Auditory Brainstem Response Wave Research Articles

Electrocochleography and Auditory Brainstem Responses in Persons with Non-Optimal Blood Pressure.

Numerous cardiometabolic factors may underlie risk of hearing loss. Modifiable risk factors such as non-optimal blood pressure (BP) are of interest. To investigate early auditory evoked potentials (AEPs) in persons with nonoptimal BP. A cross-sectional nonexperimental study was performed. Fifty-two adults (18-55 years) served as subjects. Individuals were classified as having optimal (systolic [S] BP < 120 and diastolic [D] BP < 80 mm Hg, n = 25) or non-optimal BP (SBP ≥=120 or DBP ≥=80 mm Hg or antihypertensive use, n = 27). Thirteen subjects had hypertension (HTN) (SBP ≥130 or DBP ≥80 mm Hg or use of antihypertensives). Behavioral thresholds from 0.25 to 16 kHz were collected. Threshold auditory brain stem responses (ABRs) were recorded using rarefaction clicks (17.7/second) from 80 dB nHL to wave V threshold. Electrocochleograms were obtained with 90 dB nHL 7.1/second alternating clicks and assessed for summating and compound action potentials (APs). Outcomes were compared via independent samples t tests. Linear mixed effects models for behavioral thresholds and ABR wave latencies were constructed to account for potential confounders. Wave I and III latencies were comparable between optimal and non-optimal BP groups. Wave I was prolonged in hypertensive versus optimal BP subjects at stimulus level 70 dB nHL (p = 0.016). ABR wave V latencies were prolonged in non-optimal BP at stimulus level 80 dB nHL (p = 0.048) and in HTN at levels of 80, 50, and 30 dB nHL (all p < 0.050). DBP was significantly correlated with wave V latency (r = 0.295; p = 0.039). No differences in ABR amplitudes were observed between optimal and non-optimal BP subjects. Electrocochleographic study showed statistically comparable action and summating potential amplitudes between optimal and non-optimal BP subjects. AP latencies were also similar between the groups. Analysis using a set baseline amplitude of 0 μV showed that hypertensive subjects had higher summating (p = 0.038) and AP (p = 0.047) amplitudes versus optimal BP subjects; AP latencies were comparable. Elevated BP and more specifically, HTN was associated with subtle AEP abnormalities. This study provides preliminary evidence that nonoptimal BP, and more specifically HTN, may be related to auditory neural dysfunction; larger confirmatory studies are warranted.

Peripheral Auditory Function in Young HIV-Positive Adults With Clinically Normal Hearing.

Little is known about peripheral auditory function in young adults with HIV, who might be expected to show early evidence of hearing loss if HIV infection or treatment does affect peripheral function. The goal of this study was to compare peripheral auditory function in 2 age- and gender-matched groups of young adults with clinically normal hearing with and without HIV. Matched cohort study with repeated measures. Infectious disease center in Dar es Salaam, Tanzania. Participants included HIV-positive (n = 38) and HIV-negative (n = 38) adults aged 20 to 30 years who had clinically normal hearing, defined as type A tympanograms, air conduction thresholds ≤25 dB HL bilaterally from 0.5 to 8 kHz, and distortion product otoacoustic emissions (DPOAEs) >6 dB above the noise floor bilaterally from 1.5 to 8 kHz. Participants were tested multiple times over 6-month intervals (average, 2.7 sessions/participant) for a total of 208 observations. Primary outcome measures included tympanograms, air conduction audiograms, DPOAEs, and click-evoked auditory brainstem responses. HIV groups did not significantly differ in age, static immittance, or air conduction thresholds. HIV-positive status was independently associated with approximately 3.7-dB lower DPOAE amplitudes from 2 to 8 kHz (95% CI, 1.01-6.82) in both ears and 0.04-µV lower (95% CI, 0.003-0.076) auditory brainstem response wave I amplitudes in the right ear. Young adults living with HIV have slightly but reliably smaller DPOAEs and auditory brainstem response wave I amplitudes than matched HIV-negative controls. The magnitude of these differences is small, but these results support measuring peripheral auditory function in HIV-positive individuals as they age.

Auditory brainstem responses to high-resolution audio sounds: Effects of anti-alias filters

Despite the superior technical specifications of high-resolution audio in comparison to conventional compact discs (CDs) and digital versatile discs (DVDs), whether and how high-resolution audio leads to an improved subjective listening experience remains unclear. The sound quality of conventional digital formats is deteriorated by temporal blur, which is caused by a high-cut filter applied to avoid aliasing of a digital sound source, resulting in spurious artificial sound energy before and after the actual sound onset. Using sound materials of high-resolution audio grade, this study investigated the effects of filter-induced temporal blur on the auditory neural pathway from the cochlea through the rostral brainstem by measuring the auditory brainstem responses (ABRs) of participants with normal hearing. The participants (N = 24) listened to 0.1-ms clicks, with and without a high-cut filter of 22 kHz or 11 kHz applied to them. The amplitudes and latencies of five ABR waves (<10 ms) revealed no significant effects caused by filtering. The participants could not distinguish between the original and the 22-kHz filtered click sounds, while they could distinguish between the original and the 11-kHz filtered sounds. These results indicate that a CD-level anti-alias filter does not affect initial auditory processing and the sound difference is not discernible, at least for artificial sounds with a simple acoustic structure.

Development of Tinnitus and Hyperacusis in a Mouse Model of Tobramycin Cochleotoxicity.

Aminoglycosides (AG) antibiotics are a common treatment for recurrent infections in cystic fibrosis (CF) patients. AGs are highly ototoxic, resulting in a range of auditory dysfunctions. It was recently shown that the acoustic startle reflex (ASR) can assess behavioral evidence of hyperacusis and tinnitus in an amikacin cochleotoxicity mouse model. The goal of this study was to establish if tobramycin treatment led to similar changes in ASR behavior and to establish whether ebselen can prevent the development of these maladaptive neuroplastic symptoms. CBA/Ca mice were divided into three groups: Group 1 served as a control and did not receive tobramycin or ebselen, Group 2 received tobramycin (200 mg/kg/s.c.) and the vehicle (DMSO/saline/i.p.) daily for 14 continuous days, and Group 3 received the same dose/schedule of tobramycin as Group 2 and ebselen at (20 mg/kg/i.p.). Auditory brainstem response (ABR) and ASR hearing assessments were collected at baseline and 2, 6, 10, 14, and 18 weeks from the start of treatment. ASR tests included input/output (I/O) functions which assess general hearing and hyperacusis, and Gap-induced prepulse inhibition of the acoustic startle (GPIAS) to assess tinnitus. At 18 weeks, histologic analysis showed predominantly normal appearing hair cells and spiral ganglion neuron (SGN) synapses. Following 14 days of tobramycin injections, 16 kHz thresholds increased from baseline and fluctuated over the 18-week recovery period. I/O functions revealed exaggerated startle response magnitudes in 50% of mice over the same period. Gap detection deficits, representing behavioral evidence of tinnitus, were observed in a smaller subset (36%) of animals. Interestingly, increases in ABR wave III/wave I amplitude ratios were observed. These tobramycin data corroborate previous findings that AGs can result in hearing dysfunctions. We show that a 14-day course of tobramycin treatment can cause similar levels of hearing loss and tinnitus, when compared to a 14-day course of amikacin, but less hyperacusis. Evidence suggests that tinnitus and hyperacusis might be common side effects of AG antibiotics.

Local magnetic delivery of adeno-associated virus AAV2(quad Y-F)-mediated BDNF gene therapy restores hearing after noise injury

Moderate noise exposure may cause acute loss of cochlear synapses without affecting the cochlear hair cells and hearing threshold; thus, it remains "hidden" to standard clinical tests. This cochlear synaptopathy is one of the main pathologies of noise-induced hearing loss (NIHL). There is no effective treatment for NIHL, mainly because of the lack of a proper drug-delivery technique. We hypothesized that local magnetic delivery of gene therapy into the inner ear could be beneficial for NIHL. In this study, we used superparamagnetic iron oxide nanoparticles (SPIONs) and a recombinant adeno-associated virus (AAV) vector (AAV2(quad Y-F)) to deliver brain-derived neurotrophic factor (BDNF) gene therapy into the rat inner ear via minimally invasive magnetic targeting. We found that the magnetic targeting effectively accumulates and distributes the SPION-tagged AAV2(quad Y-F)-BDNF vector into the inner ear. We also found that AAV2(quad Y-F) efficiently transfects cochlear hair cells and enhances BDNF gene expression. Enhanced BDNF gene expression substantially recovers noise-induced BDNF gene downregulation, auditory brainstem response (ABR) wave I amplitude reduction, and synapse loss. These results suggest that magnetic targeting of AAV2(quad Y-F)-mediated BDNF gene therapy could reverse cochlear synaptopathy after NIHL.

Effects of Aging Versus Noise Exposure on Auditory System in Individuals With Normal Audiometric Thresholds.

Background: The study aims at investigating the effect of aging and noise exposure on the auditory system using auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and contralateral suppression of OAEs (CSOAEs). The objective was to compare DPOAEs, CSOAEs, and ABR in aged and noise-exposed individuals with the normal, to find an indicator for early diagnosis of auditory damage.Methods: Sixty adult male participants were divided into 3 groups. Group 1 included individuals not exposed to occupational noise and group 3 included individuals exposed to occupational noise who were <35 years of age. Group 2 consisted of individuals with an age range of 45-65 years without any occupational noise exposure. DPOAE fine structure was studied at 8 points per octave at different F2 frequencies. Transient evoked otoacoustic emissions (TEOAEs) were measured with and without contralateral broad band noise (BBN) at 30 dB SL (CSOAEs). ABR was recorded using click stimuli at different levels, from 90 dB nHL down to 50 dB nHL. The absolute amplitude and peak latencies for peaks I, III, and V; and the wave V/I amplitude ratio were analyzed.Results: In CSOAEs, group 1 showed greater contralateral suppression when compared to group 2 and group 3. The amplitude of ABR wave I and the wave V/I ratio showed a significant difference between the 3 groups, and there was a reduction in amplitude of wave I for groups 2 and 3.Conclusion: The findings indicate that the functioning of the auditory system is affected by occupational noise exposure and aging. CSOAEs, ABR wave I amplitude, and wave V/I amplitude ratio serve as reliable markers in the identification of hidden hearing loss.

Envelope following response measurements in young veterans are consistent with noise-induced cochlear synaptopathy

Animal studies have demonstrated that noise exposure can lead to the loss of the synapses between the inner hair cells and their afferent auditory nerve fiber targets without impacting auditory thresholds. Although several non-invasive physiological measures appear to be sensitive to cochlear synaptopathy in animal models, including auditory brainstem response (ABR) wave I amplitude, the envelope following response (EFR), and the middle ear muscle reflex (MEMR), human studies of these measures in samples that are expected to vary in terms of the degree of noise-induced synaptopathy have resulted in mixed findings. One possible explanation for the differing results is that synaptopathy risk is lower for recreational noise exposure than for occupational or military noise exposure. The goal of this analysis was to determine if EFR magnitude and ABR wave I amplitude are reduced among young Veterans with a history of military noise exposure compared with non-Veteran controls with minimal noise exposure. EFRs and ABRs were obtained in a sample of young (19-35 years) Veterans and non-Veterans with normal audiograms and robust distortion product otoacoustic emissions (DPOAEs). The statistical analysis is consistent with a reduction in mean EFR magnitude and ABR wave I amplitude (at 90 dB peSPL) for Veterans with a significant history of noise exposure compared with non-Veteran controls. These findings are in agreement with previous ABR wave I amplitude findings in young Veterans and are consistent with animal models of noise-induced cochlear synaptopathy.

Tinnitus development is associated with synaptopathy of inner hair cells in Mongolian gerbils.

Human hearing loss (HL) is often accompanied by comorbidities like tinnitus, which is affecting up to 15% of the adult population. Rodent animal studies could show that tinnitus may not only be a result of apparent HL due to cochlear hair cell damage but can also be a consequence of synaptopathy at the inner hair cells (IHCs) already induced by moderate sound traumata. Here, we investigate synaptopathy previously shown in mice in our animal model, the Mongolian gerbil, and relate it to behavioral signs of tinnitus. Tinnitus was induced by a mild monaural acoustic trauma leading to monaural noise induced HL in the animals, quantified by auditory brainstem response (ABR) audiometry. Behavioral signs of tinnitus percepts were detected by measurement of prepulse inhibition of the acoustic startle response in a gap-noise paradigm. Fourteen days after trauma, the cochleae of both ears were isolated, and IHC synapses were counted within several spectral regions of the cochlea. Behavioral signs of tinnitus were only found in animals with IHC synaptopathy, independent of type of HL. On the other hand, animals with apparent HL but without behavioral signs of tinnitus showed a reduction in amplitudes of ABR waves I&II but no significant changes in the number of synapses at the IHC. We conclude-in line with the literature-that HL is caused by damage to the IHC or by other reasons but that the development of tinnitus, at least in our animal model, is closely linked to synaptopathy at the IHC.

Gene editing in a Myo6 semi-dominant mouse model rescues auditory function

Myosin VI（MYO6） is an unconventional myosin that is vital for auditory and vestibular function. Pathogenic variants in the human MYO6 gene cause autosomal-dominant or -recessive forms of hearing loss. Effective treatments for Myo6 mutation causing hearing loss are limited. We studied whether adeno-associated virus (AAV)-PHP.eB vector-mediated invivo delivery of Staphylococcus aureus Cas9 (SaCas9-KKH)-single-guide RNA (sgRNA) complexes could ameliorate hearing loss in a Myo6WT/C442Y mouse model that recapitulated the phenotypes of human patients. The invivo editing efficiency of the AAV-SaCas9-KKH-Myo6-g2 system on Myo6C442Y is 4.05% on average in Myo6WT/C442Y mice, which was ∼17-fold greater than editing efficiency of Myo6WT alleles. Rescue of auditory function was observed up to 5months post AAV-SaCas9-KKH-Myo6-g2 injection in Myo6WT/C442Y mice. Meanwhile, shorter latencies of auditory brainstem response (ABR) wave I, lower distortion product otoacoustic emission (DPOAE) thresholds, increased cell survival rates, more regular hair bundle morphology, and recovery of inward calcium levels were also observed in the AAV-SaCas9-KKH-Myo6-g2-treated ears compared to untreated ears. These findings provide further reference for invivo genome editing as a therapeutic treatment for various semi-dominant forms of hearing loss and other semi-dominant diseases.

Auditory brainstem response test results in normal hearing adolescents with subjective tinnitus

ObjectivesThe objective of the study was to analyze the auditory brainstem response (ABR) test results of adolescents with normal hearing threshold who have subjective tinnitus in an effort to determine the probable site of origin of tinnitus. MethodsAmong the patients who visited the outpatient clinic of the Department of Otolaryngology at our tertiary hospital from January 2016 to December 2019, adolescents aged 13–18 years with the chief complaint of unilateral subjective tinnitus and pure tone audiometry (PTA) within 25 dB HL were enrolled and retrospectively reviewed. The ABR test parameters (amplitudes and latencies of waves I, III, and V and interpeak latencies [IPLs] of waves I–III, III–V, and I–V) were analyzed and compared between tinnitus ears and contralateral ears without tinnitus. Study participants were divided into the chronic tinnitus (tinnitus duration ≥6 months) and non-chronic tinnitus (tinnitus duration <6 months) groups, and the difference between the two groups was analyzed. ResultsTen adolescents were included in the study, and their ABR test results were reviewed. IPL III–V was significantly prolonged in tinnitus ears compared to non-tinnitus ears (p = 0.035). Although other parameters were found to be statistically non-significant, there was preponderance in ABR wave I amplitude; it was smaller in tinnitus ears of chronic tinnitus adolescents than in those of non-chronic tinnitus adolescents (p = 0.114). ConclusionThe probable site of origin of tinnitus in adolescents with normal hearing might be in the upper brainstem of the auditory pathway. Further analysis of ABR test results in adolescents with tinnitus and normal hearing can help clarify the pathophysiology of tinnitus in adolescents.

Effects of Transient Cerebral Hypoperfusion on Human Auditory Brainstem Responses

Adequate cerebral blood flow perfusion is crucial to maintaining brain function. The auditory brainstem response (ABR) has been demonstrated to be the most powerful diagnostic tool for assessing auditory function. This study aimed to determine the ABR under transient cerebral hypoperfusion caused by using oscillatory lower body negative pressure (OLBNP). As chronic cerebral hypoperfusion has been associated with the prolongation of the latency of ABR waves, we hypothesized that the fluctuation of cerebral blood flow perfusion also affects this latency. As prior data showing that cerebral autoregulation is not effectively engaged when pressure fluctuations are shorter than 30 sec periods (i.e., higher than 0.03 Hz), we used the sinusoidal pattern of an 18 sec period (0.056 Hz) of 0 ~ - 40 mmHg OLBNP to induce transient cerebral hypoperfusion. Here, we measured ABR and cerebral blood flow velocity (MCAv) during 12 min of control and 12 min of OLBNP (40 cycle of 18-sec periods) in 15 subjects (3 of whom were excluded from the analysis due to an insufficient number of data for ABR). Periodical changes in cerebrovascular variables were aligned relative to each 18 sec of OLBNP cycle onset and were subdivided into three phases (phase-1: 0 ~ 6 sec, phase-2: 6 ~ 12 sec, and phase-3: 12 ~ 18 sec of OLBNP onset). For the ABR analysis, a total of 6800 individual sweeps were recorded for 12 min in the control and OLBNP conditions, and the recorded sweeps in the OLBNP condition were subdivided into three phases. We observed that OLBNP caused cyclic fluctuations of MCAv. One-way repeated-measures analysis of variance (ANOVA) and the post-hoc comparison revealed that MCAv decreased significantly in phases-1 and -2 compared to the control and phase-3 (F(3, 33) = 16.54, p < 0.001). As for the ABR data, ANOVA and the post-hoc comparison revealed that the latency of wave V of ABR at phase-2 was delayed compared to phase-1 (F(3, 33) = 3.70, p < 0.05). Moreover, the results showed that the inter-individual difference in the variance over the phase conditions of the latency of wave V was significantly related to that of cerebral blood flow (r = 0.641, p < 0.05). Our data demonstrate that the fluctuation of cerebral blood flow perfusion could lead to the prolongation of the latency of ABR waves. This suggests that the transient cerebral hypoperfusion induced by an acute orthostatic blood shift to the lower body could impair auditory function.

Evidence of Cochlear Synaptopathy and the Effect of Systemic Steroid in Acute Idiopathic Tinnitus With Normal Hearing.

To evaluate the electrophysiologic evidence of cochlear synaptopathy and the effects of systemic steroids in acute idiopathic tinnitus with normal hearing. Retrospective review of medical data. Tertiary referral center. Fifty-nine patients who experienced acute-onset idiopathic tinnitus (within 12 weeks) with normal hearing and the same number of age- and pure-tone threshold-matched control groups. Electrophysiologic studies of the auditory pathway, oral steroids, and ginkgo biloba. Pure-tone thresholds, wave I and wave V amplitudes of the auditory brainstem response (ABR), tinnitus handicap inventory (THI), and visual analog scale (VAS). Significantly reduced ABR wave I amplitude and wave I/wave V ratio were found in the tinnitus group compared with the no tinnitus group. Age and pure-tone threshold were significantly correlated with reduced wave I amplitude and small wave I/wave V ratio. The THI and VAS scores were decreased at 3 and 12 weeks after steroid administration; however, overall changes in THI and VAS scores were not significantly different between the steroid and ginkgo biloba groups. Potential cochlear synaptopathy was suspected in the early stage of acute idiopathic tinnitus, even in patients with normal hearing. Age and hearing threshold were potentially associated with the development of cochlear synaptopathy. Low-dose oral steroids and ginkgo biloba induced early subjective relief of tinnitus, which maintained up to 12 weeks, however, those changes did not differ between groups.

Acute Recreational Noise-Induced Cochlear Synaptic Dysfunction in Humans With Normal Hearing: A Prospective Cohort Study

ObjectivesThe objective of the study was to identify the acute high-intensity recreational noise-induced effects on auditory function, especially the cochlear synaptopathy-related audiological metrics, in humans with normal hearing.MethodsThis prospective cohort study enrolled 32 young adults (14 males and 18 females); the mean age was 24.1 ± 2.4 years (ranging from 20 to 29). All participants with normal hearing (audiometric thresholds ≤25 dB HL at frequencies of 0.25, 0.5, 1, 2, 3, 4, 6, and 8 kHz for both ears) had already decided to participate in the outdoor music festival. Participants were asked to measure the noise exposure dose and complete auditory examinations, including the air-conduction pure-tone audiometry (PTA), distortion product otoacoustic emission (DPOAE), contralateral suppression (CS) on transient evoked otoacoustic emission (TEOAE), auditory brainstem response (ABR) test and Mandarin Hearing in Noise Test (MHINT), at baseline and 1 day and 14 days after music festival noise exposure.ResultsThe mean time of attending the music festival was 7.34 ± 0.63 h (ranging from 6.4 to 9.5), the mean time-weighted average (TWA) of noise exposure dose was 93.2 ± 2.39 dB(A) (ranging from 87.9 to 97.7). At neither 1 day nor 14 days post exposure, there were no statistically significant effects on PTA thresholds, DPOAE amplitudes, CS on TEOAEs, or MHINT signal-to-noise ratios (SNRs) of acute outdoor music festival noise exposure, regardless of sex. While the ABR wave I amplitudes significantly decreased at 1 day after exposure and recovered at 14 days after exposure, the exposed/unexposed ABR wave I amplitude ratio was significantly correlated with MHINT SNR change at 1 day after exposure, although it was not correlated with the noise exposure dose.ConclusionIn young adults with normal hearing, we found the self-compared decrement of ABR wave I amplitudes at 1 day post acute recreational noise exposure at high intensity, which also contributes to the change in speech perceptual ability in noisy backgrounds. This study indicated that auditory electrophysiological metric changes might be a more sensitive and efficient indicator of noise-induced cochlear synaptic dysfunction in humans. More attention should be paid to the recreational noise-induced cochlear synaptopathy and auditory perceptual disorder.

Auditory Steady-State Response (ASSR) in hearing-impaired children with absent Auditory Brainstem Response (ABR) waves

Objectives: The aim of this work was to evaluate the residual hearing in children with sensorineural hearing loss and absent ABR waves by ASSR to select the appropriate way for intervention either the use of hearing aid or cochlear implant. Patients and methods: Forty children (80 ears) were included in this study in the period from May 2019 up to April 2020. All children had detailed complete history taking, otoscopic examination, immittancemetry, hearing assessment to get an accurate frequency specific threshold with play audiometry, behavioral observation audiometry, and evoked audiometry including ABR, TEOAEs, and ASSR. Results: Forty hearing impaired children with ages ranged from 1 to 5 years old, 22 were males and 18 were female. ASSR response was obtained from 53 ears, and 27 ears showed no response. The ASSR showed a better response at low-frequency regions when compared to the high-frequency regions but with no statistically significant difference. Conclusions: The absence of click-ABR waves and behavioral free-field responses do not rule out the presence of residual hearing. ASSR was done to estimate the residual hearing mainly at low-frequency regions.

Effects of combined gentamicin and furosemide treatment on cochlear ribbon synapses

It is well-established that aminoglycoside antibiotics are ototoxic, and the toxicity can be drastically enhanced by the addition of loop diuretics, resulting in rapid irreversible hair cell damage. Using both electrophysiologic and morphological approaches, we investigated whether this combined treatment affected the cochlea at the region of ribbon synapses, consequently resulting in auditory synaptopathy. A series of varied gentamicin and furosemide doses were applied to C57BL/6 mice, and auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE) were measured to assess ototoxic damage within the cochlea. In brief, the treatment effectively induced cochlear damage and promoted a certain reorganization of synaptic ribbons, while a reduction of ribbon density only occurred after a substantial loss of outer hair cells. In addition, both the ABR wave I amplitude and the ribbon density were elevated in low-dose treatment conditions, but a correlation between the two events was not significant for individual cochleae. In sum, combined gentamicin and furosemide treatment, at titrated doses below those that produce hair cell damage, typically triggers synaptic plasticity rather than a permanent synaptic loss.

Is the cochleovestibular nerve function affected in patients with hemifacial spasm?

Hemifacial spasm (HFS) is a motor disorder caused by the vascular compression of the facial nerve in the posterior fossa. The cochleovestibular nerve is close to the facial nerve and shares the same entry to the periphery, also has disorders caused by vascular compression. We evaluated the cochleovestibular nerve function in patients with HFS based on the hypothesis that vascular compression, which causes HFS, can also affect the nearby cochleovestibular nerve function. The medical charts of 49 patients with surgically confirmed HFS were reviewed retrospectively. The results of the pure-tone threshold, auditory brainstem response (ABR), video head impulse test (vHIT), and magnetic resonance imaging were analyzed. In each patient, the HFS side and the unaffected side were compared in the paired manner. The anterior inferior cerebellar artery was the major offending vessel (69.4%). There were no significant differences in the pure-tone threshold, properties of ABR waves, and vHIT gain. There was no evidence of cochleovestibular nerve compression syndrome in all patients. The angulation of the nerve by the offending vessel was more frequently identified in the HFS side than in the unaffected side (p = 0.040). The effect of HFS on cochleovestibular nerve function is limited.

Age-Related Central Gain Compensation for Reduced Auditory Nerve Output in Non-Tinnitus Patients with Normal Hearing

Tinnitus in audiometrically normal listeners has been associated with reduced wave I amplitudes of the evoked auditory brainstem response but normal wave V amplitudes, a characteristic thought to be indicative of increased central gain compensation for reduced auditory nerve output. It remains uncertain, however, if central gain compensation is specific to tinnitus or can also occur for other conditions that reduce the auditory nerve output, such as aging. Here, we investigate if central gain increases with increasing age for people with normal hearing or very mild hearing losses. For 94 such people (aged 12-68 years, 64 women), we found that the amplitude of wave I decreased with increasing age but the amplitude of wave V was not correlated with the amplitude of wave I after accounting for age-related subclinical hearing loss and cochlear mechanical damage. Furthermore, the wave I/V amplitude ratio (the inverse of central gain) decreased with increasing age. Those findings are consistent with the presence of central gain compensation in aging. An analysis of the correlation between age and wave I/III or III/V amplitude ratios suggests that central gain compensation in aging likely occurs in the cochlear nuclei. For each of seven participants with tinnitus, the amplitude of wave I, wave V, and the wave I/V amplitude ratio were not significantly different from those of the non-tinnitus group. We conclude that increased central gain occurs with aging and is not specific to tinnitus.

Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice.

Noise exposure of a short period at a moderate level can produce permanent cochlear synaptopathy without seeing lasting changes in audiometric threshold. However, due to the species differences in inner hair cell (IHC) calcium current that we have recently discovered, the susceptibility to noise exposure may vary, thereby impact outcomes of noise exposure. In this study, we investigate the consequences of noise exposure in the two commonly used animal models in hearing research, CBA/CaJ (CBA) and C57BL/6J (B6) mice, focusing on the functional changes of cochlear IHCs. In the CBA mice, moderate noise exposure resulted in a typical fully recovered audiometric threshold but a reduced wave I amplitude of auditory brainstem responses. In contrast, both auditory brainstem response threshold and wave I amplitude fully recovered in B6 mice at 2 weeks after noise exposure. Confocal microscopy observations found that ribbon synapses of IHCs recovered in B6 mice but not in CBA mice. To further characterize the molecular mechanism underlying these different phenotypes in synaptopathy, we compared the ratio of Bax/Bcl-2 with the expression of cytochrome-C and found increased activity in CBA mice after noise exposure. Under whole-cell patch clamped IHCs, we acquired two-photon calcium imaging around the active zone to evaluate the Ca2+ clearance rate and found that CBA mice have a slower calcium clearance rate. Our results indicated that excessive accumulation of calcium due to acoustic overexposure and slow clearance around the presynaptic ribbon might lead to disruption of calcium homeostasis, followed by mitochondrial dysfunction of IHCs that cause susceptibility of noise-induced cochlear synaptopathy in CBA mice.

Assessment of cochlear toxicity in response to chronic 3,3\u2032-iminodipropionitrile in mice reveals early and reversible functional loss that precedes overt histopathology

The peripheral auditory and vestibular systems rely on sensorineural structures that are vulnerable to ototoxic agents that cause hearing loss and/or equilibrium deficits. Although attention has focused on hair cell loss as the primary pathology underlying ototoxicity, evidence from the peripheral vestibular system indicates that hair cell loss during chronic exposure is preceded by synaptic uncoupling from the neurons and is potentially reversible. To determine if synaptic pathology also occurs in the peripheral auditory system, we examined the extent, time course, and reversibility of functional and morphological alterations in cochleae from mice exposed to 3,3′-iminodipropionitrile (IDPN) in drinking water for 2, 4 or 6 weeks. Functionally, IDPN exposure caused progressive high- to low-frequency hearing loss assessed by measurement of auditory brainstem response wave I absolute thresholds and amplitudes. The extent of hearing loss scaled with the magnitude of vestibular dysfunction assessed behaviorally. Morphologically, IDPN exposure caused progressive loss of outer hair cells (OHCs) and synapses between the inner hair cells (IHCs) and primary auditory neurons. In contrast, IHCs were spared from ototoxic damage. Importantly, hearing loss consistent with cochlear synaptopathy preceded loss of OHCs and synapses and, moreover, recovered if IDPN exposure was stopped before morphological pathology occurred. Our observations suggest that synaptic uncoupling, perhaps as an early phase of cochlear synaptopathy, also occurs in the peripheral auditory system in response to IDPN exposure. These findings identify novel mechanisms that contribute to the earliest stages of hearing loss in response to ototoxic agents and possibly other forms of acquired hearing loss.

Auditory Brain Stem Response Predictors of Hearing Outcomes after Middle Fossa Resection of Vestibular Schwannomas

Abstract Objectives To analyze the relationship between preoperative and intraoperative auditory brain stem response (ABR) characteristics and hearing outcomes in patients with vestibular schwannomas (VS) undergoing hearing preservation (HP) surgery via a middle cranial fossa (MCF) approach. Design Prospective study. Setting Academic tertiary skull base referral center. Methods Pre- and postoperative pure-tone average (PTA) and word recognition score (WRS) were examined. Intraoperative ABR wave III latency, wave V latency, and amplitude were recorded. HP was defined as postoperative WRS ≥50%. Participants Adult patients with VS and WRS ≥50% who underwent MCF tumor resection between November 2017 and September 2019. Main Outcome Measures Postoperative hearing outcomes. Results Sixty patients were included. Mean tumor size was 9.2 mm (range, 3–17). HP rates were 56.7% for the cohort and 69.7% for tumors &lt;10 mm. A complete loss of wave V was associated with an 82.9% increase in postoperative PTA (p &lt; 0.001) and 97.2% decrease in WRS (p &lt; 0.001), whereas a diminished wave V was correlated with 62.7% increase in PTA (p &lt; 0.001) and 55.7% decrease in WRS (p = 0.006). A diminished or absent wave V, but not increased wave III/V latency or decreased wave V amplitude, was correlated with a decline in postoperative hearing class (r = 0.735, p &lt; 0.001). Receiver-operating characteristic analysis demonstrated that a stable wave V has the highest accuracy in predicting HP (sensitivity of 82.6%, specificity of 84.8%). Conclusion Of the examined preoperative and intraoperative ABR characteristics, a stable wave V intraoperatively was the strongest predictor of HP after MCF resection of VS. Level of Evidence Level III.