Auditory Research publications

Stroboscopic holography was used to quantify dynamic deformations of the tympanic membrane (TM) of the entire surface of the TM before and after cartilage tympanoplasty of the posterior or posterior-superior part of the TM. Cartilage is widely used in tympanoplasties to provide mechanical stability for the TM. Three human cadaveric temporal bones were used. A 6 mm x 3 mm oval cartilage graft was placed through the widely opened facial recess onto the medial surface of the posterior or posterior-superior part of the TM. The graft was either in contact with the bony tympanic rim and manubrium or not. Graft thickness was either 0.5 or 1.0mm. Stroboscopic holography produced displacement amplitude and phase maps of the TM surface in response to stimulus sound. Sound stimuli were 0.5, 1, 4 and 7 (or 8)kHz tones. Middle-ear impedance was measured from the motion of the entire TM. Cartilage placement generally produced reductions in the motion of the TM apposed to the cartilage, especially at 4 kHz and 7 or 8 kHz. Some parts of the TM showed altered motion compared to the control in all three cases. In general, middle-ear impedance was either unchanged or increased somewhat after cartilage reconstruction both at low (0.5 and 1 kHz) and high (4 and 7 kHz) frequencies. At 4 kHz, with the 1.0mm thick graft that was in contact with the bony tympanic rim, the impedance slightly decreased. While our earlier work with time-averaged holography allowed us to observe differences in the pattern of TM motion caused by application of cartilage to the TM, stroboscopic holography is more sensitive to TM motions and allowed us to quantify the magnitude and phase of motion of each point on the TM surface. Nonetheless, our results are similar to those of our earlier work: The placement of cartilage on the medial surface of TM reduces the motion of the TM that apposes the cartilage. These obvious local changes occur even though the cartilage had little effect on the sound-induced motion of the stapes.

The saccule is known to play an important role in hearing in fishes. In this study we investigated spatial frequency selectivity of single saccular afferents in a teleost fish (the sleeper goby, Dormitator latifrons) to acoustic particle motion at 50–400 Hz. Saccular afferents have similar distributions of best sensitivity (−90.0 to −54.8 dB re. 1 g, mean ± s.d.=−81.1±8.0 dB) and characteristic frequencies (≤50–400 Hz, median=80 Hz) along the longitudinal, side-to-side and dorsoventral axes of fish. They were lowpass, bandpass or broadly tuned to low frequencies with Q50% at 15 dB above threshold in ranges from 0.28 to 3.30 (1.46±0.71), 0.18 to 2.54 (1.36±0.78), and 0.41 to 4.26 (2.25±0.1.12) along the three axes, showing slightly greater frequency tuning in the vertical axis than horizontal axes. At supra threshold we found tuning plasticity, i.e. best frequencies of saccular afferents shifted to high frequencies as stimulus level increased. Isolevel rate–frequency curves were asymmetrical with shallow slopes at the low-frequency edge and steep slopes at the high-frequency edge. Saccular afferents of the sleeper goby have similar capabilities of coding particle motion frequencies in the three orthogonal axes. Results from this and other studies suggest that (1) the saccule is the major hearing organ in this species, (2) the saccule of this species is capable of encoding sound frequencies in three dimensional space, and (3) saccular afferents in fishes without accessory auditory structures exhibit similar frequency selectivity in response to particle motion.

Listeners detected interaural differences of time (ITDs) or level (ILDs) carried by single 4000-Hz Gabor clicks (Gaussian-windowed tone bursts) and trains of 16 such clicks repeating at an interclick interval (ICI) of 2, 5, or 10 ms. In separate conditions, target interaural differences favored the right ear by a constant amount for all clicks (condition RR), attained their peak value at onset and diminished linearly to 0 at offset (condition R0), or grew linearly from 0 at onset to a peak value at offset (condition 0R). Threshold ITDs and ILDs were determined adaptively in separate experiments for each of these conditions and for single clicks. ITD thresholds were found to be lower for 16-click trains than for single clicks at 10-ms ICI, regardless of stimulus condition. At 2-ms ICI, thresholds in RR and R0 conditions were similar to single click thresholds at 2-ms ICI; thresholds in the 0R condition were significantly worse than for single clicks at 2-ms ICI, consistent with strong rate-dependent onset dominance in listeners’ temporal weighting of ITD. ILD thresholds, in contrast, were predominantly unaffected by ICI, suggesting little or no onset dominance for ILD of high-rate stimuli.

Acipenser fulvescens, the lake sturgeon, belongs to one of the few extant non-teleost ray-finned (bony) fishes. The sturgeons (family Acipenseridae) have a phylogenetic history that dates back about 250 million years. The study reported here is the first investigation of peripheral coding strategies for spectral analysis in the auditory system in a non-teleost bony fish. We used a shaker system to simulate the particle motion component of sound during electrophysiological recordings of isolated single units from the eighth nerve innervating the saccule and lagena. Background activity and response characteristics of saccular and lagenar afferents (such as thresholds, response–level functions and temporal firing) resembled the ones found in teleosts. The distribution of best frequencies also resembled data in teleosts (except for Carassius auratus, goldfish) tested with the same stimulation method. The saccule and lagena in A. fulvescens contain otoconia, in contrast to the solid otoliths found in teleosts, however, this difference in otolith structure did not appear to affect threshold, frequency tuning, intensity- or temporal responses of auditory afferents. In general, the physiological characteristics common to A. fulvescens, teleosts and land vertebrates reflect important functions of the auditory system that may have been conserved throughout the evolution of vertebrates.

Distortion-product otoacoustic emissions (DPOAEs) were measured with traditional DP-grams and level/phase (L/P) maps in rabbits with either normal cochlear function or unique sound-induced cochlear losses that were characterized as either low-frequency or notched configurations. To demonstrate that emission generators distributed basal to the f2 primary-tone contribute, in general, to DPOAE levels and phases, a high-frequency interference tone (IT) was presented at 1/3 of an octave (oct) above the f2 primary-tone, and DPOAEs were re-measured as “augmented” DP-grams (ADP-grams) and L/P maps. The vector difference between the control and augmented functions was then computed to derive residual DP-grams (RDP-grams) and L/P maps. The resulting RDP-grams and L/P maps, which described the DPOAEs removed by the IT, supported the notion that basal DPOAE components routinely contribute to the generation of standard measures of DPOAEs. Separate experiments demonstrated that these components could not be attributed to the effects of the 1/3-oct IT on f2, or DPOAEs generated by the addition of a third interfering tone. These basal components can “fill in” the lesion estimated by the commonly employed DP-gram. Thus, ADP-grams more accurately reveal the pattern of cochlear damage and may eventually lead to an improved DP-gram procedure.

A growing number of studies of auditory processing are being carried out in awake, behaving animals, creating a need for precisely controlled sound delivery without restricting head movements. We have designed a system for closed-field stimulus presentation in freely moving ferrets, which comprises lightweight, adjustable headphones that can be consistently positioned over the ears via a small, skull-mounted implant. The invasiveness of the implant was minimized by simplifying its construction and using dental adhesive only for attaching it to the skull, thereby reducing the surgery required and avoiding the use of screws or other anchoring devices. Attaching the headphones to a chronic implant also reduced the amount of contact they had with the head and ears, increasing the willingness of the animals to wear them. We validated sound stimulation via the headphones in ferrets trained previously in a free-field task to localize stimuli presented from one of two loudspeakers. Noise bursts were delivered binaurally over the headphones and interaural level differences (ILDs) were introduced to allow the sound to be lateralized. Animals rapidly transferred from the free-field task to indicate the perceived location of the stimulus presented over headphones. They showed near perfect lateralization with a 5 dB ILD, matching the scores achieved in the free-field task. As expected, the ferrets' performance declined when the ILD was reduced in value. This closed-field system can easily be adapted for use in other species, and provides a reliable means of presenting closed-field stimuli whilst monitoring behavioral responses in freely moving animals.

Neurons in the auditory cortex of anesthetized animals are generally considered to generate phasic responses to simple stimuli such as tones or noise bursts. In this paper, we show that under ketamine/medetomidine anesthesia, neurons in ferret auditory cortex usually exhibit complex sustained responses. We presented 100-ms broad-band noise bursts at a range of interaural level differences (ILDs) and average binaural levels (ABLs), and used extracellular electrodes to monitor evoked activity over 700 ms poststimulus onset. We estimated the degree of randomness (noise) in the response functions of individual neurons over poststimulus time; we found that neural activity was significantly modulated by sound for up to ∼500 ms following stimulus offset. Pooling data from all neurons, we found that spiking activity carries significant information about stimulus identity over this same time period. However, information about ILD decayed much more quickly over time compared with information about ABL. In addition, ILD and ABL are coded independently by the neural population even though this is not the case at individual neurons. Though most neurons responded more strongly to ILDs corresponding to the opposite side of space, as a population, they were equally informative about both contra- and ipsilateral stimuli.

Background: Barn owls integrate spatial information across frequency channels to localize sounds in space. Methodology/principal findings: We presented barn owls with synchronous sounds that contained different bands of frequencies (3-5 kHz and 7-9 kHz) from different locations in space. When the owls were confronted with the conflicting localization cues from two synchronous sounds of equal level, their orienting responses were dominated by one of the sounds: they oriented toward the location of the low frequency sound when the sources were separated in azimuth; in contrast, they oriented toward the location of the high frequency sound when the sources were separated in elevation. We identified neural correlates of this behavioral effect in the optic tectum (OT, superior colliculus in mammals), which contains a map of auditory space and is involved in generating orienting movements to sounds. We found that low frequency cues dominate the representation of sound azimuth in the OT space map, whereas high frequency cues dominate the representation of sound elevation. Conclusions/significance: Significance: We argue that the dominance hierarchy of localization cues reflects several factors: 1) the relative amplitude of the sound providing the cue, 2) the resolution with which the auditory system measures the value of a cue, and 3) the spatial ambiguity in interpreting the cue. These same factors may contribute to the relative weighting of sound localization cues in other species, including humans.

Cochlear hair cells (HCs) are mechanosensory receptors that transduce sound into electrical signals. HC damage in nonmammalian vertebrates induces surrounding supporting cells (SCs) to divide, transdifferentiate and replace lost HCs; however, such spontaneous HC regeneration does not occur in the mammalian cochlea. Here, we acutely ablate the retinoblastoma protein (Rb), a crucial cell cycle regulator, in two subtypes of postmitotic SCs (pillar and Deiters' cells) using an inducible Cre line, Prox1-CreER T2 . Inactivation of Rb in these SCs results in cell cycle reentry of both pillar and Deiters' cells, and completion of cell division with an increase in cell number of pillar cells. Interestingly, nuclei of Rb −/− mitotic pillar and Deiters' cells migrate toward the HC layer and divide near the epithelial surface in a manner similar to the SCs in the regenerating avian auditory epithelium. In contrast to postmitotic Rb −/− HCs which abort cell division, postmitotic Rb −/− pillar cells can proliferate, maintain their SC fate and survive for more than a week. However, no newly formed HCs are detected and SC death followed by HC loss occurs. Our studies accomplish a crucial step toward functional HC regeneration in the mammalian cochlea in vivo , demonstrating the critical role of Rb in maintaining quiescence of postmitotic pillar and Deiters' cells and highlighting the heterogeneity between these two cell types. Therefore, the combination of transient Rb inactivation and further manipulation of transcription factors (i.e., Atoh1 activation) in SCs may represent an effective therapeutic avenue for HC regeneration in the mammalian cochlea.

Recent studies demonstrate that mosquitoes listen to each other's wing beats just prior to mating in flight. Field potentials from sound-transducing neurons in the antennae contain both sustained and oscillatory components to pure and paired tone stimuli. Described here is a direct comparison of these two types of response in the dengue vector mosquito, Aedes aegypti. Across a wide range of frequencies and intensities, sustained responses to one- and two-tone stimuli are about equal in magnitude to oscillatory responses to the beats produced by two-tone stimuli. All of these responses are much larger than the oscillatory responses to one-tone stimuli. Similarly, the frequency range extends up to at least the fifth harmonic of the male flight tone for sustained responses to one- and two-tone stimuli and oscillatory responses at the beat frequency of two-tone stimuli, whereas the range of oscillatory response to a one-tone stimulus is limited to, at most, the third harmonic. Thresholds near the fundamental of the flight tone are lower for oscillatory responses than for sustained deflections, lower for males than for females, and within the behaviorally relevant range. A simple model of the transduction process can qualitatively account for both oscillatory and sustained responses to pure and paired tones. These data leave open the question as to which of several alternative strategies underlie flight tone matching behavior in mosquitoes.

Cluster of differentiation antigens (CD proteins) are classically used as immune cell markers. However, their expression within the inner ear is still largely undefined. In this study, we explored the possibility that specific CD proteins might be useful for defining inner ear cell populations. mRNA expression profiling of microdissected auditory and vestibular sensory epithelia revealed 107 CD genes as expressed in the early postnatal mouse inner ear. The expression of 68 CD genes was validated with real-time RT-PCR using RNA extracted from microdissected sensory epithelia of cochleae, utricles, saccules, and cristae of newborn mice. Specifically, CD44 was identified as preferentially expressed in the auditory sensory epithelium. Immunohistochemistry revealed that within the early postnatal organ of Corti, the expression of CD44 is restricted to outer pillar cells. In order to confirm and expand this finding, we characterized the expression of CD44 in two different strains of mice with loss- and gain-of-function mutations in Fgfr3 which encodes a receptor for FGF8 that is essential for pillar cell development. We found that the expression of CD44 is abolished from the immature pillar cells in homozygous Fgfr3 knockout mice. In contrast, both the outer pillar cells and the aberrant Deiters' cells in the Fgfr3 ( P244R/ ) (+) mice express CD44. The deafness phenotype segregating in DFNB51 families maps to a linkage interval that includes CD44. To study the potential role of CD44 in hearing, we characterized the auditory system of CD44 knockout mice and sequenced the entire open reading frame of CD44 of affected members of DFNB51 families. Our results suggest that CD44 does not underlie the deafness phenotype of the DFNB51 families. Finally, our study reveals multiple potential new cell type-specific markers in the mouse inner ear and identifies a new marker for outer pillar cells.

Gerbils aged in quiet show a decline of the endocochlear potential (EP) and elevated auditory nerve compound action potential (CAP) thresholds. However, establishing a direct relationship between an age-related reduction in the EP and changes in the activities of primary auditory neurons is difficult owing to the complexity of age-related histological changes in the cochlea. To address this issue, we developed a young gerbil model of "metabolic" presbyacusis that uses an osmotic pump to deliver furosemide into the round window niche for 7 days, resulting in a chronically reduced EP. In this model, the only major histopathologic changes were restricted to the hook region of the cochlea and consisted of loss of strial intermediate cells and massive edema in the lateral wall. The morphological and physiological evidence suggests that the cochlea can adapt to furosemide application over time. The morphology of spiral ganglion cells and hair cells appeared normal throughout the cochlea. CAP responses and EP values in this model are similar to those of quiet-aged ears. The spontaneous activity of single auditory fibers (n = 188) was assessed in 15 young gerbils treated with furosemide for 7 days. The percentage of recorded low-spontaneous rate (SR) fibers at characteristic frequencies (CFs) > or = 6 kHz was significantly lower in furosemide-treated than in control ears. Recovery function tests of CAP responses after prior stimulation also showed a decline in activity of the low-SR population with CFs > or = 6 kHz in the treated cochleas. A similar loss in the activity of low-SR fiber has been previously shown in quiet-aged gerbils. These results suggest that dysfunction of the cochlear lateral wall and subsequent chronic reduction in the EP can directly affect the activity patterns of primary auditory neurons in a manner similar to that seen in aged gerbils.

Psychophysical forward masking is an increase in threshold of detection of a sound (probe) when it is preceded by another sound (masker). This is reminiscent of the reduction in neuronal responses to a sound following prior stimulation. Studies in the auditory nerve and cochlear nucleus using signal detection theory techniques to derive neuronal thresholds showed that in centrally projecting neurons, increases in masked thresholds were significantly smaller than the changes measured psychophysically. Larger threshold shifts have been reported in the inferior colliculus of awake marmoset. The present study investigated the magnitude of forward masking in primary auditory cortical neurons of anaesthetised guinea-pigs. Responses of cortical neurons to unmasked and forward masked tones were measured and probe detection thresholds estimated using signal detection theory methods. Threshold shifts were larger than in the auditory nerve, cochlear nucleus and inferior colliculus. The larger threshold shifts suggest that central, and probably cortical, processes contribute to forward masking. However, although methodological differences make comparisons difficult, the threshold shifts in cortical neurons were, in contrast to subcortical nuclei, actually larger than those observed psychophysically. Masking was largely attributable to a reduction in the responses to the probe, rather than either a persistence of the masker responses or an increase in the variability of probe responses.

We measured the responses of neurons in auditory cortex of male and female ferrets to artificial vowels of varying fundamental frequency ( f 0 ), or periodicity, and compared these with the performance of animals trained to discriminate the periodicity of these sounds. Sensitivity to f 0 was found in all five auditory cortical fields examined, with most of those neurons exhibiting either low-pass or high-pass response functions. Only rarely was the stimulus dependence of individual neuron discharges sufficient to account for the discrimination performance of the ferrets. In contrast, when analyzed with a simple classifier, responses of small ensembles, comprising 3-61 simultaneously recorded neurons, often discriminated periodicity changes as well as the animals did. We examined four potential strategies for decoding ensemble responses: spike counts, relative first-spike latencies, a binary “spike or no-spike” code, and a spike-order code. All four codes represented stimulus periodicity effectively, and, surprisingly, the spike count and relative latency codes enabled an equally rapid readout, within 75 ms of stimulus onset. Thus, relative latency codes do not necessarily facilitate faster discrimination judgments. A joint spike count plus relative latency code was more informative than either code alone, indicating that the information captured by each measure was not wholly redundant. The responses of neural ensembles, but not of single neurons, reliably encoded f 0 changes even when stimulus intensity was varied randomly over a 20 dB range. Because trained animals can discriminate stimulus periodicity across different sound levels, this implies that ensemble codes are better suited to account for behavioral performance.

Localizing a sound source involves the detection and integration of various spatial cues present in the sound waves at each ear. Previous studies indicate that the brain circuits underlying sound localization are calibrated by experience of the cues available to each individual. Plasticity in spatial hearing is most pronounced during development but can also be demonstrated during adulthood under certain circumstances. Investigations into whether adult humans can adjust to reduced input in one ear and learn a new correspondence between interaural differences cues and directions in space have produced conflicting results. Here we show that humans of both sexes can relearn to localize broadband sounds with a flat spectrum in the horizontal plane after altering the spatial cues available by plugging one ear. In subjects who received daily training, localization accuracy progressively shifted back toward their pre-plug performance after 1 week of earplugging, whereas no improvement was seen if all trials were performed on the same day. However, localization performance did not improve on a task that used stimuli in which the source spectrum was randomized from trial to trial, indicating that monaural spectral cues are needed for plasticity. We also characterized the effects of the earplug on sensitivity to interaural time and level differences and found no clear evidence for adaptation to these cues as the free-field localization performance improved. These findings suggest that the mature auditory system can accommodate abnormal inputs and maintain a stable spatial percept by reweighting different cues according to how informative they are.

Objectives: To examine the impact of hearing impairment on a listener's ability to process simultaneous spoken messages. Design: Nine young listeners with bilateral sensorineural hearing loss and nine young listeners with normal hearing participated in this study. Two messages of equal level were presented separately to the two ears. The messages were systematically degraded by adding speech-shaped noise. Listeners performed a single task in which report of one message was required and a dual task in which report of both messages was required. Results: As the level of the added noise was increased, performance on both single and dual tasks declined. In the dual task, performance on the message reported second was poorer and more sensitive to the noise level than performance on the message reported first. When compared to listeners with normal hearing, listeners with hearing loss showed a larger deficit in recall of the second message than the first. This difference disappeared when performance of the hearing loss group was compared to that of the normal-hearing group at a poorer signal to noise ratio. Conclusions: A listener's ability to process a secondary message is more sensitive to noise and hearing impairment than the ability to process a primary message. Tasks involving the processing of simultaneous messages may be useful for assessing hearing handicap and the benefits of rehabilitation in realistic listening scenarios.

This project focused on the individual differences underlying observed variability in temporal processing among older listeners. Four measures of vowel temporal-order identification were completed by young (N=35; 18–31 years) and older (N=151; 60–88 years) listeners. Experiments used forced-choice, constant-stimuli methods to determine the smallest stimulus onset asynchrony (SOA) between brief (40 or 70 ms) vowels that enabled identification of a stimulus sequence. Four words (pit, pet, pot, and put) spoken by a male talker were processed to serve as vowel stimuli. All listeners identified the vowels in isolation with better than 90% accuracy. Vowel temporal-order tasks included the following: (1) monaural two-item identification, (2) monaural four-item identification, (3) dichotic two-item vowel identification, and (4) dichotic two-item ear identification. Results indicated that older listeners had more variability and performed poorer than young listeners on vowel-identification tasks, although a large overlap in distributions was observed. Both age groups performed similarly on the dichotic ear-identification task. For both groups, the monaural four-item and dichotic two-item tasks were significantly harder than the monaural two-item task. Older listeners’ SOA thresholds improved with additional stimulus exposure and shorter dichotic stimulus durations. Individual differences of temporal-order performance among the older listeners demonstrated the influence of cognitive measures, but not audibility or age.

One of the fundamental questions of auditory research is how sounds are segregated because, in natural environments, multiple sounds tend to occur at the same time. Concurrent sounds, such as two talkers, physically add together and arrive at the ear as a single input sound wave. The auditory system easily segregates this input into a coherent percept of each of the multiple sources. A common feature of speech and communication calls is their harmonic structure and in this report we used two harmonic complexes to study the role of the corticofugal pathway in the processing of concurrent sounds. We demonstrate that, in the inferior colliculus (IC) of the anesthetized guinea pig, deactivation of the auditory cortex altered the temporal and/or the spike response to the concurrent, monaural harmonic complexes. More specifically, deactivating the auditory cortex altered the representation of the relative level of the complexes. This suggests that the auditory cortex modulates the representation of the level of two harmonic complexes in the IC. Since sound level is a cue used in the segregation of auditory input, the corticofugal pathway may play a role in this segregation.

Mouse models are increasingly contributing to our understanding of the neural genetics of sensory processing and memory. For example, strain differences have helped elucidate basic mechanisms of age-related hearing loss and auditory fear conditioning. Assessing sensory differences arising in acoustic communication contexts is also important for understanding natural audition. While this topic has not been well studied, it is currently being addressed through auditory neuroethological studies in the CBA/CaJ strain, where insights will help lay a foundation for future neural genetic studies. Here, we focus on the responses of adult females to ultrasonic vocalizations of males. We tested a group of female mice in a place-preference paradigm before and after auditory and olfactory experience with a male. A control group was housed with other female cagemates between trials. All females showed an initial preference for male calls that rapidly decayed over the course of a trial. However, only females that had been pair-housed with a male during the inter-trial interval displayed a reinstated interest in male vocalizations, suggesting possible group differences in the assessment of the calls' behavioral relevance. These findings provide a timeframe during which auditory processing of male ultrasounds might be expected to show a difference depending on behavioral relevance, and also suggest an importance of social interactions in maintaining call recognition.

The ability to make intensity judgments for sequential stimuli was examined with an intensity-discrimination task involving three 50-ms noise bursts with non-overlapping frequency ranges. Targets (single bursts) presented in three-burst sequences were required to be as much as 5 dB more intense than targets presented as single bursts in isolation, especially for the later targets. Randomizing target position in the sequence did not reliably reduce performance, nor were thresholds for younger and older listeners reliably different. These increases in increment detection threshold are indications of a specific intensity-processing deficit for stimuli occurring later in a sequence.