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

Purpose: We describe a novel paradigm for evoking and measuring middle ear muscle reflex (MEMR), in which a train of broadband clicks act as probes, while a broadband noise elicitor is continuously swept in both ascending and descending sound levels. A new measure, total change, incorporates both magnitude and phase to quantify MEMR in a way that promotes meaningful averaging across a wide range of sound levels and frequencies. The aims of the study were to assess the retest reliability of the new swept-elicitor MEMR paradigm, to compare results with those obtained using traditional discrete-elicitor stimuli, and to preliminarily examine correlations with speech-in-noise performance.

Methods: MEMR was measured in 38 young, normal-hearing participants (24 female, 14 male) using both the novel swept paradigm and a more conventional paradigm with elicitor noises that were discretely varied in level. Key measures of MEMR dynamics were obtained from the swept elicitor paradigm, including maximum total change, onset and offset thresholds, hysteresis, and reflex delay. Intraclass correlation coefficients (ICCs) were used to assess repeatability, and robust linear regression was used to examine correlations with QuickSIN performance.

Results: The swept MEMR paradigm demonstrated excellent repeatability, with ICC values exceeding 0.90 for all extracted measures. MEMR thresholds from the swept elicitor correlated moderately with speech-in-noise performance.

Conclusions: Our new MEMR paradigm provides fast, repeatable measurements. Several measures of MEMR dynamics can be obtained, improving upon traditional measurement approaches. Results suggest a possible link between MEMR dynamics and speech-in-noise performance.

Purpose: Hearing loss is highly heterogeneous. Any one of hundreds of genes and dozens of cell types can be involved in the pathological processes in the auditory system. One class of hearing loss results from a reduction of the endocochlear potential (EP), a voltage maintained in the endolymph that bathes the upper surface of the sensory hair cells in the cochlea. Understanding the landscape of genes involved in reduced EP will be useful in developing targeted therapies for this type of hearing loss. Here we review these genes.

Methods: Research articles that report genes impacting EP in mutant mice were collated using several different approaches. Cell type-specific expression and patterns in their biological function were investigated.

Results: We report 55 genes associated with reduced EP as well as 43 genes shown to underlie deafness but with no change in EP. We show that of these 55 reduced EP genes, 27 are linked to deafness in humans and therefore these patient populations are candidates for having a reduced EP. We demonstrate that the expression of reduced EP genes is not clustered to a particular cell type within the stria vascularis or organ of Corti.

Conclusion: This analysis highlights the broad range of expression patterns and functions of genes involved in generating and maintaining the mammalian EP. Furthermore, the lists presented here can inform the direction of translational research for different forms of human hearing loss.

Purpose: This study aimed (1) to determine the biological basis of the interphase gap (IPG) effect and (2) to identify the most informative parameters, analytical methods, and quantitative scales for evaluating the IPG effect in human cochlear implant (CI) users.

Methods: The IPG effect was quantified using multiple parameters, analytical methods, and quantitative scales (three combinations using linear or logarithmic scales for the input and output variables) across three pediatric CI groups with differing cochlear nerve (CN) anatomy: children with cochlear nerve deficiency (CND), GJB2 mutations, and idiopathic sensorineural hearing loss (SNHL). All participants in the GJB2 and idiopathic SNHL groups had normal-sized CNs (NSCNs) in the test ear. Neural synchrony, a property depending on neural health, was assessed using phase locking value (PLV) and compared between children with CND and those with GJB2 mutations.

Results: The PLV did not differ significantly between the CND and GJB2 groups, nor did it correlate with the IPG effect in GJB2 cases, regardless of parameter, analytical method, or quantitative scale. In contrast, consistent group differences in IPG effects on stimulation level offset and maximum slope of the eCAP input/output function were observed across all analytical methods and quantitative scales. The sensitivity of other eCAP measures-threshold, maximum amplitude, and overall linear slope-to group differences varied by quantitative scale.

Conclusions: The IPG effect primarily reflects the number of active CN fibers rather than their health. Stimulation level offset and the IPG effect on maximum slope are robust indicators of CN fiber counts in CI users and are unaffected by the choice of quantitative scale.

Purpose: We report developments on the "UmboMic," a piezoelectric microphone for fully implanted cochlear implants. Internal implantation of the microphone for fully implantable cochlear implants is the goal of future technology, as it has the potential to significantly improve the device performance and user experience.

Methods: The UmboMic is designed for implantation in the middle ear cavity, where it detects the motion of the umbo via the piezoelectric effect. The UmboMic sensor is made from two layers of the piezoelectric material called polyvinylidene difluoride (PVDF). Steps towards biocompatibility necessitated material changes to the device structure, including the conducting and glue layers. Seven individual UmboMic sensors are characterized on the bench and implanted in five human cadaveric ears (1 female and 4 male).

Results: Extensive UmboMic testing and characterization demonstrates high sensitivity across frequencies, low noisefloor, shielding from electromagnetic interference, and good linearity. The UmboMic's performance is comparable to a Knowles external hearing-aid microphones, with an equivalent input noise of 32.4 dB SPL from 100 Hz to 7 kHz. Less than a 6 dB difference between UmboMic sensor sensitivity indicates fabrication repeatability. Studies on UmboMic sensor positioning demonstrate the design's resilience to implantation variations.

Conclusion: This UmboMic design represents a promising advancement towards a viable microphone for fully implanted cochlear implants. With very good microphone performances on the bench and in cadaveric human ears, research can turn towards complete device biocompatibility, fixation hardware, and testing for long-term implantation.

This systematic review evaluates the effectiveness of vestibular rehabilitation (VR) in managing vestibular migraine (VM) symptoms in adults. A systematic search of PubMed, Web of Science, Scopus, ProQuest, ScienceDirect, and CENTRAL was conducted from inception to September 30, 2024. Additional searches included the NIH Clinical Trials Register and WHO ICTRP. Key search terms included: ("Vestibular migraine" OR "migraine-associated vertigo" OR "migrainous vertigo" OR "migraine-associated dizziness") AND ("Vestibular rehabilitation" OR "Vestibular exercis*" OR "balance rehabilitation" OR "balance physiotherapy" OR "exercis*"). Studies were excluded if they were non-English studies, irrelevant topics or unacceptable study types. Eligible studies included adults over 18 years diagnosed with VM based on Barany or Neuhauser criteria, excluding those with severe comorbidities or other causes of vertigo. Comparisons involved VR versus alternative treatments or controls, using outcome measures such as subjective scales (DHI, DGI, HADS) and performance tests. Data on design, sample size, age, sex, interventions, comparators, outcomes, results, and follow-up were extracted. Eleven studies (six prospective, three retrospective, two RCTs) with 977 participants (mean age 48.46) were analyzed. VR interventions included adaptation, substitution, habituation, balance, and gait exercises, delivered home-based, therapist-supervised, or combined. Significant improvements in vertigo, dizziness, imbalance, headache, anxiety, and depression were noted, with ten studies showing better DHI scores. However, high bias risk stemmed from limited randomization, blinding, and self-reported measures. In conclusion, VR proves to be effective for managing dizziness, balance, and psychological outcomes in VM, offering a non-pharmacologic option. Future research should prioritize standardized interventions, larger cohorts, and long-term follow-ups.

Purpose: Disabling sensorineural hearing loss (SNHL) affects 5% of the global population. While congenital (CHL) and non-congenital sensorineural hearing loss (SNHL) are both strongly heritable, SNHL is a polygenic disorder, consisting of common genetic variants which individually confer small risks, requiring large studies for significance.

Methods: We present the first report of a SNHL genome-wide association study (GWAS) from the Million Veteran Program (MVP) (210,240 cases and 265,275 controls), including multi-ancestry analysis, and then combine and contrast this data with a United Kingdom Biobank (UKB) self-reported hearing loss study (87,056 cases and 163,333 controls). We perform functional mapping and annotation, gene prioritization, gene-based and gene-set analysis, and cochlear cell type enrichment, including human single-cell expression data.

Results: A total of 108 significant loci are identified, including 54 loci containing novel prioritized genes and/or protein-coding genes and implicating 17 known CHL genes. SNP-based partitioned heritability estimates show a 3.26-fold enrichment of CHL relative to other genes. Substantial genetic overlap is seen between MVP and UKB despite differences in phenotypes, demographics, and environmental exposures.

Conclusion: In this multi-ancestry GWAS, we identify 108 loci with 54 novel genes. Despite the enrichment of CHL genes, 97% of the risk for adult-onset SNHL is captured by SNPs outside of monogenic hearing loss genes. Although SNHL in the UKB and MVP were assessed using different phenotypes, genetic signals between the two cohorts are predominantly shared, and locus discovery is boosted through increased sample size in meta-analysis.

Purpose: Military personnel and veterans exposed to blast overpressure waves frequently report vestibular symptoms, including dizziness, vertigo, and imbalance. Although blast exposure is known to disrupt vestibular function, how vestibular deficits develop over time, particularly at the level of vestibular afferent signaling, remains unclear.

Methods: In this study, we used an ear-blast model to investigate the early injury responses and progression of vestibular deficits following a single, moderate-intensity blast exposure (20 PSI) in male and female Long-Evans rats. Vestibular function was assessed using single-unit recordings from vestibular afferents and vestibulo-ocular reflex (VOR) testing.

Results: Blast exposure produced progressive changes in vestibular afferent activity in both male and female rats. In males, spontaneous firing rates remained unchanged, whereas females showed a reduction at 1 day and 14 days post-blast. In both sexes, firing irregularity increased, and a greater proportion of afferents became less responsive to head rotation and translation. Although gains and phases of the remaining canal and otolith afferents were preserved, response distortion increased following blast exposure, indicating reduced precision of vestibular afferents' encoding of head movement. Despite the impairments in vestibular nerve activity, steady-state rotational and translational VOR gains remained largely unchanged, with only moderate phase changes up to 56 days post-blast. However, a subset of animals exhibited reduced step rotational VOR gains and earlier quick phase responses following blast exposure. Morphological analysis revealed stereocilia damage, significant loss of saccular hair cells, and astrocytic activation in the central vestibular nuclei.

Conclusion: Together, these findings indicate that blast-induced vestibular injury involves both peripheral and central components, with progressive changes in vestibular afferent activity that could influence sensory inputs to the CNS.

The cochlea possesses an exceptional capacity for rapid sensory transduction, enabling sound perception of at frequencies exceeding 15 kHz. This extraordinary performance depends on a specialized electrochemical environment that maintains a high endocochlear potential (EP) and facilitates efficient K⁺ circulation. The cochlear lateral wall serves as a central component, functioning as a biological battery that generates and sustains the EP via intricate ion transport mechanisms. It consists of two epithelial-like layers-the marginal cell layer and the syncytial layer-which are electrically insulated by tight junctions and interconnected via gap junctions. K⁺ enters hair cells from the K⁺-rich endolymph to initiate sensory transduction and is subsequently recycled through the perilymph and reabsorbed by the lateral wall. Our combined electrophysiological and mathematical modeling studies elucidate that the EP primarily depends on K⁺ equilibrium potentials across the apical membranes of intermediate and marginal cells, primarily mediated by K_ir4.1 and IKs channels, respectively. Pharmacological experiments confirmed that Na⁺,K⁺-ATPase and NKCC are essential for maintaining the K⁺ gradient and EP. Furthermore, our computational model successfully reproduced dynamic changes in ion concentrations and membrane potentials under hypoxic conditions and acoustic stimulation. Genetic studies further reinforce the physiological importance of lateral wall components, as mutations in associated transporters, channels, and structural proteins commonly lead to sensorineural hearing loss. Collectively, these findings underscore the cochlear lateral wall as an integrated electrochemical organ and illustrate the utility of multiscale modeling in bridging molecular mechanisms with systems-level auditory function.

The vestibular organs of birds are capable of regenerating sensory hair cells after ototoxic injury, but the regenerative ability of the mammalian vestibular organs is much more limited. The factors that inhibit regeneration in the mammalian inner ear are not known, but it has been proposed that the structure of filamentous actin cables at cell-cell junctions may be an important regulatory influence. Junctional actin cables in the chick utricle are relatively thin, while those in the mouse utricle are much thicker. These differences result in differing mechanical properties of the avian vs. mammalian inner ear, which may affect the potential for regenerative proliferation. In the present study, I characterized injury-evoked changes in junctional actin cables and supporting cell surface areas in the utricles of mice and chicks of either sex. I found that the thickness of junctional cables in the chick utricle was not affected by ototoxic injury, but that injury to the mouse utricle resulted in the formation of numerous new junctional actin bands whose thickness was comparable to those in the chick utricle. Thicker actin bands also persisted after injury, but were not necessarily associated with cellular junctions. I further found that moderate hair cell injury caused supporting cells in the chick utricle to expand their lumenal surfaces by about 50%, while comparable injury to the mouse utricle caused supporting cells to expand by only ~ 30%. I speculate that this difference may impact the injury-induced activation of Hippo/YAP signaling.

Neural hearing loss, characterized by dysfunction of the auditory nerve, including the spiral ganglion neurons (SGNs) and/or their synaptic connections, is increasingly recognized as a critical contributor to auditory deficits across diverse conditions, including Auditory Neuropathy Spectrum Disorder (ANSD), presbycusis, and noise-induced hearing loss (NIHL). It is possible that neural hearing loss is underdiagnosed, due to the lack of clinical tools with sufficient sensitivity and specificity to detect poor neural health. Current interventions, such as hearing aids and cochlear implants (CIs), primarily target sensory deficits and offer limited benefit in cases of significant neural compromise. Therapeutically, there is a growing shift towards biologically driven strategies aimed at restoring neural function. Recent developments in novel therapies, including pharmacological, gene-based, neurotrophic, and cell-based approaches, have opened new possibilities demonstrating the potential to protect, repair, and/or replace damaged SGNs, and re-establish auditory pathways. This perspectives article explores the evolving understanding of neural hearing loss, emphasizing its complex pathophysiology and the limitations of current diagnostic and therapeutic approaches, while highlighting how a diverse range of emerging solutions are moving closer to clinical application.