Auditory Research publications

Linear measures of auditory receptive fields do not always fully account for a neuron's response to spectrotemporally-complex signals such as frequency-modulated sweeps (FM) and communication sounds. A possible source of this discrepancy is cross-frequency interactions, common response properties which may be missed by linear receptive fields but captured using two-tone masking. Using a patterned tonal sequence that included a balanced set of all possible tone-to-tone transitions, we have here combined the spectrotemporal receptive field with two-tone masking to measure spectrotemporal response maps (STRM). Recording from single units in the mustached bat inferior colliculus, we found significant non-linear interactions between sequential tones in all sampled units. In particular, tone-pair STRMs revealed three common features not visible in linear single-tone STRMs: 1) two-tone facilitative interactions, 2) frequency-specific suppression, and 3) post-stimulatory suppression in the absence of spiking. We also found a correlative relationship between these nonlinear receptive field features and sensitivity for different rates and directions of FM sweeps, dynamic features found in many vocalizations, including speech. The overwhelming prevalence of cross-frequency interactions revealed by this technique provides further evidence of the central auditory system's role as a pattern-detector, and underscores the need to include nonlinearity in measures of the receptive field.

In the precedence effect, sounds emanating directly from the source are localized preferentially over their reflections. Although most studies have focused on the delay between the onset of a sound and its echo, humans still experience the precedence effect when this onset delay is removed. We tested in barn owls the hypothesis that an ongoing delay, equivalent to the onset delay, is discernible from the envelope features of amplitude-modulated stimuli and may be sufficient to evoke this effect. With sound pairs having only envelope cues, owls localized direct sounds preferentially, and neurons in their auditory space-maps discharged more vigorously to them, but only if the sounds were amplitude modulated. Under conditions that yielded the precedence effect, acoustical features known to evoke neuronal discharges were more abundant in the envelopes of the direct sounds than of the echoes, suggesting that specialized neural mechanisms for echo suppression were unnecessary.

Although lizards have highly sensitive ears, it is difficult to condition them to sound, making standard psychophysical assays of hearing sensitivity impractical. This paper describes non-invasive measurements of the auditory brainstem response (ABR) in both Tokay geckos (Gekko gecko; nocturnal animals, known for their loud vocalizations) and the green anole (Anolis carolinensis, diurnal, non-vocal animals). Hearing sensitivity was measured in 5 geckos and 7 anoles. The lizards were sedated with isoflurane, and ABRs were measured at levels of 1 and 3% isoflurane. The typical ABR waveform in response to click stimulation showed one prominent and several smaller peaks occurring within 10 ms of the stimulus onset. ABRs to brief tone bursts revealed that geckos and anoles were most sensitive between 1.6–2 kHz and had similar hearing sensitivity up to about 5 kHz (thresholds typically 20–50 dB SPL). Above 5 kHz, however, anoles were more than 20 dB more sensitive than geckos and showed a wider range of sensitivity (1–7 kHz). Generally, thresholds from ABR audiograms were comparable to those of small birds. Best hearing sensitivity, however, extended over a larger frequency range in lizards than in most bird species.

Vestibular evoked myogenic potentials (VEMPs) were measured in 22 unilateral Menière patients with monaural and binaural stimulation with 250 and 500 Hz tone bursts. For all measurement situations significantly lower VEMP amplitudes were on average measured at the affected side compared to the unaffected side. Unilateral Menière patients have, in contrast to normal subjects, asymmetric VEMPs, indicating a permanently affected vestibular (most likely otolith) system at the side of hearing loss. The diagnostic value of VEMP amplitude asymmetry measurement in individual patients is low, because of the large overlap of the VEMP amplitude asymmetry range for unilateral Menière patients with that for normal subjects.

The auditory system has two parallel streams in the brain that have been implicated in auditory fear learning. The lemniscal stream has selective neurons that are tonotopically organized and is thought to be important for sound discrimination. The nonlemniscal stream has less selective neurons, which are not tonotopically organized, and is thought to be important for multimodal processing and for several forms of learning. Therefore, it has been hypothesized that the lemniscal, but not the nonlemniscal, pathway supports discriminative fear to auditory cues. To test this hypothesis we assessed the effect of electrolytic lesions to the ventral, or medial, division of the medial geniculate nucleus (MGv or MGm, which correspond, respectively, to the lemniscal and the nonlemniscal auditory pathway to amygdala) on the acquisition, expression and extinction of fear responses in discriminative auditory fear conditioning, where one tone is followed by shock (conditioned stimulus, CS(+)), and another is not (CS(-)). Here we show that with single-trial conditioning control, MGv- and MGm-lesioned male rats acquire nondiscriminative fear of both the CS(+) and the CS(-). However, after multiple-trial conditioning, control rats discriminate between the CS(+) and CS(-), whereas MGv- and MGm-lesioned do not. Furthermore, post-training lesions of MGm, but not MGv, lead to impaired expression of discriminative fear. Finally, MGm-lesioned rats display high levels of freezing to both the CS(+) and CS(-) even after an extinction session to the CS(+). In summary, our findings suggest that the lemniscal pathway is important for discriminative learning, whereas the nonlemniscal is important for negatively regulating fear responses.

A complex of proteins scaffolded by the PDZ protein, whirlin, reside at the stereocilia tip and are critical for stereocilia development and elongation. We have shown that in outer hair cells (OHCs) whirlin is part of a larger complex involving the MAGUK protein, p55, and protein 4.1R. Whirlin interacts with p55 which is expressed exclusively in outer hair cells (OHC) in both the long stereocilia that make up the stereocilia bundle proper as well as surrounding shorter microvilli that will eventually regress. In erythrocytes, p55 forms a tripartite complex with protein 4.1R and glycophorin C promoting the assembly of actin filaments and the interaction of whirlin with p55 indicates that it plays a similar role in OHC stereocilia. However, the components directly involved in actin filament regulation in stereocilia are unknown. We have investigated additional components of the whirlin interactome by identifying interacting partners to p55. We show that the actin capping and severing protein, gelsolin, is a part of the whirlin complex. Gelsolin is detected in OHC where it localizes to the tips of the shorter rows but not to the longest row of stereocilia and the pattern of localisation at the apical hair cell surface is strikingly similar to p55. Like p55, gelsolin is ablated in the whirler and shaker2 mutants. Moreover, in a gelsolin mutant, stereocilia in the apex of the cochlea become long and straggly indicating defects in the regulation of stereocilia elongation. The identification of gelsolin provides for the first time a link between the whirlin scaffolding protein complex involved in stereocilia elongation and a known actin regulatory molecule.

Adenosine signalling has an important role in cochlear protection from oxidative stress. In most tissues, intracellular adenosine kinase (ADK) is the primary route of adenosine metabolism and the key regulator of intracellular and extracellular adenosine levels. The present study provides the first evidence for ADK distribution in the adult and developing rat cochlea. In the adult cochlea, ADK was localized to the nuclear or perinuclear region of spiral ganglion neurons, lateral wall tissues, and epithelial cells lining scala media. In the developing cochlea, ADK was strongly expressed in multiple cell types at birth and reached its peak level of expression at postnatal day 21 (P21). Ontogenetic changes in ADK expression were evident in the spiral ganglion, organ of Corti, and stria vascularis. In the spiral ganglion, ADK showed a shift from predominantly satellite cell immunolabelling at P1 to neuronal expression from P14 onward. In contrast to the role of ADK in various aspects of cochlear development, the ADK contribution to the cochlear response to noise stress was less obvious. Transcript and protein levels of ADK were unaltered in the cochlea exposed to broadband noise (90–110 dBSPL, 24 hr), and the selective inhibition of ADK in the cochlea with ABT‐702 failed to restore hearing thresholds after exposure to traumatic noise. This study indicates that ADK is involved in purine salvage pathways for nucleotide synthesis in the adult cochlea, but its role in the regulation of adenosine signalling under physiological and pathological conditions has yet to be established. © 2010 Wiley‐Liss, Inc.

The goal of this study was to determine the role of an influx copper transporter, CTR1, in the ototoxicity induced by cisplatin, a potent anticancer platinum analog used in the treatment of a variety of solid tumors. As determined through reverse transcriptase-PCR (RT-PCR), quantitative RT-PCR, Western blot, and immunohistochemistry, mouse CTR1 (Ctr1) was found to be abundantly expressed and highly localized at the primary sites of cisplatin toxicity in the inner ear, mainly outer hair cells (OHCs), inner hair cells, stria vascularis, spiral ganglia, and surrounding nerves in the mouse cochlea. A CTR1 substrate, copper sulfate, decreased the uptake and cytotoxicity of cisplatin in HEI-OC1, a cell line that expresses many molecular markers reminiscent of OHCs. Small interfering RNA-mediated knockdown of Ctr1 in this cell line caused a corresponding decrease in cisplatin uptake. In mice, intratympanic administration of copper sulfate 30 min before intraperitoneal administration of cisplatin was found to prevent hearing loss at click stimulus and 8, 16, and 32 kHz frequencies. To date, the utility of cisplatin remains severely limited because of its ototoxic effects. The studies described in this report suggest that cisplatin-induced ototoxicity and cochlear uptake can be modulated by administration of a CTR1 inhibitor, copper sulfate. The possibility of local administration of CTR1 inhibitors during cisplatin therapy as a means of otoprotection is thereby raised.

The ability of native and non-native speakers to enhance intelligibility of target vowels by speaking clearly was compared across three talker groups: monolingual English speakers and native Spanish speakers with either an earlier or a later age of immersion in an English-speaking environment. Talkers produced the target syllables “bead, bid, bayed, bed, bad” and “bod” in ‘conversational’ and clear speech styles. The stimuli were presented to native English-speaking listeners in multi-talker babble with signal-to-noise ratios of −8 dB for the monolingual and early learners and −4 dB for the later learners. The monolinguals and early learners of English showed a similar average clear speech benefit, and the early learners showed equal or greater intelligibility than monolinguals for most target vowels. The 4-dB difference in signal-to-noise ratio yielded approximately equal average intelligibility for the monolinguals and later learners. The average clear speech benefit was smallest for the later learners, and a significant clear speech decrement was obtained for the target syllable “bid.” These results suggest that later learners of English as a second language may be less able than monolinguals to accommodate listeners in noisy environments, due to a reduced ability to improve intelligibility by speaking more clearly.

Temporal weighting functions (TWFs), quantifying sensitivity to interaural time differences (ITD) and interaural level differences (ILD) over the duration of brief stimuli, were measured in 6 normal hearing subjects using trains of 16 Gabor clicks centered at 4 kHz presented dichotically at 4 rates [inter-click intervals (ICI) of 10, 5, 2.5, and 1.25 ms]. Random ITD or ILD were imposed independently on each click in the train in separate conditions. The subject’s task was to discriminate the lateral position of the click train (“left” or “right”). Receiver operating characteristic (ROC) analysis was then used to quantify the effectiveness or “weight” of each click according to individual click ITD or ILD. Although individual differences were evident, onset cues appeared to dominate at high rates. Onset dominance was apparent for both ITD and ILD at 1.25 ms ICI and for ITD at 2.5 ms ICI, but for neither cue at 5 or 10 ms ICI. Onset dominance was greater on average for ITD than ILD, although TWFs were qualitatively similar for the two cues. No evidence was found for “upweighting” of late-arriving ILD [Stecker, G. C., and Hafter, E. R. (2009), J. Acoust. Soc. Am. 125, 3914–3924].

A consistent organizational feature of auditory cortex is a clustered representation of binaural properties. Here we address two questions. What is the intrinsic organization of binaural clusters and to what extent does intracortical processing contribute to binaural representation. We address these issues in the auditory cortex of the pallid bat. The pallid bat listens to prey-generated noise transients to localize and hunt terrestrial prey. As in other species studied, binaural clusters are present in the auditory cortex of the pallid bat. One cluster contains neurons that require binaural stimulation to be maximally excited, and are commonly termed predominantly binaural (PB) neurons. These neurons do not respond to monaural stimulation of either ear but show a peaked sensitivity to interaural intensity differences (IID) centered near 0 dB IID. We show that the peak IID varies systematically within this cluster. The peak IID is also correlated with the best frequency (BF) of neurons within this cluster. In addition, the IID selectivity of PB neurons is shaped by intracortical GABAergic input. Iontophoresis of GABA A receptor antagonists on PB neurons converts a majority of them to binaurally inhibited (EI) neurons that respond best to sounds favoring the contralateral ear. These data indicate that the cortex does not simply inherit binaural properties from lower levels but instead sharpens them locally through intracortical inhibition. The IID selectivity of the PB cluster indicates that the pallid bat cortex contains an increased representation of the frontal space that may underlie increased localization accuracy in this region.

Psychophysical studies show a slower response to changes in the specifically binaural input than to changes in the monaural input (binaural sluggishness). However, there is disagreement about the time course. Tracking changes in a target yields fast time constants, while detecting a constant target against a varying background yields the slowest. Changes in the binaural properties of a target are tracked up to high rates by cells in the midbrain. Indeed cells respond rapidly to a step change and then the firing rate slowly adapts. These experiments, though, are analogues of psychophysical experiments that give the faster time constants. Sluggishness should be more apparent physiologically in a binaural masking paradigm, detecting a short tone in a noise masker with a step change in masker correlation: the small change in firing rate due to the signal must be detected against the adapting firing rate change caused by the step change in the masker. However, in 40 inferior colliculus cells in the anesthetized guinea pig, in a direct analogue of the psychophysical masking paradigm, measuring thresholds for short tones across a transition in a binaural masker (e.g., from N0S0 to NπS0) provided little evidence of sluggishness within individual cells despite masking level differences in these cells comparable with previous data. Previous studies of physiological correlates of binaural masking level difference suggested that different psychophysical thresholds arise from different populations of cells. This suggests the hypothesis that sluggishness may result from a change in focus between the different populations of cells signaling threshold in different binaural configurations rather than within the intrinsic properties of the cells themselves.

Perception of breathy voice quality is cued by a number of acoustic changes including an increase in aspiration noise level (AH) and spectral slope. Changes in AH in a vowel may be evaluated through measures such as the harmonic-to-noise ratio, cepstral peak prominence (CPP), or via auditory measures such as the partial loudness of harmonic energy and loudness of aspiration noise. Although a number of experiments have reported high correlation between such measures and ratings of perceived breathiness, a formal model to predict breathiness of a vowel has not been proposed. This research describes two computational models to predict changes in breathiness resulting from variations in AH. One model uses auditory measures, whereas the other uses CPP as independent variables to predict breathiness. For both cases, a translated and truncated power function is required to predict breathiness. Some parameters in both of these models were observed to be pitch dependent. The "unified" model based on auditory measures was observed to be more accurate than one based on CPP.

Background: Salicylate and quinine have been shown to reliably induce short-term tinnitus when administered at high doses. The present study compared salicylate and quinine-induced tinnitus in rats using the gap prepulse inhibition of acoustic startle (GPIAS). Methods: Twenty-four rats were divided into 2 groups; the first group (n = 12) was injected with salicylate (300 mg kg d), whereas the second (n = 12) was treated with quinine orally at a dose of 200 mg kg d. Animals were treated daily for 4 consecutive days. All rats were tested for tinnitus and hearing loss before and 2, 24, 48, 72, and 96 hours after the first drug administration. Tinnitus was assessed using GPIAS; hearing function was measured with distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response. Results: Salicylate treatment induced transient tinnitus with a pitch near 16 kHz starting 2 hours posttreatment, persisting over the 4-day treatment period and disappearing 24 hours later. Animals in the quinine group showed GPIAS changes at a higher pitch (20 kHz); however, changes were more variable among animals, and the mean data were not statistically significant. Hearing function varied across treatments. In the salicylate group, high-level DPOAEs were slightly affected; most changes occurred 2 hours posttreatment. Low-level DPOAEs were affected at all frequencies with a progressive dose-dependent effect. In the quinine group, only high-level DPOAEs were affected, mainly at 16 kHz. Conclusion: The present study highlights the similarities and differences in the frequency and the time course of tinnitus and hypoacusis induced by salicylate and quinine. Transient tinnitus was reliably induced pharmacologically with salicylate, whereas hearing loss remained subclinical with only minor changes in DPOAEs.

In this report we demonstrate that differences in cage type brought unexpected effects on aggressive behavior and neuroanatomical features of the mouse olfactory bulb. A careful characterization of two cage types, including a comparison of the auditory and temperature environments, coupled with a demonstration that naris occlusion abolishes the neuroanatomical changes, lead us to conclude that a likely important factor mediating the phenotypic changes we find is the olfactory environment of the two cages. We infer that seemingly innocuous changes in cage environment can affect sensory input relevant to mice and elicit profound effects on neural output. Study of the neural mechanisms underlying animal behavior in the laboratory environment should be broadened to include neuroethological approaches to examine how the laboratory environment (beyond animal well-being and enrichment) influences neural systems and behavior.

In humans, auditory perception reaches maturity over a broad age range, extending through adolescence. Despite this slow maturation, children are considered to be outstanding learners, suggesting that immature perceptual skills might actually be advantageous to improvement on an acoustic task as a result of training (perceptual learning). Previous non‐human studies have not employed an identical task when comparing perceptual performance of young and mature subjects, making it difficult to assess learning. Here, we used an identical procedure on juvenile and adult gerbils to examine the perception of amplitude modulation (AM), a stimulus feature that is an important component of most natural sounds. On average, Adult animals could detect smaller fluctuations in amplitude (i.e., smaller modulation depths) than Juveniles, indicating immature perceptual skills in Juveniles. However, the population variance was much greater for Juveniles, a few animals displaying adult‐like AM detection. To determine whether immature perceptual skills facilitated learning, we compared naïve performance on the AM detection task with the amount of improvement following additional training. The amount of improvement in Adults correlated with naïve performance: those with the poorest naïve performance improved the most. In contrast, the naïve performance of Juveniles did not predict the amount of learning. Those Juveniles with immature AM detection thresholds did not display greater learning than Adults. Furthermore, for several of the Juveniles with adult‐like thresholds, AM detection deteriorated with repeated testing. Thus, immature perceptual skills in young animals were not associated with greater learning. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 636–648, 2010

With the exception of humans, the somata of type I spiral ganglion neurons (SGNs) of most mammalian species are heavily myelinated. In an earlier study, we used Ly5.1 congenic mice as transplant recipients to investigate the role of hematopoietic stem cells in the adult mouse inner ear. An unanticipated finding was that a large percentage of the SGNs in this strain were unmyelinated. Further characterization of the auditory phenotype of young adult Ly5.1 mice in the present study revealed several unusual characteristics, including 1) large aggregates of unmyelinated SGNs in the apical and middle turns, 2) symmetrical junction‐like contacts between the unmyelinated neurons, 3) abnormal expression patterns for CNPase and connexin 29 in the SGN clusters, 4) reduced SGN density in the basal cochlea without a corresponding loss of sensory hair cells, 5) significantly delayed auditory brainstem response (ABR) wave I latencies at low and middle frequencies compared with control mice with similar ABR threshold, and 6) elevated ABR thresholds and deceased wave I amplitudes at high frequencies. Taken together, these data suggest a defect in Schwann cells that leads to incomplete myelinization of SGNs during cochlear development. The Ly5.1 mouse strain appears to be the only rodent model so far identified with a high degree of the “human‐like” feature of unmyelinated SGNs that aggregate into neural clusters. Thus, this strain may provide a suitable animal platform for modeling human auditory information processing such as synchronous neural activity and other auditory response properties. J. Comp. Neurol. 518:3254–3271, 2010. © 2010 Wiley‐Liss, Inc.

Objective: To determine whether phonophobia and dynamic mechanical (brush) allodynia are associated in episodic migraine (EM). Methods: Adult patients with EM were prospectively recruited. A structured questionnaire was used to obtain demographic and migraine related data. Phonophobia was tested quantitatively using a real time sound processor and psychoacoustic software. Sound stimuli were pure tones at frequencies of 1000 Hz, 4000 Hz and 8000 Hz, delivered to both ears at increasing intensities, until an aversive level was reached. Allodynia was assessed by brushing the patient's skin with a gauze pad at different areas. Patients were tested both between and during acute attacks. Sound aversion thresholds (SATs) in allodynic and non-allodynic patients were compared. Results: Between attacks, SATs were lower in allodynic compared with non-allodynic patients, with an average difference of -5.7 dB (p=0.04). During acute attacks, the corresponding average SAT difference (allodynic-non-allodynic) was -15.7 dB (p=0.0008). There was a significant negative correlation between allodynia scores and SATs, both within and between attacks. Conclusions: The results support an association between phonophobia and cutaneous allodynia in migraine.

Song in oscine birds is a learned behavior that plays important roles in breeding. Pronounced seasonal differences in song behavior and in the morphology and physiology of the neural circuit underlying song production are well documented in many songbird species. Androgenic and estrogenic hormones largely mediate these seasonal changes. Although much work has focused on the hormonal mechanisms underlying seasonal plasticity in songbird vocal production, relatively less work has investigated seasonal and hormonal effects on songbird auditory processing, particularly at a peripheral level. We addressed this issue in Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii), a highly seasonal breeder. Photoperiod and hormone levels were manipulated in the laboratory to simulate natural breeding and non-breeding conditions. Peripheral auditory function was assessed by measuring the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) of males and females in both conditions. Birds exposed to breeding-like conditions demonstrated elevated thresholds and prolonged peak latencies when compared with birds housed under non-breeding-like conditions. There were no changes in DPOAEs, however, which indicates that the seasonal differences in ABRs do not arise from changes in hair cell function. These results suggest that seasons and hormones impact auditory processing as well as vocal production in wild songbirds.

Recent perceptual studies suggest that listeners with sensorineural hearing loss (SNHL) have a reduced ability to use temporal fine-structure cues, whereas the effects of SNHL on temporal envelope cues are generally thought to be minimal. Several perceptual studies suggest that envelope coding may actually be enhanced following SNHL and that this effect may actually degrade listening in modulated maskers (e.g., competing talkers). The present study examined physiological effects of SNHL on envelope coding in auditory nerve (AN) fibers in relation to fine-structure coding. Responses were compared between anesthetized chinchillas with normal hearing and those with a mild-moderate noise-induced hearing loss. Temporal envelope coding of narrowband-modulated stimuli (sinusoidally amplitude-modulated tones and single-formant stimuli) was quantified with several neural metrics. The relative strength of envelope and fine-structure coding was compared using shuffled correlogram analyses. On average, the strength of envelope coding was enhanced in noise-exposed AN fibers. A high degree of enhanced envelope coding was observed in AN fibers with high thresholds and very steep rate-level functions, which were likely associated with severe outer and inner hair cell damage. Degradation in fine-structure coding was observed in that the transition between AN fibers coding primarily fine structure or envelope occurred at lower characteristic frequencies following SNHL. This relative fine-structure degradation occurred despite no degradation in the fundamental ability of AN fibers to encode fine structure and did not depend on reduced frequency selectivity. Overall, these data suggest the need to consider the relative effects of SNHL on envelope and fine-structure coding in evaluating perceptual deficits in temporal processing of complex stimuli.