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

Chronic suppurative otitis media (CSOM) affects up to 330 million people globally and is one of the leading causes of pediatric hearing loss. Defined by a state of chronic infection in the middle ear in the setting of a tympanic membrane perforation, CSOM is traditionally most frequently associated with infection with Pseudomonas and Staphylococcus aureus species. The current therapeutic options for CSOM include medical therapy in the form of topical antibiotics or antiseptics (i.e., boric acid, acetic acid, povo-iodine), as well as surgical intervention with tympanoplasty or tympanomastoidectomy in refractory cases. While topical fluoroquinolones have the strongest level of evidence supporting their use for CSOM treatment, they are frequently associated with long-term treatment failure. Treatment failure is secondary to the presence of persister cells in CSOM, which are antibiotic tolerant and have the potential to proliferate and gain additional antibiotic resistance. As biofilms and persister cells are not routinely tested for in clinical medicine, there is limited data on therapeutic options that may eradicate biofilms and persister cells while limiting ototoxic effects. While future research should aim to identify such ototopical treatment options, clinicians may also consider surgical intervention earlier in patients with disease refractory to topical treatment to both minimize the risk of encouraging antibiotic resistance and to maximize the ability to debride the biofilm.

Purpose: Present-day cochlear-implant (CI) users can achieve high levels of speech reception in quiet surroundings. Nevertheless, sensitivity to the temporal pitch of sounds is limited, which contributes to deficits in speech reception amid multiple talkers and in appreciation of musical melodies. Short-term, invasive neurophysiological studies in animals have demonstrated limitations in neural phase locking in the tonotopic range of the auditory pathway that is activated by CIs. It remains an open question, however, whether those neural limitations can account for perceptual deficits in those animal species, let alone in human CI users. For that reason, we have evaluated non-invasive recordings of phase locking from cats chronically implanted with a CI.

Methods: Ten deafened cats (eight female) were implanted with an animal version of a clinical CI array. The electrically evoked frequency following response (eFFRs) was recorded from the scalps of sedated animals at ≥ 10 weeks post-implantation. Stimuli consisted of constant-amplitude electrical pulse trains at rates from ~ 40 to 640 pulses per second.

Results: Recordings of the eFFR demonstrated robust responses synchronized to electrical pulse trains across all stimulus rates. Analyses of eFFR amplitude and phase transfer functions confirmed that the eFFR, as with its normal-hearing counterpart, originates from multiple subcortical and cortical generators. The slopes of segments of eFFR phase transfer functions revealed stimulus-to-response latencies of generators that dominated the eFFR across restricted ranges of pulse rates. Those rate ranges must coincide with the limits of phase locking by putative generators at successive levels of the auditory neuroaxis and could inform our understanding of the limits to perceptual temporal acuity.

Conclusion: The eFFR demonstrated here in an animal model provides a valuable non-invasive measure of temporal processing in electric cochlear stimulation that can be related to ongoing perceptual measures in the same animals and is well-suited to evaluate novel modes of auditory prosthesis for enhancing temporal acuity.

Studies of hearing often conclude that the ear is "remarkable" or that its performance is "exceptional." Some common examples include the following: $▹$  the ears of mammals are encased in the hardest bone in the body; $▹$  the ear contains the most vascularized tissue in body; $▹$  the ear has the highest resting potential in the body; $▹$  ears have a unique "fingerprint"; $▹$  the ear can detect signals below the thermal noise floor; and $▹$  the ear is highly nonlinear (or highly linear, depending upon who you ask). Some claims hold up to further scrutiny, while others do not. Additionally, several claims hold for animals in one taxon, while others are shared across taxa. Most frequently, our sense of wonder results from the differences between ears as products of natural selection (over eons) and artificial systems as products of engineering design. Our goal in analyzing claims of remarkable or exceptional performance is to deepen our appreciation of these differences.

Objective: Differentiating between Meniere's disease (MD) and vestibular migraine (VM) is challenging due to overlapping symptoms and limited diagnostic tools. Traditional statistical methods often rely on physician judgment and struggle with complex, high-dimensional data. This study applies the random forest (RF) machine learning algorithm to enhance the clinical differentiation between MD and VM.

Methods: We retrospectively analyzed data from 36 VM (26 female) and 100 unilateral MD patients (51 female). The data were anonymized and labeled. Symptomatic and examination parameters were selected as features, and exploratory data analysis identified key parameters for diagnosis. An RF model was used to rank these features.

Results: MD patients more commonly experienced ear-related symptoms, while VM patients reported more headaches and dizziness. Examination findings showed greater asymmetry in vHIT saccade latency in MD patients, particularly on the affected side. A total of 40 key parameters were identified. Heatmap and clustering analysis revealed that time constant (Tc) in velocity step test (VST) correlated more strongly with headache and other symptoms, while saccade latencies and velocities correlated with pure tone averages. The RF model selected 27 parameters for prediction, achieving 91.86% accuracy (95% confidence interval [85.37%, 95.18%]). Tc and saccade velocity were among the top 10 contributing features. Additionally, MD patients had earlier saccades and shorter Tc values on the affected side compared to both healthy controls and VM patients.

Conclusions: Machine learning successfully classified MD and VM patients, with Tc and saccade velocity identified as key diagnostic indicators alongside symptoms.

Purpose: Several therapeutic approaches for hearing disorders involve attaching medical devices to the tympanic membrane. The attachment of these devices can change the mechanical and acoustical properties of the middle ear, affecting the middle-ear vibrations. The alteration of passive mechanical properties results from the mass, stiffness, and geometry of the attached device. Additionally, procedures like tympanostomy tube attachment create perforations on the tympanic membrane, altering both the mechanical and acoustical properties of the middle ear. This study examined the acoustical effects of these as well as the combination of acoustical and mechanical effects of the attached devices on middle-ear vibrations.

Methods: A finite-element model of the middle ear, including the middle-ear cavity, was used to systematically study the effects of perforation size and location on vibration outputs. Experimental data from the literature were used to tune the model. This model was then employed to investigate the combined mechanical and acoustical effects of tympanostomy tubes on vibration outputs.

Results: In presence of both the mechanical effects of the device (due to its mass and stiffness) and the acoustical effects of it (due to perforations), the reduction in the motion of the stapes footplate resulting from the acoustical effects is more remarkable at low frequencies (below about 1 kHz). However, at higher frequencies, the mechanical effects of the device are dominant.

Conclusion: The findings of this study provide insights into the optimal design of the shape, location, and other characteristics of medical devices implanted on the tympanic membrane.

Purpose: To explore the feasibility of cochlear-implant (CI) processing strategies that aim to improve pitch perception by presenting information on the stimulus temporal fine structure (TFS) in low-frequency channels to the corresponding apical electrodes.

Methods: Eight users of the MED-EL CI pitch-ranked stimuli consisting of isochronous pulse trains presented concurrently to the four most apical CI electrodes.

Results: When the same rate was applied to all electrodes, pitch ranks increased with increasing rates up to 200-300 pulses-per-second (pps), consistent with previous research. Presenting rates of 100, 200, 300, and 400 pps to one electrode per rate produced a pitch rank between that of the 100- and 200-pps same-rate stimuli. The assignation of pulse rate to electrode did not have a consistent effect on pitch ranks. However, maximising the delay between pulses on the different electrodes generally produced higher pitch ranks compared to when the between-electrode pulse delay was very short.

Conclusion: Our results show no evidence that listeners combine the rates of TFS applied to different channels so as to estimate the fundamental frequency but do show that pitch can be affected by between-electrode delays. We conclude that presenting different temporal patterns to adjacent electrodes is unlikely to produce a clear and robust pitch and propose an alternative method for conveying the F0 of complex sounds on multiple electrodes of a CI.

Purpose: The majority of adult cochlear implant (CI) recipients are over the age of 65, and previous research in non-implanted older adults shows that auditory nerve (AN) pathophysiology contributes to senescent declines in speech understanding. However, age-related changes to AN structure and function have not yet been explored as a contributory factor to poorer speech understanding outcomes in older CI users. Here, we explore how estimates of AN disengagement (i.e., AN density) and dyssynchrony in CI users contribute to poorer speech recognition performance observed in older CI users.

Methods: We examined electrically evoked compound action potentials (ECAPs) in 47 adult (Male = 25) CI recipients. We measured the interphase gap (IPG) effect for the amplitude-growth function (AGF) slope and the N1-P2 interpeak latency as independent metrics of AN density and dyssynchrony, respectively.

Results: Estimates of AN density and dyssynchrony worsen with increasing age in older CI listeners. These measures were not significantly correlated with one another, but were independently related to speech recognition in noise performance. Lower ECAP IPG effect values (lower density of AN fibers) are observed in older CI users. Longer N1-P2 interpeak latency values (poorer neural synchrony) are also observed in older CI users. When controlling for listener age, poorer AN dyssynchrony contributes to declines in speech-recognition-in-noise performance in CI users.

Conclusion: These results suggest that AN dyssynchrony rather than density is the primary contributing factor to age-related declines in speech understanding in CI users. These results have important implications for better understanding neural contributions to speech understanding in adult CI users.

Purpose: Whrn, encoding whirlin, is one of the genes highly relevant to Usher syndrome (USH) that has been known as an autosomal recessive genetic disorder that is characterized with sensorineural hearing loss with retinitis pigmentosa. Although recent studies on the other USH genes, PDZD7 and Ush1 g, showed a possibility of haploinsufficiency effect, the potential contribution of heterozygous Whrn loss to hearing loss remains unclear.

Methods: To investigate the effect of Whrn haploinsufficiency, we conducted a longitudinal study assessing auditory function in heterozygous Whrn mutant (Whrn^+/-) mice in which long isoform of Whrn was deleted by replacing exon 1 with Neo cassette without disturbing short isoform. The threshold of auditory brainstem responses (ABRs) was measured on 135 Whrn^+/- mice and littermate 133 wild-type (WT) mice from 1 to 6 months of ages. From those data, the threshold from male and female were separately analyzed to investigate sex-dependent effect. To further investigate underlie mechanisms, hair cell death was investigated using immunohistostaining from 4 to 5 WT, 5 female Whrn^+/-, and 7 male Whrn^+/- mice at 4-5 months old.

Results: Hearing threshold was significantly increased with aging in Whrn^+/- mice compared to WT controls. Both WT and Whrn^+/- mice exhibited sex-dependent variations in hearing sensitivity. Notably, Whrn^+/- males showed a progressive hearing loss with age, while Whrn^+/- females exhibited elevated hearing thresholds as early as 1-2 month of age compared to WT females.

Conclusion: These results provide evidence for a haploinsufficiency effect of Whrn on auditory function and highlight its potential role in progressive sensorineural hearing loss.

Purpose: Cochlear implants (CIs) are an effective rehabilitation option for individuals with severe-to-profound sensorineural hearing loss (SNHL). While genetic factors play a significant role in SNHL, the variability in CI outcomes remains unclear. This study evaluated short- and long-term CI outcomes in a large genotyped cohort and investigated correlations with genetic defects and their cochlear site-of-lesion.

Methods: This retrospective, single-center, cohort study included 220 subjects (127 females; 299 ears) with pathogenic variants identified in 31 different nuclear genes and in mitochondrial genes. Audiological outcomes were measured pre- and post-implantation. Cochlear site-of-lesion was categorized as pre-synaptic, post-synaptic, or mitochondrial, based on gene function or expression. Multiple regression analysis assessed factors influencing outcomes, including age at implantation, SNHL duration, hearing aid (HA) use, and cochlear site-of-lesion.

Results: Results showed a median phoneme score of 90%, with better outcomes in early implantation (≤ 6 years). Variability in outcomes was not linked to cochlear site-of-lesion, but to subject-specific factors, such as age at implantation, duration of SNHL, pre-implantation HA use, and CI experience. A model incorporating these subject-specific factors explained 19% of the total variance in outcomes. Poorer outcomes (phoneme scores < 70%) were more common in individuals with prolonged auditory deprivation or older age at implantation.

Conclusion: Genotyped CI recipients demonstrated excellent outcomes, with variability largely attributed to non-genetic factors. These findings show that cochlear implantation is a beneficial type of rehabilitation for most individuals with hereditary SNHL and underscore the importance of early implantation.

Purpose: In the receptor organs of the inner ear, hair cells detect mechanical stimuli such as sounds and accelerations by deflection of their hair bundles. Myosin regulatory light chain (RLC) and non-muscle myosin II (NM2) are expressed at the apical surfaces of hair cells, and NM2 and the phosphorylation of RLC by myosin light chain kinase (MLCK) have earlier been shown to regulate the shapes of hair cells' apical surfaces in rodents. The aim of our study was to elucidate the function of myosin molecules on hair cell physiology.

Methods: We investigated the expression of NM2 and RLC in the bullfrog's saccule by immunostaining. Using NM2 and MLCK inhibitors, we measured the stiffness, spontaneous oscillation, and resting open probability of frog hair bundles. Six to ten saccules from pleural animals were used in each experiment. In addition, we recorded auditory brainstem responses in ten mice after transtympanic injection of an MLCK inhibitor.

Results: We confirmed the expression of NM2A/B and MYL9 on the apical surfaces of hair cells and of NM2A and MYL12A in hair bundles. We found that NM2 and MLCK inhibitors reduce the stiffness of hair bundles from the bullfrog's saccule. Moreover, MLCK inhibition inhibits the spontaneous oscillation of hair bundles and increases the resting open probability of transduction channels. In addition, MLCK inhibition elevates hearing thresholds in mice.

Conclusion: We conclude that NM2 and the phosphorylation of RLC modulate the physiological function of hair cells and thereby help to set the normal operating conditions of hair bundles.