Auditory Brainstem Response Waveforms Research Articles

Investigating the Effects of Level-Specific CE-Chirp on Auditory Brainstem Response Waves in Normal Hearing Infants.

Auditory brainstem response (ABR) to the level-specific (LS) CE-Chirp has been reported to provide optimum neural synchrony along cochlear partitions, theoretically improving ABR waveform resolution. Despite this promising finding, limited studies have been conducted to contrast the results between LS CE-Chirp and Click stimuli. The current study aimed to compare the results of ABR between the two stimuli (Click and LS CE-Chirp). Sixty-seven normal-hearing infants, both with and without risk factors, aged less than 7 months old, participated in this study. The ABR test was conducted at 70 dBnHL using 33.3 stimulus repetition rates with both Click and LS CE-Chirp stimuli. The signal averaging was stopped at a maximum fixed signal average of 2,500 sweeps. Data were statistically compared between the two stimuli using the Wilcoxon signed-rank test. The waves I and V ABRs elicited by LS CE-Chirp exhibited significantly larger amplitudes than the Click stimulus. However, the amplitude of wave III and absolute latencies were similar in both stimuli at a supra-threshold level. LS CE-Chirp has the advantage of larger amplitudes than the ABR from Click at the supra-threshold level (70 dBnHL) in normal-hearing infants.

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.

Auditory brainstem response (ABR) waveform analysis program

Auditory brainstem responses (ABR) are a high-throughput assessment of auditory function. Many studies determine changes to the threshold at frequencies that span the normal hearing range of their test subjects, but fewer studies evaluate changes in waveform morphology. The goal of developing this program was to make a user-friendly semiautomatic peak-detection algorithm to encourage widespread analysis of the amplitudes and latencies of the ABR, which may yield informative details about the integrity of the auditory system with development, aging, genetic manipulations, or damaging conditions. This method incorporates automated peak detection with manual override and inter-rater validation to calculate the amplitude and latency for waves 1–5, as well as interpeak latencies and amplitude ratios between waves. The output includes raw data and calculations in a format compatible with graphical and statistical software.•The method yields a high-throughput peak-detection algorithm with manual override and inter-rater capabilities to streamline ABR waveform analysis.•Data output includes amplitudes, latencies, amplitude ratios, and interpeak latencies for generation of input-output curves.•While complete automation of peak detection with this tool is dependent on good signal-to-noise ratios, relevant amplitude and latency calculations are fully automated, and manual spot-checking is simplified to significantly reduce the time to analyze waveforms.

Aging leads to impairment of spatial hearing abilities in the Mongolian Gerbil

Aging in humans is known to affect spatial hearing and speech in noise recognition, often even when hearing thresholds are normal. The Mongolian Gerbil (Meriones unguiculatus) can provide a model organism to investigate these changes. We performed auditory brainstem responses (ABRs), prepulse inhibition of the acoustic startle (PPI) behavior, and cochlear histology to assess age-related changes of the gerbil auditory brainstem. Aging (>33month) gerbils showed reduced ABR waveform amplitudes compared to young gerbils (2-10 months). Aging gerbils also show a reduced amplitude of the binaural interaction component (BIC), a biomarker for spatial hearing. However, ABR thresholds were not significantly different between cohorts. Aging gerbils showed impaired performance in our behavior tasks: young gerbils detected shorter gaps in noise and smaller minimum audible angles than aging animals, indicating that aging impairs temporal and spatial hearing abilities. Cochlear histology revealed an increase in cochlear synaptopathy in aging animals, revealing a potential mechanism for age-related dysfunction in the auditory pathway. Taken together, these data reveal structural and physiological changes in the auditory brainstem that underlie spatial hearing deficits in the gerbil. [Work supported by R01-DC017924.]

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.

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.

Short-term outcomes of infants with hyperbilirubinemia-associated auditory neuropathy spectrum disorder in neonatal intensive care unit

Hyperbilirubinemia is a high-risk factor for auditory neuropathy spectrum disorder (ANSD) as well as hearing loss in general. This study described the outcomes of hyperbilirubinemia-associated ANSD infants diagnosed in hearing screening in the neonatal intensive care unit (NICU).A total of 578 children with hyperbilirubinemia admitted to the NICU between October 2020 and October 2021 were included in this study. The distortion product otoacoustic emission (DPOAE) and automatic auditory brainstem response (AABR) were combined for hearing screening, and those who failed the DPOAE or/and AABR underwent an auditory brainstem response (ABR) test. Infants with ANSD were followed up for 12 months.Forty infants (40/578, 6.9%) failed the DPOAE or/and AABR tests, of which, 13 (13/578, 2.2%) were diagnosed as ANSD, and 27 (27/578, 4.7%) were diagnosed as having sensorineural hearing loss (SNHL). Of the 13 ANSD infants followed up for 12 months, 7 recovered, 3 improved, 3 did not recover, and 1 was lost, equating to improved or recovered hearing in 75% (9/12) of ANSD infants at 12 months of age. Moreover, the maximum bilirubin in recovered or improved ANSD infants was 408.6 ± 129.0 μmol/L, while the maximum bilirubin in unrecovered ANSD infants was 749.3 ± 323.0 μmol/L. Furthermore, poorly differentiated and absent ABR waveforms were observed in 6 and 14 ears at 1 month, 2 ears were lost, 6 (6/6, 100.0%) and 6 (6/12, 50.0%) ears were recovered or improved at 12 months of age.s: The incidence of hyperbilirubinemia associated-ANSD was 2.2% of infants screened in the NICU. ANSD caused by hyperbilirubinemia may be transient, with most infants improving or recovering hearing by 12 months of age. Infants with poorly differentiated ABR waveforms and low bilirubin concentration are more likely to recover and hearing aids are not recommended in hyperbilirubinemia-associated ANSD below 12 months of age.

Auditory brainstem response in autistic children: implications for sensory processing

Purpose Autistic individuals frequently experience sensory processing difficulties. Such difficulties can significantly impact important functions and quality of life. We are only beginning to understand the neural mechanisms of atypical sensory processing. However, one established way to measure aspects of auditory function is the auditory brainstem response (ABR). While ABR has been primarily hypothesised thus far as a means of early detection/diagnosis in autism, it has the potential to aid in examining sensory processing in this population. Method Thus, we investigated standard ABR waveform characteristics in age-matched groups of autistic and typically developing children during various stimulus and intensity conditions. We also examined within ear waveform cross-correlations and inter-aural cross-correlations (IACC) to assess replicability and synchrony of participants’ ABRs, which was a novel approach to ABR analysis in this population. Results We observed longer peak latencies (esp. wave III and V) and interpeak latencies in the autism and typically developing groups in different conditions. There were no statistically significant results in cross-correlation or IACC. Conclusions These results suggest that brainstem auditory function may differ slightly, but is mostly similar, between autistic and typically developing children. We discuss these findings in terms of their implications for sensory processing and future utility.

Characteristics of auditory brainstem response in wild yellow grouper Epinephelus awoara

Auditory brainstem response (ABR) technology is used to set up a fish auditory threshold detection system, and the auditory threshold of wild yellow grouper Epinephelus awoara caught in the Taiwan Strait is studied. The ABRs of 10 wild yellow groupers (TL150-200 mm) to 12 different frequencies of sound stimulation from 100 to 2000 Hz are recorded and analyzed. The results show that the auditory threshold of wild yellow grouper fish increases with the increase of frequency in the frequency of 200-2000Hz. The fish is sensitive to low frequency sound signal of 100-300Hz with the most sensitive frequency of 200Hz, and the auditory threshold is 90 dB re 1μPa. The ABR waveform shows three periods: response period, real hearing period and extension period. In the range of 100-2000Hz, the response time decreases with the increase of frequency at the same sound pressure level. At the same frequency, the response time increases with the decrease of sound pressure level. The first amplitude sound pressure of real hearing period is between 50-150nv, and the real hearing period contains the greatest amplitude. When the greatest amplitude is about 50nv and the next sound pressure level is below 50nv, the sound pressure level is the auditory threshold. The extension period is proportional to the response period.

Assessing Medial Olivocochlear Reflex Strengths via Auditory Brainstem Response: Measurement and Variability in Normal-Hearing Individuals

Optimal measurement settings to measure the medial olivocochlear reflex (MOCR) in humans have not yet been defined. The purpose of this study was to advance the representation of the MOCR in auditory brainstem response (ABR) as an addition to the current diagnostic portfolio. Twelve female and 14 male normal-hearing adults participated in the study. Potential effects of a contralateral acoustic stimulus (CAS) on amplitude changes were investigated by recording ABR waveform profiles on the left side at click intensities of 50/60/70 dB nHL with and without CAS (60 dB SPL). Secondly, to detect potential chronological order influences, measurement settings were rearranged on the right side and measurements were repeated. Additionally, ABR thresholds were recorded with and without a CAS in 10 patients. When the effect of contralateral suppression was analyzed on the basis of amplitude changes, there was a change under administration of the CAS signal that was statistically significant. Interestingly, the order of recordings affected the degree of amplitude change. In three out of 10 patients, reproducible suppression effects on ABR thresholds were detectable upon CAS presentation. To our knowledge, this is the largest study dealing with the recording of the MOCR elicited by a contralateral noise via ABR in normal-hearing individuals. Effects of MOCR are measurable via amplitude changes upon CAS administration. Chronological orders influence the impact of this effect on amplitude changes. Optimal measurement settings have not yet been defined. However, experiments such as this study may help to further improve measurements, and thus advance the representation of the MOC reflex in ABR as an addition to the current diagnostic portfolio.

Towards Optimizing the Quality of Long-Term Physiological Signals Monitoring by Using Anhydrous Carbon Paste Electrode.

Long-term physiological signal monitoring is very important for the diagnosis of health conditions that occur randomly and cannot be easily detected by a short period of a hospital visit. However, the conventional wet electrodes suffered from the problem of signal quality degradation due to the gradual dehydration of the conductive gel. An anhydrous carbon paste electrode (CPE) constructed by a composite of carbon black and polydimethylsiloxane was proposed to enable long-term physiological signal monitoring without signal quality degradation as time elapses. The performance was systematically compared with conventional electrodes when measuring long-term physiological signals including electrocardiogram (ECG), electromyogram (EMG), electroencephalogram (EEG) and auditory brainstem response (ABR). The proposed CPE showed more stable skin-electrode impedance and higher signal qualities as the monitoring time increased up to 48 days, with signal-to-noise ratios (SNRs) of 16.43 ± 10.39 dB higher for ECG and 24.30 ± 7.79 dB higher for EMG when compared with wet electrodes. The CPE method could also obtain more consistent ABR waveform morphologies and could measure EEG under sweating conditions. It is believed that the proposed CPE could be a potential candidate for durable and robust wearable sensors systems on long-term physiological signal monitoring.

Semi-Automated Analysis of Peak Amplitude and Latency for Auditory Brainstem Response Waveforms Using R.

Many reports in the last 15 years have assessed changes in the auditory brainstem response (ABR) waveform after insults such as noise exposure. Common changes include reductions in the peak 1 amplitude and the relative latencies of the later peaks, as well as increased central gain, which is reflected by a relative increase in the amplitudes of the later peaks compared to the amplitude of peak 1. Many experimenters identify the peaks and troughs visually to assess their relative heights and latencies, which is a laborious process when the waveforms are collected in 5 dB increments throughout the hearing range for each frequency and condition. This paper describes free routines that may be executed in the open-source platform R with the RStudio interface to semi-automate the measurements of the peaks and troughs of auditory brainstem response (ABR) waveforms. The routines identify the amplitudes and latencies of peaks and troughs, display these on a generated waveform for inspection, collate and annotate the results into a spreadsheet for statistical analysis, and generate averaged waveforms for figures. In cases when the automated process misidentifies the ABR waveform, there is an additional tool to assist in correction. The goal is to reduce the time and effort needed to analyze the ABR waveform so that more researchers will include these analyses in the future.

Semi-Automated Analysis of Peak Amplitude and Latency for Auditory Brainstem Response Waveforms Using R

Semi Automated Analysis Peak Amplitude Latency For Auditory Brainstem - Video. JoVE publishes peer-reviewed scientific video protocols to accelerate biological, medical, chemical and physical research. Watch our scientific video articles. JoVE is the world-leading producer and provider of science videos with the mission to improve scientific research, scientific journals, and education. Millions of scientists, educators and students at thousands of universities, colleges, hospitals and biopharmaceutical companies worldwide use JoVE for their research, teaching and learning.

Visualizing Contralateral Suppression of Hearing Sensitivity via Acoustic and Electric Brainstem Audiometry in Bimodal Cochlear Implant Patients: A Feasibility Study

Introduction: The medial olivocochlear reflex (MOCR) is a part of the binaural processing strategies and influences the efferent auditory pathway in normal-hearing individuals. Patients with asymmetric hearing loss often benefit from a bimodal hearing solution with a cochlear implant (CI) and a hearing aid (HA). However, hearing performances may vary with some surprisingly high- or low-performing CI/HA users. A potential role of the MOCR among these patients warrants further investigation. Otoacustics emissions are an established method to visualize the reflex; however, this technique implies some disadvantages. To visualize the MOCR via auditory brainstem response (ABR) could be a promising alternative. Methods: Twenty-three bimodal CI/HA users were enrolled. Experimental setup was as follows: I. electrical ABR on the CI side was recorded with and without simultaneous contralateral noise signal at the HA side, II. acoustic ABR was recorded on the HA side with and without simultaneous contralateral noise at the CI side. Brainstem thresholds and amplitudes of waveforms I–V with and without contralateral noise were compared. Potential correlations of patient-related factors and hearing performances were analysed. Results: In four individuals, a reduction of brainstem audiometry thresholds could be observed at the acoustic brainstem audiometry. In these cases, results could be reproduced. Summarizing ABR measurements at the HA side of all individuals, no relevant changes of ABR thresholds (dB nHL) or waveform amplitude reductions (nV) could be observed irrespective of the presence or absence of a contralateral suppression signal. Conclusion: Threshold changes of acoustic ABR upon presentation of a contralateral suppression signal could not generally be measured in bimodal CI users. However, in a subgroup, a highly reproducible effect was demonstrated if a contralateral suppression signal was applied. A reactivated rather than rehabilitated MOCR may have accounted for this effect in this subgroup. One could speculate that in these patients, bimodal fitting could be affected by the MOCR efferents.

Longitudinal analysis of auditory dysfunction in Alzheimer’s disease mice 5xFAD

AbstractBackgroundThere is no cure for AD at this moment. All available therapies require accurate diagnosis and staging of AD to ensure proper strategy. Current diagnosis methods rely on high‐cost technologies with radioactive agents, and those are not necessarily included in regular health screenings. Thus, a low‐cost, non‐invasive approach of AD analysis is in great need. The comorbidity between Alzheimer’s disease and hearing loss has been shown to be significant. Beyond hearing loss, AD patients also showed auditory processing disorders. However, it remains unclear if auditory deficits can be a good biomarker for AD analysis, especially for early stages.Method5xFAD animals were bred in CBA/B6 hybrid background to compensate the hearing loss deficits in C57/B6 strain and only F1 animals were used in this study. The auditory features were monitored by Auditory Brainstem Response (ABR) test and Distortion Product Otoacoustic Emission (DPOAE) test at 3, 6, 9 and 12‐month‐old, which correlate to young ‐ middle age of human lifespan. Their anti‐masking ability was evaluated by masking ABR and notched noise ABR in 3 and 12‐month‐old animals. Fluorescent immunostaining was performed to evaluate anatomical change in cochlea.ResultAD animals showed accelerated age‐related hearing loss comparing to their WT littermates. The ABR threshold showed significant change at lower frequencies first, then extended to all testing frequencies. DPOAE threshold did not show significant change at any testing frequency. Aged AD animals showed significantly higher threshold increase in masking ABR and notched‐noise ABR. In addition to the increased hearing threshold, ABR waveform abnormalities were also observed in the AD animals. Longitudinal analysis revealed that ABR waveform abnormalities develop along with the progression of AD. Those abnormalities suggest auditory neuropathy and auditory processing deficits in AD animals. Histology analysis showed no significant change in synapse number or efference morphology.ConclusionAuditory dysfunction is a possible outcome of AD, and more likely reflecting the anatomical changes in central nervous system rather than periphery. Auditory dysfunction is a good candidate as a biomarker for AD progression at early stages.

A Robust Extraction Approach of Auditory Brainstem Response Using Adaptive Kalman Filtering Method.

The Auditory brainstem response (ABR) can provide valuable information on the function of the auditory pathway. However, the ABR signal has a very small amplitude, and it is easily submerged in different background noises with large amplitude. Conventional ABR extraction methods such as time-domain averaging (TDA) and Kalman filter (KF) were greatly affected by noise intensity, and the result relies on the empirical settings of parameters. ABR extraction method that can automatically adjust parameters to adapt different background noises was needed. An adaptive Kalman filtering (AKF) based ABR signal extraction method was proposed, in which two recursive rules were introduced to constantly update the parameters according to the real-time noise properties. It was used for ABR extraction from recordings in noises with different orders of larger magnitude. The AKF method demonstrated the best performance in obtaining reliable ABR waveform morphologies in the presence of large EMG noises compared with traditional methods of TDA or KF. It could extract satisfactory ABR signal with fewer trials of acoustic stimulus repetition, even from noise 10000 times larger than ABR signal. The AKF results also showed smaller absolute errors and higher correlation coefficients with the target ABR signal when different types (gum chewing, mouth opening and milk drinking) or levels of noises were introduced. The proposed AKF method is a great candidate to increase the robustness of current ABR measurements. It could provide reduced testing time and relaxed recording conditions for ABR and other evoked potentials extraction.

Auditory Brainstem Responses at 6 and 8 kHz in Infants With Normal Hearing.

Normative auditory brainstem response (ABR) data for infants and young children are available for 0.25-4 kHz, limiting clinical assessment to this range. As such, the high-frequency hearing sensitivity of infants and young children remains unknown until behavioral testing can be completed, often not until late preschool or early school ages. The purpose of this study was to obtain normative ABR data at 6 and 8 kHz in young infants. Participants were 173 full-term infants seen clinically for ABR testing at 0.4-6.7 months chronological age (M = 1.4 months, SD = 1.0), 97% of whom were ≤ 12 weeks chronological age. Stimuli included 6 and 8 kHz tone bursts presented at a rate of 27.7/s or 30.7/s using Blackman window gating with six cycles (6 kHz) or eight cycles (8 kHz) rise/fall time and no plateau. Presentation levels included 20, 40, and 60 dB nHL. The ABR threshold was estimated in 5- to 10-dB steps. As previously observed with lower frequency stimuli, ABR waveforms obtained in response to 6 and 8 kHz tone bursts decreased in latency with increasing intensity and increasing age. Latency was shorter for 8-kHz tone bursts than 6-kHz tone bursts. Data tables are presented for clinical reference for infants ≤ 4 weeks, 4.1-8 weeks, and 8.1-12 weeks chronological age including median ABR latency for Waves I, III, and V and the upper and lower boundaries of the 90% prediction interval. Interpeak Latencies I-III, III-V, and I-V are also reported. The results from this study demonstrate that ABR assessment at 6 and 8 kHz is feasible for young infants within a standard clinical appointment and provide reference data for clinical interpretation of ABR waveforms for frequencies above 4 kHz.

Hearing impairment in murine model of Down syndrome.

Hearing impairment is a cardinal feature of Down syndrome (DS), but its clinical manifestations have been attributed to multiple factors. Murine models could provide mechanistic insights on various causes of hearing loss in DS. To investigate mechanisms of hearing loss in DS in the absence of the cadherin 23 mutation, we backcrossed our DS mice, Dp(16)1Yey, onto normal-hearing CBA/J mice and evaluated their auditory function. Body weights of wild type (WT) and DS mice were similar at 3-months of age, but at 9-months, WT weighed 30% more than DS mice. Distortion product otoacoustic emissions (DPOAE), a test of sensory outer hair cell (OHC) function negatively impacted by conductive hearing loss, were reduced in amplitude and sensitivity across all frequencies in DS mice. The middle ear space in DS mice appeared normal with no evidence of infection. MicroCT structural imaging of DS temporal bones revealed a smaller tympanic membrane diameter, oval window, and middle ear space and localized thickening of the bony otic capsule, but no gross abnormalities of the middle ear ossicles. Histological analysis of the cochlear and vestibular sensory epithelium revealed a normal density of cochlear and vestibular hair cells; however, the cochlear basal membrane was approximately 0.6 mm shorter in DS than WT mice so that the total number of hair cells was greater in WT than DS mice. In DS mice, the early and late peaks in the auditory brainstem response (ABR), reflecting neural responses from the cochlear auditory nerve followed by subsequent neural centers in the brainstem, were reduced in amplitude and ABR thresholds were elevated to a similar degree across all frequencies, consistent with a conductive hearing impairment. The latency of the peaks in the ABR waveform were longer in DS than WT mice when compared at the same intensity; however, the latency delays disappeared when the data were compared at the same intensity above thresholds to compensate for the conductive hearing loss. Future studies using wideband tympanometry and absorbance together with detailed histological analysis of the middle ear could illuminate the nature of the conductive hearing impairment in DS mice.

The Effects of Different Reference Methods on Decision-Making Implications of Auditory Brainstem Response.

Hearing loss is a common disease affecting public health all around the world. In clinic, auditory brainstem response (ABR) has been widely used for the detection of hearing loss based on its convenience and accuracy. The different reference methods directly influence the quality of the ABR waveform which in turn affects the ABR-based diagnosis. Therefore, in this study, a reference electrode standardization technique (REST) was adopted to systematically investigate and evaluate the effect of different reference methods on the quality of ABR waveform in comparison with the conventional average reference (AR) and mean mastoid (MM) methods. In this study, ABR signals induced by click stimulus were acquired via an EEG electrode cap arrays, and those located on the six channels along the midline were compared systemically. The results showed that, when considering the different channels, the ABR in the Cz channel showed the best morphology. Then, the ABR waveforms acquired via the REST method possessed better morphologies with large amplitude (0.06 ± 0.02 μV for wave I, 0.07 ± 0.02 μV for wave III, and 0.21 ± 0.04 μV for wave V) when compared with the traditional method. Summarily, we found that the REST and MM methods improved the quality of ABR on both amplitude and morphology under different stimulation rates and levels without changing the latencies of ABR when compared with the conventional AR method, suggesting that the REST and MM methods have the potential to help physicians with high accurate ABR-based clinical diagnosis. Moreover, this study might also provide a theoretic basis of reference methods on the acquisition of electroencephalogram over public health issues.

Predicting synapse counts in living humans by combining computational models with auditory physiology.

Aging, noise exposure, and ototoxic medications lead to cochlear synapse loss in animal models. As cochlear function is highly conserved across mammalian species, synaptopathy likely occurs in humans as well. Synaptopathy is predicted to result in perceptual deficits including tinnitus, hyperacusis, and difficulty understanding speech-in-noise. The lack of a method for diagnosing synaptopathy in living humans hinders studies designed to determine if noise-induced synaptopathy occurs in humans, identify the perceptual consequences of synaptopathy, or test potential drug treatments. Several physiological measures are sensitive to synaptopathy in animal models including auditory brainstem response (ABR) wave I amplitude. However, it is unclear how to translate these measures to synaptopathy diagnosis in humans. This work demonstrates how a human computational model of the auditory periphery, which can predict ABR waveforms and distortion product otoacoustic emissions (DPOAEs), can be used to predict synaptic loss in individual human participants based on their measured DPOAE levels and ABR wave I amplitudes. Lower predicted synapse numbers were associated with advancing age, higher noise exposure history, increased likelihood of tinnitus, and poorer speech-in-noise perception. These findings demonstrate the utility of this modeling approach in predicting synapse counts from physiological data in individual human subjects.