Biology subjects

Heinz, M. G.

Publications and source records attributed to Heinz, M. G..

13 recordsLinked to original sources

bioRxiv2026

SEDATION DIFFERENTIALLY AFFECTS DISTORTION-PRODUCT AND STIMULUS-FREQUENCY OTOACOUSTIC EMISSIONS IN CHINCHILLAS

Purpose: Otoacoustic emissions (OAEs) are used to assess outer hair cell (OHC) function. Clinical interpretation of OAE responses, however, is often limited to a present/absent binary since both physiological factors and measurement variability affect the measured OAE amplitude. Prior work showed elevated OAE responses in sedated compared to awake chinchillas, pointing to the potential influence of the medial olivocochlear (MOC) efferents on amplitudes, but this finding is inconsistent across species and OAE type. Here, we aimed to further investigate the effect of anesthesia on distortion- and reflection-type emissions in chinchillas using swept stimuli and more reliable calibration methods. Methods: Swept distortion-product (DP) and stimulus-frequency (SF) OAEs were measured in chinchillas with and without ketamine/xylazine sedation. Stimuli were presented using in-ear forward pressure level calibrations. DPOAE and SFOAE amplitudes and estimated Qerb from SFOAE group delays were compared across the two conditions. Results: We found that low-frequency DPOAE amplitudes were elevated when animals were sedated. The difference in SFOAE amplitudes was more variable across animals but appeared mildly reduced in sedated animals. Qerb estimates were slightly higher in sedated animals at some frequencies. The effect of sedation was not different across sexes. Conclusion: Taken together, these findings suggest that sedation impacts OAE measurements in chinchillas. MOC modulation could account for the present findings and differences across species. For diagnostic precision, OAE responses should be considered in the context of not only intrinsic OHC function but also extrinsic physiological processes that can modulate OHCs.

physiology↗

bioRxiv2026

Ototoxicity-induced inner-hair-cell specific dysfunction degrades neurometric modulation detection in noise without altering peripheral tuning

Sensorineural hearing loss can result from different pathologies, but the primary diagnostic method is a threshold-based audiogram, which is insensitive to some forms of cochlear dysfunction. Individuals may experience difficulty understanding speech in noise despite normal audiometric thresholds. Because most cochlear insults damage both inner (IHCs) and outer hair cells (OHCs), the contribution of IHC dysfunction to auditory-nerve coding has been difficult to isolate. We used the IHC-selective ototoxicity of carboplatin in chinchillas to examine how IHC dysfunction, with preserved OHC function, affects temporal-envelope coding in auditory-nerve fibers (ANFs). Carboplatin produced 10 to 20% IHC loss with stereocilia damage in surviving IHCs, while OHC-dependent measures such as DPOAEs and ANF thresholds were unchanged. Suprathreshold ABR wave 1 was reduced, whereas wave 5 was preserved, suggesting central compensation. Both spontaneous and driven firing rates decreased following exposure. Mean vector strength to amplitude-modulated tones was unchanged, but response variability increased. Neurometric analysis and mutual information showed degraded AM detection in carboplatin-exposed fibers, an effect accounted for by reduced driven rate (i.e., normalizing spike counts across groups removed the group difference). Background noise degraded AM coding similarly in both groups. Pooled-neurometric modeling showed that population redundancy compensated for impaired fibers in quiet, but not in noise, where carboplatin-exposed pools remained worse. These findings indicate that IHC dysfunction degrades envelope coding by reducing neural output rather than by altering temporal synchrony. This study suggests IHC dysfunction is a phenotype consistent with "hidden hearing loss" (but distinct from cochlear synaptopathy), and motivates suprathreshold clinical assays.

neuroscience↗

bioRxiv2024

Impact of Reduced Spectral Resolution on Temporal-Coherence-Based Source Segregation

1.Hearing-impaired listeners struggle to understand speech in noise, even when using cochlear implants (CIs) or hearing aids. Successful listening in noisy environments depends on the brains ability to organize a mixture of sound sources into distinct perceptual streams (i.e., source segregation). In normal-hearing listeners, temporal coherence of sound fluctuations across frequency channels supports this process by promoting grouping of elements belonging to a single acoustic source. We hypothesized that reduced spectral resolution--a hallmark of both electric/CI (from current spread) and acoustic (from broadened tuning) hearing with sensorineural hearing loss--degrades segregation based on temporal coherence. This is because reduced frequency resolution decreases the likelihood that a single sound source dominates the activity driving any specific channel; concomitantly, it increases the correlation in activity across channels. Consistent with our hypothesis, predictions from a physiologically plausible model of temporal-coherence-based segregation suggest that CI current spread reduces comodulation masking release (CMR; a correlate of temporal-coherence processing) and speech intelligibility in noise. These predictions are consistent with our behavioral data with simulated CI listening. Our model also predicts smaller CMR with increasing levels of outer-hair-cell damage. These results suggest that reduced spectral resolution relative to normal hearing impairs temporal-coherence-based segregation and speech-in-noise outcomes.

neuroscience↗

bioRxiv2023

Induced Alpha And Beta Electroencephalographic Rhythms Covary With Single-Trial Speech Intelligibility In Competition

1.Neurophysiological studies suggest that intrinsic brain oscillations influence sensory processing, especially of rhythmic stimuli like speech. Prior work suggests that brain rhythms may mediate perceptual grouping and selective attention to speech amidst competing sound, as well as more linguistic aspects of speech processing like predictive coding. However, we know of no prior studies that have directly tested, at the single-trial level, whether brain oscillations relate to speech-in-noise outcomes. Here, we combined electroencephalography while simultaneously measuring intelligibility of spoken sentences amidst two different interfering sounds: multi-talker babble or speech-shaped noise. We find that induced parieto-occipital alpha (7-15 Hz; thought to modulate attentional focus) and frontal beta (13-30 Hz; associated with maintenance of the current sensorimotor state and predictive coding) oscillations covary with trial-wise percent-correct scores; importantly, alpha and beta power provide significant independent contributions to predicting single-trial behavioral outcomes. These results can inform models of speech processing and guide noninvasive measures to index different neural processes that together support complex listening.

neuroscience↗

bioRxiv2022

Estimation of cochlear frequency selectivity using a convolution model of forward-masked compound action potentials

Frequency selectivity is a fundamental property of the peripheral auditory system; however, the invasiveness of auditory nerve (AN) experiments limits its study in the human ear. Compound action potentials (CAPs) associated with forward-masking have been suggested as an alternative means to assess cochlear frequency selectivity. Previous methods relied on an empirical comparison of AN and CAP tuning curves in animal models, arguably not taking full advantage of the information contained in forward-masked CAPs. In this work, we seek to provide a direct estimate of the quality factor characterizing AN frequency tuning using many forward-masked CAP responses. The method is based on a convolution model of the CAP that takes into account the masking of AN populations induced by notched-noise maskers with various notch widths and attenuations. The model produces masking patterns that, once convolved by a unitary response, predict forward-masked CAP waveforms. Model parameters, including those characterizing frequency selectivity, are fine-tuned by minimizing waveform prediction errors across the different masking conditions, yielding robust estimates. The method was applied to click-evoked CAPs at the round window of anesthetized chinchillas. The estimated quality factor Q10 as a function of center frequency is shown to closely match the average quality factor obtained from AN-fiber tuning curves, without the need for an empirical correction factor. Beyond the estimation of frequency selectivity, the proposed model proves to be accurate in predicting forward-masked CAP responses, and therefore could be extended to study more complex aspects of cochlear signal processing using a similar experimental approach.

neuroscience↗

bioRxiv2022

Enhanced envelope coding following acoustic trauma is detrimental to neural coding of speech in noise

People with hearing loss struggle understanding speech in noisy backgrounds. Speech-intelligibility models highlight the importance of slow-varying envelopes of speech and noise; however, the physiological basis of impaired perception remains unclear. We provide neurophysiological evidence that, although acoustic trauma enhances both speech and noise envelopes, disruptions in cochlear tonotopicity preferentially enhance neural responses to noise in noisy speech. These results provide mechanistic insights into everyday-communication challenges created by hearing loss.

neuroscience↗

bioRxiv2021

Speech categorization reveals the role of early-stage temporal-coherence processing in auditory scene analysis

Temporal coherence of sound fluctuations across spectral channels is thought to aid auditory grouping and scene segregation. Although prior studies on the neural bases of temporal-coherence processing focused mostly on cortical contributions, neurophysiological evidence suggests that temporal-coherence-based scene analysis may start as early as the cochlear nucleus (i.e., the first auditory region supporting cross-channel processing over a wide frequency range). Accordingly, we hypothesized that aspects of temporal-coherence processing that could be realized in early auditory areas may shape speech understanding in noise. We then explored whether physiologically plausible computational models could account for results from a behavioral experiment that measured consonant categorization in different masking conditions. We tested whether within-channel masking of target-speech modulations predicted consonant confusions across the different conditions, and whether predicted performance was improved by adding across-channel temporal-coherence processing mirroring the computations known to exist in the cochlear nucleus. Consonant confusions provide a rich characterization of error patterns in speech categorization, and are thus crucial for rigorously testing models of speech perception; however, to the best of our knowledge, they have not been utilized in prior studies of scene analysis. We find that within-channel modulation masking can reasonably account for category confusions, but that it fails when temporal fine structure (TFS) cues are unavailable. However, the addition of across-channel temporal-coherence processing significantly improves confusion predictions across all tested conditions. Our results suggest that temporal-coherence processing strongly shapes speech understanding in noise, and that physiological computations that exist early along the auditory pathway may contribute to this process.

neuroscience↗

bioRxiv2021

Temporal fine structure influences voicing confusions for consonant identification in multi-talker babble

To understand the mechanisms of speech perception in everyday listening environments, it is important to elucidate the relative contributions of different acoustic cues in transmitting phonetic content. Previous studies suggest that the envelope of speech in different frequency bands conveys most speech content, while the temporal fine structure (TFS) can aid in segregating target speech from background noise. However, the role of TFS in conveying phonetic content beyond what envelopes convey for intact speech in complex acoustic scenes is poorly understood. The present study addressed this question using online psychophysical experiments to measure the identification of consonants in multi-talker babble for intelligibility-matched intact and 64-channel envelope-vocoded stimuli. Consonant confusion patterns revealed that listeners had a greater tendency in the vocoded (versus intact) condition to be biased toward reporting that they heard an unvoiced consonant, despite envelope and place cues being largely preserved. This result was replicated when babble instances were varied across independent experiments, suggesting that TFS conveys voicing information beyond what is conveyed by envelopes for intact speech in babble. Given that multi-talker babble is a masker that is ubiquitous in everyday environments, this finding has implications for the design of assistive listening devices such as cochlear implants.

neuroscience↗

bioRxiv2021

Distorted tonotopy severely degrades neural representations of natural speech in noise following acoustic trauma

Listeners with sensorineural hearing loss (SNHL) struggle to understand speech, especially in noise, despite audibility compensation. These real-world suprathreshold deficits are hypothesized to arise from degraded frequency tuning and reduced temporal-coding precision; however, peripheral neurophysiological studies testing these hypotheses have been largely limited to in-quiet artificial vowels. Here, we measured single auditory-nerve-fiber responses to a natural speech sentence in noise from anesthetized chinchillas with normal hearing (NH) or noise-induced hearing loss (NIHL). Our results demonstrate that temporal precision was not degraded, and broader tuning was not the major factor affecting peripheral coding of natural speech in noise. Rather, the loss of cochlear tonotopy, a hallmark of normal hearing, had the most significant effects (both on vowels and consonants). Because distorted tonotopy varies in degree across etiologies (e.g., noise exposure, age), these results have important implications for understanding and treating individual differences in speech perception for people suffering from SNHL.

neuroscience↗

bioRxiv2021

Modulation masking and fine structure shape neural envelope coding to predict speech intelligibility across diverse listening conditions

A fundamental question in the neuroscience of everyday communication is how scene acoustics shape the neural processing of attended speech sounds and in turn impact speech intelligibility. While it is well known that the temporal envelopes in target speech are important for intelligibility, how the neural encoding of target-speech envelopes is influenced by background sounds or other acoustic features of the scene is unknown. Here, we combine human electroencephalography with simultaneous intelligibility measurements to address this key gap. We find that the neural envelope-domain signal-to-noise ratio in target-speech encoding, which is shaped by masker modulations, predicts intelligibility over a range of strategically chosen realistic listening conditions unseen by the predictive model. This provides neurophysiological evidence for modulation masking. Moreover, using high-resolution vocoding to carefully control peripheral envelopes, we show that target-envelope coding fidelity in the brain depends not only on envelopes conveyed by the cochlea, but also on the temporal fine structure (TFS), which supports scene segregation. Our results are consistent with the notion that temporal coherence of sound elements across envelopes and/or TFS influences scene analysis and attentive selection of a target sound. Our findings also inform speech-intelligibility models and technologies attempting to improve real-world speech communication.

neuroscience↗

bioRxiv2021

Cross-Species Experiments Reveal Widespread Cochlear Neural Damage in Normal Hearing

Animal models suggest that cochlear afferent nerve endings may be more vulnerable than sensory hair cells to damage from acoustic overexposure and aging, but that such damage cannot be detected in standard clinical audiometry. Co-ordinated experiments in at-risk humans and a chinchilla model using two distinct physiological assays suggest that cochlear neural damage exists even in populations without clinically recognized hearing loss.

neuroscience↗

bioRxiv2020

Spectrally specific temporal analyses of spike-train responses to complex sounds: A unifying framework

Significant scientific and translational questions remain in auditory neuroscience surrounding the neural correlates of perception. Relating perceptual and neural data collected from humans can be useful; however, human-based neural data are typically limited to evoked far-field responses, which lack anatomical and physiological specificity. Laboratory-controlled preclinical animal models offer the advantage of comparing single-unit and evoked responses from the same animals. This ability provides opportunities to develop invaluable insight into proper interpretations of evoked responses, which benefits both basic-science studies of neural mechanisms and translational applications, e.g., diagnostic development. However, these comparisons have been limited by a disconnect between the types of spectrotemporal analyses used with single-unit spike trains and evoked responses, which results because these response types are fundamentally different (point-process versus continuous-valued signals) even though the responses themselves are related. Here, we describe a unifying framework to study temporal coding of complex sounds that allows spike-train and evoked-response data to be analyzed and compared using the same advanced signal-processing techniques. The framework uses alternating-polarity peristimulus-time histograms computed from single-unit spike trains to allow advanced spectral analyses of both slow (envelope) and rapid (temporal fine structure) response components. Demonstrated benefits include: (1) novel spectrally specific temporal-coding measures that are less corrupted by analysis distortions due to hair-cell transduction, synaptic rectification, and neural stochasticity compared to previous metrics, e.g., the correlogram peak-height, (2) spectrally specific analyses of spike-train modulation coding (magnitude and phase), which can be directly compared to modern perceptually based models of speech intelligibility (e.g., that depend on modulation filter banks), and (3) superior spectral resolution in analyzing the neural representation of nonstationary sounds, such as speech and music. This unifying framework significantly expands the potential of preclinical animal models to advance our understanding of the physiological correlates of perceptual deficits in real-world listening following sensorineural hearing loss. Author summaryDespite major technological and computational advances, we remain unable to match human auditory perception using machines, or to restore normal-hearing communication for those with sensorineural hearing loss. An overarching reason for these limitations is that the neural correlates of auditory perception, particularly for complex everyday sounds, remain largely unknown. Although neural responses can be measured in humans noninvasively and compared with perception, these evoked responses lack the anatomical and physiological specificity required to reveal underlying neural mechanisms. Single-unit spike-train responses can be measured from preclinical animal models with well-specified pathology; however, the disparate response types (point-process versus continuous-valued signals) have limited application of the same advanced signal-processing analyses to single-unit and evoked responses required for direct comparison. Here, we fill this gap with a unifying framework for analyzing both spike-train and evoked neural responses using advanced spectral analyses of both the slow and rapid response components that are known to be perceptually relevant for speech and music, particularly in challenging listening environments. Numerous benefits of this framework are demonstrated here, which support its potential to advance the translation of spike-train data from animal models to improve clinical diagnostics and technological development for real-world listening.

neuroscience↗

bioRxiv2019

Non-Invasive Assays of Cochlear Synaptopathy -- Candidates and Considerations

Studies in multiple species, including in post-mortem human tissue, have shown that normal aging and/or acoustic overexposure can lead to a significant loss of afferent synapses innervating the cochlea. Hypothetically, this cochlear synaptopathy can lead to perceptual deficits in challenging environments and can contribute to central neural effects such as tinnitus. However, because cochlear synaptopathy can occur without any measurable changes in audiometric thresholds, synaptopathy can remain hidden from standard clinical diagnostics. To understand the perceptual sequelae of synaptopathy and to evaluate the efficacy of emerging therapies, sensitive and specific non-invasive measures at the individual patient level need to be established. Pioneering experiments in specific mice strains have helped identify many candidate assays. These include auditory brainstem responses, the middle-ear muscle reflex, envelope-following responses, and extended high-frequency audiograms. Unfortunately, because these non-invasive measures can be also affected by extraneous factors other than synaptopathy, their application and interpretation in humans is not straightforward. Here, we systematically examine six extraneous factors through a series of interrelated human experiments aimed at understanding their effects. Using strategies that may help mitigate the effects of such extraneous factors, we then show that these suprathreshold physiological assays exhibit across-individual correlations with each other indicative of contributions from a common physiological source consistent with cochlear synaptopathy. Finally, we discuss the application of these assays to two key outstanding questions, and discuss some barriers that still remain.

neuroscience↗