Single Auditory Nerve Fibers Research Articles

Effects of Age on Responses of Principal Cells of the Mouse Anteroventral Cochlear Nucleus in Quiet and Noise.

Older listeners often report difficulties understanding speech in noisy environments. It is important to identify where in the auditory pathway hearing-in-noise deficits arise to develop appropriate therapies. We tested how encoding of sounds is affected by masking noise at early stages of the auditory pathway by recording responses of principal cells in the anteroventral cochlear nucleus (AVCN) of aging CBA/CaJ and C57BL/6J mice in vivo. Previous work indicated that masking noise shifts the dynamic range of single auditory nerve fibers (ANFs), leading to elevated tone thresholds. We hypothesized that such threshold shifts could contribute to increased hearing-in-noise deficits with age if susceptibility to masking increased in AVCN units. We tested this by recording the responses of AVCN principal neurons to tones in the presence and absence of masking noise. Surprisingly, we found that masker-induced threshold shifts decreased with age in primary-like units and did not change in choppers. In addition, spontaneous activity decreased in primary-like and chopper units of old mice, with no change in dynamic range or tuning precision. In C57 mice, which undergo early-onset hearing loss, units showed similar changes in threshold and spontaneous rate at younger ages, suggesting they were related to hearing loss and not simply aging. These findings suggest that sound information carried by AVCN principal cells remains largely unchanged with age. Therefore, hearing-in-noise deficits may result from other changes during aging, such as distorted across-channel input from the cochlea and changes in sound coding at later stages of the auditory pathway.

Frequency selectivity in monkey auditory nerve studied with suprathreshold multicomponent stimuli

Data from non-human primates can help extend observations from non-primate species to humans. Here we report measurements on the auditory nerve of macaque monkeys in the context of a controversial topic important to human hearing. A range of techniques have been used to examine the claim, which is not generally accepted, that human frequency tuning is sharper than traditionally thought, and sharper than in commonly used animal models. Data from single auditory-nerve fibers occupy a pivotal position to examine this claim, but are not available for humans. A previous study reported sharper tuning in auditory-nerve fibers of macaque relative to the cat. A limitation of these and other single-fiber data is that frequency selectivity was measured with tonal threshold-tuning curves, which do not directly assess spectral filtering and whose shape is sharpened by cochlear nonlinearity. Our aim was to measure spectral filtering with wideband suprathreshold stimuli in the macaque auditory nerve. We obtained responses of single nerve fibers of anesthetized macaque monkeys and cats to a suprathreshold, wideband, multicomponent stimulus designed to allow characterization of spectral filtering at any cochlear locus. Quantitatively the differences between the two species are smaller than in previous studies, but consistent with these studies the filters obtained show a trend of sharper tuning in macaque, relative to the cat, for fibers in the basal half of the cochlea. We also examined differences in group delay measured on the phase data near the characteristic frequency versus in the low-frequency tail. The phase data are consistent with the interpretation of sharper frequency tuning in monkey in the basal half of the cochlea. We conclude that use of suprathreshold, wide-band stimuli supports the interpretation of sharper frequency selectivity in macaque nerve fibers relative to the cat, although the difference is less marked than apparent from the assessment with tonal threshold-based data.

Altered neural encoding of vowels in noise does not affect behavioral vowel discrimination in gerbils with age-related hearing loss.

Understanding speech in a noisy environment, as opposed to speech in quiet, becomes increasingly more difficult with increasing age. Using the quiet-aged gerbil, we studied the effects of aging on speech-in-noise processing. Specifically, behavioral vowel discrimination and the encoding of these vowels by single auditory-nerve fibers were compared, to elucidate some of the underlying mechanisms of age-related speech-in-noise perception deficits. Young-adult and quiet-aged Mongolian gerbils, of either sex, were trained to discriminate a deviant naturally-spoken vowel in a sequence of vowel standards against a speech-like background noise. In addition, we recorded responses from single auditory-nerve fibers of young-adult and quiet-aged gerbils while presenting the same speech stimuli. Behavioral vowel discrimination was not significantly affected by aging. For both young-adult and quiet-aged gerbils, the behavioral discrimination between /eː/ and /iː/ was more difficult to make than /eː/ vs. /aː/ or /iː/ vs. /aː/, as evidenced by longer response times and lower d' values. In young-adults, spike timing-based vowel discrimination agreed with the behavioral vowel discrimination, while in quiet-aged gerbils it did not. Paradoxically, discrimination between vowels based on temporal responses was enhanced in aged gerbils for all vowel comparisons. Representation schemes, based on the spectrum of the inter-spike interval histogram, revealed stronger encoding of both the fundamental and the lower formant frequencies in fibers of quiet-aged gerbils, but no qualitative changes in vowel encoding. Elevated thresholds in combination with a fixed stimulus level, i.e., lower sensation levels of the stimuli for old individuals, can explain the enhanced temporal coding of the vowels in noise. These results suggest that the altered auditory-nerve discrimination metrics in old gerbils may mask age-related deterioration in the central (auditory) system to the extent that behavioral vowel discrimination matches that of the young adults.

A Computational Model of a Single Auditory Nerve Fiber for Electric-Acoustic Stimulation

Cochlear implant (CI) recipients with preserved acoustic low-frequency hearing in the implanted ear are a growing group among traditional CI users who benefit from hybrid electric-acoustic stimulation (EAS). However, combined ipsilateral electric and acoustic stimulation also introduces interactions between the two modalities that can affect the performance of EAS users. A computational model of a single auditory nerve fiber that is excited by EAS was developed to study the interaction between electric and acoustic stimulation. Two existing models of sole electric or acoustic stimulation were coupled to simulate responses to combined EAS. Different methods of combining both models were implemented. In the coupled model variant, the refractoriness of the simulated fiber leads to suppressive interaction between electrically evoked and acoustically evoked spikes as well as spontaneous activity. The second model variant is an uncoupled EAS model without electric-acoustic interaction. By comparing predictions between the coupled and the noninteracting EAS model, it was possible to infer electric-acoustic interaction at the level of the auditory nerve. The EAS model was used to simulate fiber populations with realistic inter-unit variability, where each unit was represented by the single-fiber model. Predicted thresholds and dynamic ranges, spike rates, latencies, jitter, and vector strengths were compared to empirical data. The presented EAS model provides a framework for future studies of peripheral electric-acoustic interaction.

Auditory Nerve Fiber Discrimination and Representation of Naturally-Spoken Vowels in Noise.

To understand how vowels are encoded by auditory nerve (AN) fibers, a number of representation schemes have been suggested that extract the vowel’s formant frequencies from AN-fiber spiking patterns. The current study aims to apply and compare these schemes for AN-fiber responses to naturally-spoken vowels in a speech-shaped background noise. Responses to three vowels were evaluated; based on behavioral experiments in the same species, two of these were perceptually difficult to discriminate from each other (/e/ vs /i/), and one was perceptually easy to discriminate from the other two (/a:/). Single-unit AN fibers were recorded from ketamine/xylazine-anesthetized Mongolian gerbils of either sex (n = 8). First, single-unit discrimination between the three vowels was studied. Compared with the perceptually easy discriminations, the average spike timing-based discrimination values were significantly lower for the perceptually difficult vowel discrimination. This was not true for an average rate-based discrimination metric, the rate d-prime (d’). Consistently, spike timing-based representation schemes, plotting the temporal responses of all recorded units as a function of their best frequency (BF), i.e., dominant component schemes, average localized interval rate, and fluctuation profiles, revealed representation of the vowel’s formant frequencies, whereas no such representation was apparent in the rate-based excitation pattern. Making use of perceptual discrimination data, this study reveals that discrimination difficulties of naturally-spoken vowels in speech-shaped noise originate peripherally and can be studied in the spike timing patterns of single AN fibers.

Temporal Correlates to Monaural Edge Pitch in the Distribution of Interspike Interval Statistics in the Auditory Nerve.

Pitch is a perceptual attribute enabling perception of melody. There is no consensus regarding the fundamental nature of pitch and its underlying neural code. A stimulus which has received much interest in psychophysical and computational studies is noise with a sharp spectral edge. High-pass (HP) or low-pass (LP) noise gives rise to a pitch near the edge frequency (monaural edge pitch; MEP). The simplicity of this stimulus, combined with its spectral and autocorrelation properties, make it an interesting stimulus to examine spectral versus temporal cues that could underly its pitch. We recorded responses of single auditory nerve (AN) fibers in chinchilla to MEP-stimuli varying in edge frequency. Temporal cues were examined with shuffled autocorrelogram (SAC) analysis. Correspondence between the population’s dominant interspike interval and reported pitch estimates was poor. A fuller analysis of the population interspike interval distribution, which incorporates not only the dominant but all intervals, results in good matches with behavioral results, but not for the entire range of edge frequencies that generates pitch. Finally, we also examined temporal structure over a slower time scale, intermediate between average firing rate and interspike intervals, by studying the SAC envelope. We found that, in response to a given MEP stimulus, this feature also systematically varies with edge frequency, across fibers with different characteristic frequency (CF). Because neural mechanisms to extract envelope cues are well established, and because this cue is not limited by coding of stimulus fine-structure, this newly identified slower temporal cue is a more plausible basis for pitch than cues based on fine-structure.

Cues to monaural edge pitch in single auditory nerve fibers

The spectral edge of a bandlimited noise can create a pitch sensation, called “edge pitch,” which is slightly mismatched to the edge frequency. This pitch is usually speculated to reflect neural lateral inhibition but could also reflect temporal cues. We looked for such cues recording responses of single auditory nerve fibers in the anesthetized chinchilla to edge pitch stimuli. For every stimulus, we compute shuffled autocorrelograms for all recorded fibers and pool them in a population interval distribution (PID) from which we obtain the most common interval. We also quantify the slower “envelope” fluctuations in firing resulting from cochlear bandpass filtering of the bandlimited noise stimulus. Single fibers shows systematic temporal changes related to the spectral edge of the stimulus when it does not cover the fiber's frequency filter. Across the population of fibers, the estimated pitch based on the dominant interspike interval shows trends that are similar, qualitatively and quantitatively, to those observed behaviorally. Slower envelope fluctuations also systematically vary with the relationship of edge frequency to fiber CF, and are another potential temporal cue to the presence of the edge frequency. We conclude that temporal cues to edge-pitch are present in the auditory nerve at multiple time scales.

Temporal Coding of Single Auditory Nerve Fibers Is Not Degraded in Aging Gerbils.

People suffering from age-related hearing loss typically present with deficits in temporal processing tasks. Temporal processing deficits have also been shown in single-unit studies at the level of the auditory brainstem, midbrain, and cortex of aged animals. In this study, we explored whether temporal coding is already affected at the level of the input to the central auditory system. Single-unit auditory nerve fiber recordings were obtained from 41 Mongolian gerbils of either sex, divided between young, middle-aged, and old gerbils. Temporal coding quality was evaluated as vector strength in response to tones at best frequency, and by constructing shuffled and cross-stimulus autocorrelograms, and reverse correlations, from responses to 1 s noise bursts at 10-30 dB sensation level (dB above threshold). At comparable sensation levels, all measures showed that temporal coding was not altered in auditory nerve fibers of aging gerbils. Furthermore, both temporal fine structure and envelope coding remained unaffected. However, spontaneous rates were decreased in aging gerbils. Importantly, despite elevated pure tone thresholds, the frequency tuning of auditory nerve fibers was not affected. These results suggest that age-related temporal coding deficits arise more centrally, possibly due to a loss of auditory nerve fibers (or their peripheral synapses) but not due to qualitative changes in the responses of remaining auditory nerve fibers. The reduced spontaneous rate and elevated thresholds, but normal frequency tuning, of aged auditory nerve fibers can be explained by the well known reduction of endocochlear potential due to strial dysfunction in aged gerbils.SIGNIFICANCE STATEMENT As our society ages, age-related hearing deficits become ever more prevalent. Apart from decreased hearing sensitivity, elderly people often suffer from a reduced ability to communicate in daily settings, which is thought to be caused by known age-related deficits in auditory temporal processing. The current study demonstrated, using several different stimuli and analysis techniques, that these putative temporal processing deficits are not apparent in responses of single-unit auditory nerve fibers of quiet-aged gerbils. This suggests that age-related temporal processing deficits may develop more central to the auditory nerve, possibly due to a reduced population of active auditory nerve fibers, which will be of importance for the development of treatments for age-related hearing disorders.

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.

Mammalian behavior and physiology converge to confirm sharper cochlear tuning in humans

Frequency analysis of sound by the cochlea is the most fundamental property of the auditory system. Despite its importance, the resolution of this frequency analysis in humans remains controversial. The controversy persists because the methods used to estimate tuning in humans are indirect and have not all been independently validated in other species. Some data suggest that human cochlear tuning is considerably sharper than that of laboratory animals, while others suggest little or no difference between species. We show here in a single species (ferret) that behavioral estimates of tuning bandwidths obtained using perceptual masking methods, and objective estimates obtained using otoacoustic emissions, both also employed in humans, agree closely with direct physiological measurements from single auditory-nerve fibers. Combined with human behavioral data, this outcome indicates that the frequency analysis performed by the human cochlea is of significantly higher resolution than found in common laboratory animals. This finding raises important questions about the evolutionary origins of human cochlear tuning, its role in the emergence of speech communication, and the mechanisms underlying our ability to separate and process natural sounds in complex acoustic environments.

Measurements and models of auditory nerve spike rate and timing to electrical stimulation

Physiological measurements of the response of auditory nerve (AN) fibers to electrical stimulation from a cochlear implant (CI) have in general exhibited much higher maximal entrainment rates and higher temporal precision than is observed for acoustical stimulation. However, it appears that this superior rate coding in the AN for electrical stimulation does not translate to better coding of rate in the midbrain or for the percept of temporal pitch. Similarly, the enhanced temporal precision for electrical stimulation does not lead to improved coding of interaural timing differences. In this talk, I will review physiological data and computational model simulations that indicate that the superior spike rate and timing representation for CI stimulation may only hold when considering the response of some single AN fibers to repeated identical stimuli. In fact, there is a large heterogeneity in spiking responses that can change dramatically as a function of stimulus current level. A multi-compartmental computational model will be used to demonstrate how the electrode- fiber geometry and the membrane biophysics could be contributing to these phenomena. I will also discuss the implications of the likely population response of the AN to CI stimulation for brainstem processing. [Work supported by NSERC Discovery Grant 261736.]

RIM-Binding Protein 2 Promotes a Large Number of CaV1.3 Ca2+-Channels and Contributes to Fast Synaptic Vesicle Replenishment at Hair Cell Active Zones.

Ribbon synapses of inner hair cells (IHCs) mediate high rates of synchronous exocytosis to indefatigably track the stimulating sound with sub-millisecond precision. The sophisticated molecular machinery of the inner hair cell active zone realizes this impressive performance by enabling a large number of synaptic voltage-gated CaV1.3 Ca2+-channels, their tight coupling to synaptic vesicles (SVs) and fast replenishment of fusion competent SVs. Here we studied the role of RIM-binding protein 2 (RIM-BP2)—a multidomain cytomatrix protein known to directly interact with Rab3 interacting molecules (RIMs), bassoon and CaV1.3—that is present at the inner hair cell active zones. We combined confocal and stimulated emission depletion (STED) immunofluorescence microscopy, electron tomography, patch-clamp and confocal Ca2+-imaging, as well as auditory systems physiology to explore the morphological and functional effects of genetic RIM-BP2 disruption in constitutive RIM-BP2 knockout mice. We found that RIM-BP2 (1) positively regulates the number of synaptic CaV1.3 channels and thereby facilitates synaptic vesicle release and (2) supports fast synaptic vesicle recruitment after readily releasable pool (RRP) depletion. However, Ca2+-influx—exocytosis coupling seemed unaltered for readily releasable SVs. Recordings of auditory brainstem responses (ABR) and of single auditory nerve fiber firing showed that RIM-BP2 disruption results in a mild deficit of synaptic sound encoding.

A Model of Electrically Stimulated Auditory Nerve Fiber Responses with Peripheral and Central Sites of Spike Generation

A computational model of cat auditory nerve fiber (ANF) responses to electrical stimulation is presented. The model assumes that (1) there exist at least two sites of spike generation along the ANF and (2) both an anodic (positive) and a cathodic (negative) charge in isolation can evoke a spike. A single ANF is modeled as a network of two exponential integrate-and-fire point-neuron models, referred to as peripheral and central axons of the ANF. The peripheral axon is excited by the cathodic charge, inhibited by the anodic charge, and exhibits longer spike latencies than the central axon; the central axon is excited by the anodic charge, inhibited by the cathodic charge, and exhibits shorter spike latencies than the peripheral axon. The model also includes subthreshold and suprathreshold adaptive feedback loops which continuously modify the membrane potential and can account for effects of facilitation, accommodation, refractoriness, and spike-rate adaptation in ANF. Although the model is parameterized using data for either single or paired pulse stimulation with monophasic rectangular pulses, it correctly predicts effects of various stimulus pulse shapes, stimulation pulse rates, and level on the neural response statistics. The model may serve as a framework to explore the effects of different stimulus parameters on psychophysical performance measured in cochlear implant listeners.

Low-frequency bias tone suppression of auditory-nerve responses to low-level clicks and tones

We used low-frequency “bias” tones (BT's) to explore whether click and tone responses are affected in the same way by cochlear active processes. In nonlinear systems the responses to clicks are not always simply related to the responses to tones. Cochlear amplifier gain depends on the incremental slope of the outer-hair-cell (OHC) stereocilia mechano-electric transduction (MET) function. BTs transiently change the operating-point of OHC MET channels and can suppress cochlear-amplifier gain by pushing OHC METs into low-slope saturation regions. BT effects on single auditory-nerve (AN) fibers have been studied on tone responses but not on click responses. We recorded from AN fibers in anesthetized cats and compared tone and click responses using 50 Hz BTs at 70–120 dB SPL to manipulate OHC stereocilia position. BTs can also excite and thereby obscure the BT suppression. We measured AN-fiber response synchrony to BTs alone so that we could exclude suppression measurements when the BT synchrony might obscure the suppression. BT suppression of low-level tone and click responses followed the traditional pattern of twice-a-BT-cycle suppression with more suppression at one phase than the other. The major suppression phases of most fibers were tightly grouped with little difference between click and tone suppressions, which is consistent with low-level click and tone responses being amplified in the same way. The data are also consistent with the operating point of the OHC MET function varying smoothly from symmetric in the base to offset in the apex, and, in contrast, with the IHC MET function being offset throughout the cochlea. As previously reported, bias-tones presented alone excited AN fibers at one or more phases, a phenomena termed “peak splitting” with most BT excitation phases ∼¼ cycle before or after the major suppression phase. We explain peak splitting as being due to distortion in multiple fluid drives to inner-hair-cell stereocilia.

Relation between temporal envelope coding, pitch discrimination, and compression estimates in listeners with sensorineural hearing loss

Recent physiological studies in animals showed that noise-induced sensorineural hearing loss (SNHL) increased the amplitude of envelope coding in single auditory-nerve fibers. The present study investigated whether SNHL in human listeners was associated with enhanced temporal envelope coding, whether this enhancement affected pitch discrimination performance, and whether loss of compression following SNHL was a potential factor in envelope coding enhancement. Envelope processing was assessed in normal-hearing (NH) and hearing-impaired (HI) listeners in a behavioral amplitude-modulation detection task. Fundamental frequency difference limens (F0DLs) were obtained in the same listeners for complex tones with varying harmonic resolvability. Basilar-membrane input/output functions were measured to assess individual compression ratios. For NH listeners, F0DLs decreased with increasing harmonic resolvability. For the unresolved conditions, all five HI listeners performed as good as or better than NH listeners with matching musical experience. Two HI listeners showed lower amplitude-modulation detection thresholds than NH listeners for low modulation rates, and one of these listeners also showed a loss of cochlear compression. Overall, these findings suggest that some HI listeners may benefit from an enhancement of temporal envelope coding in pitch discrimination of unresolved complex tones, and that this enhancement may be also ascribed to a reduction of cochlear compression following SNHL.

Electric-acoustic interactions in the hearing cochlea: Single fiber recordings

The present study investigates interactions of simultaneous electric and acoustic stimulation in single auditory nerve fibers in normal hearing cats. First, the auditory nerve was accessed with a microelectrode and response areas of single nerve fibers were determined for acoustic stimulation. Second, response thresholds to extracochlear sinusoidal electric stimulation using ball electrodes positioned at the round window were measured. Third, interactions that occurred with combined electric-acoustic stimulation were investigated in two areas: (1) the spectral domain (frequency response areas) and (2) the temporal domain (phase-locking to each stimulus) at moderate stimulus intensities (electric: 6 dB re threshold, acoustic: 20–40 dB re threshold at the characteristic frequency, CF). For fibers responding to both modalities responses to both electric and acoustic stimulation could be clearly identified. CFs, thresholds, and bandwidth (Q10dB) of acoustic responses were not significantly affected by simultaneous electric stimulation. Phase-locking of electric responses decreased in the presence of acoustic stimulation. Indication for electric stimulation of inner hair cells with 125 and 250 Hz were observed. However, these did not disturb the acoustic receptive fields of auditory nerve fibers. There was a trade-off between these responses when the intensities of the stimulation were varied: Relatively more intense stimulation dominated less intense stimulation. The scarcity of interaction between the different stimulus modalities demonstrates the ability of electric-acoustic stimulation to transfer useful information through both stimulation channels at the same time despite cochlear electrophonic effects. Application of 30 Hz electric stimulation resulted in a strong suppression of acoustic activity in the anodic phase of the stimulus. An electric stimulation like this might thus be used to control acoustic responses.This article is part of a Special Issue entitled <Lasker Award>.

Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity

Neurons of the lateral olivocochlear (LOC) system project from the auditory brainstem to the cochlea, where they synapse on radial dendrites of auditory nerve fibers. Selective LOC disruption depresses sound-evoked auditory nerve activity in the guinea pig, but enhances it in the mouse. Here, LOC disruption depressed spontaneous auditory nerve activity in the guinea pig. Recordings from single auditory nerve fibers revealed a significantly reduced proportion of fibers with the highest spontaneous firing rates (SRs) and an increased proportion of neurons with lower SRs. Ensemble activity, estimated using round window noise, also decreased after LOC disruption. Decreased spontaneous activity after LOC disruption may be a consequence of reduced tonic release of excitatory transmitters from the LOC terminals in guinea pigs.

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).

The Auditory Nerve Overlapped Waveform (ANOW) Originates in the Cochlear Apex

Measurements of cochlear function with compound action potentials (CAPs), auditory brainstem responses, and otoacoustic emissions work well with high-frequency sounds but are problematic at low frequencies. We have recently shown that the auditory nerve overlapped waveform (ANOW) can objectively quantify low-frequency (<1 kHz) auditory sensitivity, as thresholds for ANOW at low frequencies and for CAP at high frequencies relate similarly to single auditory nerve fiber thresholds. This favorable relationship, however, does not necessarily mean that ANOW originates from auditory nerve fibers innervating low-frequency regions of the cochlear apex. In the present study, we recorded the cochlear response to tone bursts of low frequency (353, 500, and 707 Hz) and high frequency (2 to 16 kHz) during administration of tetrodotoxin (TTX) to block neural function. TTX was injected using a novel method of slow administration from a pipette sealed into the cochlear apex, allowing real-time measurements of systematic neural blocking from apex to base. The amplitude of phase-locked (ANOW) and onset (CAP) neural firing to moderate-level, low-frequency sounds were markedly suppressed before thresholds and responses to moderate-level, high-frequency sounds were affected. These results demonstrate that the ANOW originates from responses of auditory nerve fibers innervating cochlear apex, confirming that ANOW provides a valid physiological measure of low-frequency auditory nerve function.

Efferent-mediated reduction in cochlear gain does not alter tuning estimates from stimulus-frequency otoacoustic emission group delays

The existence of efferent feedback from cortical and subcortical brain centers to the hair cells of the cochlea has been recognized for many years, but the role that efferent neurons play in hearing is not completely known. Stimulation of medial olivocochlear (MOC) efferent neurons suppresses sound-evoked basilar membrane responses and changes the tuning of single auditory nerve fibers in animal models. Both of these effects are linked to a MOC-induced reduction in the gain of the cochlear amplification provided by outer hair cells. To non-invasively examine the link between cochlear suppression and tuning in humans, stimulus-frequency otoacoustic emissions (SFOAEs) were recorded in conditions with and without contralateral acoustic stimulation (CAS) from 28 normal-hearing participants. SFOAEs were measured using clusters of closely-spaced probe-tone frequencies centered near 1.4 and 2.0kHz. An index of cochlear tuning, QERB, was calculated based on measures of SFOAE group delay at both 1.4 and 2.0kHz. A statistically significant (p<0.01) decrease in SFOAE levels acquired during CAS was detected only for the SFOAE cluster centered at 2kHz. No statistically significant differences in QERB were found between conditions with and without CAS at 1.4 and 2.0kHz. These findings suggest that in humans, tuning based on SFOAE group delay estimates is not appreciably altered at cochlear locations with MOC efferent-induced reductions in cochlear gain.