Click-evoked Auditory Brainstem Responses Research Articles

Auditory Neural Responses and Communicative Functioning in Children With Microcephaly Related to Congenital Zika Syndrome.

Children with microcephaly exhibit neurodevelopmental delays and compromised communicative functioning, yielding challenges for clinical assessment and informed intervention. This study characterized auditory neural function and communication abilities in children with microcephaly due to congenital Zika syndrome (CZS). Click-evoked auditory brainstem responses (ABR) at fast and slow stimulation rates and natural speech-evoked cortical auditory evoked potentials (CAEP) were recorded in 25 Brazilian children with microcephaly related to CZS ( M age: 5.93 ± 0.62 years) and a comparison group of 25 healthy children ( M age: 5.59 ± 0.80 years) matched on age, sex, ethnicity, and socioeconomic status. Communication abilities in daily life were evaluated using caregiver reports on Vineland Adaptive Behavior Scales-3. Caregivers of children with microcephaly reported significantly lower than typical adaptive functioning in the communication and socialization domains. ABR wave I latency did not differ significantly between the groups, suggesting comparable peripheral auditory function. ABR wave V absolute latency and waves I-V interwave latency were significantly shorter in the microcephaly group for both ears and rates. CAEP analyses identified reduced N2 amplitudes in children with microcephaly as well as limited evidence of speech sound differentiation, evidenced mainly by the N2 response latency. Conversely, in the comparison group, speech sound differences were observed for both the P1 and N2 latencies. Exploratory analyses in the microcephaly group indicated that more adaptive communication was associated with greater speech sound differences in the P1 and N2 amplitudes. The trimester of virus exposure did not have an effect on the ABRs or CAEPs. Microcephaly related to CZS is associated with alterations in subcortical and cortical auditory neural function. Reduced ABR latencies differ from previous reports, possibly due to the older age of this cohort and careful assessment of peripheral auditory function. Cortical speech sound detection and differentiation are present but reduced in children with microcephaly. Associations between communication performance in daily life and CAEPs highlight the value of auditory evoked potentials in assessing clinical populations with significant neurodevelopmental disabilities.

Revisiting the Chicken Auditory Brainstem Response: Frequency Specificity, Threshold Sensitivity, and Cross Species Comparison.

The auditory brainstem response (ABR) is important for both clinical and basic auditory research. It is a non-invasive measure of hearing function with millisecond-level precision. The ABR can not only measure the synchrony, speed, and efficacy of auditory physiology but also detect different modalities of hearing pathology and hearing loss. ABRs are easily acquired in vertebrate animal models like reptiles, birds, and mammals, and complement existing molecular, developmental, and systems-level research. One such model system is the chicken; an excellent animal for studying auditory development, structure, and function. However, the ABR for chickens was last reported nearly 4 decades ago. The current study examines how decades of ABR characterization in other animal species support findings from the chicken ABR. We replicated and expanded on previous research using 43 chicken hatchlings 1- and 2-day post-hatch. We report that click-evoked chicken ABRs presented with a peak waveform morphology, amplitude, and latency like previous avian studies. Tone-evoked ABRs were found for frequencies from 250 to 4000 Hertz (Hz) and exhibited a range of best sensitivity between 750 and 2000 Hz. Objective click-evoked and tone-evoked ABR thresholds were comparable to subjective thresholds. With these revisited measurements, the chicken ABR still proves to be an excellent example of precocious avian development that complements decades of molecular, neuronal, and systems-level research in the same model organism.

Impact on Hearing Among SARS COV-2 Infected Adults and Children Born to Gestational COVID-19 Infected Mothers: A Prospective Case Control Study.

SARS COV 2 infection affects primarily the respiratory system and various organs in humans is responsible for higher mortality secondary to cytokine storm during the COVID-19 pandemic. It affects the internal auditory system is responsible for Sensory neural hearing loss in adults as well as children born to COVID-19 infected mothers. This study was aimed to detect the pattern of hearing loss in COVID-19 infected adults and pattern of hearing loss in children born to gestational COVID-19 infected mothers. Fifty asymptomatic RT-PCR COVID-19 infected adults and age, sex matched healthy controls were evaluated for audiological profile using Pure Tone Audiometry (PTA). Children born to COVID-19 infected mothers were tested using Transient product otoacoustic emissions and click-evoked auditory brainstem responses (ABRs) compared with children born to non-COVID mothers. PTA auditory profile of COVID-19 infected adults on day 7 had 30% (16 out of 50) significant high frequency sensory neural hearing impairment for 4000Hz (p value 0.003), 6000Hz (p value 0.001), 8000Hz (p value 0.001). Repeat PTA testing on day 30 showed normal hearing. Whereas in children, 40% (n = 20) born to COVID-19 infected mothers had OAE as "Refer". BERA (ABRs) testing of that OAE "Refer" children revealed 30% (n = 6) hearing impairment. COVID-19 infection cause transient type of high frequency sensory neural hearing loss in adults. Whereas in children born to COVID-19 infected mothers there is risk of developing permanent, progressive or long-standing transient type of sensory neural hearing loss.

Audiological findings in children aged 2-6 years with isolated speech-language delay.

The present study aimed to assess the prevalence and characteristics of hearing loss (HL) among preschoolers with speech-language delay who had passed the universal newborn hearing screening (UNHS). This retrospective study included children aged 2-6 years with isolated speech-language delay who were referred to a third-level audiological center for a comprehensive audiological assessment, including otomicroscopy, tympanometry, and click-evoked auditory brainstem responses. A total of 375 speech-language delayed children (285 male and 90 female) were assessed. The mean age was 41±12.4 months. Overall, 133 children (35.5%) were diagnosed with HL: 16 children (12.0%) had sensorineural HL (six unilaterally and 10 bilaterally), six (4.5%) had mixed HL (one unilaterally and five bilaterally), and 111 (83.5%) had conductive HL (19 unilaterally and 92 bilaterally). Regarding the presence of HL, no significant differences were found between males and females (P=0.60) or age groups (P=0.29). Among children with HL, 24 (18.0%) underwent tympanostomy tube placement (all bilaterally), one (0.8%) underwent unilateral cochlear implantation, eight (6.0%) were fitted with hearing aids (one unilaterally and seven bilaterally), two (1.5%) received a bimodal hearing solution (a cochlear implant on one ear and a hearing aid on the other ear), and 98 (73.7%) received no treatment. Although UNHS and audiological surveillance programs have been implemented over the years, all children with speech-language delay should undergo audiological evaluation. Indeed, the prevalence of undetected HL is not negligible among preschoolers with speech-language delay and requires early diagnosis and prompt treatment.

Preserved Auditory Steady State Response and Envelope-Following Response in Severe Brainstem Dysfunction Highlight the Need for Cross-Checking.

Commercially available auditory steady state response (ASSR) systems are widely used to obtain hearing thresholds in the pediatric population objectively. Children are often examined during natural or induced sleep so that the recorded ASSRs are of subcortical origin, the inferior colliculus being often designated as the main ASSR contributor in these conditions. This report presents data from a battery of auditory neurophysiological objective tests obtained in 3 cases of severe brainstem dysfunction in sleeping children. In addition to ASSRs, envelope-following response (EFR) recordings designed to distinguish peripheral (cochlear nerve) from central (brainstem) were recorded to document the effect of brainstem dysfunction on the two types of phase-locked responses. Results obtained in the 3 children with severe brainstem dysfunctions were compared with those of age-matched controls. The cases were identified as posterior fossa tumor, undiagnosed (UD), and Pelizaeus-Merzbacher-Like Disease. The standard audiological objective tests comprised tympanograms, distortion product otoacoustic emissions, click-evoked auditory brainstem responses (ABRs), and ASSRs. EFRs were recorded using horizontal (EFR-H) and vertical (EFR-V) channels and a stimulus phase rotation technique allowing isolation of the EFR waveforms in the time domain to obtain direct latency measurements. The brainstem dysfunctions of the 3 children were revealed as abnormal (weak, absent, or delayed) ABRs central waves with a normal wave I. In addition, they all presented a summating and cochlear microphonic potential in their ABRs, coupled with a normal wave I, which implies normal cochlear and cochlear nerve function. EFR-H and EFR-V waveforms were identified in the two cases in whom they were recorded. The EFR-Hs onset latencies, response durations, and phase-locking values did not differ from their respective age-matched control values, indicating normal cochlear nerve EFRs. In contrast, the EFR-V phase-locking value and onset latency varied from their control values. Both patients had abnormal but identifiable and significantly phase-locked brainstem EFRs, even in a case with severely distorted ABR central waves. ASSR objective audiograms were recorded in two cases. They showed normal or slightly elevated (explained by a slight transmission loss) thresholds that do not yield any clue about their brainstem dysfunction, revealing the method's lack of sensitivity to severe brainstem dysfunction. The present study, performed on 3 sleeping children with severe brainstem dysfunction but normal cochlear responses (cochlear microphonic potential, summating potential, and ABR wave I), revealed the differential sensitivity of three auditory electrophysiological techniques. Estimated thresholds obtained by standard ASSR recordings (cases UD and Pelizaeus-Merzbacher-Like Disease) provided no clue to the brainstem dysfunction clearly revealed by the click-evoked ABR. EFR recordings (cases posterior fossa tumor and UD) showed preserved central responses with abnormal latencies and low phase-locking values, whereas the peripheral EFR attributed to the cochlear nerve was normal. The one case (UD) for which the three techniques could be performed confirms this sensitivity gradient, emphasizing the need for applying the Cross-Check Principle by avoiding resorting to ASSR recording alone. The entirely normal EFR-H recordings observed in two cases further strengthen the hypothesis of its cochlear nerve origin in sleeping children.

Subclinical hearing loss associated with aging

ObjectiveContribute to clarifying the existence of subclinical hearing deficits associated with aging. DesignIn this work, we study and compare the auditory perceptual and electrophysiological performance of normal-hearing young and adult subjects (tonal audiometry, high-frequency tone threshold, a triplet of digits in noise, and click-evoked auditory brainstem response). Study sample45 normal hearing volunteers were evaluated and divided into two groups according to age. 27 subjects were included in the “young group” (mean 22.1 years), and 18 subjects (mean 42.22 years) were included in the “adult group.” ResultsIn the perceptual tests, the adult group presented significantly worse tonal thresholds in the high frequencies (12 and 16 kHz) and worse performance in the digit triplet tests in noise. In the electrophysiological test using the auditory brainstem response technique, the adult group presented significantly lower I and V wave amplitudes and higher V wave latencies at the supra-threshold level. At the threshold level, we observed a significantly higher latency in wave V in the adult group. In addition, in the partial correlation analysis, controlling for the hearing level, we observed a relationship (negative) between age and speech in noise performance and high-frequency thresholds. No significant association was observed between age and the auditory brainstem response. ConclusionThe results are compatible with subclinical hearing loss associated with aging.

The Effect of Tinnitus and Related Characteristics on Subcortical Auditory Processing.

The primary aim of this study was to evaluate whether individuals with tinnitus exhibited evidence of reduced inhibition and increased excitation at the subcortical auditory processing level. Based on the proposed mechanism of tinnitus generation, including peripheral auditory insult that triggers reduced inhibition and subcortical hyperactivity, it was hypothesized that a tinnitus group would yield reduced amplitudes for the most peripheral auditory brainstem response (ABR) component (wave I) and larger amplitudes for the most central ABR component (wave V) relative to controls matched on factors of age, sex, and hearing loss. Further, this study assessed the relative influence of tinnitus presence versus other related individual characteristics, including hearing loss, age, noise exposure history, and speech perception in noise on these ABR outcomes. Subcortical processing was examined using click-evoked ABR in an independent groups experimental design. A group of adults who perceived daily unilateral or bilateral tinnitus were matched with a control group counterpart without tinnitus by age, hearing, and sex (in each group n = 18; 10 females, 8 males). Amplitudes for ABR waves I, III, V, and the V/I ratio were compared between groups by independent t-tests. The relative influence of tinnitus (presence/absence), age (in years), noise exposure history (subjective self-report), hearing loss (audiometric thresholds), and speech perception in noise (SNR-50) was determined based on the proportional reduction in error associated with accounting for each variable of interest using multiple regression. Between-group trends were consistent with smaller amplitudes for all ABR components in individuals with tinnitus. Contrary to our hypotheses, however, none of the tinnitus compared with control group differences in ABR outcomes were statistically significant. In the multiple regression models, none of the factors including tinnitus presence, age, noise exposure history, hearing loss, and speech perception in noise significantly predicted ABR V/I ratio outcomes. The presence of reduced inhibition and subcortical hyperactivity in the tinnitus group was not supported in the current study. There were trends in ABR outcomes consistent with reduced peripheral to central brainstem auditory activity in the tinnitus group, but none of the group differences reached significance. It should also be noted that the tinnitus group had poorer extended high-frequency thresholds compared with controls. Regardless, neither tinnitus presence nor any of the proposed related characteristics were found to significantly influence the ABR V/I ratio. These findings suggest that either reduced subcortical inhibition was not a primary underlying mechanism for the tinnitus perceived by these subjects, or that ABR was not a reliable indicator of reduced subcortical inhibition possibly due to characteristics of the sample including a skewed distributions toward young and normal hearing individuals with little tinnitus distress.

Peripheral Auditory Function in Tanzanian Children Living With HIV With Clinically Normal Hearing

Despite normal audiometry, adults living with HIV have lower distortion product otoacoustic emissions (DPOAEs) compared with HIV-negative controls, but the degree of these differences in children living with HIV is unknown. If subclinical auditory deficits are present, results could affect developmental outcomes in children living with HIV (CLWH). To compare DPOAEs and auditory brainstem responses (ABR) between 2 age- and sex-matched groups of younger children with normal audiometry, 1 infected with HIV and the other uninfected. Cohort study in an infectious disease center in Dar es Salaam, Tanzania. Participants included 340 Tanzanian children aged 3 to 9 years with clinically normal hearing, type A tympanograms bilaterally, and air-conduction thresholds of 20 dB HL or less from 0.5 to 8 kHz. Participants in the cohort repeated testing approximately every 6 months (approximately 2.2 sessions per participant) for a total of 744 total observations. Data were analyzed from March 2020 to January 2022. DPOAE amplitudes from 1.5 to 8 kHz using an f2 to f1 ratio of 1.2 and L1/L2 values of 65/55 dB sound pressure level and click-evoked ABR using a slow (21.1/s) and fast (61.1/s) click rate. A total of 141 CLWH (70 female participants [49.3%]; mean [SD] age, 7.24 [1.67] years) and 199 HIV-negative individuals (99 female participants [49.7%]; mean [SD] age, 7.26 [1.44] years) participated in the study. The groups did not differ significantly in age, static immittance, or air-conduction thresholds. HIV status was independently associated with approximately 1.4 dB (95% CI, -3.28 to 0.30 dB) to 3.8 dB (95% CI, 6.03 to -1.99 dB) lower DPOAE amplitudes at 6 and 8 kHz bilaterally and 0.28 μV (95% CI, 0.01 to 0.33 μV) lower ABR wave V amplitudes in the right ear. Consistent with previous findings in young adults, CLWH had slightly, but reliably, lower DPOAEs and ABR wave V amplitudes than HIV-negative controls. The magnitude of these differences was small, but results suggest an early and consistent association between HIV infection or treatment and outer hair cell and auditory brainstem responses in children as young as 3 years. These subclinical changes suggest tracking both auditory function and development outcomes in CLWH is warranted.

Audiograms and click spectra of seven novel and seldom-tested odontocetes

The use of auditory evoked potentials has been promoted as a means by which to collect audiometric information from odontocete cetaceans that are rarely encountered in stranding situations. This article presents the results of auditory evoked potential hearing tests collected from stranded odontocetes over nearly a decade. For six species, no audiograms previously existed – the dwarf sperm whale (Kogia sima), pygmy sperm whale (Kogia breviceps), northern right whale dolphin (Lissodelphis borealis), melon-headed whale (Peponocephala electra), long-beaked common dolphin (Delphinus capensis), and Atlantic spotted dolphin (Stenella frontalis). Additional hearing information was gathered for the pygmy killer whale (Feresa attenuata), a species for which only two prior audiograms had been collected. Audiograms for the delphinids demonstrated a typical dolphin-like form with upper-frequency limits of hearing > 149 kHz, except for the pygmy killer whales whose upper-frequency limit was between 103-107 kHz. The kogiid audiograms had a narrower region of increased sensitivity (80-128 kHz) closely aligned with their narrowband, high-frequency echolocation signals. Distinctions between kogiids and delphinids existed in the latencies of peaks of click-evoked auditory brainstem responses, with longer interwave intervals between P4 and N5 in the kogiids (mean of 0.60 ms vs. a mean of 0.37 ms in the delphinids). Modulation rate transfer functions collected in three of the species, suggested group-wide similarities in temporal processing capabilities.

Hearing outcomes in preterm infants with confirmed hearing loss

ObjectivesPremature infants are at high risk for hearing loss (HL). The aim of the present study is to assess the frequency of preterm infants affected by HL who experience hearing improvement over months and evaluate possible factors associated with hearing changes. MethodsThis retrospective study was conducted in a third-level referral audiologic center.Preterm infants with a confirmed diagnosis of sensorineural HL within the first 3 months of life were reassessed at 18 months corrected age using the click-evoked auditory brainstem response between January 1, 2012, and June 30, 2020. The frequency of hearing improvement and associations between possible risk factors and hearing changes were evaluated. ResultsA total of 138 preterm infants (71 male and 67 female; mean gestational age: 30+2 weeks) were assessed. The percentages of hearing improvement and hearing threshold normalization were 58.7% (81/138) and 35.5% (49/138), respectively. We observed a higher frequency of hearing improvement among preterm infants who had received exclusive breastfeeding or mixed feeding compared with those who had received exclusive infant formula (80% versus 29.3%, P < 0.001). ConclusionThis study confirms the importance of performing a long audiological follow-up and postponing the indication for cochlear implantation in children with a history of preterm birth.Because of the expression of mesenchymal stem cells and high total antioxidant capacity, breast milk might play a protective role in the auditory system of preterm infants. These findings could have important implications for clinical practice, positively impacting the long-term hearing outcomes of preterm infants.

Click-evoked auditory brainstem responses (ABRs) are intact in schizophrenia and not sensitive to cognitive training

Patients with schizophrenia have impairments in early auditory system functioning that relate to clinical, cognitive, and psychosocial functioning. Some neurophysiological biomarkers of auditory information processing are sensitive to and predictive of clinically relevant outcomes following auditory-based targeted cognitive training (TCT) in schizophrenia. It is not known, however, whether schizophrenia patients show abnormalities at the earliest stage of sensory processing reflecting the integrity of the ascending auditory pathway at the level of the brainstem, or whether such abnormalities can serve as biomarkers. This study aimed to determine whether click-evoked auditory brainstem responses (click ABRs) are 1) abnormal in schizophrenia patients relative to healthy comparison subjects (HCS), 2) acutely sensitive to or predictive of TCT response, and 3) associated with clinically relevant symptoms. We also sought to determine whether 4) click ABRs show adequate psychometric reliability. Click ABRs were examined in 52 patients with schizophrenia and 32 HCS. Patients were randomized to either TCT ( n = 30), which comprised 30 h of training, or treatment as usual (TAU; n = 23). Patients showed intact click ABRs relative to HCS and click ABRs did not change significantly after 1 or 30 h of TCT. Exploratory analyses revealed modest relationships between click ABRs and baseline measures of positive symptoms and speech-in-noise perception; acute changes in ABRs were modestly related to improvements on measures of cognition independent of treatment. ABR measurements showed adequate internal consistency indicating their suitability for cross-sectional studies of individual differences, but poor test-retest reliability indicating poor suitability for clinical trials. In contrast to a growing literature demonstrating the utility of later cortical neurophysiological measures for translational research, the present findings indicate that brainstem-mediated responses are intact in schizophrenia and are not sensitive to or predictive of clinical changes in the context of TCT. These data provide guidance for establishing future neurophysiology-guided interventions in schizophrenia.

COVID-19 during pregnancy and its impact on the developing auditory system

BackgroundThis study compared distortion product otoacoustic emissions (DPOAEs) and click-evoked auditory brainstem responses (ABRs) recorded from infants whose mother had Covid-19 during pregnancy (Covid-19 group) to infants whose mother did not have Covid-19 (Control group) during pregnancy. MethodsThis study retrospectively examined records of infants in the Covid-19 group (n = 15) and control group (n = 46) who had distortion product otoacoustic emissions (DPOAEs) and click-evoked auditory brainstem responses (ABRs) recorded as part of their clinical assessment. DPOAE amplitudes, absolute latencies (I, III, and V), and I-V interpeak intervals were examined. ResultsDPOAE amplitudes were similar between the Covid-19 group and the control group. The absolute latency of wave I was similar between groups. But absolute latencies III and V and I-V interpeak intervals of the Covid-19 group were significantly prolonged compared to the control group. ConclusionCovid-19 infection and its complications during pregnancy may not affect the cochlear function but may affect the functioning of the auditory brainstem.

Neural Measures of Pitch Processing in EEG Responses to Running Speech.

Linearized encoding models are increasingly employed to model cortical responses to running speech. Recent extensions to subcortical responses suggest clinical perspectives, potentially complementing auditory brainstem responses (ABRs) or frequency-following responses (FFRs) that are current clinical standards. However, while it is well-known that the auditory brainstem responds both to transient amplitude variations and the stimulus periodicity that gives rise to pitch, these features co-vary in running speech. Here, we discuss challenges in disentangling the features that drive the subcortical response to running speech. Cortical and subcortical electroencephalographic (EEG) responses to running speech from 19 normal-hearing listeners (12 female) were analyzed. Using forward regression models, we confirm that responses to the rectified broadband speech signal yield temporal response functions consistent with wave V of the ABR, as shown in previous work. Peak latency and amplitude of the speech-evoked brainstem response were correlated with standard click-evoked ABRs recorded at the vertex electrode (Cz). Similar responses could be obtained using the fundamental frequency (F0) of the speech signal as model predictor. However, simulations indicated that dissociating responses to temporal fine structure at the F0 from broadband amplitude variations is not possible given the high co-variance of the features and the poor signal-to-noise ratio (SNR) of subcortical EEG responses. In cortex, both simulations and data replicated previous findings indicating that envelope tracking on frontal electrodes can be dissociated from responses to slow variations in F0 (relative pitch). Yet, no association between subcortical F0-tracking and cortical responses to relative pitch could be detected. These results indicate that while subcortical speech responses are comparable to click-evoked ABRs, dissociating pitch-related processing in the auditory brainstem may be challenging with natural speech stimuli.

AudioChip: A Deep Phenotyping Approach for Deconstructing and Quantifying Audiological Phenotypes of Self-Reported Speech Perception Difficulties.

About 15% of U.S. adults report speech perception difficulties despite showing normal audiograms. Recent research suggests that genetic factors might influence the phenotypic spectrum of speech perception difficulties. The primary objective of the present study was to describe a conceptual framework of a deep phenotyping method, referred to as AudioChipping, for deconstructing and quantifying complex audiometric phenotypes. In a sample of 70 females 18 to 35 years of age with normal audiograms (from 250 to 8000 Hz), the study measured behavioral hearing thresholds (250 to 16,000 Hz), distortion product otoacoustic emissions (1000 to 16,000 Hz), click-evoked auditory brainstem responses (ABR), complex ABR (cABR), QuickSIN, dichotic digit test score, loudness discomfort level, and noise exposure background. The speech perception difficulties were evaluated using the Speech, Spatial, and Quality of Hearing Scale-12-item version (SSQ). A multiple linear regression model was used to determine the relationship between SSQ scores and audiometric measures. Participants were categorized into three groups (i.e., high, mid, and low) using the SSQ scores before performing the clustering analysis. Audiometric measures were normalized and standardized before performing unsupervised k-means clustering to generate AudioChip. The results showed that SSQ and noise exposure background exhibited a significant negative correlation. ABR wave I amplitude, cABR offset latency, cABR response morphology, and loudness discomfort level were significant predictors for SSQ scores. These predictors explained about 18% of the variance in the SSQ score. The k-means clustering was used to split the participants into three major groups; one of these clusters revealed 53% of participants with low SSQ. Our study highlighted the relationship between SSQ and auditory coding precision in the auditory brainstem in normal-hearing young females. AudioChip was useful in delineating and quantifying internal homogeneity and heterogeneity in audiometric measures among individuals with a range of SSQ scores. AudioChip could help identify the genotype-phenotype relationship, document longitudinal changes in auditory phenotypes, and pair individuals in case-control groups for the genetic association analysis.

Ωto_abR: A Web Application for the Visualization and Analysis of Click-Evoked Auditory Brainstem Responses

Since its inception by Jewett and Williston in the late 1960s, the auditory brainstem response (ABR) has been an indispensable diagnostic tool, used by audiologists around the world. Click-evoked ABR testing proves to be a reliable tool, as it provides an objective representation of the auditory function, an estimate of hearing thresholds and the ability to pinpoint a potential issue in the auditory neural pathway. The present study describes state-of-the-art ABR analytics-related platforms and provides an overview of their functionality. In conjunction, we introduce the design and development of a newly developed, user-friendly web application, built in R language. This application provides several well-known and newly key characteristics for the analysis of ABR waveforms. These include absolute peak latencies, amplitudes, and interpeak latencies.

Peripheral Auditory Function in Young HIV-Positive Adults With Clinically Normal Hearing.

Little is known about peripheral auditory function in young adults with HIV, who might be expected to show early evidence of hearing loss if HIV infection or treatment does affect peripheral function. The goal of this study was to compare peripheral auditory function in 2 age- and gender-matched groups of young adults with clinically normal hearing with and without HIV. Matched cohort study with repeated measures. Infectious disease center in Dar es Salaam, Tanzania. Participants included HIV-positive (n = 38) and HIV-negative (n = 38) adults aged 20 to 30 years who had clinically normal hearing, defined as type A tympanograms, air conduction thresholds ≤25 dB HL bilaterally from 0.5 to 8 kHz, and distortion product otoacoustic emissions (DPOAEs) >6 dB above the noise floor bilaterally from 1.5 to 8 kHz. Participants were tested multiple times over 6-month intervals (average, 2.7 sessions/participant) for a total of 208 observations. Primary outcome measures included tympanograms, air conduction audiograms, DPOAEs, and click-evoked auditory brainstem responses. HIV groups did not significantly differ in age, static immittance, or air conduction thresholds. HIV-positive status was independently associated with approximately 3.7-dB lower DPOAE amplitudes from 2 to 8 kHz (95% CI, 1.01-6.82) in both ears and 0.04-µV lower (95% CI, 0.003-0.076) auditory brainstem response wave I amplitudes in the right ear. Young adults living with HIV have slightly but reliably smaller DPOAEs and auditory brainstem response wave I amplitudes than matched HIV-negative controls. The magnitude of these differences is small, but these results support measuring peripheral auditory function in HIV-positive individuals as they age.

Click-evoked auditory brainstem responses and autism spectrum disorder: a meta-analytic investigation of disorder specificity.

BackgroundClick-evoked auditory brainstem response (ABR) alterations are associated with autism spectrum disorder (ASD), but the specificity of these findings to the disorder are unclear. We therefore performed a meta-analysis on ABRs and attention deficit/hyperactivity disorder (ADHD), a neurodevelopmental disorder that shares some etiologic and symptom overlap with ASD.MethodSeven papers compared ABR latency components (I, III, V, I–III, III–V, I–V) between participants with and without ADHD. We used random-effects regression to generate component-specific estimates (Hedges’ g) that adjusted for study sample sizes and the number of studies contributing to each estimate. We compared these estimates to our recently published meta-analysis of ABRs and ASD.ResultsAll ADHD studies employed cross-sectional designs. ADHD was associated with longer latencies for Waves III and V (g=0.6, 95%CI 0.3,1.0 and g=0.6, 95%CI 0.2,0.9) and Waves I–III and I–V (g=0.7, 95%CI 0.2, 1.3 and g=0.6, 95%CI 0.3, 1.0). Effect sizes from the ASD and ADHD meta-analyses did not differ from each other.ConclusionSimilar patterns of ABR alterations are observed in ADHD and ASD. However, studies rarely screen for middle ear dysfunction or hearing loss and rely upon cross-sectional designs. Addressing these issues will inform the viability of ABRs as a prognostic and/or etiologic biomarker for these disorders.

Non-stimulus-evoked activity as a measure of neural noise in the frequency-following response

BackgroundThe frequency-following response, or FFR, is a neurophysiologic response that captures distinct aspects of sound processing. Like all evoked responses, FFR is susceptible to electric and myogenic noise contamination during collection. Click-evoked auditory brainstem response collection standards have been adopted for FFR collection, however, whether these standards sufficiently limit FFR noise contamination is unknown. Thus, a critical question remains: to what extent do distinct FFR components reflect noise contamination? This is especially relevant for prestimulus amplitude (i.e., activity preceding the evoked response), as this measure has been used to index both noise contamination and neural noise. New methodWe performed two experiments. First, using >1000 young-adult FFRs, we ran regressions to determine the variance explained by myogenic and electrical noise, as indexed by artifact rejection count and electrode impedance, on each FFR component. Second, we reanalyzed prestimulus amplitude differences attributed to athletic experience and socioeconomic status, adding covariates of artifact rejection and impedance. ResultsWe found that non-neural noise marginally contributed to FFR components and could not explain group differences on prestimulus amplitude. Comparison with existing methodPrestimulus amplitude has been considered a measure of non-neural noise contamination. However, non-neural noise was not the sole contributor to variance in this measure and did not explain group differences. ConclusionsResults from the two experiments suggest that the effects of non-neural noise on FFR components are minimal and do not obscure individual differences in the FFR and that prestimulus amplitude indexes neural noise.

Lack of collagen α6(IV) chain in mice does not cause severe-to-profound hearing loss or cochlear malformation, a distinct phenotype from nonsyndromic hearing loss with COL4A6 missense mutation.

Congenital hearing loss affects 1 in every 1000 births, with genetic mutations contributing to more than 50% of all cases. X-linked nonsyndromic hereditary hearing loss is associated with six loci (DFNX1-6) and five genes. Recently, the missense mutation (c.1771G>A, p.Gly591Ser) in COL4A6, encoding the basement membrane (BM) collagen α6(IV) chain, was shown to be associated with X-linked congenital nonsyndromic hearing loss with cochlear malformation. However, the mechanism by which the COL4A6 mutation impacts hereditary hearing loss has not yet been elucidated. Herein, we investigated Col4a6 knockout (KO) effects on hearing function and cochlear formation in mice. Immunohistochemistry showed that the collagen α6(IV) chain was distributed throughout the mouse cochlea within subepithelial BMs underlying the interdental cells, inner sulcus cells, basilar membrane, outer sulcus cells, root cells, Reissner’s membrane, and perivascular BMs in the spiral limbus, spiral ligament, and stria vascularis. However, the click-evoked auditory brainstem response analysis did not show significant changes in the hearing threshold of Col4a6 KO mice compared with wild-type (WT) mice with the same genetic background. In addition, the cochlear structures of Col4a6 KO mice did not exhibit morphological alterations, according to the results of high-resolution micro-computed tomography and histology. Hence, loss of Col4a6 gene expression in mice showed normal click ABR thresholds and normal cochlear formation, which differs from humans with the COL4A6 missense mutation c.1771G>A, p.Gly591Ser. Therefore, the deleterious effects in the auditory system caused by the missense mutation in COL4A6 are likely due to the dominant-negative effects of the α6(IV) chain and/or α5α6α5(IV) heterotrimer with an aberrant structure that would not occur in cases with loss of gene expression.

Neonatal exposure to monosodium glutamate results in impaired auditory brainstem structure and function

Excitotoxic injury during the neonatal period has been shown to result in neurodegenerative changes in several different brain regions. Exposure to monosodium glutamate (MSG) during the first two postnatal weeks results in glutamate neurotoxicity in the cochlea and has been shown to result in damage to cochlear hair cells and fewer neurons in the spiral ganglion. Further, we have shown that such exposure results in fewer neurons in the cochlear nucleus and superior olivary complex and abnormal expression of the calcium binding proteins calbindin and calretinin. Based on these findings, we hypothesized that neonatal MSG exposure would result in loss of neurons at more rostral levels in the auditory brainstem, and this exposure would result in abnormal brainstem auditory evoked potentials. We identified a significantly lower density of neurons in the spiral ganglion, heterogenous loss of neurons in the globular bushy cell-trapezoid body circuit, and fewer neurons in the nuclei of the lateral lemniscus and central nucleus of the inferior colliculus. The most severe loss of neurons was found in the inferior colliculus. Click-evoked auditory brainstem responses revealed significantly higher thresholds and longer latency responses, but these did not deteriorate with age. These results, together with our previous findings, indicate that neonatal exposure to MSG results in fewer neurons throughout the entire auditory brainstem and results in abnormal auditory brainstem responses.