Auditory Research publications

The directionality of hair cell stimulation combined with the vibration of the basilar membrane causes the auditory nerve fiber action potentials, in response to low-frequency stimuli, to occur at a particular phase of the stimulus waveform. Because direct mechanical measurements at the cochlear apex are difficult, such phase locking has often been used to indirectly infer the basilar membrane motion. Here, we confirm and extend earlier data from mammals using sine wave stimulation over a wide range of sound levels (up to 90 dB sound pressure level). We recorded phase-locked responses to pure tones over a wide range of frequencies and sound levels of a large population of auditory nerve fibers in the anesthetized guinea pig. The results indicate that, for a constant frequency of stimulation, the phase lag decreases with increases in the characteristic frequency (CF) of the nerve fiber. The phase lag decreases up to a CF above the stimulation frequency, beyond which it decreases at a much slower rate. Such phase changes are consistent with known basal cochlear mechanics. Measurements from individual fibers showed smaller but systematic variations in phase with sound level, confirming previous reports. We found a "null" stimulation frequency at which little variation in phase occurred with sound level. This null frequency was often not at the CF. At stimulation frequencies below the null, there was a progressive lag with sound level and a progressive lead for stimulation frequencies above the null. This was maximally 0.2 cycles.

Humans perceive a harmonic series as a single auditory object with a pitch equivalent to the fundamental frequency (F0) of the series. When harmonics are presented to alternate ears, the repetition rate of the waveform at each ear doubles. If the harmonics are resolved, then the pitch perceived is still equivalent to F0, suggesting the stimulus is binaurally integrated before pitch is processed. However, unresolved harmonics give rise to the doubling of pitch which would be expected from monaural processing (Bernstein and Oxenham, J. Acoust. Soc. Am., 113:3323-3334, 2003). We used similar stimuli to record responses of multi-unit clusters in the central nucleus of the inferior colliculus (IC) of anesthetized guinea pigs (urethane supplemented by fentanyl/fluanisone) to determine the nature of the representation of harmonic stimuli and to what extent there was binaural integration. We examined both the temporal and rate-tuning of IC clusters and found no evidence for binaural integration. Stimuli comprised all harmonics below 10 kHz with fundamental frequencies (F0) from 50 to 400 Hz in half-octave steps. In diotic conditions, all the harmonics were presented to both ears. In dichotic conditions, odd harmonics were presented to one ear and even harmonics to the other. Neural characteristic frequencies (CF, n = 85) were from 0.2 to 14.7 kHz; 29 had CFs below 1 kHz. The majority of clusters responded predominantly to the contralateral ear, with the dominance of the contralateral ear increasing with CF. With diotic stimuli, over half of the clusters (58%) had peaked firing rate vs. F0 functions. The most common peak F0 was 141 Hz. Almost all (98%) clusters phase locked diotically to an F0 of 50 Hz, and approximately 40% of clusters still phase locked significantly (Rayleigh coefficient >13.8) at the highest F0 tested (400 Hz). These results are consistent with the previous reports of responses to amplitude-modulated stimuli. Clusters phase locked significantly at a frequency equal to F0 for contralateral and diotic stimuli but at 2F0 for dichotic stimuli. We interpret these data as responses following the envelope periodicity in monaural channels rather than as a binaurally integrated representation.

Belgian Waterslager canaries (BWC), bred for a distinct low-pitched song, have an inherited high-frequency hearing loss associated with hair cell abnormalities. Hair cells near the abneural edge of the papilla, which receive primarily efferent innervation in normal birds, are among the most severely affected. These cells are thought to support nonlinear active processing in the avian ear, though the mechanisms are poorly understood. Here we present psychophysical evidence that suggests degraded active processing in BWC compared to normal-hearing non-BWC. Critical ratios, psychophysical masking patterns and phase effects on masking by harmonic complexes were measured in BWC and non-BWC using operant conditioning procedures. Critical ratios were much larger in BWC than in non-BWC at high frequencies. Psychophysical tuning curves derived from the masking patterns for BWC were broadened at high frequencies. BWC also showed severely reduced phase effects on masking by harmonic complexes compared to non-BWC. As has been hypothesized previously for hearing-impaired humans, these results are consistent with a loss of active processing mechanisms in BWC.

Adult cortical circuits possess considerable plasticity, which can be induced by modifying their inputs. One mechanism proposed to underlie changes in neuronal responses is spike-timing-dependent plasticity (STDP), an up- or downregulation of synaptic efficacy contingent upon the order and timing of presynaptic and postsynaptic activity. The repetitive and asynchronous pairing of a sensory stimulus with either another sensory stimulus or current injection can alter the response properties of visual and somatosensory neurons in a manner consistent with STDP. To examine whether such plasticity also exists in the auditory system, we recorded from neurons in the primary auditory cortex of anesthetized and awake adult ferrets. The repetitive pairing of pure tones of different frequencies induced shifts in neuronal frequency selectivity, which exhibited a temporal specificity akin to STDP. Only pairs with stimulus onset asynchronies of 8 or 12 ms were effective and the direction of the shifts depended upon the order in which the tones within a pair were presented. Six hundred stimulus pairs (lasting ∼70 s) were enough to produce a significant shift in frequency tuning and the changes persisted for several minutes. The magnitude of the observed shifts was largest when the frequency separation of the conditioning stimuli was < ∼1 octave. Moreover, significant shifts were found only in the upper cortical layers. Our findings highlight the importance of millisecond-scale timing of sensory input in shaping neural function and strongly suggest STDP as a relevant mechanism for plasticity in the mature auditory system.

In a variation on a procedure originally developed by Broadbent [(1952). “Failures of attention in selective listening,” J. Exp. Psychol. 44, 428–433] listeners were presented with two sentences spoken in a sequential, interleaved-word format. Sentence one (target) comprised the odd-numbered words in the sequence and sentence two (masker) comprised the even-numbered words in the sequence. The task was to report the words in sentence one. The goal was to determine the effectiveness of cues linking the words of the target (or masker) over time. Three such “linkage variables” were examined: (1) fixed talker, (2) fixed perceived interaural location, and (3) correct syntactic structure. All of the linkage variables provided a significant advantage when applied to the target compared to the baseline condition in which the linkage variables were randomized. However, these linkage variables were not effective when applied to the masker. Word position effects were found such that performance in the baseline condition declined, and the advantages of the linkage variables increased, for the words near the end of the sentence. Overall, this approach appears to be useful for examining interference in speech recognition that has little or no peripheral component. The results suggest that variables that link target words together improve their resiliency to interference and/or their recall.

In studies of the cocktail party problem, the number and locations of maskers are typically fixed throughout a block of trials, which leaves out uncertainty that exists in real-world environments. The current experiments examined whether there is (1) improved speech intelligibility and (2) increased spatial release from masking (SRM), as predictability of the number/locations of speech maskers is increased. In the first experiment, subjects identified a target word presented at a fixed level in the presence of 0, 1, or 2 maskers as predictability of the masker configuration ranged from 10% to 80%. The second experiment examined speech reception thresholds and SRM as (a) predictability of the masker configuration is increased from 20% to 80% and/or (b) the complexity of the listening environment is decreased. In the third experiment, predictability of the masker configuration was increased from 20% up to 100% while minimizing the onset delay between maskers and the target. All experiments showed no effect of predictability of the masker configuration on speech intelligibility or SRM. These results suggest that knowing the number and location(s) of maskers may not necessarily contribute significantly to solving the cocktail party problem, at least not when the location of the target is known.

Stereotyped intervals between successive sound pulses characterize the acoustic signals of anurans and other organisms and provide critical information to receivers. One class of midbrain neuron responds selectively when pulses are repeated at slow rates (long intervals). To examine the mechanisms that underlie long-interval selectivity, we made whole cell recordings, in vivo, from neurons in the anuran inferior colliculus (anuran IC). In most cases, long-pass interval selectivity appeared to arise from interplay between excitation and inhibition; in ∼25% of these cases, the delayed inhibition to a pulse overlapped with the excitation to the following pulse at fast pulse repetition rates (PRRs), resulting in a phasic “onset” response. In the remaining cases, inhibition appeared to precede excitation. These neurons did not respond to fast PRRs apparently because delayed excitation to a pulse overlapped with the inhibition to the following pulse. These results suggest that the relative timing of inhibition and excitation govern differences in the response properties of these two cell types. Loading cells with cesium increased their responses to fast AM rates, supporting a role for inhibition in long-interval selectivity. Three cells showed little or no evidence of inhibition and exhibited strong depression of excitation. These findings are discussed in the context of current models for long-pass interval selectivity.

Immediate effects of sequential and progressively enlarged spiral ganglion (SG) lesions were recorded from cochleas and inferior colliculi. Small SG-lesions produced modest elevations in cochlear tone-evoked compound action potential (CAP) thresholds across narrow frequency ranges; progressively enlarged lesions produced progressively higher CAP-threshold elevations across progressively wider frequency ranges. No comparable changes in distortion product otoacoustic emissions (DPOAEs) amplitudes were observed consistent with silencing of auditory nerve sectors without affecting organ of Corti function. Frequency response areas (FRAs) of inferior colliculus (IC) neurons were recorded before and immediately after SG-lesions using multi-site silicon arrays fixed in place with recording sites arrayed along IC frequency gradient. Individual post-lesion FRAs exhibited progressively elevated response thresholds and diminished response amplitudes at lesion frequencies, whereas responses at non-lesion frequencies were either unchanged or enhanced. Characteristic frequencies were shifted and silent areas were introduced within these FRAs. Sequentially larger lesions produced sequentially larger shifts in CF and/or enlarged silent areas within affected FRAs, producing immediate changes in IC frequency organization. These results contrast with those from the auditory nerve, extend previous reports of experience-induced plasticity in the auditory CNS, and support results indicating afferent convergence onto ICC neurons across broad frequency bands.

The Kv1.1 potassium channel subunit, encoded by the Kcna1 gene, is heavily expressed in the auditory brainstem and is thought to have a critical role in producing the high temporal precision of action potentials characteristic of the auditory system. Our intent was to determine whether temporal acuity was reduced in Kcna1 null-mutant (-/-) mice, compared to wild-type (+/+) and heterozygotic mice (+/-), as measured by the encoding of gaps in the inferior colliculus by near-field auditory evoked potentials (NFAEP) or behavioral gap detection (BGD) using a prepulse inhibition paradigm. NFAEPs were collected at 40, 60 and 80 dB SPL with gap durations from 0.5 to 64 ms. BGD data were collected using silent gaps in 70 dB noise from 1 to 15 ms in duration. There were no systematic effects of Kcna1 genotype on NFAEP recovery functions, NFAEP latencies, or the time constant for BGD, but there was a small reduction in asymptotic prepulse inhibition for the longest gap stimuli in -/- mice. Gap thresholds were approximately 1-2 ms across genotypes, stimulus conditions, and paradigms. These data suggest that the neural pathways encoding behaviorally relevant, rapid auditory temporal fluctuations are not limited by the absence of Kv1.1 expression.

Purpose K. Nishi and D. Kewley-Port (2007) trained Japanese listeners to perceive 9 American English monophthongs and showed that a protocol using all 9 vowels (fullset) produced better results than the one using only the 3 more difficult vowels (subset). The present study extended the target population to Koreans and examined whether protocols combining the 2 vowel sets would provide more effective training. Method Three groups of 5 Korean listeners were trained on American English vowels for 9 days using one of the 3 protocols: fullset only, first 3 days on subset then 6 days on fullset, or first 6 days on fullset then 3 days on subset. Participants' performance was assessed by pre- and posttraining tests, as well as by a midtraining test. Results (a) Fullset training was effective for Koreans as well as Japanese, (b) no advantage was found for the 2 combined protocols over the fullset-only protocol, and (c) sustained “nonimprovement” was observed for training using one of the combined protocols. Conclusions In using subsets for training on American English vowels, care should be taken not only in the selection of subset vowels but also in the training orders of subsets.

This study asked whether or not listeners with sensorineural hearing loss have an impaired ability to use top-down attention to enhance speech intelligibility in the presence of interfering talkers. Listeners were presented with a target string of spoken digits embedded in a mixture of five spatially separated speech streams. The benefit of providing simple visual cues indicating when and/or where the target would occur was measured in listeners with hearing loss, listeners with normal hearing, and a control group of listeners with normal hearing who were tested at a lower target-to-masker ratio to equate their baseline (no cue) performance with the hearing-loss group. All groups received robust benefits from the visual cues. The magnitude of the spatial-cue benefit, however, was significantly smaller in listeners with hearing loss. Results suggest that reduced utility of selective attention for resolving competition between simultaneous sounds contributes to the communication difficulties experienced by listeners with hearing loss in everyday listening situations.

This thesis is divided into six chapters (following Introduction). Each chapter was intended to be self-contained, so they do not have to be read in the order they are presented. Second chapter (Sec. 2) contains a detailed description of experimental techniques: surgery, recording, and training techniques we used in awake head-fixed rats. We have also included a detailed description of all sets of stimuli we used to probe neurons, analytical methods used to analyze data, and description of computational models used in other parts of the thesis.Third chapter (Sec. 3) focuses on description of single-neuron responses in primary auditory cortex of awake head-fixed rats. The primary emphasis of this part is on the sparse representation of various auditory stimuli we used to probe neurons, and the heterogeneity of responses of single neurons. To characterize population responses to sound in the auditory cortex we asked the question "What is the typical response to acoustic stimuli?" instead of what is usually asked "What is the stimulus that evokes a response?" We found that the population response was sparse, with many unresponsive neurons. In addition, the responsive neurons showed a great variety of responses. This heterogeneity of neuronal responses ("response zoo," courtesy of Anthony M. Zádor) was, however, surprisingly well characterized by lognormal distribution of firing rates. The observation that firing rates in awake auditory cortex were lognormally distributed was even more interesting given the observation of lognormal distribution of synaptic weights in the cerebral cortex.The fourth chapter (Sec. 4) focuses on mechanisms which could give rise to lognormal distribution of firing rates, as well as synaptic weights. We proposed specific types of correlations among synaptic connections, and formulated a multiplicative learning rule which led to the observed distributions. We were also able to characterize intracellular activity of neurons in awake auditory cortex. The fifth chapter (Sec. 5) contains analysis of so-called up and down states in awake auditory cortex. We show that up and down states—the "signature" subthreshold dynamics so often described in various cortical areas of anesthetized animals—were rare in the primary auditory cortex of awake rats, instead, subthreshold dynamics was consisted of brief, infrequent fluctuations of membrane potential.The experiments described and analyzed in chapters 2—-4 were conducted in naïve awake rats. As behavior or attention can influence neuronal activity even in primary sensory areas, we developed a setup for head-fixed behavior. In the sixth chapter (Sec. 6) we describe the sound discrimination task we have used to study behavior in head-fixed rats. We present a comparison of basic behavioral parameters between restrained and unrestrained rats, as well as evidence of nonauditory modulations of single neuron activity in auditory cortex.

The brain selectively extracts the most relevant information in top-down processing manner. Does the corticofugal system, a “back projection system,” constitute the neural basis of such top-down selection? Here, we show how focal activation of the auditory cortex with 500 nA electrical pulses influences the auditory information processing in the cochlear nucleus (CN) that receives almost unprocessed information directly from the ear. We found that cortical activation increased the response magnitudes and shortened response latencies of physiologically matched CN neurons, whereas decreased response magnitudes and lengthened response latencies of unmatched CN neurons. In addition, cortical activation shifted the frequency tunings of unmatched CN neurons toward those of the activated cortical neurons. Our data suggest that cortical activation selectively enhances the neural processing of particular auditory information and attenuates others at the first processing level in the brain based on sound frequencies encoded in the auditory cortex. The auditory cortex apparently implements a long-range feedback mechanism to select or filter incoming signals from the ear.

Auditory neurons in the superior colliculus (SC) respond preferentially to sounds from restricted directions to form a map of auditory space. The development of this representation is shaped by sensory experience, but little is known about the relative contribution of peripheral and central factors to the emergence of adult responses. By recording from the SC of anesthetized ferrets at different age points, we show that the map matures gradually after birth; the spatial receptive fields (SRFs) become more sharply tuned and topographic order emerges by the end of the second postnatal month. Principal components analysis of the head-related transfer function revealed that the time course of map development is mirrored by the maturation of the spatial cues generated by the growing head and external ears. However, using virtual acoustic space stimuli, we show that these acoustical changes are not by themselves responsible for the emergence of SC map topography. Presenting stimuli to infant ferrets through virtual adult ears did not improve the order in the representation of sound azimuth in the SC. But by using linear discriminant analysis to compare different response properties across age, we found that the SRFs of infant neurons nevertheless became more adult-like when stimuli were delivered through virtual adult ears. Hence, although the emergence of auditory topography is likely to depend on refinements in neural circuitry, maturation of the structure of the SRFs (particularly their spatial extent) can be largely accounted for by changes in the acoustics associated with growth of the head and ears.

Rodents have proven to be a useful model system to screen genes, ototoxic compounds and sound exposure protocols that may play a role in hearing loss. High-throughput screening depends upon a rapid and reliable functional assay for hearing loss. This study describes the use of a frequency modulated (FM) chirp stimulus as an alternative to the click to derive a rapid assessment of auditory brainstem response (ABR) threshold in the rodent. We designed a rising frequency A-chirp based upon the spatial mapping of preferred frequency along the rat basilar membrane to provide a more synchronous and equipotent input across the length of the cochlea. We observed that the ABR wave I and wave IV amplitudes evoked by the A-chirp were significantly greater than the click and that A-chirp minimum response thresholds were lower than the click. Subsequent analyses compared the efficacy of the A-chirp to linear, time-reversed and amplitude-reversed chirps and confirmed that the A-chirp was most effective chirp configuration. These data suggest that the A-chirp may be optimally suited as a single screening broad-frequency stimulus for rapid ABR threshold estimations in the rodent and could serve to complement more detailed frequency-specific physiologic and behavioral estimates of hearing threshold.

A survey of papers using auditory evoked potentials (AEPs) published over the last 10years (Table I) demonstrates that most AEP studies in animals have used subjective methods for auditory threshold determination. Subjective methods greatly reduce the value of statistical hypothesis testing and jeopardize tests of hypothetical experimental group differences in hearing sensitivity. Correspondingly, many attempts have been made to develop objective threshold determination methods, but these have not been used widely. Further, they seldom include an appreciation of the effects of residual noise in the AEP. In this study, AEPs evoked by tonal and noise stimuli in goldfish (Carassius auratus) were recorded and the residual background noise was measured and analyzed in detail. High variability was found in residual noise, but can be effectively controlled with a simple modification of averaging routines. Considerable interobserver disagreements were found using subjective threshold estimation. An objective method of threshold determination was developed based on comparison between AEP amplitude and controlled residual noise, using a signal detection theory approach to set specific threshold criteria. The usefulness of AEP in hypothesis testing for auditory function requires more control over residual background noise amplitudes and the use of objective threshold determination techniques.

Single-unit responses to infinitely iterated rippled noise and wideband noise were recorded from the cochlear nucleus of anesthetized chinchillas. Rippled noises had a fixed delay of 4ms, and spectral depth was varied by attenuating the delayed version of the noise. Temporal discharge patterns were analyzed using neural autocorrelograms, and responses to rippled noises were compared to wideband noise responses. Chopper units with best frequencies in the range of the first to second harmonics of the rippled noise showed large differences in discharge patterns between rippled noise and wideband noise responses, but chopper units with best frequencies centered at higher harmonics did not show large differences. Consequently, the Chopper group of units showed no evidence of a neural representation of the dominance region. Primarylike units did show a neural representation of dominance that is related to behavioral performance. For Primarylike units with best frequencies around the third to fifth harmonics of the rippled noise, large differences in discharge patterns between rippled noise and wideband noise responses were observed. The results suggest that bushy cells play an important role in processing pitch-related information and should be included as important elements in neural models of periodicity processing.

This study investigated the interaction between hearing loss, reverberation, and age on the benefit of spatially separating multiple masking talkers from a target talker. Four listener groups were tested based on hearing status and age. On every trial listeners heard three different sentences spoken simultaneously by different female talkers. Listeners reported keywords from the target sentence, which was presented at a fixed and known location. Maskers were colocated with the target or presented from spatially separated and symmetrically placed loudspeakers, creating a situation with no simple “better-ear.” Reverberation was also varied. The target-to-masker ratio at threshold for identification of the fixed-level target was measured by adapting the level of the maskers. On average, listeners with hearing loss showed less spatial release from masking than normal-hearing listeners. Age was a significant factor although small differences in hearing sensitivity across age groups may have contributed to this effect. Spatial release was reduced in the more reverberant room condition but in most cases a significant advantage remained. These results provide evidence for a large benefit of spatial separation in a multitalker situation that is likely due to perceptual factors. However, this benefit is significantly reduced by both hearing loss and reverberation.

Accurate temporal processing of sound is essential for detecting word structures in speech. Maternal smoking affects speech processing in newborns and may influence child language development; however, it is unclear how neonatal exposure to nicotine, present in cigarettes, affects the normal development of temporal processing. The present study used the gap-induced prepulse inhibition (gap-PPI) of the acoustic startle response to investigate the effects of neonatal nicotine exposure on the normal development of gap detection, a behavioral testing procedure of auditory temporal resolution. Neonatal rats were injected twice per day with saline (control), 1mg/kg nicotine (N-1 mg) or 5 mg/kg nicotine (N-5 mg) from postnatal day 8-12 (P8-P12). During the first month after birth, rats showed poor gap-PPI in all three groups. At P45 and P60, gap-PPI in control rats improved significantly, whereas rats exposed to nicotine exhibited less improvement. At P60, the gap-detection threshold in the N-5 mg group was significantly higher than in the control group, suggesting that neonatal nicotine exposure affects the normal development of gap-detection acuity. Additionally, 1h after receiving an acute nicotine injection (1 mg/kg), gap-PPI recorded in adult rats from the N-5 mg group showed a temporary significant improvement. These results suggest that neonatal nicotine exposure reduces gap-PPI implying an impairment of the normal development of auditory temporal processing by inducing changes in cholinergic systems.

The survival of the auditory nerve in cases of sensorineural hearing loss is believed to be a major factor in effective cochlear implant function. The current study assesses two measures of cochlear implant thresholds following a post-deafening treatment intended to halt auditory nerve degeneration. We used an adenoviral construct containing a gene insert for brain-derived neurotrophic factor (BDNF), a construct that has previously been shown to promote neuronal survival in a number of biological systems. We implanted ototoxically deafened guinea pigs with a multichannel cochlear implant and delivered a single inoculation of an adenovirus suspension coding for BDNF (Ad.BDNF) into the scala tympani at the time of implantation. Thresholds to electrical stimulation were assessed both psychophysically and electrophysiologically over a period of 80 days. Spiral ganglion cell survival was analyzed at the 80 days time point. Compared to the control group, the Ad.BDNF treated group had lower psychophysical and electrophysiological thresholds as well as higher survival of spiral ganglion cells. Electrophysiological, but not psychophysical, thresholds correlated well with the density of spiral ganglion cells. These results indicate that the changes in the anatomy of the auditory nerve induced by the combination of Ad.BDNF inoculation and the electrical stimulation used for testing improved functional measures of CI performance.