Effects of Apelin-13 on auditory system in STZ-induced diabetic rats.

AIM: Damage to the auditory pathways is one of the complications of diabetes. The aim of this study was to investigate the potential therapeutic effects of apelin-13 in the auditory pathways of rats with experimentally induced diabetes by examining its effect on auditory brainstem responses, cochlear oxidative stress and inflammatory cytokines. METHODS: Thirty-two male Wistar albino rats were divided into four groups: sham control, diabetes, apelin and diabetes + apelin. A single dose of 45 mg/kg streptozotocin (STZ) was administered to induce diabetes. The apelin group received 50 µg/kg apelin-13 for seven days intraperitoneally (ip). At the end of the apelin and STZ applications auditory brainstem responses (ABR) was recorded. At the end of the experiment, cochlea was removed and biochemical analyzes were performed. RESULTS: In ABR recordings, the latencies of wave V in diabetic group were observed to be longer than those of the control, with the apelin treatment exhibiting a partial reversal of this situation, particularly at specific frequencies and intensity levels. Apelin treatment leads to a significant increase in total antioxidant status (TAS) and a reduction in total oxidant status (TOS) and oxidative stress index (OSI) in cochlea compared to diabetic groups. The levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1 beta) in cochlear tissue were found to be significantly reduced in the apelin-treated group compared to the diabetic group. CONCLUSION: Apelin-13 may have a protective effect on the auditory system and may be proposed as a potential new therapeutic strategy for the management diabetic auditory impairment.

Age-dependent deficits of auditory brainstem responses in juvenile Neurexin1α knockout rats.

Abnormal sensory processing is core to neuropsychiatric and neurodevelopmental disorders, such as schizophrenia and autism spectrum disorders. Developing efficient therapies requires understanding the basic sensory pathways and identifying circuit abnormalities during early development. Auditory brainstem responses (ABRs) are well-established biomarkers for auditory processing on the brainstem level. Beyond their advantage of being easily applicable in clinics (given their non-invasive nature), ABRs have high reproducibility in rodents and translate well to humans (e.g. wave identity), despite species differences (e.g. wave features). We hypothesized that ABRs would reveal sensory abnormalities in neurodevelopmental models with construct validity, such as Neurexin1α knockout (Nrxn1α KO) rats during their development. In a previous study, adult Nrxn1α KO rats showed altered cortical auditory-evoked potentials and impaired prediction error to auditory stimuli (Janz in Transl Psychiat, 12:455, 2022 ). This study used ABR measurements to assess brainstem physiology during auditory processing in Nrxn1α KO rats and their wild-type littermates. Therefore, we followed the development trajectories of ABRs from the age of 3 weeks to 12 weeks longitudinally. We found that juvenile Nrxn1α KO rats (3 weeks of age) show altered ABRs, which normalized during further development. This alteration was confined to increased latency in waves II, III, and IV of the ABRs, suggesting impaired auditory processing on the level of the superior olivary complex and inferior colliculus. In conclusion, our results suggest that early but transient deficits in the processing of auditory information on the level of the brainstem are present in Nrxn1α KO rats, which may contribute to later cortical auditory processing deficits observed in adulthood. Our study emphasizes the value of ABRs as a functional readout of auditory brainstem circuit function with potential value as a translational biomarker.

Intraoperative Hearing Monitoring Using ABR and TT-ECochG and Hearing Preservation during Vestibular Schwannoma Resection.

Background: Quick and appropriate diagnostics and the use of intraoperative monitoring (IM) of hearing during vestibular schwannoma (VS) resection increase the likelihood of hearing preservation. During surgery, various methods of IM can be used, i.e., auditory brainstem responses (ABRs), transtympanic electrocochleography (TT-ECochG), and direct cochlear nerve action potentials. The aim of the study was to evaluate the prognostic values of IM of hearing using ABR and TT-ECochG in predicting postoperative hearing preservation and to evaluate relationships between them during various stages of surgery. Methods: This retrospective study presents the pre- and postoperative audiological test results and IM of hearing records (TT-ECochG and ABR) in 75 (43 women, 32 men, aged 18-69) patients with diagnosed VS. Results: The preoperative pure tone average hearing threshold was 25.02 dB HL, while after VS resection, it worsened on average by 30.03 dB HL. According to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Hearing Classification, before and after (pre/post) surgery, there were 47/24 patients in hearing class A, 9/8 in B, 2/1 in C, and 17/42 in D. In speech audiometry, the average preoperative speech discrimination score at an intensity of 60 dB SPL was 70.93%, and after VS resection, it worsened to 38.93%. The analysis of electrophysiological tests showed that before the tumor removal the I-V ABR interlatencies was 5.06 ms, and after VS resection, it was 6.43 ms. Conclusions: The study revealed correlations between worse postoperative hearing and changes in intraoperatively measured ABR and TT-ECochG. IM of hearing is very useful in predicting postoperative hearing in VS patients and increases the chance of postoperative hearing preservation in these patients.

Auditory brainstem response to paired clicks as a candidate marker of cochlear synaptopathy in humans.

OBJECTIVE: This study aimed to evaluate whether auditory brainstem response (ABR) using a paired-click stimulation paradigm could serve as a tool for detecting cochlear synaptopathy (CS). METHODS: The ABRs to single-clicks and paired-clicks with various inter-click intervals (ICIs) and scores for word intelligibility in degraded listening conditions were obtained from 57 adults with normal hearing. The wave I peak amplitude and root mean square values for the post-wave I response within a range delayed from the wave I peak (referred to as the RMSpost-w1) were calculated for the single- and second-click responses. RESULTS: The wave I peak amplitudes did not correlate with age except for the second-click responses at an ICI of 7 ms, and the word intelligibility scores. However, we found that the RMSpost-w1 values for the second-click responses significantly decreased with increasing age. Moreover, the RMSpost-w1 values for the second-click responses at an ICI of 5 ms correlated significantly with the scores for word intelligibility in degraded listening conditions. CONCLUSIONS: The magnitude of the post-wave I response for the second-click response could serve as a tool for detecting CS in humans. SIGNIFICANCE: Our findings shed new light on the analytical methods of ABR for quantifying CS.

L-Ergothioneine slows the progression of age-related hearing loss in CBA/CaJ mice.

The naturally occurring amino acid, l-ergothioneine (EGT), has immense potential as a therapeutic, having shown promise in the treatment of other disease models, including neurological disorders. EGT is naturally uptaken into cells via its specific receptor, OCTN1, to be utilized by cells as an antioxidant and anti-inflammatory. In our current study, EGT was administered over a period of 6 months to 25-26-month-old CBA/CaJ mice as a possible treatment for age-related hearing loss (ARHL), since presbycusis has been linked to higher levels of cochlear oxidative stress, apoptosis, and chronic inflammation. Results from the current study indicate that EGT can prevent aging declines of some key features of ARHL. However, we found a distinct sex difference for the response to the treatments, for hearing - Auditory Brainstem Responses (ABRs) and Distortion Product Otoacoustic Emissions (DPOAEs). Males exhibited lower threshold declines in both low dose (LD) and high dose (HD) test groups throughout the testing period and did not display some of the characteristic aging declines in hearing seen in Control animals. In contrast, female mice did not show any therapeutic effects with either treatment dose. Further confirming this sex difference, EGT levels in whole blood sampling throughout the testing period showed greater uptake of EGT in males compared to females. Additionally, RT-PCR results from three tissue types of the inner ear confirmed EGT activity in the cochlea in both males and females. Males and females exhibited significant differences in biomarkers related to apoptosis (Cas-3), inflammation (TNF-a), oxidative stress (SOD2), and mitochondrial health (PGC1a).These changes were more prominent in males as compared to females, especially in stria vascularis tissue. Taken together, these findings suggest that EGT has the potential to be a naturally derived therapeutic for slowing down the progression of ARHL, and possibly other neurodegenerative diseases. EGT, while effective in the treatment of some features of presbycusis in aging males, could also be modified into a general prophylaxis for other age-related disorders where treatment protocols would include eating a larger proportion of EGT-rich foods or supplements. Lastly, the sex difference discovered here, needs further investigation to see if therapeutic conditions can be developed where aging females show better responsiveness to EGT.

Auditory brainstem responses are resistant to pharmacological modulation in Sprague Dawley wild-type and Neurexin1α knockout rats.

Sensory processing in the auditory brainstem can be studied with auditory brainstem responses (ABRs) across species. There is, however, a limited understanding of ABRs as tools to assess the effect of pharmacological interventions. Therefore, we set out to understand how pharmacological agents that target key transmitter systems of the auditory brainstem circuitry affect ABRs in rats. Given previous studies, demonstrating that Nrxn1α KO Sprague Dawley rats show substantial auditory processing deficits and altered sensitivity to GABAergic modulators, we used both Nrxn1α KO and wild-type littermates in our study. First, we probed how different commonly used anesthetics (isoflurane, ketamine/xylazine, medetomidine) affect ABRs. In the next step, we assessed the effects of different pharmacological compounds (diazepam, gaboxadol, retigabine, nicotine, baclofen, and bitopertin) either under isoflurane or medetomidine anesthesia. We found that under our experimental conditions, ABRs are largely unaffected by diverse pharmacological modulation. Significant modulation was observed with (i) nicotine, affecting the late ABRs components at 90 dB stimulus intensity under isoflurane anesthesia in both genotypes and (ii) retigabine, showing a slight decrease in late ABRs deflections at 80 dB stimulus intensity, mainly in isoflurane anesthetized Nrxn1α KO rats. Our study suggests that ABRs in anesthetized rats are resistant to a wide range of pharmacological modulators, which has important implications for the applicability of ABRs to study auditory brainstem physiology.

Multisession anodal epidural direct current stimulation of the auditory cortex delays the progression of presbycusis in the Wistar rat.

Presbycusis or age-related hearing loss (ARHL) is one of the most prevalent chronic health problems facing aging populations. Along the auditory pathway, the stations involved in transmission and processing, function as a system of interconnected feedback loops. Regulating hierarchically auditory processing, auditory cortex (AC) neuromodulation can, accordingly, activate both peripheral and central plasticity after hearing loss. However, previous ARHL-prevention interventions have mainly focused on preserving the structural and functional integrity of the inner ear, overlooking the central auditory system. In this study, using an animal model of spontaneous ARHL, we aim at assessing the effects of multisession epidural direct current stimulation of the AC through stereotaxic implantation of a 1-mm silver ball anode in Wistar rats. Consisting of 7 sessions (0.1 mA/10 min), on alternate days, in awake animals, our stimulation protocol was applied at the onset of hearing loss (threshold shift detection at 16 months). Click- and pure-tone auditory brainstem responses (ABRs) were analyzed in two animal groups, namely electrically stimulated (ES) and non-stimulated (NES) sham controls, comparing recordings at 18 months of age. At 18 months, NES animals showed significantly increased threshold shifts, decreased wave amplitudes, and increased wave latencies after click and tonal ABRs, reflecting a significant, spontaneous ARHL evolution. Conversely, in ES animals, no significant differences were detected in any of these parameters when comparing 16 and 18 months ABRs, indicating a delay in ARHL progression. Electrode placement in the auditory cortex was accurate, and the stimulation did not cause significant damage, as shown by the limited presence of superficial reactive microglial cells after IBA1 immunostaining. In conclusion, multisession DC stimulation of the AC has a protective effect on auditory function, delaying the progression of presbycusis.

The influence of intraoperative auditory brainstem responses on vibroplasty coupling-quality and analysis of the impact of different fixation steps on the coupling.

PURPOSE: The Vibrant Soundbridge (VSB) is an established active-middle-ear-implant for patients with moderate-to-profound hearing-loss. This surgery is referred to as "Vibroplasty". Sufficient transfer of the VSB's floating-mass-transducers (FMT) energy to the inner ear is a crucial factor influencing the coupling-quality (CQ). However, assessing CQ is hamper by two issues: the method of CQ-assessment itself and the method of FMT-fixation during Vibroplasty. METHODS: This prospective study explored the influence of intraoperative auditory-brainstem-response (+ ABR) measurements and various fixation methods on postoperative CQ after Vibroplasty as compared to matched-patients after Vibroplasty without intraoperative ABR (-ABR). Propensity-score-matching was performed based on preoperative bone-conduction-pure-tone-average-3 (BC-PTA3) at 1-, 2- and 4 kHz. Primary outcome parameters were postoperative CQ-PTA3, intraoperative ABR threshold for various fixation methods and postoperative BC-PTA3. RESULTS: A total of 28 patients were included, of which 14 were + ABR. Preoperative BC-PTA3, sex, age, and number of previous surgeries did not differ significantly between groups (all p > 0.301). Mean postoperative CQ-PTA3 was significantly better for + ABR (1.8 vs. 12.3 dB-HL; p = 0.006). Mean intraoperative ABR threshold was superior for cartilage-counter-bearing and cartilage-housing compared to additional fixation with injectable-platelet-rich- fibrin (53 vs. 56 & 57 dB-HL, respectively; p = 0.04; η2 = 0.33). Mean postoperative BC-PTA3 did not significantly differ between patients (41.4 vs. 41.8 dB-HL; p = 0.77). A total of 7% of the patients required intraoperative readjustment of the FMT based on unsatisfactory intraoperative ABR threshold. CONCLUSION: Intraoperative ABR measurement resulted in significantly better postoperative CQ. Cartilage-counter-bearing and cartilage-housing were observed to have superior CQ. A total of 7% of the patients could be spared revision-Vibroplasty due to intraoperative ABR measurement.

Comprehensive behavioral and physiologic assessment of peripheral and central auditory function in individuals with mild traumatic brain injury.

Auditory complaints are frequently reported by individuals with mild traumatic brain injury (mTBI) yet remain difficult to detect in the absence of clinically significant hearing loss. This highlights a growing need to identify sensitive indices of auditory-related mTBI pathophysiology beyond pure-tone thresholds for improved hearing healthcare diagnosis and treatment. Given the heterogeneity of mTBI etiology and the diverse peripheral and central processes required for normal auditory function, the present study sought to determine the audiologic assessments sensitive to mTBI pathophysiology at the group level using a well-rounded test battery of both peripheral and central auditory system function. This test battery included pure-tone detection thresholds, word understanding in quiet, sentence understanding in noise, distortion product otoacoustic emissions (DPOAEs), middle-ear muscle reflexes (MEMRs), and auditory evoked potentials (AEPs), including auditory brainstem responses (ABRs), middle latency responses (MLRs), and late latency responses (LLRs). Each participant also received magnetic resonance imaging (MRI). Compared to the control group, we found that individuals with mTBI had reduced DPOAE amplitudes that revealed a compound effect of age, elevated MEMR thresholds for an ipsilateral broadband noise elicitor, longer ABR Wave I latencies for click and 4 kHz tone burst elicitors, longer ABR Wave III latencies for 4 kHz tone bursts, larger MLR Na and Nb amplitudes, smaller MLR Pb amplitudes, longer MLR Pa latencies, and smaller LLR N1 amplitudes for older individuals with mTBI. Further, mTBI individuals with combined hearing difficulty and noise sensitivity had a greater number of deficits on thalamic and cortical AEP measures compared to those with only one/no self-reported auditory symptoms. This finding was corroborated with MRI, which revealed significant structural differences in the auditory cortical areas of mTBI participants who reported combined hearing difficulty and noise sensitivity, including an enlargement of left transverse temporal gyrus (TTG) and bilateral planum polare (PP). These findings highlight the need for continued investigations toward identifying individualized audiologic assessments and treatments that are sensitive to mTBI pathophysiology.

Enhanced Place Specificity of the Parallel Auditory Brainstem Response: A Modeling Study.

While each place on the cochlea is most sensitive to a specific frequency, it will generally respond to a sufficiently high-level stimulus over a wide range of frequencies. This spread of excitation can introduce errors in clinical threshold estimation during a diagnostic auditory brainstem response (ABR) exam. Off-frequency cochlear excitation can be mitigated through the addition of masking noise to the test stimuli, but introducing a masker increases the already long test times of the typical ABR exam. Our lab has recently developed the parallel ABR (pABR) paradigm to speed up test times by utilizing randomized stimulus timing to estimate the thresholds for multiple frequencies simultaneously. There is reason to believe parallel presentation of multiple frequencies provides masking effects and improves place specificity while decreasing test times. Here, we use two computational models of the auditory periphery to characterize the predicted effect of parallel presentation on place specificity in the auditory nerve. We additionally examine the effect of stimulus rate and level. Both models show the pABR is at least as place specific as standard methods, with an improvement in place specificity for parallel presentation (vs. serial) at high levels, especially at high stimulus rates. When simulating hearing impairment in one of the models, place specificity was also improved near threshold. Rather than a tradeoff, this improved place specificity would represent a secondary benefit to the pABR's faster test times.

Electrically evoked auditory responses: A classification for brainstem implant placement in Neurofibromatosis Type 2.

OBJECTIVE: In auditory brainstem implant (ABI) surgery, array placement may be optimized by electrophysiological information of adequate brainstem activation gained from electrically evoked auditory brainstem responses (EABR). This study aims 1) to characterize in detail the EABR from ABI implantation, 2) to introduce an EABR Classification Scheme, and 3) to analyze data for their correlation with individual patients' findings. METHODS: Out of a continuous series of 54 patients who received an ABI between 2005 and 2019, 23 Neurofibromatosis Type 2 patients with complete documentation of 154 recordings were selected for offline analysis and for development and evaluation of a new EABR Classification Scheme comprising Class A: three vertex positive peaks, Class B:two peaks, Class C: a combination of one peak and a second melted double peak, Class D: one sole vertex positive peak and Class E: no peaks. RESULTS: All 23 subjects showed EABR at final ABI position and experienced auditory sensations at first activation. The most frequent morphology consisted of two peaks, Classes B and C. Identified mean latencies were for P1 0.42 ms (±0.095), P2 1.42 ms (±0.244) and P3 2.41 ms (±0.329). Peak latencies correlated positively with tumor extensions (p < 0.005). CONCLUSIONS: This study provides clear instructions on optimal EABR performance and evaluation. SIGNIFICANCE: The new EABR Classification Scheme relies on a fast "online" identification of vertex positive peaks at the estimated post-artifact phase. The variability in EABR morphology provides an individual snapshot of the actual structural and functional status of the brainstem.

Quantitative Threshold Determination of Auditory Brainstem Responses in Mouse Models.

The auditory brainstem response (ABR) is a scalp recording of potentials produced by sound stimulation, and is commonly used as an indicator of auditory function. However, the ABR threshold, which is the lowest audible sound pressure, cannot be objectively determined since it is determined visually using a measurer, and this has been a problem for several decades. Although various algorithms have been developed to objectively determine ABR thresholds, they remain lacking in terms of accuracy, efficiency, and convenience. Accordingly, we proposed an improved algorithm based on the mutual covariance at adjacent sound pressure levels. An ideal ABR waveform with clearly defined waves I-V was created; moreover, using this waveform as a standard template, the experimentally obtained ABR waveform was inspected for disturbances based on mutual covariance. The ABR testing was repeated if the value was below the established cross-covariance reference value. Our proposed method allowed more efficient objective determination of ABR thresholds and a smaller burden on experimental animals.

Universal Recommendations on Planning and Performing the Auditory Brainstem Responses (ABR) with a Focus on Mice and Rats.

Translational audiology research aims to transfer basic research findings into practical clinical applications. While animal studies provide essential knowledge for translational research, there is an urgent need to improve the reproducibility of data derived from these studies. Sources of variability in animal research can be grouped into three areas: animal, equipment, and experimental. To increase standardization in animal research, we developed universal recommendations for designing and conducting studies using a standard audiological method: auditory brainstem response (ABR). The recommendations are domain-specific and are intended to guide the reader through the issues that are important when applying for ABR approval, preparing for, and conducting ABR experiments. Better experimental standardization, which is the goal of these guidelines, is expected to improve the understanding and interpretation of results, reduce the number of animals used in preclinical studies, and improve the translation of knowledge to the clinic.

Assessing Auditory Processing in Children with Listening Difficulties: A Pilot Study.

BACKGROUND: Auditory processing disorders (APD) may be one of the problems experienced by children with listening difficulties (LiD). The combination of auditory behavioural and electrophysiological tests could help to provide a better understanding of the abilities/disabilities of children with LiD. The current study aimed to quantify the auditory processing abilities and function in children with LiD. METHODS: Twenty children, ten with LiD (age = 8.46; SD = 1.39) and ten typically developing (TD) (age = 9.45; SD = 1.57) participated in this study. All children were evaluated with auditory processing tests as well as with attention and phonemic synthesis tasks. Electrophysiological measures were also conducted with click and speech auditory brainstem responses (ABR). RESULTS: Children with LiD performed significantly worse than TD children for most behavioural tasks, indicating shortcomings in functional auditory processing. Moreover, the click-ABR wave I amplitude was smaller, and the speech-ABR waves D and E latencies were longer for the LiD children compared to the results of TD children. No significant difference was found when evaluating neural correlates between groups. CONCLUSIONS: Combining behavioural testing with click-ABR and speech-ABR can highlight functional and neurophysiological deficiencies in children with learning and listening issues, especially at the brainstem level.

Electrical Field Interactions during Adjacent Electrode Stimulations: eABR Evaluation in Cochlear Implant Users.

The present study investigates how electrically evoked Auditory Brainstem Responses (eABRs) can be used to measure local channel interactions along cochlear implant (CI) electrode arrays. eABRs were recorded from 16 experienced CI patients in response to electrical pulse trains delivered using three stimulation configurations: (1) single electrode stimulations (E11 or E13); (2) simultaneous stimulation from two electrodes separated by one (En and En+2, E11 and E13); and (3) stimulations from three consecutive electrodes (E11, E12, and E13). Stimulation level was kept constant at 70% electrical dynamic range (EDR) on the two flanking electrodes (E11 and E13) and was varied from 0 to 100% EDR on the middle electrode (E12). We hypothesized that increasing the middle electrode stimulation level would cause increasing local electrical interactions, reflected in characteristics of the evoked compound eABR. Results show that group averaged eABR wave III and V latency and amplitude were reduced when stimulation level at the middle electrode was increased, in particular when stimulation level on E12 reached 40, 70, and 100% EDR. Compound eABRs can provide a detailed individual quantification of electrical interactions occurring at specific electrodes along the CI electrode array. This approach allows a fine determination of interactions at the single electrode level potentially informing audiological decisions regarding mapping of CI systems.

The association of auditory function measures with low-level methylmercury from oceanic fish consumption and mercury vapor from amalgam: The Seychelles Child Development Study Nutrition 1 Cohort.

BACKGROUND: Some authors have reported that low-level exposure to methylmercury (MeHg) adversely impacts measures of auditory function. These reports, however, are not consistent in their findings. Consequently, we examined auditory function in a population exposed to low-level methylmercury (MeHg) exposure from fish consumption and to mercury vapor (Hg0) from dental amalgams. We analyzed their associations with the participants hearing acuity, absolute and interwave ABR latencies, and otoacoustic emissions (distortion product/DPOAE and click evoked/CEOAE). DESIGN: We administered an audiometry test battery to 246 participants from the Seychelles Child Development Study (SCDS) Nutrition Cohort 1 (NC1) at 9 years of age. The test battery included standard pure-tone audiometry, tympanometry, Auditory Brainstem Responses (ABR) and Distortion Product and Click Evoked Otoacoustic Emissions (DPOAE and CEOAE) testing. We measured prenatal MeHg exposure in maternal hair and postnatal MeHg in children's hair. We approximated prenatal Hg0 exposure using maternal amalgam surface area and postnatal Hg0 using children amalgam surface area. Complete exposure records and audiometric data were available on 210 participants and in them we analyzed the association of MeHg and Hg0 exposures with auditory outcomes using covariate-adjusted linear regression models adjusted for sex and tympanometric pressure. RESULTS: Hg exposures were similar for both sexes. Seven of the 210 evaluable participants examined had either a mild (5) or moderate (2) hearing loss. Four had a mild monaural hearing loss and 3 had either a mild (1) or moderate (2) bilateral hearing loss. No participant had greater than a moderate hearing loss in either ear. Hg exposures were higher in participants with either a mild or moderate hearing loss, but these differences were not statistically significant. Among the 210 with complete data, neither prenatal nor postnatal MeHg nor Hg0 exposure was statistically significantly associated with any of the ABR endpoints (p > 0.05 for all 72 associations). Neither prenatal nor postnatal Hg0 exposure was associated with any of the OAE endpoints (p > 0.05). MeHg exposure was statistically associated with 6 of the 56 DPOAE endpoints (p-values between 0.0001 and 0.023), but none of the 40 CEOAE endpoints. Two of the associations occurred with prenatal MeHg exposures and 1 of those would suggest a beneficial effect. Four of the other associations occurred with postnatal MeHg exposures with only 2 found in left ears of both males and females and the other 2 in the left and right ear of females at only one frequency. CONCLUSION: Overall, these data do not present a clear and consistent pattern to suggest that the auditory system is negatively affected by low-level methylmercury exposure due to dietary consumption of oceanic fish or mercury vapor exposure from dental amalgams.

Normal reference values of low frequency specific air-conducted auditory brainstem responses among normal hearing children of different ages: A retrospective observational study.

OBJECTIVES: To explore and compare the normal reference values (NRV) for low frequency specific air-conducted tone-burst auditory brainstem response (tb-ABR) among children of different ages and with normal hearing, because tb-ABR is often used to supplement the lack of click-evoked ABR (click-ABR) frequency but the NRV of this response threshold in different populations remain inconclusive. METHODS: This retrospective observational study included children younger than 5 years of age with normal hearing in Hubei Province between November 2020 and September 2021. These children came to center of audiology for audiological examination including click-ABR due to different purposes and had accepted suggestion of tb-ABR test (0.5 kHz, 1 kHz). The children were divided into 5 groups according to age (0-12, 13-24, 25-36, 37-48, and 49-60 months of age), and 20 children (40 ears) met the inclusion criteria were selected from each group. The responding thresholds, peak latencies (PL), and inter-peak latencies (IPL) of the major waves were counted and compared in each group. RESULTS: NRV of responding thresholds (dBnHL) in children aged 0-12, 13-24, 25-36, 37-48, and 49-60 months were 27.25 ± 9.47, 22.63 ± 5.31, 21.5 ± 5.33, 18.25 ± 5.83, and 21.63 ± 6.24 at 0.5 kHz, and 23.63 ± 7.16, 20.88 ± 7.06, 22 ± 4.21, 17.75 ± 6.09, and 21.38 ± 4.53 at 1 kHz, respectively. The response thresholds of children aged 0-12 months were significantly higher compared to children in other age groups at 0.5 kHz (all P < 0.05) and significantly higher than in children aged 37-48 months at 1 kHz (P < 0.05). There were significant differences among children of different ages in Wave III (P < 0.001) and Wave V (P < 0.001) in the peak latencies, and Waves I-III (P = 0.003) and Waves I-V (P < 0.001) in the inter-peak latencies at 0.5 kHz. Also, there were significant differences among children of different ages in Wave III and Wave V in the PL, and Waves I-III, Waves III-V, and Waves I-V in the IPL at 1 kHz (all P < 0.001). CONCLUSION: The NRV of tb-ABR at 0.5 kHz and 1 kHz might differ among children of different ages. Newborn infants (<12 months old) might have a higher response threshold, while children aged 37-48 months might have a lower response threshold. However, it was a retrospective analysis with a small sample size, prospective contrast studies with larger samples are needed in the future.

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

Abstract 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.

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.

Brainstem evoked auditory potentials in tinnitus: A best-evidence synthesis and meta-analysis.

Introduction: Accumulating evidence suggests a role of the brainstem in tinnitus generation and modulation. Several studies in chronic tinnitus patients have reported latency and amplitude changes of the different peaks of the auditory brainstem response, possibly reflecting neural changes or altered activity. The aim of the systematic review was to assess if alterations within the brainstem of chronic tinnitus patients are reflected in short- and middle-latency auditory evoked potentials (AEPs). Methods: A systematic review was performed and reported according to the PRISMA guidelines. Studies evaluating short- and middle-latency AEPs in tinnitus patients and controls were included. Two independent reviewers conducted the study selection, data extraction, and risk of bias assessment. Meta-analysis was performed using a multivariate meta-analytic model. Results: Twenty-seven cross-sectional studies were included. Multivariate meta-analysis revealed that in tinnitus patients with normal hearing, significantly longer latencies of auditory brainstem response (ABR) waves I (SMD = 0.66 ms, p < 0.001), III (SMD = 0.43 ms, p < 0.001), and V (SMD = 0.47 ms, p < 0.01) are present. The results regarding possible changes in middle-latency responses (MLRs) and frequency-following responses (FFRs) were inconclusive. Discussion: The discovered changes in short-latency AEPs reflect alterations at brainstem level in tinnitus patients. More specifically, the prolonged ABR latencies could possibly be explained by high frequency sensorineural hearing loss, or other modulating factors such as cochlear synaptopathy or somatosensory tinnitus generators. The question whether middle-latency AEP changes, representing subcortical level of the auditory pathway, are present in tinnitus still remains unanswered. Future studies should identify and correctly deal with confounding factors, such as age, gender and the presence of somatosensory tinnitus components. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021243687, PROSPERO [CRD42021243687].