Jaro-Journal of the Association for Research in Otolaryngology最新文献

Purpose: Vestibular implants that target the three semicircular canal branches of the vestibular nerve can partially restore the 3-dimensional vestibulo-ocular reflex (3D VOR) in individuals disabled by bilateral vestibular hypofunction. A key goal of implant design is optimizing the number, spacing, and placement of stimulating and return electrodes to maximize response strength and selectivity. While computational models provide initial insights, empirical data are essential to validate performance.

Methods: We unilaterally implanted stimulating electrodes in each semicircular canal and positioned return electrodes both inside the labyrinth and outside the temporal bone in three female rhesus macaques. Using mixed-effects ANOVA, we quantified how electrode location influenced 3D VOR response magnitude and misalignment.

Results: We found that: (1) the deepest stimulating electrode in each canal generally yielded the strongest and most aligned responses; (2) a 600-750 µm difference in electrode position significantly impacted VOR outcomes; (3) return electrodes placed inside the labyrinth produced significantly larger VOR responses than those placed outside the temporal bone when stimulus current is constrained to levels that elicit no sign of facial nerve excitation; and (4) "near-bipolar" stimulation-using a return electrode in the same ampulla as the stimulating electrode-yielded better alignment.

Conclusion: Although including multiple stimulating electrodes per canal may lower the risk of missing the target, a VI limited to one deep stimulating electrode per canal and one common return electrode can suffice if array design and surgical technique ensure placement near the crista ampullaris. Unused stimulator channels could be repurposed in designs intended to stimulate the utricle, saccule and/or cochlea. Moreover, spatial selectivity is improved by placing return electrodes within the labyrinth or ampullae, rather than outside the temporal bone. VIs that use a single common return electrode shared by all stimulation channels could achieve better performance in the future by incorporating multiple independent return electrode channels to permit near-bipolar stimulation.

Purpose: To evaluate whether optical coherence tomography (OCT) vibrometry can differentiate causes of conductive hearing loss (CHL) following ossiculoplasty, specifically distinguishing among effusion, soft-tissue fixation, and prosthesis disconnection.

Methods: We simulated three post-surgical CHL conditions, effusion, soft-tissue fixation, and prosthesis disconnection, in a cadaveric temporal bone model (N = 10 per condition), with a partial ossicular replacement prosthesis (PORP) and cartilage graft implanted via a retrotympanic approach. A custom-built swept-source middle-ear OCT system (λ₀ = 1550 nm, Δλ = 40 nm) was used to capture cross-sectional images and mobility measurements at the umbo and center of the cartilage graft across six stimulus frequencies (500, 750, 1000, 1500, 2000, and 3000 Hz). Mobility values (point velocity normalized to sound pressure) served as input features for a Random Forest classifier. Changes in mobility from baseline were also statistically analyzed.

Results: The classifier achieved 90.9% accuracy (40/44 datasets) in differentiating conditions in leave-one-out cross-validation, and 100% when trained on the full dataset. Simulated effusion and soft-tissue fixation were associated with broadband mobility decreases of 17.5 dB and 8.0 dB, respectively, averaged across both locations. Prosthesis disconnection at the stapes and at the tympanic membrane led to low-frequency (500 and 750 Hz) mobility increases of 9.9 dB and 11.1 dB, respectively, averaged across both locations.

Conclusion: In a cadaveric model of post-surgical CHL, OCT vibrometry accurately distinguished effusion, soft-tissue fixation, and prosthesis disconnection. The ability to identify the cause of post-surgical CHL highlights OCT vibrometry's potential to assist clinical decision-making in revision surgery.

Vestibular and spiral ganglion neurons (VGNs and SGNs) developed in the inner ear, where they extend fibers to innervate the vestibular and cochlear hair cells and project centrally to the vestibular and cochlear nuclei. This review focuses on representative molecular factors that regulate key processes in the development of inner ear neurons, including their specification, differentiation, axon targeting, and functional diversification. A temporal regulatory cascade defines the initial precursors through factors such as Smarca4, Six1, Eya1, followed by Sox2. While Sox2 deletion abolishes hair cell formation, a subset of inner ear neurons transiently develops but undergoes apoptosis before birth. In contrast, Neurog1 deletion eliminates all ear-derived neurons but results in differential reductions in cochlear and vestibular hair cells. The development and survival of inner ear neurons depend on TrkB and TrkC signaling. Although deletion of TrkB and TrkC results in a complete loss of neurons, each shows distinct effects on VGN and SGN survival and innervation. Downstream of early transcriptional regulators, Neurod1 and Isl1 promote neuronal differentiation, survival, migration, and the formation of peripheral and central projections. The development of VGNs depends on at least two progenitor populations that give rise to three neuronal subtypes that differ in their innervation of vestibular hair cells but show incomplete segregation in the vestibular nuclei. In contrast, SGNs develop later and exhibit sequential segregation into four neuronal subtypes, corresponding to the two types of cochlear hair cells, with tonotopically organized projections to both the cochlea and cochlear nuclei.

Introduction: The human cochlea is encased within the otic capsule, the densest bone in the body, posing significant challenges for anatomical imaging of cochlear structures. Because of difficult access and the fragility of cochlear structures, our understanding of intracochlear anatomy has historically relied on postmortem histology. We thus have a limited understanding of human cochlear anatomy in its native, unfixed state. Clinical diagnostics for hearing loss, such as audiometry and otoacoustic emissions, offer functional assessments but fail to elucidate the often diverse underlying structural pathologies with any degree of precision.

Methods: To address the critical need for assessing the human cochlear anatomy and associated pathologies without the risk of traumatizing cochlear structures, we imaged fresh cochleae (N = 23, 15 males, 8 females) in situ soon after death through the intact round window membrane with Optical Coherence Tomography (OCT) without inserting instruments inside or opening the cochlea.

Results: Micron-resolution OCT cross-sectional images of the human intracochlear structures were acquired and compared with corresponding histology systematically to aid in the identification of fine structural features and possible pathologies. With OCT imaging, we observed varied anatomy of the organ of Corti, and developed a cochlear "integrity" rating system to differentiate healthy-appearing cochleae from various pathological states.

Conclusion: These results demonstrate the capability of OCT to non-traumatically visualize cochlear integrity, highlighting its potential as a diagnostic tool. This work shows promise in translating the ability to determine the likelihood of existing or lack of hair cells and supporting cells in live patients, which would enable appropriate targeted treatments.

Birds have contributed to important hearing-science discoveries. Examples include cochlear development, hair cell regeneration and brainstem circuit organization in chickens, sound localization in owls, vocal learning in songbirds, and cognition in parrots and corvids. Recent findings demonstrate the power and relevance of the avian cortex in studying auditory function.

Inner ear research has experienced exponential growth for the last fifty years spurring the creation of novel scientific approaches and clinical intervention strategies. Here we utilize data mining of publicly available records (PubMed, NIHReporter, and ClinicalTrials.gov) to assess the rate of inner ear research output quantitatively. We combined this approach with systematic review of published literature to understand the prevalence and monetary costs of seeking treatment for hearing and balance. The data show that the expansive growth period of inner ear research presents a new challenge for scientists and clinicians as auditory research output metrics have begun to significantly outpace vestibular research. There are unique challenges associated with diagnosing and treating patients with vestibular dysfunction that may explain some of the discrepancies in research output. A renewed enthusiasm to investigate the vestibular system may help facilitate broader understanding of the inner ear and has potential to produce improved scientific methods and clinical interventions for patients.

Purpose: Although human temporal bones suggest that cochlear synapse numbers decline with age and noise exposure, no validated diagnostic method exists. In animal models, cochlear synaptopathy is associated with reduced auditory brainstem response (ABR) wave 1 amplitude and envelope following response (EFR) magnitude for a sinusoidally amplitude modulated (SAM) tone. However, measuring SAM EFR at the optimal modulation frequency (1000 Hz) is difficult in humans. A rectangular amplitude modulated (RAM) tone may be more sensitive to synaptopathy, but this has not been validated in animals. In addition, because synaptopathy likely co-occurs with outer hair cell dysfunction (OHC), a diagnostic assay needs to be robust to abnormal auditory thresholds. The objective of this study was to evaluate the relative ability of ABR and EFR measures to predict synapse numbers in mice with varying degrees of synaptopathy and OHC dysfunction.

Methods: Distortion product otoacoustic emissions (DPOAEs), ABR, SAM EFR, and RAM EFR were recorded from 57 mice with a range of auditory thresholds and degrees of synaptopathy. Cross-validation was used to compare the relative ability of linear regression models incorporating different measures to predict synapse numbers. Predictions were confirmed histologically.

Results: RAM EFR modulated at 1000 Hz was the single best predictor of synapse numbers for broad synapse loss across frequency, while combining RAM EFR with ABR further improved predictions. In contrast, ABR best predicted focal synaptopathy. Incorporating DPOAEs improved predictions for EFR, but not ABR.

Conclusion: RAM EFR, ABR, and DPOAEs should be used in the future when predicting synapse numbers.

Age-related auditory dysfunction affects half of all individuals 60 years and older, yet its causes are poorly understood. While commonly associated with cochlear dysfunction, a growing body of literature suggests that dysfunction originating in the auditory cortex itself is also a major contributor. Here, we review recent literature that describes the effects of aging on the primary auditory cortex in humans, non-human primates, rodents, and a variety of other species. During aging, individuals with auditory cortical dysfunction experience deficits in spectral and temporal processing of sounds, resulting not only from a loss of inhibition but also from an extensive restructuring of cortical circuits. Importantly, aging in the auditory cortex is sex-dependent, yet few studies account for this variable. A lack of comprehensive knowledge on aging in the auditory cortex hinders the path toward restoring cortical function through auditory training or broader cortical rehabilitation paradigms. Thus, we propose a cohesive mechanism of aging in the primary auditory cortex that involves a complex interaction between excitatory and inhibitory neurons, which several factors can modify. These factors include input from higher-order cortical areas, such as the orbitofrontal cortex, as well as the wide-ranging effects of neuromodulators and the external sensory environment, which must be accounted for in a sex-dependent manner.

Brief acoustic tinnitus suppression (BATS) is a well-known phenomenon among tinnitus patients. Most knowledge about BATS comes from experiments applying filtered, modulated, or customized stimuli in selected patient populations. Testing BATS in clinical routine could provide valuable information for patient subtyping and assistance in treatment decision-making. Here, we investigated the feasibility of BATS tests beyond controlled experimental settings. Seventy individuals with tinnitus (29 female) were tested for BATS using white noise as part of a first consultation visit at the Interdisciplinary Tinnitus Center in Regensburg. The procedure turned out to be feasible under clinical routine conditions. Thirty-five patients (50%) reported some form of tinnitus suppression, with 6 (8.6%) reporting at least 50% reduction and 1 (1.4%) complete absence of their tinnitus percept. The degree of suppression was rated as relevant improvement by most patients. In summary, the integration of BATS assessments was feasible and provided valuable information about the patients' tinnitus.