Electrophysiology publications

In everyday settings, information processing depends on attentional focus, available cognitive resources, and stimulus characteristics such as its valence. Despite insights from laboratory studies, multisensory information processing in complex, realistic environments remains poorly understood. Using whole-head magnetoencephalography and eye tracking in a driving simulation, we addressed two research questions: (1) What are the distinct signatures of (socio-)emotional speech processing and visuo-spatial cognition in the dual task of driving and listening and (2) is information processing co-modulated by valence of speech and workload? We hypothesised two antagonistic processing modes: A top-down guided mode for (socio-)emotional speech processing and a bottom-up stimulus-driven mode for visuo-spatial cognition under high workload. A third mode was proposed to regulate emotional interference during driving under high visuo-spatial load and limited cognitive capacity. Its involvement is hypothesised to be co-modulated by valence and workload. Spatial clustering of oscillatory source activity supported the hypotheses: During emotional compared with neutral speech, parietal beta-band power increased, which likely supported processes related to predictive listening and socio-emotional cognition. In this top-down guided mode, driving-related activity decreased, as indicated by greater parietal alpha- and reduced gamma-band power. During high visuo-spatial workload, linked to the bottom-up stimulus-driven mode, gamma-band power increased in motor and orbitofrontal cortices, whereas beta-band power decreased in motor and temporo-parietal regions. Moreover, increased pupil dilation and decreased gaze dispersion were associated with this bottom-up stimulus-driven mode and visuo-spatial cognitive demands. Multivariate pattern analyses identified the third regulatory mode reflected in fronto-temporal gamma-band oscillations. It was co-modulated by valence and workload: Under low workload drives, gamma-band activity increased for negative compared with positive speech, pointing to the recruitment of inhibitory control processes. Under high workload drives with heightened visuo-spatial demands, gamma-band activity increased for positive speech, but decreased for negative speech, suggesting reduced cognitive resources and impaired control. To conclude, we found converging evidence of distinct signatures for (socio-)emotional speech, visuo-spatial cognition, and interference regulation in naturalistic multisensory environments. We propose that the top-down guided mode represents anticipatory listening and socio-emotional cognition, whereas the bottom-up stimulus-driven mode reflects the allocation of resources to driving-related spatial and sensorimotor processing but also cognitive strain under heightened task demands. Fronto-temporal gamma oscillations likely enable flexible up- and down-regulation of emotional speech processing in response to potential interference in complex, naturalistic environments.

Stories, Chirps, And Noisy Sentences (MEG-SCANS) is a dataset that provides raw magnetoencephalography (MEG) recordings from 24 German-speaking subjects. Each subject listened to approximately one hour of stimuli, including two audiobooks, sentences from the Oldenburger Matrix Sentence Test (OLSA) for Speech Reception Threshold (SRT) assessment, and short up-chirps used to assess MEG signal quality. The dataset includes MEG data, structural MRI (Magnetic Resonance Imaging) scans of the head, corresponding audio material (audiobooks, OLSA envelopes, and chirp stimuli), and behavioral audiogram and SRT results from hearing screenings. Organized according to the Brain Imaging Data Structure (BIDS), this resource offers a robust benchmark for large-scale encoding/decoding analyses of temporally-resolved brain responses to speech. Comprehensive Matlab and Python code are included to replicate key data validations, ensuring transparency and reproducibility.

Frequency analysis by the cochlea forms a key foundation for all subsequent auditory processing. Stimulus-frequency otoacoustic emissions (SFOAEs) are a potentially powerful alternative to traditional behavioral experiments for estimating cochlear tuning without invasive testing, as is necessary in humans. Which methods accurately predict cochlear tuning remains controversial due to only a single animal study comparing SFOAE-based, behavioral, and cochlear frequency tuning in the same species. The budgerigar ( Melopsittacus undulatus ) is a parakeet species with human-like behavioral sensitivity to many sounds and the capacity to mimic speech. Intriguingly, previous studies of critical bands, psychophysical tuning curves, and critical ratios in budgerigars show that behavioral tuning sharpness increases dramatically with increasing frequency from 1 to 3.5 kHz, doubling once per octave with peak tuning sharpness from 3.5 to 4 kHz. The pattern contrasts with slower monotonic growth of behavioral tuning sharpness with increasing frequency in other animals, including most avian species, suggesting a possible auditory specialization in budgerigars. We measured SFOAE-based and cochlear-afferent tuning in budgerigars, for comparison to previously reported behavioral results. SFOAE-based and cochlear-afferent tuning sharpness both increased monotonically and relatively slowly for higher frequencies, in contrast to the behavioral pattern. SFOAE-based tuning in budgerigars accurately predicted cochlear frequency tuning, and both measures aligned with typical patterns of cochlear tuning in other species. Divergent behavioral tuning in budgerigars is unlikely attributable to the periphery and could reflect specializations for central processing of masked signals. Our findings highlight the value of SFOAEs for estimating cochlear tuning and caution against direct inference of peripheral tuning from behavioral critical bands, psychophysical tuning curves, and critical ratios.

We hypothesized that active outer hair cells drive cochlear fluid circulation. The hypothesis was tested by delivering the neurotoxin, kainic acid, to the intact round window of young gerbil cochleae while monitoring auditory responses in the cochlear nucleus. Sounds presented at a modest level significantly expedited kainic acid delivery. When outer-hair-cell motility was suppressed by salicylate, the facilitation effect was compromised. A low-frequency tone was more effective than broadband noise, especially for drug delivery to apical locations. Computational model simulations provided the physical basis for our observation, which incorporated solute diffusion, fluid advection, fluid–structure interaction, and outer-hair-cell motility. Active outer hair cells deformed the organ of Corti like a peristaltic tube to generate apically streaming flows along the tunnel of Corti and basally streaming flows along the scala tympani. Our measurements and simulations coherently suggest that active outer hair cells in the tail region of cochlear traveling waves drive cochlear fluid circulation.

Speech intelligibility declines with age and sensorineural hearing damage (SNHL). However, it remains unclear whether cochlear synaptopathy (CS), a recently discovered form of SNHL, significantly contributes to this issue. CS refers to damaged auditory-nerve synapses that innervate the inner hair cells and there is currently no go-to diagnostic test available. Furthermore, age-related hearing damage can comprise various aspects (e.g., hair cell damage, CS) that each can play a role in impaired sound perception. To explore the link between cochlear damage and speech intelligibility deficits, this study examines the role of CS for word recognition among older listeners. We first validated an envelope-following response (EFR) marker for CS using a Budgerigar model. We then applied this marker in human experiments, while restricting the speech material’s frequency content to ensure that both the EFR and the behavioral tasks engaged similar cochlear frequency regions. Following this approach, we identified the relative contribution of hearing sensitivity and CS to speech intelligibility in two age-matched (65-year-old) groups with clinically normal ( n = 15, 8 females) or impaired audiograms ( n = 13, 8 females). Compared to a young normal-hearing control group ( n = 13, 7 females), the older groups demonstrated lower EFR responses and impaired speech reception thresholds. We conclude that age-related CS reduces supra-threshold temporal envelope coding with subsequent speech coding deficits in noise that cannot be explained based on hearing sensitivity alone.

Negative-going responses in sensory cortex co-vary with perceptual awareness of sensory stimuli. Given that this awareness negativity has also been observed for undetected stimuli, some have challenged its role for perception. To address this question, we combined magnetoencephalography, electroencephalography, and pupillometry to study how sustained attention and response criterion affect the auditory awareness negativity. Participants first detected distractor sounds and denied hearing task-irrelevant near-threshold tones, which evoked neither awareness negativity nor pupil dilation. These same tones evoked both responses when task-relevant, stronger for hit but also present for miss trials. Participants then rated their perception on a six-point scale to test whether response criterion explains the presence of these responses for miss trials. Decreasing perception ratings were associated with gradually reduced evoked responses, consistent with signal detection theory. These results support the concept of an awareness negativity that is modulated by attention but does not require a non-linear threshold mechanism.

The P2 component of the auditory evoked potential has previously been shown to depend on the acoustic stimulus properties and prior exposure to the materials. Here, we show that it is also affected by acoustic changes, as P2 amplitudes were strongly enhanced in response to voice pitch changes with a stepwise pattern compared to dynamic pitch changes typical for natural speech, and also reflected the magnitude of these pitch changes. Furthermore, it is demonstrated that neither the P2 nor any other component is affected by the harmonicity of the materials. Despite no prior exposure and a weaker pitch, artificially created inharmonic versions of the materials elicited similar activity throughout the auditory cortex. This suggests that so-called harmonic template neurons observed in animal studies are either absent or do not exist in sufficient number in the human auditory cortex to detect their activity extracranially. Crucially, morphology as well as scalp maps and source reconstructions of the EEG data showed that the P2 appears to consist of two separate subcomponents. While the “P2a” was localised to the auditory cortex, the subsequent “P2b” included generators spread across the auditory cortex and association areas. The two subcomponents thus likely reflect processing at different stages of the auditory pathway.

Advancements in cochlear implants (CIs) have led to a significant increase in bilateral CI users, especially among children. Yet, most bilateral CI users do not fully achieve the intended binaural benefit due to potential limitations in signal processing and/or surgical implant positioning. One crucial auditory cue that normal hearing (NH) listeners can benefit from is the interaural time difference (ITD), i.e ., the time difference between the arrival of a sound at two ears. The ITD sensitivity is thought to be heavily relying on the effective utilization of temporal fine structure (very rapid oscillations in sound). Unfortunately, most current CIs do not transmit such true fine structure. Nevertheless, bilateral CI users have demonstrated sensitivity to ITD cues delivered through envelope or interaural pulse time differences, i.e ., the time gap between the pulses delivered to the two implants. However, their ITD sensitivity is significantly poorer compared to NH individuals, and it further degrades at higher CI stimulation rates, especially when the rate exceeds 300 pulse per second. The overall purpose of this research thread is to improve spatial hearing abilities in bilateral CI users. This study aims to develop electroencephalography (EEG) paradigms that can be used with clinical settings to assess and optimize the delivery of ITD cues, which are crucial for spatial hearing in everyday life. The research objective of this article was to determine the effect of CI stimulation pulse rate on the ITD sensitivity, and to characterize the rate-dependent degradation in ITD perception using EEG measures. To develop protocols for bilateral CI studies, EEG responses were obtained from NH listeners using sinusoidal-amplitude-modulated (SAM) tones and filtered clicks with changes in either fine structure ITD (ITD FS ) or envelope ITD (ITD ENV ). Multiple EEG responses were analyzed, which included the subcortical auditory steady-state responses (ASSRs) and cortical auditory evoked potentials (CAEPs) elicited by stimuli onset, offset, and changes. Results indicated that acoustic change complex (ACC) responses elicited by ITD ENV changes were significantly smaller or absent compared to those elicited by ITD FS changes. The ACC morphologies evoked by ITD FS changes were similar to onset and offset CAEPs, although the peak latencies were longest for ACC responses and shortest for offset CAEPs. The high-frequency stimuli clearly elicited subcortical ASSRs, but smaller than those evoked by lower carrier frequency SAM tones. The 40-Hz ASSRs decreased with increasing carrier frequencies. Filtered clicks elicited larger ASSRs compared to high-frequency SAM tones, with the order being 40 > 160 > 80> 320 Hz ASSR for both stimulus types. Wavelet analysis revealed a clear interaction between detectable transient CAEPs and 40-Hz ASSRs in the time-frequency domain for SAM tones with a low carrier frequency.

This dataset was collected to study the functional consequences of age-related hearing loss for the auditory nerve, which carries acoustic information from the periphery to the central auditory system. Using high-impedance glass electrodes, raw voltage traces and spike times were recorded from more than one thousand single fibres of the auditory nerve of young-adult, middle-aged, and old Mongolian gerbils raised in a quiet environment. The dataset contains not only responses to simple acoustic stimuli to characterize the fibres, but also to more complex stimuli, such as speech logatomes in background noise and Schroeder-phase stimuli. A software toolbox is provided to search through the dataset, to plot various analysed outcomes, and to give insight into the analyses. This dataset may serve as a valuable resource to test further hypotheses about age-related hearing loss. Additionally, it can aid in optimizing available computational models of the auditory system, which can contribute to, or eventually even fully replace, animal experiments.

The P2 component of the auditory evoked potential is commonly thought to reflect acoustic stimulus properties as well as prior exposure to the materials, rather than change-related cortical activity. Here, we challenge this view by showing that the P2 is strongly increased in response to voice pitch changes with a stepwise pattern compared to changes in dynamic pitch contours typical for natural speech, and also reflects the magnitude of these pitch changes. Furthermore, it is demonstrated that neither the P2 nor any other component are affected by the harmonicity of the materials. Despite no prior exposure, artificially created inharmonic versions of the speech materials elicited similar activity throughout auditory cortex. This suggests that so-called harmonic template neurons observed in animal studies are either absent or do not exist in sufficient number in human auditory cortex to detect their activity extracranially. Crucially, both morphology and source reconstructions of the EEG data showed that the P2 appears to consist of two separate subcomponents. Whereas source activity for the “P2a” was strongest in right auditory cortex, the subsequent “P2b” included generators spread across auditory cortex and association areas, bilaterally. The two subcomponents thus likely reflect processing at different stages of the auditory pathway.

Differences in the timing and intensity of sounds arriving at the two ears provide fundamental binaural cues that help us localize and segregate sounds in the environment. Neural encoding of these cues is commonly represented asymmetrically in the cortex with stronger activation in the hemisphere contralateral to the perceived spatial location. Although advancing age is known to degrade the perception of binaural cues, less is known about how the neural representation of such cues is impacted by age. Here, we use electroencephalography (EEG) to investigate age-related changes in the hemispheric distribution of interaural time difference (ITD) encoding based on cortical auditory evoked potentials (CAEPs) and derived binaural interaction component (BIC) measures in ten younger and ten older normal-hearing adults. Sensor-level analyses of the CAEP and BIC showed age-related differences in global field power, where older listeners had significantly larger responses than younger for both binaural metrics. Source-level analyses showed hemispheric differences in auditory cortex activity for left and right lateralized stimuli in younger adults, consistent with a contralateral activation model for processing ITDs. Older adults, however, showed reduced hemispheric asymmetry across ITDs, despite having overall larger responses than younger adults. Further, when averaged across ITD condition to evaluate changes in cortical asymmetry over time, there was a significant shift in laterality corresponding to the peak components (P1, N1, P2) in the source waveform that also was affected by age. These novel results demonstrate across-hemisphere cortical dynamics during binaural temporal processing that are altered with advancing age.

To obtain combined behavioural and electrophysiological measures of pitch perception, we presented harmonic complexes, bandpass filtered to contain only high-numbered harmonics, to normal-hearing listeners. These stimuli resemble bandlimited pulse trains and convey pitch using a purely temporal code. A core set of conditions consisted of six stimuli with baseline pulse rates of 94, 188 and 280 pps, filtered into a HIGH (3365–4755 Hz) or VHIGH (7800–10,800 Hz) region, alternating with a 36% higher pulse rate. Brainstem and cortical processing were measured using the frequency following response (FFR) and auditory change complex (ACC), respectively. Behavioural rate change difference limens (DLs) were measured by requiring participants to discriminate between a stimulus that changed rate twice (up-down or down-up) during its 750-ms presentation from a constant-rate pulse train. FFRs revealed robust brainstem phase locking whose amplitude decreased with increasing rate. Moderate-sized but reliable ACCs were obtained in response to changes in purely temporal pitch and, like the psychophysical DLs, did not depend consistently on the direction of rate change or on the pulse rate for baseline rates between 94 and 280 pps. ACCs were larger and DLs lower for stimuli in the HIGH than in the VHGH region. We argue that the ACC may be a useful surrogate for behavioural measures of rate discrimination, both for normal-hearing listeners and for cochlear-implant users. We also showed that rate DLs increased markedly when the baseline rate was reduced to 48 pps, and compared the behavioural and electrophysiological findings to recent cat data obtained with similar stimuli and methods.

The human brain networks responsible for selectively listening to a voice amid other talkers remain to be clarified. The present study aimed to investigate relationships between cortical activity and performance in a speech-in-speech task, before (Experiment I) and after training-induced improvements (Experiment II). In Experiment I, 74 participants performed a speech-in-speech task while their cortical activity was measured using a functional near infrared spectroscopy (fNIRS) device. One target talker and one masker talker were simultaneously presented at three different target-to-masker ratios (TMRs): adverse, intermediate and favorable. Behavioral results show that performance may increase monotonically with TMR in some participants and failed to decrease, or even improved, in the adverse-TMR condition for others. On the neural level, an extensive brain network including the frontal (left prefrontal cortex, right dorsolateral prefrontal cortex and bilateral inferior frontal gyri) and temporal (bilateral auditory cortex) regions was more solicited by the intermediate condition than the two others. Additionally, bilateral frontal gyri and left auditory cortex activities were found to be positively correlated with behavioral performance in the adverse-TMR condition. In Experiment II, 27 participants, whose performance was the poorest in the adverse-TMR condition of Experiment I, were trained to improve performance in that condition. Results show significant performance improvements along with decreased activity in bilateral inferior frontal gyri, the right dorsolateral prefrontal cortex, the left inferior parietal cortex and the right auditory cortex in the adverse-TMR condition after training. Arguably, lower neural activity reflects higher efficiency in processing masker inhibition after speech-in-speech training. As speech-in-noise tasks also imply frontal and temporal regions, we suggest that regardless of the type of masking (speech or noise) the complexity of the task will prompt the implication of a similar brain network. Furthermore, the initial significant cognitive recruitment will be reduced following a training leading to an economy of cognitive resources.

Listening in an acoustically cluttered scene remains a difficult task for both machines and hearing-impaired listeners. Normal-hearing listeners accomplish this task with relative ease by segregating the scene into its constituent sound sources, then selecting and attending to a target source. An assistive listening device that mimics the biological mechanisms underlying this behavior may provide an effective solution for those with difficulty listening in acoustically cluttered environments (e.g., a cocktail party). Here, we present a binaural sound segregation algorithm based on a hierarchical network model of the auditory system. In the algorithm, binaural sound inputs first drive populations of neurons tuned to specific spatial locations and frequencies. The spiking response of neurons in the output layer are then reconstructed into audible waveforms via a novel reconstruction method. We evaluate the performance of the algorithm with a speech-on-speech intelligibility task in normal-hearing listeners. This two-microphone-input algorithm is shown to provide listeners with perceptual benefit similar to that of a 16-microphone acoustic beamformer. These results demonstrate the promise of this biologically inspired algorithm for enhancing selective listening in challenging multi-talker scenes.

A prospective cross-sectional design was used to characterize congenital bilateral sensorineural hearing loss (SNHL). The underlying material of >30,000 consecutively screened newborns comprised 11 subjects with nonprofound, alleged nonsyndromic, SNHL. Comprehensive audiological testing was performed at ≈11 years of age. Results showed symmetrical sigmoid-like median pure-tone thresholds (PTTs) reaching 50–60 dB HL. The congenital SNHL revealed recruitment, increased upward spread of masking, distortion product otoacoustic emission (DPOAE) dependent on PTT (≤60 dB HL), reduced auditory brainstem response (ABR) amplitude, and normal magnetic resonance imaging. Unaided recognition of speech in spatially separate competing speech (SCS) deteriorated with increasing uncomfortable loudness level (UCL), plausibly linked to reduced afferent signals. Most subjects demonstrated hearing aid (HA) benefit in a demanding laboratory listening situation. Questionnaires revealed HA benefit in real-world listening situations. This functional characterization should be important for the outline of clinical guidelines. The distinct relationship between DPOAE and PTT, up to the theoretical limit of cochlear amplification, and the low ABR amplitude remain to be elucidated. The significant relation between UCL and SCS has implications for HA-fitting. The fitting of HAs based on causes, mechanisms, and functional characterization of the SNHL may be an individualized intervention approach and deserves future research.

Auditory brainstem responses (ABRs) to broadband clicks are strongly affected by dyssynchrony, or “latency dispersion”, of their frequency-specific cochlear contributions. Optimized chirp stimuli, designed to compensate for cochlear dispersion, can afford substantial increase in broadband ABR amplitudes, particularly for the prominent wave-V deflection. Reports on the smaller wave I, however, which may be useful for measuring cochlear synaptopathy, have been mixed. This study aimed to test previous claims that ABR latency dispersion differs between waves I and V, and between males and females, and thus that using wave- and/or sex-tailored chirps may provide more reliable wave-I benefit. Using the derived-band technique, we measured responses from frequency-restricted (one-octave-wide) cochlear regions to energy-matched click and chirp stimuli. The derived-band responses’ latencies were used to assess any wave- and/or sex-related dispersion differences across bands, and their amplitudes, to evaluate any within-band dispersion differences. Our results suggest that sex-related dispersion difference within the lowest-frequency cochlear regions (< 1 kHz), where dispersion is generally greatest, may be a predominant driver of the often-reported sex difference in broadband ABR amplitude. At the same time, they showed no systematic dispersion difference between waves I and V. Instead, they suggest that reduced chirp benefit on wave I may arise as a result of chirp-induced desynchronization of on- and off-frequency responses generated at the same cochlear places, and resultant reduction in response contributions from higher-frequency cochlear regions, to which wave I is thought to be particularly sensitive.

We describe a scalp-recorded measure of tonotopic selectivity, the “cortical onset response” (COR) and compare the results between humans and cats. The COR results, in turn, were compared with psychophysical masked-detection thresholds obtained using similar stimuli and obtained from both species. The COR consisted of averaged responses elicited by 50-ms tone-burst probes presented at 1-s intervals against a continuous noise masker. The noise masker had a bandwidth of 1 or 1/8th octave, geometrically centred on 4000 Hz for humans and on 8000 Hz for cats. The probe frequency was either − 0.5, − 0.25, 0, 0.25 or 0.5 octaves re the masker centre frequency. The COR was larger for probe frequencies more distant from the centre frequency of the masker, and this effect was greater for the 1/8th-octave than for the 1-octave masker. This pattern broadly reflected the masked excitation patterns obtained psychophysically with similar stimuli in both species. However, the positive signal-to-noise ratio used to obtain reliable COR measures meant that some aspects of the data differed from those obtained psychophysically, in a way that could be partly explained by the upward spread of the probe’s excitation pattern. Our psychophysical measurements also showed that the auditory filter width obtained at 8000 Hz using notched-noise maskers was slightly wider in cat than previous measures from humans. We argue that although conclusions from COR measures differ in some ways from conclusions based on psychophysics, the COR measures provide an objective, noninvasive, valid measure of tonotopic selectivity that does not require training and that may be applied to acoustic and cochlear-implant experiments in humans and laboratory animals.

Hearing depends on glutamatergic synaptic transmission mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). AMPARs are tetramers, where inclusion of the GluA2 subunit reduces overall channel conductance and Ca 2+ permeability. Cochlear afferent synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs) contain the AMPAR subunits GluA2, 3, and 4. However, the tetrameric complement of cochlear AMPAR subunits is not known. It was recently shown in mice that chronic intracochlear delivery of IEM-1460, an antagonist selective for GluA2-lacking AMPARs [also known as Ca 2+ -permeable AMPARs (CP-AMPARs)], before, during, and after acoustic overexposure prevented both the trauma to ANF synapses and the ensuing reduction of cochlear nerve activity in response to sound. Surprisingly, baseline measurements of cochlear function before exposure were unaffected by chronic intracochlear delivery of IEM-1460. This suggested that cochlear afferent synapses contain GluA2-lacking CP-AMPARs alongside GluA2-containing Ca 2+ -impermeable AMPA receptors (CI-AMPARs), and that the former can be antagonized for protection while the latter remain conductive. Here, we investigated hearing function in the guinea pig during acute local or systemic delivery of CP-AMPAR antagonists. Acute intracochlear delivery of IEM-1460 or systemic delivery of IEM-1460 or IEM-1925 reduced the amplitude of the ANF compound action potential (CAP) significantly, for all tone levels and frequencies, by > 50% without affecting CAP thresholds or distortion product otoacoustic emissions (DPOAE). Following systemic dosing, IEM-1460 levels in cochlear perilymph were ~ 30% of blood levels, on average, consistent with pharmacokinetic properties predicting permeation of the compounds into the brain and ear. Both compounds were metabolically stable with half-lives >5 h in vitro , and elimination half-lives in vivo of 118 min (IEM-1460) and 68 min (IEM-1925). Heart rate monitoring and off-target binding assays suggest an enhanced safety profile for IEM-1925 over IEM-1460. Compound potency on CAP reduction (IC 50 ~ 73 μM IEM-1460) was consistent with a mixture of GluA2-lacking and GluA2-containing AMPARs. These data strongly imply that cochlear afferent synapses of the guinea pig contain GluA2-lacking CP-AMPARs. We propose these CP-AMPARs may be acutely antagonized with systemic dosing, to protect from glutamate excitotoxicity, while transmission at GluA2-containing AMPARs persists to mediate hearing during the protection.