Auditory Brainstem Response Measurements Research Articles

Auditory Effects of Acoustic Noise From 3-T Brain MRI in Neonates With Hearing Protection.

Neonates with immature auditory function (eg, weak/absent middle ear muscle reflex) could conceivably be vulnerable to noise-induced hearing loss; however, it is unclear if neonates show evidence of hearing loss following MRI acoustic noise exposure. To explore the auditory effects of MRI acoustic noise in neonates. Prospective. Two independent cohorts of neonates (N = 19 and N = 18; mean gestational-age, 38.75 ± 2.18 and 39.01 ± 1.83 weeks). T1-weighted three-dimensional gradient-echo sequence, T2-weighted fast spin-echo sequence, single-shot echo-planar imaging-based diffusion-tensor imaging, single-shot echo-planar imaging-based diffusion-kurtosis imaging and T2-weighted fluid-attenuated inversion recovery sequence at 3.0 T. All neonates wore ear protection during scan protocols lasted ~40 minutes. Equivalent sound pressure levels (SPLs) were measured for both cohorts. In cohort1, left- and right-ear auditory brainstem response (ABR) was measured before (baseline) and after (follow-up) MRI, included assessment of ABR threshold, wave I, III and V latencies and interpeak interval to determine the functional status of auditory nerve and brainstem. In cohort2, baseline and follow-up left- and right-ear distortion product otoacoustic emission (DPOAE) amplitudes were assessed at 1.2 to 7.0 kHz to determine cochlear function. Wilcoxon signed-rank or paired t-tests with Bonferroni's correction were used to compare the differences between baseline and follow-up ABR and DPOAE measures. Equivalent SPLs ranged from 103.5 to 113.6 dBA. No significant differences between baseline and follow-up were detected in left- or right-ear ABR measures (P > 0.999, Bonferroni corrected) in cohort1, or in DPOAE levels at 1.2 to 7.0 kHz in cohort2 (all P > 0.999 Bonferroni corrected except for left-ear levels at 3.5 and 7.0 kHz with corrected P = 0.138 and P = 0.533). A single 40-minute 3-T MRI with equivalent SPLs of 103.5-113.6 dBA did not result in significant transient disruption of auditory function, as measured by ABR and DPOAE, in neonates with adequate hearing protection. 2. Stage 5.

Ototoxicity: a high risk to auditory function that needs to be monitored in drug development.

Hearing loss constitutes a major global health concern impacting approximately 1.5 billion people worldwide. Its incidence is undergoing a substantial surge with some projecting that by 2050, a quarter of the global population will experience varying degrees of hearing deficiency. Environmental factors such as aging, exposure to loud noise, and the intake of ototoxic medications are implicated in the onset of acquired hearing loss. Ototoxicity resulting in inner ear damage is a leading cause of acquired hearing loss worldwide. This could be minimized or avoided by early testing of hearing functions in the preclinical phase of drug development. While the assessment of ototoxicity is well defined for drug candidates in the hearing field - required for drugs that are administered by the otic route and expected to reach the middle or inner ear during clinical use - ototoxicity testing is not required for all other therapeutic areas. Unfortunately, this has resulted in more than 200 ototoxic marketed medications. The aim of this publication is to raise awareness of drug-induced ototoxicity and to formulate some recommendations based on available guidelines and own experience. Ototoxicity testing programs should be adapted to the type of therapy, its indication (targeting the ear or part of other medications classes being potentially ototoxic), and the number of assets to test. For multiple molecules and/or multiple doses, screening options are available: in vitro (otic cell assays), ex vivo (cochlear explant), and in vivo (in zebrafish). In assessing the ototoxicity of a candidate drug, it is good practice to compare its ototoxicity to that of a well-known control drug of a similar class. Screening assays provide a streamlined and rapid method to know whether a drug is generally safe for inner ear structures. Mammalian animal models provide a more detailed characterization of drug ototoxicity, with a possibility to localize and quantify the damage using functional, behavioral, and morphological read-outs. Complementary histological measures are routinely conducted notably to quantify hair cells loss with cochleogram. Ototoxicity studies can be performed in rodents (mice, rats), guinea pigs and large species. However, in undertaking, or at the very least attempting, all preclinical investigations within the same species, is crucial. This encompasses starting with pharmacokinetics and pharmacology efficacy studies and extending through to toxicity studies. In life read-outs include Auditory Brainstem Response (ABR) and Distortion Product OtoAcoustic Emissions (DPOAE) measurements that assess the activity and integrity of sensory cells and the auditory nerve, reflecting sensorineural hearing loss. Accurate, reproducible, and high throughput ABR measures are fundamental to the quality and success of these preclinical trials. As in humans, in vivo otoscopic evaluations are routinely carried out to observe the tympanic membrane and auditory canal. This is often done to detect signs of inflammation. The cochlea is a tonotopic structure. Hair cell responsiveness is position and frequency dependent, with hair cells located close to the cochlea apex transducing low frequencies and those at the base transducing high frequencies. The cochleogram aims to quantify hair cells all along the cochlea and consequently determine hair cell loss related to specific frequencies. This measure is then correlated with the ABR & DPOAE results. Ototoxicity assessments evaluate the impact of drug candidates on the auditory and vestibular systems, de-risk hearing loss and balance disorders, define a safe dose, and optimize therapeutic benefits. These types of studies can be initiated during early development of a therapeutic solution, with ABR and otoscopic evaluations. Depending on the mechanism of action of the compound, studies can include DPOAE and cochleogram. Later in the development, a GLP (Good Laboratory Practice) ototoxicity study may be required based on otic related route of administration, target, or known potential otic toxicity.

Effects of Cochlear Implantation and Steroids on the Aging Guinea Pig Cochlea.

The objective was to determine the effects of older age on hearing preservation after cochlear implantation (CI), and whether steroids improve hearing preservation in older animals. We hypothesized greater hearing preservation would be observed in (1) young animals compared to older animals and (2) older animals receiving steroids compared to no steroids. The secondary objective was to assess levels of fibrosis utilizing optical coherence tomography (OCT). Experimental Animal Study. Laboratory. Three groups of guinea pigs: young (YCI; 8.5 ± 0.5 weeks; n = 10), old (OCI; 19.1 ± 1.0 months; n = 9) and old + steroids (OCI+S; 19.1 ± 1.0 months; n = 9) underwent CI. The OCI+S group received a steroid taper over 7 days starting 2 days before surgery to 4 days after. Auditory brainstem response (ABR) measurements were performed preoperatively and postoperatively. OCT imaging was performed to assess cochleae for extent of fibrotic tissue growth in the scala tympani. The YCI group had significantly better hearing preservation as measured by smaller increases in ABR thresholds [mean shift: 2.79 ± 0.66] compared to the OCI group [mean shift = 12.44 ± 5.6]. The OCI+S group had significantly better hearing preservation [2.66 ± 1.50] compared to the OCI group. No significant differences was seen in fibrosis across groups. Young animals and older animals that received steroids had better hearing after CI than older animals not given steroids, but hearing preservation was not correlated with the level of fibrosis assessed using OCT. This work is the first to investigate differences in hearing preservation by age in an animal model, and supports the protective effects of steroids on hearing preservation in older individuals.

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.

Age-Related Deficits in Binaural Hearing: Contribution of Peripheral and Central Effects.

Pure-tone audiograms often poorly predict elderly humans' ability to communicate in everyday complex acoustic scenes. Binaural processing is crucial for discriminating sound sources in such complex acoustic scenes. The compromised perception of communication signals presented above hearing threshold has been linked to both peripheral and central age-related changes in the auditory system. Investigating young and old Mongolian gerbils of both sexes, an established model for human hearing, we demonstrate age-related supra-threshold deficits in binaural hearing using behavioral, electrophysiological, anatomical, and imaging methods. Binaural processing ability was measured as the binaural masking level difference (BMLD), an established measure in human psychophysics. We tested gerbils behaviorally with "virtual headphones," recorded single-unit responses in the auditory midbrain and evaluated gross midbrain and cortical responses using positron emission tomography (PET) imaging. Furthermore, we obtained additional measures of auditory function based on auditory brainstem responses, auditory-nerve synapse counts, and evidence for central inhibitory processing revealed by PET. BMLD deteriorates already in middle-aged animals having normal audiometric thresholds and is even worse in old animals with hearing loss. The magnitude of auditory brainstem response measures related to auditory-nerve function and binaural processing in the auditory brainstem also deteriorate. Furthermore, central GABAergic inhibition is affected by age. Because the number of synapses in the apical turn of the inner ear was not reduced in middle-aged animals, we conclude that peripheral synaptopathy contributes little to binaural processing deficits. Exploratory analyses suggest increased hearing thresholds, altered binaural processing in the brainstem and changed central GABAergic inhibition as potential contributors.

Hearing loss in juvenile rats leads to excessive play fighting and hyperactivity, mild cognitive deficits and altered neuronal activity in the prefrontal cortex

BackgroundIn children, hearing loss has been associated with hyperactivity, disturbed social interaction, and risk of cognitive disturbances. Mechanistic explanations of these relations sometimes involve language. To investigate the effect of hearing loss on behavioral deficits in the absence of language, we tested the impact of hearing loss in juvenile rats on motor, social, and cognitive behavior and on physiology of prefrontal cortex. MethodsHearing loss was induced in juvenile (postnatal day 14) male Sprague-Dawley rats by intracochlear injection of neomycin under general anesthesia. Sham-operated and non-operated hearing rats served as controls. One week after surgery auditory brainstem response (ABR) measurements verified hearing loss or intact hearing in sham-operated and non-operated controls. All rats were then tested for locomotor activity (open field), coordination (Rotarod), and for social interaction during development in weeks 1, 2, 4, 8, 16, and 24 after surgery. From week 8 on, rats were trained and tested for spatial learning and memory (4-arm baited 8-arm radial maze test). In a final setting, neuronal activity was recorded in the medial prefrontal cortex (mPFC). ResultsIn the open field deafened rats moved faster and covered more distance than sham-operated and non-operated controls from week 8 on (both p < 0.05). Deafened rats showed significantly more play fighting during development (p < 0.05), whereas other aspects of social interaction, such as following, were not affected. Learning of the radial maze test was not impaired in deafened rats (p > 0.05), but rats used less next-arm entries than other groups indicating impaired concept learning (p < 0.05). In the mPFC neuronal firing rate was reduced and enhanced irregular firing was observed. Moreover, oscillatory activity was altered, both within the mPFC and in coherence of mPFC with the somatosensory cortex (p < 0.05). ConclusionsHearing loss in juvenile rats leads to hyperactive behavior and pronounced play-fighting during development, suggesting a causal relationship between hearing loss and cognitive development. Altered neuronal activities in the mPFC after hearing loss support such effects on neuronal networks outside the central auditory system. This animal model provides evidence of developmental consequences of juvenile hearing loss on prefrontal cortex in absence of language as potential confounding factor.

KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans.

Individuals with Kabuki syndrome type 1 (KS1) often have hearing loss recognized in middle childhood. Current clinical dogma suggests that this phenotype is caused by frequent infections due to the immune deficiency in KS1 and/or secondary to structural abnormalities of the ear. To clarify some aspects of hearing loss, we collected information on hearing status from 21 individuals with KS1 and found that individuals have both sensorineural and conductive hearing loss, with the average age of presentation being 7 years. Our data suggest that while ear infections and structural abnormalities contribute to the observed hearing loss, these factors do not explain all loss. Using a KS1 mouse model, we found hearing abnormalities from hearing onset, as indicated by auditory brainstem response measurements. In contrast to mouse and human data for CHARGE syndrome, a disorder possessing overlapping clinical features with KS and a well-known cause of hearing loss and structural inner ear abnormalities, there are no apparent structural abnormalities of the cochlea in KS1 mice. The KS1 mice also display diminished distortion product otoacoustic emission levels, which suggests outer hair cell dysfunction. Combining these findings, our data suggests that KMT2D dysfunction causes sensorineural hearing loss compounded with external factors, such as infection.

Fatty acid binding protein type 7 deficiency preserves auditory function in noise-exposed mice

Fatty acid-binding protein 7 (FABP7) is vital for uptake and trafficking of fatty acids in the nervous system. To investigate the involvement of FABP7 in noise-induced hearing loss (NIHL) pathogenesis, we used Fabp7 knockout (KO) mice generated via CRISPR/Cas9 in the C57BL/6 background. Initial auditory brainstem response (ABR) measurements were conducted at 9 weeks, followed by noise exposure at 10 weeks. Subsequent ABRs were performed 24 h later, with final measurements at 12 weeks. Inner ears were harvested 24 h after noise exposure for RNA sequencing and metabolic analyses. We found no significant differences in initial ABR measurements, but Fabp7 KO mice showed significantly lower thresholds in the final ABR measurements. Hair cell survival was also enhanced in Fabp7 KO mice. RNA sequencing revealed that genes associated with the electron transport chain were upregulated or less impaired in Fabp7 KO mice. Metabolomic analysis revealed various alterations, including decreased glutamate and aspartate in Fabp7 KO mice. In conclusion, FABP7 deficiency mitigates cochlear damage following noise exposure. This protective effect was supported by the changes in gene expression of the electron transport chain, and in several metabolites, including excitotoxic neurotransmitters. Our study highlights the potential therapeutic significance of targeting FABP7 in NIHL.

Case history factors and audiological screening outcomes in HEU and HIV unexposed neonates at a district level hospital in Gauteng, South Africa

While progress has been made in reducing vertical Mother to Child Transmission (MTCT) of HIV, limited research exists on the health needs of HIV-exposed uninfected (HEU) neonates, particularly in the field of audiology. This lack of research and evidence could impact early detection and intervention efforts. This study aimed to establish relationships and compare outcomes between case history factors and audiological screening results in HEU and HIV-unexposed neonates at a district-level hospital in Gauteng, South Africa. A non-experimental quantitative, descriptive, cross-sectional, comparative research design was employed. Data was collected with a sample size of 212 participants (100 HEU, 112 HIV-unexposed neonates) recruited using quota sampling. The hearing screening process involved case history assessment, medical file review, otoscopy, tympanometry testing, Distortion Product Evoked Otoacoustic Emissions (DPOAE), and Automated Auditory Brainstem Response (AABR) measurements. Descriptive and inferential statistics, including measures of central tendency and parametric tests, were used for data analysis. The findings indicated that 43% of HEU neonates exhibited refer findings on DPOAE, and 43% on AABR, compared to 26% and 25% respectively in the HIV-unexposed neonatal group. Therefore, a statistically significant relationship was established when comparing audiological results between the HEU and HIV-unexposed groups. Case history factors such as mode of delivery, birth weight, and Apgar scores were not associated with hearing loss in either group. However, in the HEU group, a higher proportion of participants referred on the overall screening in the maternal Retroviral Disease (RVD) stage IV group, although statistical significance was not established. This study fills an evidence gap regarding HEU neonates and highlights the need to include this vulnerable population in policy and clinical guidelines related to early hearing detection, intervention, and preventive audiology initiatives.

Associations Between Physiological Correlates of Cochlear Synaptopathy and Tinnitus in a Veteran Population.

Animal models and human temporal bones indicate that noise exposure is a risk factor for cochlear synaptopathy, a possible etiology of tinnitus. Veterans are exposed to high levels of noise during military service. Therefore, synaptopathy may explain the high rates of noise-induced tinnitus among Veterans. Although synaptopathy cannot be directly evaluated in living humans, animal models indicate that several physiological measures are sensitive to synapse loss, including the auditory brainstem response (ABR), the middle ear muscle reflex (MEMR), and the envelope following response (EFR). The purpose of this study was to determine whether tinnitus is associated with reductions in physiological correlates of synaptopathy that parallel animal studies. Participants with normal audiograms were grouped according to Veteran status and tinnitus report (Veterans with tinnitus, Veterans without tinnitus, and non-Veteran controls). The effects of being a Veteran with tinnitus on ABR, MEMR, and EFR measurements were independently modeled using Bayesian regression analysis. Modeled point estimates of MEMR and EFR magnitude showed reductions for Veterans with tinnitus compared with non-Veterans, with the most evident reduction observed for the EFR. Two different approaches were used to provide context for the Veteran tinnitus effect on the EFR by comparing to age-related reductions in EFR magnitude and synapse numbers observed in previous studies. These analyses suggested that EFR magnitude/synapse counts were reduced in Veterans with tinnitus by roughly the same amount as over 20 years of aging. These findings suggest that cochlear synaptopathy may contribute to tinnitus perception in noise-exposed Veterans. https://doi.org/10.23641/asha.24347761.

Otologic safety of intratympanic N-acetylcysteine in an animal model.

N-acetylcysteine (NAC) is an anti-oxidant and mucolytic effective against bacterial biofilms, making it useful in the treatment of chronically discharging ears that are unresponsive to traditional treatment methods. The objective of this study was to evaluate the otologic safety of intratympanic NAC combined with Ciprodex® in an animal model. Baseline distortion product otoacoustic emissions (DPOAE) and auditory brainstem response (ABR) measurements were performed for both ears on thirteen guinea pigs from the animal care research facilities of the McGill University Health Center. This was followed by intratympanic administration of control solution (Ciprofloxacin 0.3%/Dexamethasone 0.1%) to the left ear and experimental solution (1.25% NAC/Ciprofloxacin 0.3%/Dexamethasone 0.1%) to the right ear. Three additional intratympanic injections were performed over the next fourteen days. DPOAE and ABR measurements were repeated 3-4 weeks after the initial procedure. Outcome measures included differences in DPOAE and ABR thresholds after intervention, clinical evidence of vestibular dysfunction and histological evidence of ototoxicity. There were no significant differences in the ABR thresholds and DPOAE results of the control and experimental ears at baseline and after intervention. There was neither clinical manifestation of vestibular dysfunction nor histological evidence of ototoxicity. Our study suggests that intratympanic 1.25% NAC with ciprofloxacin and dexamethasone is safe in guinea pigs and support its potential use in the treatment of chronically discharging ears. Further studies in humans are required to analyze its efficacy relative to conventional treatments. Animal Research.

Comparison of different auto-detection methods for wave V with a wireless automated auditory brainstem response (AABR) measurement system

The wireless automatic auditory brainstem response measurement system developed in the previous research uses Kalman filter with exponential weight averaging method (Kalman filter with EWA) to filter signal and used the differential method to detect the Wave V of ABR. However, the signals are too noisy to be accurately determined. Therefore, this study compares the Wavelet Kalman filter and Moving average to the Kalman filter with EWA, and the fitted parametric peak (FPP) to the differential method, respectively. The simulation results showed that the signal-to-noise ratio of ABR is the highest after Wavelet Kalman filtering, and the audiologist can mark the waves III and V of ABR the most. The latency of the wave V detected by FPP was used to calculate the Pearson product-moment correlation coefficient with the audiologist’s manual mark. The two latencies are highly correlated, and the correlation coefficient is higher than the differential method. Therefore, the Wavelet-Kalman filter and FPP algorithm were implemented in the AABR measurement system. To evaluate the accuracy of the algorithm in this study, subjective experiments were conducted with four normal hearing subjects. The Mann-Whitney U test was used to test thedifference between the average value of automatic detection and reproducibility.

The impact of menopausal status on auditory brainstem responses

ObjectiveTo determine the effect of decreased estrogen levels due to menopause on auditory brainstem response measurements (ABR). Study designRetrospective chart review. SettingAcademic. PatientsPre- and post-menopausal females (pre-M, post-M) and age-matched males. MethodsABR measurements of wave I, III, and V latencies, and interpeak latencies; amplitudes of waves I, III, V, and V/I ratio. Outcome measureDifferences in ABR measurements between pre-M and post-M. Results164 subjects (101 female and 64 male) were included. Post-M had significantly greater latencies (msec) than pre-M of wave V. Post-M had a significantly smaller wave I amplitude (uV) than pre-M. Post-M had a significantly higher wave V/I amplitude ratio than pre-M. Pre-M had significantly shorter latencies than young males for wave III, and wave V. Post-M had significantly shorter latencies than older males at wave III, and wave V. A two-way ANOVA revealed a significant interaction between the effects of age category and gender on V/I amplitude. ConclusionPost-M group showed a significant drop in wave I amplitude compared with pre-M group, even in the absence of hearing loss, suggesting that the gender differences in hearing are related to estrogen signaling along the auditory pathway. If wave I amplitude changes between older and younger groups resulted from decreased peripheral hearing sensitivity, we would expect larger drops in amplitude in males since rates of presbycusis are higher. We observed much larger drops in wave I amplitude in females, which cannot be attributed to peripheral hearing loss. These results may assist in understanding gender differences in presbycusis and a possible protective effect of estrogen on the auditory system. Knowledge of gender differences in wave I may be important when ABR is used to assess possible synaptopathy.

Comparison of auditory brainstem response and electrocochleography to assess the coupling efficiency of active middle ear implants.

This study aimed to compare the effectiveness of auditory brainstem response (ABR) and extracochlear electrocochleography (ECochG) in objectively evaluating the coupling efficiency of floating mass transducer (FMT) placement during active middle ear implant (AMEI) surgery. We enrolled 15 patients (mean age 58.5 ± 19.4 years) with mixed hearing loss who underwent AMEI implantation (seven ossicular chain and eight round window couplings). Before the surgical procedure, an audiogram was performed. We utilized a clinical measurement system to stimulate and record intraoperative ABR and ECochG recordings. The coupling efficiency of the VSB was evaluated through ECochG and ABR threshold measurements. Postoperatively, we conducted an audiogram and a vibrogram. In all 15 patients, ABR threshold testing successfully determined intraoperative coupling efficiency, while ECochG was successful in only eight patients. In our cohort, ABR measurements were more practical, consistent, and robust than ECochG measurements. Coupling efficiency, calculated as the difference between vibrogram thresholds and postoperative bone conduction thresholds, was found to be more accurately predicted by ABR measurements (p = 0.016, R2 = 0.37) than ECochG measurements (p = 0.761, R2 = 0.02). We also found a non-significant trend toward better results with ossicular chain coupling compared to round window coupling. Our findings suggest that ABR measurements are more practical, robust, and consistent than ECochG measurements for determining coupling efficiency during FMT placement surgery. The use of ABR measurements can help to identify the optimal FMT placement, especially with round window coupling. Finally, we offer normative data for both techniques, which can aid other clinical centers in using intraoperative monitoring for AMEI placement.

Re-evaluation of local anesthesia transtympanic electrical auditory brainstem response in cochlear implant candidacy

Abstract Introduction: The trans-tympanic electrically evoked auditory brainstem response measurement in local anesthesia (= LA-TT-EABR) has been shown as a useful tool in doubtful CI candidacy to objectively evaluate the excitability of the auditory pathway up to the brainstem. Previous studies in this matter were of relatively low subjects number. To update the knowledge of the reliability of LA-TTEABR, we re-evaluated the latest results from a bigger subjects dataset from our clinic and follow up regarding hearing sensation post-operatively. Methods: LA-TT-EABR was performed, as described in previous publications, with a trans-tympanic golf-club electrode in the round window niche for pre-operative stimulation in local anesthesia and with an evoked potential device for EABR recording. Hearing sensations were monitored in the implanted CI subjects. Results: 39 of 40 planned subjects were included in this study. In 22 subjects, a positive LA-TT-EABR was recorded. In 11 subjects, the response was insecure. In 6 subjects, no response was recorded. One subject was excluded because of pain during the paracentesis. Among them, 19 were implanted with a CI, and 18 had hearing sensations with a hearing prosthesis post-operative. The sensitivity and specificity of LA-TTEABR in estimating the excitability of the auditory nerve preoperatively are both 100%. Conclusion: LA-TT-EABR was shown as a reliable pre-operative test to objectively evaluate the auditory brainstem response. In addition to LA-TT-EABR, an analysis of the auditory cortex using LA-TT-EALR may provide correlation and confirmation of LA-TT-EABR results and additional information about cortical reorganization after long deafness.

A multi-channel EEG mini-cap can improve reliability for recording auditory brainstem responses in chinchillas

Background:Disabling hearing loss affects nearly 466 million people worldwide (World Health Organization). The auditory brainstem response (ABR) is the most common non-invasive clinical measure of evoked potentials, e.g., as an objective measure for universal newborn hearing screening. In research, the ABR is widely used for estimating hearing thresholds and cochlear synaptopathy in animal models of hearing loss. The ABR contains multiple waves representing neural activity across different peripheral auditory pathway stages, which arise within the first 10 ms after stimulus onset. Multi-channel (e.g., 32 or higher) caps provide robust measures for a wide variety of EEG applications for the study of human hearing. However, translational studies using preclinical animal models typically rely on only a few subdermal electrodes. New Method:We evaluated the feasibility of a 32-channel rodent EEG mini-cap for improving the reliability of ABR measures in chinchillas, a common model of human hearing. Results:After confirming initial feasibility, a systematic experimental design tested five potential sources of variability inherent to the mini-cap methodology. We found each source of variance minimally affected mini-cap ABR waveform morphology, thresholds, and wave-1 amplitudes. Comparison with Existing Method:The mini-cap methodology was statistically more robust and less variable than the conventional subdermal-needle methodology, most notably when analyzing ABR thresholds. Additionally, fewer repetitions were required to produce a robust ABR response when using the mini-cap. Conclusions:These results suggest the EEG mini-cap can improve translational studies of peripheral auditory evoked responses. Future work will evaluate the potential of the mini-cap to improve the reliability of more centrally evoked (e.g., cortical) EEG responses.

Evaluation of Hearing and Auditory Pathways in Fabry Disease Patients

Background Hearing and the auditory pathway are affected in Fabry diseases (FD). There is limited data on hearing and auditory pathways in this population. Therefore, we aimed to investigate auditory functions and auditory pathways using auditory brainstem responses (ABR), otoacoustic distortion emission (DPOAE), pure tone audiometry (PTA), and tympanometry in patients with FD and to compare these results with those of healthy individuals.&#x0D; Material and Methods This study included 16 patients with FD (F/M: 8/8, age: 33.5±15.4 years) and 16 healthy controls (F/M: 5/11, age: 33.6±6.3 years). Hearing functions and auditory pathways were assessed with ABR, DPOAE, PTA, and tympanometry.&#x0D; Results According to the results of PTA, conductive hearing loss was detected in 4 (25%) of the patients with FD. When the 500-4,000 Hz frequencies were assessed, the bone pathway hearing threshold in both ears was significantly higher in the patients with FD than in the control group (p=0.014 and p=0.014, respectively). When we compared the DPOAE measurements of the patients with FD and the control groups, the dB value measured at 2.8 kHz was significantly lower in the patient group than in the control group (p=0.018). When we compared the ABR measurements, the right ear's 3-5 interpeak latency at 60 dB was significantly lower in the patient with FD than in the control group (1.8±0.3 ms vs 2±0.2 ms, p=0.033).&#x0D; Conclusions We found that the hearing loss rate and hearing threshold were statistically significantly higher in FD patients than in the control group. Hearing screening should be systematically performed in these patients.

Application of an Intraoperative Auditory Brainstem Response Measurement System in Active Middle Ear Implant Revision Surgery.

To investigate the benefit of intraoperative auditory brainstem response (ABR) measurements in revision active middle ear implant surgery. Retrospective data analysis. Tertiary referral center with a large active middle ear implant program. Intraoperative ABR thresholds, audiogram, sound field thresholds, speech understanding in the Freiburger monosyllabic word test. Fourteen patients with active middle ear implant revision surgery. The application of the ABR measurement resulted in improved sound field thresholds and enhanced speech understanding. Analysis revealed a significant correlation of intraoperative gain in ABR threshold with the postoperative gain in sound field thresholds. ABR monitoring can be a useful tool to provide information intraoperatively about the coupling efficiency of the FMT. Especially in revision surgeries, this might help to improve postoperative hearing success.

Noise-Induced Hearing Loss.

Noise-induced hearing loss (NIHL) is the second most common cause of sensorineural hearing loss, after age-related hearing loss, and affects approximately 5% of the world's population. NIHL is associated with substantial physical, mental, social, and economic impacts at the patient and societal levels. Stress and social isolation in patients' workplace and personal lives contribute to quality-of-life decrements which may often go undetected. The pathophysiology of NIHL is multifactorial and complex, encompassing genetic and environmental factors with substantial occupational contributions. The diagnosis and screening of NIHL are conducted by reviewing a patient's history of noise exposure, audiograms, speech-in-noise test results, and measurements of distortion product otoacoustic emissions and auditory brainstem response. Essential aspects of decreasing the burden of NIHL are prevention and early detection, such as implementation of educational and screening programs in routine primary care and specialty clinics. Additionally, current research on the pharmacological treatment of NIHL includes anti-inflammatory, antioxidant, anti-excitatory, and anti-apoptotic agents. Although there have been substantial advances in understanding the pathophysiology of NIHL, there remain low levels of evidence for effective pharmacotherapeutic interventions. Future directions should include personalized prevention and targeted treatment strategies based on a holistic view of an individual's occupation, genetics, and pathology.

USH2A Gene Mutations in Rabbits Lead to Progressive Retinal Degeneration and Hearing Loss.

Mutations in USH2A gene are responsible for the greatest proportion of the Usher Syndrome (USH) population, among which more than 30% are frameshift mutations on exon 13. A clinically relevant animal model has been absent for USH2A-related vision loss. Here we sought to establish a rabbit model carrying USH2A frameshift mutation on exon 12 (human exon 13 equivalent). CRISPR/Cas9 reagents targeting the rabbit USH2A exon 12 were delivered into rabbit embryos to produce an USH2A mutant rabbit line. The USH2A knockout animals were subjected to a series of functional and morphological analyses, including acoustic auditory brainstem responses, electroretinography, optical coherence tomography, fundus photography, fundus autofluorescence, histology, and immunohistochemistry. The USH2A mutant rabbits exhibit hyper-autofluorescent signals on fundus autofluorescence and hyper-reflective signals on optical coherence tomography images as early as 4 months of age, which indicate retinal pigment epithelium damage. Auditory brainstem response measurement in these rabbits showed moderate to severe hearing loss. Electroretinography signals of both rod and cone function were decreased in the USH2A mutant rabbits starting from 7 months of age and further decreased at 15 to 22 months of age, indicating progressive photoreceptor degeneration, which is confirmed by histopathological examination. Disruption of USH2A gene in rabbits is sufficient to induce hearing loss and progressive photoreceptor degeneration, mimicking the USH2A clinical disease. To our knowledge, this study presents the first mammalian model of USH2 showing the phenotype of retinitis pigmentosa. This study supports the use of rabbits as a clinically relevant large animal model to understand the pathogenesis and to develop novel therapeutics for Usher syndrome.