Identifying Slim Modiolar Electrode Tip Fold-Over With Intracochlear Electrocochleography.

OBJECTIVE: To evaluate the predictive value of intracochlear electrocochleography (ECochG) for identifying tip fold-over during cochlear implantation (CI) using the slim modiolar electrode (SME) array. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. METHODS: From July 2022 to June 2023, 142 patients, including adults and children, underwent intracochlear ECochG monitoring during and after SME placement. Tone-bursts were presented from 250 Hz to 2 kHz at 108 to 114 dB HL. A fast Fourier transform (FFT) allowed for frequency-specific evaluation of ECochG response. ECochG patterns during insertion and postinsertion were evaluated using sensitivity and specificity analysis to predict tip fold-over. Intraoperative plain radiographs served as a reference standard. RESULTS: Fifteen tip fold-over cases occurred (10.6%) with significant ECochG response (>2 µV). Sixty-one cases without tip fold-over occurred (43.0%) with significant ECochG response. All tip fold-overs had both a nontonotopic postinsertion sweep and nonrobust active insertion pattern. No patients with robust insertion or tonotopic sweep patterns had tip fold-over. Sensitivity of detecting tip fold-over when having both nonrobust insertion and nontonotopic sweep patterns was 100% (95% confidence inteval [CI] 78.2%-100%), specificity was 68.9% (95% CI 55.7%-80.1%), and the overall accuracy was 72.0% (95% CI 60.5%-81.7%). CONCLUSION: Intracochlear ECochG monitoring during cochlear implantation with the SME can be a valuable tool for identifying properly positioned electrode arrays. In cases where ECochG patterns are nonrobust on insertion and nontonotopic for electrode sweeps, there may be a concern for tip fold-over, and intraoperative imaging is necessary to confirm proper insertion.

Improved Cochlear Implant Performance Estimation Using Tonotopic-Based Electrocochleography.

Importance: Cochlear implantation produces remarkable results in postlingual deafness, although auditory outcomes vary. Electrocochleography (ECochG) has emerged as a valuable tool for assessing the cochlear-neural substrate and evaluating patient prognosis. Objective: To assess whether ECochG-total response (ECochG-TR) recorded at the best-frequency electrode (BF-ECochG-TR) correlates more strongly with speech perception performance than ECochG-TR measured at the round window (RW-ECochG-TR). Design, Setting, and Participants: This single-center cross-sectional study recruited 142 patients from July 1, 2021, to April 30, 2022, with 1-year follow-up. Exclusions included perilymph suctioning, crimped sound delivery tubes, non-native English speakers, inner ear malformations, nonpatent external auditory canals, or cochlear implantation revision surgery. Exposures: Cochlear implantation. Main Outcomes and Measures: Speech perception testing, including the consonant-nucleus-consonant (CNC) words test, AzBio sentences in quiet, and AzBio sentences in noise plus 10-dB signal to noise ratio (with low scores indicating poor performance and high scores indicating excellent performance on all tests), at 6 months postoperatively; and RW-ECochG-TR and BF-ECochG-TR (measured for 250, 500, 1000, and 2000 Hz). Results: A total of 109 of the 142 eligible postlingual adults (mean [SD] age, 68.7 [15.8] years; 67 [61.5%] male) were included in the study. Both BF-ECochG-TR and RW-ECochG-TR were correlated with 6-month CNC scores (BF-ECochG-TR: r = 0.74; 95% CI, 0.62-0.82; RW-ECochG-TR: r = 0.67; 95% CI, 0.54-0.76). A multivariate model incorporating age, duration of hearing loss, and angular insertion depth did not outperform BF-ECochG-TR or RW-ECochG-TR alone. The BF-ECochG-TR correlation with CNC scores was significantly stronger than the RW-ECochG-TR correlation (r difference = -0.18; 95% CI, -0.31 to -0.01; z = -2.02). More moderate correlations existed between 6-month AzBio scores in noise, Montreal Cognitive Assessment (MoCA) scores (r = 0.46; 95% CI, 0.29-0.60), and BF-ECochG-TR (r = 0.42; 95% CI, 0.22-0.58). MoCA and the interaction between BF-ECochG-TR and MoCA accounted for a substantial proportion of variability in AzBio scores in noise at 6 months (R2 = 0.50; 95% CI, 0.36-0.61). Conclusions and Relevance: In this case series, BF-ECochG-TR was identified as having a stronger correlation with cochlear implantation performance than RW-ECochG-TR, although both measures highlight the critical role of the cochlear-neural substrate on outcomes. Demographic, audiologic, and surgical factors demonstrated weak correlations with cochlear implantation performance, and performance in noise was found to require a robust cochlear-neural substrate (BF-ECochG-TR) as well as sufficient cognitive capacity (MoCA). Future cochlear implantation studies should consider these variables when assessing performance and related interventions.

Factors Affecting Performance in Adults With Cochlear Implants: A Role for Cognition and Residual Cochlear Function.

OBJECTIVE: To evaluate the impact of preoperative and perioperative factors on postlinguistic adult cochlear implant (CI) performance and design a multivariate prediction model. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS AND INTERVENTIONS: Two hundred thirty-nine postlinguistic adult CI recipients. MAIN OUTCOME MEASURES: Speech-perception testing (consonant-nucleus-consonant [CNC], AzBio in noise +10-dB signal-to-noise ratio) at 3, 6, and 12 months postoperatively; electrocochleography-total response (ECochG-TR) at the round window before electrode insertion. RESULTS: ECochG-TR strongly correlated with CNC word score at 6 months ( r = 0.71, p < 0.0001). A multivariable linear regression model including age, duration of hearing loss, angular insertion depth, and ECochG-TR did not perform significantly better than ECochG-TR alone in explaining the variability in CNC. AzBio in noise at 6 months had moderate linear correlations with Montreal Cognitive Assessment (MoCA; r = 0.38, p < 0.0001) and ECochG-TR ( r = 0.42, p < 0.0001). ECochG-TR and MoCA and their interaction explained 45.1% of the variability in AzBio in noise scores. CONCLUSIONS: This study uses the most comprehensive data set to date to validate ECochG-TR as a measure of cochlear health as it relates to suitability for CI stimulation, and it further underlies the importance of the cochlear neural substrate as the main driver in speech perception performance. Performance in noise is more complex and requires both good residual cochlear function (ECochG-TR) and cognition (MoCA). Other demographic, audiologic, and surgical variables are poorly correlated with CI performance suggesting that these are poor surrogates for the integrity of the auditory substrate.

Place Coding in the Human Cochlea.

The cochlea's capacity to decode sound frequencies is enhanced by a unique structural arrangement along its longitudinal axis, a feature termed 'tonotopy' or place coding. Auditory hair cells at the cochlea's base are activated by high-frequency sounds, while those at the apex respond to lower frequencies. Presently, our understanding of tonotopy primarily hinges on electrophysiological, mechanical, and anatomical studies conducted in animals or human cadavers. However, direct in vivo measurements of tonotopy in humans have been elusive due to the invasive nature of these procedures. This absence of live human data has posed an obstacle in establishing an accurate tonotopic map for patients, potentially limiting advancements in cochlear implant and hearing enhancement technologies. In this study, we conducted acoustically-evoked intracochlear recordings in 50 human subjects using a longitudinal multi-electrode array. These electrophysiological measures, combined with postoperative imaging to accurately locate the electrode contacts allow us to create the first in vivo tonotopic map of the human cochlea. Furthermore, we examined the influences of sound intensity, electrode array presence, and the creation of an artificial third window on the tonotopic map. Our findings reveal a significant disparity between the tonotopic map at daily speech conversational levels and the conventional (i.e., Greenwood) map derived at close-to-threshold levels. Our findings have implications for advancing cochlear implant and hearing augmentation technologies, but also offer novel insights into future investigations into auditory disorders, speech processing, language development, age-related hearing loss, and could potentially inform more effective educational and communication strategies for those with hearing impairments. Significance Statement: The ability to discriminate sound frequencies, or pitch, is vital for communication and facilitated by a unique arrangement of cells along the cochlear spiral (tonotopic place). While earlier studies have provided insight into frequency selectivity based on animal and human cadaver studies, our understanding of the in vivo human cochlea remains limited. Our research offers, for the first time, in vivo electrophysiological evidence from humans, detailing the tonotopic organization of the human cochlea. We demonstrate that the functional arrangement in humans significantly deviates from the conventional Greenwood function, with the operating point of the in vivo tonotopic map showing a basal (or frequency downward) shift. This pivotal finding could have far-reaching implications for the study and treatment of auditory disorders.

Audiologic Follow-up in Patients With Head and Neck Cancer Treated With Cisplatin and Radiation.

OBJECTIVES: Evaluate factors associated with adherence to ototoxicity monitoring among patients with head and neck cancer treated with cisplatin and radiation therapy at a tertiary care center. METHODS: We performed a single-institution retrospective cohort study on adults with head and neck cancer treated with cisplatin and radiation therapy who participated in an ototoxicity monitoring program. The primary outcomes were rates of post-treatment audiograms at the following time points: one, three, six, 12, and greater than 12 months. Multivariable logistic regression was performed to identify risk factors associated with complete loss of follow-up after pre-treatment evaluation. RESULTS: Two hundred ninety-four head and neck cancer patients were analyzed. Overall, 220 (74.8%) patients had at least one post-treatment audiogram; 58 (20.0%) patients had more than one audiogram. The time point with the highest follow-up rate was at 3 months (n = 170, 57.8%); rates at the remaining times ranged from 7.1% to 14.3%. When controlling for covariates, patients without insurance and those with stage IV cancers were associated with complete loss of audiologic follow-up (aOR = 7.18, 95% CI = 2.75-19.90; aOR = 1.96, 95% CI = 1.02-3.77, respectively). Among 156 patients recommended for a hearing aid, only 39 (24.8%) patients received one. CONCLUSIONS: Head and neck cancer patients enrolled in an ototoxicity monitoring program demonstrate moderately high follow-up rates for at least one post-treatment audiogram. However, follow-up tapers dramatically after 6 months, and overall hearing aid utilization is low. Further research is needed to understand barriers to long-term audiologic follow-up and hearing aid utilization to decrease untreated hearing loss in cancer survivorship. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 133:3161-3168, 2023.

Is Characteristic Frequency Limiting Real-Time Electrocochleography During Cochlear Implantation?

Objectives: Electrocochleography (ECochG) recordings during cochlear implantation have shown promise in estimating the impact on residual hearing. The purpose of the study was (1) to determine whether a 250-Hz stimulus is superior to 500-Hz in detecting residual hearing decrement and if so; (2) to evaluate whether crossing the 500-Hz tonotopic, characteristic frequency (CF) place partly explains the problems experienced using 500-Hz. Design: Multifrequency ECochG comprising an alternating, interleaved acoustic complex of 250- and 500-Hz stimuli was used to elicit cochlear microphonics (CMs) during insertion. The largest ECochG drops (≥30% reduction in CM) were identified. After insertion, ECochG responses were measured using the individual electrodes along the array for both 250- and 500-Hz stimuli. Univariate regression was used to predict whether 250- or 500-Hz CM drops explained low-frequency pure tone average (LFPTA; 125-, 250-, and 500-Hz) shift at 1-month post-activation. Postoperative CT scans were performed to evaluate cochlear size and angular insertion depth. Results: For perimodiolar insertions (N = 34), there was a stronger linear correlation between the largest ECochG drop using 250-Hz stimulus and LFPTA shift (r = 0.58), compared to 500-Hz (r = 0.31). The 250- and 500-Hz CM insertion tracings showed an amplitude peak at two different locations, with the 500-Hz peak occurring earlier in most cases than the 250-Hz peak, consistent with tonotopicity. When using the entire array for recordings after insertion, a maximum 500-Hz response was observed 2-6 electrodes basal to the most-apical electrode in 20 cases (58.9%). For insertions where the apical insertion angle is >350 degrees and the cochlear diameter is <9.5 mm, the maximum 500-Hz ECochG response may occur at the non-apical most electrode. For lateral wall insertions (N = 14), the maximum 250- and 500-Hz CM response occurred at the most-apical electrode in all but one case. Conclusion: Using 250-Hz stimulus for ECochG feedback during implantation is more predictive of hearing preservation than 500-Hz. This is due to the electrode passing the 500-Hz CF during insertion which may be misidentified as intracochlear trauma; this is particularly important in subjects with smaller cochlear diameters and deeper insertions. Multifrequency ECochG can be used to differentiate between trauma and advancement of the apical electrode beyond the CF.

Can Electrocochleography Help Preserve Hearing After Cochlear Implantation With Full Electrode Insertion?

OBJECTIVES: To evaluate the utility of intracochlear electrocochleography (ECochG) monitoring during cochlear implant (CI) surgery on postoperative hearing preservation. STUDY DESIGN: Prospective, randomized clinical trial. SETTING: Ten high-volume, tertiary care CI centers. PATIENTS: Adult patients with sensorineural hearing loss meeting the CI criteria who selected an Advanced Bionics CI. METHODS: Patients were randomized to CI surgery either with audible ECochG monitoring available to the surgeon during electrode insertion or without ECochG monitoring. Hearing preservation was determined by comparing preoperative unaided low-frequency (125-, 250-, and 500-Hz) pure-tone average (LF-PTA) to postoperative LF-PTA at CI activation. Pre- and post-CI computed tomography was used to determine electrode scalar location and electrode translocation. RESULTS: Eighty-five adult CI candidates were enrolled. The mean (standard deviation [SD]) unaided preoperative LF-PTA across the sample was 54 (17) dB HL. For the whole sample, hearing preservation was "good" (i.e., LF-PTA change 0-15 dB) in 34.5%, "fair" (i.e., LF-PTA change >15-29 dB) in 22.5%, and "poor" (i.e., LF-PTA change ≥30 dB) in 43%. For patients randomized to ECochG "on," mean (SD) LF-PTA change was 27 (20) dB compared with 27 (23) dB for patients randomized to ECochG "off" ( p = 0.89). Seven percent of patients, all of whom were randomized to ECochG off, showed electrode translocation from the scala tympani into the scala vestibuli. CONCLUSIONS: Although intracochlear ECochG during CI surgery has important prognostic utility, our data did not show significantly better hearing preservation in patients randomized to ECochG "on" compared with ECochG "off."

Promontory Electrocochleography Recordings to Predict Speech-Perception Performance in Cochlear Implant Recipients.

OBJECTIVE: 1) To determine the relationship of electrocochleography (ECochG) responses measured on the promontory with responses measured at the round window (RW) and various intracochlear sites. 2) To evaluate if promontory ECochG responses correlate with postoperative speech-perception performance using the cochlear implant (CI). STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS AND INTERVENTIONS: Ninety-six adult CI recipients with no cochlear malformations or previous otologic surgery. MAIN OUTCOME MEASURES: Acoustically evoked ECochG responses were measured intraoperatively at both extracochlear and intracochlear locations. ECochG total response (ECochG-TR), a measure of residual cochlear function, was calculated by summing the fast Fourier transformation amplitudes in response to 250-Hz to 2-kHz acoustic stimuli. Speech-perception performance was measured at 3 months. RESULTS: There were strong linear correlations for promontory ECochG-TR with the ECochG-TRs measured at the RW ( r = 0.95), just inside scala tympani ( r = 0.91), and after full insertion ( r = 0.83). For an individual subject, the morphology of the ECochG response was similar in character across all positions; however, the response amplitude increased from promontory to RW (~1.6-fold) to just inside scala tympani (~2.6-fold), with the largest response at full insertion (~13.1-fold). Promontory ECochG-TR independently explained 51.8% of the variability ( r2 ) in consonant-nucleus-consonant at 3 months. CONCLUSIONS: Promontory ECochG recordings are strongly correlated with responses previously recorded at extracochlear and intracochlear sites and explain a substantial portion of the variability in CI performance. These findings are a critical step in supporting translation of transtympanic ECochG into the clinic preoperatively to help predict postoperative CI performance.

Electrocochleography and cognition are important predictors of speech perception outcomes in noise for cochlear implant recipients.

Although significant progress has been made in understanding outcomes following cochlear implantation, predicting performance remains a challenge. Duration of hearing loss, age at implantation, and electrode positioning within the cochlea together explain ~ 25% of the variability in speech-perception scores in quiet using the cochlear implant (CI). Electrocochleography (ECochG) responses, prior to implantation, account for 47% of the variance in the same speech-perception measures. No study to date has explored CI performance in noise, a more realistic measure of natural listening. This study aimed to (1) validate ECochG total response (ECochG-TR) as a predictor of performance in quiet and (2) evaluate whether ECochG-TR explained variability in noise performance. Thirty-five adult CI recipients were enrolled with outcomes assessed at 3-months post-implantation. The results confirm previous studies showing a strong correlation of ECochG-TR with speech-perception in quiet (r = 0.77). ECochG-TR independently explained 34% of the variability in noise performance. Multivariate modeling using ECochG-TR and Montreal Cognitive Assessment (MoCA) scores explained 60% of the variability in speech-perception in noise. Thus, ECochG-TR, a measure of the cochlear substrate prior to implantation, is necessary but not sufficient for explaining performance in noise. Rather, a cognitive measure is also needed to improve prediction of noise performance.

Hearing Preservation After Cochlear Reimplantation Using Electrocochleography: A Case Report.

Studies have shown that hearing preservation is possible in the context of reimplantation, but residual hearing could not be predicted or expected in these cases. We describe a case in which a patient with mild to profound sensorineural hearing loss who underwent cochlear implantation with a lateral wall array and had hearing preserved postoperatively. She developed facial nerve stimulation which was unresponsive to reprogramming. Using electrocochleography to measure intracochlear trauma during the insertion process, the patient underwent reimplantation with a perimodiolar electrode and hearing was preserved postoperatively. This case demonstrates the potential to use electrocochleography for hearing preservation during reimplantation. Laryngoscope, 131:2348-2351, 2021.

Intraoperative Cochlear Nerve Monitoring for Vestibular Schwannoma Resection and Simultaneous Cochlear Implantation in Neurofibromatosis Type 2: A Case Series.

BACKGROUND: Neurofibromatosis type 2 (NF2) often results in profound hearing loss and cochlear implantation is an emerging hearing rehabilitation option. However, cochlear implant (CI) outcomes in this population vary, and intraoperative monitoring to predict cochlear nerve viability and subsequent outcomes is not well-established. OBJECTIVE: To review the use of intraoperative electrically evoked cochlear nerve monitoring in patients with NF2 simultaneous translabyrinthine (TL) vestibular schwannoma (VS) resection and cochlear implantation. METHODS: A retrospective review was performed of 3 patients with NF2 that underwent simultaneous TL VS resection and cochlear implantation with electrical auditory brainstem response (eABR) measured throughout tumor resection. Patient demographics, preoperative assessments, surgical procedures, and outcomes were reviewed. RESULTS: Patients 1 and 3 had a reliable eABR throughout tumor removal. Patient 2 had eABR pretumor removal, but post-tumor removal eABR presence could not be reliably determined because of electrical artifact interference. All patients achieved auditory percepts upon CI activation. Patients 1 and 2 experienced a decline in CI performance after 1 yr and after 3 mo, respectively. Patient 3 continues to perform well at 9 mo. Patients 2 and 3 are daily users of their CI. CONCLUSION: Cochlear implantation is attainable in cases of NF2-associated VS resection. Intraoperative eABR may facilitate cochlear nerve preservation during tumor removal, though more data and long-term outcomes are needed to refine eABR methodology and predictive value for this population.

Intracochlear Electrocochleography and Speech Perception Scores in Cochlear Implant Recipients.

OBJECTIVES/HYPOTHESIS: Previous studies have demonstrated that electrocochleography (ECochG) measurements made at the round window prior to cochlear implant (CI) electrode insertion can account for 47% of the variability in 6-month speech perception scores. Recent advances have made it possible to use the apical CI electrode to record intracochlear responses to acoustic stimuli. Study objectives were to determine 1) the relationship between intracochlear ECochG response amplitudes and 6-month speech perception scores and 2) to determine the relationship between behavioral auditory thresholds and ECochG threshold estimates. The hypothesis was that intracochlear ECochG response amplitudes made immediately after electrode insertion would be larger than historical controls (at the extracochlear site) and explain more variability in speech perception scores. STUDY DESIGN: Prospective case series. METHODS: Twenty-two adult CI recipients with varying degrees of low-frequency hearing had intracochlear ECochG measurements made immediately after CI electrode insertion using 110 dB SPL tone bursts. Tone bursts were centered at five octave-spaced frequencies between 125 and 2,000 Hz. RESULTS: There was no association between intracochlear ECochG response amplitudes and speech perception scores. But, the data suggest a mild to moderate relationship between preoperative behavioral audiometric testing and intraoperative ECochG threshold estimates. CONCLUSION: Performing intracochlear ECochG is highly feasible and results in larger response amplitudes, but performing ECochG before, rather than after, CI insertion may provide a more accurate assessment of a patient's speech perception potential. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2681-E2688, 2021.

Weakened Cochlear Nonlinearity During Human Aging and Perceptual Correlates.

OBJECTIVE: As humans age, compressive nonlinearity-a hallmark of healthy cochlear function-changes. The nonlinear distortion-component of the distortion product otoacoustic emission (DPOAE) provides a noninvasive gauge of cochlear nonlinearity. Earlier published work has suggested that weakened nonlinearity begins in middle age; the current work extends this investigation into the eight decade of life using advanced DPOAE data collection and analysis methods as well as multiple metrics of nonlinearity, including a test of loudness scaling. DESIGN: The 2f1-f2 DPOAE was recorded in 20 young adults, 25 middle-aged adults and 32 older adults from f2 = 0.78 to 9.4 kHz with primary tones (f2/f1 = 1.22) swept upward at a rate of 0.5 octave/sec. Only frequencies with audiometric thresholds ≤20 dB HL were included in the analysis and to the extent possible, ears were audiometrically matched to eliminate hearing threshold as a contributing factor to the observed age effects. Input/output functions were generated for the separated distortion-component of the DPOAE to probe compressive nonlinearity of the cochlea, and ipsilateral suppression of the DPOAE was conducted to probe two-tone suppression. To investigate the perceptual effects of weakening nonlinearity on loudness perception, the same subjects performed categorical loudness scaling. Age effects on both DPOAE and loudness scaling variables were assessed, and correlations were conducted between key OAE and perceptual metrics. RESULTS: Age × Frequency ANOVAs revealed that the compression knee of the DPOAE I/O function occurred at higher stimulus levels in both groups of older adults compared to young adults, suggesting an expanded linear range with aging; also, the compressive slope (growth beyond the knee point) was steeper in older-adults compared to young adults. These results were most notable at high frequencies. ANOVAs including age and auditory threshold as factors confirmed that the age effect observed was independent of threshold. Additionally, in smaller subsets of subjects with audiometrically matched data, these same trends persisted, further ruling out hearing threshold as an influential factor. The growth of DPOAE ipsilateral suppression was shallower near 4 kHz in middle-aged and older adults compared to young adults and elevated suppression thresholds were observed. Results of categorical loudness scaling showed steeper growth of loudness for older adults and, at fixed sensation levels (dB SL), the older-adult group rated tones as louder than did their young-adult counterparts, suggesting abnormal loudness growth and perception. Several correlations between the compression knee of the DPOAE I/O function and key metrics of loudness scaling were significant and accounted for up to one-third of the variance. CONCLUSIONS: Results indicate that the aging cochlea begins to show weakened nonlinearity in middle age and it progressively weakens further into senescence. The perceptual impact of weakened nonlinearity during aging is manifested as abnormal loudness judgments; that is, in older-adult ears, a tone considered comfortable or medium in young-adult ears can be considered loud. The biophysical origin of this weakened nonlinearity is not known. It is hypothesized to reflect aging-related damage to, or loss of, outer hair cells and their stereocilia. More work is warranted to better define the perceptual impact of a linearized cochlear response in older adults and to consider how this deficit might impact the fitting of hearing aids and other intervention strategies.

Is cochlear synapse loss an origin of low-frequency hearing loss associated with endolymphatic hydrops?

There is a strong association between endolymphatic hydrops and low-frequency hearing loss, but the origin of the hearing loss remains unknown. A reduction in the number of cochlear afferent synapses between inner hair cells and auditory nerve fibres may be the origin of the low-frequency hearing loss, but this hypothesis has not been directly tested in humans or animals. In humans, measurements of hearing loss and postmortem temporal-bone based measurements of endolymphatic hydrops are generally separated by large amounts of time. In animals, there has not been a good objective, physiologic, and minimally invasive measurement of low-frequency hearing. We overcame this obstacle with the combined use of a reliable surgical approach to ablate the endolymphatic sac in guinea pigs and create endolymphatic hydrops, the Auditory Nerve Overlapped Waveform to measure low-frequency hearing loss (≤ 1 kHz), and immunohistofluorescence-based confocal microscopy to count cochlear synapses. Results showed low- and mid-(1-4 kHz) frequency hearing loss at all postoperative days, 1, 4, and 30. There was no statistically significant loss of cochlear synapses, and there was no correlation between synapse loss and hearing function. We conclude that cochlear afferent synaptic loss is not the origin of the low-frequency hearing loss in the early days following endolymphatic sac ablation. Understanding what is, and is not, the origin of a hearing loss can help guide preventative and therapeutic development.

Noise in the neonatal intensive care unit: a new approach to examining acoustic events.

INTRODUCTION: Environmental noise is associated with negative developmental outcomes for infants treated in the neonatal intensive care unit (NICU). The existing noise level recommendations are outdated, with current studies showing that these standards are universally unattainable in the modern NICU environment. STUDY AIM: This study sought to identify the types, rate, and levels of acoustic events that occur in the NICU and their potential effects on infant physiologic state. MATERIALS AND METHODS: Dosimeters were used to record the acoustic environment in open and private room settings of a large hospital NICU. Heart and respiratory rate data of three infants located near the dosimeters were obtained. Infant physiologic data measured at time points when there was a marked increase in sound levels were compared to data measured at time points when the acoustic levels were steady. RESULTS: All recorded sound levels exceeded the recommended noise level of 45 decibels, A-weighted (dBA). The 4-h Leq of the open-pod environment was 58.1 dBA, while the private room was 54.7 dBA. The average level of acoustic events was 11-14 dB higher than the background noise. The occurrence of transient events was 600% greater in the open room when compared to the private room. While correlations between acoustic events and infant physiologic state could not be established due to the extreme variability of infant state, a few trends were visible. Increasing the number of data points to overcome the extreme physiologic variability of medically fragile neonates would not be feasible or cost-effective in this environment. CONCLUSION: NICU noise level recommendations need to be modified with an emphasis placed on reducing acoustic events that disrupt infant state. The goal of all future standards should be to optimize infant neurodevelopmental outcomes.

Reflection- and Distortion-Source Otoacoustic Emissions: Evidence for Increased Irregularity in the Human Cochlea During Aging.

Previous research on distortion product otoacoustic emission (DPOAE) components has hinted at possible differences in the effect of aging on the two basic types of OAEs: those generated by a reflection mechanism in the cochlea and those created by nonlinear distortion (Abdala and Dhar in J Assoc Res Otolaryngol 13:403-421, 2012). This initial work led to the hypothesis that micromechanical irregularity ("roughness") increases in the aging cochlea, perhaps as the result of natural tissue degradation. Increased roughness would boost the backscattering of traveling waves (i.e., reflection emissions) while minimally impacting DPOAEs. To study the relational effect of aging on both types of emissions and address our hypothesis of its origin, we measured reflection- and distortion-type OAEs in 77 human subjects aged 18-76 years. The stimulus-frequency OAE (SFOAE), a reflection emission, and the distortion component of the DPOAE, a nonlinear distortion emission, were recorded at multiple stimulus levels across a four-octave range in all ears. Although the levels of both OAE types decreased with age, the rate of decline in OAE level was consistently greater for DPOAEs than for SFOAEs; that is, SFOAEs are relatively preserved with advancing age. Multiple regression analyses and other controls indicate that aging per se, and not hearing loss, drives this effect. Furthermore, SFOAE generation was simulated using computational modeling to explore the origin of this result. Increasing the amount of mechanical irregularity with age produced an enhancement of SFOAE levels, providing support for the hypothesis that increased intra-cochlear roughness during aging may preserve SFOAE levels. The characteristic aging effect-relatively preserved reflection-emission levels combined with more markedly reduced distortion-emission levels-indicates that SFOAE magnitudes in elderly individuals depend on more than simply the gain of the cochlear amplifier. This relative pattern of OAE decline with age may provide a diagnostic marker for aging-related changes in the cochlea.

Changes in the Compressive Nonlinearity of the Cochlea During Early Aging: Estimates From Distortion OAE Input/Output Functions.

OBJECTIVES: The level-dependent growth of distortion product otoacoustic emissions (DPOAEs) provides an indirect metric of cochlear compressive nonlinearity. Recent evidence suggests that aging reduces nonlinear distortion emissions more than those associated with linear reflection. Therefore, in this study, we generate input/output (I/O) functions from the isolated distortion component of the DPOAE to probe the effects of early aging on the compressive nonlinearity of the cochlea. DESIGN: Thirty adults whose ages ranged from 18 to 64 years participated in this study, forming a continuum of young to middle-age subjects. When necessary for analyses, subjects were divided into a young-adult group with a mean age of 21 years, and a middle-aged group with a mean age of 52 years. All young-adult subjects and 11 of the middle-aged subjects had normal hearing; 4 middle-aged ears had slight audiometric threshold elevation at mid-to-high frequencies. DPOAEs (2f1 - f2) were recorded using primary tones swept upward in frequency from 0.5 to 8 kHz, and varied from 25 to 80 dB sound pressure level. The nonlinear distortion component of the total DPOAE was separated and used to create I/O functions at one-half octave intervals from 1.3 to 7.4 kHz. Four features of OAE compression were extracted from a fit to these functions: compression threshold, range of compression, compression slope, and low-level growth. These values were compared between age groups and correlational analyses were conducted between OAE compression threshold and age with audiometric threshold controlled. RESULTS: Older ears had reduced DPOAE amplitude compared with young-adult ears. The OAE compression threshold was elevated at test frequencies above 2 kHz in the middle-aged subjects by 19 dB (35 versus 54 dB SPL), thereby reducing the compression range. In addition, middle-aged ears showed steeper amplitude growth beyond the compression threshold. Audiometric threshold was initially found to be a confound in establishing the relationship between compression and age; however, statistical analyses allowed us to control its variance. Correlations performed while controlling for age differences in high-frequency audiometric thresholds showed significant relationships between the DPOAE I/O compression threshold and age: Older subjects tended to have elevated compression thresholds compared with younger subjects and an extended range of monotonic growth. CONCLUSIONS: Cochlear manifestations of nonlinearity, such as the DPOAE, weaken during early aging, and DPOAE I/O functions become linearized. Commensurate changes in high-frequency audiometric thresholds are not sufficient to fully explain these changes. The results suggest that age-related changes in compressive nonlinearity could produce a reduced dynamic range of hearing, and contribute to perceptual difficulties in older listeners.

Inheritance patterns of noise vulnerability and "protectability" in (C57BL/6J × CBA/J) F1 hybrid mice.

BACKGROUND: Interindividual variation in cochlear vulnerability to noise and ototoxins must in part reflect allelic variation in genes that largely remain unknown. Work in our laboratory has shown that young adult CBA/J mice are more vulnerable to cochlear noise injury than are similar-aged mice of other well-studied strains such as C57BL/6J (B6). Conversely, young CBA/J mice are dramatically protected against noise exposure by low-dose kanamycin (KM) treatment, while B6 mice are not. Genetic differences that distinguish these two strains may include genes that help establish the early "sensitive period" in mammals, as well as genes that shape innate protective responses to stress. These genes may have human homologs that exert similar influences and thereby partly govern individual risk of acquired hearing loss. PURPOSE: We hypothesize that young CBA/J and B6 mice carry different alleles at unknown loci that mediate their characteristic sensitivities to noise and responses to kanamycin. The first step in any experimental genetic analysis of two divergent populations is to examine F1 hybrids formed from these. Accordingly, we evaluated both noise vulnerability and the extent of protection from noise by low-dose KM in 6-wk-old F1 hybrids derived from a B6 × CBA/J cross. STUDY SAMPLE: The study included 52 CBA/J, 59 C57BL/6J (B6), and 45 (B6 × CBA/J) F1 hybrid mice, aged 6 wk at time of noise exposure. Both genders were included. INTERVENTION: For experiments aimed at noise vulnerability, B6 and F1 mice were exposed to loud broadband noise (4-45 kHz, 110 dB SPL) for varying durations, and the resulting noise-induced permanent threshold shifts (NIPTSs, measured 2 wk postnoise) were compared with previous data from CBA/J mice. For experiments aimed at KM-based "protectability," CBA/J, B6, and F1 mice received either kanamycin (300 mg/kg, sc) or saline twice daily for 10 days and then were noise exposed for 30 min, followed by measurement of NIPTS at 2 wk postnoise. DATA COLLECTION AND ANALYSIS: Data comprised auditory brainstem response (ABR) thresholds examined by two-way ANOVA (threshold × frequency, group) and derived metrics for NIPTS, plotted versus noise duration. RESULTS: The "threshold" noise exposure duration for NIPTS in F1 hybrid mice was similar to that in CBA/J. Like CBA/J mice, F1 mice were also significantly protected from noise by KM although the protection appeared less robust than in the CBA/J parent strain. B6 mice appeared harmed by KM alone, even without noise exposure. None of the experimental groups provided any evidence for synergistic interactions between noise and KM. CONCLUSIONS: Our data support the hypothesis that young CBA/J and B6 mice carry different alleles that underlie their divergent responses to KM and sensitivities to noise exposure. While the number and type of genes remain unknown, they are worth pursuing because they establish completely novel hearing phenotypes with potential relevance to humans. Our results lay the foundation for mapping of the underlying genes, and ultimately gene identification.

Sudden sensorineural hearing loss and delayed complete sudden spontaneous recovery.

This is a case report of a 53-yr-old female who experienced sudden sensorineural hearing loss (SSNHL) accompanied by roaring tinnitus in her right ear. The patient's hearing partially improved in the low frequencies in response to intratympanic injections. Given that her hearing loss did not improve further, the patient was fitted with a hearing aid to mask the tinnitus and restore a sense of balance between the two ears. Approximately 9 mo postonset of the SSNHL, a complete spontaneous recovery of hearing occurred. Such a delayed and complete recovery is highly unusual. This case highlights that the spontaneous recovery in hearing indicates that the pathological cause for the SSNHL involved a process that was capable of repair or regeneration, thus ruling out pathologies related to cochlear hair cell destruction or nerve fiber loss. This leaves a possibility that the event causing the onset of the SSNHL resulted in a disruption of the ion homeostatic properties of the cochlea via the production of the endocochlear potential.

Divergence of noise vulnerability in cochleae of young CBA/J and CBA/CaJ mice.

CBA/CaJ and CBA/J inbred mouse strains appear relatively resistant to age- and noise-related cochlear pathology, and constitute the predominant 'good hearing' control strains in mouse studies of hearing and deafness. These strains have often been treated as nearly equivalent in their hearing characteristics, and have even been mixed in some studies. Nevertheless, we recently showed that their trajectories with regard to age-associated cochlear pathology diverge after one year of age (Ohlemiller et al., 2010a). We also recently reported that they show quite different susceptibility to cochlear noise injury during the 'sensitive period' of heightened vulnerability to noise common to many models, CBA/J being far more vulnerable than CBA/CaJ (Fernandez et al., 2010 J. Assoc. Res. Otolaryngol. 11:235-244). Here we explore this relation in a side-by-side comparison of the effect of varying noise exposure duration in young (6 week) and older (6 month) CBA/J and CBA/CaJ mice, and in F1 hybrids formed from these. Both the extent of permanent noise-induced threshold shifts (NIPTS) and the probability of a defined NIPTS were determined as exposure to intense broadband noise (4-45 kHz, 110 dB SPL) increased by factors of two from 7 s to 4 h. At 6 months of age the two strains appeared very similar by both measures. At 6 weeks of age, however, both the extent and probability of NIPTS grew much more rapidly with noise duration in CBA/J than in CBA/CaJ. The 'threshold' exposure duration for NIPTS was <1.0 min in CBA/J versus >4.0 min in CBA/CaJ. F1 hybrid mice showed both NIPTS and hair cell loss similar to that in CBA/J. This suggests that dominant-acting alleles at unknown loci distinguish CBA/J from CBA/CaJ. These loci have novel effects on hearing phenotype, as they come into play only during the sensitive period, and may encode factors that demarcate this period. Since the cochlear cells whose fragility defines the early window appear to be hair cells, these loci may principally impact the mechanical or metabolic resiliency of hair cells or the organ of Corti.