Auditory Research publications

During anesthesia, slow-wave sleep and quiet wakefulness, neuronal membrane potentials collectively switch between de- and hyperpolarized levels, the cortical UP and DOWN states. Previous studies have shown that these cortical UP/DOWN states affect the excitability of individual neurons in response to sensory stimuli, indicating that a significant amount of the trial-to-trial variability in neuronal responses can be attributed to ongoing fluctuations in network activity. However, as intracellular recordings are frequently not available, it is important to be able to estimate their occurrence purely from extracellular data. Here, we combine in vivo whole cell recordings from single neurons with multi-site extracellular microelectrode recordings, to quantify the performance of various approaches to predicting UP/DOWN states from the deep-layer local field potential (LFP). We find that UP/DOWN states in deep cortical layers of rat primary auditory cortex (A1) are predictable from the phase of LFP at low frequencies (< 4 Hz), and that the likelihood of a given state varies sinusoidally with the phase of LFP at these frequencies. We introduce a novel method of detecting cortical state by combining information concerning the phase of the LFP and ongoing multi-unit activity.

Simultaneous measurements of middle ear-conducted sound pressure in the cochlear vestibule PV and stapes velocity VS have been performed in only a few individuals from a few mammalian species. In this paper, simultaneous measurements of PV and VS in six chinchillas are reported, enabling computation of the middle ear pressure gain GME (ratio of PV to the sound pressure in the ear canal PTM), the stapes velocity transfer function SVTF (ratio of the product of VS and area of the stapes footplate AFP to PTM), and, for the first time, the cochlear input impedance ZC (ratio of PV to the product of VS and AFP) in individuals. |GME| ranged from 25 to 35 dB over 125 Hz–8 kHz; the average group delay between 200 Hz and 10 kHz was about 52 μs. SVTF was comparable to that of previous studies. ZC was resistive from the lowest frequencies up to at least 10 kHz, with a magnitude on the order of 1011 acoustic ohms. PV, VS, and the acoustic power entering the cochlea were good predictors of the shape of the audiogram at frequencies between 125 Hz and 2 kHz.

The use of the effective antineoplastic agent cisplatin is limited by its serious side effects, such as oto- and nephrotoxicity. Ototoxicity is a problem of special importance in children, because deafness hampers their language and psychosocial development. Recently, organic cation transporters (OCTs) were identified in vitro as cellular uptake mechanisms for cisplatin. In the present study, we investigated in an in vivo model the role of OCTs in the development of cisplatin oto- and nephrotoxicity. The functional effects of cisplatin treatment on kidney (24 hours excretion of glucose, water, and protein) and hearing (auditory brainstem response) were studied in wild-type and OCT1/2 double-knockout (KO) mice. No sign of ototoxicity and only mild nephrotoxicity were observed after cisplatin treatment of knockout mice. Comedication of wild-type mice with cisplatin and the organic cation cimetidine protected from ototoxicity and partly from nephrotoxicity. For the first time we showed that OCT2 is expressed in hair cells of the cochlea. Furthermore, cisplatin-sensitive cell lines from pediatric tumors showed no expression of mRNA for OCTs, indicating the feasibility of therapeutic approaches aimed to reduce cisplatin toxicities by competing OCT2-mediated cisplatin uptake in renal proximal tubular and cochlear hair cells. These findings are very important to establish chemotherapeutical protocols aimed to maximize the antineoplastic effect of cisplatin while reducing the risk of toxicities.

The role of auditory cortex in sound localization and its recalibration by experience was explored by measuring the accuracy with which ferrets turned toward and approached the source of broadband sounds in the horizontal plane. In one group, large bilateral lesions were made of the middle ectosylvian gyrus, where the primary auditory cortical fields are located, and part of the anterior and/or posterior ectosylvian gyrus, which contain higher-level fields. In the second group, the lesions were intended to be confined to primary auditory cortex (A1). The ability of the animals to localize noise bursts of different duration and level was measured before and after the lesions were made. A1 lesions produced a modest disruption of approach-to-target responses to short-duration stimuli (<500 ms) on both sides of space, whereas head orienting accuracy was unaffected. More extensive lesions produced much greater auditory localization deficits, again primarily for shorter sounds. In these ferrets, the accuracy of both the approach-to-target behavior and the orienting responses was impaired, and they could do little more than correctly lateralize the stimuli. Although both groups of ferrets were still able to localize long-duration sounds accurately, they were, in contrast to ferrets with an intact auditory cortex, unable to relearn to localize these stimuli after altering the spatial cues available by reversibly plugging one ear. These results indicate that both primary and nonprimary cortical areas are necessary for normal sound localization, although only higher auditory areas seem to contribute to accurate head orienting behavior. They also show that the auditory cortex, and A1 in particular, plays an essential role in training-induced plasticity in adult ferrets, and that this is the case for both head orienting responses and approach-to-target behavior.

Experiments to study voice quality have typically used rating scales or direct magnitude estimation to obtain listener judgments. Unfortunately, the data obtained using these tasks are context dependent, which makes it difficult to compare perceptual judgments of voice quality across experiments. The present experiment describes a simple matching task to quantify voice quality. The data obtained through this task were compared to perceptual judgments obtained using rating scale and direct magnitude estimation tasks to determine whether the three tasks provide equivalent perceptual distances across stimuli. Ten synthetic vowel continua that varied in terms of their aspiration noise were evaluated for breathiness using each of the three tasks. Linear and nonlinear regressions were used to compare the perceptual distances between stimuli obtained through each technique. Results show that the perceptual distances estimated from matching and direct magnitude estimation task are similar, but both differ from the rating scale task, suggesting that the matching task provides perceptual distances with ratio-level measurement properties. The matching task is advantageous for measurement of vocal quality because it provides reliable measurement with ratio-level scale properties. It allows the use of a fixed reference signal for all comparisons, thus allowing researchers to directly compare findings across different experiments.

The rapidly increasing use of the local field potential (LFP) has motivated research to better understand its relation to the gold standard of neural activity, single unit (SU) spiking. We addressed this in an in vivo, awake, restrained mouse auditory cortical electrophysiology preparation by asking whether the LFP could actually be used to predict stimulus-evoked SU spiking. Implementing a Bayesian algorithm to predict the likelihood of spiking on a trial by trial basis from different representations of the despiked LFP signal, we were able to predict, with high quality and fine temporal resolution (2 ms), the time course of a SU's excitatory or inhibitory firing rate response to natural species-specific vocalizations. Our best predictions were achieved by representing the LFP by its wide-band Hilbert phase signal, and approximating the statistical structure of this signal at different time points as independent. Our results show that each SU's action potential has a unique relationship with the LFP that can be reliably used to predict the occurrence of spikes. This "signature" interaction can reflect both pre- and post-spike neural activity that is intrinsic to the local circuit rather than just dictated by the stimulus. Finally, the time course of this "signature" may be most faithful when the full bandwidth of the LFP, rather than specific narrow-band components, is used for representation.

Frequency modulation (FM) is a prominent feature in animal vocalization and human speech. Although many neurons in the auditory cortex are known to be selective for FM direction, the synaptic mechanisms underlying this selectivity are not well understood. Previous studies of both visual and auditory neurons have suggested two general mechanisms for direction selectivity: (1) differential delays of excitatory inputs across the spatial/spectral receptive field and (2) spatial/spectral offset between excitatory and inhibitory inputs. In this study, we have examined the contributions of both mechanisms to FM direction selectivity in rat primary auditory cortex. The excitatory and inhibitory synaptic inputs to each cortical neuron were measured by in vivo whole-cell recording. The spectrotemporal receptive field of each type of inputs was mapped with random tone pips and compared with direction selectivity of the neuron measured with FM stimuli. We found that both the differential delay of the excitatory input and the spectral offset between excitation and inhibition are positively correlated with direction selectivity of the neuron. Thus, both synaptic mechanisms are likely to contribute to FM direction selectivity in the auditory cortex. Finally, direction selectivity measured from the spiking output is significantly stronger than that based on the subthreshold membrane potentials, indicating that the selectivity is further sharpened by the spike generation mechanism.

Deaf people who use cochlear implants show surprisingly poor sensitivity to the temporal fine structure of sounds. One possible reason is that conventional cochlear implants cannot activate selectively the auditory-nerve fibers having low characteristic frequencies (CFs), which, in normal hearing, phase lock to stimulus fine structure. Recently, we tested in animals an alternative mode of auditory prosthesis using penetrating auditory-nerve electrodes that permit frequency-specific excitation in all frequency regions. We present here measures of temporal transmission through the auditory brainstem, from pulse trains presented with various auditory-nerve electrodes to phase-locked activity of neurons in the central nucleus of the inferior colliculus (ICC). On average, intraneural stimulation resulted in significant ICC phase locking at higher pulse rates (i.e., higher “limiting rates”) than did cochlear-implant stimulation. That could be attributed, however, to the larger percentage of low-CF neurons activated selectively by intraneural stimulation. Most ICC neurons with limiting rates >500 pulses per second had CFs <1.5 kHz, whereas neurons with lower limiting rates tended to have higher CFs. High limiting rates also correlated strongly with short first-spike latencies. It follows that short latencies correlated significantly with low CFs, opposite to the correlation observed with acoustical stimulation. These electrical-stimulation results reveal a high-temporal-acuity brainstem pathway characterized by low CFs, short latencies, and high-fidelity transmission of periodic stimulation. Frequency-specific stimulation of that pathway by intraneural stimulation might improve temporal acuity in human users of a future auditory prosthesis, which in turn might improve musical pitch perception and speech reception in noise.

Stimulus selection for gaze and spatial attention involves competition among stimuli across sensory modalities and across all of space. We demonstrate that such cross-modal, global competition takes place in the intermediate and deep layers of the optic tectum, a structure known to be involved in gaze control and attention. A variety of either visual or auditory stimuli located anywhere outside of a neuron's receptive field (RF) were shown to suppress or completely eliminate responses to a visual stimulus located inside the RF in nitrous oxide sedated owls. The essential mechanism underlying this stimulus competition is global, divisive inhibition. Unlike the effect of the classical inhibitory surround, which decreases with distance from the RF center and shapes neuronal responses to individual stimuli, global inhibition acts across the entirety of space and modulates responses primarily in the context of multiple stimuli. Whereas the source of this global inhibition is as yet unknown, our data indicate that different networks mediate the classical surround and global inhibition. We hypothesize that this global, cross-modal inhibition, which acts automatically in a bottom-up manner even in sedated animals, is critical to the creation of a map of stimulus salience in the optic tectum.

Studies of visual processing in rodents have conventionally been performed on anesthetized animals, precluding examination of the effects of behavior on visually evoked responses. We have now studied the response properties of neurons in primary visual cortex of awake mice that were allowed to run on a freely rotating spherical treadmill with their heads fixed. Most neurons showed more than a doubling of visually evoked firing rate as the animal transitioned from standing still to running, without changes in spontaneous firing or stimulus selectivity. Tuning properties in the awake animal were similar to those measured previously in anesthetized animals. Response magnitude in the lateral geniculate nucleus did not increase with locomotion, demonstrating that the striking change in responsiveness did not result from peripheral effects at the eye. Interestingly, some narrow-spiking cells were spontaneously active during running but suppressed by visual stimuli. These results demonstrate powerful cell-type-specific modulation of visual processing by behavioral state in awake mice.

Previous auditory perturbation studies have demonstrated that talkers spontaneously compensate for real-time formant-shifts by altering formant production in a manner opposite to the perturbation. Here, two experiments were conducted to examine the effect of amplitude of perturbation on the compensatory behavior for the vowel /ε/. In the first experiment, 20 male talkers received three step-changes in acoustic feedback: F1 was increased by 50, 100, and 200 Hz, while F2 was simultaneously decreased by 75, 125, and 250 Hz. In the second experiment, 21 male talkers received acoustic feedback in which the shifts in F1 and F2 were incremented by +4 and −5 Hz on each utterance to a maximum of +350 and −450 Hz, respectively. In both experiments, talkers altered production of F1 and F2 in a manner opposite to that of the formant-shift perturbation. Compensation was approximately 25%–30% of the perturbation magnitude for shifts in F1 and F2 up to 200 and 250 Hz, respectively. As larger shifts were applied, compensation reached a plateau and then decreased. The similarity of results across experiments suggests that the compensatory response is dependent on the perturbation magnitude but not on the rate at which the perturbation is introduced.

The possibility that “dead regions” or “spectral holes” can account for some differences in performance between bilateral cochlear implant (CI) users and normal-hearing listeners was explored. Using a 20-band noise-excited vocoder to simulate CI processing, this study examined effects of spectral holes on speech reception thresholds (SRTs) and spatial release from masking (SRM) in difficult listening conditions. Prior to processing, stimuli were convolved through head-related transfer-functions to provide listeners with free-field directional cues. Processed stimuli were presented over headphones under binaural or monaural (right ear) conditions. Using Greenwood’s [(1990). J. Acoust. Soc. Am. 87, 2592–2605] frequency-position function and assuming a cochlear length of 35mm, spectral holes were created for variable sizes (6 and 10mm) and locations (base, middle, and apex). Results show that middle-frequency spectral holes were the most disruptive to SRTs, whereas high-frequency spectral holes were the most disruptive to SRM. Spectral holes generally reduced binaural advantages in difficult listening conditions. These results suggest the importance of measuring dead regions in CI users. It is possible that customized programming for bilateral CI processors based on knowledge about dead regions can enhance performance in adverse listening situations.

The lateral superior olive (LSO) is one of the earliest sites in the auditory pathway involved in processing acoustical cues to sound location. LSO neurons encode the interaural level difference (ILD) cue to azimuthal location. Here we investigated the effect of variations in the overall stimulus levels of sounds at the two ears on the sensitivity of LSO neurons to small differences in ILDs of pure tones. The neuronal firing rate versus ILD functions were found to depend greatly on the overall stimulus level, typically shifting along the ILD axis toward the excitatory ear and attaining greater maximal firing rates as stimulus level increased. Seventy-five percent of neurons showed significant shifts with changes in overall sound level. The range of ILDs corresponding to best neural acuity for ILDs shifted accordingly. In a simulation using the empirical data, when the overall stimulus level was randomly changed from one trial to the next, the neural discrimination thresholds for ILD, or ILD acuities, were worsened by 50–60% across the population of neurons relative to fixed stimulus levels whether ILD acuity was measured at the azimuthal midline or the ILD pedestal producing the best acuity. The impairment in ILD discrimination was attributed to the increased neural response variance imparted by varying the stimulus level. These results contrast to those observed in psychophysical studies where ILD discrimination thresholds under similar experimental conditions are invariant to overall changes in stimulus level. A simple computational model that incorporated the antagonistic inputs of bilateral LSO nuclei as well as the dorsal nuclei of the lateral lemniscus to the inferior colliculus produced a more robust encoding of ILD even in the setting of roving stimulus level. Testable predictions of this model and comparison to other computational models addressing stimulus invariance were considered.

The most important acoustic cues available to the brain for sound localization are produced by the interaction of sound with the animal's head and external ears. As a first step in understanding the relation between these cues and their neural representation in a vocal new-world primate, we measured head-related transfer functions (HRTFs) across frequency for a wide range of sound locations in three anesthetized marmoset monkeys. The HRTF magnitude spectrum has a broad resonance peak at 6-12 kHz that coincides with the frequency range of the major call types of this species. A prominent first spectral notch (FN) in the HRTF magnitude above this resonance was observed at most source locations. The center frequency of the FN increased monotonically from approximately 12 to 26 kHz with increases in elevation in the lateral field. In the frontal field FN frequency changed in a less orderly fashion with source position. From the HRTFs we derived interaural time (ITDs) and level differences (ILDs). ITDs and ILDs (below 12 kHz) varied as a function of azimuth between +/-250 micros and +/-20dB, respectively. A reflexive orienting behavioral paradigm was used to confirm that marmosets can orient to sound sources.

Spontaneous activity is a well-known neural phenomenon that occurs throughout the brain and is essential for normal development of auditory circuits and for processing of sounds. Spontaneous activity could interfere with sound processing by reducing the signal-to-noise ratio. Multiple studies have reported that spontaneous activity in auditory neurons can be suppressed by sound stimuli. The goal of this study was to determine the stimulus conditions that cause this suppression and to identify possible underlying mechanisms. Experiments were conducted in the inferior colliculus (IC) of awake little brown bats using extracellular and intracellular recording techniques. The majority of IC neurons (82%) fired spontaneously, with a median spontaneous firing rate of 6 spikes/s. After offset of a 4 ms sound, more than half of these neurons exhibited suppression of spontaneous firing that lasted hundreds of milliseconds. The duration of suppression increased with sound level. Intracellular recordings showed that a short (<50 ms) membrane hyperpolarization was often present during the beginning of suppression, but it was never observed during the remainder of the suppression. Beyond the initial 50 ms period, the absence of significant changes in input resistance during suppression suggests that suppression is presynaptic in origin. Namely, it may occur on presynaptic terminals and/or elsewhere on presynaptic neurons. Suppression of spontaneous firing may serve as a mechanism for enhancing signal-to-noise ratios during signal processing.

It has been demonstrated that neural encoding of pitch in the auditory brainstem is shaped by long-term experience with language. To date, however, all stimuli have exhibited a high degree of pitch saliency. The experimental design herein permits us to determine whether experience-dependent pitch representation in the brainstem is less susceptible to progressive degradation of the temporal regularity of iterated rippled noise (IRN). Brainstem responses were recorded from Chinese and English participants in response to IRN homologues of Mandarin Tone 2 (T2(IRN)). Six different iterations steps were utilized to systematically vary the degree of temporal regularity in the fine structure of the IRN stimuli to produce a pitch salience continuum ranging from low to high. Pitch-tracking accuracy and pitch strength were computed from the brainstem responses using autocorrelation algorithms. Analysis of variance of brainstem responses to T2(IRN) revealed that pitch-tracking accuracy is higher in the native tone language group (Chinese) relative to the non-tone language group (English) except for the three lowest steps along the continuum, and moreover, that pitch strength is greater in the Chinese group even in severely degraded stimuli for two of the six 40-ms sections of T2(IRN) that exhibit rapid changes in pitch. For these same two sections, exponential time constants for the stimulus continuum revealed that pitch strength emerges 2-3 times faster in the tone language than in the non-tone language group as a function of increasing pitch salience. These findings altogether suggest that experience-dependent brainstem mechanisms for pitch are especially sensitive to those dimensions of tonal contours that provide cues of high perceptual saliency in degraded as well as normal listening conditions.

Vision and audition represent the outside world in spatial synergy that is crucial for guiding natural activities. Input conveying eye-in-head position is needed to maintain spatial congruence because the eyes move in the head while the ears remain head-fixed. Recently, we reported that the human perception of auditory space shifts with changes in eye position. In this study, we examined whether this phenomenon is 1) dependent on a visual fixation reference, 2) selective for frequency bands (high-pass and low-pass noise) related to specific auditory spatial channels, 3) matched by a shift in the perceived straight-ahead (PSA), and 4) accompanied by a spatial shift for visual and/or bimodal (visual and auditory) targets. Subjects were tested in a dark echo-attenuated chamber with their heads fixed facing a cylindrical screen, behind which a mobile speaker/LED presented targets across the frontal field. Subjects fixated alternating reference spots (0, ±20°) horizontally or vertically while either localizing targets or indicating PSA using a laser pointer. Results showed that the spatial shift induced by ocular eccentricity is 1) preserved for auditory targets without a visual fixation reference, 2) generalized for all frequency bands, and thus all auditory spatial channels, 3) paralleled by a shift in PSA, and 4) restricted to auditory space. Findings are consistent with a set-point control strategy by which eye position governs multimodal spatial alignment. The phenomenon is robust for auditory space and egocentric perception, and highlights the importance of controlling for eye position in the examination of spatial perception and behavior.

Background: Surveys of ontogenetic development of hearing and sound production in fish are scarce, and the ontogenetic development of acoustic communication has been investigated in only two fish species so far. Studies on the labyrinth fish Trichopsis vittata and the toadfish Halobatrachus didactylus show that the ability to detect conspecific sounds develops during growth. In otophysine fish, which are characterized by Weberian ossicles and improved hearing sensitivities, the ontogenetic development of sound communication has never been investigated. We analysed the ontogeny of the auditory sensitivity and vocalizations in the mochokid catfish Synodontis schoutedeni. Mochokid catfishes of the genus Synodontis are commonly called squeakers because they produce broadband stridulation sounds during abduction and adduction of pectoral fin spines. Fish from six different size groups - from 22 mm standard length to 126 mm - were studied. Hearing thresholds were measured between 50 Hz and 6 kHz using the auditory evoked potentials recording technique; stridulation sounds were recorded and their sound pressure levels determined. Finally, absolute sound power spectra were compared to auditory sensitivity curves within each size group. Results: The smallest juveniles showed the poorest hearing abilities of all size groups between 50 and 1,000 Hz and highest hearing sensitivity at 5 and 6 kHz. The duration of abduction and adduction sounds and the pulse period increased and sound pressure level (in animals smaller than 58 mm) increased, while the dominant frequency of sounds decreased with size in animals larger than 37 mm. Comparisons between audiograms and sound spectra revealed that the most sensitive frequencies correlate with the dominant frequencies of stridulation sounds in all S. schoutedeni size groups and that all specimens are able to detect sounds of all size groups. Conclusions: This study on the squeaker catfish S. schoutedeni is the first to demonstrate that absolute hearing sensitivity changes during ontogeny in an otophysine fish. This contrasts with prior studies on two cypriniform fish species in which no such change could be observed. Furthermore, S. schoutedeni can detect conspecific sounds at all stages of development, again contrasting with prior findings in fishes.

Functional and anatomical studies suggest that acoustic signals are processed hierarchically in auditory cortex. Although most regions of acoustically responsive cortex are not tonotopically organized, all previous electrophysiological investigations of interfield interactions have only examined tonotopically represented areas. The purpose of the present study was to investigate the functional interactions between tonotopically and nontonotopically organized fields in auditory cortex. We accomplished this goal by examining the bidirectional contributions between the cochleotopically organized primary auditory cortex (A1) and the noncochleotopically organized second auditory field (A2). Multiunit acute recording procedures in combination with reversible cooling deactivation techniques were used in eight mature cats. The synaptic activity of A1 or A2 was suppressed while the neuronal response to tonal stimuli of the noninactivated area (A1 or A2) was measured. Response strength, neuronal threshold, receptive field bandwidths, and latency measures were collected at each recorded site before, during, and after cooling deactivation epochs. Our analysis revealed comparable changes in A1 and A2 neuronal response properties. Specifically, significant decreases in neuronal response strength, increases in neuronal threshold, and shortening of response latency were found in both fields during periods of cooling deactivation. The weak anatomical connections between the two fields investigated make these findings unexpected. Furthermore, the observed neuronal changes suggest a model of corticocortical interaction among auditory fields in which neither differences in the magnitude of anatomical projections nor cortical representation of sensory stimuli are reliable determinants of modulatory functions.

Animal studies indicate that a combination of kanamycin (KM) and noise produces a synergistic effect, whereby the threshold shift from the combination is greater than the sum of the shifts caused by either agent alone. Most such studies have focused on adult animals, and it has remained unclear whether younger, presumably more susceptible, animals show an even greater synergistic effect. The present study tested the hypothesis that young CBA/J mice receiving a low dose of KM (300 mg/kg, 2x/day, s.c.) from 20 to 30 days post-gestational age followed by brief noise exposure (110 dB SPL; 4-45 kHz, 30 s) would show greater noise-induced permanent threshold shifts (NIPTS) than mice receiving either treatment alone. Noise exposure produced 30-40 dB of NIPTS and moderate hair cell loss in young saline-treated mice. KM alone at this dose had no effect on thresholds. Surprisingly, mice receiving KM plus noise were protected from NIPTS, showing ABR thresholds not significantly different from unexposed controls. Mice receiving KM prior to noise exposure also showed significantly less outer hair cell loss than saline-treated mice. Additional experiments indicated protection by KM when the noise was applied either 24 or 48 h after the last KM injection. Our results demonstrate a powerful protective effect of sub-chronic low-dose kanamycin against NIPTS in young CBA/J mice. Repeated kanamycin exposure may establish a preconditioned protective state, the molecular bases of which remain to be determined.