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

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.

Many perceptual skills improve with a few days of training. However, weeks or months of practice may be required to reach a level of expertise on complex tasks (Watson, 1980). Here, we explored how gerbils attain expertise on a difficult task: amplitude modulation (AM) rate discrimination at very shallow AM depths, similar to the depths used during vocal communication. Using an appetitive Go-Nogo procedure, we first trained 6 gerbils to perform an AM discrimination task (Nogo: 4 Hz; Go: 4.25-10 Hz) at a depth of 0 dB (re: 100% depth). Animals were then trained to perform AM discrimination at successively shallower depths, from -3 to -18 dB, requiring an average of 5-10 days of practice to reach a performance metric of d[≥]1 for each depth. Finally, we determined that AM discrimination thresholds were nearly identical between 0 to -12 dB, and only slightly elevated at -15 dB. Improvements in performance were accompanied by a large reduction in response time during procedural learning, and a gradual reduction of response time during perceptual learning, even as AM depth became shallower (i.e., more difficult). The shallowest depth at which gerbils displayed peak performance on the AM discrimination task is similar to their lowest AM depth detection thresholds. These results suggest performance on challenging auditory perceptual tasks require prolonged practice, and is accompanied by increased automaticity (i.e., lower response time) that stabilizes once expertise is achieved.

Musical rhythm is often experienced with a periodic beat, serving as a temporal reference for coordination with the rhythm. Thus far, models of beat processing have mainly relied on representing sensory inputs as patterns of onset timing, with limited consideration of other sensory features. Here, we challenge this view by showing that the internal representation of beat is affected by other temporal features of the stimulus beyond onset timing alone. We recorded electroencephalography (EEG) while participants listened to rhythmic sequences designed to elicit a beat. Across conditions, we manipulated the duration of the tones conveying the rhythms, while keeping all other parameters identical, including overall intensity, speed, and rhythmic pattern structure. Crucially, the beat periodicity was enhanced in neural activity with increased sound duration, even though the beat periodicity was not prominent in the acoustic features, thus ruling out basic sensory confounds. These results demonstrate the preferential role of longer sound durations in fostering temporal scaffolding processes that integrate fast rhythmic inputs into behavior-relevant internal structures such as the beat. More generally, our findings are compatible with a holistic processing account whereby a range of features beyond onset timing may be integrated into a neural representation of rhythm. Graphical Abstract: Fig. 2EEG was recorded while listeners heard rhythmic sequences eliciting a beat. Sound duration (sonic duty cycle) was varied across four conditions while speed, pattern, and intensity stayed constant. Beat-related EEG responses increased with longer sounds, and were enhanced in all conditions compared to auditory nerve model envelopes, which did not show prominent energy at the beat periodicity, ruling out sensory confounds. Results support holistic rhythm processing beyond onset timing alone. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/721298v1_fig2.gif" ALT="Figure 2"> View larger version (27K): org.highwire.dtl.DTLVardef@10a0599org.highwire.dtl.DTLVardef@f5a95forg.highwire.dtl.DTLVardef@42d1ceorg.highwire.dtl.DTLVardef@dc58a7_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 2.C_FLOATNO EEG and auditory nerve model output analysis based on magnitude spectrum and autocorrelation. Each row represents a duty cycle condition. The two columns on the left represent the magnitude spectrum-based analysis. The first column represents the group-level averaged magnitude spectra at a pool of fronto-central electrodes, across conditions. Beat-related frequencies are shown in red, and beat-unrelated frequencies are shown in blue. Scalp topographies of the neural activity measured at the average magnitudes of beat-related (in red circle) and unrelated (in blue circle) frequencies are represented as insets. The second column represents the normalized magnitude spectra obtained from the auditory nerve model output for each duty cycle sequence. The two columns on the right represent the autocorrelation-based analysis (for visualization purposes, only a subset of lags from 0 to 2.4 s corresponding to the pattern duration is shown). The first column represents the group-level averaged autocorrelation function measured from the same pool of fronto-central electrodes, across conditions. Beat-related lags are shown in red, and beat-unrelated lags are shown in blue. The second column represents the autocorrelation function of the auditory nerve model output for each duty cycle sequence. C_FIG

When hearing fails, stimulation of the auditory nerve by electrical cochlear implants (eCIs) partially restores hearing, with most eCI users achieving open speech understanding. However, the broad current spread from each electrode limits frequency coding and speech understanding in daily situations with background noise. Spatially confined optogenetic stimulation by future optical cochlear implants (oCIs) improves frequency coding but millisecond closing kinetics of channelrhodopsins (ChRs) might limit temporal coding. Here, we evaluated the utility of fast-closing ChR f-Chrimson for processing temporal information in the auditory system of Mongolian gerbils. We recorded neural activity in the inferior colliculus evoked by f-Chrimson-mediated optogenetic stimulation of the cochlea. F-Chrimson enabled energy-efficient stimulation of the auditory pathway at rates [≥]150 Hz, outperforming the slower ChR variants CatCh (blue) and ChReef (green). Energy thresholds for activation of the auditory pathway were in the low {micro}J range, between ChReef (sub-{micro}J) and CatCh. Dynamic range and frequency selectivity were comparable to previous observations with CatCh and outperformed electrical stimulation. In conclusion, employing fast-gating ChRs harnesses improved spectral coding without degrading temporal coding. The Paper ExplainedO_ST_ABSProblemC_ST_ABSElectrical cochlear implants (eCIs) partially restore speech comprehension in most of 1 million otherwise severely deaf people. However, most CI-users face challenges hearing in daily situations. Spectrally more selective stimulation of the auditory nerve by optical cochlear implants (oCIs) promises to overcome this limitation. However, the closing kinetics of channelrhodopsins (ChR) limit the temporal bandwidth of bionic sound coding. Improving the ChR properties and evaluating temporal coding remain major objectives for developing hearing restoration by oCI. ResultsHere, we evaluate the utility of waveguide-based oCI using the fast-closing ChR Chrimson (f-Chrimson) for encoding of temporal, spectral and intensity information by multi-electrode-array (MEA) recordings from the midbrain. We compare f-Chrimson-mediated bionic coding to acoustic coding as well as to previous data acquired with optogenetic stimulation using other ChRs and with electrical stimulation. F-Chrimson enabled energy-efficient stimulation of the auditory pathway at rates [≥]150 Hz, outperforming the slower ChR variants CatCh (blue) and ChReef (green). Intensity and frequency coding were comparable to previous observations with CatCh and outperformed electrical stimulation. ImpactThis study demonstrates near physiological temporal coding with the fast-closing ChR f-Chrimson, indicating that improved spectral coding by oCI is not traded off by poor temporal fidelity.

PurposeTo characterize the frequency-dependent bioimpedance properties of major ocular tissues in intact ex vivo porcine eyes under simulated surgical conditions and evaluate tissue separability at discrete frequencies. MethodsBioimpedance spectra were acquired from sclera, corneal epithelium, iris, lens, vitreous, and retina in intact ex vivo porcine eyes using a two-electrode probe and a precision LCR meter over 5 kHz to 1 MHz. Measurements were obtained under balanced salt solution and ophthalmic viscosurgical device conditions. Probe-tissue contact was verified by microscope visualization and optical coherence tomography. Tissue separability at 5, 50, 100, and 900 kHz was evaluated using global and pairwise statistical comparisons, effect sizes, and ROC-based separability metrics. Robotic-stabilized and handheld measurements were also compared. ResultsOcular tissues demonstrated distinct, frequency-dependent impedance magnitude distributions. Across sampled frequencies, 60% to 80% of tissue pairs showed significant differences after multiplicity correction. Median pairwise effect sizes ranged from Cohens d = 0.48 at 5 kHz to 1.04 to 1.06 at 50 to 100 kHz. Median ROC-based separability was 0.91 at 5 kHz and 0.76 to 0.77 at 50 to 900 kHz. Robotic-stabilized measurements showed lower variance than handheld measurements, although tissue-specific impedance ranges and frequency-dependent trends were preserved across acquisition modes. ConclusionsMajor ocular tissues exhibit reproducible, frequency-dependent bioimpedance signatures in intact ex vivo eyes under simulated surgical preparation. These findings establish a physiologically relevant ocular impedance reference dataset and support bioimpedance as a complementary modality for tissue differentiation in ophthalmic microsurgery.

Elite athletes exhibit sport-specific neural adaptations, yet it remains unclear whether such changes reflect general effects of training or the unique demands of individual sports. Skiing requires postural control and whole-body coordination under dynamically unstable environments, placing high demands on somatosensory processing and sensorimotor integration. The present study aimed to identify structural brain characteristics specific to elite skiers by comparing them with athletes from other sports disciplines and non-athletes. T1-weighted MRI data were analyzed using voxel-based morphometry in 13 skiers, 23 non-ski control athletes and 25 non-athletes. Whole-brain analysis comparing skiers with non-ski athletes revealed a significant cluster showing greater gray matter volume in skiers compared with non-ski athletes in the left postcentral gyrus, extending into the superior parietal lobule. The identified cluster primarily encompassed cytoarchitectonic Areas 2 and 5L. These regions are involved in higher-order somatosensory processing and multisensory integration. Importantly, region-of-interest analysis demonstrated that gray matter volume within this cluster was greater in skiers compared with non-ski athletes and non-athletes, with no difference between non-ski athletes and non-athletes. These findings highlight the relative prominence of structural adaptations within somatosensory-parietal networks, reflecting the unique integration of proprioceptive and other sensory information required for elite skiing. Overall, these findings provide evidence for sport-specific structural brain differences in elite athletes and highlight the importance of somatosensory and parietal regions in sensorimotor integration relevant to skiing. These findings may have implications for understanding neural markers of expertise and may inform future approaches to training and performance evaluation in skiing.

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.

Understanding speech in noisy environments (SPIN) is an important everyday ability, and engaging in musical activities has been proposed as a factor that may support this ability. However, the cognitive mechanisms underlying a potential musical advantage in SPIN perception remain unclear. Here we investigated whether musical sophistication is associated with better SPIN perception in a large population-based sample, and whether this relationship is mediated by auditory working memory (AWM), verbal working memory (VWM), or non-verbal intelligence. We recruited 203 participants and measured SPIN perception at both word and sentence levels. Musical sophistication was assessed using the Goldsmiths Musical Sophistication Index (Gold-MSI). AWM was measured using delayed matching of tone frequency or the modulation rate of amplitude modulated white noise, VWM was based on backward digit span task, and non-verbal intelligence used matrix reasoning. Mediation analyses revealed that AWM fully mediated the relationship between musical sophistication and SPIN perception, whereas VWM showed no mediation effect. Non-verbal intelligence showed a partial mediating effect. Additional control analyses using structural equation modelling revealed that the indirect effect through AWM remained significant after accounting for age, hearing thresholds, and non-verbal intelligence. Together, these findings suggest that individuals with greater musical sophistication demonstrate better daily life listening abilities, and that superior auditory working memory may be the key cognitive mechanism underlying this advantage.

Calibration of sound localization behavior in species with mobile eyes requires not only accurate visual input but also accurate oculomotor signals across the lifespan. The recent discovery of eye movement-related eardrum oscillations suggest that oculomotor signals may be incorporated into auditory processing at the level of the ear. One inference of this discovery is that individual variation in such signals might be correlated with individual variation in sound localization accuracy. Here, we tested this hypothesis in humans with normal hearing. We discovered that there is considerable variation in the accuracy of sound localization (here, saccades to sounds) even in normal individuals: median horizontal errors ranged from 2-6{degrees}, and median vertical errors could be as large as 36{degrees}. We separated the subject pool into groups with "good" performance (median vectorial error < 8{degrees}) vs "poor" performance (median vectorial error > 10{degrees}) and evaluated their respective EMREOs. The EMREOs differed across the two groups in both horizontal and vertical dimensions, in how saccade amplitude vs. initial eye position was encoded, and across time with respect to the saccade. These results are consistent with the interpretation that EMREOs are associated with underlying processes that ensure the accuracy of sound localization. HIGHLIGHTSO_LIThe accuracy of eye movements to look at sounds varied across individuals, with median errors spanning a greater than 10-fold range. This range is surprising given that the participants passed screening for normal hearing. C_LIO_LI"Good" vs "poor" sound localizers exhibited differences in their eye movement-related eardrum oscillations (EMREOs) C_LIO_LIEMREOs differed in both horizontal and vertical sensitivity, for both saccade amplitude and initial eye position, and the differences varied in timing with respect to saccade onset. C_LIO_LIWe interpret the results under the theory that poor sound localization may be a consequence of poor eye movement encoding, without which linking visual and auditory space is likely inaccurate. C_LI

Electrical transmission is mediated by intercellular channels that cluster into structures known as gap junctions (GJ). In vertebrates, GJ channels are encoded by the gene family of connexin (Cx) proteins that assemble as hexamers, termed hemichannels, in the pre- and postsynaptic membranes, and that subsequently dock to form GJ channels. Auditory contacts on the fish Mauthner cells serve as model to study the properties and organization of vertebrate electrical synapses. Electrical transmission at these synapses is mediated by multiple co-existing GJs at which the presence of intercellular channels is regulated by a molecular scaffold. Zebrafish contain four homologs of the neuronal Cx36: Cx35.5 and Cx35.1 (gjd2a and b, respectively), and Cx34.1 and Cx34.7 (gjd1a and b). Cx mutations suggested that GJs are formed by heterotypic channels made of presynaptic Cx35.5 and postsynaptic Cx34.1. Using transgenic fish in which Cxs were tagged, we found that a second Cx, Cx34.7, is present together with Cx34.1 on the postsynaptic side at some but not all GJs at these terminals. When exogenously expressed, both Cx34.1 and Cx34.7 formed heterotypic functional channels with Cx35.5, each with substantially different voltage-dependent properties, indicating they can serve differential functions. However, we previously demonstrated that electrical transmission is lost in Cx34.1 but not Cx34.7 null mutants, suggesting that Cx34.7 cannot compensate for the loss of Cx34, despite the intrinsic ability of Cx34.1 and Cx34.7 to create functional channels. The findings reveal an unanticipated functional organization in the electrical synapse, where Cx34.1 is obligatory and Cx34.7 accessory, roles that appear to be defined by the postsynaptic molecular scaffold, with two postsynaptic Cxs possibly assembling under specific functional contexts. Thus, our results indicate that electrical synapses share an organizational motif with chemical synapses, akin to how they combine postsynaptic receptor types to modify synaptic function.

Zebrafish (Danio rerio) are an important vertebrate model for vision and neuroscience research. In the larval stages, the aquatic species begins to elicit the optomotor response (OMR) to stabilize themselves in water -- a behaviour that may be exploited in the laboratory to measure visual acuity. However, up to now, the measurement of the OMR in juvenile and adult zebrafish has been limited due to their behavioural complexity. Here, we optimize a protocol to assay zebrafish aged between 4 and 9 weeks-post-fertilization, by displaying sinusoidal gratings parallel to the zebrafish eye to elicit a robust OMR. We assessed the visual spatial-frequency tuning function of an environmentally induced myopia model to confirm the sensitivity and robustness of the protocol. Additionally, we show the OMR is sensitive to the contrast and temporal resolution of the sinusoidal gratings. Furthermore, we found that the time between stimulus presentations impact the spatial-frequency tuning function likely as time is required for zebrafish to return to baseline swimming after eliciting the OMR. Finally, we found that the OMR after ten versus twenty seconds of stimulus onset appears comparable; indicating that robust OMR responses in zebrafish can be elicited through relatively short stimulus presentations. Through the experiments conducted, we present an optimized protocol specific to zebrafish. The protocol may be used to follow the progression or treatment efficacy of progressive neurological disorders including specific visual disorders and higher brain functions with visual endophenotypes. Ultimately, this protocol allows for high-throughput robust measures of visual and neural function in zebrafish.

AO_SCPLOWBSTRACTC_SCPLOWVision can shape auditory perception, especially when visual cues occur at different times and locations than sounds. Simultaneous but spatially misaligned lights bias the perceived location of a sound--a phenomenon known as the ventriloquism effect. Temporally misaligned lights can also affect the latency of auditory responses. However, it remains unclear how multiple visual stimuli that differ from sounds in both space and time jointly influence localization behaviour. We investigated how visual distractors, spatially misaligned by 10{degrees}, presented before and/or during a target sound influence localization accuracy and response latency in a rapid head-pointing task. Human listeners localized brief (150 ms) broadband noise bursts with an average root-mean-square error of 5{degrees} and a baseline latency of 252 ms. Simultaneous visual cues induced the ventriloquism effect, in which the perceived sound location was biased by 1.8{degrees}. Response latency also increased by 21 ms (273 ms). Preceding visual stimuli (2 s duration) did not induce a bias, but increased latency by 55 ms (307 ms). Introducing a 200 ms gap between the preceding light and the sound reduced this latency increase to 24 ms (276 ms), still not inducing a significant bias. When we presented both a preceding and a simultaneous light on opposite sides of the sound, localization reflected the bias induced by the simultaneous light (1.8{degrees}) and the latency increase induced by the preceding light (by 48 ms). These findings reveal a dissociation in audiovisual integration: preceding visual stimuli primarily influence when a sound is responded to (latency), while simultaneous stimuli influence where it is perceived (accuracy). This supports causal inference models of multisensory integration and suggests distinct underlying mechanisms for spatial and temporal processing of sounds in sensorimotor circuits.

When hearing fails, cochlear implants (CIs) partially restore auditory perception. Yet, poor coding of spectral information remains a bottleneck as each electrode broadly activates the auditory nerve. As light can be more conveniently confined, optical (o)CIs present a promising alternative. Here, we combined expression of the potent channelrhodopsin ChReef in spiral ganglion neurons (SGNs) and oCIs based on 5-10 green LED in gerbils. We characterized the oCI encoding of intensity and spectral information by ChReef-SGNs using recordings from the central nucleus of the inferior colliculus (ICC). ChReef aligned light sensitivity of SGNs well with the radiant fluxes provided by individual LEDs: ICC-activity had thresholds <200 nJ and reached a maximum close to that achieved with 46 dB tones. Multichannel oCIs enabled tonotopically ordered and spectrally distinct stimulation indistinguishable from acoustic stimulation for up to moderate activity levels. Some LEDs elicited >1 spectral peaks for stronger intensities. Representational Similarity Analysis and Linear Discriminant Analysis of ICC activity indicated improved channel discriminability of optical over electrical stimulation. In summary, {micro}J oCI stimulation achieves near-physiological spectral resolution. The Paper ExplainedO_ST_ABSProblemC_ST_ABSElectrical cochlear implants (eCIs) partially restore speech comprehension in most of >1 million otherwise deaf users, who still face challenges hearing in daily situations. This is primarily due to poor spectral selectivity of electrical sound encoding. Spatially more confined optogenetic activation of the auditory nerve by optical cochlear implants (oCI) promises to overcome this limitation. However, a thorough characterization of bionic coding of sound information by multichannel oCI is needed to evaluate the potential for improved hearing restoration. ResultsHere, we combine the potent channelrhodopsin ChReef and 10-channel oCI based on green LEDs in gerbils and characterize their utility for encoding of spectral and intensity information by multielectrode array recordings from the midbrain. ChReef enabled activation of the auditory pathway with nano-joule thresholds and up to high levels of midbrain activity with low {micro}J radiant energy. The cochlear spread of excitation and channel discriminability for low to medium activity levels were close to what we observed with acoustic stimulation. ImpactOur work demonstrates great potential of multichannel optogenetic stimulation for encoding sound frequency information.

Introduction: Early exposure to otolaryngology (ENT) procedural skills in undergraduate medical education is limited by patient safety concerns, restricted clinical opportunities, and the cost of commercial simulators. As a result, essential ENT skills are often underrepresented in structured, hands-on curricula for medical students. Methods: We developed a low-cost, multistation ENT simulation curriculum consisting of five reproducible task trainers: ear examination and otologic procedures, mirror laryngoscopy, rigid and flexible endoscopic navigation, introductory mastoid drilling, and emergency cricothyrotomy. The curriculum was delivered as a 2-hour, faculty-led workshop during a third-year medical student otolaryngology rotation. Learners rotated through stations in small groups. Pre- and post-workshop surveys assessed self-reported anatomical familiarity, procedural confidence, and educational value using a 5-point Likert scale, with additional qualitative feedback collected. Results: All participants completed pre- and post-workshop evaluations. Learners demonstrated increased confidence across all assessed anatomical and procedural domains, including otoscopy, endoscopy, mirror laryngoscopy, mastoid drilling orientation, and cricothyroid membrane identification. Educational value ratings were high across all stations, with mean scores ranging from 4.33 to 5.00. Qualitative feedback emphasized the realism, accessibility, and benefit of hands-on practice in a low-stakes learning environment. Conclusion: This low-cost, multistation ENT simulation curriculum provides a feasible and reproducible approach for introducing foundational otolaryngology skills to medical students. The structured format and affordable models support early procedural exposure and may enhance learner preparedness prior to supervised clinical encounters, particularly in settings with limited simulation resources.

Estrogen-related receptor gamma (ESRRG), an orphan nuclear receptor with structural homology to the classical estrogen receptors, is widely recognised as a key metabolic regulator involved in mitochondrial, synaptic, and ion-homeostatic pathways. Previous clinical studies suggest a link between ESRRG and auditory function; for example, ESRRG has been associated with susceptibility to age-related hearing loss in women and implicated in congenital hearing loss. However, the biological mechanisms by which ESRRG may mediate hearing function remain largely unknown. Here, using a combination of in vivo auditory physiological recordings, immunofluorescence analyses, single hair-cell electrophysiology, and transcriptomic approaches, we characterise the phenotype of a new inner-ear conditional Esrrg knockout (Esrrg-cKO) to investigate the role of Esrrg in the auditory system. We found that Esrrg-cKO mice of both sexes develop early-onset hearing loss, as evidenced by elevated auditory brainstem response thresholds and reduced wave 1 amplitudes from two weeks of age. These auditory deficits arise from a combination of early-onset cochlear neuronal and innervation malformations, together with inner hair cell synaptic defects and delayed myelination that persist into adulthood. Furthermore, distortion product otoacoustic emissions and endocochlear potential recordings are normal in Esrrg-cKO mice, and although sensory hair cells are preserved, IHCs retain immature biophysical properties. These findings are consistent with auditory neuropathy, and together with our comparative transcriptome analyses, indicate that Esrrg is an essential molecular driver of normal cochlear innervation and maturation.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory airway disease associated with impaired mucociliary clearance and persistent inflammation. While prior work has focused on inflammatory and molecular pathways, the physicochemical properties of mucus itself remain poorly characterized. This study aimed to define compositional and biophysical features of CRS mucus that may contribute to dysfunction. Methods: A prospective cross-sectional study was conducted in 15 adults undergoing endoscopic sinus surgery (11 CRS, 4 controls). Mucus was collected from the middle meatus. Hydration was measured by lyophilization. Ionic composition was quantified using mass spectrometry. Viscoelasticity was assessed via oscillatory shear rheology. Total protein, total carbohydrate, sialic acid (Sia) and fucose (Fuc) content were quantified using enzymatic and chemical assays. Statistical comparisons were performed using nonparametric tests. Results: CRS mucus exhibited significantly higher Ca2+; and Mg2+; concentrations (approximately two-fold; p<0.05) and increased variability in hydration and ion content compared to controls. Rheology showed greater heterogeneity and a non-significant trend toward increased viscoelasticity in CRS. Total protein and carbohydrate content were not significantly different; however, the carbohydrate-to-protein ratio was significantly reduced in CRS (p=0.04). Sia content and Sia-to-carbohydrate ratio were significantly elevated in CRS (p=0.04 and p=0.002), particularly in CRS with nasal polyps. Fuc content did not differ between groups. Conclusions: CRS mucus demonstrates coordinated alterations in ionic composition and glycosylation, characterized by increased cation content, hypersialylation, and reduced carbohydrate-to-protein ratios. These changes may contribute to altered mucus properties and impaired mucociliary clearance, highlighting mucus composition as a potential therapeutic target in CRS.

PurposeAlthough electroretinography (ERG) is vital for evaluating retinal function, conventional corneal electrodes slide or detach in animals. This study aimed to investigate the effectiveness of a novel approach to ERG recording using a metal eyelid speculum for both active and reference electrodes in conjunction with a skin electrode-based ERG device. MethodsWe tested a stainless-steel eyelid speculum as both active and reference electrodes with a skin-electrode ERG system (HE-2000vet) in six healthy Japanese White rabbits. Dark-adapted rod and maximal responses and light-adapted cone and 30 Hz flicker ERGs were recorded in three weekly sessions. ResultsReproducible waveforms with identifiable a- and b-waves were obtained in every eye; rod b-waves reached 50-90 {micro}V and cone b-waves 40-55 {micro}V. Intraclass correlation coefficients revealed substantial interocular agreement and moderate-to-substantial inter-session reproducibility for b-wave amplitude and implicit time, whereas a-wave metrics were less reliable owing to lower amplitudes. The advantages of speculum electrode over corneal electrodes are that it requires no fur shaving, maintains stable contact regardless of globe orientation, and allows real-time observation. ConclusionsThis study demonstrated that an eyelid-speculum electrode is a practical, non-invasive alternative for veterinary and experimental ERG recordings, producing signal quality sufficient for longitudinal and interocular analyses while avoiding cosmetic and technical drawbacks of conventional methods.

Vestibular neurons are core elements of the pathways involved in vestibulo-motor functions, such as vestibulo-spinal and vestibulo-ocular reflexes. To meet behavioral needs, electrophysiological neuronal properties are adequately adapted to the sensory-motor computation sustaining these distinct vestibular reflexes. During frog metamorphosis, there is a complete reorganization of the posturo-locomotor system while the oculomotor system remains minimally changed, probably associated to so far unknown changes in vestibular neuronal properties. We used this unique model to investigate the central developmental mechanisms underlying such a reconfiguration of vestibular-associated behaviors. Central vestibular neurons exhibit two types of electrophysiological phenotypes: tonic neurons with a continuous discharge and phasic neurons with a transitory discharge mainly due to the activation of Kv1.1 channel. Electrophysiological recordings and Kv1.1 immunolabeling of vestibulospinal (VS) and vestibulo-ocular (VO) neurons at both larval and juvenile stages revealed that the majority of VS neurons exhibited a tonic discharge in larvae but a phasic discharge in juvenile, while VO neurons remained mainly tonic throughout development. Changes in phasic and tonic neurons proportions in VS population are partly explained by neurogenesis. But we provide evidences that an electrophysiological phenotype switch is a concomitant developmental mechanism participating in the maturation of these central vestibular neurons. All together our results showed that the maturation process in central vestibular neuronal groups is highly related to the metamorphosis-induced remodeling of vestibulo-motor functions they are involved in, with the ultimate purpose of ensuring an adequate adaptation of neuronal elements properties to the developmental changes of behavioral constrains.

Quantifying the diagnostic dispersion of inferred parameter distributions is a challenge in uncertainty-aware modeling. Scalar summaries such as credible interval width are topology-blind; fundamentally different posterior morphologies can yield identical scores, obscuring whether a parameter is precisely estimated or constrained to a range. We propose a Composite Certainty Framework that addresses this metric degeneracy by aggregating five complementary uncertainty metrics including interquartile range, standard deviation, full width at half maximum, Shannon entropy, and mass width. These metrics are aggregated through non-parametric Borda rank voting into a single, unitless consensus certainty score. Applied to a simulation-based inference pipeline for a finite-element model of the human middle ear tuned to cadaveric acoustic measurements, the framework reveals parameter-specific identifiability profiles invisible to any individual metric. It produces two actionable clinical thresholds: (1) the maximum tolerable measurement noise for reliable parameter recovery, and (2) the minimum simulation budget for posterior convergence. We demonstrated that no single metric captures all aspects of posterior dispersion, as spread-based metrics and entropy diverge systematically for clinically critical parameters, whereas their aggregation produces a consensus reflecting genuine diagnostic certainty. The framework is generalizable to any model-based diagnostic pipeline where posterior distribution not merely its coverage, but determines clinical certainty.