A multi-channel EEG mini-cap can improve reliability for recording auditory brainstem responses in chinchillas.

BACKGROUND: Disabling hearing loss affects nearly 466 million people worldwide (World Health Organization). The auditory brainstem response (ABR) is the most common non-invasive clinical measure of evoked potentials, e.g., as an objective measure for universal newborn hearing screening. In research, the ABR is widely used for estimating hearing thresholds and cochlear synaptopathy in animal models of hearing loss. The ABR contains multiple waves representing neural activity across different peripheral auditory pathway stages, which arise within the first 10 ms after stimulus onset. Multi-channel (e.g., 32 or higher) caps provide robust measures for a wide variety of EEG applications for the study of human hearing. However, translational studies using preclinical animal models typically rely on only a few subdermal electrodes. NEW METHOD: We evaluated the feasibility of a 32-channel rodent EEG mini-cap for improving the reliability of ABR measures in chinchillas, a common model of human hearing. RESULTS: After confirming initial feasibility, a systematic experimental design tested five potential sources of variability inherent to the mini-cap methodology. We found each source of variance minimally affected mini-cap ABR waveform morphology, thresholds, and wave-1 amplitudes. COMPARISON WITH EXISTING METHOD: The mini-cap methodology was statistically more robust and less variable than the conventional subdermal-needle methodology, most notably when analyzing ABR thresholds. Additionally, fewer repetitions were required to produce a robust ABR response when using the mini-cap. CONCLUSIONS: These results suggest the EEG mini-cap can improve translational studies of peripheral auditory evoked responses. Future work will evaluate the potential of the mini-cap to improve the reliability of more centrally evoked (e.g., cortical) EEG responses.

Distorted Tonotopy Severely Degrades Neural Representations of Connected 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 connected speech sentence in noise from anesthetized male chinchillas with normal hearing (NH) or noise-induced hearing loss (NIHL). Our results demonstrated that temporal precision was not degraded following acoustic trauma, and furthermore that sharpness of cochlear frequency tuning was not the major factor affecting impaired peripheral coding of connected speech in noise. Rather, the loss of cochlear tonotopy, a hallmark of NH, contributed the most to both consonant-coding and vowel-coding degradations. 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.SIGNIFICANCE STATEMENT Difficulty understanding speech in noise is the primary complaint in audiology clinics and can leave people with sensorineural hearing loss (SNHL) suffering from communication difficulties that affect their professional, social, and family lives, as well as their mental health. We measured single-neuron responses from a preclinical SNHL animal model to characterize salient neural-coding deficits for naturally spoken speech in noise. We found the major mechanism affecting neural coding was not a commonly assumed factor, but rather a disruption of tonotopicity, the systematic mapping of acoustic frequency to cochlear place that is a hallmark of normal hearing. Because the degree of distorted tonotopy varies across hearing-loss etiologies, these results have important implications for precision audiology approaches to diagnosis and treatment of SNHL.

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 a set of peristimulus-time histograms computed from single-unit spike trains in response to polarity-alternating stimuli 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 confounded by 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.

Noninvasive Measures of Distorted Tonotopic Speech Coding Following Noise-Induced Hearing Loss.

Animal models of noise-induced hearing loss (NIHL) show a dramatic mismatch between cochlear characteristic frequency (CF, based on place of innervation) and the dominant response frequency in single auditory-nerve-fiber responses to broadband sounds (i.e., distorted tonotopy, DT). This noise trauma effect is associated with decreased frequency-tuning-curve (FTC) tip-to-tail ratio, which results from decreased tip sensitivity and enhanced tail sensitivity. Notably, DT is more severe for noise trauma than for metabolic (e.g., age-related) losses of comparable degree, suggesting that individual differences in DT may contribute to speech intelligibility differences in patients with similar audiograms. Although DT has implications for many neural-coding theories for real-world sounds, it has primarily been explored in single-neuron studies that are not viable with humans. Thus, there are no noninvasive measures to detect DT. Here, frequency following responses (FFRs) to a conversational speech sentence were recorded in anesthetized male chinchillas with either normal hearing or NIHL. Tonotopic sources of FFR envelope and temporal fine structure (TFS) were evaluated in normal-hearing chinchillas. Results suggest that FFR envelope primarily reflects activity from high-frequency neurons, whereas FFR-TFS receives broad tonotopic contributions. Representation of low- and high-frequency speech power in FFRs was also assessed. FFRs in hearing-impaired animals were dominated by low-frequency stimulus power, consistent with oversensitivity of high-frequency neurons to low-frequency power. These results suggest that DT can be diagnosed noninvasively. A normalized DT metric computed from speech FFRs provides a potential diagnostic tool to test for DT in humans. A sensitive noninvasive DT metric could be used to evaluate perceptual consequences of DT and to optimize hearing-aid amplification strategies to improve tonotopic coding for hearing-impaired listeners.

The upper frequency limit for the use of phase locking to code temporal fine structure in humans: A compilation of viewpoints.

The relative importance of neural temporal and place coding in auditory perception is still a matter of much debate. The current article is a compilation of viewpoints from leading auditory psychophysicists and physiologists regarding the upper frequency limit for the use of neural phase locking to code temporal fine structure in humans. While phase locking is used for binaural processing up to about 1500 Hz, there is disagreement regarding the use of monaural phase-locking information at higher frequencies. Estimates of the general upper limit proposed by the contributors range from 1500 to 10000 Hz. The arguments depend on whether or not phase locking is needed to explain psychophysical discrimination performance at frequencies above 1500 Hz, and whether or not the phase-locked neural representation is sufficiently robust at these frequencies to provide useable information. The contributors suggest key experiments that may help to resolve this issue, and experimental findings that may cause them to change their minds. This issue is of crucial importance to our understanding of the neural basis of auditory perception in general, and of pitch perception in particular.

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

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

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

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

Implications of within-fiber temporal coding for perceptual studies of F0 discrimination and discrimination of harmonic and inharmonic tone complexes.

Recent psychophysical studies suggest that normal-hearing (NH) listeners can use acoustic temporal-fine-structure (TFS) cues for accurately discriminating shifts in the fundamental frequency (F0) of complex tones, or equal shifts in all component frequencies, even when the components are peripherally unresolved. The present study quantified both envelope (ENV) and TFS cues in single auditory-nerve (AN) fiber responses (henceforth referred to as neural ENV and TFS cues) from NH chinchillas in response to harmonic and inharmonic complex tones similar to those used in recent psychophysical studies. The lowest component in the tone complex (i.e., harmonic rank N) was systematically varied from 2 to 20 to produce various resolvability conditions in chinchillas (partially resolved to completely unresolved). Neural responses to different pairs of TEST (F0 or frequency shifted) and standard or reference (REF) stimuli were used to compute shuffled cross-correlograms, from which cross-correlation coefficients representing the degree of similarity between responses were derived separately for TFS and ENV. For a given F0 shift, the dissimilarity (TEST vs. REF) was greater for neural TFS than ENV. However, this difference was stimulus-based; the sensitivities of the neural TFS and ENV metrics were equivalent for equal absolute shifts of their relevant frequencies (center component and F0, respectively). For the F0-discrimination task, both ENV and TFS cues were available and could in principle be used for task performance. However, in contrast to human performance, neural TFS cues quantified with our cross-correlation coefficients were unaffected by phase randomization, suggesting that F0 discrimination for unresolved harmonics does not depend solely on TFS cues. For the frequency-shift (harmonic-versus-inharmonic) discrimination task, neural ENV cues were not available. Neural TFS cues were available and could in principle support performance in this task; however, in contrast to human-listeners' performance, these TFS cues showed no dependence on N. We conclude that while AN-fiber responses contain TFS-related cues, which can in principle be used to discriminate changes in F0 or equal shifts in component frequencies of peripherally unresolved harmonics, performance in these two psychophysical tasks appears to be limited by other factors (e.g., central processing noise).

Sensorineural hearing loss amplifies neural coding of envelope information in the central auditory system of chinchillas.

People with sensorineural hearing loss often have substantial difficulty understanding speech under challenging listening conditions. Behavioral studies suggest that reduced sensitivity to the temporal structure of sound may be responsible, but underlying neurophysiological pathologies are incompletely understood. Here, we investigate the effects of noise-induced hearing loss on coding of envelope (ENV) structure in the central auditory system of anesthetized chinchillas. ENV coding was evaluated noninvasively using auditory evoked potentials recorded from the scalp surface in response to sinusoidally amplitude modulated tones with carrier frequencies of 1, 2, 4, and 8 kHz and a modulation frequency of 140 Hz. Stimuli were presented in quiet and in three levels of white background noise. The latency of scalp-recorded ENV responses was consistent with generation in the auditory midbrain. Hearing loss amplified neural coding of ENV at carrier frequencies of 2 kHz and above. This result may reflect enhanced ENV coding from the periphery and/or an increase in the gain of central auditory neurons. In contrast to expectations, hearing loss was not associated with a stronger adverse effect of increasing masker intensity on ENV coding. The exaggerated neural representation of ENV information shown here at the level of the auditory midbrain helps to explain previous findings of enhanced sensitivity to amplitude modulation in people with hearing loss under some conditions. Furthermore, amplified ENV coding may potentially contribute to speech perception problems in people with cochlear hearing loss by acting as a distraction from more salient acoustic cues, particularly in fluctuating backgrounds.

The use of confusion patterns to evaluate the neural basis for concurrent vowel identification.

Normal-hearing listeners take advantage of differences in fundamental frequency (F0) to segregate competing talkers. Computational modeling using an F0-based segregation algorithm and auditory-nerve temporal responses captures the gradual improvement in concurrent-vowel identification with increasing F0 difference. This result has been taken to suggest that F0-based segregation is the basis for this improvement; however, evidence suggests that other factors may also contribute. The present study further tested models of concurrent-vowel identification by evaluating their ability to predict the specific confusions made by listeners. Measured human confusions consisted of at most one to three confusions per vowel pair, typically from an error in only one of the two vowels. An improvement due to F0 difference was correlated with spectral differences between vowels; however, simple models based on acoustic and cochlear spectral patterns predicted some confusions not made by human listeners. In contrast, a neural temporal model was better at predicting listener confusion patterns. However, the full F0-based segregation algorithm using these neural temporal analyses was inconsistent across F0 difference in capturing listener confusions, being worse for smaller differences. The inability of this commonly accepted model to fully account for listener confusions suggests that other factors besides F0 segregation are likely to contribute.

Effects of sensorineural hearing loss on temporal coding of harmonic and inharmonic tone complexes in the auditory nerve.

Listeners with sensorineural hearing loss (SNHL) often show poorer thresholds for fundamental-frequency (F0) discrimination and poorer discrimination between harmonic and frequency-shifted (inharmonic) complex tones, than normal-hearing (NH) listeners-especially when these tones contain resolved or partially resolved components. It has been suggested that these perceptual deficits reflect reduced access to temporal-fine-structure (TFS) information and could be due to degraded phase locking in the auditory nerve (AN) with SNHL. In the present study, TFS and temporal-envelope (ENV) cues in single AN-fiber responses to band-pass-filtered harmonic and inharmonic complex tones were -measured in chinchillas with either normal-hearing or noise-induced SNHL. The stimuli were comparable to those used in recent psychophysical studies of F0 and harmonic/inharmonic discrimination. As in those studies, the rank of the center component was manipulated to produce -different resolvability conditions, different phase relationships (cosine and random phase) were tested, and background noise was present. Neural TFS and ENV cues were quantified using cross-correlation coefficients computed using shuffled cross correlograms between neural responses to REF (harmonic) and TEST (F0- or frequency-shifted) stimuli. In animals with SNHL, AN-fiber tuning curves showed elevated thresholds, broadened tuning, best-frequency shifts, and downward shifts in the dominant TFS response component; however, no significant degradation in the ability of AN fibers to encode TFS or ENV cues was found. Consistent with optimal-observer analyses, the results indicate that TFS and ENV cues depended only on the relevant frequency shift in Hz and thus were not degraded because phase locking remained intact. These results suggest that perceptual "TFS-processing" deficits do not simply reflect degraded phase locking at the level of the AN. To the extent that performance in F0- and harmonic/inharmonic discrimination tasks depend on TFS cues, it is likely through a more complicated (suboptimal) decoding mechanism, which may involve "spatiotemporal" (place-time) neural representations.

Auditory-nerve responses predict pitch attributes related to musical consonance-dissonance for normal and impaired hearing.

Human listeners prefer consonant over dissonant musical intervals and the perceived contrast between these classes is reduced with cochlear hearing loss. Population-level activity of normal and impaired model auditory-nerve (AN) fibers was examined to determine (1) if peripheral auditory neurons exhibit correlates of consonance and dissonance and (2) if the reduced perceptual difference between these qualities observed for hearing-impaired listeners can be explained by impaired AN responses. In addition, acoustical correlates of consonance-dissonance were also explored including periodicity and roughness. Among the chromatic pitch combinations of music, consonant intervals/chords yielded more robust neural pitch-salience magnitudes (determined by harmonicity/periodicity) than dissonant intervals/chords. In addition, AN pitch-salience magnitudes correctly predicted the ordering of hierarchical pitch and chordal sonorities described by Western music theory. Cochlear hearing impairment compressed pitch salience estimates between consonant and dissonant pitch relationships. The reduction in contrast of neural responses following cochlear hearing loss may explain the inability of hearing-impaired listeners to distinguish musical qualia as clearly as normal-hearing individuals. Of the neural and acoustic correlates explored, AN pitch salience was the best predictor of behavioral data. Results ultimately show that basic pitch relationships governing music are already present in initial stages of neural processing at the AN level.

Precursor effects on behavioral estimates of frequency selectivity and gain in forward masking.

The experiments presented in this paper explore the hypothesis that cochlear gain is reduced, in a frequency-specific manner, over the course of a sound (called a "precursor") which was designed to activate the medial olivo-cochlear reflex (MOCR). Psychophysical tuning curves (PTCs) and off-frequency growth of masking (GOM) functions were measured with two precursors. The on-frequency precursor condition, which was hypothesized to activate the MOCR at the signal frequency, produced a PTC with a lower best frequency in all subjects consistent with less gain. This same condition produced a GOM function with less gain and an elevated compression breakpoint. The data were analyzed with two models. The gain-reduction model, which assumed a change in the basilar membrane input-output function, was superior at predicting the data relative to a model of additivity of masking.