Auditory Brainstem Research Articles

Genetic characteristic analysis of slight-to-moderate sensorineural hearing loss in children

Objective:To analyze genetic factors and phenotype characteristics in pediatric population with slight-to-moderate sensorineural hearing loss. Methods:Children with slight-to-moderate sensorineural hearing loss of and their parents, enrolled from the Chinese Deafness Genome Project, were studied. Hearing levels were assessed using pure tone audiometry, behavioral audiometry, auditory steady state response（ASSR）, auditory brainstem response（ABR） thresholds, and deformed partial otoacoustic emission（DPOAE）. Classification of hearing loss is according to the 2022 American College of Medical Genetics and Genomics（ACMG） Clinical Practice Guidelines for Hearing Loss. Whole exome sequencing（WES） and deafness gene Panel testing were performed on peripheral venous blood from probands and validations were performed on their parents by Sanger sequencing. Results:All 134 patients had childhood onset, exhibiting bilateral symmetrical slight-to-moderate sensorineural hearing loss, as indicated by audiological examinations. Of the 134 patients, 29（21.6%） had a family history of hearing loss, and the rest were sporadic patients. Genetic causative genes were identified in 66（49.3%） patients. A total of 11 causative genes were detected, of which GJB2 was causative in 34 cases（51.5%）, STRC in 10 cases（15.1%）, MPZL2 gene in six cases（9.1%）, and USH2A in five cases（7.6%）.The most common gene detected in slight-to-moderate hearing loss was GJB2, with c. 109G>A homozygous mutation found in 16 cases（47.1%） and c. 109G>A compound heterozygous mutation in 9 cases（26.5%）. Conclusion:This study provides a crucial genetic theory reference for early screening and detection of mild to moderate hearing loss in children, highlighting the predominance of recessive inheritance and the significance of gene like GJB2, STRC, MPZL2, USH2A.

ABR-Attention: An Attention-Based Model for Precisely Localizing Auditory Brainstem Response.

Auditory Brainstem Response (ABR) is an evoked potential in the brainstem's neural centers in response to sound stimuli. Clinically, characteristic waves, especially Wave V latency, extracted from ABR can objectively indicate auditory loss and diagnose diseases. Several methods have been developed for the extraction of characteristic waves. To ensure the effectiveness of the method, most of the methods are time-consuming and rely on the heavy workloads of clinicians. To reduce the workload of clinicians, automated extraction methods have been developed. However, the above methods also have limitations. This study introduces a novel deep learning network for automatic extraction of Wave V latency, named ABR-Attention. ABR-Attention model includes a self-attention module, first and second-derivative attention module, and regressor module. Experiments are conducted on the accuracy with 10-fold cross-validation, the effects on different sound pressure levels (SPLs), the effects of different error scales and the effects of ablation. ABR-Attention shows efficacy in extracting Wave V latency of ABR, with an overall accuracy of 96.76 ± 0.41 % and an error scale of 0.1ms, and provides a new solution for objective localization of ABR characteristic waves.

How should hyperbilirubinemia be considered in the definition of the hearing screening protocol for neonates at risk?

To analyze hyperbilirubinemia as an indicator for the definition of risk protocol in newborn hearing screening (NHS) and in auditory monitoring in full-term and preterm neonates. This is an observational, cross-sectional and retrospective study. A total of 554 children born in a public maternity hospital were included and divided into two groups: (G1) with 373 full-terms neonates; (G2) with 181 preterm neonates. Data were collected from the participant's medical records to obtain information regarding the result of the NHS, performed by recording the automated auditory brainstem response (AABR), birth conditions, clinical characteristics, interventions performed, and results of the first test of total bilirubin (TB) and indirect bilirubin (IB) as well as the peak of TB and IB. A descriptive statistical analysis of the results was performed, and the level of significance adopted was 5%. On the NHS test, quotes of retest referral rates were smaller in G1 when compared to G2. There was no significant difference between the groups regarding type of delivery, gender, presence of Rh and ABO incompatibility, G6PD enzyme deficiency, and performance of phototherapy. TB and IB levels at the first exam and at peak time did not differ between neonates with "pass" and "fail" results on the NHS test in both groups. Bilirubin levels in the neonatal period below the recommended values for indication of exchange transfusion are not directly related to the "fail" result on the NHS tests in term and preterm neonates.

Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.

Evaluation of the auditory brainstem response test in patients with type 2 diabetes mellitus.

Hearing loss is an unknown complication of diabetes mellitus (DM). The aim of this study was to evaluate hearing function using auditory brainstem response (ABR) in diabetic patients. The present case-control study was performed on thirty diabetic patients as a case group and thirty healthy individuals as a control group. Baseline demographic information, HbA1c level, and duration of diabetes were obtained from all diabetic patients. In all subjects, the ABR and pure-tone audiometry (PTA) tests were performed and the results were analyzed using the t-test and logistic regression. The absolute latency of I was significantly lower in diabetes patients. The absolute latency of III and the interpeak latencies (IPL) I-III were significantly higher in diabetic patients. No significant relationship was noticed in the absolute latency of V and the IPL I-V among diabetic patients in the right and left ears (P>0.05). The results of this study suggested that diabetes may cause central auditory dysfunction manifested on the absolute latency of III, the IPL I-III and III-V.

Liquid Metal‐Based High‐Density Interconnect Technology for Stretchable Printed Circuits

AbstractHigh‐density interconnect (HDI) technology for liquid metal (LM)‐based stretchable printed circuit boards is crucial for expanding their applicability. HDI technology provides high‐resolution multilayer circuits with a high density of components, as required for next generation of neuroprobes and ultrasonic and sensor arrays. This study presents a HDI technique utilizing laser engraved micro grooves in silicone with a protective lift‐off mask of polyvinyl alcohol (PVA) and subsequent microscale LM particle spray deposition. This approach achieves high‐resolution LM patterns and enables multilayer connectivity and high‐density integration of components simultaneously, that is, realizing HDI technology. It is demonstrated using a stretchable 0201 LED display with a density of six leads per mm2 and a cochlear implant (CI) electrode array. The demonstrated manufacturing of the CI has the potential to enable fully automated printed circuit board manufacturing of such implants with increased precision and throughput. Implants in guinea pigs show that the CI is capable of activating the auditory neuron with electrical auditory brainstem response (eABR) and electrical compound action potential (eCAP) of high quality. Moreover, the U‐shaped cross section of the LM interconnects provides a higher mechanical shock resistance of the circuit than that of normal rectangular cross sections.

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.

Assessment of Auditory Brainstem Response in Infants Suffering from Congenital Heart Disease

Background: Congenital heart defects are the singular most common congenital anomalies and account for a significant fraction of childhood mortality and morbidity. Hearing impairment was the most frequent sensory deficit. Auditory brainstem response (ABR) was determined to assess the maturation and function of brainstem, and hence, hearing in infants. Therefore, we used ABR for hearing assessment in infants diagnosed with congenital heart disease.
 Methods: This observational cross-sectional study was carried out on 60 infants, below or above the age of 12 months, both sexes, with CHD. Infants were furtherly divided into two equal groups: Group A with a cyanotic infant, and group B with cyanotic infants. All patients were subjected to Echocardiography.
 Results: 20% of our cases to be affected with varying degrees of hearing loss. No significant difference was found between the cyanotic and a cyanotic infant. However, cyanotic infants below 12 months had higher incidence of hearing loss when compared to those above the age of 12 months; whether the cyanotic or the cyanotic peers.
 Conclusions: High prevalence of hearing loss amongst patients with CHD warrants the addition of those patients to the high-risk registry for hearing loss, in order that they may benefit from early detection and intervention, and ergo protected against the affection of hearing impairment on their neurodevelopment. Routine follow-ups for patients with cyanotic heart disease from the age of 6 months to assess the effect of chronic hypoxemia on the inner ear and monitor the rate of improvement in ABR results, as to establish an accepted rate of improvement, and an appropriate time of intervention, if needed.

NOWY PATOGENICZNY WARIANT GENU <i>LOXHD1</i> W GRECJI: STUDIUM PRZYPADKU IZOLOWANEGO NIEDOSŁUCHU ZWIĄZANEGO Z MUTACJĄ DNFB77

BackgroundGenetic deficits cause 80% of congenital prelingual hearing loss. Some 80% of these cases are nonsyndromic and most follow an autosomal recessive pattern of inheritance. More than 80 genes have so far been identified as pathogenic. In this study, we focus on a recently mapped gene, <i>LOXHD1</i>, whose mutated form causes DFNB77 hearing loss, and find a new variant.Case reportThis is a case study of a 7-year-old male who was admitted to our audiology department with progressive hearing impairment. Pure tone audiometry showed bilateral symmetric hearing impairment, especially at mid to high frequencies. Acoustic immittance tests were normal, but transient evoked otoacoustic emissions and auditory brainstem responses were abnormal for both ears. After physical, clinical, and imaging evaluations, the patient and his parents were genetically tested. Genetic screening showed <i>LOXHD1</i> hearing loss with a novel combination of alleles, the first such case diagnosed in Greece. The patient now has hearing aids and is being regularly monitored.ConclusionsAutosomal recessive nonsyndromic hearing loss (ARNSHL), including DFNB77, is the most common sensory deficit in children. Our work describes the first <i>LOXHD1</i> hearing loss case diagnosed in Greece and adds a novel pathogenic variant to the list of pathogenic <i>LOXHD1</i> gene variants.

BRAK NASTĘPSTW INFEKCJI COVID-19 W ODNIESIENIU DO STANDARDOWYCH TESTÓW AUDIOLOGICZNYCH

IntroductionCoronavirus disease (COVID-19), considered to be caused by a novel coronavirus (SARS-CoV-2), is an acute respiratory disease which was declared a pandemic by the World Health Organization. Previously published reports have shown contradictory findings on the involvement of the auditory system in individuals infected with COVID-19. The present study aims to assess auditory system functioning in individuals post-COVID-19 infection and compare the results with individuals without COVID-19 infection.Material and methodsParticipants in this study were 30 individuals who had experienced mild COVID-19 infection and 30 individuals who never had COVID-19. Participants were aged between 18 and 40 years. Testing was done 1 to 6 months after infection, and involved conventional and extended high-frequency audiometry, speech perception in quiet and at different signal-to-noise ratios (SPIN), transient evoked otoacoustic emissions (TEOAEs) in quiet and in the presence of contralateral noise, and auditory brainstem response (ABR) in the ipsilateral and contralateral mode.ResultsNone of the tests – pure-tone thresholds, speech perception in quiet and in noise, TEOAE with and without contralateral noise, and ABR – showed any significant difference between individuals who never had COVID-19 infection and those who had recovered from the infection. Both afferent and efferent auditory pathways showed normal findings in individuals post-COVID-19 infection.ConclusionsIndividuals who have been infected with mild COVID-19 did not show any significant deficit in any of the audiological tests, suggesting that the disease does not cause any permanent harm to the auditory system after the infection has subsided.

Changes of FGF23 and hearing in chronic renal failure and their correlation analysis

BackgroundTo explore the association between fibroblast growth factor 23 (FGF23) and hearing in chronic renal failure (CRF). MethodsPure tone audiometry was used to detect the hearing of patients with CRF; the level of serum FGF23, creatinine, blood urea nitrogen (BUN), parathyroid hormone (PTH), and mean binaural hearing threshold were compared to the control group (people without kidney disease). The rat model of renal failure was established by 5/6 nephrectomy, and the auditory brainstem response (ABR) of rats after modeling was detected by the Tucker Davis Technologies (TDT) system; the expression level of FGF23 in the peripheral blood, renal and cochlear tissue was also detected. ResultsThe incidence of hearing loss (HL) and serum FGF23 were higher in CRF patients than the control group; the sFGF23 was positively correlated with the mean binaural hearing threshold. Animal studies showed that the ABR threshold, creatinine, FGF23, BUN, and PTH increased after modeling; although, an increase in FGF23 was observed earlier than other indicators. The HL of rats with renal failure was significantly correlated with BUN, phosphate, PTH, sFGF23, kFGF23/β-actin, eFGF23/β-actin, weight, and modeling cycle. ConclusionsBoth CRF patients and rat models showed high-frequency HL. FGF23 was highly expressed in the serum of HL renal failure patients and rats, as well as in the renal tissue and cochlea of renal failure rats. Therefore, FGF23 may be involved in the occurrence and development of HL caused by CRF.

Analysis of audiological outcomes of children referred from a universal newborn hearing screening program over 9 years in Beijing, China

Universal newborn hearing screening (UNHS) and audiological diagnosis are crucial for children with congenital hearing loss (HL). The objective of this study was to analyze hearing screening techniques, audiological outcomes and risk factors among children referred from a UNHS program in Beijing. A retrospective analysis was performed in children who were referred to our hospital after failing UNHS during a 9-year period. A series of audiological diagnostic tests were administered to each case, to confirm and determine the type and degree of HL. Risk factors for HL were collected. Of 1839 cases, 53.0% were referred after only transient evoked otoacoustic emission (TEOAE) testing, 46.1% were screened by a combination of TEOAE and automatic auditory brainstem response (AABR) testing, and 1.0% were referred after only AABR testing. HL was confirmed in 55.7% of cases. Ears with screening results that led to referral experienced a more severe degree of HL than those with results that passed. Risk factors for HL were identified in 113 (6.1%) cases. The main risk factors included craniofacial anomalies (2.7%), length of stay in the neonatal intensive care unit longer than 5 days (2.4%) and birth weight less than 1500 g (0.8%). The statistical data showed that age (P < 0.001) and risk factors, including craniofacial anomalies (P < 0.001) and low birth weight (P = 0.048), were associated with the presence of HL. This study suggested that hearing screening plays an important role in the early detection of HL and that children with risk factors should be closely monitored.

Estrogen as a guardian of auditory health: Tsp1–CD47 axis regulation and noise-induced hearing loss

Objectives This study aimed to analyze the role of estrogen in noise-induced hearing loss (NIHL) and uncover underlying mechanisms. Methods An ovariectomized Sprague-Dawley rat model (OVX) was constructed to investigate the hearing threshold and auditory latency before and after noise exposure using the auditory brainstem response (ABR) test. The morphological changes were assessed using immunofluorescence, scanning electron microscopy and transmission electron microscopy. Proteomics and bioinformatics were used to analyze the mechanism. The findings were further verified through western blot and Luminex liquid suspension chip technology. Results After noise exposure, OVX rats exhibited substantially elevated hearing thresholds. A conspicuous delay in ABR wave I latency was observed, alongside increased loss of outer hair cells, severe collapse of stereocilia and pronounced deformation of the epidermal plate. Accordingly, OVX rats with estrogen supplementation exhibited tolerance to NIHL. Additionally, a remarkable upregulation of the thrombospondin 1 (Tsp1)–CD47 axis in OVX rats was discovered and verified. Conclusions OVX rats were more susceptible to NIHL, and the protective effect of estrogen was achieved through regulation of the Tsp1–CD47 axis. This study presents a novel mechanism through which estrogen regulates NIHL and offers a potential intervention strategy for the clinical treatment of NIHL.

Zinc deficiency triggers hearing loss by reducing ribbon synapses of inner hair cells in CBA/N mice

Zinc plays a vital role in our metabolism, encompassing antioxidant regulation, immune response, and auditory function. Several studies have reported that zinc levels correlate with hearing loss. We have previously demonstrated that the auditory brainstem response (ABR) threshold increased in mice fed a zinc-deficient diet. However, the effects of zinc deficiency on hearing were not fully elucidated. The present study investigated whether zinc deficiency affects hearing in association with neuronal components or cochlear structures. CBA/N mice were fed a normal or zinc-deficient diet for 8 weeks and assessed for ABR and distortion product otoacoustic emissions (DPOAE). The cochlear sections were stained with hematoxylin and eosin solution. Also, we observed the expression of synaptic ribbons, neurofilaments, and alpha-synuclein (α-Syn). The 8-week zinc-deficient diet mice had an elevated ABR threshold but no changed DPOAE threshold or cochlear structures. A reduced number of synaptic ribbons of inner hair cells (IHCs) and impaired efferent nerve fibers were observed in the zinc-deficient diet mice. The number of outer hair cells (OHCs) and expression of α-Syn remained unchanged. Our results suggest that zinc-mediated hearing loss is associated with the loss of neuronal components of IHCs.

Abnormal Cholesterol Metabolism and Lysosomal Dysfunction Induce Age-Related Hearing Loss by Inhibiting mTORC1-TFEB-Dependent Autophagy.

Cholesterol is a risk factor for age-related hearing loss (ARHL). However, the effect of cholesterol on the organ of Corti during the onset of ARHL is unclear. We established a mouse model for the ARHL group (24 months, n = 12) and a young group (6 months, n = 12). Auditory thresholds were measured in both groups using auditory brainstem response (ABR) at frequencies of 8, 16, and 32 kHz. Subsequently, mice were sacrificed and subjected to histological analyses, including transmission electron microscopy (TEM), H&E, Sudan Black B (SBB), and Filipin staining, as well as biochemical assays such as IHC, enzymatic analysis, and immunoblotting. Additionally, mRNA extracted from both young and aged cochlea underwent RNA sequencing. To identify the mechanism, in vitro studies utilizing HEI-OC1 cells were also performed. RNA sequencing showed a positive correlation with increased expression of genes related to metabolic diseases, cholesterol homeostasis, and target of rapamycin complex 1 (mTORC1) signaling in the ARHL group as compared to the younger group. In addition, ARHL tissues exhibited increased cholesterol and lipofuscin aggregates in the organ of Corti, lateral walls, and spiral ganglion neurons. Autophagic flux was inhibited by the accumulation of damaged lysosomes and autolysosomes. Subsequently, we observed a decrease in the level of transcription factor EB (TFEB) protein, which regulates lysosomal biosynthesis and autophagy, together with increased mTORC1 activity in ARHL tissues. These changes in TFEB and mTORC1 expression were observed in a cholesterol-dependent manner. Treatment of ARHL mice with atorvastatin, a cholesterol synthesis inhibitor, delayed hearing loss by reducing the cholesterol level and maintaining lysosomal function and autophagy by inhibiting mTORC1 and activating TFEB. The above findings were confirmed using stress-induced premature senescent House Ear Institute organ of Corti 1 (HEI-OC1) cells. The findings implicate cholesterol in the pathogenesis of ARHL. We propose that atorvastatin could prevent ARHL by maintaining lysosomal function and autophagy by inhibiting mTORC1 and activating TFEB during the aging process.

Potential uses of auditory nerve stimulation to modulate immune responses in the inner ear and auditory brainstem.

Bioelectronic medicine uses electrical stimulation of the nervous system to improve health outcomes throughout the body primarily by regulating immune responses. This concept, however, has yet to be applied systematically to the auditory system. There is growing interest in how cochlear damage and associated neuroinflammation may contribute to hearing loss. In conjunction with recent findings, we propose here a new perspective, which could be applied alongside advancing technologies, to use auditory nerve (AN) stimulation to modulate immune responses in hearing health disorders and following surgeries for auditory implants. In this article we will: (1) review the mechanisms of inflammation in the auditory system in relation to various forms of hearing loss, (2) explore nerve stimulation to reduce inflammation throughout the body and how similar neural-immune circuits likely exist in the auditory system (3) summarize current methods for stimulating the auditory system, particularly the AN, and (4) propose future directions to use bioelectronic medicine to ameliorate harmful immune responses in the inner ear and auditory brainstem to treat refractory conditions. We will illustrate how current knowledge from bioelectronic medicine can be applied to AN stimulation to resolve inflammation associated with implantation and disease. Further, we suggest the necessary steps to get discoveries in this emerging field from bench to bedside. Our vision is a future for AN stimulation that includes additional protocols as well as advances in devices to target and engage neural-immune circuitry for therapeutic benefits.

Noise-induced hearing loss reduces inhibitory neurotransmitter synthesis in ventral hippocampus and contributes to the social memory deficits of mice

Despite affecting over 1.5 billion people globally, hearing loss (HL) has been referred to as an “invisible disability”, with noise exposure being a major causative factor. Accumulating evidence suggests that HL can induce cognitive impairment. However, relatively little is known about the effects of noise-induced hearing loss (NIHL) on social memory. This study aimed to further investigate the effect of NIHL on social behaviours in mice. We established a rodent model of NIHL using 4-week-old C57BL/6J mice who experienced narrow noise exposure at 116 dB for 3 h per day over two consecutive days. Hearing ability was subsequently evaluated through auditory brainstem response (ABR) testing, and potential changes in the morphology of cochlear hair cells were assessed using immunofluorescence. The sociability and social memory of the mice were evaluated using the three-chamber social interaction test. Noise exposure resulted in complete and persistent HL in C57BL/6J mice, accompanied by severe loss of cochlear hair cells. More importantly, social memory was impaired in adult NIHL mice, whereas their sociability remained intact, these changes were accompanied by a decrease in the protein levels of the inhibitory neuron marker glutamic acid decarboxylase 67 (GAD67) in the ventral hippocampus. This study is the first to confirm that long-term auditory deprivation from HL induced by noise exposure results in social memory deficits in mice without altering their sociability.

Comparison of ASSR and frequency specificity ABR induced by NB CE-Chirp for prediction of behavioral hearing thresholds in children with conductive hearing loss

BackgroundElectrophysiological tests are often used to evaluate hearing loss in infants and young children with conductive hearing loss, no matter to quantify or characterize. However, there are advantages and disadvantages associated with the various electrophysiological tests that are currently available. Therefore, there is no gold standard test. This study aimed to compare the value of narrow-band (NB) CE-Chirp-induced auditory steady-state response (ASSR) and auditory brainstem response (ABR) for assessing hearing thresholds in children with conductive hearing loss. We hope to identify an effective electrophysiological testing method to evaluate conductive hearing loss and provide a reference for clinical hearing assessment of infants with conductive hearing loss. Subjectsand Methods: We selected 27 children (41 ears) aged 3–6 years with otitis media with effusion (OME). Within 1 day, they underwent behavioral audiometry and NB CE-Chirp-induced ASSR and ABR tests in sequence. Pearson's correlation analysis was performed to compare behavioral audiometry thresholds and ASSR and ABR response thresholds at 500, 1000, 2000, and 4000 Hz. ResultsThe behavioral audiometry thresholds of all children were strongly correlated with the response thresholds of the two electrophysiological tests, with correlation coefficients of 0.659, 0.605, 0.723, and 0.857 for ASSR, and 0.587, 0.684, 0.753, and 0.802 for ABR. The proportion of children with a difference of ≤10 dB between ASSR and behavioral audiometry thresholds or between ABR and behavioral audiometry thresholds was not high, especially in the low frequencies. ABR results were superior to ASSR results in terms of predicting actual hearing levels. At 0.5, 1, 2, and 4 kHz, the average differences between the behavioral hearing thresholds and ASSR thresholds in the 41 ears were 5.6, 5.7, 2, and 5.6 dB, respectively. The average differences between behavioral hearing thresholds and ABR thresholds was −5.6, −1.4, −6.8, and 3.2 dB, respectively. The hearing loss configuration of the ASSR exhibited a peaked pattern, similar to behavioral audiometry, whereas the ABR exhibited an ascending pattern. The time to perform the single-ear ASSR test was 5.9 min, whereas the ABR test took 17.0 min. ConclusionASSR and ABR induced by the NB CE-Chirp correlated well with behavioral audiometry in children with conductive hearing loss. The NB CE-Chirp ASSR has advantages in terms of testing time and hearing configuration evaluation, whereas ABR has better reliability than ASSR. However, the stability of ASSR and ABR induced by the NB CE-Chirp is poor, and the thresholds obtained cannot replace behavioral audiometry in evaluating the true hearing of children with conductive hearing loss. However, ASSR and ABR can be used as auxiliary tests for cross-validation.

Auditory brainstem responses in the nine-banded armadillo (Dasypus novemcinctus).

The auditory brainstem response (ABR) to tone burst stimuli of thirteen frequencies ranging from 0.5 to 48 kHz was recorded in the nine-banded armadillo (Dasypus novemcinctus), the only extant member of the placental mammal superorder Xenarthra in North America. The armadillo ABR consisted of five main peaks that were visible within the first 10 ms when stimuli were presented at high intensities. The latency of peak I of the armadillo ABR increased as stimulus intensity decreased by an average of 20 μs/dB. Estimated frequency-specific thresholds identified by the ABR were used to construct an estimate of the armadillo audiogram describing the mean thresholds of the eight animals tested. The majority of animals tested (six out of eight) exhibited clear responses to stimuli from 0.5 to 38 kHz, and two animals exhibited responses to stimuli of 48 kHz. Across all cases, the lowest thresholds were observed for frequencies from 8 to 12 kHz. Overall, we observed that the armadillo estimated audiogram bears a similar pattern as those observed using ABR in members of other mammalian clades, including marsupials and later-derived placental mammals.

Gentamicin administration leads to synaptic dysfunction in inner hair cells

Ototoxicity is a major side effect of aminoglycosides, which can cause irreversible hearing loss. Previous studies on aminoglycoside-induced ototoxicity have primarily focused on the loss of sensory hair cells. Recent investigations have revealed that aminoglycosides can also lead to the loss of ribbon synapses in inner hair cells (IHCs). However, the functional implications of ribbon synapse loss and the underlying mechanisms remain unclear. In this study, we intraperitoneally injected C57BL/6 J mice with 300 mg/kg gentamicin once daily for 3, 10, and 20 days. Then, we performed immunofluorescence staining, patch-clamp recording, proteomics analysis and western blotting to characterize the changes in ribbon synapses in IHCs and the associated mechanisms. After gentamicin treatment, the auditory brainstem response (ABR) threshold was elevated, and the ABR wave I amplitude was decreased. We also observed loss of ribbon synapses in IHCs. Interestingly, ribbon synapse loss occurred on both the modiolar and pillar sides of IHCs. Whole-cell patch-clamp recordings in IHCs revealed a reduction in the calcium current amplitude, along with a shifted half-activation voltage and altered calcium voltage dependency. Moreover, exocytosis of IHCs was reduced, consistent with the reduction in the ABR wave I amplitude. Through proteomic analysis, western blotting, and immunofluorescence staining, we found that gentamicin treatment resulted in downregulation of myosin VI, a protein crucial for synaptic vesicle recycling and replenishment in IHCs. Furthermore, we evaluated the kinetics of endocytosis and found a significant reduction in IHC exocytosis, possibly reflecting the impact of myosin VI downregulation on synaptic vesicle recycling. In summary, our findings demonstrate that gentamicin treatment leads to synaptic dysfunction in IHCs, highlighting the important role of myosin VI downregulation in gentamicin-induced synaptic damage.