Auditory Research publications

The dominant cue for localization of low-frequency sounds are microsecond differences in the time-of-arrival of sounds at the two ears [interaural time difference (ITD)]. In mammals, ITD sensitivity is established in the medial superior olive (MSO) by coincidence detection of excitatory inputs from both ears. Hence the relative delay of the binaural inputs is crucial for adjusting ITD sensitivity in MSO cells. How these delays are constructed is, however, still unknown. Specifically, the question of whether inhibitory inputs are involved in timing the net excitation in MSO cells, and if so how, is controversial. These inhibitory inputs derive from the nuclei of the trapezoid body, which have physiological and structural specializations for high-fidelity temporal transmission, raising the possibility that well timed inhibition is involved in tuning ITD sensitivity. Here, we present physiological and pharmacological data from in vivo extracellular MSO recordings in anesthetized gerbils. Reversible blockade of synaptic inhibition by iontophoretic application of the glycine antagonist strychnine increased firing rates and significantly shifted ITD sensitivity of MSO neurons. This indicates that glycinergic inhibition plays a major role in tuning the delays of binaural excitation. We also tonically applied glycine, which lowered firing rates but also shifted ITD sensitivity in a way analogous to strychnine. Hence tonic glycine application experimentally decoupled the effect of inhibition from the timing of its inputs. We conclude that, for proper ITD processing, not only is inhibition necessary, but it must also be precisely timed.

Rodent ultrasonic vocalizations (USVs) are ethologically critical social signals. Rats emit 22kHz USVs and 50kHz USVs, respectively, in conjunction with negative and positive affective states. Little is known about what controls emotional reactivity to these social signals. Using male Sprague-Dawley rats, we examined unconditional and conditional freezing behavior in response to the following auditory stimuli: three 22kHz USVs, a discontinuous tone whose frequency and on-off pattern matched one of the USVs, a continuous tone with the same or lower frequencies, a 4kHz discontinuous tone with an on-off pattern matched to one of the USVs, and a 50kHz USV. There were no differences among these stimuli in terms of the unconditional elicitation of freezing behavior. Thus, the stimuli were equally neutral before conditioning. During differential fear conditioning, one of these stimuli (the CS(+)) always co-terminated with a footshock unconditional stimulus (US) and another stimulus (the CS(-)) was explicitly unpaired with the US. There were no significant differences among these cues in CS(+)-elicited freezing behavior. Thus, the stimuli were equally salient or effective as cues in supporting fear conditioning. When the CS(+) was a 22kHz USV or a similar stimulus, rats discriminated based on the principal frequency and/or the temporal pattern of the stimulus. However, when these same stimuli served as the CS(-), discrimination failed due to generalization from the CS(+). Thus, the stimuli differed markedly in the specificity of conditioning. This strikingly asymmetrical stimulus generalization is a novel bias in discrimination.

Nicotinic acetylcholine receptors (nAChRs) contribute to sensory-cognitive function, as demonstrated by evidence that nAChR activation enhances, and nAChR blockade impairs, neural processing of sensory stimuli and sensory-cognitive behavior. To better understand the relationship between nAChR function and behavior, here we compare the strength of nAChR-mediated physiology in individual animals to their prior auditory behavioral performance. Adult rats were trained on an auditory-cued, active avoidance task over 4 days and classified as "good," "intermediate" or "poor" performers based on their initial rate of learning and eventual level of performance. Animals were then anesthetized, and tone-evoked local field potentials (LFPs) recorded in layer 4 of auditory cortex (ACx) before and after a test dose of nicotine (0.7mg/kg, s.c.) or saline. In "good" performers, nicotine enhanced LFP amplitude and decreased response threshold to characteristic frequency (CF) stimuli, yet had opposite effects (decreased amplitude, increased threshold) on responses to spectrally distant stimuli; i.e., cortical receptive fields became more selective for CF stimuli. In contrast, nicotine had little effect on LFP amplitude in "intermediate" or "poor" performing animals. Nicotine did, however, reduce LFP onset latency in all three groups, indicating that all received an effective dose of the drug. Our findings suggest that nicotinic regulation of cortical receptive fields may be a distinguishing feature of the best-performing animals, and may facilitate sensory-related learning by enhancing receptive field selectivity.

Cochlear implant speech processors transmit temporal features of sound as amplitude modulation of constant-rate electrical pulse trains. This study evaluated the central representation of amplitude modulation in the form of phase-locked firing of neurons in the auditory cortex. Anesthetized pigmented guinea pigs were implanted with cochlear electrode arrays. Stimuli were 254 pulse/s (pps) trains of biphasic electrical pulses, sinusoidally modulated with frequencies of 10–64 Hz and modulation depths of −40 to −5 dB re 100% (i.e., 1–56.2% modulation). Single- and multiunit activity was recorded from multi-site silicon-substrate probes. The maximum frequency for significant phase locking (limiting modulation frequency) was ≥60 Hz for 42% of recording sites, whereas phase locking to pulses of unmodulated pulse trains rarely exceeded 30 pps. The strength of phase locking to frequencies ≥40 Hz often varied nonmonotonically with modulation depth, commonly peaking at modulation depths around −15 to −10 dB. Cortical phase locking coded modulation frequency reliably, whereas a putative rate code for frequency was confounded by rate changes with modulation depth. Group delay computed from the slope of mean phase versus modulation frequency tended to increase with decreasing limiting modulation frequency. Neurons in cortical extragranular layers had lower limiting modulation frequencies than did neurons in thalamic afferent layers. Those observations suggest that the low-pass characteristic of cortical phase locking results from intracortical filtering mechanisms. The results show that cortical neurons can phase lock to modulated electrical pulse trains across the range of modulation frequencies and depths presented by cochlear implant speech processors.

Little is known about the basic processes underlying the behavior of singing. This experiment was designed to examine differences in the representation of the mapping between fundamental frequency (F0) feedback and the vocal production system in singers and nonsingers. Auditory feedback regarding F0 was shifted down in frequency while participants sang the consonant-vowel /ta/. During the initial frequency-altered trials, singers compensated to a lesser degree than nonsingers, but this difference was reduced with continued exposure to frequency-altered feedback. After brief exposure to frequency altered auditory feedback, both singers and nonsingers suddenly heard their F0 unaltered. When participants received this unaltered feedback, only singers' F0 values were found to be significantly higher than their F0 values produced during baseline and control trials. These aftereffects in singers were replicated when participants sang a different note than the note they produced while hearing altered feedback. Together, these results suggest that singers rely more on internal models than nonsingers to regulate vocal productions rather than real time auditory feedback.

Middle-ear sound transmission was evaluated as the middle-ear transfer admittance HMY (the ratio of stapes velocity to ear-canal sound pressure near the umbo) in gerbils during closed-field sound stimulation at frequencies from 0.1to60kHz, a range that spans the gerbil’s audiometric range. Similar measurements were performed in two laboratories. The HMY magnitude (a) increased with frequency below 1kHz, (b) remained approximately constant with frequency from 5to35kHz, and (c) decreased substantially from 35to50kHz. The HMY phase increased linearly with frequency from 5to35kHz, consistent with a 20–29μs delay, and flattened at higher frequencies. Measurements from different directions showed that stapes motion is predominantly pistonlike except in a narrow frequency band around 10kHz. Cochlear input impedance was estimated from HMY and previously-measured cochlear sound pressure. Results do not support the idea that the middle ear is a lossless matched transmission line. Results support the ideas that (1) middle-ear transmission is consistent with a mechanical transmission line or multiresonant network between 5 and 35kHz and decreases at higher frequencies, (2) stapes motion is pistonlike over most of the gerbil auditory range, and (3) middle-ear transmission properties are a determinant of the audiogram.

Previous studies have shown large decreases in cochlear implant psychophysical detection thresholds during the weeks following the onset of electrical testing. The current study sought to determine the variables underlying these threshold decreases by examining the effects of four deafening and implantation procedures on detection thresholds and implant impedances. Thirty-two guinea pigs were divided into four matched groups. Group I was deafened and implanted Day 0 and began electrical testing Day 1. Group II was deafened and implanted Day 0 and began electrical testing Day 45. Group III was deafened Day 0, implanted Day 45 and began electrical testing Day 46. Group IV was not predeafened but was implanted Day 0 and began electrical testing Day 1. All groups showed threshold decreases over time but the magnitude of change, time course and final stable threshold levels depended on the type and time course of treatment. Impedances increased over the first two weeks following the onset of electrical testing except in Group II. Results suggest that multiple mechanisms underlie the observed threshold shifts including (1) recovery of the cochlea from a temporary pathology caused by the deafening and/or implantation procedures, (2) effects of electrical stimulation on the auditory pathway, and (3) tissue growth in the implanted cochlea. They also suggest that surviving hair cells influence electrical threshold levels.

Studies of the F344 rat have shown a variety of age-related auditory anatomy and physiology changes. The current study was undertaken to clarify the ARHL in the F344 rat, by examining the auditory pathway of the F344/NHsd substrain that is distributed by Harlan Laboratories for research in the United States. The F344/NHsd rat begins to lose its hearing at about 12 months, and by 24 months, there are 50-60 dB auditory brainstem response threshold shifts at 20 and 40 kHz and 20 dB losses at 5-10 kHz. Distortion product otoacoustic emissions (DPOAE) amplitudes at 1.8-12 kHz stimuli were depressed in the older (18-24 months) rats. Amplitude input-output functions of the compound action potential (CAP) were also depressed across frequency. The endocochlear potential (EP) was 90-100 mV in the 3 month old rats. All but one of the 24 month old rats' EPs were in the +75-85 mV range. Tympanometry revealed no differences in middle ear function between the young and older rats. Collectively, these findings suggest damage to the outer hair cells, but anatomical examination of the outer hair cells revealed a relative lack of cell loss compared to the magnitude of the hearing and DPOAE loss.

Cisplatin, a widely used anticancer drug, preferentially damages outer hair cells (OHCs) of the inner ear. In this study, an antibody microarray was used to identify early changes in protein expression in the rat cochlea induced by cisplatin. Only small changes in hearing thresholds (4-34 dB elevation) were detected two days after cisplatin treatment (12 mg/kg). OHC function, measured by otoacoustic emissions, was slightly depressed (10 dB), and little or no receptor cell loss was observed. However, cisplatin induced large changes in the expression of 19 proteins involved in apoptosis, cell survival, or progression through the cell cycle. Fifteen of the proteins are novel to the study of the inner ear. Immunoblotting confirmed increases in the levels of the pro-survival activating transcription factor 2 (ATF2), of pro-apoptotic serine-threonine protein kinase, receptor interacting protein, and a 70/75 kDa nitrotyrosine bearing doublet of unknown function. Anti-nitrotyrosine antibodies localized these oxidatively damaged proteins to the stereocilia of OHCs, the Golgi-centrosome region of Hensen's cells, nuclei of outer pillar cells, and tunnel crossing fibers innervating OHCs. The results of this proteomic analysis reflect the commencement of ototoxic and cell survival responses before the observation of a significant functional or anatomical loss.

Studies of sound localization in humans have used various behavioral measures to quantify the observers' perceptions; a non-comprehensive list includes verbal reports, head pointing, gun pointing, stylus pointing, and laser aiming. Comparison of localization performance reveals that in humans, just as in animals, different results are obtained with different experimental tasks. Accordingly, to circumvent problems associated with task selection and training, this study used gaze, an ethologically valid behavior for spatial pointing in species with a specialized area of the fovea, to measure sound localization perception of human subjects. Orienting using gaze as a pointer does not require training, preserves the natural link between perception and action, and allows for direct behavioral comparisons across species. The results revealed, unexpectedly, a large degree of variability across subjects in both accuracy and precision. The magnitude of the average angular localization errors for the most eccentric horizontal targets, however, were very similar to those documented in studies that used head pointing, whereas the magnitude of the localization errors for the frontal targets were considerably larger. In addition, an overall improvement in sound localization in the context of the memory-saccade task, as well as a lack of effect of initial eye and head position on perceived sound location were documented.

Auditory neurons must represent accurately a wide range of sound levels using firing rates that vary over a far narrower range of levels. Recently, we demonstrated that this "dynamic range problem" is lessened by neural adaptation, whereby neurons adjust their input-output functions for sound level according to the prevailing distribution of levels. These adjustments in input-output functions increase the accuracy with which levels around those occurring most commonly are coded by the neural population. Here, we examine how quickly this adaptation occurs. We recorded from single neurons in the auditory midbrain during a stimulus that switched repeatedly between two distributions of sound levels differing in mean level. The high-resolution analysis afforded by this stimulus showed that a prominent component of the adaptation occurs rapidly, with an average time constant across neurons of 160 ms after an increase in mean level, much faster than our previous experiments were able to assess. This time course appears to be independent of both the timescale over which sound levels varied and that over which sound level distributions varied, but is related to neural characteristic frequency. We find that adaptation to an increase in mean level occurs more rapidly than to a decrease. Finally, we observe an additional, slow adaptation in some neurons, which occurs over a timescale of tens of seconds. Our findings provide constraints in the search for mechanisms underlying adaptation to sound level. They also have functional implications for the role of adaptation in the representation of natural sounds.

The acoustical cues for sound location are generated by spatial- and frequency-dependent filtering of propagating sound waves by the head and external ears. Although rats have been a common model system for anatomy, physiology, and psychophysics of localization, there have been few studies of the acoustical cues available to rats. Here, directional transfer functions (DTFs), the directional components of the head-related transfer functions, were measured in six adult rats. The cues to location were computed from the DTFs. In the frontal hemisphere, spectral notches were present for frequencies from ∼16to30kHz; in general, the frequency corresponding to the notch increased with increases in source elevation and in azimuth toward the ipsilateral ear. The maximum high-frequency envelope-based interaural time differences (ITDs) were 130μs, whereas low-frequency (<3.5kHz) fine-structure ITDs were 160μs; both types of ITDs were larger than predicted from spherical head models. Interaural level differences (ILDs) strongly depended on location and frequency. Maximum ILDs were <10dB for frequencies <8kHz and were as large as 20–40dB for frequencies >20kHz. Removal of the pinna eliminated the spectral notches, reduced the acoustic gain and ILDs, altered the acoustical axis, and reduced the ITDs.

Purpose This study examined how repeated presentations of words in noise affected understanding of both trained and untrained words in noise (in isolation and in sentences). Method Eight older listeners with hearing impairment completed a word-based auditory training protocol lasting approximately 12 weeks. Training materials were presented in a closed-set condition with both orthographic and auditory feedback on a trial-to-trial basis. Performance on both trained and untrained lexically easy and hard words, as well as generalization to sentences, was measured. Listeners then returned for an additional 14 weeks to monitor retention of the trained materials. Results Training listeners on 1 set of words improved both their open- and closed-set recognition of the trained materials but did not improve performance on another set of untrained words. When training switched to the other set, performance for the new set of words improved significantly, whereas significant improvements on the previously trained words were maintained. Training generalized to unfamiliar talkers but did not generalize to untrained words or untrained keywords within running speech. Listeners were able to maintain improved performance over an extended period. Conclusion Older listeners were able to improve their word-recognition performance in noise on a set of 150 words with training.

This study investigated the extent to which language familiarity affects the perception of the indexical properties of speech by testing listeners’ identification and discrimination of bilingual talkers across two different languages. In one experiment, listeners were trained to identify bilingual talkers speaking in only one language and were then tested on their ability to identify the same talkers speaking in another language. In the second experiment, listeners discriminated between bilingual talkers across languages in an AX discrimination paradigm. The results of these experiments indicate that there is sufficient language-independent indexical information in speech for listeners to generalize knowledge of talkers’ voices across languages and to successfully discriminate between bilingual talkers regardless of the language they are speaking. However, the results of these studies also revealed that listeners do not solely rely on language-independent information when performing these tasks. Listeners use language-dependent indexical cues to identify talkers who are speaking a familiar language. Moreover, the tendency to perceive two talkers as the “same” or “different” depends on whether the talkers are speaking in the same language. The combined results of these experiments thus suggest that indexical processing relies on both language-dependent and language-independent information in the speech signal.

Listeners are relatively good at estimating the true content of each physical source in a sound mixture in most everyday situations. However, if there is a spectrotemporal element that logically could belong to more than one object, the correct way to group that element can be ambiguous. Many psychoacoustic experiments have implicitly assumed that when a sound mixture contains ambiguous sound elements, the ambiguous elements “trade” between competing sources, such that the elements contribute more to one object in conditions when they contribute less to others. However, few studies have directly tested whether such trading occurs. While some studies found trading, trading failed in some recent studies in which spatial cues were manipulated to alter the perceptual organization. The current study extended this work by exploring whether trading occurs for similar sound mixtures when frequency content, rather than spatial cues, was manipulated to alter grouping. Unlike when spatial cues were manipulated, results are roughly consistent with trading. Together, results suggest that the degree to which trading is obeyed depends on how stimuli are manipulated to affect object formation.

WD40 repeat 1 protein (WDR1) was first reported in the acoustically injured chicken inner ear, and bioinformatics revealed that WDR1 has numerous WD40 repeats, important for protein-protein interactions. It has significant homology to actin interacting protein 1 (Aip1) in several lower species such as yeast, roundworm, fruitfly and frog. Several studies have shown that Aip1 binds cofilin/actin depolymerizing factor, and that these interactions are pivotal for actin disassembly via actin filament severing and actin monomer capping. However, the role of WDR1 in auditory function has yet to be determined. WDR1 is typically restricted to hair cells of the normal avian basilar papilla, but is redistributed towards supporting cells after acoustic overstimulation, suggesting that WDR1 may be involved in inner ear response to noise stress. One aim of the present study was to resolve the question as to whether stress factors, other than intense sound, could induce changes in WDR1 presence in the affected avian inner ear. Several techniques were used to assess WDR1 presence in the inner ears of songbird strains, including Belgian Waterslager (BW) canary, an avian strain with degenerative hearing loss thought to have a genetic basis. Reverse transcription, followed by polymerase chain reactions with WDR1-specific primers, confirmed WDR1 presence in the basilar papillae of adult BW, non-BW canaries, and zebra finches. Confocal microscopy examinations, following immunocytochemistry with anti-WDR1 antibody, localized WDR1 to the hair cell cytoplasm along the avian sensory epithelium. In addition, little, if any, staining by anti-WDR1 antibody was observed among supporting cells in the chicken or songbird ear. The present observations confirm and extend the early findings of WDR1 localization in hair cells, but not in supporting cells, in the normal avian basilar papilla. However, unlike supporting cells in the acoustically damaged chicken basilar papilla, the inner ear of the BW canary showed little, if any, WDR1 up-regulation in supporting cells. This may be due to the fact that the BW canary already has established hearing loss and/or to the possibility that the mechanism(s) involved in BW hearing loss may not be related to WDR1.

Loss of temporal processing is characteristic of age-related loss of speech understanding observed in the elderly. Inhibitory glycinergic circuits provide input onto dorsal cochlear nucleus (DCN) projection neurons which likely serve to modulate excitatory responses to time-varying complex acoustic signals. The present study sought to test the hypothesis that age-related loss of inhibition would compromise the ability of output neurons to encode sinusoidally amplitude modulated (SAM) tones. Extracellular recordings were obtained from young and aged FBN rat DCN putative fusiform cells. Stimuli were SAM tones at three modulation depths (100, 50, and 20%) at 30 dB hearing level with the carrier frequency set to the unit's characteristic frequency. Discharge rate and synchrony were calculated to describe SAM responses. There were significant age-related changes in the shape and peak vector strength [best modulation frequency (BMF)] of temporal modulation transfer functions (tMTFs), with no significant age-related changes in rate modulation transfer functions (rMTFs) at BMF. Young neurons exhibited band-pass tMTFs for most SAM conditions while aged fusiform cells exhibited significantly more low-pass or double-peaked tMTFs. There were significant differences in tMTFs between buildup, pauser-buildup, and wide-chopper temporal response types. Young and aged wide-choppers displayed significantly lower vector strength values than the other two temporal DCN response types. Age-related decreases in the number of pauser-buildup response types and increases in wide-chopper types reported previously, could account, in part, for the observed loss of temporal coding of the aged fusiform cell. Age-related changes in SAM coding were similar to changes observed with receptor blockade of glycinergic inhibition onto fusiform cells and consistent with previously observed age-related loss of endogenous glycine levels and changes in normal adult glycine receptor function. DCN changes in SAM coding could, in part, underpin temporal processing deficits observed in the elderly.

We assessed the spatial-tuning properties of units in the cat's anterior auditory field (AAF) and compared them with those observed previously in the primary (A1) and posterior auditory fields (PAF). Multi-channel, silicon-substrate probes were used to record single- and multi-unit activity from the right hemispheres of alpha-chloralose-anesthetized cats. Spatial tuning was assessed using broadband noise bursts that varied in azimuth or elevation. Response latencies were slightly, though significantly, shorter in AAF than A1, and considerably shorter in both of those fields than in PAF. Compared to PAF, spike counts and latencies were more poorly modulated by changes in stimulus location in AAF and A1, particularly at higher sound pressure levels. Moreover, units in AAF and A1 demonstrated poorer level tolerance than units in PAF with spike rates modulated as much by changes in stimulus intensity as changes in stimulus location. Finally, spike-pattern-recognition analyses indicated that units in AAF transmitted less spatial information, on average, than did units in PAF-an observation consistent with recent evidence that PAF is necessary for sound-localization behavior, whereas AAF is not.

Sensory experiences contribute to the development and specialization of signal processing capacities in the mammalian auditory system during a "critical period" of postnatal development. Earlier studies have shown that passive exposure to tonal stimuli during this postnatal epoch induces a large-scale expansion of the representations of those stimuli within the primary auditory cortex (A1) [Zhang LI, Bao S, Merzenich MM (2001) Persistent and specific influences of early acoustic environments on primary auditory cortex. Nat Neurosci 4:1123-1130]. Here, we show that exposing rat pups through the normal critical period epoch and beyond to continuous, un-modulated, moderate-level tones induces no such representational distortion, and in fact disrupts the normal development of frequency response selectivity and tonotopicity all across area A1. The area of cortex responding selectively to continuously exposed sound frequencies was actually reduced, when compared with rats reared in normal environments. Strong exposure-driven plasticity characteristic of the critical period could be induced well beyond the normal end of the critical period, by simply modulating the tonal stimulus. Thus, continuous tone exposure, like continuous noise exposure [Chang EF, Merzenich MM (2003) Environmental noise retards auditory cortical development. Science 300:498-502], ineffectively induces critical period plasticity, and indefinitely blocks the closure of a normally-brief critical period window. These findings again demonstrate the crucial role of temporally structured inputs for inducing the progressive cortical maturational changes that result in the closure of the critical period window.

Auditory localization experiments typically either require subjects to judge the location of a sound source from a discrete set of response alternatives or involve measurements of the accuracy of orienting responses made toward the source location. To compare the results obtained by both methods, we trained ferrets by positive conditioning to stand on a platform at the center of a circular arena prior to stimulus presentation and then approach the source of a broadband noise burst delivered from 1 of 12 loudspeakers arranged at 30 degrees intervals in the horizontal plane. Animals were rewarded for making a correct choice. We also obtained a non-categorized measure of localization accuracy by recording head-orienting movements made during the first second following stimulus onset. The accuracy of the approach-to-target responses declined as the stimulus duration was reduced, particularly for lateral and posterior locations, although responses to sounds presented in the frontal region of space and directly behind the animal remained quite accurate. Head movements had a latency of approximately 200 ms and varied systematically in amplitude with stimulus direction. However, the final head bearing progressively undershot the target with increasing eccentricity and rarely exceeded 60 degrees to each side of the midline. In contrast to the approach-to-target responses, the accuracy of the head orienting responses did not change much with stimulus duration, suggesting that the improvement in percent correct scores with longer stimuli was due, at least in part, to re-sampling of the acoustical stimulus after the initial head turn had been made. Nevertheless, for incorrect trials, head orienting responses were more closely correlated with the direction approached by the animals than with the actual target direction, implying that at least part of the neural circuitry for translating sensory spatial signals into motor commands is shared by these two behaviors.