Animal models of hidden hearing loss: Does auditory-nerve-fiber loss cause real-world listening difficulties?

Afferent innervation of the cochlea by the auditory nerve declines during aging and potentially after sound overexposure, producing the common pathology known as cochlear synaptopathy. Auditory-nerve-fiber loss is difficult to detect with the clinical audiogram and has been proposed to cause 'hidden hearing loss' including impaired speech-in-noise perception. While evidence that auditory-nerve-fiber loss causes hidden hearing loss in humans is controversial, behavioral animal models hold promise to rigorously test this hypothesis because neural lesions can be induced and histologically validated. Here, we review recent animal behavioral studies on the impact of auditory-nerve-fiber loss on perception in a range of species. We first consider studies of tinnitus and hyperacusis inferred from acoustic startle reflexes, followed by a review of operant-conditioning studies of the audiogram, temporal integration for tones of varying duration, temporal resolution of gaps in noise, and tone-in-noise detection. Studies quantifying the audiogram show that tone-in-quiet sensitivity is unaffected by auditory-nerve-fiber loss unless neural lesions exceed 80%, at which point large deficits are possible. Changes in other aspects of perception, which were typically investigated for moderate-to-severe auditory-nerve-fiber loss of 50-70%, appear heterogeneous across studies and might be small compared to impairment caused by hair-cell pathologies. Future studies should pursue recent findings that behavioral sensitivity to brief tones and silent gaps in noise may be particularly vulnerable to auditory-nerve-fiber loss. Furthermore, aspects of auditory perception linked to central inhibition and fine neural response timing, such as modulation masking release and spatial hearing, may be productive directions for further animal behavioral research.

Normal Tone-In-Noise Sensitivity in Trained Budgerigars despite Substantial Auditory-Nerve Injury: No Evidence of Hidden Hearing Loss.

Loss of auditory-nerve (AN) afferent cochlear innervation is a prevalent human condition that does not affect audiometric thresholds and therefore remains largely undetectable with standard clinical tests. AN loss is widely expected to cause hearing difficulties in noise, known as "hidden hearing loss," but support for this hypothesis is controversial. Here, we used operant conditioning procedures to examine the perceptual impact of AN loss on behavioral tone-in-noise (TIN) sensitivity in the budgerigar (Melopsittacus undulatus; of either sex), an avian animal model with complex hearing abilities similar to humans. Bilateral kainic acid (KA) infusions depressed compound AN responses by 40-70% without impacting otoacoustic emissions or behavioral tone sensitivity in quiet. Surprisingly, animals with AN damage showed normal thresholds for tone detection in noise (0.1 ± 1.0 dB compared to control animals; mean difference ± SE), even under a challenging roving-level condition with random stimulus variation across trials. Furthermore, decision-variable correlations (DVCs) showed no difference for AN-damaged animals in their use of energy and envelope cues to perform the task. These results show that AN damage has less impact on TIN detection than generally expected, even under a difficult roving-level condition known to impact TIN detection in individuals with sensorineural hearing loss (SNHL). Perceptual deficits could emerge for different perceptual tasks or with greater AN loss but are potentially minor compared with those caused by SNHL.SIGNIFICANCE STATEMENT Loss of auditory-nerve (AN) cochlear innervation is a common problem in humans that does not affect audiometric thresholds on a clinical hearing test. AN loss is widely expected to cause hearing problems in noise, known as "hidden hearing loss," but existing studies are controversial. Here, using an avian animal model with complex hearing abilities similar to humans, we examined for the first time the impact of an experimentally induced AN lesion on behavioral tone sensitivity in noise. Surprisingly, AN-lesioned animals showed no difference in hearing performance in noise or detection strategy compared with controls. These results show that perceptual deficits from AN damage are smaller than generally expected, and potentially minor compared with those caused by sensorineural hearing loss (SNHL).

Midbrain-Level Neural Correlates of Behavioral Tone-in-Noise Detection: Dependence on Energy and Envelope Cues.

Hearing in noise is a problem often assumed to depend on encoding of energy level by channels tuned to target frequencies, but few studies have tested this hypothesis. The present study examined neural correlates of behavioral tone-in-noise (TIN) detection in budgerigars (Melopsittacus undulatus, either sex), a parakeet species with human-like behavioral sensitivity to many simple and complex sounds. Behavioral sensitivity to tones in band-limited noise was assessed using operant-conditioning procedures. Neural recordings were made in awake animals from midbrain-level neurons in the inferior colliculus, the first processing stage of the ascending auditory pathway with pronounced rate-based encoding of stimulus amplitude modulation. Budgerigar TIN detection thresholds were similar to human thresholds across the full range of frequencies (0.5-4 kHz) and noise levels (45-85 dB SPL) tested. Also as in humans, thresholds were minimally affected by a challenging roving-level condition with random variation in background-noise level. Many midbrain neurons showed a decreasing response rate as TIN signal-to-noise ratio (SNR) was increased by elevating the tone level, a pattern attributable to amplitude-modulation tuning in these cells and the fact that higher SNR tone-plus-noise stimuli have flatter amplitude envelopes. TIN thresholds of individual neurons were as sensitive as behavioral thresholds under most conditions, perhaps surprisingly even when the unit's characteristic frequency was tuned an octave or more away from the test frequency. A model that combined responses of two cell types enhanced TIN sensitivity in the roving-level condition. These results highlight the importance of midbrain-level envelope encoding and off-frequency neural channels for hearing in noise.SIGNIFICANCE STATEMENT Detection of target sounds in noise is often assumed to depend on energy-level encoding by neural processing channels tuned to the target frequency. In contrast, we found that tone-in-noise sensitivity in budgerigars was often greatest in midbrain neurons not tuned to the test frequency, underscoring the potential importance of off-frequency channels for perception. Furthermore, the results highlight the importance of envelope processing for hearing in noise, especially under challenging conditions with random variation in background noise level over time.

Divergent Auditory Nerve Encoding Deficits Between Two Common Etiologies of Sensorineural Hearing Loss.

Speech intelligibility can vary dramatically between individuals with similar clinically defined severity of hearing loss based on the audiogram. These perceptual differences, despite equal audiometric-threshold elevation, are often assumed to reflect central-processing variations. Here, we compared peripheral-processing in auditory nerve (AN) fibers of male chinchillas between two prevalent hearing loss etiologies: metabolic hearing loss (MHL) and noise-induced hearing loss (NIHL). MHL results from age-related reduction of the endocochlear potential due to atrophy of the stria vascularis. MHL in the present study was induced using furosemide, which provides a validated model of age-related MHL in young animals by reversibly inhibiting the endocochlear potential. Effects of MHL on peripheral processing were assessed using Wiener-kernel (system identification) analyses of single AN fiber responses to broadband noise, for direct comparison to previously published AN responses from animals with NIHL. Wiener-kernel analyses show that even mild NIHL causes grossly abnormal coding of low-frequency stimulus components. In contrast, for MHL the same abnormal coding was only observed with moderate to severe loss. For equal sensitivity loss, coding impairment was substantially less severe with MHL than with NIHL, probably due to greater preservation of the tip-to-tail ratio of cochlear frequency tuning with MHL compared with NIHL rather than different intrinsic AN properties. Differences in peripheral neural coding between these two pathologies-the more severe of which, NIHL, is preventable-likely contribute to individual speech perception differences. Our results underscore the need to minimize noise overexposure and for strategies to personalize diagnosis and treatment for individuals with sensorineural hearing loss.SIGNIFICANCE STATEMENT Differences in speech perception ability between individuals with similar clinically defined severity of hearing loss are often assumed to reflect central neural-processing differences. Here, we demonstrate for the first time that peripheral neural processing of complex sounds differs dramatically between the two most common etiologies of hearing loss. Greater processing impairment with noise-induced compared with an age-related (metabolic) hearing loss etiology may explain heightened speech perception difficulties in people overexposed to loud environments. These results highlight the need for public policies to prevent noise-induced hearing loss, an entirely avoidable hearing loss etiology, and for personalized strategies to diagnose and treat sensorineural hearing loss.

Sensorineural Hearing Loss Diminishes Use of Temporal Envelope Cues: Evidence From Roving-Level Tone-in-Noise Detection.

OBJECTIVES: The objective of our study is to understand how listeners with and without sensorineural hearing loss (SNHL) use energy and temporal envelope cues to detect tones in noise. Previous studies of low-frequency tone-in-noise detection have shown that when energy cues are made less reliable using a roving-level paradigm, thresholds of listeners with normal hearing (NH) are only slightly increased. This result is consistent with studies demonstrating the importance of temporal envelope cues for masked detection. In contrast, roving-level detection thresholds are more elevated in listeners with SNHL at the test frequency, suggesting stronger weighting of energy cues. The present study extended these tests to a wide range of frequencies and stimulus levels. The authors hypothesized that individual listeners with SNHL use energy and temporal envelope cues differently for masked detection at different frequencies and levels, depending on the degree of hearing loss. DESIGN: Twelve listeners with mild to moderate SNHL and 12 NH listeners participated. Tone-in-noise detection thresholds at 0.5, 1, 2, and 4 kHz in 1/3 octave bands of simultaneously gated Gaussian noise were obtained using a novel, two-part tracking paradigm. A track refers to the sequence of trials in an adaptive test procedure; the signal to noise ratio was the tracked variable. Each part of the track consisted of a two-alternative, two-interval, forced-choice procedure. The initial portion of the track estimated detection threshold using a fixed masker level. When the track continued, stimulus levels were randomly varied over a 20-dB rove range (±10 dB with respect to mean masker level), and a second threshold was estimated. Rove effect (RE) was defined as the difference between thresholds for the fixed- and roving-level tests. The size of the RE indicated how strongly a listener weighted energy-based cues for masked detection. Participants were tested at one to three masker levels per frequency, depending on audibility. RESULTS: Across all stimulus frequencies and levels, NH listeners had small REs (≈1 dB), whereas listeners with SNHL typically had larger REs. Some listeners with SNHL had larger REs at higher frequencies, where pure-tone audiometric thresholds were typically elevated. RE did not vary significantly with masker level for either group. Increased RE for the SNHL group was consistent with simulations in which energy cues were more heavily weighted than envelope cues. CONCLUSIONS: Tone-in-noise detection thresholds in NH listeners were typically elevated only slightly by the roving-level paradigm at any frequency or level tested, consistent with the primary use of level-independent cues, such as temporal envelope cues that are conveyed by fluctuations in neural responses. In comparison, thresholds of listeners with SNHL were more affected by the roving-level paradigm, suggesting stronger weighting of energy cues. For listeners with SNHL, the largest RE was observed at 4000 Hz, for which pure-tone audiometric thresholds were most elevated. Specifically, RE size at 4000 Hz was significantly correlated with higher pure-tone audiometric thresholds at the same frequency, after controlling for the effect of age. Future studies will explore strategies for restoring or enhancing neural fluctuation cues that may lead to improved hearing in noise for listeners with SNHL.

Identifying cues for tone-in-noise detection using decision variable correlation in the budgerigar (Melopsittacus undulatus).

Previous studies evaluated cues for masked tone detection using reproducible noise waveforms. Human results founded on this approach suggest that tone detection is based on combined energy and envelope (ENV) cues, but detection cues in nonhuman species are less clear. Decision variable correlation (DVC) was used to evaluate tone-in-noise detection cues in the budgerigar, an avian species with human-like behavioral sensitivity to many complex sounds. DVC quantifies a model's ability to predict trial-by-trial variance in behavioral responses. Budgerigars were behaviorally conditioned to detect 500-Hz tones in wideband (WB; 100-3000 Hz) and narrowband (NB; 452-552 Hz) noise. Behavioral responses were obtained using a single-interval, two-alternative discrimination task and two-down, one-up adaptive tracking procedures. Tone-detection thresholds in WB noise were higher than human thresholds, putatively due to broader peripheral frequency tuning, whereas NB thresholds were within ∼1 dB of human results. Budgerigar average hit and false-alarm rates across noise waveforms were consistent, highly correlated across subjects, and correlated to human results. Trial-by-trial behavioral results in NB noise were best explained by a model combining energy and ENV cues. In contrast, WB results were better predicted by ENV-based or multiple-channel energy detector models. These results suggest that budgerigars and humans use similar cues for tone-in-noise detection.

Challenging One Model With Many Stimuli: Simulating Responses in the Inferior Colliculus.

Existing models to explain human psychophysics or neural responses are typically designed for a specific stimulus type and often fail for other stimuli. The ultimate goal for a neural model is to simulate responses to many stimuli, which may provide better insights into neural mechanisms. We tested the ability of modified same-frequency inhibition-excitation models for inferior colliculus neurons to simulate individual neuron responses to both amplitude-modulated sounds and tone-in-noise stimuli. Modifications to the model were guided by receptive fields computed with 2nd-order Wiener kernel analysis. This approach successfully simulated many individual neurons' responses to different types of stimuli. Other neurons suggest limitations and future directions for modeling efforts.

Distorted Tonotopic Coding of Temporal Envelope and Fine Structure with Noise-Induced Hearing Loss.

People with cochlear hearing loss have substantial difficulty understanding speech in real-world listening environments (e.g., restaurants), even with amplification from a modern digital hearing aid. Unfortunately, a disconnect remains between human perceptual studies implicating diminished sensitivity to fast acoustic temporal fine structure (TFS) and animal studies showing minimal changes in neural coding of TFS or slower envelope (ENV) structure. Here, we used general system-identification (Wiener kernel) analyses of chinchilla auditory nerve fiber responses to Gaussian noise to reveal pronounced distortions in tonotopic coding of TFS and ENV following permanent, noise-induced hearing loss. In basal fibers with characteristic frequencies (CFs) >1.5 kHz, hearing loss introduced robust nontonotopic coding (i.e., at the wrong cochlear place) of low-frequency TFS, while ENV responses typically remained at CF. As a consequence, the highest dominant frequency of TFS coding in response to Gaussian noise was 2.4 kHz in noise-overexposed fibers compared with 4.5 kHz in control fibers. Coding of ENV also became nontonotopic in more pronounced cases of cochlear damage. In apical fibers, more classical hearing-loss effects were observed, i.e., broadened tuning without a significant shift in best frequency. Because these distortions and dissociations of TFS/ENV disrupt tonotopicity, a fundamental principle of auditory processing necessary for robust signal coding in background noise, these results have important implications for understanding communication difficulties faced by people with hearing loss. Further, hearing aids may benefit from distinct amplification strategies for apical and basal cochlear regions to address fundamentally different coding deficits. SIGNIFICANCE STATEMENT: Speech-perception problems associated with noise overexposure are pervasive in today's society, even with modern digital hearing aids. Unfortunately, the underlying physiological deficits in neural coding remain unclear. Here, we used innovative system-identification analyses of auditory nerve fiber responses to Gaussian noise to uncover pronounced distortions in coding of rapidly varying acoustic temporal fine structure and slower envelope cues following noise trauma. Because these distortions degrade and diminish the tonotopic representation of temporal acoustic features, a fundamental principle of auditory processing, the results represent a critical advancement in our understanding of the physiological bases of communication disorders. The detailed knowledge provided by this work will help guide the design of signal-processing strategies aimed at alleviating everyday communication problems for people with hearing loss.

Formant-frequency discrimination of synthesized vowels in budgerigars (Melopsittacus undulatus) and humans.

Vowels are complex sounds with four to five spectral peaks known as formants. The frequencies of the two lowest formants, F1and F2, are sufficient for vowel discrimination. Behavioral studies show that many birds and mammals can discriminate vowels. However, few studies have quantified thresholds for formant-frequency discrimination. The present study examined formant-frequency discrimination in budgerigars (Melopsittacus undulatus) and humans using stimuli with one or two formants and a constant fundamental frequency of 200 Hz. Stimuli had spectral envelopes similar to natural speech and were presented with random level variation. Thresholds were estimated for frequency discrimination of F1, F2, and simultaneous F1 and F2 changes. The same two-down, one-up tracking procedure and single-interval, two-alternative task were used for both species. Formant-frequency discrimination thresholds were as sensitive in budgerigars as in humans and followed the same patterns across all conditions. Thresholds expressed as percent frequency difference were higher for F1 than for F2, and were unchanged between stimuli with one or two formants. Thresholds for simultaneous F1 and F2 changes indicated that discrimination was based on combined information from both formant regions. Results were consistent with previous human studies and show that budgerigars provide an exceptionally sensitive animal model of vowel feature discrimination.

Neural correlates of behavioral amplitude modulation sensitivity in the budgerigar midbrain.

Amplitude modulation (AM) is a crucial feature of many communication signals, including speech. Whereas average discharge rates in the auditory midbrain correlate with behavioral AM sensitivity in rabbits, the neural bases of AM sensitivity in species with human-like behavioral acuity are unexplored. Here, we used parallel behavioral and neurophysiological experiments to explore the neural (midbrain) bases of AM perception in an avian speech mimic, the budgerigar (Melopsittacus undulatus). Behavioral AM sensitivity was quantified using operant conditioning procedures. Neural AM sensitivity was studied using chronically implanted microelectrodes in awake, unrestrained birds. Average discharge rates of multiunit recording sites in the budgerigar midbrain were insufficient to explain behavioral sensitivity to modulation frequencies <100 Hz for both tone- and noise-carrier stimuli, even with optimal pooling of information across recording sites. Neural envelope synchrony, in contrast, could explain behavioral performance for both carrier types across the full range of modulation frequencies studied (16-512 Hz). The results suggest that envelope synchrony in the budgerigar midbrain may underlie behavioral sensitivity to AM. Behavioral AM sensitivity based on synchrony in the budgerigar, which contrasts with rate-correlated behavioral performance in rabbits, raises the possibility that envelope synchrony, rather than average discharge rate, might also underlie AM perception in other species with sensitive AM detection abilities, including humans. These results highlight the importance of synchrony coding of envelope structure in the inferior colliculus. Furthermore, they underscore potential benefits of devices (e.g., midbrain implants) that evoke robust neural synchrony.

Habitat-related differences in auditory processing of complex tones and vocal signal properties in four songbirds.

We examined temporal processing of harmonic tone complexes in two woodland species (tufted titmice and white-breasted nuthatches) and two open-habitat species (house sparrows and white-crowned sparrows). Envelope and fine-structure processing were quantified using the envelope following response (EFR) and frequency following response (FFR). We predicted stronger EFRs in the open-habitat species based on broader auditory filters and greater amplitude modulation of vocal signals in this group. We predicted stronger FFRs in woodland species based on narrower auditory filters. As predicted, EFR amplitude was generally greatest in the open habitat species. FFR amplitude, in contrast, was greatest in white-crowned sparrows with no clear difference between habitats. This result cannot be fully explained by species differences in audiogram shape and might instead reflect greater acoustic complexity of songs in the white-crowned sparrow. Finally, we observed stronger FFRs in woodland species when tones were broadcast with the next higher harmonic in the complex. Thus, species such as nuthatches that have songs with strong harmonics may process these sounds using enhanced spectral processing instead of enhanced amplitude-envelope processing. The results suggest coevolution between signal design and temporal processing of complex signals and underscore the need to study auditory processing with a diversity of signals.

Normal behavioral discrimination of envelope statistics in budgerigars with kainate-induced cochlear synaptopathy.

Cochlear synaptopathy is a common pathology in humans associated with aging and potentially sound overexposure. Synaptopathy is widely expected to cause "hidden hearing loss," including difficulty perceiving speech in noise, but support for this hypothesis is controversial. Here in budgerigars (Melopsittacus undulatus), we evaluated the impact of long-term cochlear synaptopathy on behavioral discrimination of Gaussian noise (GN) and low-noise noise (LNN) signals processed to have a flatter envelope. Stimuli had center frequencies of 1-3kHz, 100-Hz bandwidth, and were presented at sensation levels (SLs) from 10 to 30dB. We reasoned that narrowband, low-SL stimuli of this type should minimize spread of excitation across auditory-nerve fibers, and hence might reveal synaptopathy-related defects if they exist. Cochlear synaptopathy was induced without hair-cell injury using kainic acid (KA). Behavioral threshold tracking experiments characterized the minimum stimulus duration above which animals could reliably discriminate between LNN and GN. Budgerigar thresholds for LNN-GN discrimination ranged from 40 to 60ms at 30dB SL, were similar across frequencies, and increased for lower SLs. Notably, animals with long-term 39-77% estimated synaptopathy performed similarly to controls, requiring on average a ∼7.5% shorter stimulus duration (-0.7±1.0dB; mean difference ±SE) for LNN-GN discrimination. Decision-variable correlation analyses of detailed behavioral response patterns showed that individual animals relied on envelope cues to discriminate LNN and GN, with lesser roles of FM and energy cues; no difference was found between KA-exposed and control groups. These results suggest that long-term cochlear synaptopathy does not impair discrimination of low-level signals with different envelope statistics.

Otoacoustic emissions predict cochlear-nerve but not behavioral frequency tuning in an avian vocal-communication specialist.

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 is a parakeet species with human-like behavioral sensitivity to many sounds and the capacity to mimic speech. Multiple studies show that budgerigars exhibit a perceptual "auditory fovea" with sharpest behavioral frequency tuning at mid frequencies from 3.5-4 kHz, in contrast to the typical pattern of monotonically increasing tuning sharpness for higher characteristic frequencies. 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 for higher frequencies, in contrast to the behavioral pattern. Thus, SFOAE-based tuning in budgerigars accurately predicted cochlear tuning, and both measures aligned with typical patterns of cochlear frequency tuning in other species. Given divergent behavioral tuning in the budgerigars, which could reflect specializations for central processing of masked signals, these results highlight the value of SFOAEs for estimating cochlear tuning and caution against direct inference of cochlear tuning from behavioral results.

Outer hair cells stir cochlear fluids.

Recent observations regarding the non-selective action of outer hair cells contradict frequency-selective cochlear amplification. We hypothesized that active outer hair cells drive cochlear fluid circulation. The hypothesis was tested by delivering a neurotoxin, kainic acid, to the 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 indicate that broadband outer-hair-cell action is for cochlear fluid circulation.

Sensitivity to direction and velocity of fast frequency chirps in the inferior colliculus of awake rabbit.

Neurons in the mammalian inferior colliculus (IC) are sensitive to the velocity (speed and direction) of fast frequency chirps contained in Schroeder-phase harmonic complexes (SCHR). However, IC neurons are also sensitive to stimulus periodicity, a prominent feature of SCHR stimuli. Here, to disentangle velocity sensitivity from periodicity tuning, we introduced a novel stimulus consisting of aperiodic random chirps. Extracellular, single-unit recordings were made in the IC of Dutch-belted rabbits in response to both SCHR and aperiodic chirps. Rate-velocity functions were constructed from aperiodic-chirp responses and compared to SCHR rate profiles, revealing interactions between stimulus periodicity and neural velocity sensitivity. A generalized linear model analysis demonstrated that periodicity tuning influences SCHR response rates more strongly than velocity sensitivity. Principal component analysis of rate-velocity functions revealed that neurons were more often sensitive to the direction of lower-velocity chirps and were less often sensitive to the direction of higher-velocity chirps. Overall, these results demonstrate that sensitivity to chirp velocity is common in the IC. Harmonic sounds with complex phase spectra, such as speech and music, contain chirps, and velocity sensitivity would shape IC responses to these sounds.

Histological Correlates of Auditory Nerve Injury from Kainic Acid in the Budgerigar (Melopsittacus undulatus).

PURPOSE: Loss of auditory nerve afferent synapses with cochlear hair cells, called cochlear synaptopathy, is a common pathology in humans caused by aging and noise overexposure. The perceptual consequences of synaptopathy in isolation from other cochlear pathologies are still unclear. Animal models provide an effective approach to resolve uncertainty regarding the physiological and perceptual consequences of auditory nerve loss, because neural lesions can be induced and readily quantified. The budgerigar, a parakeet species, has recently emerged as an animal model for synaptopathy studies based on its capacity for vocal learning and ability to behaviorally discriminate simple and complex sounds with acuity similar to humans. Kainic acid infusions in the budgerigar produce a profound reduction of compound auditory nerve responses, including wave I of the auditory brainstem response, without impacting physiological hair cell measures. These results suggest selective auditory nerve damage. However, histological correlates of neural injury from kainic acid are still lacking. METHODS: We quantified the histological effects caused by intracochlear infusion of kainic acid (1 mM; 2.5 µL), and evaluated correlations between the histological and physiological assessments of auditory nerve status. RESULTS: Kainic acid infusion in budgerigars produced pronounced loss of neural auditory nerve soma (60% on average) in the cochlear ganglion, and of peripheral axons, at time points 2 or more months following injury. The hair cell epithelium was unaffected by kainic acid. Neural loss was significantly correlated with reduction of compound auditory nerve responses and auditory brainstem response wave I. CONCLUSION: Compound auditory nerve responses and wave I provide a useful index of cochlear synaptopathy in this animal model.

Mechanisms of masking by Schroeder-phase harmonic tone complexes in the budgerigar (Melopsittacus undulatus).

Schroeder-phase harmonic tone complexes can have a flat temporal envelope and rising or falling instantaneous-frequency sweeps within F0 periods, depending on the phase-scaling parameter C. Human tone-detection thresholds in a concurrent Schroeder masker are 10-15 dB lower for positive C values (rising frequency sweeps) compared to negative (falling sweeps), potentially due to cochlear mechanics, though this hypothesis remains controversial. Birds provide an interesting model for studies of Schroeder masking because many species produce vocalizations containing frequency sweeps. Prior behavioral studies in birds suggest less behavioral threshold difference between maskers with opposite C values than in humans, but focused on low masker F0s and did not explore neural mechanisms. We performed behavioral Schroeder-masking experiments in budgerigars (Melopsittacus undulatus) using a wide range of masker F0 and C values. Signal frequency was 2800 Hz. Neural recordings from the midbrain characterized encoding of behavioral stimuli in awake animals. Behavioral thresholds increased with increasing masker F0 and showed minimal difference between opposite C values, consistent with prior budgerigar studies. Midbrain recordings showed prominent temporal and rate-based encoding of Schroeder F0, and in many cases, marked asymmetry in Schroeder responses between C polarities. Neural thresholds for Schroeder-masked tone detection were often based on a response decrement compared to the masker alone, consistent with prominent modulation tuning in midbrain neurons, and were generally similar between opposite C values. The results highlight the likely importance of envelope cues in Schroeder masking and show that differences in supra-threshold Schroeder responses do not necessarily result in neural threshold differences.

Two measures of temporal resolution in brown-headed cowbirds (Molothrus ater).

Studies of auditory temporal resolution in birds have traditionally examined processing capabilities by assessing behavioral discrimination of sounds varying in temporal structure. Here, temporal resolution of the brown-headed cowbird (Molothrus ater) was measured using two auditory evoked potential (AEP)-based methods: auditory brainstem responses (ABRs) to paired clicks and envelope following responses (EFRs) to amplitude-modulated tones. The basic patterns observed in cowbirds were similar to those found in other songbird species, suggesting similar temporal processing capabilities. The amplitude of the ABR to the second click was less than that of the first click at inter-click intervals less than 10 ms, and decreased to 30% at an interval of 1 ms. EFR amplitude was generally greatest at modulation frequencies from 335 to 635 Hz and decreased at higher and lower modulation frequencies. Compared to data from terrestrial mammals these results support recent behavioral findings of enhanced temporal resolution in birds. General agreement between these AEP results and behaviorally based studies suggests that AEPs can provide a useful assessment of temporal resolution in wild bird species.

Responses to dichotic tone-in-noise stimuli in the inferior colliculus.

Human listeners are more sensitive to tones embedded in diotic noise when the tones are out-of-phase at the two ears (N0Sπ) than when they are in-phase (N0S0). The difference between the tone-detection thresholds for these two conditions is referred to as the binaural masking level difference (BMLD) and reflects a benefit of binaural processing. Detection in the N0Sπ condition has been explained in modeling studies by changes in interaural correlation (IAC), but this model has only been directly tested physiologically for low frequencies. Here, the IAC-based hypothesis for binaural detection was examined across a wide range of frequencies and masker levels using recordings in the awake rabbit inferior colliculus (IC). IAC-based cues were strongly correlated with neural responses to N0Sπ stimuli. Additionally, average rate-based thresholds were calculated for both N0S0 and N0Sπ conditions. The rate-based neural BMLD at 500 Hz matched rabbit behavioral data, but the trend of neural BMLDs across frequency differed from that of humans.

Tone in Noise Detection in Children with a History of Temporary Conductive Hearing Loss.

Children with a history of temporary conductive hearing loss (CHL) during early development may show long-term impairments in auditory processes that persist after restoration of normal audiometric hearing thresholds. Tones in noise provide a simplified paradigm for studying hearing in noise. Prior research has shown that adults with sensorineural hearing loss may alter their listening strategy to use single-channel energy cues for tone-in-noise (TIN) detection rather than rove-resistant envelope or spectral profile cues. Our objective was to determine the effect of early CHL on TIN detection in healthy children compared to controls. Children ages 4-7 years, with and without a history of CHL due to otitis media with effusion (OME) before age 3 years, participated in a two-alternative forced choice TIN detection task. Audiometric thresholds were normal at the time of testing. Thresholds for detection of a 1000 Hz tone were measured in fixed-level noise and in roving-level noise that made single-channel energy cues unreliable. Participants included 23 controls and 23 with a history of OME-related CHL. TIN thresholds decreased with increasing age across participants. Children in both groups showed similar TIN sensitivity and little or no threshold elevation in the roving-level condition compared to fixed-level tracks, consistent with use of rove-resistant cues. In contrast to older listeners with sensorineural hearing loss, there was no detectable change in TIN sensitivity with roving level for children with a history of OME-related CHL.