Auditory Research publications

The spectral, temporal, and intensive selectivity of neurons in the adult primary auditory cortex (A1) is easily degraded in early postnatal life by raising rat pups in the presence of pulsed noise. The nonselective frequency tuning recorded in these rats substantially endures into adulthood. Here we demonstrate that perceptual training applied in these developmentally degraded postcritical-period rats results in the recovery of normal representational fidelity. By using a modified go/no-go training strategy, structured noise-reared rats were trained to identify target auditory stimuli of specific frequency from a set of distractors varying in frequency. Target stimuli changed daily on a random schedule. Consistent with earlier findings, structured noise exposure within the critical period resulted in disrupted tonotopicity within A1 and in degraded frequency-response selectivity for A1 neurons. Tonotopicity and frequency-response selectivity were normalized by perceptual training. Changes induced by training endured without loss for at least 2 months after training cessation. The results further demonstrate the potential utility of perceptual learning as a strategy for normalizing deteriorated auditory representations in older (postcritical-period) children and adults.

The intensity of a noise-induced startle response can be reduced by the presentation of an otherwise neutral stimulus immediately before the noise (“prepulse inhibition” or PPI). This effect has been used to study the detection of gaps and other stimuli, but has been applied infrequently to complex stimuli or the ability to discriminate among multiple stimuli. To address both issues and explore the potential of PPI, rats were presented a series of 5 tasks, most contrasting a pair of speech sounds. One of these (the “standard” stimulus) occurred frequently but rarely preceded the startle stimulus. The second occurred infrequently (as an “oddball”) and always preceded a noise. In each such task, startle responses were inhibited more by the oddball than by the standard stimulus, usually within the first test. This suggests that PPI can be adapted to studies of the discrimination of speech and other complex sounds, and that this method can provide useful information on subjects' ability to discriminate with greater ease and speed than other methods.

Sound pressure was mapped in the bony ear canal of gerbils during closed-field sound stimulation at frequencies from 0.1to80kHz. A 1.27-mm-diam probe-tube microphone or a 0.17-mm-diam fiber-optic miniature microphone was positioned along approximately longitudinal trajectories within the 2.3-mm-diam ear canal. Substantial spatial variations in sound pressure, sharp minima in magnitude, and half-cycle phase changes occurred at frequencies >30kHz. The sound frequencies of these transitions increased with decreasing distance from the tympanic membrane (TM). Sound pressure measured orthogonally across the surface of the TM showed only small variations at frequencies below 60kHz. Hence, the ear canal sound field can be described fairly well as a one-dimensional standing wave pattern. Ear-canal power reflectance estimated from longitudinal spatial variations was roughly constant at 0.2–0.5 at frequencies between 30 and 45kHz. In contrast, reflectance increased at higher frequencies to at least 0.8 above 60kHz. Sound pressure was also mapped in a microphone-terminated uniform tube—an “artificial ear.” Comparison with ear canal sound fields suggests that an artificial ear or “artificial cavity calibration” technique may underestimate the in situ sound pressure by 5–15dB between 40 and 60kHz.

Processing mechanisms used for detection of tones in noise can be revealed by using reproducible noise maskers and analyzing the pattern of results across masker waveforms. This study reports detection of a 500-Hz tone in broadband reproducible noise by rabbits using a set of masker waveforms for which human results are available. An appetitive-reinforcement, operant-conditioning procedure with bias control was used. Both fixed-level and roving-level noises were used to explore the utility of energy-related cues for detection. An energy-based detection model was able to partially explain the fixed-level results across reproducible noise waveforms for both rabbit and human. A multiple-channel energy model was able to explain fixed-level results, as well as the robust performance observed with roving-level noises. Further analysis using the energy model indicated a difference between species: human detection was influenced most by the noise spectrum surrounding the tone frequency, whereas rabbit detection was influenced most by the noise spectrum at frequencies above that of the tone. In addition, a temporal envelope-based model predicted detection by humans as well as the single-channel energy model did, but the envelope-based model failed to predict detection by rabbits. This result indicates that the contributions of energy and temporal cues to auditory processing differ across species. Overall, these findings suggest that caution must be used when evaluating neural encoding mechanisms in one species on the basis of behavioral results in another.

Audition and vision both form spatial maps of the environment in the brain, and their congruency requires alignment and calibration. Because audition is referenced to the head and vision is referenced to movable eyes, the brain must accurately account for eye position to maintain alignment between the two modalities as well as perceptual space constancy. Changes in eye position are known to variably, but inconsistently, shift sound localization, suggesting subtle shortcomings in the accuracy or use of eye position signals. We systematically and directly quantified sound localization across a broad spatial range and over time after changes in eye position. A sustained fixation task addressed the spatial (steady-state) attributes of eye position-dependent effects on sound localization. Subjects continuously fixated visual reference spots straight ahead (center), to the left (20°), or to the right (20°) of the midline in separate sessions while localizing auditory targets using a laser pointer guided by peripheral vision. An alternating fixation task focused on the temporal (dynamic) aspects of auditory spatial shifts after changes in eye position. Localization proceeded as in sustained fixation, except that eye position alternated between the three fixation references over multiple epochs, each lasting minutes. Auditory space shifted by ∼40% toward the new eye position and dynamically over several minutes. We propose that this spatial shift reflects an adaptation mechanism for aligning the “straight-ahead” of perceived sensory–motor maps, particularly during early childhood when normal ocular alignment is achieved, but also resolving challenges to normal spatial perception throughout life.

Delayed auditory feedback (DAF) regarding speech can cause dysfluency. The purpose of this study was to explore whether providing visual feedback in addition to DAF would ameliorate speech disruption. Speakers repeated sentences and heard their auditory feedback delayed with and without simultaneous visual feedback. DAF led to increased sentence durations and an increased number of speech disruptions. Although visual feedback did not reduce DAF effects on duration, a promising but nonsignificant trend was observed for fewer speech disruptions when visual feedback was provided. This trend was significant in speakers who were overall less affected by DAF. The results suggest the possibility that speakers strategically use alternative sources of feedback.

Space-specific neurons in the barn owl's auditory space map gain spatial selectivity through tuning to combinations of the interaural time difference (ITD) and interaural level difference (ILD). The combination of ITD and ILD in the subthreshold responses of space-specific neurons in the external nucleus of the inferior colliculus (ICx) is well described by a multiplication of ITD- and ILD-dependent components. It is unknown, however, how ITD and ILD are combined at the site of ITD and ILD convergence in the lateral shell of the central nucleus of the inferior colliculus (ICcl) and therefore whether ICx is the first site in the auditory pathway where multiplicative tuning to ITD- and ILD-dependent signals occurs. We used extracellular recording of single neurons to determine how ITD and ILD are combined in ICcl of the anesthetized barn owl ( Tyto alba). A comparison of additive, multiplicative, and linear-threshold models of neural responses shows that ITD and ILD are combined nonlinearly in ICcl, but the interaction of ITD and ILD is not uniformly multiplicative over the sample. A subset (61%) of the neural responses is well described by the multiplicative model, indicating that ICcl is the first site where multiplicative tuning to ITD- and ILD-dependent signals occurs. ICx, however, is the first site where multiplicative tuning is observed consistently. A network model shows that a linear combination of ICcl responses to ITD–ILD pairs is sufficient to produce the multiplicative subthreshold responses to ITD and ILD seen in ICx.

Although the auditory cortex is known to be essential for normal sound localization in the horizontal plane, its contribution to vertical localization has not so far been examined. In this study, we measured the acuity with which ferrets could discriminate between two speakers in the midsagittal plane before and after silencing activity bilaterally in the primary auditory cortex (A1). This was achieved either by subdural placement of Elvax implants containing the GABA A receptor agonist muscimol or by making aspiration lesions after determining the approximate location of A1 electrophysiologically. Psychometric functions and minimum audible angles were measured in the upper hemifield for 500-, 200-, and 40-ms noise bursts. Muscimol-Elvax inactivation of A1 produced a small but significant deficit in the animals’ ability to localize brief (40-ms) sounds, which was reversed after removal of the Elvax implants. A similar deficit in vertical localization was observed after bilateral aspiration lesions of A1, whereas performance at longer sound durations was unaffected. Another group of ferrets received larger lesions, encompassing both primary and nonprimary auditory cortical areas, and showed a greater deficit with performance being impaired for long- and short-duration (500- and 40-ms, respectively) stimuli. These data suggest that the integrity of the auditory cortex is required to successfully utilize spectral localization cues, which are thought to provide the basis for vertical localization, and that multiple cortical fields, including A1, contribute to this task.

Rats emit ultrasonic vocalizations (USVs) as social signals in several situations. Lesion studies have shown that rat perirhinal cortex (PR), a polymodal sensory region that is reciprocally connected with the amygdala, is critical for normal fear conditioning to so-called "22 kHz USVs". Here we evaluated single-unit responses in rat PR to 22 kHz USVs and other acoustic stimuli. One question was whether PR circuits are specifically and preferentially tuned, prior to fear conditioning, to respond to USVs and USV-like stimuli. Two 22 kHz USVs were pre-recorded from different conspecifics. Each USV consisted of a "bout" of several discrete calls. Using experimentally naïve rats, single-unit responses to the USVs were compared with responses to continuous or discontinuous tones that had the same root frequency as the USVs (19 or 22 kHz). The on/off patterns of the discontinuous tones were temporally matched to the call structure in the corresponding USVs. Compared to continuous tones, the USVs were no more likely to elicit single-unit firing changes in PR. On the other hand, the continuous tones and USVs clearly did elicit different firing patterns in many units. More specifically, the USVs sometimes elicited a transient increase in discharge frequency to each call in a bout of calls. Interestingly, the USVs and the temporally matched tone segments usually elicited similar firing patterns. The USV-elicited firing pattern in PR thus appears to be controlled by the on/off temporal structure of the calls rather than by the frequency or amplitude modulations associated with each call in a bout of calls.

Background: Mucopolysaccharidosis (MPS) IIIB (Sanfilippo Syndrome type B) is caused by a deficiency in the lysosomal enzyme N-acetyl-glucosaminidase (Naglu). Children with MPS IIIB develop disturbances of sleep, activity levels, coordination, vision, hearing, and mental functioning culminating in early death. The murine model of MPS IIIB demonstrates lysosomal distention in multiple tissues, a shortened life span, and behavioral changes. Principal findings: To more thoroughly assess MPS IIIB in mice, alterations in circadian rhythm, activity level, motor function, vision, and hearing were tested. The suprachiasmatic nucleus (SCN) developed pathologic changes and locomotor analysis showed that MPS IIIB mice start their daily activity later and have a lower proportion of activity during the night than wild-type controls. Rotarod assessment of motor function revealed a progressive inability to coordinate movement in a rocking paradigm. Purkinje cell counts were significantly reduced in the MPS IIIB animals compared to age matched controls. By electroretinography (ERG), MPS IIIB mice had a progressive decrease in the amplitude of the dark-adapted b-wave response. Corresponding pathology revealed shortening of the outer segments, thinning of the outer nuclear layer, and inclusions in the retinal pigmented epithelium. Auditory-evoked brainstem responses (ABR) demonstrated progressive hearing deficits consistent with the observed loss of hair cells in the inner ear and histologic abnormalities in the middle ear. Conclusions/significance: The mouse model of MPS IIIB has several quantifiable phenotypic alterations and is similar to the human disease. These physiologic and histologic changes provide insights into the progression of this disease and will serve as important parameters when evaluating various therapies.

The BETA2/NeuroD1 null mouse has cochlear dysplasia. Its cochlear duct is shorter than normal, there is a lack of spiral ganglion neurons, and there is hair cell disorganization. We measured vertical movements of the tectorial membrane at acoustic frequencies in excised cochleae in response to mechanical stimulation of the stapes using laser doppler vibrometry. While tuning curve sharpness was similar between wild-type, heterozygotes, and null mice in the base, null mutants had broader tuning in the apex. At both the base and the apex, null mice had less phase lag accumulation with increasing stimulus frequency than wild-type or heterozygote mice. In vivo studies demonstrated that the null mouse lacked distortion product otoacoustic emissions, and the cochlear microphonic and endocochlear potential were found to be severely reduced. Electrically evoked otoacoustic emissions could be elicited, although the amplitudes were lower than those of wild-type mice. Cochlear cross-sections revealed an incomplete partition malformation, with fenestrations within the modiolus that connected the cochlear turns. Outer hair cells from null mice demonstrated the normal pattern of prestin expression within their lateral walls and normal FM 1-43 dye entry. Overall, these data demonstrate that while tonotopicity can exist with cochlear dysplasia, traveling wave propagation is abnormally fast. Additionally, the presence of electrically evoked otoacoustic emissions suggests that outer hair cell reverse transduction is present, although the acoustic response is shaped by the alterations in cochlear mechanics.

Transcallosal excitation and inhibition have been theorized based on the effect of callosotomy on intractable epilepsy and dichotic listening research, respectively. We studied bilateral interaction of cortical auditory neurons and found that this interaction consisted of focused facilitation and widespread lateral inhibition. The frequency modulated (FM)–FM area of the auditory cortex of the mustached bat is composed of delay-tuned neurons tuned to the combination of the emitted biosonar pulse and its echo with a specific echo delay [best delay (BD)] and consists of three subdivisions in terms of the combination sensitivity of neurons. We found that focal electric stimulation of one of these three subdivisions evoked BD shifts of delay-tuned neurons in all three subdivisions of the contralateral FM–FM area, presumably via the corpus callosum. The effect of electric stimulation of the delay-tuned neurons on the contralateral delay-tuned neurons was different depending on whether the BD of a recorded neuron was matched or unmatched in BD with that of the stimulated neurons. BD-matched neurons did not change their BDs and increased the responses at their BDs, whereas BD-unmatched neurons shifted their BDs away from the BD of the stimulated neurons and reduced their responses. The ipsilateral and contralateral BD shifts evoked by the electric stimulation were identical to each other. The contralateral modulation, in addition to the ipsilateral modulation, increases the contrast in the neural representation of the echo delay to which the stimulated neurons are tuned.

Deprivation from normal sensory input has been shown to alter tonotopic organization of the human auditory cortex. In this context, cochlear implant subjects provide an interesting model in that profound deafness is made partially reversible by the cochlear implant. In restoring afferent activity, cochlear implantation may also reverse some of the central changes related to deafness. The purpose of the present study was to address whether the auditory cortex of cochlear implant subjects is tonotopically organized. The subjects were thirteen adults with at least 3 months of cochlear implant experience. Auditory event-related potentials were recorded in response to electrical stimulation delivered at different intracochlear electrodes. Topographic analysis of the auditory N1 component (∼85 ms latency) showed that the locations on the scalp and the relative amplitudes of the positive/negative extrema differ according to the stimulated electrode, suggesting that distinct sets of neural sources are activated. Dipole modeling confirmed electrode-dependent orientations of these sources in temporal areas, which can be explained by nearby, but distinct sites of activation in the auditory cortex. Although the cortical organization in cochlear implant users is similar to the tonotopy found in normal-hearing subjects, some differences exist. Nevertheless, a correlation was found between the N1 peak amplitude indexing cortical tonotopy and the values given by the subjects for a pitch scaling task. Hence, the pattern of N1 variation likely reflects how frequencies are coded in the brain.

In this study, we investigated the relationship between c-fos expression in the auditory thalamus and corticofugal activation. The contribution of neurotransmitters and related receptors, the involvement of thalamic reticular nucleus (TRN), and the role of neuronal firing patterns in this process were also examined. The principal nuclei of the medial geniculate body (MGB) showed c-fos expression when the auditory cortex (AC) was activated by direct injection of bicuculline methobromide. However, no expression was detectable with acoustic stimuli alone. This indicated that c-fos expression in the principal nuclei of the MGB was triggered by the corticofugal projection. c-fos expression could be elicited in the MGB by direct injection of glutamate. Direct administration of acetylcholine, alternatively, had no effect. Bicuculline methobromide injection in the AC also triggered synchronized oscillatory activities sequentially in the AC and MGB. Cortically induced c-fos expression in the MGB was not mediated by a pathway involving the TRN because it remained intact after a TRN lesion with kainic acid. The present results also conclude that c-fos expression is not simply associated with firing rate, but also with neuronal firing pattern. Burst firings that are synchronized with the cortical oscillations are proposed to lead to c-fos expression in the principal nuclei of the MGB.

The rat auditory cortex is divided anatomically into several areas, but little is known about the functional differences in information processing between these areas. To determine the filter properties of rat posterior auditory field (PAF) neurons, we compared neurophysiological responses to simple tones, frequency modulated (FM) sweeps, and amplitude modulated noise and tones with responses of primary auditory cortex (A1) neurons. PAF neurons have excitatory receptive fields that are on average 65% broader than A1 neurons. The broader receptive fields of PAF neurons result in responses to narrow and broadband inputs that are stronger than A1. In contrast to A1, we found little evidence for an orderly topographic gradient in PAF based on frequency. These neurons exhibit latencies that are twice as long as A1. In response to modulated tones and noise, PAF neurons adapt to repeated stimuli at significantly slower rates. Unlike A1, neurons in PAF rarely exhibit facilitation to rapidly repeated sounds. Neurons in PAF do not exhibit strong selectivity for rate or direction of narrowband one octave FM sweeps. These results indicate that PAF, like nonprimary visual fields, processes sensory information on larger spectral and longer temporal scales than primary cortex.

Cochlear fibrocytes play important roles in normal hearing as well as in several types of sensorineural hearing loss attributable to inner ear homeostasis disorders. Recently, we developed a novel rat model of acute sensorineural hearing loss attributable to fibrocyte dysfunction induced by a mitochondrial toxin. In this model, we demonstrate active regeneration of the cochlear fibrocytes after severe focal apoptosis without any changes in the organ of Corti. To rescue the residual hearing loss, we transplanted mesenchymal stem cells into the lateral semicircular canal; a number of these stem cells were then detected in the injured area in the lateral wall. Rats with transplanted mesenchymal stem cells in the lateral wall demonstrated a significantly higher hearing recovery ratio than controls. The mesenchymal stem cells in the lateral wall also showed connexin 26 and connexin 30 immunostaining reminiscent of gap junctions between neighboring cells. These results indicate that reorganization of the cochlear fibrocytes leads to hearing recovery after acute sensorineural hearing loss in this model and suggest that mesenchymal stem cell transplantation into the inner ear may be a promising therapy for patients with sensorineural hearing loss attributable to degeneration of cochlear fibrocytes.

Plasticity studies suggest that behavioral relevance can change the cortical processing of trained or conditioned sensory stimuli. However, whether this occurs in the context of natural communication, where stimulus significance is acquired through social interaction, has not been well investigated, perhaps because neural responses to species-specific vocalizations can be difficult to interpret within a systematic framework. The ultrasonic communication system between isolated mouse pups and adult females that either do or do not recognize the calls' significance provides an opportunity to explore this issue. We applied an information-based analysis to multi- and single unit data collected from anesthetized mothers and pup-naïve females to quantify how the communicative significance of pup calls affects their encoding in the auditory cortex. The timing and magnitude of information that cortical responses convey (at a 2-ms resolution) for pup call detection and discrimination was significantly improved in mothers compared to naïve females, most likely because of changes in call frequency encoding. This was not the case for a non-natural sound ensemble outside the mouse vocalization repertoire. The results demonstrate that a sensory cortical change in the timing code for communication sounds is correlated with the vocalizations' behavioral relevance, potentially enhancing functional processing by improving its signal to noise ratio.

Purpose The purposes were (a) to compare masking of consonant bursts by adjacent vowels for listeners with and without hearing loss and (b) to determine the extent to which the temporal intraspeech masking can be reduced by a simulated hearing-aid frequency-response shaping. Method Fourteen adults with sensorineural hearing loss and 10 with normal hearing participated. Seven of the participants with hearing loss had flat or gradually sloping audiograms, and 7 had steeply sloping losses. Stimuli consisted of 3 consonant bursts (/t/, /p/, /k/) presented in isolation and in vowel-consonant-vowel combinations using the vowel /a/ with formant transition information removed. Normal-hearing listeners were tested using unfiltered stimuli. Listeners with hearing loss were tested using unfiltered stimuli and stimuli filtered to approximate a hearing aid frequency response prescribed by NAL-R. All listeners were tested under earphones at the most comfortable level for the vowel stimulus. Temporal intraspeech masking was quantified as the threshold shift produced by the adjacent vowels. Results Average intraspeech masking for listeners with steeply sloping hearing loss was significantly higher than that of normal-hearing listeners and those with flat/gradually sloping losses. Greater intraspeech masking was observed for /t/ and /p/ than for /k/. On average, frequency shaping significantly reduced the amount of intraspeech masking for listeners with steeply sloping hearing losses. Even with appropriate amplification/spectral shaping, however, temporal intraspeech masking remained greater than normal for several individuals. Conclusion Findings suggest that some individuals with steeply sloping losses may need additional signal processing to supplement frequency shaping to overcome the effect of temporal intraspeech masking.

Auditory-evoked potentials (AEPs) have become a widely utilized measure of hearing sensitivity. Most investigators use pharmacological paralysis to reduce myogenic noise and immobilize the animal for stable electrical recordings, but additional anesthesia is generally not used because the most commonly available fish anesthetic, the cholinergic antagonist tricaine methanosulfate (MS222), is known to disrupt hair cell and primary afferent physiology. Anesthetic agents that do not interfere with auditory function would be a useful adjunct to paralytic immobilization and would reduce any possible distress incurred by prolonged immobilization. In this report we tested the opiate anesthetic fentanyl and compared hearing thresholds in immobilized versus immobilized and anesthetized animals. Short-term effects of mild MS222 anesthesia were also measured via evoked potential audiometry. Animals were tested before and after fentanyl injection (100, 500 and 2500 microg g(-1) fish body-weight) using standard evoked potential audiometry. Tone pips, 0.2-3 kHz, from an aerial loudspeaker served as stimuli. Fentanyl altered evoked potential waveforms slightly but did not alter estimated threshold sensitivity. These results suggest fentanyl be considered as a possible addition to AEP techniques in goldfish (Carassius auratus) and poikilothermic vertebrates generally.

Individuals with age-related hearing loss often have difficulty understanding complex sounds such as basic speech. The C57BL/6 mouse suffers from progressive sensorineural hearing loss and thus is an effective tool for dissecting the neural mechanisms underlying changes in complex sound processing observed in humans. Neural mechanisms important for processing complex sounds include multiple tuning and combination sensitivity, and these responses are common in the inferior colliculus (IC) of normal hearing mice. We examined neural responses in the IC of C57Bl/6 mice to single and combinations of tones to examine the extent of spectral integration in the IC after age-related high frequency hearing loss. Ten percent of the neurons were tuned to multiple frequency bands and an additional 10% displayed non-linear facilitation to the combination of two different tones (combination sensitivity). No combination-sensitive inhibition was observed. By comparing these findings to spectral integration properties in the IC of normal hearing CBA/CaJ mice, we suggest that high frequency hearing loss affects some of the neural mechanisms in the IC that underlie the processing of complex sounds. The loss of spectral integration properties in the IC during aging likely impairs the central auditory system's ability to process complex sounds such as speech.