of imprinting conditions, while Experiment 3 confirmed that chicks do not have an inherent preference for longer sounds. These findings suggest that chicks are sensitive to overall magnitude in the auditory domain but do not spontaneously discriminate numerical differences when other continuous variables are held constant. Future studies will explore how specific stimulus features, such as heterogeneity of sounds, influence these preferences.

Background Functional neurological disorder (FND) is a common neurological condition characterised by symptoms which vary characteristically with attention. In the sensory realm, these symptoms frequently take the form of 'phantom' perception in the absence of sensation. While the condition is generally regarded not to cause auditory symptoms, tinnitus is a phantom perception which varies with symptom-focused attention, and is suggested to have similar underlying mechanisms to those proposed for FND. Based on this, we hypothesized that tinnitus might reflect the same underlying process as FND, and that it would therefore be more common in people with FND (pwFND). Methods Using an international database, we compared the proportions of pwFND who reported tinnitus with a control group. To ensure that observed differences were not attributable to agreement bias in symptom reporting, we also conducted an experiment where pwFND and controls were asked to report which symptoms they had experienced in the past month, 14 of which were symptoms of FND, and 7 of which were unrelated. Results Rates of tinnitus were significantly higher in the FND group (54% HDI 50 - 57%, n=732) than the control group (17% HDI 8.5 - 25%, n=59). In the symptom reporting experiment, pwFND (n=38) reported more FND-related symptoms than controls (n=38), but there was no between-group difference in reporting of non-FND related symptoms. Discussion Based on the markedly higher prevalence of tinnitus in pwFND than controls, and the substantial overlap in mechanisms and phenomenology, we believe tinnitus should be considered a possible symptom of FND, where both conditions reflect a failure of symptom resolution after incitement by a peripheral stimulus.

Spiral ganglion neurons (SGNs) are the primary auditory afferents in the inner ear. These neurons degenerate in response to a number of conditions, including auditory neuropathies, concussions, and aging. Research to assess the extent of degeneration and to test the efficacy of protective or rehabilitative strategies requires quantification of SGNs from tissue sections. However, manual counting of SGNs can be arduous and time-consuming due to dense crowding and the lack of reliable nuclear-specific labels. SGNs receive afferent input via GluA2-containing AMPA receptors. As the Gria2 transcripts that code for GluA2 must undergo RNA editing to ensure calcium impermeability, we hypothesized that SGNs would express high levels of the adenosine deaminase acting on RNA (ADAR) enzyme ADARB1. Here we confirm enriched expression of Adarb1 in SGNs via in situ hybridization and show that anti-ADARB1 antibodies robustly label the nuclei of both type I and type II SGNs in cochlear sections from young and aged mice. Neuronal specificity was confirmed using antibodies against neurofilament heavy chain (NFH), human antigen D (HuD), GATA binding protein 3 (GATA3), and SRY-box 2 (SOX2). A blinded investigator manually counted SGNs via NFH staining, and these were compared to automated counts of ADARB1-positive nuclei using the analyze particles function in ImageJ. A concordance correlation coefficient and Bland-Altman analysis demonstrated strong agreement between the manual and automated counts. Additionally, immunolabeling of ADARB1 in macaque and human temporal bone sections confirm robust labeling of SGN nuclei, suggesting broad utility of ADARB1 immunolabeling for automated counts of SGNs across species.

Computational bioacoustics has seen significant advances in recent decades. However, the rate of insights from automated analysis of bioacoustic audio lags behind our rate of collecting the data - due to key capacity constraints in data annotation and bioacoustic algorithm development. Gaps in analysis methodology persist: not because they are intractable, but because of resource limitations in the bioacoustics community. To bridge these gaps, we advocate the open science method of data challenges, structured as public contests. We conducted a bioacoustics data challenge named BioDCASE, within the format of an existing event (DCASE). In this work we report on the procedures needed to select and then conduct useful bioacoustics data challenges. We consider aspects of task design such as dataset curation, annotation, and evaluation metrics. We report the three tasks included in BioDCASE 2025 and the resulting progress made. Based on this we make recommendations for open community initiatives in computational bioacoustics.

Abstract Background Understanding the phenotypic spectrum of disease-associated genes is essential for accurate diagnosis and targeted therapy. FRMPD4 (FERM and PDZ Domain Containing 4) has previously been associated with intellectual disability and epilepsy. However, its potential role in non-syndromic hearing loss has not been explored. Methods We performed genetic analysis in two unrelated families presenting with non-syndromic sensorineural hearing loss, identifying maternally inherited missense variants in FRMPD4. Clinical phenotyping included audiological assessment and evaluation for neurodevelopmental involvement. Cross-species expression analyses were conducted in Drosophila, zebrafish, and mouse. Functional characterization included quantitative evaluation of sound-evoked responses in Drosophila nicht gut hoerend (ngh) mutants, assessment of neuronal development and acoustic startle responses in zebrafish loss of function models, and morphological cochlear analyses with auditory brainstem response measurements in knockout mice. Results Three affected males from two unrelated families presented with prelingual, bilaterally symmetrical sensorineural hearing loss, with confirmed congenital onset in one individual and no evidence of neurodevelopmental abnormalities. Cross-species analyses demonstrated evolutionarily conserved expression of FRMPD4 in auditory structures. In Drosophila, quantitative analysis of sound-evoked responses in ngh mutants revealed impaired auditory function. Zebrafish loss of function models exhibited reduced neuronal populations in the otic vesicle and posterior lateral line, abnormal neuromast development, and diminished acoustic startle responses. In mice, Frmpd4 knockout resulted in high-frequency hearing loss and cochlear abnormalities consistent with the human phenotype. Conclusions Our findings expand the phenotypic spectrum of FRMPD4 to include non-syndromic sensorineural hearing loss and establish its evolutionarily conserved role in auditory function. These results have direct implications for genetic diagnosis and variant interpretation in patients with hearing loss.

Variable recovery in vestibular rehabilitation underscores the need for objective biomarkers to identify patients at risk of poor clinical outcomes. This study aimed to establish proof of concept for a multidimensional prognostic framework using structural cervical vestibular evoked myogenic potential (cVEMP) and functional modified Clinical Test of Sensory Interaction on Balance (mCTSIB) markers to predict therapeutic success. This prospective cohort study was conducted at a tertiary rehabilitation center between June 2023 and May 2025. Participants were adults with peripheral vestibular disorders, including unilateral vestibular dysfunction, Meniere disease, or superior semicircular canal dehiscence. All participants underwent a customized five-session vestibular rehabilitation protocol. Primary outcomes were subjective clinical success, defined as an 18-point reduction in Dizziness Handicap Inventory (DHI) score, and functional success, defined as a 3-point increase in Dynamic Gait Index score. Among 30 participants (mean age 60.8 years; 77% female), the rehabilitation protocol was associated with significant improvements in mean DHI (53.7 to 37.8; P = .003) and Dynamic Gait Index (19.5 to 22.1; P = .003) scores. While 83% of participants showed raw DHI improvement, only 37% achieved the 18-point minimal clinically important difference. Notably, no participants in the bilateral cVEMP absence group achieved subjective success, compared with 52.6% in the bilateral present group (P trend = .08). Multivariable logistic regression identified baseline DHI severity as an independent predictor of success (odds ratio, 1.05; 95% CI, 1.00-1.10; P = .04). Functional gait success was significantly correlated with baseline vestibular and visual preference ratios. These findings suggest that baseline otolithic structural integrity is a primary determinant of subjective recovery. Bilateral structural loss may represent a "structural floor" where meaningful relief is physiologically limited despite functional gains. These results support a precision-based model using structural and sensory biomarkers to tailor rehabilitation

BackgroundHow does neuronal activity change as an animal transitions from being awake to a state of general anesthesia? Previous studies used C. elegans to investigate awake and anesthetized states, emergence from anesthesia, and to establish metrics characterizing how system-wide neuronal dynamics differ under these conditions. This study employs a new technique to image pan-neuronal activity in C. elegans continuously during induction of anesthesia with isoflurane. MethodsC. elegans worms expressing pan-neuronal nuclear RFP and cytosolic GCaMP6s were imaged with light sheet microscopy to measure single cell activity in the majority of neurons in the animals head during induction via isoflurane exposure. Stable concentrations of isoflurane were maintained throughout the experiment by measured flow vaporization of isoflurane into a specially designed gas enclosure compatible with the imaging system. Building on our previous work investigating emergence from anesthesia, we analyzed ensemble neuronal activity, spectrograms of frequency over time, and metrics of information flow between neurons. ResultsInduction of isoflurane anesthesia caused a progressive reduction in neuronal activity over the course of 40 minutes. Spectrograms indicated a loss of bulk signal power across all frequencies, notably in low frequencies too. State Decoupling and Internal Predictability were among the most useful metrics for discriminating the anesthetized state, demonstrating induction kinetics that are the inverse of emergence. However, each animal does not arrive at the anesthetized state at the same time; response times are highly individualized. ConclusionsInformation metrics of neurodynamic activity demonstrate that isoflurane induction results in a gradual increase in neuronal disconnection and disorganization. Thus, at the level of individual neuron connectivity and system dynamics, the induction of anesthesia in C. elegans nematodes is in essence the reverse of emergence. Induction however occurs more rapidly and shows marked variability between individuals. Future genetic studies will show which molecular targets define sensitivity to volatile anesthetics like isoflurane. Summary StatementIsoflurane-induced unconsciousness is a common phenomenon across species. Does the induction of anesthesia arise by distinct state transitions, or through gradual changes in system dynamics when activity is measured at the level of individual neurons?

Language impairments in aphasia are characterized by various representational disruptions that may be reflected in discourse production. This research examines the capacity of transformer-based language models, particularly GPT-2, to serve as a computational framework for analyzing variations in aphasic narrative speech. A longitudinal dataset of narrative speech samples collected at six time points from individuals with aphasia (N = 47) was utilized as part of an intervention study. All transcripts were processed via the GPT-2 language model to obtain activation values from each of the 12 transformer layers. Statistically significant differences in activation magnitude across aphasia subtypes were found at every layer (all p < .001), with the most pronounced effects in the deeper layers. Pairwise Tukey HSD tests revealed consistent distinctions between Brocas aphasia and both Anomic and Wernickes aphasia, suggesting a shared activation profile between the latter two. Longitudinal tests revealed significant changes over time, especially in the final three layers (10-12). These findings suggest that transformer-based activation patterns reflect meaningful variation in aphasic discourse and could complement current diagnostic tools. Overall, GPT-2 provides a scalable tool to model representational dynamics in aphasia and enhance the clinical interpretability of deep language models.

ObjectiveThe objective of this study is to assess the quality, empathy, and readability of large language model (LLM) responses regarding otologic questions from patients as they compare to verified physician responses in other patient-driven forums. This study aims to predict the potential utility of LLMs in patient-centered communication. Study DesignComparative study SettingsInternet MethodsA sample of 49 otology-related questions posted on Reddit r/AskDocs1 between January 2020 and June 2025 were selected using search terms including "hearing loss," "ear infection," "tinnitus," "ear pain," and "vertigo." Posts were retrieved using Reddits "Top" filter. Each question was answered by a verified doctor on Reddit and three AI LLMs (ChatGPT-4o, ClaudeAI, Google Gemini). Responses were scored by five evaluators. ResultsCommon otologic concerns posed in patient questions were otalgia (38.7%), vertigo (28.6%), tinnitus (24.5%), hearing loss (22.4%), and aural fullness (20.4%). LLM responses were longer than physician responses (mean 145 vs 67 words; p < .05) and rated higher in quality (10.95 vs 9.58), empathy (7.26 vs 5.18), and readability (4.00 vs 3.73); (all p < .05). Evaluators correctly identified AI versus physician responses in 89.4% of cases with higher sensitivity for detecting physician responses (93.5%). By Flesch-Kincaid grade level, ChatGPT produced the most readable content (mean 7.25), while ClaudeAI responses were more complex (11.86; p < .05). ConclusionLLM responses received higher ratings in quality, empathy, and readability than those of physicians in response to a variety of otologic concerns. When appropriately implemented, such systems may enhance access to understandable otologic information and complement clinician-delivered care.

Age-related hearing loss (ARHL) is a rapidly growing public health concern, affecting two-thirds of adults over 65 years old, with no effective therapeutics available. As the aging population grows at an unprecedented rate, the burden of ARHL will only increase. The causes of ARHL are multifactorial, but an understudied major contributor is glial dysfunction. The auditory nerve (AN) conducts sound from the cochlea to the brainstem and holds a diverse population of immune cells and myelinating glia. As the AN fibers bundle together within the cochlea to project to the brainstem, they are first myelinated by Schwann cells in the peripheral AN, then myelinated by oligodendrocytes in the central AN. The region where myelination shifts from Schwann cells to oligodendrocytes is the glial transition zone (GTZ), located in the cochlear modiolus, creating a unique biological niche. While central-peripheral interfaces are recognized in other cranial nerves, the AN GTZ is understudied. This region integrates the peripheral and central microenvironments within the confined bony cochlea, positioning it as a niche for glial dysfunction in pathological conditions, such as aging. We hypothesize that the GTZ is a site of enhanced glial dysfunction contributing to age-related AN demyelination, an important contributor to ARHL. We evaluated this in an ARHL mouse model combining RNA-sequencing, quantitative immunohistochemistry, and 3D high-resolution imaging. We examined the AN GTZ from human temporal bone donors. RNA-sequencing of the AN revealed age-associated increases in abnormal myelination/glial function and inflammation. There was a significant age-dependent increase in Iba1+ macrophages/microglia, with accumulation at the AN GTZ, and an increase in cellular volume and surface area, suggesting greater age-related activation. Macrophages/microglia contained significantly more internalized myelin debris in the AN (peripheral, central, and GTZ) with aging. More importantly, we found structurally intact myelin within macrophages/microglia only at the GTZ, suggesting a unique microenvironment at the GTZ altering phagocytic activity in aging. Together, our data suggest that the GTZ, a previously unrecognized central-peripheral interface, is a critical site of immune-glial interactions and especially vulnerable to age-related demyelination and neuroinflammation. This study highlights the GTZ as a potential target for preserving AN myelination and mitigating ARHL.