A Clinically Viable Medial Olivocochlear Reflex Assay Using Transient-Evoked Otoacoustic Emissions.

OBJECTIVES: The contralateral medial olivocochlear reflex (MOCR) strength may indicate various auditory conditions in humans, but a clinically viable assay and equipment are needed for quick, accurate, and reliable measurements. The first experiment compared an earlier version of the assay, which used a nonlinear-mode chirp stimulus, with a new assay using a linear-mode click stimulus, designed to give reliable MOCR measurements in most normal-hearing ears. The second experiment extended the improved assay on a purpose-built binaural hardware platform that used forward-pressure level (FPL) calibration for both the stimulus and the contralateral MOCR elicitor. DESIGN: Transient-evoked otoacoustic emission (TEOAE) tests were measured with and without a 60-dB SPL MOCR-evoking contralateral broadband noise. The normalized MOCR strength (MOCR%) was derived from the TEOAE responses for each trial pair using the complex pressure difference weighted by the TEOAE magnitude. Experiment 1 compared MOCR% within-subject and across-day using two TEOAE stimuli: nonlinear-mode chirps (50 dB SPL, bandpass 1-5 kHz, 14 ms window delayed by 2 ms) and linear-mode clicks (50 dB SPL, bandpass 0.5-2.5 kHz, 13 ms window delayed by 5 ms). TEOAE responses were analyzed in the 0.5 to 2.5 kHz band. Thirty adult participants with normal hearing (30 ears) completed the study. The TEOAE stimulus was calibrated in situ using spectral flattening, and the contralateral noise was calibrated in a coupler. Twelve TEOAE trial pairs were collected for each participant and condition. Experiment 2 used a purpose-built binaural system. The TEOAE stimuli were linear-mode clicks (50 dB SPL, bandpass 1-3 kHz, 13 ms window delayed by 5 ms), analyzed in the 1 to 3 kHz band over ~12 trial pairs. After a probe refit, an additional trial pair was collected for the two early-stopping signal-to-noise ratio criteria (15 and 20 dB). They were evaluated for single-trial reliability and test time. Nineteen adult participants with normal hearing (38 ears) completed the study. The TEOAE clicks and contralateral elicitor noise were calibrated in situ using FPL and delivered with automated timing. RESULTS: MOCR% for linear-mode clicks was distinguishable from measurement variability in 98% to 100% of participants' ears (both experiments), compared with only 73% for the nonlinear-mode chirp (experiment 1). MOCR detectability was assessed using the MOCR% across-subject/within-subject variance ratio. The ratio in experiment 1 for linear-mode clicks was higher (8.0) than for nonlinear-mode chirps (6.4). The ratio for linear-mode clicks (8.9) in experiment 2 was slightly higher than for the comparable linear-mode stimulus (8.0) in experiment 1. TEOAEs showed excellent reliability with high signal-to-noise ratios in both experiments, but reliability was higher for linear-mode clicks than nonlinear-mode chirps. MOCR reliability for the two stimuli was comparable. The FPL pressure response retest reliability derived from the SPL at the microphone was higher than the SPL retest reliability across 0.4 to 8 kHz. Stable results required 2 to 3 trial pairs for the linear-mode click (experiments 1 and 2) and three for the nonlinear-mode chirp (experiment 1), taking around 2 min on average. CONCLUSIONS: The linear-mode click assay produced measurable, reliable, and stable TEOAE and MOCR results on both hardware platforms in around 2 min per ear. The stimulus design and response window ensured that any stimulus artifact in linear mode was unlikely to confound the results. The refined assay is ready to produce high-quality data quickly for clinical and field studies to develop population norms, recognize diagnostic patterns, and determine risk profiles.

Reliable Long-Term Serial Evaluation of Cochlear Function Using Pulsed Distortion-Product Otoacoustic Emissions: Analyzing Levels and Pressure Time Courses.

OBJECTIVES: To date, there is no international standard on how to use distortion-product otoacoustic emissions (DPOAEs) in serial measurements to accurately detect changes in the function of the cochlear amplifier due, for example, to ototoxic therapies, occupational noise, or the development of regenerative therapies. The use of clinically established standard DPOAE protocols for serial monitoring programs appears to be hampered by multiple factors, including probe placement and calibration effects, signal-processing complexities associated with multiple sites of emission generation as well as suboptimal selection of stimulus parameters. DESIGN: Pulsed DPOAEs were measured seven times within 3 months for f2 = 1 to 14 kHz and L2 = 25 to 80 dB SPL in 20 ears of 10 healthy participants with normal hearing (mean age = 32.1 ± 9.7 years). L1 values were computed from individual optimal-path parameters derived from the corresponding individual DPOAE level map in the first test session. Three different DPOAE metrics for evaluating the functional state of the cochlear amplifier were investigated with respect to their test-retest reliability: (1) the interference-free, nonlinear-distortion component level ( LOD ), (2) the time course of the DPOAE-envelope levels, LDP ( t ), and (3) the squared, zero-lag correlation coefficient ( ) between the time courses of the DPOAE-envelope pressures, pDP ( t ), measured in two sessions. The latter two metrics include the two main DPOAE components and their state of interference. RESULTS: Collated over all sessions and frequencies, the median absolute difference for LOD was 1.93 dB and for LDP ( t ) was 2.52 dB; the median of was 0.988. For the low ( f2 = 1 to 3 kHz), mid ( f2 = 4 to 9 kHz), and high ( f2 = 10 to 14 kHz) frequency ranges, the test-retest reliability of LOD increased with increasing signal to noise ratio (SNR). CONCLUSIONS: On the basis of the knowledge gained from this study on the test-retest reliability of pulsed DPOAE signals and the current literature, we propose a DPOAE protocol for future serial monitoring applications that takes into account the following factors: (1) separation of DPOAE components, (2) use of individually optimal stimulus parameters, (3) SNR of at least 15 dB, (4) accurate pressure calibration, (5) consideration of frequency- and level-dependent test-retest reliabilities and corresponding reference ranges, and (6) stimulus levels L2 that are as low as possible with sufficient SNR to capture the nonlinear functional state of the cochlear amplifier operating at its highest gain.

Preservation of Distortion Product Otoacoustic Emissions in OTOF -Related Hearing Impairment.

OBJECTIVES: Attenuation of otoacoustic emissions over time has been reported for many patients with hearing impairment harboring mutations in the OTOF gene. In this study, the time course of changes of distortion product otoacoustic emissions (DPOAEs) has been analyzed in a cohort of patients in the light of tympanometry results. DESIGN: The changes of DPOAEs in 16 patients with OTOF -related hearing impairment were retrospectively analyzed. RESULTS: All but one subject showed DPOAEs bilaterally at the time of diagnosis. Three patients diagnosed as adults still had DPOAEs at ages of 27, 31, and 47 years, respectively. Follow-up was available for 7 children diagnosed at the age of 1 to 3 years, who still showed preservation of DPOAEs at ages of 5 to 16 years. The responses were absent or attenuated in amplitude at some follow-up appointments in association with type B or C tympanograms. CONCLUSIONS: DPOAEs are preserved much longer than expected in a cohort of patients with OTOF -related hearing impairment. The previously reported loss of DPOAEs may have been caused in some children by increased middle ear impedance due to otitis media.

Deep Learning Models for Predicting Hearing Thresholds Based on Swept-Tone Stimulus-Frequency Otoacoustic Emissions.

OBJECTIVES: This study aims to develop deep learning (DL) models for the quantitative prediction of hearing thresholds based on stimulus-frequency otoacoustic emissions (SFOAEs) evoked by swept tones. DESIGN: A total of 174 ears with normal hearing and 388 ears with sensorineural hearing loss were studied. SFOAEs in the 0.3 to 4.3 kHz frequency range were recorded using linearly swept tones at a rate of 2 Hz/msec, with stimulus level changing from 40 to 60 dB SPL in 10 dB steps. Four DL models were used to predict hearing thresholds at octave frequencies from 0.5 to 4 kHz. The models-a conventional convolutional neural network (CNN), a hybrid CNN-k-nearest neighbor (KNN), a hybrid CNN-support vector machine (SVM), and a hybrid CNN-random forest (RF)-were individually built for each frequency. The input to the DL models was the measured raw SFOAE amplitude spectra and their corresponding signal to noise ratio spectra. All DL models shared a CNN-based feature self-extractor. They differed in that the conventional CNN utilized a fully connected layer to make the final regression decision, whereas the hybrid CNN-KNN, CNN-SVM, and CNN-RF models were designed by replacing the last fully connected layer of CNN model with a traditional machine learning (ML) regressor, that is, KNN, SVM, and RF, respectively. The model performance was evaluated using mean absolute error and SE averaged over 20 repetitions of 5 × 5 fold nested cross-validation. The performance of the proposed DL models was compared with two types of traditional ML models. RESULTS: The proposed SFOAE-based DL models resulted in an optimal mean absolute error of 5.98, 5.22, 5.51, and 6.06 dB at 0.5, 1, 2, and 4 kHz, respectively, superior to that obtained by the traditional ML models. The produced SEs were 8.55, 7.27, 7.58, and 7.95 dB at 0.5, 1, 2, and 4 kHz, respectively. All the DL models outperformed any of the traditional ML models. CONCLUSIONS: The proposed swept-tone SFOAE-based DL models were capable of quantitatively predicting hearing thresholds with satisfactory performance. With DL techniques, the underlying relationship between SFOAEs and hearing thresholds at disparate frequencies was explored and captured, potentially improving the diagnostic value of SFOAEs.

Effects of Tympanic Membrane Electrodes on Sound Transmission From the Ear Canal to the Middle and Inner Ears.

OBJECTIVES: The first objective of the study was to compare approaches to eardrum electrode insertion as they relate to the likelihood of introducing an acoustic leak between the ear canal and eartip. A common method for placing a tympanic membrane electrode involves securing the electrode in the canal by routing it underneath a foam eartip. This method is hypothesized to result in a slit leak between the canal and foam tip due to the added bulk of the electrode wire. An alternative approach involves creating a bore in the wall of the foam tip that the electrode can be threaded through. This method is hypothesized to reduce the likelihood of a slit leak before the electrode wire is integrated into the foam tip. The second objective of the study was to investigate how sound transmission in the ear is affected by placing an electrode on the eardrum. It was hypothesized that an electrode in contact with the eardrum increases the eardrum's mass, with the potential to reduce sound transmission at high frequencies. DESIGN: Wideband acoustic immittance and distortion product otoacoustic emissions (DPOAEs) were measured in eight human ears. Measurements were completed for five different conditions: (1) baseline with no electrode in the canal, (2) dry electrode in the canal but not touching the eardrum, secured underneath the eartip, (3) dry electrode in the canal not touching the eardrum, secured through a bore in the eartip (subsequent conditions were completed using this method), (4) hydrated electrode in the canal but not touching the eardrum, and (5) hydrated electrode touching the eardrum. To create the bore, a technique was developed in which a needle is heated and pushed through the foam eartip. The electrode is then thread through the bore and advanced slowly by hand until contacting the eardrum. Analysis included comparing absorbance, admittance phase angle, and DPOAE levels between measurement conditions. RESULTS: Comparison of the absorbance and admittance phase angle measurements between the electrode placement methods revealed significantly higher absorbance and lower admittance phase angle from 0.125 to 1 kHz when the electrode is routed under the eartip. Absorbance and admittance phase angle were minimally affected when the electrode was inserted through a bore in the eartip. DPOAE levels across the different conditions showed changes approximating test-retest variability. Upon contacting the eardrum, the absorbance tended to decrease below 1 kHz and increase above 1 kHz. However, changes were within the range of test-retest variability. There was evidence of reduced levels below 1 kHz and increased levels above 1 kHz upon the electrode contacting the eardrum. However, differences between conditions approximated test-retest variability. CONCLUSIONS: Routing the eardrum electrode through the foam tip reduces the likelihood of incurring an acoustic leak between the canal walls and eartip, compared with routing the electrode under the eartip. Changes in absorbance and DPOAE levels resulting from electrode contact with the eardrum implicate potential stiffening of eardrum; however, the magnitude of changes suggests minimal effect of the electrode on sound transmission in the ear.

Occupational Lead Exposure Ototoxicity Evaluated With Distortion-Product Otoacoustic Emissions.

OBJECTIVES: To evaluate the extent of hearing loss among pottery workers in Mexico exposed to lead. DESIGN: The authors conducted a cross-sectional study including 315 adult pottery workers. Auditory function was evaluated by air conduction pure-tone audiometry (pure-tone average) and distortion-product otoacoustic emission (DPOAE) levels (amplitude and signal-to-noise ratio). Lead exposure was assessed with a single blood sample test and classified as low, medium, and high according to blood lead tertiles. Logistic regression models were calculated for the association between blood lead levels, pure-tone average, and DPOAE records. RESULTS: Median (25th-75th) blood lead levels were 14 µg/dL (7.5-22.6 µg/dL). The audiometric pattern and DPOAE records were similar across blood lead levels groups in all frequencies, and no statistically significant differences were found. Adjusted logistic regression models showed no increase in the odds for hearing thresholds >25 dB (HL) and DPOAE absence associated with blood lead levels, and no dose-response pattern was observed ( p > 0.05). CONCLUSIONS: Given the results from this cross-sectional study, no association was found between blood lead levels and hearing loss assessed with DPOAE. Future longitudinal work should consider chronic lead exposure estimates among underrepresented populations, which can potentially inform safer work practices to minimize the risk of ototoxicity.

Hearing dysfunction heralds an increase in non-motor burden and a worse quality of life in Parkinson's disease: new insights from non-motor spectrum.

BACKGROUND: Sensorial non-motor symptoms (NMSs) in Parkinson's disease (PD) still lack appropriate investigation in clinical practice. This study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient's quality of life (QoL). METHODS: We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. Demographic and clinical data were collected. Patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed Non-Motor Symptoms Scale (NMSS) and Parkinson's Disease Questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis. RESULTS: 60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25 dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS. CONCLUSION: This study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. Our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL.

Evaluation of the auditory findings of patients with obstructive sleep apnea syndrome.

OBJECTIVES: To investigate the effects of hypoxia occurring in patients with Obstructive Sleep Apnea Syndrome (OSAS) on Auditory evoked late latency, Auditory brainstem response, and the contralateral suppression of otoacoustic emissions. MATERIALS AND METHODS: 46 patients diagnosed with OSAS were divided into groups as moderate and severe based on their Apnea Hipopnea Index (AHI) values. The control group consisted of 22 healthy individuals. All participants underwent an Auditory Brainstem Response (ABR) test, Auditory Evoked Late Latency Response (LLR), and Contralateral Suppression Otoacoustic Emission (CS-OAE). FINDINGS: There was no statistical difference between the OSAS group and the control group regarding P1 latency, N1 latency, and P1 and N1 wave amplitude (p > 0.05). In ABR, statistically significant differences were found between the control, moderate OSAS, and severe OSAS groups in wave I in the right and left ear (p < 0.05). In the analyses performed for the otoacoustic emission frequencies with and without contralateral suppression of the right and left ear, suppression was not observed at some frequencies, and this was regarded as statistically significant (p < 0.05). CONCLUSION: It is considered that OSAS does not have cortical effects but impacts the brainstem region and the cochlea. Bilateral impact, especially observed in wave I of ABR, is prominent on the auditory nerve. Considering that the medial olivo-cochlear (MOC) system is affected in patients with OSAS, it is thought that these patients are inadequate in suppressing noise, and this may cause various problems, particularly the inability to distinguish speech in noisy environments.

The effect of tympanostomy tubes on otoacoustic emissions.

PURPOSE: Otoacoustic emissions (OAE) are a common screening tool to evaluate cochlear function. Middle ear dysfunction has been shown to impact results of otoacoustic emission testing, but there are limited data on the effect of tympanostomy tubes on OAE. The purpose of this study was to determine whether tympanostomy tube placement significantly improved OAE. METHODS: A retrospective review of charts was completed for patients younger than 18 years old who underwent tympanostomy tube placement from January 1, 2018 to September 1, 2023 and had preoperative and postoperative OAE testing within 6 months of surgery. The primary variable was presence of OAE preoperatively and postoperatively. Chi-square analysis and t test were used for statistical analysis. RESULTS: A total of 212 ears were examined from 111 pediatric patients who underwent tympanostomy tube placement during the study period. Presence of OAE at 3000, 4000, and 5000 Hz were all noted to significantly increase following tympanostomy tube placement, with OAE presence increasing from approximately 27.8% of the sample preoperatively to 95.3% postoperatively at 3000 and 4000 Hz. Patients who noted improvement had a significantly higher proportion of type B tympanogram preoperatively, compared to a higher proportion of type A tympanogram noted in patients who did not note improvement. CONCLUSION: Tympanostomy tubes can significantly improve otoacoustic emissions in patients with middle ear dysfunction.

Click evoked otoacoustic emissions in occupational exposure to lead, concentrations of selected essential elements and markers of oxidative stress.

PURPOSE: This study focused on the selected markers of oxidative stress, impact of elevated lead levels on long-term hearing quality. We investigated whether the presence of certain essential minerals might provide protection to the auditory system against the effects of lead (and cadmium) compounds. METHODS: The research group included 280 male employees of the zinc and lead smelter, which was divided into: L-Pb-low blood lead concentration (PbB) subgroup, H-Pb-high PbB subgroup. Hearing tests were performed using the click evoked otoacoustic emission (CEOAE). RESULTS: Zinc protoporphyrin level was significantly higher in the H-Pb subgroup by 68%. Cd concentration was significantly higher in H-Pb by 33%. The Ca concentration was significantly lower in the H-Pb by - 2%. Selected oxidative stress markers concentration were significantly higher in the H-Pb group: malondialdehyde (MDA) by 4%, and lipofuscin (LPS) by 9%. In the CEOAE results showed statistically significant differences between the L-Pb and H-Pb subgroups. Larger negative changes in otoemission amplitude were observed in H-Pb subgroup. All otoemission results showed a statistically significant negative correlation with age, time of work, MDA concentration, and with PbB. Selected CEOAE parameters showed a significant negative correlation with cadmium blood concentration (CdB), and a positive correlation with Ca and Zn. CONCLUSION: Elevated blood lead content in occupational exposure is associated with an increase in MDA and LPS concentration, which negatively correlates with CEOAE parameters. This suggests an important role of oxidative stress in the long-term deterioration of hearing.

The influence of tympanic-membrane orientation on acoustic ear-canal quantities: A finite-element analysis.

Assuming plane waves, ear-canal acoustic quantities, collectively known as wideband acoustic immittance (WAI), are frequently used in research and in the clinic to assess the conductive status of the middle ear. Secondary applications include compensating for the ear-canal acoustics when delivering stimuli to the ear and measuring otoacoustic emissions. However, the ear canal is inherently non-uniform and terminated at an oblique angle by the conical-shaped tympanic membrane (TM), thus potentially confounding the ability of WAI quantities in characterizing the middle-ear status. This paper studies the isolated possible confounding effects of TM orientation and shape on characterizing the middle ear using WAI in human ears. That is, the non-uniform geometry of the ear canal is not considered except for that resulting from the TM orientation and shape. This is achieved using finite-element models of uniform ear canals terminated by both lumped-element and finite-element middle-ear models. In addition, the effects on stimulation and reverse-transmission quantities are investigated, including the physical significance of quantities seeking to approximate the sound pressure at the TM. The results show a relatively small effect of the TM orientation on WAI quantities, except for a distinct delay above 10 kHz, further affecting some stimulation and reverse-transmission quantities.

Detection of mild sensory hearing loss using a joint reflection-distortion otoacoustic emission profile.

Measuring and analyzing both nonlinear-distortion and linear-reflection otoacoustic emissions (OAEs) combined creates what we have termed a "joint-OAE profile." Here, we test whether these two classes of emissions have different sensitivities to hearing loss and whether our joint-OAE profile can detect mild-moderate hearing loss better than conventional OAE protocols have. 2f1-f2 distortion-product OAEs and stimulus-frequency OAEs were evoked with rapidly sweeping tones in 300 normal and impaired ears. Metrics included OAE amplitude for fixed-level stimuli as well as slope and compression features derived from OAE input/output functions. Results show that mild-moderate hearing loss impacts distortion and reflection emissions differently. Clinical decision theory was applied using OAE metrics to classify all ears as either normal-hearing or hearing-impaired. Our best OAE classifiers achieved 90% or better hit rates (with false positive rates of 5%-10%) for mild hearing loss, across a nearly five-octave range. In summary, results suggest that distortion and reflection emissions have distinct sensitivities to hearing loss, which supports the use of a joint-OAE approach for diagnosis. Results also indicate that analyzing both reflection and distortion OAEs together to detect mild hearing loss produces outstanding accuracy across the frequency range, exceeding that achieved by conventional OAE protocols.

[Pulsed DPOAEs in serial measurements : Combined analysis paradigm of simultaneously occurring changes in hearing thresholds and DPOAEs. German version]. / Gepulste DPOAE in Verlaufsmessungen : Kombiniertes Analyseparadigma von gleichzeitig auftretenden Veränderungen in Hörschwellen und DPOAE.

BACKGROUND: To date, there is no consensus on how to standardize the assessment of ototoxicity in serial measurements. For the diagnosis of damage to the cochlear amplifier, measurement methods are required that have the highest possible test-retest reliability and validity for detecting persistent damage. Estimated distortion-product thresholds (LEDPT) based on short-pulse distortion-product otoacoustic emission (DPOAE) level maps use individually optimal DPOAE stimulus levels and allow reliable quantitative estimation of cochlea-related hearing loss. MATERIALS AND METHODS: Hearing thresholds were estimated objectively using LEDPT and subjectively using modified Békésy tracking audiometry (LTA). Recordings were performed seven times within three months at 14 frequencies (f2 = 1-14 kHz) in 20 ears (PTA4 (0.5-4 kHz) < 20 dB HL). Reconstruction of the DPOAE growth behavior as a function of the stimulus levels L1, L2 was performed on the basis of 21 DPOAE amplitudes. A numerical fit of a nonlinear mathematical function to the three-dimensional DPOAE growth function yielded LEDPT for each stimulus frequency. For the combined analysis, probability distributions of hearing thresholds (LTA, LEDPT), DPOAE levels (LDP), and combinations thereof were determined. RESULTS: LTA and LEDPT each exhibited a test-retest reliability with a median of absolute differences (AD) of 3.2 dB and 3.3 dB, respectively. Combining LEDPT, LDP, and LTA into a single parameter yielded a significantly smaller median AD of 2.0 dB. CONCLUSION: It is expected that an analysis paradigm based on a combination of LEDPT, suprathreshold LDP, and fine-structure-reduced LTA would achieve higher test performance (sensitivity and specificity), allowing reliable detection of pathological or regenerative changes in the outer hair cells.

Auditory and Vestibular Findings in Brazilian Adults Affected by COVID-19: An Exploratory Study.

INTRODUCTION: The aim of the study was to describe auditory and vestibular findings in Brazilian adults after COVID-19 in a municipality from the outskirts of the São Paulo state. METHODS: This was a transversal and exploratory study comprising sixteen participants infected by the SARS-CoV-2 virus, confirmed through RT-PCR detection, aged 20 to 55 years. Subjects underwent anamnesis, vestibular and auditory testing. Fisher's exact test was used to evaluate medication use, chemical and physical exposure, and occupational risk and McNemar test was used to compare auditory and vestibular symptoms pre- and post-COVID-19. RESULTS: Most patients were women (75%) and had been exposed to the virus over 90 days before testing (50%). 18.8% used hydroxychloroquine, 68.8% used ivermectin, and 87.5% used azithromycin to treat COVID-19. Auditory complaints were reported by 31.2% and vestibular by 18.7%. There was no statistical difference before and after the disease. Other reported symptomatology was hair loss, pain, fatigue, memory loss, difficulty to concentrate, and headache. Auditory findings were relevant in contralateral acoustic reflex, in the distortion-product otoacoustic emissions, and in the brainstem auditory evoked potential, characterizing a neurosensorial compromise. 43.74% of patients had altered vectonystagmography. When comparing both ears, no statistical relevance was found; however, when results were crossed with medication use and exposures, there was statistical relevance in the amplitude of the V wave for medications and absolute latency of the V wave to exposure to physical agents. DISCUSSION/CONCLUSION: This study demonstrated auditory and vestibular findings of neurosensorial nature, considering hearing and of a peripheral vestibulopathy. As it is a study of transversal nature, it is not possible to extend results to general population; yet it may be a finding to future studies.

Inter-Subject Variability in the Dependence of Medial-Olivocochlear Reflex Strength on Noise Bandwidth.

OBJECTIVES: The objective of the study was to quantify inter-subject variability in the dependence of the medial-olivocochlear reflex (MOCR) on noise bandwidth. Of specific interest was whether inter-subject variability in MOCR dependence on bandwidth explained variability in the MOCR response elicited by wideband noise. DESIGN: Thirty-two young adults with normal hearing participated in the study. Click-evoked otoacoustic emissions were measured in the ipsilateral ear with and without noise presented in the contralateral ear. Presentation of contralateral noise served to activate the MOCR. The MOCR was activated using five different noise stimuli with bandwidths ranging from 1- to 5-octaves wide (center frequency of 2 kHz; bandwidth incremented in 1-octave steps). Noise spectral levels (19.6 dB SPL/Hz) were held constant across all bandwidths. MOCR metrics included the normalized-percent change in the otoacoustic emission (OAE), the MOCR-induced OAE magnitude shift, and the MOCR-induced OAE phase shift. Linear mixed-effect models were fit to model the dependence of MOCR-induced OAE magnitude and phase changes on noise bandwidth. The use of a mixed-effect modeling approach allowed for the estimation of subject-specific model parameters that capture on- and off-frequency contributions to the MOCR effects. Regression analysis was performed to evaluate the predictive capacity of subject-specific model parameters on the MOCR response elicited by wideband noise. RESULTS: All OAE-based MOCR metrics increased as the noise bandwidth increased from 1- to 5-octaves wide. The dependence of MOCR-induced OAE magnitude and phase shifts on activator bandwidth was well approximated using a linear model with intercept and slope terms. On average, MOCR-induced magnitude and phase shifts increased at a rate of 0.3 dB/octave and 0.01 cycles/octave, respectively, as bandwidth extended beyond the predicted region of OAE generation. A statistically significant random effect of subject was found for both the intercept and slope parameter of each model. Subject-specific slope estimates were statistically significant predictors of a repeated measure of the wideband MOCR response. A higher slope was predictive of larger wideband MOCR effects. CONCLUSIONS: MOCR-induced changes to the OAE are greatest when the MOCR is elicited using wideband noise. Variability in the process of spectral integration within the MOCR pathway appears to explain, in part, inter-subject variability in OAE-based estimates of the MOCR response elicited by wideband noise.

Changing the Paradigm for School Hearing Screening Globally: Evaluation of Screening Protocols From Two Randomized Trials in Rural Alaska.

OBJECTIVES: Diagnostic accuracy was evaluated for various screening tools, including mobile health (mHealth) pure-tone screening, tympanometry, distortion product otoacoustic emissions (DPOAE), and inclusion of high frequencies to determine the most accurate screening protocol for identifying children with hearing loss in rural Alaska where the prevalence of middle ear disease is high. DESIGN: Hearing screening data were collected as part of two cluster randomized trials conducted in 15 communities in rural northwest Alaska. All children enrolled in school from preschool to 12th grade were eligible. Analysis was limited to data collected 2018 to 2019 (n = 1449), when both trials were running and measurement of high frequencies were included in the protocols. Analyses included estimates of diagnostic accuracy for each screening tool, as well as exploring performance by age and grade. Multiple imputation was used to assess diagnostic accuracy in younger children, where missing data were more prevalent due to requirements for conditioned responses. The audiometric reference standard included otoscopy, tympanometry, and high frequencies to ensure detection of infection-related and noise-induced hearing loss. RESULTS: Both the mHealth pure-tone screen and DPOAE screen performed better when tympanometry was added to the protocol (increase in sensitivity of 19.9%, 95% Confidence Interval (CI): 15.9 to 24.1 for mHealth screen, 17.9%, 95% CI: 14.0 to 21.8 for high-frequency mHealth screen, and 10.4%, 95% CI: 7.5 to 13.9 for DPOAE). The addition of 6 kHz to the mHealth pure-tone screen provided an 8.7 percentage point improvement in sensitivity (95% CI: 6.5 to 11.3). Completeness of data for both the reference standard and the mHealth screening tool differed substantially by age, due to difficulty with behavioral testing in young children. By age 7, children were able to complete behavioral testing, and data indicated that high-frequency mHealth pure-tone screen with tympanometry was the superior tool for children 7 years and older. For children 3 to 6 years of age, DPOAE plus tympanometry performed the best, both for complete data and multiply imputed data, which better approximates accuracy for children with missing data. CONCLUSIONS: This study directly evaluated pure-tone, DPOAE, and tympanometry tools as part of school hearing screening in rural Alaskan children (3 to 18+ years). Results from this study indicate that tympanometry is a key component in the hearing screening protocol, particularly in environments with higher prevalence of infection-related hearing loss. DPOAE is the preferred hearing screening tool when evaluating children younger than 7 years of age (below 2nd grade in the United States) due to the frequency of missing data with behavioral testing in this age group. For children 7 years and older, the addition of high frequencies to pure-tone screening increased the accuracy of screening, likely due to improved identification of hearing loss from noise exposure. The lack of a consistent reference standard in the literature makes comparing across studies challenging. In our study with a reference standard inclusive of otoscopy, tympanometry, and high frequencies, less than ideal sensitivities were found even for the most sensitive screening protocols, suggesting more investigation is necessary to ensure screening programs are appropriately identifying noise- and infection-related hearing loss in rural, low-resource settings.

Expectations of the timing and intensity of a stimulus propagate to the auditory periphery through the medial olivocochlear reflex.

Expectations concerning the timing of a stimulus enhance attention at the time at which the event occurs, which confers significant sensory and behavioral benefits. Herein, we show that temporal expectations modulate even the sensory transduction in the auditory periphery via the descending pathway. We measured the medial olivocochlear reflex (MOCR), a sound-activated efferent feedback that controls outer hair cell motility and optimizes the dynamic range of the sensory system. MOCR was noninvasively assessed using otoacoustic emissions. We found that the MOCR was enhanced by a visual cue presented at a fixed interval before a sound but was unaffected if the interval was changing between trials. The MOCR was also observed to be stronger when the learned timing expectation matched with the timing of the sound but remained unvaried when these two factors did not match. This implies that the MOCR can be voluntarily controlled in a stimulus- and goal-directed manner. Moreover, we found that the MOCR was enhanced by the expectation of a strong but not a weak, sound intensity. This asymmetrical enhancement could facilitate antimasking and noise protective effects without disrupting the detection of faint signals. Therefore, the descending pathway conveys temporal and intensity expectations to modulate auditory processing.

Distinct roles of stereociliary links in the nonlinear sound processing and noise resistance of cochlear outer hair cells.

Outer hair cells (OHCs) play an essential role in hearing by acting as a nonlinear amplifier which helps the cochlea detect sounds with high sensitivity and accuracy. This nonlinear sound processing generates distortion products, which can be measured as distortion-product otoacoustic emissions (DPOAEs). The OHC stereocilia that respond to sound vibrations are connected by three kinds of extracellular links: tip links that connect the taller stereocilia to shorter ones and convey force to the mechanoelectrical transduction channels, tectorial membrane-attachment crowns (TM-ACs) that connect the tallest stereocilia to one another and to the overlying TM, and horizontal top connectors (HTCs) that link adjacent stereocilia. While the tip links have been extensively studied, the roles that the other two types of links play in hearing are much less clear, largely because of a lack of suitable animal models. Here, while analyzing genetic combinations of tubby mice, we encountered models missing both HTCs and TM-ACs or HTCs alone. We found that the tubby mutation causes loss of both HTCs and TM-ACs due to a mislocalization of stereocilin, which results in OHC dysfunction leading to severe hearing loss. Intriguingly, the addition of the modifier allele modifier of tubby hearing 1 in tubby mice selectively rescues the TM-ACs but not the HTCs. Hearing is significantly rescued in these mice with robust DPOAE production, indicating an essential role of the TM-ACs but not the HTCs in normal OHC function. In contrast, the HTCs are required for the resistance of hearing to damage caused by noise stress.

Preventing presbycusis in mice with enhanced medial olivocochlear feedback.

"Growing old" is the most common cause of hearing loss. Age-related hearing loss (ARHL) (presbycusis) first affects the ability to understand speech in background noise, even when auditory thresholds in quiet are normal. It has been suggested that cochlear denervation ("synaptopathy") is an early contributor to age-related auditory decline. In the present work, we characterized age-related cochlear synaptic degeneration and hair cell loss in mice with enhanced α9α10 cholinergic nicotinic receptors gating kinetics ("gain of function" nAChRs). These mediate inhibitory olivocochlear feedback through the activation of associated calcium-gated potassium channels. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses. Cochlear structure was characterized in immunolabeled organ of Corti whole mounts using confocal microscopy to quantify hair cells, auditory neurons, presynaptic ribbons, and postsynaptic glutamate receptors. Aged wild-type mice had elevated acoustic thresholds and synaptic loss. Afferent synapses were lost from inner hair cells throughout the aged cochlea, together with some loss of outer hair cells. In contrast, cochlear structure and function were preserved in aged mice with gain-of-function nAChRs that provide enhanced olivocochlear inhibition, suggesting that efferent feedback is important for long-term maintenance of inner ear function. Our work provides evidence that olivocochlear-mediated resistance to presbycusis-ARHL occurs via the α9α10 nAChR complexes on outer hair cells. Thus, enhancement of the medial olivocochlear system could be a viable strategy to prevent age-related hearing loss.

Newborn hearing screening methodology impacts the timing of diagnosis for auditory neuropathy spectrum disorder.

INTRODUCTION: Auditory Neuropathy Spectrum Disorder (ANSD) accounts for 10 % to 15 % of pediatric hearing loss. In most cases, otoacoustic emissions (OAE) are present as the outer hair cell function is normal, and the auditory brainstem response (ABR) is abnormal. Newborn hearing screen (NBHS) is completed using OAE or ABR depending on the institution. Because OAEs are often present in ANSD, NBHS done solely with OAE can miss and delay diagnosis of patients with ANSD. OBJECTIVES: To assess whether NBHS methodology impacts the age of diagnosis of ANSD. METHODS: This is a retrospective study of patients, 0-18 years of age, diagnosed with ANSD at two tertiary pediatric hospitals from 1/01/2010 to 12/31/2018 after referral from NBHS performed in the community. Data recorded included patient demographics, method of NBHS, NICU stay, and age at ANSD diagnosis. RESULTS: 264 patients were diagnosed with ANSD. Of those, 123 (46.6 %) were female, and 141 (53.4 %) were male. Ninety-seven (36.8 %) were admitted to NICU and the mean stay was 6.98 weeks (STD = 10.7; CI = 4.8-9.1). The majority (244, 92.4 %) of patients had NBHS with ABR, and 20 (7.5 %) had NBHS with OAE. Patients screened with ABR were diagnosed with ANSD earlier than those who screened with OAE, with a mean age of 14.1 versus 27.3 weeks (p = 0.0397, CI = 15.2-39.3). Among those screened with ABR, median age at diagnosis was 4 months for NICU infants and 2.5 months for infants with no history of NICU stay over 5 days. In comparison, median diagnosis age was 8 months for non-NICU infants screened with OAEs. CONCLUSION: Patients with ANSD who had NBHS with ABR were diagnosed earlier than those with OAE. Our data suggest that universal screening with ABR may facilitate earlier diagnosis of ANSD and earlier evaluation for aural rehabilitation, especially in high-risk cohorts such as NICU patients. Further research is needed into factors that contribute to earlier diagnosis among patients screened with ABR.