Acoustic reflexes: should we be paying more attention?

OBJECTIVE: The clinical audiology test battery often involves playing physically simple sounds with questionable ecological value to the listener. In this technical report, we revisit how valid this approach is using an automated, involuntary auditory response; the acoustic reflex threshold (ART). DESIGN: The ART was estimated four times in each individual in a quasi-random ordering of task conditions. The baseline condition (referred to as Neutral) measured the ART following a standard clinical practice. Three experimental conditions were then used in which a secondary task was performed whilst the reflex was measured: auditory attention, auditory distraction and visual distraction tasks. STUDY SAMPLE: Thirty-eight participants (27 males) with a mean age of 23 years were tested. All participants were audiometrically healthy. RESULTS: The ART was elevated when a visual task was performed at the same time as the measurements were taken. Performing an auditory task did not affect the ART. CONCLUSIONS: These data indicate that simple audiometric measures widely used in the clinic, can be affected by central, non-auditory processes even in healthy, normal-hearing volunteers. The role of cognition and attention on auditory responses will become ever more important in the coming years.

Binaural temporal coding and the middle ear muscle reflex in audiometrically normal young adults.

Noise exposure may damage the synapses that connect inner hair cells with auditory nerve fibers, before outer hair cells are lost. In humans, this cochlear synaptopathy (CS) is thought to decrease the fidelity of peripheral auditory temporal coding. In the current study, the primary hypothesis was that higher middle ear muscle reflex (MEMR) thresholds, as a proxy measure of CS, would be associated with smaller values of the binaural intelligibility level difference (BILD). The BILD, which is a measure of binaural temporal coding, is defined here as the difference in thresholds between the diotic and the antiphasic versions of the digits in noise (DIN) test. This DIN BILD may control for factors unrelated to binaural temporal coding such as linguistic, central auditory, and cognitive factors. Fifty-six audiometrically normal adults (34 females) aged 18 - 30 were tested. The test battery included standard pure tone audiometry, tympanometry, MEMR using a 2 kHz elicitor and 226 Hz and 1 kHz probes, the Noise Exposure Structured Interview, forward digit span test, extended high frequency (EHF) audiometry, and diotic and antiphasic DIN tests. The study protocol was pre-registered prior to data collection. MEMR thresholds did not predict the DIN BILD. Secondary analyses showed no association between MEMR thresholds and the individual diotic and antiphasic DIN thresholds. Greater lifetime noise exposure was non-significantly associated with higher MEMR thresholds, larger DIN BILD values, and lower (better) antiphasic DIN thresholds, but not with diotic DIN thresholds, nor with EHF thresholds. EHF thresholds were associated with neither MEMR thresholds nor any of the DIN outcomes, including the DIN BILD. Results provide no evidence that young, audiometrically normal people incur CS with impacts on binaural temporal processing.

The Role of the Clinically Obtained Acoustic Reflex as a Research Tool for Subclinical Hearing Pathologies.

The acoustic reflex (AR) shows promise as an objective test for the presence of cochlear synaptopathy in rodents. The AR has also been shown to be reduced in humans with tinnitus compared to those without. The aim of the present study was twofold: (a) to determine if AR strength (quantified as both threshold and growth) varied with lifetime noise exposure, and thus provided an estimate of the degree of synaptopathy and (b) to identify which factors should be considered when using the AR as a quantitative measure rather than just present/absent responses. AR thresholds and growth functions were measured using ipsilateral and contralateral, broadband and tonal elicitors in adults with normal hearing and varying levels of lifetime noise exposure. Only the clinical standard 226 Hz probe tone was used. AR threshold and growth were not related to lifetime noise exposure, suggesting that routine clinical AR measures are not a sensitive measure when investigating the effects of noise exposure in audiometrically normal listeners. Our secondary, exploratory analyses revealed that AR threshold and growth were significantly related to middle-ear compliance. Listeners with higher middle-ear compliance (though still in the clinically normal range) showed lower AR thresholds and steeper AR growth functions. Furthermore, there was a difference in middle-ear compliance between the sexes, with males showing higher middle-ear compliance values than females. Therefore, it may be necessary to factor middle-ear compliance values into any analysis that uses the AR as an estimate of auditory function.

No Effect of Interstimulus Interval on Acoustic Reflex Thresholds.

The acoustic reflex (AR), a longstanding component of the audiological test battery, has received renewed attention in the context of noise-induced cochlear synaptopathy-the destruction of synapses between inner hair cells and auditory nerve fibers. Noninvasive proxy measures of synaptopathy are widely sought, and AR thresholds (ARTs) correlate closely with synaptic survival in rodents. However, measurement in humans at high stimulus frequencies-likely important when testing for noise-induced pathology-can be challenging; reflexes at 4 kHz are frequently absent or occur only at high stimulus levels, even in young people with clinically normal audiograms. This phenomenon may partly reflect differences across stimulus frequency in the temporal characteristics of the response; later onset of the response, earlier onset of adaptation, and higher rate of adaptation have been observed at 4 kHz than at 1 kHz. One temporal aspect of the response that has received little attention is the interstimulus interval (ISI); inadequate duration of ISI might lead to incomplete recovery of the response between successive presentations and consequent response fatigue. This research aimed to test for effects of ISI on ARTs in normally hearing young humans, measured at 1 and 4 kHz. Contrary to our hypotheses, increasing ISIs from 2.5 to 8.5 s did not reduce ART level, nor raise ART reliability. Results confirm that clinically measured ARTs-including those at 4 kHz-can exhibit excellent reliability and that relatively short (2.5 s) ISIs are adequate for the measurement of sensitive and reliable ARTs.

Effects of Age and Noise Exposure on Proxy Measures of Cochlear Synaptopathy.

Although there is strong histological evidence for age-related synaptopathy in humans, evidence for the existence of noise-induced cochlear synaptopathy in humans is inconclusive. Here, we sought to evaluate the relative contributions of age and noise exposure to cochlear synaptopathy using a series of electrophysiological and behavioral measures. We extended an existing cohort by including 33 adults in the age range 37 to 60, resulting in a total of 156 participants, with the additional older participants resulting in a weakening of the correlation between lifetime noise exposure and age. We used six independent regression models (corrected for multiple comparisons), in which age, lifetime noise exposure, and high-frequency audiometric thresholds were used to predict measures of synaptopathy, with a focus on differential measures. The models for auditory brainstem responses, envelope-following responses, interaural phase discrimination, and the co-ordinate response measure of speech perception were not statistically significant. However, both age and noise exposure were significant predictors of performance on the digit triplet test of speech perception in noise, with greater noise exposure (unexpectedly) predicting better performance in the 80 dB sound pressure level (SPL) condition and greater age predicting better performance in the 40 dB SPL condition. Amplitude modulation detection thresholds were also significantly predicted by age, with older listeners performing better than younger listeners at 80 dB SPL. Overall, the results are inconsistent with the predicted effects of synaptopathy.

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.

Impaired speech perception in noise with a normal audiogram: No evidence for cochlear synaptopathy and no relation to lifetime noise exposure.

In rodents, noise exposure can destroy synapses between inner hair cells and auditory nerve fibers ("cochlear synaptopathy") without causing hair cell loss. Noise-induced cochlear synaptopathy usually leaves cochlear thresholds unaltered, but is associated with long-term reductions in auditory brainstem response (ABR) amplitudes at medium-to-high sound levels. This pathophysiology has been suggested to degrade speech perception in noise (SPiN), perhaps explaining why SPiN ability varies so widely among audiometrically normal humans. The present study is the first to test for evidence of cochlear synaptopathy in humans with significant SPiN impairment. Individuals were recruited on the basis of self-reported SPiN difficulties and normal pure tone audiometric thresholds. Performance on a listening task identified a subset with "verified" SPiN impairment. This group was matched with controls on the basis of age, sex, and audiometric thresholds up to 14 kHz. ABRs and envelope-following responses (EFRs) were recorded at high stimulus levels, yielding both raw amplitude measures and within-subject difference measures. Past exposure to high sound levels was assessed by detailed structured interview. Impaired SPiN was not associated with greater lifetime noise exposure, nor with any electrophysiological measure. It is conceivable that retrospective self-report cannot reliably capture noise exposure, and that ABRs and EFRs offer limited sensitivity to synaptopathy in humans. Nevertheless, the results do not support the notion that noise-induced synaptopathy is a significant etiology of SPiN impairment with normal audiometric thresholds. It may be that synaptopathy alone does not have significant perceptual consequences, or is not widespread in humans with normal audiograms.

Effects of noise exposure on young adults with normal audiograms II: Behavioral measures.

An estimate of lifetime noise exposure was used as the primary predictor of performance on a range of behavioral tasks: frequency and intensity difference limens, amplitude modulation detection, interaural phase discrimination, the digit triplet speech test, the co-ordinate response speech measure, an auditory localization task, a musical consonance task and a subjective report of hearing ability. One hundred and thirty-eight participants (81 females) aged 18-36 years were tested, with a wide range of self-reported noise exposure. All had normal pure-tone audiograms up to 8 kHz. It was predicted that increased lifetime noise exposure, which we assume to be concordant with noise-induced cochlear synaptopathy, would elevate behavioral thresholds, in particular for stimuli with high levels in a high spectral region. However, the results showed little effect of noise exposure on performance. There were a number of weak relations with noise exposure across the test battery, although many of these were in the opposite direction to the predictions, and none were statistically significant after correction for multiple comparisons. There were also no strong correlations between electrophysiological measures of synaptopathy published previously and the behavioral measures reported here. Consistent with our previous electrophysiological results, the present results provide no evidence that noise exposure is related to significant perceptual deficits in young listeners with normal audiometric hearing. It is possible that the effects of noise-induced cochlear synaptopathy are only measurable in humans with extreme noise exposures, and that these effects always co-occur with a loss of audiometric sensitivity.

Magnified Neural Envelope Coding Predicts Deficits in Speech Perception in Noise.

Verbal communication in noisy backgrounds is challenging. Understanding speech in background noise that fluctuates in intensity over time is particularly difficult for hearing-impaired listeners with a sensorineural hearing loss (SNHL). The reduction in fast-acting cochlear compression associated with SNHL exaggerates the perceived fluctuations in intensity in amplitude-modulated sounds. SNHL-induced changes in the coding of amplitude-modulated sounds may have a detrimental effect on the ability of SNHL listeners to understand speech in the presence of modulated background noise. To date, direct evidence for a link between magnified envelope coding and deficits in speech identification in modulated noise has been absent. Here, magnetoencephalography was used to quantify the effects of SNHL on phase locking to the temporal envelope of modulated noise (envelope coding) in human auditory cortex. Our results show that SNHL enhances the amplitude of envelope coding in posteromedial auditory cortex, whereas it enhances the fidelity of envelope coding in posteromedial and posterolateral auditory cortex. This dissociation was more evident in the right hemisphere, demonstrating functional lateralization in enhanced envelope coding in SNHL listeners. However, enhanced envelope coding was not perceptually beneficial. Our results also show that both hearing thresholds and, to a lesser extent, magnified cortical envelope coding in left posteromedial auditory cortex predict speech identification in modulated background noise. We propose a framework in which magnified envelope coding in posteromedial auditory cortex disrupts the segregation of speech from background noise, leading to deficits in speech perception in modulated background noise.SIGNIFICANCE STATEMENT People with hearing loss struggle to follow conversations in noisy environments. Background noise that fluctuates in intensity over time poses a particular challenge. Using magnetoencephalography, we demonstrate anatomically distinct cortical representations of modulated noise in normal-hearing and hearing-impaired listeners. This work provides the first link among hearing thresholds, the amplitude of cortical representations of modulated sounds, and the ability to understand speech in modulated background noise. In light of previous work, we propose that magnified cortical representations of modulated sounds disrupt the separation of speech from modulated background noise in auditory cortex.

Effects of noise exposure on young adults with normal audiograms I: Electrophysiology.

Noise-induced cochlear synaptopathy has been demonstrated in numerous rodent studies. In these animal models, the disorder is characterized by a reduction in amplitude of wave I of the auditory brainstem response (ABR) to high-level stimuli, whereas the response at threshold is unaffected. The aim of the present study was to determine if this disorder is prevalent in young adult humans with normal audiometric hearing. One hundred and twenty six participants (75 females) aged 18-36 were tested. Participants had a wide range of lifetime noise exposures as estimated by a structured interview. Audiometric thresholds did not differ across noise exposures up to 8 kHz, although 16-kHz audiometric thresholds were elevated with increasing noise exposure for females but not for males. ABRs were measured in response to high-pass (1.5 kHz) filtered clicks of 80 and 100 dB peSPL. Frequency-following responses (FFRs) were measured to 80 dB SPL pure tones from 240 to 285 Hz, and to 80 dB SPL 4 kHz pure tones amplitude modulated at frequencies from 240 to 285 Hz (transposed tones). The bandwidth of the ABR stimuli and the carrier frequency of the transposed tones were chosen to target the 3-6 kHz characteristic frequency region which is usually associated with noise damage in humans. The results indicate no relation between noise exposure and the amplitude of the ABR. In particular, wave I of the ABR did not decrease with increasing noise exposure as predicted. ABR wave V latency increased with increasing noise exposure for the 80 dB peSPL click. High carrier-frequency (envelope) FFR signal-to-noise ratios decreased as a function of noise exposure in males but not females. However, these correlations were not significant after the effects of age were controlled. The results suggest either that noise-induced cochlear synaptopathy is not a significant problem in young, audiometrically normal adults, or that the ABR and FFR are relatively insensitive to this disorder in young humans, although it is possible that the effects become more pronounced with age.

Tinnitus with a normal audiogram: Relation to noise exposure but no evidence for cochlear synaptopathy.

In rodents, exposure to high-level noise can destroy synapses between inner hair cells and auditory nerve fibers, without causing hair cell loss or permanent threshold elevation. Such "cochlear synaptopathy" is associated with amplitude reductions in wave I of the auditory brainstem response (ABR) at moderate-to-high sound levels. Similar ABR results have been reported in humans with tinnitus and normal audiometric thresholds, leading to the suggestion that tinnitus in these cases might be a consequence of synaptopathy. However, the ABR is an indirect measure of synaptopathy and it is unclear whether the results in humans reflect the same mechanisms demonstrated in rodents. Measures of noise exposure were not obtained in the human studies, and high frequency audiometric loss may have impacted ABR amplitudes. To clarify the role of cochlear synaptopathy in tinnitus with a normal audiogram, we recorded ABRs, envelope following responses (EFRs), and noise exposure histories in young adults with tinnitus and matched controls. Tinnitus was associated with significantly greater lifetime noise exposure, despite close matching for age, sex, and audiometric thresholds up to 14 kHz. However, tinnitus was not associated with reduced ABR wave I amplitude, nor with significant effects on EFR measures of synaptopathy. These electrophysiological measures were also uncorrelated with lifetime noise exposure, providing no evidence of noise-induced synaptopathy in this cohort, despite a wide range of exposures. In young adults with normal audiograms, tinnitus may be related not to cochlear synaptopathy but to other effects of noise exposure.

Neural mechanisms underlying song and speech perception can be differentiated using an illusory percept.

The issue of whether human perception of speech and song recruits integrated or dissociated neural systems is contentious. This issue is difficult to address directly since these stimulus classes differ in their physical attributes. We therefore used a compelling illusion (Deutsch et al. 2011) in which acoustically identical auditory stimuli are perceived as either speech or song. Deutsch's illusion was used in a functional MRI experiment to provide a direct, within-subject investigation of the brain regions involved in the perceptual transformation from speech into song, independent of the physical characteristics of the presented stimuli. An overall differential effect resulting from the perception of song compared with that of speech was revealed in right midposterior superior temporal sulcus/right middle temporal gyrus. A left frontotemporal network, previously implicated in higher-level cognitive analyses of music and speech, was found to co-vary with a behavioural measure of the subjective vividness of the illusion, and this effect was driven by the illusory transformation. These findings provide evidence that illusory song perception is instantiated by a network of brain regions that are predominantly shared with the speech perception network.

Perceptual consequences of "hidden" hearing loss.

Dramatic results from recent animal experiments show that noise exposure can cause a selective loss of high-threshold auditory nerve fibers without affecting absolute sensitivity permanently. This cochlear neuropathy has been described as hidden hearing loss, as it is not thought to be detectable using standard measures of audiometric threshold. It is possible that hidden hearing loss is a common condition in humans and may underlie some of the perceptual deficits experienced by people with clinically normal hearing. There is some evidence that a history of noise exposure is associated with difficulties in speech discrimination and temporal processing, even in the absence of any audiometric loss. There is also evidence that the tinnitus experienced by listeners with clinically normal hearing is associated with cochlear neuropathy, as measured using Wave I of the auditory brainstem response. To date, however, there has been no direct link made between noise exposure, cochlear neuropathy, and perceptual difficulties. Animal experiments also reveal that the aging process itself, in the absence of significant noise exposure, is associated with loss of auditory nerve fibers. Evidence from human temporal bone studies and auditory brainstem response measures suggests that this form of hidden loss is common in humans and may have perceptual consequences, in particular, regarding the coding of the temporal aspects of sounds. Hidden hearing loss is potentially a major health issue, and investigations are ongoing to identify the causes and consequences of this troubling condition.

Stimulus variability affects the amplitude of the auditory steady-state response.

In this study we investigate whether stimulus variability affects the auditory steady-state response (ASSR). We present cosinusoidal AM pulses as stimuli where we are able to manipulate waveform shape independently of the fixed repetition rate of 4 Hz. We either present sounds in which the waveform shape, the pulse-width, is fixed throughout the presentation or where it varies pseudo-randomly. Importantly, the average spectra of all the fixed-width AM stimuli are equal to the spectra of the mixed-width AM. Our null hypothesis is that the average ASSR to the fixed-width AM will not be significantly different from the ASSR to the mixed-width AM. In a region of interest beamformer analysis of MEG data, we compare the 4 Hz component of the ASSR to the mixed-width AM with the 4 Hz component of the ASSR to the pooled fixed-width AM. We find that at the group level, there is a significantly greater response to the variable mixed-width AM at the medial boundary of the Middle and Superior Temporal Gyri. Hence, we find that adding variability into AM stimuli increases the amplitude of the ASSR. This observation is important, as it provides evidence that analysis of the modulation waveform shape is an integral part of AM processing. Therefore, standard steady-state studies in audition, using sinusoidal AM, may not be sensitive to a key feature of acoustic processing.

Spatiotemporal reconstruction of the auditory steady-state response to frequency modulation using magnetoencephalography.

The aim of this study was to investigate the mechanisms involved in the perception of perceptually salient frequency modulation (FM) using auditory steady-state responses (ASSRs) measured with magnetoencephalography (MEG). Previous MEG studies using frequency-modulated amplitude modulation as stimuli (Luo et al., 2006, 2007) suggested that a phase modulation encoding mechanism exists for low (<5 Hz) FM modulation frequencies but additional amplitude modulation encoding is required for faster FM modulation frequencies. In this study single-cycle sinusoidal FM stimuli were used to generate the ASSR. The stimulus was either an unmodulated 1-kHz sinusoid or a 1-kHz sinusoid that was frequency-modulated with a repetition rate of 4, 8, or 12 Hz. The fast Fourier transform (FFT) of each MEG channel was calculated to obtain the phase and magnitude of the ASSR in sensor-space and multivariate Hotelling's T(2) statistics were used to determine the statistical significance of ASSRs. MEG beamformer analyses were used to localise the ASSR sources. Virtual electrode analyses were used to reconstruct the time series at each source. FFTs of the virtual electrode time series were calculated to obtain the amplitude and phase characteristics of each source identified in the beamforming analyses. Multivariate Hotelling's T(2) statistics were used to determine the statistical significance of these reconstructed ASSRs. The results suggest that the ability of auditory cortex to phase-lock to FM is dependent on the FM pulse rate and that the ASSR to FM is lateralised to the right hemisphere.

Source stability index: a novel beamforming based localisation metric.

Many experimental studies into human brain function now use magnetoencephalography (MEG) to non-invasively investigate human neuronal activity. A number of different analysis techniques use the observed magnetic fields outside of the head to estimate the location and strength of the underlying neural generators. One such technique, a spatial filtering method known as Beamforming, produces whole-head volumetric images of activation. Typically, a differential power map throughout the head is generated between a time window containing the response to a stimulus of interest and a window containing background brain activity. A statistical test is normally performed to reveal locations which show a significantly different response in the presence of the stimulus. Despite this being a widely used measure, for both phase-locked and non-phase-locked information, it requires a number of assumptions; namely that the baseline activity defined is stable and also that a change in total power is the most effective way of revealing the neuronal sources required for the task. This paper introduces a metric which evaluates the consistency of the response at each location within a cortical volume. Such a method of localisation negates the need for a baseline period of activity to be defined and also moves away from simply considering the energy content of brain activity. The paper presents both simulated and real data. It demonstrates that this new metric of stability is able to more accurately and, crucially, more reliably draw inferences about neuronal sources of interest.