Suprathreshold Auditory Brainstem Response Research Articles

The curvature quantification of waveI in auditory brainstem responses detects cochlear synaptopathy in human beings.

Patients with age-related hearing loss complain often about reduced speech perception in adverse listening environment. Studies on animals have suggested that cochlear synaptopathy may be one of the primary mechanisms responsible for this phenomenon. A decreased waveI amplitude in supra-threshold auditory brainstem response (ABR) can diagnose this pathology non-invasively. However, the interpretation of the waveI amplitude in humans remains controversial. Recent studies in mice have established a robust and reliable mathematic algorithm, i.e., curve curvature quantification, for detecting cochlear synaptopathy. This study aimed to determine whether the curve curvature has sufficient test-retest reliability to detect cochlear synaptopathy in aging humans. Healthy participants were recruited into this prospective study. All subjects underwent an audiogram examination with standard and extended high frequencies ranging from 0.125 to 16kHz and an ABR with a stimulus of 80dBnHL click. The peak amplitude, peak latency, curvature at the peak, and the area under the curve of waveI were calculated and analyzed. A total of 80 individuals with normal hearing, aged 18 to 61 years, participated in this study, with a mean age of 26.4 years.Pearson correlation analysis showed a significant negative correlation between curvature and age, as well as between curvature and extended high frequency (EHF) threshold (10-16kHz). Additionally, the same correlation was observed between age and area as well as age and EHF threshold. The model comparison demonstrated that the curvature at the peak of waveI is thebest metric to correlate with EHF threshold. The curvature at the peak of wave I is the most sensitive metric for detecting cochlear synaptopathy in humans and may be applied in routine diagnostics to detectearly degenerations of the auditory nerve.

Supra-Threshold LS CE-Chirp Auditory Brainstem Response in the Elderly

Introduction: Aging deteriorates peripheral and central auditory structures and functions. In elders, for an accurate audiological evaluation, it is important to explore beyond the cochlear receptor. Audiograms provide an estimation of hearing thresholds, while the amplitudes and latencies of supra-threshold auditory brainstem response (ABR) can offer noninvasive measures of the auditory pathways functioning. Regarding ABR, in young populations, level-specific chirp (LS CE-chirp) stimulus has been proposed as an alternative synchronizing method to obtain larger ABR responses than those evoked by clicks. However, the supra-threshold characteristics of chirp evoked ABR, and their association to hearing thresholds is relatively unknown in the elderly. The aim of this study was to evaluate supra-threshold LS CE-chirp ABRs in an aged population by comparing their features with click ABRs, and evaluating their relationship with audiometric hearing thresholds. Methods: We carried out a cross-sectional study to characterize the hearing of 125 adults aged over 65 years. We determined the audiometric hearing thresholds and supra-threshold ABRs elicited by LS CE-chirp and click stimuli at 80 dB nHL. We evaluated associations by means of partial correlations and covariate adjustment. We performed specific frequencies’ analysis and subgroup analysis per hearing level. Results: Wave V responses had significantly shorter latencies and larger amplitudes when elicited by LS CE-chirp as compared to click-evoked responses. Audiometric hearing thresholds correlated with age, but ABR characteristics did not. We found mild correlations between hearing thresholds and ABR characteristics, predominantly at higher frequencies and with chirp. We found scarce evidence of correlation between ABR characteristics and the average of behavioral hearing thresholds between 0.5 to 4 kHz (0.5–4 kHz PTA). After subgroup analysis according to the hearing level, no stronger or more significant correlations were found between ABR characteristics and 0.5–4 kHz PTA. Discussion: In this study, we found that supra-threshold LS CE-chirp ABR presented some of the previously described similitudes and differences with supra-threshold click ABR in younger populations. Although, the average amplitude and latency of wave V evoked by LS CE-chirp were larger and faster than those evoked by clicks, these results should be taken with caution at the individual level, and further studies are required to state that LS CE-chirp ABRs are better than click ABRs in elders for clinical evaluations. We did not find consistent associations between hearing thresholds and supra-threshold wave V features, suggesting that these measures should be considered independently in the elderly.

Suprathreshold Auditory Measures for Detecting Early-Stage Noise-Induced Hearing Loss in Young Adults.

Over 1 billion young adults are at risk for developing noise-induced hearing loss (NIHL) due to their habit of listening to music at loud levels. The gold standard for detecting NIHL is the audiometric notch around 3,000 to 6,000 Hz observed in pure tone audiogram. However, recent studies suggested that suprathreshold auditory measures might be more sensitive to detect early-stage NIHL in young adults. The present study compared suprathreshold measures in individuals with high and low noise exposure backgrounds (NEBs). We hypothesized that individuals with high NEB would exhibit reduced performance on suprathreshold measures than those with low NEB. An initial sample of 100 English-speaking healthy adults (18-35 years; females = 70) was obtained from five university classes. We identified 15 participants with the lowest NEB scores (10 females) and 15 participants with the highest NEB scores (10 females). We selected a sample of healthy young adults with no history of middle ear infection, and those in the low NEB group were selected with no history of impulse noise exposure. The study included conventional audiometry, extended high-frequency audiometry, middle ear muscle reflex (MEMR) thresholds, distortion-product otoacoustic emissions (DPOAEs), QuickSIN, and suprathreshold auditory brainstem response (ABR) measures. We used independent sample t-tests, correlation coefficients, and linear mixed model analysis to compare the audiometric measures between the NEB groups. The prevalence of audiometric notch was low in the study sample, even for individuals with high NEB. We found that: (1) individuals with high NEB revealed significantly reduced QuickSIN performance than those with low NEB; (2) music exposure via earphone revealed a significant association with QuickSIN; (3) individuals with high NEB revealed significantly reduced DPOAEs and ABR wave I amplitude compared with individuals with low NEB; (4) MEMR and ABR latency measures showed a modest association with NEB; and (5) audiometric thresholds across the frequency range did not show statistically significant association with NEB. Our results suggest that young adults with high NEB might exhibit impaired peripheral neural coding deficits leading to reduced speech-in-noise (SIN) performance despite clinically normal hearing thresholds. SIN measures might be more sensitive than audiometric notch for detecting early-stage NIHL in young adults.

Limitation of Conventional Audiometry in Identifying Hidden Hearing Loss in Acute Noise Exposure.

PurposeThe concept of hidden hearing loss can explain the discrepancy between a listener's perception of hearing ability and hearing evaluation using pure tone audiograms. This study investigated the utility of the suprathreshold auditory brainstem response (ABR) for the evaluation of hidden hearing loss in noise-exposed ear with normal audiograms.Materials and MethodsA total of 15 patients (24 ears) with normal auditory thresholds and normal distortion product otoacoustic emissions were included in a retrospective analysis of medical records of 80 patients presenting with histories of acute noise exposure. The control group included 12 subjects (24 ears) with normal audiograms and no history of noise exposure. Pure tone audiometry and suprathreshold ABR testing at 90 dB peSPL were performed. The amplitudes and latencies of ABR waves I and V were compared between the noise-exposed and control groups.ResultsWe found no significant difference in the wave I or V amplitude, or the wave I/V ratio, between the two groups. The latencies of ABR wave I, V, and I-V interpeak interval were compared, and no significant intergroup difference was observed.ConclusionThe results suggest that either hidden hearing loss may not be significant in this cohort of patients with acute noise exposure history, or the possible damage by noise exposure is not reflected in the ABRs. Further studies are needed to inquire about the role of ABR in identification of hidden hearing loss.

Integrated stress response inhibition provides sex-dependent protection against noise-induced cochlear synaptopathy

Noise-induced hearing loss (NIHL) is a common health concern with significant social, psychological, and cognitive implications. Moderate levels of acoustic overstimulation associated with tinnitus and impaired speech perception cause cochlear synaptopathy, characterized physiologically by reduction in wave I of the suprathreshold auditory brainstem response (ABR) and reduced number of synapses between sensory hair cells and auditory neurons. The unfolded protein response (UPR), an endoplasmic reticulum stress response pathway, has been implicated in the pathogenesis and treatment of NIHL as well as neurodegeneration and synaptic damage in the brain. In this study, we used the small molecule UPR modulator Integrated Stress Response InhiBitor (ISRIB) to treat noise-induced cochlear synaptopathy in a mouse model. Mice pretreated with ISRIB prior to noise-exposure were protected against noise-induced synapse loss. Male, but not female, mice also exhibited ISRIB-mediated protection against noise-induced suprathreshold ABR wave-I amplitude reduction. Female mice had higher baseline wave-I amplitudes but greater sensitivity to noise-induced wave-I reduction. Our results suggest that the UPR is implicated in noise-induced cochlear synaptopathy, and can be targeted for treatment.

The Genetics of Variation of the Wave 1 Amplitude of the Mouse Auditory Brainstem Response

This is the first genome-wide association study with the Hybrid Mouse Diversity Panel (HDMP) to define the genetic landscape of the variation in the suprathreshold wave 1 amplitude of the auditory brainstem response (ABR) both pre- and post-noise exposure. This measure is correlated with the density of the auditory neurons (AN) and/or the compliment of synaptic ribbons within the inner hair cells of the mouse cochlea. We analyzed suprathreshold ABR for 635 mice from 102 HMDP strains pre- and post-noise exposure (108dB 10kHz octave band noise exposure for 2h) using auditory brainstem response (ABR) wave 1 suprathreshold amplitudes as part of a large survey (Myint et al., Hear Res 332:113-120, 2016). Genome-wide significance levels for pre- and post-exposure wave 1 amplitude across the HMDP were performed using FaST-LMM. Synaptic ribbon counts (Ctbp2 and mGluR2) were analyzed for the extreme strains within the HMDP. ABR wave 1 amplitude varied across all strains of the HMDP with differences ranging between 2.42 and 3.82-fold pre-exposure and between 2.43 and 7.5-fold post-exposure with several tone burst stimuli (4kHz, 8kHz, 12kHz, 16kHz, 24kHz, and 32kHz). Immunolabeling of paired synaptic ribbons and glutamate receptors of strains with the highest and lowest wave 1 values pre- and post-exposure revealed significant differences in functional synaptic ribbon counts. Genome-wide association analysis identified genome-wide significant threshold associations on chromosome 3 (24kHz; JAX00105429; p < 1.12E-06) and chromosome 16 (16kHz; JAX00424604; p < 9.02E-07) prior to noise exposure and significant associations on chromosomes 2 (32kHz; JAX00497967; p < 3.68E-08) and 13 (8kHz; JAX00049416; 1.07E-06) after noise exposure. In order to prioritize candidate genes, we generated cis-eQTLs from microarray profiling of RNA isolated from whole cochleae in 64 of the tested strains.This is the first report of a genome-wide association analysis, controlled for population structure, to explore the genetic landscape of suprathreshold wave 1 amplitude measurements of the mouse ABR. We have defined two genomic regions associated with wave 1 amplitude variation prior to noise exposure and an additional two associated with variation after noise exposure.

Effects of High-Intensity Airborne Ultrasound Exposure on Behavioural and Electrophysiological Measures of Auditory Function

Regulations on safe ultrasound exposure limits are based on a very limited number of studies, which have only considered audiometric threshold shifts as indicators of hearing deficits. The purpose of the current study was to assess the effects of exposure to high-intensity ultrasound on a range of measures of hearing function, which included audiometric thresholds, as well as subclinical measures of hearing deficits: speech-in-noise understanding, supra-threshold auditory brainstem response wave I amplitude and latency, and frequency following response levels to amplitude modulated (AM) tones. Changes in these measures were assessed before and after exposure of the left ear to high-intensity ultrasound in a group of nine young listeners. These changes were compared to those observed in a control group of nine young listeners. Exposure consisted in the presentation of a 40-kHz AM tone at levels of 105, 110, 115, and 120 dB SPL for 10 minutes at each level, plus an exposure to a 40-kHz unmodulated tone during an ultrasound detection task, for a total duration of 50 seconds. None of the measures of hearing function was found to change significantly more for the left compared to the right ear, for participants of the exposure group compared to control participants. Electroencephalographic recordings obtained during exposure to the AM tone did not show significant phase-locked activity at the modulation frequency or at low-frequency subharmonics of the ultrasound tone. One out of nine participants was able to perform the ultrasound detection task above chance level, although due to limitations of the experimental setup the mechanism by which she could detect the presentation of the tone remains unclear.

Behavioral and physiological measures of auditory processing in individuals with autism spectrum disorder

Sensory processing abnormalities are a hallmark of autism spectrum disorder (ASD). In the auditory domain, hyper- and hypo-sensitivity to sound, reduced orientation to speech, and difficulty listening in noise are commonly reported. However, the etiology of these auditory processing abnormalities is poorly understood. In this preliminary study, multi-talker speech perception thresholds, otoacoustic emissions, electrophysiological responses, as well as standardized measures of cognition, language, and adaptive function were measured in each individual subject with ASD and their age-matched controls. Speech perception was assessed by estimating target-to-masker ratios at 50% correct for speech targets (0° azimuth) presented with two spatially separated (±45° azimuth) simultaneous speech maskers. The electrophysiological battery used to characterize the transmission and representation of sound included: (1) a click-evoked supra-threshold auditory brainstem response, (2) an envelope following response recorded to a 400-ms-long 4 kHz pure tone carrier amplitude modulated at 100 Hz at two modulations depths (0 and -6 dB) and (3) a binaural potential evoked by an interaural phase difference embedded in an amplitude-modulated carrier tone. Together, these measures provide a behavioral and physiological assay of auditory function and show the potential to further our understanding of the mechanisms underlying auditory abnormalities in individuals with ASD.

Supra-threshold auditory brainstem response amplitudes in humans: Test-retest reliability, electrode montage and noise exposure

The auditory brainstem response (ABR) is a sub-cortical evoked potential in which a series of well-defined waves occur in the first 10 ms after the onset of an auditory stimulus. Wave V of the ABR, particularly wave V latency, has been shown to be remarkably stable over time in individual listeners. However, little attention has been paid to the reliability of wave I, which reflects auditory nerve activity. This ABR component has attracted interest recently, as wave I amplitude has been identified as a possible non-invasive measure of noise-induced cochlear synaptopathy. The current study aimed to determine whether ABR wave I amplitude has sufficient test-retest reliability to detect impaired auditory nerve function in an otherwise normal-hearing listener. Thirty normal-hearing females were tested, divided equally into low- and high-noise exposure groups. The stimulus was an 80 dB nHL click. ABR recordings were made from the ipsilateral mastoid and from the ear canal (using a tiptrode). Although there was some variability between listeners, wave I amplitude had high test-retest reliability, with an intraclass correlation coefficient (ICC) comparable to that for wave V amplitude. There were slight gains in reliability for wave I amplitude when recording from the ear canal (ICC of 0.88) compared to the mastoid (ICC of 0.85). The summating potential (SP) and ratio of SP to wave I were also quantified and found to be much less reliable than measures of wave I and V amplitude. Finally, we found no significant differences in the amplitude of any wave components between low- and high-noise exposure groups. We conclude that, if the other sources of between-subject variability can be controlled, wave I amplitude is sufficiently reliable to accurately characterize individual differences in auditory nerve function.

Auditory Brainstem Response Altered in Humans With Noise Exposure Despite Normal Outer Hair Cell Function.

Recent animal studies demonstrated that cochlear synaptopathy, a partial loss of inner hair cell-auditory nerve fiber synapses, can occur in response to noise exposure without any permanent auditory threshold shift. In animal models, this synaptopathy is associated with a reduction in the amplitude of wave I of the auditory brainstem response (ABR). The goal of this study was to determine whether higher lifetime noise exposure histories in young people with clinically normal pure-tone thresholds are associated with lower ABR wave I amplitudes. Twenty-nine young military Veterans and 35 non Veterans (19 to 35 years of age) with normal pure-tone thresholds were assigned to 1 of 4 groups based on their self-reported lifetime noise exposure history and Veteran status. Suprathreshold ABR measurements in response to alternating polarity tone bursts were obtained at 1, 3, 4, and 6 kHz with gold foil tiptrode electrodes placed in the ear canal. Wave I amplitude was calculated from the difference in voltage at the positive peak and the voltage at the following negative trough. Distortion product otoacoustic emission input/output functions were collected in each participant at the same four frequencies to assess outer hair cell function. After controlling for individual differences in sex and distortion product otoacoustic emission amplitude, the groups containing participants with higher reported histories of noise exposure had smaller ABR wave I amplitudes at suprathreshold levels across all four frequencies compared with the groups with less history of noise exposure. Suprathreshold ABR wave I amplitudes were reduced in Veterans reporting high levels of military noise exposure and in non Veterans reporting any history of firearm use as compared with Veterans and non Veterans with lower levels of reported noise exposure history. The reduction in ABR wave I amplitude in the groups with higher levels of noise exposure cannot be accounted for by sex or variability in outer hair cell function. This change is similar to the decreased ABR wave I amplitudes observed in animal models of noise-induced cochlear synaptopathy. However, without post mortem examination of the temporal bone, no direct conclusions can be drawn concerning the presence of synaptopathy in the study groups with higher noise exposure histories.

Speech-in-Noise Tests and Supra-threshold Auditory Evoked Potentials as Metrics for Noise Damage and Clinical Trial Outcome Measures.

In humans, the accepted clinical standards for detecting hearing loss are the behavioral audiogram, based on the absolute detection threshold of pure-tones, and the threshold auditory brainstem response (ABR). The audiogram and the threshold ABR are reliable and sensitive measures of hearing thresholds in human listeners. However, recent results from noise-exposed animals demonstrate that noise exposure can cause substantial neurodegeneration in the peripheral auditory system without degrading pure-tone audiometric thresholds. It has been suggested that clinical measures of auditory performance conducted with stimuli presented above the detection threshold may be more sensitive than the behavioral audiogram in detecting early-stage noise-induced hearing loss in listeners with audiometric thresholds within normal limits. Supra-threshold speech-in-noise testing and supra-threshold ABR responses are reviewed here, given that they may be useful supplements to the behavioral audiogram for assessment of possible neurodegeneration in noise-exposed listeners. Supra-threshold tests may be useful for assessing the effects of noise on the human inner ear, and the effectiveness of interventions designed to prevent noise trauma. The current state of the science does not necessarily allow us to define a single set of best practice protocols. Nonetheless, we encourage investigators to incorporate these metrics into test batteries when feasible, with an effort to standardize procedures to the greatest extent possible as new reports emerge.

Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates

Acoustic overexposure can cause a permanent loss of auditory nerve fibers without destroying cochlear sensory cells, despite complete recovery of cochlear thresholds (Kujawa and Liberman 2009), as measured by gross neural potentials such as the auditory brainstem response (ABR). To address this nominal paradox, we recorded responses from single auditory nerve fibers in guinea pigs exposed to this type of neuropathic noise (4- to 8-kHz octave band at 106 dB SPL for 2 h). Two weeks postexposure, ABR thresholds had recovered to normal, while suprathreshold ABR amplitudes were reduced. Both thresholds and amplitudes of distortion-product otoacoustic emissions fully recovered, suggesting recovery of hair cell function. Loss of up to 30% of auditory-nerve synapses on inner hair cells was confirmed by confocal analysis of the cochlear sensory epithelium immunostained for pre- and postsynaptic markers. In single fiber recordings, at 2 wk postexposure, frequency tuning, dynamic range, postonset adaptation, first-spike latency and its variance, and other basic properties of auditory nerve response were all completely normal in the remaining fibers. The only physiological abnormality was a change in population statistics suggesting a selective loss of fibers with low- and medium-spontaneous rates. Selective loss of these high-threshold fibers would explain how ABR thresholds can recover despite such significant noise-induced neuropathy. A selective loss of high-threshold fibers may contribute to the problems of hearing in noisy environments that characterize the aging auditory system.

ATP-gated ion channels mediate adaptation to elevated sound levels

The sense of hearing is remarkable for its auditory dynamic range, which spans more than 10(12) in acoustic intensity. The mechanisms that enable the cochlea to transduce high sound levels without damage are of key interest, particularly with regard to the broad impact of industrial, military, and recreational auditory overstimulation on hearing disability. We show that ATP-gated ion channels assembled from P2X2 receptor subunits in the cochlea are necessary for the development of temporary threshold shift (TTS), evident in auditory brainstem response recordings as sound levels rise. In mice null for the P2RX2 gene (encoding the P2X2 receptor subunit), sustained 85-dB noise failed to elicit the TTS that wild-type (WT) mice developed. ATP released from the tissues of the cochlear partition with elevation of sound levels likely activates the broadly distributed P2X2 receptors on epithelial cells lining the endolymphatic compartment. This purinergic signaling is supported by significantly greater noise-induced suppression of distortion product otoacoustic emissions derived from outer hair cell transduction and decreased suprathreshold auditory brainstem response input/output gain in WT mice compared with P2RX2-null mice. At higher sound levels (≥95 dB), additional processes dominated TTS, and P2RX2-null mice were more vulnerable than WT mice to permanent hearing loss due to hair cell synapse disruption. P2RX2-null mice lacked ATP-gated conductance across the cochlear partition, including loss of ATP-gated inward current in hair cells. These data indicate that a significant component of TTS represents P2X2 receptor-dependent purinergic hearing adaptation that underpins the upper physiological range of hearing.

On chirp stimuli and neural synchrony in the suprathreshold auditory brainstem response

The chirp-evoked ABR has been regarded as a more synchronous response than the click-evoked ABR, referring to the belief that the chirp stimulates lower-, mid-, and higher-frequency regions of the cochlea simultaneously. In this study a variety of tools were used to analyze the synchronicity of ABRs evoked by chirp- and click-stimuli at 40 dB HL in 32 normal hearing subjects aged 18 to 55 years (mean=24.8 years, SD=7.1 years). Compared to the click-evoked ABRs, the chirp-evoked ABRs showed larger wave V amplitudes, but an absence of earlier waves in the grand averages, larger wave V latency variance, smaller FFT magnitudes at the higher component frequencies, and larger phase variance at the higher component frequencies. These results strongly suggest that the chirp-evoked ABRs exhibited less synchrony than the click-evoked ABRs in this study. It is proposed that the temporal compensation offered by chirp stimuli is sufficient to increase neural recruitment (as measured by wave V amplitude), but that destructive phase interactions still exist along the cochlea partition, particularly in the low frequency portions of the cochlea where more latency jitter is expected. The clinical implications of these findings are discussed.

Automated Analysis of the Auditory Brainstem Response Using Derivative Estimation Wavelets

In this paper, we describe an algorithm that automatically detects and labels peaks I–VII of the normal, suprathreshold auditory brainstem response (ABR). The algorithm proceeds in three stages, with the option of a fourth: (1) all candidate peaks and troughs in the ABR waveform are identified using zero crossings of the first derivative, (2) peaks I–VII are identified from these candidate peaks based on their latency and morphology, (3) if required, peaks II and IV are identified as points of inflection using zero crossings of the second derivative and (4) interpeak troughs are identified before peak latencies and amplitudes are measured. The performance of the algorithm was estimated on a set of 240 normal ABR waveforms recorded using a stimulus intensity of 90 dBnHL. When compared to an expert audiologist, the algorithm correctly identified the major ABR peaks (I, III and V) in 96–98% of the waveforms and the minor ABR peaks (II, IV, VI and VII) in 45–83% of waveforms. Whilst peak II was correctly identified in only 83% and peak IV in 77% of waveforms, it was shown that 5% of the peak II identifications and 31% of the peak IV identifications came as a direct result of allowing these peaks to be found as points of inflection.