Auditory Research publications

In the primary auditory cortex (AI), the development of tone frequency selectivity and tonotopic organization is influenced by patterns of neural activity. Introduction of synchronous inputs into the auditory pathway achieved by exposing rat pups to pulsed white noise at a moderate intensity during P9–P28 resulted in a disrupted tonotopicity and degraded frequency-response selectivity for neurons in the adult AI. The latter was manifested by broader-than-normal tuning curves, multipeaks, and discontinuous, tone-evoked responses within AI-receptive fields. These effects correlated with the severe impairment of normal, developmental sharpening, and refinement of receptive fields and tonotopicity. In addition, paradoxically weaker than normal temporal correlations between the discharges of nearby AI neurons were recorded in exposed rats. In contrast, noise exposure of rats older than P30 did not cause significant change of auditory cortical maps. Thus, patterned auditory inputs appear to play a crucial role in shaping neuronal processing/decoding circuits in the primary auditory cortex during a critical period.

To study putative brain circuits involved in habituation to stress, rats were exposed daily (30 min for 15 days) to an environment in the presence (Chronic) or absence (Acute) of loud noise (105 dB sound pressure level--SPL A Scale). Behavioral and endocrine measures of stress were taken throughout this habituation period, and both measures displayed strong habituation in the Chronic group. All rats were killed immediately after the day 16 exposure, constituting an acute stressor for the Acute group, and regional brain activity was assessed using c-fos mRNA induction with in situ hybridization. Hearing damage could not easily explain these results because additional rats exposed to a similar stress protocol exhibited no changes in auditory brainstem evoked potentials. c-fos mRNA induction in the central auditory system was similar between the Acute and Chronic groups, particularly at lower auditory processing levels, also arguing against a simple reduction in auditory processing in the chronically stressed rats. However, c-fos mRNA expression was reduced in chronically, as compared to acutely, stressed rats in several regions previously implicated in audiogenic stress (lateral septum, bed nucleus of the stria terminalis, some preoptic areas, and the paraventricular hypothalamic nucleus). Interestingly, the orbitofrontal cortex was the only region displaying higher c-fos mRNA induction in the chronically as compared to acutely stressed rats. This region has connections to several stress-responsive areas and may thus be a critical region actively inhibiting stress.

Space-specific neurons in the owl's inferior colliculus have spatial receptive fields (RFs) computed from interaural time (ITD) and level (ILD) differences. Because of the shape of the owl's head, these cues vary with frequency in a manner specific for each location. We sought to determine the contribution of ILD to spatial selectivity. We measured the normal spatial receptive fields of space-specific neurons using virtual sound sources (i.e., noises filtered to simulate external sound sources, presented using headphones). The virtual-source filters were then altered so that ITD was fixed while frequency-specific ILDs varied according to location in the usual manner. The resulting “ILD-alone” RF typically revealed a horizontal band of excitation that included the normal RF. Above and below, the neurons were inhibited. Interestingly, the maxima of ILD-alone RFs were generally outside the normal RF, suggesting that space-specific neurons are not optimally tuned to the ILD spectrum occurring at the normal RF location. Congruously, frequency-specific ILD tuning, assessed with tones, better matched the ILDs at the peak of the ILD-alone RF than those at the peak of the normal RF. The firing evoked from the normal RF may thus reflect the balance of excitatory and inhibitory inputs needed to appropriately restrict the receptive field. Frequency-specific ILD tuning curves were combined with measured head-filtering characteristics to predict responses to the frequency-specific ILDs at each location. The predicted ILD-alone RFs, which are based on a simple sum of frequency-specific inputs, accounted for 56% of the variance in our measured ILD-alone RFs.

The role of the cortico-tectal pathways in the processing of auditory signals was investigated by recording the click-evoked responses and extracellular multiple unit activity in the inferior colliculus (IC) after functional ablation of the auditory cortex (AC) by local intracortical application of a sodium channel blocker, tetrodotoxin (TTX). Click-evoked IC responses (IC-ER) and multiple unit activity in response to tone bursts were recorded with implanted electrodes in the IC of rats lightly anaesthetized with xylazine. Neural activity was recorded before and after the application of TTX into the ipsilateral auditory cortex (AC) through three implanted cannulas in a total dose of 30 ng. The functional status of the AC was monitored by recording click-evoked middle latency responses from a ball electrode implanted on the AC. During inactivation of the AC, IC-ER amplitudes were either increased (48 % of the cases), decreased (32 % of the cases) or not evidently changed (20 % of the cases). Corresponding effects were observed in the firing rate of IC neurons. Functional ablation of the AC also resulted in a significant prolongation of the latencies of individual waves of the IC-ER. However, the discharge pattern of the multiple unit responses, response thresholds and tuning were not altered during AC inactivation. IC neural activity recovered within several hours, and maximally during 2 days. The results reveal principles of the interaction of cortico-tectal pathways with IC neuronal activity.

The auditory system uses delay lines and coincidence detection to measure the interaural time difference (ITD). Both axons and the cochlea could provide such delays. The stereausis theory assumes that differences in wave propagation time along the basilar membrane can provide the necessary delays, if the coincidence detectors receive input from fibers innervating different loci on the left and right basilar membranes. If this hypothesis were true, the left and right inputs to coincidence detectors should differ in their frequency tuning. The owl's nucleus laminaris contains coincidence detector neurons that receive input from the left and right cochlear nuclei. Monaural frequency-tuning curves of nucleus laminaris neurons showed small interaural differences. In addition, their preferred ITDs were not correlated with the interaural frequency mismatches. Instead, the preferred ITD of the neuron agrees with that predicted from the distribution of axonal delays. Thus, there is no need to invoke mechanisms other than neural delays to explain the detection of ITDs by the barn owl's laminaris neurons.

Objective: The purpose of this study was to examine working memory for sequences of auditory and visual stimuli in prelingually deafened pediatric cochlear implant users with at least 4 yr of device experience. Design: Two groups of 8- and 9-yr-old children, 45 normal-hearing and 45 hearing-impaired users of cochlear implants, completed a novel working memory task requiring memory for sequences of either visual-spatial cues or visual-spatial cues paired with auditory signals. In each sequence, colored response buttons were illuminated either with or without simultaneous auditory presentation of verbal labels (color-names or digit-names). The child was required to reproduce each sequence by pressing the appropriate buttons on the response box. Sequence length was varied and a measure of memory span corresponding to the longest list length correctly reproduced under each set of presentation conditions was recorded. Additional children completed a modified task that eliminated the visual-spatial light cues but that still required reproduction of auditory color-name sequences using the same response box. Data from 37 pediatric cochlear implant users were collected using this modified task. Results: The cochlear implant group obtained shorter span scores on average than the normal-hearing group, regardless of presentation format. The normal-hearing children also demonstrated a larger "redundancy gain" than children in the cochlear implant group-that is, the normal-hearing group displayed better memory for auditory-plus-lights sequences than for the lights-only sequences. Although the children with cochlear implants did not use the auditory signals as effectively as normal-hearing children when visual-spatial cues were also available, their performance on the modified memory task using only auditory cues showed that some of the children were capable of encoding auditory-only sequences at a level comparable with normal-hearing children. Conclusions: The finding of smaller redundancy gains from the addition of auditory cues to visual-spatial sequences in the cochlear implant group as compared with the normal-hearing group demonstrates differences in encoding or rehearsal strategies between these two groups of children. Differences in memory span between the two groups even on a visual-spatial memory task suggests that atypical working memory development irrespective of input modality may be present in this clinical population.

Alport syndrome is an inherited disorder of type IV collagen with progressive nephropathy, ocular abnormalities, and high-tone sensorineural deafness. In X-linked Alport syndrome, mutations in the COL4A5 gene encoding the alpha5 chain of type IV collagen lead to loss of the alpha3/alpha4/alpha5 network and increased susceptibility of the glomerular basement membrane to long-term damage. The molecular defects that underlie the otopathology in this disease remain poorly understood. We used a canine model of X-linked Alport syndrome to determine the expression of type IV collagen alpha-chains in the inner ear. By 1 month in normal adult dogs, the alpha3, alpha4, and alpha5 chains were co-expressed in a thin continuous line extending along the basilar membrane and the internal and external sulci, with the strongest expression along the lateral aspect of the spiral ligament in the basal turn of the cochlea. Affected dogs showed complete absence of the alpha3/alpha4/alpha5 network. The lateral aspect of the spiral ligament is populated by tension fibroblasts that express alpha-smooth muscle actin and nonmuscle myosin and are postulated to generate radial tension on the basilar membrane via the extracellular matrix for reception of high frequency sound. We propose that in Alport syndrome, the loss of the alpha3/alpha4/alpha5 network eventually weakens the interaction of these cells with their extracellular matrix, resulting in reduced tension on the basilar membrane and the inability to respond to high frequency sounds.

Thyroid hormone receptors are encoded by the TRalpha (NR1A1) and TRbeta (NR1A2) loci. These genes are transcribed into multiple variants whose functions are unclear. Analysis by gene inactivation in mice has provided new insights into the functional complexity of these products. Different strategies designed to modify the TRalpha locus have led to strikingly different phenotypes. In order to analyze the molecular basis for these alterations, we generated mice devoid of all known isoforms produced from the TRalpha locus (TRalpha(0/0)). These mice are viable and exhibit reduced linear growth, bone maturation delay, moderate hypothermia, and reduced thickness of the intestinal mucosa. Compounding TRalpha(0) and TRbeta(-) mutations produces viable TRalpha(0/0)beta(-/-) mice, which display a more severe linear growth reduction and a more profound hypothermia as well as impaired hearing. A striking phenotypic difference is observed between TRalpha(0/0) and the previously described TRalpha(-/-) mice, which retain truncated TRDeltaalpha isoforms arising from a newly described promoter in intron 7. The lethality and severe impairment of the intestinal maturation in TRalpha(-/-) mice are rescued in TRalpha(0/0) animals. We demonstrate that the TRDeltaalpha protein isoforms, which are natural products of the TRalpha locus, are the key determinants of these phenotypical differences. These data reveal the functional importance of the non-T3-binding variants encoded by the TRalpha locus in vertebrate postnatal development and homeostasis.

Preschoolers and adults were asked to detect a 1000-Hz signal, which was masked by a multitone complex. The frequencies and amplitudes of the components in the complex varied randomly and independently on each presentation. A staircase, cued two-interval, forced-choice procedure disguised as a “listening game” was used to obtain signal thresholds in quiet and in the presence of the multitone maskers. The number of components in the masker was fixed within an experimental condition and varied from 2 to 906 across experimental conditions. Thresholds were also measured with a broadband noise masker. Eight preschool children and eight adults were tested. Although individual differences were large, among both adults and children, there was little difference between the groups in the mean amount of masking produced by the maskers with large numbers of components (400 and 906). There was also a small but significant difference between adults and children in the mean amount of masking produced by the broadband noise. The difference between the groups was much larger with smaller numbers of components. Data obtained from the adults were basically similar to that previously reported [cf. Neff and Green, Percept. Psychophys. 41, 409–415 (1987); Oh and Lutfi, J. Acoust. Soc. Am. 104, 3489–3499 (1998)]: maskers comprised of 10–40 components produced as much as 30 to 60 dB of masking in some, but not all listeners. Those same maskers produced larger amounts of masking (70–83 dB) in many of the preschool children, although, as in the adult group, individual differences were large. The component-relative-entropy (CoRE) model [Lutfi, J. Acoust. Soc. Am. 94, 748–758 (1993)] was used to describe the differences in performance between the children and adults. According to this model the average child appears to integrate information over a larger number of auditory filters than the average adult.

Acoustic behaviors including orientation and social communication depend on neural integration of information across the sound spectrum. In many species, spectral integration is performed by combination-sensitive neurons, responding best when distinct spectral elements in sounds are combined. These are generally considered a feature of information processing in the auditory forebrain. In the mustached bat's inferior colliculus (IC), they are common in frequency representations associated with sonar signals but have not been reported elsewhere in this bat's IC or the IC of other species. We examined the presence of combination-sensitive neurons in frequency representations of the mustached bat's IC not associated with biosonar. Seventy-five single-unit responses were recorded with the best frequencies in 10–23 or 32–47 kHz bands. Twenty-six displayed single excitatory tuning curves in one band with no additional responsiveness to a second signal in another band. The remaining 49 responded to sounds in both 10–23 and 32–47 kHz bands, but response types varied. Sounds in the higher band were usually excitatory, whereas sounds in the lower band either facilitated or inhibited responses to the higher frequency signal. Interactions were usually strongest when the higher and lower frequency stimuli were presented simultaneously, but the strength of interactions varied. Over one-third of the neurons formed a distinct subset; they responded most sensitively to bandpass noise, and all were combination sensitive. We suggest that these combination-sensitive interactions are activated by elements of mustached bat social vocalizations. If so, neuronal integration characterizing analysis of social vocalizations in many species occurs in the IC.

Both mammals and birds use the interaural time difference (ITD) for localization of sound in the horizontal plane. They may localize either real or phantom sound sources, when the signal consists of a narrow frequency band. This ambiguity does not occur with broadband signals. A plot of impulse rates or amplitude of excitatory postsynaptic potentials against ITDs (ITD curve) consists of peaks and troughs. In the external nucleus (ICX) of the owl's inferior colliculus, ITD curves show multiple peaks when the signal is narrow-band, such as tones. Of these peaks, one occurs at ITDi, which is independent of frequency, and others at ITDi ± T, where T is the tonal period. The ITD curve of the same neuron shows a large peak (main peak) at ITDi and no or small peaks (side peaks) at ITDi ± T, when the signal is broadband. ITD curves for postsynaptic potentials indicate that ICX neurons integrate the results of binaural cross-correlation in different frequency bands. However, the difference between the main and side peaks is small. ICX neurons further enhance this difference in the process of converting membrane potentials to impulse rates. Inhibition also appears to augment the difference between the main and side peaks.

Recent progress has been made regarding the prevention of hearing loss. However, the complete protection of both hair cells and spiral ganglion neurons, with restored function, has not yet been achieved. It has been shown that spiral ganglion neuronal loss can be prevented by neurotrophin 3 (NT3) and hair cell damage by N- methyl- d -aspartate (NMDA) receptor antagonists. Here we demonstrate that the combined treatment with MK801, a NMDA antagonist, and NT3 protect both cochlear morphology and physiology from injury. Pretreatment with MK801 prevented hearing loss and the dendrites of the spiral ganglion neurons from swelling after noise-induced damage. The acute phase of insult with the aminoglycoside antibiotic amikacin resulted in swollen afferent dendrites beneath the inner hair cells. The chronic phase resulted in complete hair cell loss and near-complete loss of spiral ganglion neurons. This damage caused a near-complete loss of hearing sensitivity as displayed by elevated (>90-dB sound pressure levels) auditory brainstem response thresholds. The treatment of amikacin-exposed animals with MK801 gave only a partial protection of hearing. However, the combined treatment with NT3 and MK801 in the amikacin-comprised ear resulted in improved mean hearing within 20 dB of normal. Furthermore, hair cell loss was prevented in these animals and spiral ganglion neurons were completely protected. These results suggest that the NMDA antagonist MK801 protects against noise-induced excitotoxicity in the cochlea whereas the combined treatment of NT3 and MK801 has a potent effect on preserving both auditory physiology and morphology against aminoglycoside toxicity.

The relationship between sensory sensitivity and reading performance was examined to test the hypothesis that the orthographic and phonological skills engaged in visual word recognition are constrained by the ability to detect dynamic visual and auditory events. A test battery using sensory psychophysics, psychometric tests, and measures of component literacy skills was administered to 32 unselected 10-year-old primary school children. The results suggest that children's sensitivity to both dynamic auditory and visual stimuli are related to their literacy skills. Importantly, after controlling for intelligence and overall reading ability, visual motion sensitivity explained independent variance in orthographic skill but not phonological ability, and auditory FM sensitivity covaried with phonological skill but not orthographic skill. These results support the hypothesis that sensitivity at detecting dynamic stimuli influences normal children's reading skills. Vision and audition separately may affect the ability to extract orthographic and phonological information during reading.

We examined the coding of sound-source location by ensembles of neurons in the auditory cortex. Broadband noise bursts were presented from loudspeakers throughout 360° in the horizontal plane. Sound levels varied from 20 to 40 dB above neural thresholds. We recorded temporal spike patterns simultaneously at 16 recording sites in area A2 of α-chloralose-anesthetized cats. Spike patterns of individual units varied in spike counts and in spike timing as a function of sound-source location. Ensembles of up to 19 units recorded simultaneously demonstrated additional location sensitivity in the form of relative spike counts and relative spike timing among neurons. We used an artificial neural network (ANN) algorithm to recognize ensemble spike patterns and, thereby, to infer the locations of sound sources. The ANN could estimate stimulus locations based on ensemble responses to single-stimulus presentations. Median errors (MEs) averaged 49.2 ± 11.9° (mean ± SD; n = 34; chance level, 90°). The ANN maintained better-than-chance performance even when input spike patterns were expressed as relative spike counts across units (i.e., no information available from absolute spike counts of individual units; ME, 63.0 ± 11.8°) or when spike latencies were represented as time relative to the first spike for each trial (i.e., no external time reference available; ME, 54.3 ± 12.4°). The ANN performance improved monotonically as the sizes of ensemble patterns were increased by combining patterns across the entire unit sample. The performance by ensembles of 128 units approached the level of localization performance of behaving cats.

Conductive hearing loss, produced by otitis media with effusion, is widespread in young children. However, little is known about its short- or long-term effects on hearing or the brain. To study the consequences of a conductive loss for the perception and processing of sounds, we plugged the left ear canal of ferrets for 7–15 months during either infancy or adulthood. Before or during plugging, the ferrets were trained to perform a binaural task requiring the detection of a 500 Hz tone, positioned 90° to the right, that was masked by two sources of broad-band noise. In one condition (“control”), both noise sources were 90° right and, in the second condition (“bilateral”), one noise source was moved to 90° left. Normal ferrets showed binaural unmasking: tone detection thresholds were lower (mean 10.1 dB) for the bilateral condition than for the control condition. Both groups of ear-plugged ferrets had reduced unmasking; the mean residual unmasking was 2.3 dB for the infant and 0.7 dB for the adult ear-plugged animals. After unplugging, unmasking increased in both groups (infant, 7.1 dB; adult, 6.9 dB) but not to normal levels. Repeated testing during the 22 months after unplugging revealed a gradual return to normal levels of unmasking. These results show that a unilateral conductive hearing loss, in either infancy or adulthood, impairs binaural hearing both during and after the hearing loss. They show scant evidence for adaptation to the plug and demonstrate a recovery from the impairment that occurs over a period of several months after restoration of normal peripheral function.

Basilar-membrane responses to clicks were measured, using laser velocimetry, at a site of the chinchilla cochlea located about 3.5 mm from the oval window (characteristic frequency or CF: typically 8–10 kHz). They consisted of relatively undamped oscillations with instantaneous frequency that increased rapidly (time constant: 200 μs) from a few kHz to CF. Such frequency modulation was evident regardless of stimulus level and was also present post-mortem. Responses grew linearly at low stimulus levels, but exhibited a compressive nonlinearity at higher levels. Velocity-intensity functions were almost linear near response onset but became nonlinear within 100 μs. Slopes could be as low as 0.1–0.2 dB/dB at later times. Hence, the response envelopes became increasingly skewed at higher stimulus levels, with their center of gravity shifting to earlier times. The phases of near-CF response components changed by nearly 180 degrees as a function of time. At high stimulus levels, this generated cancellation notches and phase jumps in the frequency spectra. With increases in click level, sharpness of tuning deteriorated and the spectral maximum shifted to lower frequencies. Response phases also changed as a function of increasing stimulus intensity, exhibiting relative lags and leads at frequencies somewhat lower and higher than CF, respectively. In most respects, the magnitude and phase frequency spectra of responses to clicks closely resembled those of responses to tones. Post-mortem responses were similar to in vivo responses to very intense clicks.

Low-frequency cells in the anteroventral cochlear nucleus (AVCN) can be sensitive to changes in the spatiotemporal pattern of discharges across their auditory nerve (AN) inputs (Carney, 1990). This sensitivity suggests that these cells may be tuned to particular spatiotemporal patterns, or features, in the discharge patterns of populations of AN fibers. To evaluate and characterize this sensitivity, we developed a technique whereby the physiological responses of AVCN cells to wide-band noise were analyzed using the simulated response of a population of AN fibers to the same noise stimulus. By averaging the simulated two-dimensional spatiotemporal pattern of AN activity that preceded each AVCN discharge, it was possible to derive a two-dimensional reverse-correlation function that characterized the spatiotemporal tuning of each AVCN cell. The derived spatiotemporal tuning pattern represented a feature in the AN population response that was most likely to precede discharges of the AVCN cell. To test the spatiotemporal tuning characterizations, we used these patterns to predict the responses of cells to noise stimuli statistically independent from the stimuli used to characterize the cells. This technique provides a general tool for the study of any neural system that involves the analysis of spatiotemporal input patterns.