Auditory Brainstem Response Amplitudes Research Articles

Alpha9alpha10 knockout mice show altered physiological and behavioral responses to signals in masking noise.

Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.

Gaussian Processes for Hearing Threshold Estimation Using Auditory Brainstem Responses.

The Auditory Brainstem Response (ABR) plays an important role in diagnosing and managing hearing loss, but can be challenging and time-consuming to measure. Test times are especially long when multiple ABR measurements are needed, e.g., when estimating hearing threshold at a range of frequencies. While many detection methods have been developed to reduce ABR test times, the majority were designed to detect the ABR at a single stimulus level and do not consider correlations in ABR waveforms across levels. These correlations hold valuable information, and can be exploited for more efficient hearing threshold estimation. This was achieved in the current work using a Gaussian Process (GP), i.e., a Bayesian approach for non-linear regression. The function to estimate with the GP was the ABR's amplitude across stimulus levels, from which hearing threshold was ultimately inferred. Active learning rules were also designed to automatically adjust the stimulus level and efficiently locate hearing threshold. Simulation results show test time reductions of up to ∼50% for the GP compared to a sequentially applied Hotelling's T2 test, which does not consider correlations across ABR waveforms. A case study was also included to briefly assess the GP approach in ABR data from an adult volunteer.

Electrophysiological Changes Associated with the Progression of Noise-Induced Hearing Loss.

The aim of this study is to evaluate the clinical characteristics and electrophysiological changes in patients with different degrees of noise-induced hearing loss compared with those of normal controls to elucidate the progression of auditory neural damage attributed to noise exposure. A retrospective cohort study was conducted through a review of the medical records for the patients who presented to a tertiary referral center. Sixty-nine participants were included in the study: 29 had noise-induced hearing loss, and 40 were healthy controls. All the participants underwent electrophysiological tests and pure-tone audiometry. Nine patients showed mild hearing loss (mild hearing loss group), while the others showed worse than moderate hearing loss on puretone audiometry (severe hearing loss group). Significantly reduced wave I and V amplitudes of auditory brainstem response were present in both mild and severe hearing loss groups compared to the control group (P -lt; .001 and P=.002, respectively), without significant differences between the mild and severe hearing loss groups. In the multivariate analysis, auditory brainstem response wave V amplitude was negatively associated with auditory brainstem response wave I-V inter-peak latency delay (B=-0.48, P=.02). The results of the present study confirm the similarity in the electrophysiological characteristics between the mild and severe hearing loss groups. Thus, widespread disruption in the auditory neural conduction could have been established in the early period when the patient developed mild hearing loss following noise exposure.

Investigating the optimal stimulus to evoke the binaural interaction component of the auditory brainstem response

Objective assessment of spatial and binaural hearing deficits remains a major clinical challenge. The binaural interaction component (BIC) of the auditory brainstem response (ABR) holds promise as a non-invasive biomarker for diagnosing such deficits. However, while comparative studies have reported robust BIC in animal models, BIC in humans can sometimes be unreliably evoked even in subjects with normal hearing. Here we explore the hypothesis that the standard methodology for collecting monaural ABRs may not be ideal for electrophysiological assessment of binaural hearing. This study aims to improve ABR BIC measurements by determining more optimal stimuli to evoke it. Building on previous methodology demonstrated to enhance peak amplitude of monaural ABRs, we constructed a series of level-dependent chirp stimuli based on empirically derived latencies of monaural-evoked ABR waves I, IV and the binaural-evoked BIC DN1, the most prominent BIC peak, in a cohort of ten chinchillas. We hypothesized that chirps designed based on BIC DN1 latency would specifically enhance across-frequency temporal synchrony in the afferent inputs leading to the binaural circuits that produce the BIC and would thus produce a larger DN1 than either traditional clicks or chirps designed to optimize monaural ABRs. Compared to clicks, we found that level-specific chirp stimuli evoked significantly greater BIC DN1 amplitudes, and that this effect persisted across all stimulation levels tested. However, we found no significant differences between BICs resulting from chirps created using binaural-evoked BIC DN1 latencies and those using monaural-evoked ABR waves I or IV. These data indicate that existing level-specific, monaural-based chirp stimuli may improve BIC detectability and reduce variability in human BIC measurements.

Input compensation of dolphin and sea lion auditory brainstem responses using frequency-modulated up-chirps.

Frequency-modulated "chirp" stimuli that offset cochlear dispersion (i.e., input compensation) have shown promise for increasing auditory brainstem response (ABR) amplitudes relative to traditional sound stimuli. To enhance ABR methods with marine mammal species known or suspected to have low ABR signal-to-noise ratios, the present study examined the effects of broadband chirp sweep rate and level on ABR amplitude in bottlenose dolphins and California sea lions. "Optimal" chirps were designed based on previous estimates of cochlear traveling wave speeds (using high-pass subtractive masking methods) in these species. Optimal chirps increased ABR peak amplitudes by compensating for cochlear dispersion; however, chirps with similar (or higher) frequency-modulation rates produced comparable results. The optimal chirps generally increased ABR amplitudes relative to noisebursts as threshold was approached, although this was more obvious when sound pressure level was used to equate stimulus levels (as opposed to total energy). Chirps provided progressively less ABR amplitude gain (relative to noisebursts) as stimulus level increased and produced smaller ABRs at the highest levels tested in dolphins. Although it was previously hypothesized that chirps would provide larger gains in sea lions than dolphins-due to the lower traveling wave speed in the former-no such pattern was observed.

Can auditory evoked responses elicited to click and/or verbal sound identify children with or at risk of central auditory processing disorder: A scoping review.

(Central) auditory processing disorders, (C)APDs are clinically identified using behavioral tests. However, changes in attention and motivation may easily affect true identification. Although auditory electrophysiological tests, such as Auditory Brainstem Responses (ABR), are independent of most confounding cognitive factors, there is no consensus that click and/or speech-evoked ABR can be used to identify children with or at-risk of (C)APDs due to heterogeneity among studies. This study aimed to review the possibility of using ABR evoked by click and/or speech stimuli to identify children with or at risk of (C)APDs. The online databases of PubMed, Web of Science, Medline, Embase, and CINAHL were explored using combined keywords for all English and French articles published until April 2021. Additional gray literature was also included such as conference abstracts, dissertations, and editorials in ProQuest Dissertations. Thirteen papers met the eligibility criteria and were included in the scoping review. Fourteen papers were cross-sectional and two were interventional studies. Eleven papers used click stimuli to assess children with/at risk of (C)APDs, and speech stimuli were utilized in the remaining studies. Despite the diversity of the results, especially in click ABR assessments, most studies indicated increases in the wave latencies and/or decreases in the wave amplitudes of click ABR in children with/at risk of (C)APDs. The results of speech ABR assessments were more consistent, as prolongation of the transient components of speech ABR was observed in these children, while sustained components remained almost unchanged. Although both click and speech-evoked ABRs could be used to assess children with (C)APDs, it appears that speech-evoked ABR assessments yield more reliable findings. These findings, however, should be interpreted with caution given the heterogeneity among studies. Well-designed studies on children with confirmed (C)APDs using standard diagnostic and assessment protocols are recommended.

Piccolino is required for ribbon architecture at cochlear inner hair cell synapses and for hearing.

Cochlear inner hair cells (IHCs) form specialized ribbon synapses with spiral ganglion neurons that tirelessly transmit sound information at high rates over long time periods with extreme temporal precision. This functional specialization is essential for sound encoding and is attributed to a distinct molecular machinery with unique players or splice variants compared to conventional neuronal synapses. Among these is the active zone (AZ) scaffold protein piccolo/aczonin, which is represented by its short splice variant piccolino at cochlear and retinal ribbon synapses. While the function of piccolo at synapses of the central nervous system has been intensively investigated, the role of piccolino at IHC synapses remains unclear. In this study, we characterize the structure and function of IHC synapses in piccolo gene-trap mutant rats (Pclogt/gt ). We find a mild hearing deficit with elevated thresholds and reduced amplitudes of auditory brainstem responses. Ca2+ channel distribution and ribbon morphology are altered in apical IHCs, while their presynaptic function seems to be unchanged. We conclude that piccolino contributes to the AZ organization in IHCs and is essential for normal hearing.

The Correlation between Binaural Interaction Component of the Auditory Brainstem Response and Total Score of the Persian Version of the Spatial Hearing Questionnaire

Background and Aim: People with spatial hearing impairment have difficulty perception of speech in the presence of noise, sound localization, and estimating the distance from the sound source. In this study, the comparison between amplitude and latency of the Binaural Interaction Component of the Auditory Brainstem Response (ABR-BIC) with the total score of the Persian version of the Spatial Hearing Questionnaire (SHQ) in adults with normal hearing and moderate sensorineural hearing loss (SNHL) was evaluated.
 Methods: In this cross-sectional comparative study 55, 18–45-year-old individuals including 35 of normal hearing and 20 moderate SNHL participated. All participants underwent the assessments of medical history, otoscopy, conventional audiometry, tympanometry, SHQ questionnaire, and auditory brainstem response (ABR).
 Results: There was no significant correlation between the amplitude and latency of the ABR- BIC and the Persian version of the SHQ in normal groups (r=–0.085, r=0.116) and in moderate SNHL groups (r=0.030, r=0.119). The mean value of ABR-BIC range of people with normal hearing and SNHL is statistically significant (p=0.001).
 Conclusion: The results showed that the amplitude and latency of ABR-BIC were not correlated with the Persian version of the SHQ in people with normal hearing and with moderate SNHL but statistically significant between the mean amplitude and latency of ABR- BIC in people with normal hearing and people with hearing loss.
 Keywords: Auditory brainstem response; spatial hearing questionnaire; binaural interaction component; spatial hearing; spatial hearing disorder

Effect of Electromagnetic Radiation from Mobile Phones on Auditory Brainstem Response.

Mobile phones are being used by around 70% of the global population. A simple non-invasive procedure to detect early impairment of the acoustic nerve and auditory pathway is by auditory brainstem response (ABR). It's a response to the sound stimulus generated from the brainstem in the form of electrical impulses. To determine the effect of long-term usage of mobile phones on auditory brainstem responses (ABRs). This Epidemiological, cross-sectional study was undertaken at a tertiary care hospital and includes 865 individuals aged between 18 to 45years using mobile phone for > 2years. Users were categorized into various groups according to the minutes of mobile usage per day, years of mobile usage and total duration of mobile phone use in dominant (mobile using) and non-Dominant (non-mobile using) ears. The changes in ABR were studied in each ear to ascertain the effect of EMF exposure due to chronic mobile phone use. Mean age of subjects was 27.01years. (M: F = 1.57:1.0). Range of mobile phone usage was from 4 to 900min/day, with mean as 85.94min/day. No significant differences were seen between dominant and non-dominant ears in regard to amplitudes of wave I, III and V, latencies of wave I and V and Inter peak latency (IPL) of wave I-III, III-V and I-V. No statistically significant difference for I-III, III-V and I-V IPL were found b/w two groups/ears except for usage of mobile phone for > 180min/day in wave I-V, usage for 0-4years in wave I-III and I-V and net hours usage for > 1500h in wave I-V. The mean IPL in all the waves increases with the increase in years of mobile usage and is maximum in all waves in > 12years mobile users. The long-term exposure to EMF does induce measurable changes in ABRs. Amplitude and IPLs of ABR were found comparable between the dominant and non-dominant ears using mobile phones, except for those using mobile usage for > 180min/day and with increasing years of usage of mobile phone. Therefore, prudent use of mobile phone should be encouraged for a shorter period of time and for essential purpose only.

Hidden Hearing Loss: Causes, Current Knowledge, and Future Directions

Introduction: Hidden hearing loss (HHL) is a type of auditory disorder that affects the auditory neural processing and hearing sensitivity in subjects with normal hearing thresholds. Unlike central auditory processing disorders, HHL happens when the cochlea (the peripheral auditory organ) is affected. There are several known risk factors to HHL which includes noise exposure, ototoxic drugs, and peripheral neuropathies, and age. Recent studies have shed light on this type of hearing loss, its etiology, prevalence, and how it can affect the auditory acuity in humans. Methods: This paper covers the current research regarding HHL, its causes, the different mechanisms involved in this disorder, and the diagnosis and potential treatments related to it. We will delve deeply into different researches concerning HHL. 4 articles from 285 were selected focusing on normal hearing individuals with bad speech intelligibility were discussed in this paper. In addition, articles discussing the effects of noise exposure on hearing impaired individuals were not considered as this study solely aims to focus on normal hearing sensitivity individuals with HHL, resulting in 4 articles from 285. Results: Numerous literatures over the decades have suggested that HHL is due to the degeneration of cochlear ribbon synapses, or hair cells synapses without hair cell damage. Their association with HHL was noted several times through this study, whether we were studying the effect of noise exposure, of age, or of ototoxicity. In all cases, no significant hair cell damage was observed, and normal thresholds were recovered. However, a decline in the amplitude of Auditory Brainstem Response (ABR) peak I from auditory nerve (AN) responses in noise exposed subjects and a decline in compound action potential (CAP) was measured when certain drugs were applied to the round window of Guinea pigs. Conclusion: Most studies, have proven that cochlear synaptophysin is the major contributor to noise induced, age, and ototoxic related HHL. There are several audiometric tests that were used to help identify HHL including Puretone audiometry in background noise, ABR, CAP, Distortion Product Otoacoustic Emission (DPOAE).

Congenital Nonprofound Bilateral Sensorineural Hearing Loss in Children: Comprehensive Characterization of Auditory Function and Hearing Aid Benefit.

A prospective cross-sectional design was used to characterize congenital bilateral sensorineural hearing loss (SNHL). The underlying material of >30,000 consecutively screened newborns comprised 11 subjects with nonprofound, alleged nonsyndromic, SNHL. Comprehensive audiological testing was performed at ≈11 years of age. Results showed symmetrical sigmoid-like median pure-tone thresholds (PTTs) reaching 50–60 dB HL. The congenital SNHL revealed recruitment, increased upward spread of masking, distortion product otoacoustic emission (DPOAE) dependent on PTT (≤60 dB HL), reduced auditory brainstem response (ABR) amplitude, and normal magnetic resonance imaging. Unaided recognition of speech in spatially separate competing speech (SCS) deteriorated with increasing uncomfortable loudness level (UCL), plausibly linked to reduced afferent signals. Most subjects demonstrated hearing aid (HA) benefit in a demanding laboratory listening situation. Questionnaires revealed HA benefit in real-world listening situations. This functional characterization should be important for the outline of clinical guidelines. The distinct relationship between DPOAE and PTT, up to the theoretical limit of cochlear amplification, and the low ABR amplitude remain to be elucidated. The significant relation between UCL and SCS has implications for HA-fitting. The fitting of HAs based on causes, mechanisms, and functional characterization of the SNHL may be an individualized intervention approach and deserves future research.

Temporary threshold shift from continuous 20–40 kHz hyperbolic upsweeps in bottlenose dolphins (Tursiops truncatus)

Naval continuous active sonar (CAS) can operate at high duty cycles and result in sound exposure levels (SELs, in dB re 1 μPa2s) that may induce temporary threshold shift (TTS) in marine mammals. Estimating the impacts of CAS on marine mammal hearing is difficult however, given the scarcity of TTS data for long-duration tonal exposures. For this ongoing study, bottlenose dolphin TTS was measured following exposure to continuous playback of 19-s hyperbolic upsweeps from 20–40 kHz, at multiple sound pressure levels and exposure durations from 2 to 60 min (100% duty cycle). The upsweep was based on characteristics of naval CAS, but frequency-shifted into the dolphin’s range of best hearing to predict how baleen whales might be affected by CAS exposures below 10 kHz. Hearing was measured using both psychophysical and auditory brainstem response measurements. To date, the greatest cumulative exposures of 180 dB SEL (normal-hearing dolphin) and 183 dB SEL (dolphin with elevated hearing thresholds) resulted in less than 6 dB of behavioral TTS. Auditory brainstem response amplitudes for these exposures did not indicate noise-induced fatigue. Future testing will evaluate TTS following exposure to 28-kHz pure tones with comparable SELs. [Work funded by US Navy Living Marine Resources.]

Envelope following responses following partial cochlear deafferentation in guinea pigs

The sound-induced loss of ribbon synapses connecting inner hair cells to auditory nerve fibers primarily exhibiting high thresholds has been the subject of numerous investigations. The condition resulting from this inner ear abnormality is commonly referred to as hidden hearing loss, a name that reflects the relative invulnerability of low threshold auditory nerve fibers that survive noise-exposure and function normally. Although auditory sensitivity recovers completely among animals experiencing hidden hearing loss, recovery of auditory brainstem response amplitudes is incomplete. The residual loss of function reflected in diminished response amplitudes to transient stimuli serves as a highly reliable indicator of the condition. The extent to which responses to sustained stimuli might serve as indicators of pathology is less clear. To that end, we will review findings related to differences in spectral magnitudes of envelope following responses to a battery of sinusoidally-amplitude modulated test conditions that include level dependent response growth, modulation transfer functions under a variety of carrier conditions, the influence of varying modulation depths, as well as the influence of maskers on responses acquired from control and noise-exposed animals. [Work supported by the Department of Defense Award #W81XWH-19-1-0862.]

Killer or helper? The mechanism underlying the role of adenylate activated kinase in sound conditioning.

ObjectiveTo investigate whether sound conditioning influences auditory system protection by activating adenylate activated kinase (AMPK), and if such adaption protects ribbon synapses from high-intensity noise exposure.Materials and methodsCBA mice (12 weeks old) were randomly divided into four groups (n = 24 mice per group): control, sound conditioning (SC), sound conditioning plus noise exposure (SC+NE), and noise exposure (NE). Hearing thresholds were assessed before testing, after sound conditioning, and 0, 3, 7, and 14 days after 110 dB noise exposure. Amplitudes and latencies of wave I at 90 dB intensity were assessed before test, after conditioning, and at 0 and 14 days after 110 dB noise exposure. One cochlea from each mouse was subjected to immunofluorescence staining to assess synapse numbers and AMPK activation, while the other cochlea was analyzed for phosphorylated adenylate activated kinase (p-AMPK) protein expression by western blot.ResultsThere was no significant difference in auditory brainstem response (ABR) threshold between SC and control mice. The degree of hearing loss of animals in the two SC groups was significantly reduced compared to the NE group after 110 dB noise exposure. Animals in the SC group showed faster recovery to normal thresholds, and 65 dB SPL sound conditioning had a stronger auditory protection effect. After sound conditioning, the amplitude of ABR I wave in the SC group was higher than that in the control group. Immediately after noise exposure (D0), the amplitudes of ABR I wave decreased significantly in all groups; the most significant decrease was in the NE group, with amplitude in 65SC+NE group significantly higher than that in the 85SC+NE group. Wave I latency in the SC group was significantly shorter than that in the control group. At D0, latency was prolonged in the NE group compared with the control group. In contrast, there was no significant difference in latency between the 65SC+NE and 85SC+NE groups. Further, at D14, there was no significant difference between the NE and control groups, while latency remained significantly shorter in the 65SC+NE and 85SC+NE groups compared with controls. Number of ribbon synapses in SC mice did not differ significantly from that in controls. After 110 dB noise exposure, there were significantly more ribbon synapses in the SC+NE group than the NE group. Ribbon synapses of all groups were recovered 14 days after the noise exposure, while the SC group had a shorter recovery time than the non-SC groups (p < 0.05). AMPK was highly activated in the SC group, and p-AMPK expression was detected; however, after 110 dB noise exposure, the strongest protein expression was detected in the NE group, followed by the SC+NE groups, and the lowest protein expression was detected in the control group.ConclusionSound conditioning animals were more noise resistant and recovered hearing faster than non-SC animals. Further, 65 dB SPL SC offered better hearing protection than 85 dB SPL SC. Early AMPK activation may protect hearing by increasing ATP storage and reducing the release of large quantities of p-AMPK, which could help to inhibit synapse damage.

Could Tailored Chirp Stimuli Benefit Measurement of the Supra-threshold Auditory Brainstem Wave-I Response?

Auditory brainstem responses (ABRs) to broadband clicks are strongly affected by dyssynchrony, or “latency dispersion”, of their frequency-specific cochlear contributions. Optimized chirp stimuli, designed to compensate for cochlear dispersion, can afford substantial increase in broadband ABR amplitudes, particularly for the prominent wave-V deflection. Reports on the smaller wave I, however, which may be useful for measuring cochlear synaptopathy, have been mixed. This study aimed to test previous claims that ABR latency dispersion differs between waves I and V, and between males and females, and thus that using wave- and/or sex-tailored chirps may provide more reliable wave-I benefit. Using the derived-band technique, we measured responses from frequency-restricted (one-octave-wide) cochlear regions to energy-matched click and chirp stimuli. The derived-band responses’ latencies were used to assess any wave- and/or sex-related dispersion differences across bands, and their amplitudes, to evaluate any within-band dispersion differences. Our results suggest that sex-related dispersion difference within the lowest-frequency cochlear regions (< 1 kHz), where dispersion is generally greatest, may be a predominant driver of the often-reported sex difference in broadband ABR amplitude. At the same time, they showed no systematic dispersion difference between waves I and V. Instead, they suggest that reduced chirp benefit on wave I may arise as a result of chirp-induced desynchronization of on- and off-frequency responses generated at the same cochlear places, and resultant reduction in response contributions from higher-frequency cochlear regions, to which wave I is thought to be particularly sensitive.

Physiological Evidence for Delayed Age-related Hearing Loss in Two Long-lived Rodent Species (Peromyscus leucopus and P. californicus).

Deer mice (genus Peromyscus) are an emerging model for aging studies due to their longevity relative to rodents of similar size. Although Peromyscus species are well-represented in genetic, developmental, and behavioral studies, relatively few studies have investigated auditory sensitivity in this genus. Given the potential utility of Peromyscus for investigations of age-related changes to auditory function, we recorded auditory brainstem responses (ABRs) in two Peromyscus species, P. californicus, and P. leucopus, across the lifespan. We compared hearing sensitivity and ABR wave metrics measured in these species with measurements from Mus musculus (CBA/CaJ strain) to assess age-related effects on hearing across species. Recordings in young animals showed that all species had similar hearing ranges and thresholds with peak sensitivity ranging from 8 to 16kHz; however, P. californicus and P. leucopus were more sensitive to frequencies below 8kHz. Although M. musculus showed significant threshold shifts across a broad range of frequencies beginning at middle age and worsening among old individuals, older Peromyscus mice retained good sensitivity to sound across their lifespan. Middle-aged P. leucopus had comparable thresholds to young for frequencies below 24kHz. P. leucopus also had notably large ABRs that were robust to age-related amplitude reductions, although response latencies increased with age. Old P. californicus were less sensitive to mid-range tones (8-16kHz) than young individuals; however, there were no significant age-effects on ABR amplitudes or latencies in this species. These results indicate that longevity in Peromyscus mice may be correlated with delayed aging of the auditory system and highlight these species as promising candidates for longitudinal hearing research.

Head and neck radiotherapy causes significant disruptions of cochlear ribbon synapses and consequent sensorineural hearing loss

PurposeTo investigate the possible effects of head and neck radiotherapy on hearing function in mice. MethodAdult C57BL/6J mice were irradiated to the head and neck once with cobalt-60 rays at doses of 10 Gy or 20 Gy. Hearing function was estimated by the detection of auditory brainstem response (ABR) thresholds and the suprathreshold function of cochlear was indicated by the peak amplitudes and latencies of wave I. The mice were tested on days 1, 7, 14, and 21 after radiation treatment, and untreated mice in littermates served as controls. The cochlear pre-synaptic ribbons were labeled using an anti-RIBEYE/CtBP2 antibody, and the synaptic vesicle membrane was traced using anti-vesicular glutamate transporter 3 (VGLUT-3) antibody. The number and size of the pre-synaptic ribbons were counted along the cochlear axis from the apex to the base. The expression of VGLUT-3 was measured by the intensity of immunofluorescence. Hematoxylin and eosin (H&E) staining was also performed to evaluate the structural changes in the cochlea. ResultsCompared with the controls, mice treated with 10 Gy and 20 Gy doses on days 1, 7, 14, and 21 were found to have significant disruptions in ABR thresholds and amplitudes (p < 0.05). Moreover, mice in the 20 Gy group, compared with the 10 Gy group, showed greater hearing loss and suprathreshold deficits (p < 0.05). Quantitative analysis revealed a decrease in the number and size of CtBP2-positive puncta in both the 10 Gy and 20 Gy groups compared with the controls (p < 0.05); in the 20 Gy group, the number and size of CtBP2-positive puncta were less than those in the 10 Gy group (p < 0.05). We observed a significant disruption in the expression of VGLUT-3 in the group treated with 20 Gy. However, compared with the control group, both immunofluorescence and H&E staining revealed no significant changes in the number of hair cells or the array for the 10 or 20 Gy treatments (p > 0.05). ConclusionRadiation therapy targeting the head and neck can cause sensorineural hearing loss via disruption specific to the cochlear ribbon synapses. To our knowledge, this is the first study to demonstrate that cochlear ribbon synapses may be a subcellular target of radiation-induced hearing loss.

The Relationship between Contralateral Suppression of Transient Evoked Otoacoustic Emission and Unmasking of Speech Evoked Auditory Brainstem Response

Introduction Several studies have shown that efferent pathways of the auditory system improve perception of speech-in-noise. But, the majority of investigations assessing the role of efferent pathways on speech perception have used contralateral suppression of otoacoustic emissions as a measure of efferent activity. By studying the effect of efferent activity on the speech-evoked auditory brainstem response (ABR), some more light could be shed on the effect of efferent pathways on the encoding of speech in the auditory pathway. Objectives To investigate the relationship between contralateral suppression of transient evoked otoacoustic emission (CSTEOAE) and unmasking of speech ABR. Methods A total of 23 young adults participated in the study. The CSTEOAE was measured using linear clicks at 60 dB peSPL and white noise at 60 dB sound pressure level (SPL). The speech ABR was recorded using the syllable /da/ at 80 dB SPL in quiet, ipsilateral noise, and binaural noise conditions. In the ipsilateral noise condition, white noise was presented to the test ear at 60 dB SPL, and, in the binaural noise condition, two separate white noises were presented to both ears. Results The F0 amplitude of speech ABR was higher in quiet condition; however, the mean amplitude of F0 was not significantly different across conditions. Correlation analysis showed a significant positive correlation between the CSTEOAE and the magnitude of unmasking of F0 amplitude of speech ABR. Conclusions The findings of the present study suggests that the efferent pathways are involved in speech-in-noise processing.

Comparison of click and chirp stimuli in evoking the binaural interaction component of the auditory brainstem response

Chirp stimuli enhance synchrony in the auditory nerve by compensating for frequency- and level-dependent delays accrued by the traveling wave in the cochlea. Chirps produce larger amplitudes in specific waves of the monaural auditory brainstem response (ABR). We test whether chirps increase the amplitude of the binaural interaction component (BIC) of the ABR, a potential biomarker for binaural hearing. ABR latencies were measured across multiple stimulus frequencies and intensities in chinchillas. Tone bursts (1–16 kHz) were presented ∼10 dB below to 50 dB above threshold. Latencies of ABR waves I-IV and BIC were plotted against frequency and fit to a power function: Tau = k*f(-d), where tau is latency, f is frequency, and k and d are constants. The values of k and d were used to construct chirps for three intensity-levels based on monaural ABR waves I and IV, and BIC. Monaural ABR latencies decreased with increasing frequency as expected from cochlear delay. Monaural ABR amplitudes were enhanced by chirps relative to clicks. Surprisingly, BIC DN1 latencies did not show a similar shift but rather appeared constant across frequency. Traditional chirp stimuli appear ill-suited for eliciting optimal BIC amplitudes. Traditional broadband clicks or non-traditional chirps may be preferable for evoking the BIC.

Possible Existence of Cochlear Synaptopathy in Patients Completely Recovered from Idiopathic Sudden Sensorineural Hearing Loss.

Cochlear synaptopathy refers to a subclinical hearing pathology which could potentially explain hearing difficulties within the normal hearing threshold; it is also called “hidden hearing loss”. We hypothesized that a temporary threshold shift in sudden sensorineural hearing loss (ISSNHL) also affects the function in the synapse. The aim of the study was to evaluate the presence of cochlear synaptopathy in patients who had completely recovered from unilateral SSNHL Nineteen patients who had completely recovered from ISSNHL from January 2018 to June 2021 were assessed. Complete recovery was established by pure tone audiometry (PTA) 3 months after treatment, according to the American Academy of Otolaryngology–Head and Neck Surgery criteria. Subjects completed the pure tone audiometry, speech audiometry and auditory brain stem response (ABR) test, and completed a questionnaire regarding hearing loss after hearing recovery. The ABR amplitudes of wave I and wave V, and the ratio of wave I/V of both ears (recovered side and healthy side) were assessed. A visual analog scale (VAS) and a hidden hearing loss questionnaire were used to evaluate subjective hearing difficulty. The ABR waves I of the recovered ears had a significantly lower amplitude (p = 0.002) than those of the healthy side, whereas there was no difference in wave V (p = 0.985) or in the ratio of wave I/V (p = 0.107). Some patients still felt mild hearing difficulty although their PTA results were normal, but there was no clear relationship between the VAS score, wave I amplitude and speech recognition scores. The present findings point to the possible existence of cochlear synaptopathy in ears that have completely recovered from unilateral sudden sensorineural hearing loss. We suggest that the causes of cochlear synaptopathy and of idiopathic sudden hearing loss may have something in common.