ABR/DPOAE publications

Even though the principles of recording brain electrical activity remain unchanged since their discovery, their acquisition has seen major improvements. The cEEGrid, a recently developed flex-printed multi-channel sensory array, can be placed around the ear and successfully record well-known cortical electrophysiological potentials such as late auditory evoked potentials (AEPs) or the P300. Due to its fast and easy application as well as its long-lasting signal recording window, the cEEGrid technology offers great potential as a flexible and 'wearable' solution for the acquisition of neural correlates of hearing. Early potentials of auditory processing such as the auditory brainstem response (ABR) are already used in clinical assessment of sensorineural hearing disorders and envelope following responses (EFR) have shown promising results in the diagnosis of suprathreshold hearing deficits. This study evaluates the suitability of the cEEGrid electrode configuration to capture these AEPs. cEEGrid potentials were recorded and compared to cap-EEG potentials for young normal-hearing listeners and older listeners with high-frequency sloping audiograms to assess whether the recordings are adequately sensitive for hearing diagnostics. ABRs were elicited by presenting clicks (70 and 100-dB peSPL) and stimulation for the EFRs consisted of 120 Hz amplitude-modulated white noise carriers presented at 70-dB SPL. Data from nine bipolar cEEGrid channels and one classical cap-EEG montage (earlobes to vertex) were analysed and outcome measures were compared. Results show that the cEEGrid is able to record ABRs and EFRs with comparable shape to those recorded using a conventional cap-EEG recording montage and the same amplifier. Signal strength is lower but can still produce responses above the individual neural electrophysiological noise floor. This study shows that the application of the cEEGrid can be extended to the acquisition of early auditory evoked potentials.

Objectives: The aims of this study were to systematically explore the effects of stimulus duration, background (quiet versus noise), and three consonant–vowels on speech-auditory brainstem responses (ABRs). Additionally, the minimum number of epochs required to record speech-ABRs with clearly identifiable waveform components was assessed. The purpose was to evaluate whether shorter duration stimuli could be reliably used to record speech-ABRs both in quiet and in background noise to the three consonant–vowels, as opposed to longer duration stimuli that are commonly used in the literature. Shorter duration stimuli and a smaller number of epochs would require shorter test sessions and thus encourage the transition of the speech-ABR from research to clinical practice. Design: Speech-ABRs in response to 40 msec [da], 50 msec [ba] [da] [ga], and 170 msec [ba] [da] [ga] stimuli were collected from 12 normal-hearing adults with confirmed normal click-ABRs. Monaural (right-ear) speech-ABRs were recorded to all stimuli in quiet and to 40 msec [da], 50 msec [ba] [da] [ga], and 170 msec [da] in a background of two-talker babble at +10 dB signal to noise ratio using a 2-channel electrode montage (Cz-Active, A1 and A2-reference, Fz-ground). Twelve thousand epochs (6000 per polarity) were collected for each stimulus and background from all participants. Latencies and amplitudes of speech-ABR peaks (V, A, D, E, F, O) were compared across backgrounds (quiet and noise) for all stimulus durations, across stimulus durations (50 and 170 msec) and across consonant–vowels ([ba], [da], and [ga]). Additionally, degree of phase locking to the stimulus fundamental frequency (in quiet versus noise) was evaluated for the frequency following response in speech-ABRs to the 170 msec [da]. Finally, the number of epochs required for a robust response was evaluated using F sp statistic and bootstrap analysis at different epoch iterations. Results: Background effect: the addition of background noise resulted in speech-ABRs with longer peak latencies and smaller peak amplitudes compared with speech-ABRs in quiet, irrespective of stimulus duration. However, there was no effect of background noise on the degree of phase locking of the frequency following response to the stimulus fundamental frequency in speech-ABRs to the 170 msec [da]. Duration effect: speech-ABR peak latencies and amplitudes did not differ in response to the 50 and 170 msec stimuli. Consonant–vowel effect: different consonant–vowels did not have an effect on speech-ABR peak latencies regardless of stimulus duration. Number of epochs: a larger number of epochs was required to record speech-ABRs in noise compared with in quiet, and a smaller number of epochs was required to record speech-ABRs to the 40 msec [da] compared with the 170 msec [da]. Conclusions: This is the first study that systematically investigated the clinical feasibility of speech-ABRs in terms of stimulus duration, background noise, and number of epochs. Speech-ABRs can be reliably recorded to the 40 msec [da] without compromising response quality even when presented in background noise. Because fewer epochs were needed for the 40 msec [da], this would be the optimal stimulus for clinical use. Finally, given that there was no effect of consonant–vowel on speech-ABR peak latencies, there is no evidence that speech-ABRs are suitable for assessing auditory discrimination of the stimuli used.

The frequency-specific tone-evoked auditory brainstem response (ABR) is an indispensable tool in both the audiology clinic and research laboratory. Most frequently, the toneburst ABR is used to estimate hearing thresholds in infants, toddlers, and other patients for whom behavioral testing is not feasible. Therefore, results of the ABR exam form the basis for decisions regarding interventions and hearing habilitation with implications extending far into the child’s future. Currently, responses are elicited by periodic sequences of toneburst stimuli presented serially to one ear at a time, which take a long time to measure multiple frequencies and intensities, and provide incomplete information if the infant wakes up early. Here, we describe a new method, the parallel ABR (pABR), which uses randomly timed toneburst stimuli to simultaneously acquire ABR waveforms to five frequencies in both ears. Here, we describe the pABR and quantify its effectiveness in addressing the greatest drawback of current methods: test duration. We show that in adults with normal hearing the pABR yields high-quality waveforms over a range of intensities, with similar morphology to the standard ABR in a fraction of the recording time. Furthermore, longer latencies and smaller amplitudes for low frequencies at a high intensity evoked by the pABR versus serial ABR suggest that responses may have better place specificity due to the masking provided by the other simultaneous toneburst sequences. Thus, the pABR has substantial potential for facilitating faster accumulation of more diagnostic information that is important for timely identification and treatment of hearing loss.

Evaluation of patients who are unable to provide behavioral responses on standard clinical measures is challenging due to the lack of standard objective (non-behavioral) clinical audiological measures that assess the outcome of an intervention (e.g., hearing aids). Brainstem responses to short consonant-vowel stimuli (speech-auditory brainstem responses [speech-ABRs]) have been proposed as a measure of subcortical encoding of speech, speech detection, and speech-in-noise performance in individuals with normal hearing. Here, we investigated the potential application of speech-ABRs as an objective clinical outcome measure of speech detection, speech-in-noise detection and recognition, and self-reported speech understanding in 98 adults with sensorineural hearing loss. We compared aided and unaided speech-ABRs, and speech-ABRs in quiet and in noise. In addition, we evaluated whether speech-ABR F0 encoding (obtained from the complex cross-correlation with the 40 ms [da] fundamental waveform) predicted aided behavioral speech recognition in noise or aided self-reported speech understanding. Results showed that (a) aided speech-ABRs had earlier peak latencies, larger peak amplitudes, and larger F0 encoding amplitudes compared to unaided speech-ABRs; (b) the addition of background noise resulted in later F0 encoding latencies but did not have an effect on peak latencies and amplitudes or on F0 encoding amplitudes; and (c) speech-ABRs were not a significant predictor of any of the behavioral or self-report measures. These results show that speech-ABR F0 encoding is not a good predictor of speech-in-noise recognition or self-reported speech understanding with hearing aids. However, our results suggest that speech-ABRs may have potential for clinical application as an objective measure of speech detection with hearing aids.

Auditory nerve single-unit recordings were obtained from two groups of young barn owls (age, between posthatching days 11 and 86) in terminal experiments under two different anesthetic regimes: ketamine (6-11 mg/kg) plus xylazine (∼2 mg/kg); or isoflurane (1-1.5%) in oxygen, delivered via artificial respiration. In a second series of minimally invasive experiments, auditory brainstem responses (ABRs) were recorded in the same four adult barn owls (Tyto alba; age, between 5 and 32 months) under three different anesthetic protocols: ketamine (10 mg/kg) plus xylazine (3 mg/kg), isoflurane (1-1.5%), and sevoflurane (2-3%) in carbogen. Finally, the ABR measurements on adult owls were repeated in terminal experiments including more invasive procedures such as artificial respiration and higher isoflurane dosage. The main finding was a significant deterioration of auditory sensitivity in barn owls under gas anesthesia, at the level of the auditory nerve (i.e., a very peripheral level of the auditory system). The effect was drastic in the young animals that experienced threshold elevations in auditory nerve single-unit responses of ≥20 dB. ABR thresholds assessed repeatedly in experiments on adult owls were also significantly higher under isoflurane and sevoflurane, on average by 7 and 15 dB, compared with ketamine/xylazine. This difference already occurred with minimal dosages and was reversibly enlarged with increased isoflurane concentration. Finally, there was evidence for confounding detrimental effects associated with artificial respiration over many hours, which suggested oxygen toxicity.

Speech is an ecologically essential signal, whose processing crucially involves the subcortical nuclei of the auditory brainstem, but there are few experimental options for studying these early responses in human listeners under natural conditions. While encoding of continuous natural speech has been successfully probed in the cortex with neurophysiological tools such as electroencephalography (EEG) and magnetoencephalography, the rapidity of subcortical response components combined with unfavorable signal-to-noise ratios signal-to-noise ratio has prevented application of those methods to the brainstem. Instead, experiments have used thousands of repetitions of simple stimuli such as clicks, tone-bursts, or brief spoken syllables, with deviations from those paradigms leading to ambiguity in the neural origins of measured responses. In this study we developed and tested a new way to measure the auditory brainstem response (ABR) to ongoing, naturally uttered speech, using EEG to record from human listeners. We found a high degree of morphological similarity between the speech-derived ABRs and the standard click-evoked ABR, in particular, a preserved Wave V, the most prominent voltage peak in the standard click-evoked ABR. Because this method yields distinct peaks that recapitulate the canonical ABR, at latencies too short to originate from the cortex, the responses measured can be unambiguously determined to be subcortical in origin. The use of naturally uttered speech to measure the ABR allows the design of engaging behavioral tasks, facilitating new investigations of the potential effects of cognitive processes like language and attention on brainstem processing.

Acoustic trauma is being reported to damage the auditory periphery and central system, and the compromised cortical inhibition is involved in auditory disorders, such as hyperacusis and tinnitus. Parvalbumin-containing neurons (PV neurons), a subset of GABAergic neurons, greatly shape and synchronize neural network activities. However, the change of PV neurons following acoustic trauma remains to be elucidated. The present study investigated how auditory cortical PV neurons change following unilateral 1 hour noise exposure (left ear, one octave band noise centered at 16 kHz, 116 dB SPL). Noise exposure elevated the auditory brainstem response threshold of the exposed ear when examined 7 days later. More detectable PV neurons were observed in both sides of the auditory cortex of noise-exposed rats when compared to control. The detectable PV neurons of the left auditory cortex (ipsilateral to the exposed ear) to noise exposure outnumbered those of the right auditory cortex (contralateral to the exposed ear). Quantification of Western blotted bands revealed higher expression level of PV protein in the left cortex. These findings of more active PV neurons in noise-exposed rats suggested that a compensatory mechanism might be initiated to maintain a stable state of the brain.

Development of electrophysiological means to assess the medial olivocochlear (MOC) system in humans is important to further our understanding of the function of that system and for the refinement and validation of psychoacoustical and otoacoustic emission methods which are thought to probe the MOC. Based on measurements in anesthetized animals it has been hypothesized that the MOC-reflex (MOCR) can enhance the response to signals in noise, and several lines of evidence support such a role in humans. A difficulty in these studies is the isolation of efferent effects. Efferent activation can be triggered by acoustic stimulation of the contralateral or ipsilateral ear, but ipsilateral stimulation is thought to be more effective. However, ipsilateral stimulation complicates interpretation of effects since these sounds can affect the perception of other ipsilateral sounds by mechanisms not involving olivocochlear efferents. We assessed the ipsilaterally evoked MOCR in human using a transtympanic procedure to record mass-potentials from the cochlear promontory or the niche of the round window. Averaged compound action potential (CAP) responses to masked probe tones of 4 kHz with and without a precursor (designed to activate the MOCR but not the stapedius reflex) were extracted with a polarity alternating paradigm. The masker was either a simultaneous narrow band noise masker or a short (20-ms) tonal ON- or OFF-frequency forward masker. The subjects were screened for normal hearing (audiogram, tympanogram, threshold stapedius reflex) and psychoacoustically tested for the presence of a precursor effect. We observed a clear reduction of CAP amplitude by the precursor, for different masking conditions. Even without an MOCR, this is expected because the precursor will affect the response to subsequent stimuli via neural adaptation. To determine whether the precursor also activated the efferent system, we measured the CAP over a range of masker levels, with or without precursor, and for different types of masker. The results show CAP reduction consistent with the type of gain reduction caused by the MOCR. These results generally support psychoacoustical paradigms designed to probe the efferent system as indeed activating the MOCR system, but not all observations are consistent with this mechanism.

Little is known about how outer hair cell loss interacts with noise-induced and age-related auditory nerve degradation (i.e., cochlear synaptopathy) to affect auditory brainstem response (ABR) wave characteristics. Given that listeners with impaired audiograms likely suffer from mixtures of these hearing deficits and that ABR amplitudes have successfully been used to isolate synaptopathy in listeners with normal audiograms, an improved understanding of how different hearing pathologies affect the ABR source generators will improve their sensitivity in hearing diagnostics. We employed a functional model for human ABRs in which different combinations of hearing deficits were simulated and show that high-frequency cochlear gain loss steepens the slope of the ABR Wave-V latency versus intensity and amplitude versus intensity curves. We propose that grouping listeners according to a ratio of these slope metrics (i.e., the ABR growth ratio) might offer a way to factor out the outer hair cell loss deficit and maximally relate individual differences for constant ratios to other peripheral hearing deficits such as cochlear synaptopathy. We compared the model predictions to recorded click-ABRs from 30 participants with normal or high-frequency sloping audiograms and confirm the predicted relationship between the ABR latency growth curve and audiogram slope. Experimental ABR amplitude growth showed large individual differences and was compared with the Wave-I amplitude, Wave-V/I ratio, or the interwave I – W latency in the same listeners. The model simulations along with the ABR recordings suggest that a hearing loss profile depicting the ABR growth ratio versus the Wave-I amplitude or Wave-V/I ratio might be able to differentiate outer hair cell deficits from cochlear synaptopathy in listeners with mixed pathologies.

Auditory information relayed by auditory nerve fibers and somatosensory information relayed by granule cell parallel fibers converge on the fusiform cells (FCs) of the dorsal cochlear nucleus, the first brain station of the auditory pathway. In vitro, parallel fiber synapses on FCs exhibit spike-timing-dependent plasticity with Hebbian learning rules, partially mediated by the NMDA receptor (NMDAr). Well-timed bimodal auditory-somatosensory stimulation, in vivo equivalent of spike-timing-dependent plasticity, can induce stimulus-timing-dependent plasticity (StTDP) of the FCs spontaneous and tone-evoked firing rates. In healthy guinea pigs, the resulting distribution of StTDP learning rules across a FC neural population is dominated by a Hebbian profile while anti-Hebbian, suppressive and enhancing LRs are less frequent. In this study, we investigate in vivo, the NMDAr contribution to FC baseline activity and long term plasticity. We find that blocking the NMDAr decreases the synchronization of FC- spontaneous activity and mediates differential modulation of FC rate-level functions such that low, and high threshold units are more likely to increase, and decrease, respectively, their maximum amplitudes. Three significant alterations in mean learning-rule profiles were identified: transitions from an initial Hebbian profile towards (1) an anti-Hebbian; (2) a suppressive profile; and (3) transitions from an anti-Hebbian to a Hebbian profile. FC units preserving their learning rules showed instead, NMDAr-dependent plasticity to unimodal acoustic stimulation, with persistent depression of tone-evoked responses changing to persistent enhancement following the NMDAr antagonist. These results reveal a crucial role of the NMDAr in mediating FC baseline activity and long-term plasticity which have important implications for signal processing and auditory pathologies related to maladaptive plasticity of dorsal cochlear nucleus circuitry.

The nonsteroidal antiinflammatory drug (NSAID) ketorolac is a candidate for use as a supplemental analgesic during major surgery in anesthetized rodents. The use of ketorolac during surgery is believed to reduce the anesthetic dose required to achieve and maintain an adequate surgical plane, thus improving the physiologic condition and survival of animals during long experimental procedures. Ketorolac has reported side effects that include dizziness, ear pain, hearing loss, tinnitus, and vertigo in humans, but ketorolac has not been reported to affect the vestibular system in animals. To investigate this possibility, we evaluated the acute effects of ketorolac on vestibular compound action potentials in C57BL/6 mice. Linear vestibular sensory-evoked potentials (VsEP) were recorded during the administration of ketorolac at doses 3 to 14 times the effective analgesic dose. VsEP results for ketorolac were compared with those from a control group maintained under anesthesia for the same period. Ketorolac did not significantly affect the temporal profiles of response latencies and amplitudes or the rate of change in response measures over time between controls and ketorolac-treated mice. These findings demonstrate that ketorolac can be used as an analgesic to supplement anesthesia in mice without concerns of modifying the amplitudes and latencies of the linear VsEP.

Increasing evidence suggests the involvement of oxidative stress in noise-induced hearing loss. The present study analysed, in an animal experimental model, the time course of the pathogenic mechanisms of noise-induced cochlear damage and the efficacy of the antioxidant drug N-acetylcysteine in reducing noise ototoxicity. Animals were divided into two groups, exposed to noise one treated with N-acetylcysteine for 3 days and one (the control group) with saline. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 minutes. Electrocochleographic recordings were made from an implanted round window electrode and the compound action potentials were measured daily at 2-16 kHz for 7 days. Morphological changes were analysed by scanning electron microscopy. The acoustic threshold measured 1 hour after acoustic trauma was elevated in the control group to 70-90 dB in the higher frequencies of the compound action potential audiogram, with a maximum threshold elevation ranging between 12 and 16 kHz. During the first 24 h, following acoustic trauma, there was a partial recovery of compound action potential thresholds of about 20 dB to reach a final threshold elevation of about 50-70 dB; there was no further improvement over the remaining experimental week. Animals treated with N-acetylcysteine showed a similar temporary threshold shift but a clear improvement in the recovery of compound action potential thresholds, with significantly reduced permanent threshold shift and hair cell loss. These data suggest that N-acetylcysteine is able to attenuate the toxic effect of acoustic trauma and could represent an interesting molecule for preventing inner ear injuries.