Auditory Research publications

The warble songs of budgerigars (Melopsittacus undulatus) are composed of a number of complex, variable acoustic elements that are sung by male birds in intimate courtship contexts for periods lasting up to several minutes. If these variable acoustic elements can be assigned to distinct acoustic-perceptual categories, it provides the opportunity to explore whether birds are perceptually sensitive to the proportion or sequential combination of warble elements belonging to different categories. By the inspection of spectrograms and by listening to recordings, humans assigned the acoustic elements in budgerigar warble from several birds to eight broad, overlapping categories. A neural-network program was developed and trained on these warble elements to simulate human categorization. The classification reliability between human raters and between human raters and the neural network classifier was better than 80% both within and across birds. Using operant conditioning and a psychophysical task, budgerigars were tested on large sets of these elements from different acoustic categories and different individuals. The birds consistently showed high discriminability for pairs of warble elements drawn from between acoustic categories and low discriminability for pairs drawn from within acoustic categories. With warble elements reliably assigned to different acoustic categories by humans and birds, it affords the opportunity to ask questions about the ordering of elements in natural warble streams and the perceptual significance of this ordering.

Objective . Inhibition of inflammation and free radical formation in the cochlea may be involved in antioxidant treatment in acute acoustic trauma. Procedure . Chinchilla were exposed to 105 dB sound pressure level octave band noise for 6 hours. One group of chinchilla was treated with antioxidants after noise exposure. Auditory brainstem responses, outer hair cell counts, and immunohistochemical analyses of biomarkers in the cochlea were conducted. Results . The antioxidant treatment significantly reduced hearing threshold shifts, outer hair cell loss, numbers of CD45 + cells, as well as 4-hydroxy-2-nonenal and nitrotyrosine formation in the cochlea. Conclusion . Antioxidant treatment may provide protection to sensory cells by inhibiting formation of reactive oxygen and nitrogen products and migration of mononuclear phagocytes in the cochlea. The present study provides further evidence of effectiveness of antioxidant treatment in reducing permanent hearing loss.

Goldfish (Carassius auratus) were conditioned to suppress respiration to a 40-Hz vibratory source and subsequently tested for stimulus generalization to frequency, stimulus amplitude, and position (azimuth). Animals completely failed to generalize to frequencies separated by octave intervals both lesser and greater than the CS. However, they did appear to generalize weakly to an aerial loudspeaker stimulus of the same frequency (40 Hz) after conditioning with an underwater vibratory source. Animals had a gradually decreasing amount of generalization to amplitude changes, suggesting a perceptual dimension of loudness. Animals generalized largely or completely to the same underwater source presented at a range of source azimuths. When these azimuths were presented at a transect of 3 cm, some animals did show decrements in generalization, while others did not. This suggests that although azimuth may be perceived more saliently at distances closer to a dipole source, perception of position is not immediately salient in conditioned vibratory source detection. Differential responding to test stimuli located toward the head or tail suggests the presence of perceptual differences between sources that are rostral or caudal with respect to the position of the animal or perhaps the head.

Reversible inactivation of the cortex by surface cooling is a powerful method for studying the function of a particular area. Implanted cooling cryoloops have been used to study the role of individual cortical areas in auditory processing of awake-behaving cats. Cryoloops have also been used in rodents for reversible inactivation of the cortex, but recently there has been a concern that the cryoloop may also cool non-cortical structures either directly or via the perfusion of blood, cooled as it passed close to the cooling loop. In this study we have confirmed that the loop can inactivate most of the auditory cortex without causing a significant reduction in temperature of the auditory thalamus or other subcortical structures. We placed a cryoloop on the surface of the guinea pig cortex, cooled it to 2°C and measured thermal gradients across the neocortical surface. We found that the temperature dropped to 20-24°C among cells within a radius of about 2.5 mm away from the loop. This temperature drop was sufficient to reduce activity of most cortical cells and led to the inactivation of almost the entire auditory region. When the temperature of thalamus, midbrain, and middle ear were measured directly during cortical cooling, there was a small drop in temperature (about 4°C) but this was not sufficient to directly reduce neural activity. In an effort to visualize the extent of neural inactivation we measured the uptake of thallium ions following an intravenous injection. This confirmed that there was a large reduction of activity across much of the ipsilateral cortex and only a small reduction in subcortical structures.

Objectives: Cisplatin, a widely used chemotherapeutic agent, has serious side effects, including nephrotoxicity and ototoxicity. Minocycline is a semisynthetic second-generation tetracycline that exerts anti-inflammatory and neuroprotective effects. The purpose of this study was to elucidate the protective effect of minocycline against cisplatin-induced ototoxicity in the auditory hair cell. Methods: The House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line and guinea pigs were used for in vitro and in vivo experiments. Cells were exposed to cisplatin with or without pre-treatment with minocycline. Cell survival was analyzed using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Whole-cell lysates were collected and immunoblotted with antibodies against Bcl-2, p-c-Jun, active caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), and apoptosis-inducing factor (AIF). The guinea pigs received intraperitoneal injections of cisplatin alone or following minocycline pretreatment. The auditory brainstem response was tested and the cochleae were harvested and evaluated using scanning electron microscopy. Results: Survival significantly increased in cells pretreated with minocycline compared with cells exposed to cisplatin alone. Cisplatin treatment increased the expression of active caspase 3, p-c Jun, PARP, and AIF, and pretreatment with minocycline attenuated this response. In animal study, the threshold shift by cisplatin injection in the auditory brainstem response was less pronounced in animals pretreated with minocycline. Scanning electron microscopy revealed more severe damage to the outer hair cells at the basal and middle turns than the apical turn. Conclusion: Minocycline partially protects against cisplatin-induced ototoxicity via both caspase-dependent and independent apoptosis pathways.

Disturbance of sensory input during development can have disastrous effects on the development of sensory cortical areas. To examine how moderate perturbations of hearing can impact the development of primary auditory cortex, we examined markers of excitatory synapses in mice who lacked prestin, a protein responsible for somatic electromotility of cochlear outer hair cells. While auditory brain stem responses of these mice show an approximately 40 dB increase in threshold, we found that loss of prestin produced no changes in spine density or morphological characteristics on apical dendrites of cortical layer 5 pyramidal neurons. PSD-95 immunostaining also showed no changes in overall excitatory synapse density. Surprisingly, behavioral assessments of auditory function using the acoustic startle response showed only modest changes in prestin KO animals. These results suggest that moderate developmental hearing deficits produce minor changes in the excitatory connectivity of layer 5 neurons of primary auditory cortex and surprisingly mild auditory behavioral deficits in the startle response.

The present study focuses on auditory discrimination abilities in older adults aged 65-89 years. We applied the "Leipzig inventory for patient psychoacoustic" (LIPP), a psychoacoustic test battery specifically designed to identify deficits in central auditory processing. These tests quantify the just noticeable differences (JND) for the three basic acoustic parameters (i.e., frequency, intensity, and signal duration). Three different test modes [monaural, dichotic signal/noise (s/n) and interaural] were used, stimulus level was 35 dB sensation level. The tests are designed as three-alternative forced-choice procedure with a maximum-likelihood procedure estimating p = 0.5 correct response value. These procedures have proven to be highly efficient and provide a reliable outcome. The measurements yielded significant age-dependent deteriorations in the ability to discriminate single acoustic features pointing to progressive impairments in central auditory processing. The degree of deterioration was correlated to the different acoustic features and to the test modes. Most prominent, interaural frequency and signal duration discrimination at low test frequencies was elevated which indicates a deterioration of time- and phase-dependent processing at brain stem and cortical levels. LIPP proves to be an effective tool to identify basic pathophysiological mechanisms and the source of a specific impairment in auditory processing of the elderly.

Ultimately associative learning is a function of the temporal features and relationships between experienced stimuli. Nevertheless how time affects the neural circuit underlying this form of learning remains largely unknown. To address this issue, we used single-trial auditory trace fear conditioning and varied the length of the interval between tone and foot-shock. Through temporary inactivation of the amygdala, medial prefrontal-cortex (mPFC), and dorsal-hippocampus in rats, we tested the hypothesis that different temporal intervals between the tone and the shock influence the neuronal structures necessary for learning. With this study we provide the first experimental evidence showing that temporarily inactivating the amygdala before training impairs auditory fear learning when there is a temporal gap between the tone and the shock. Moreover, imposing a short interval (5 s) between the two stimuli also relies on the mPFC, while learning the association across a longer interval (40 s) becomes additionally dependent on a third structure, the dorsal-hippocampus. Thus, our results suggest that increasing the interval length between tone and shock leads to the involvement of an increasing number of brain areas in order for the association between the two stimuli to be acquired normally. These findings demonstrate that the temporal relationship between events is a key factor in determining the neuronal mechanisms underlying associative fear learning.

In addition to auditory inputs, dorsal cochlear nucleus (DCN) pyramidal cells in the guinea pig receive and respond to somatosensory inputs and perform multisensory integration. DCN pyramidal cells respond to sounds with characteristic spike‐timing patterns that are partially controlled by rapidly inactivating potassium conductances. Deactivating these conductances can modify both spike rate and spike timing of responses to sound. Somatosensory pathways are known to modify response rates to subsequent acoustic stimuli, but their effect on spike timing is unknown. Here, we demonstrate that preceding tonal stimulation with spinal trigeminal nucleus (Sp5) stimulation significantly alters the first spike latency, the first interspike interval and the average discharge regularity of firing evoked by the tone. These effects occur whether the neuron is excited or inhibited by Sp5 stimulation alone. Our results demonstrate that multisensory integration in DCN alters spike‐timing representations of acoustic stimuli in pyramidal cells. These changes likely occur through synaptic modulation of intrinsic excitability or synaptic inhibition.

Perinatal asphyxia, a naturally and commonly occurring risk factor in birthing, represents one of the major causes of neonatal encephalopathy with long term consequences for infants. Here, degraded spectral and temporal responses to sounds were recorded from neurons in the primary auditory cortex (A1) of adult rats exposed to asphyxia at birth. Response onset latencies and durations were increased. Response amplitudes were reduced. Tuning curves were broader. Degraded successive-stimulus masking inhibitory mechanisms were associated with a reduced capability of neurons to follow higher-rate repetitive stimuli. The architecture of peripheral inner ear sensory epithelium was preserved, suggesting that recorded abnormalities can be of central origin. Some implications of these findings for the genesis of language perception deficits or for impaired language expression recorded in developmental disorders, such as autism spectrum disorders, contributed to by perinatal asphyxia, are discussed.

Activity in the primary auditory cortex (A1) is essential for normal sound localization behavior, but previous studies of the spatial sensitivity of neurons in A1 have found broad spatial tuning. We tested the hypothesis that spatial tuning sharpens when an animal engages in an auditory task. Cats performed a task that required evaluation of the locations of sounds and one that required active listening, but in which sound location was irrelevant. Some 26-44% of the units recorded in A1 showed substantially sharpened spatial tuning during the behavioral tasks as compared with idle conditions, with the greatest sharpening occurring during the location-relevant task. Spatial sharpening occurred on a scale of tens of seconds and could be replicated multiple times in ∼1.5-h test sessions. Sharpening resulted primarily from increased suppression of responses to sounds at least-preferred locations. That and an observed increase in latencies suggest an important role of inhibitory mechanisms.

The significance of the mismatch negativity (MMN), an event-related potential measured in humans which indexes novelty in the auditory environment, has motivated a search for a cellular correlate of this process. A leading candidate is stimulus-specific adaptation (SSA) in auditory cortex units, which shares several characteristics with the MMN. Whether auditory cortex responses encode sensory novelty, a defining property of the MMN, however, has not been resolved. To evaluate this key issue, we used several variations of the auditory oddball paradigm from the human literature and examined psychophysical and pharmacological properties of multiunit activity in the auditory cortex of awake rodents. We found converging evidence dissociating SSA from sensory novelty and the MMN. First, during an oddball paradigm with frequency deviants, neuronal responses showed clear SSA but failed to encode novelty in a manner analogous to the human MMN. Second, oddball paradigms using intensity or duration deviants revealed a pattern of unit responses that showed sensory adaptation, but again without any measurable novelty correlates aligning to the human MMN. Finally NMDA antagonists, which are known to disrupt the MMN, suppressed the magnitude of multiunit responses in a nonspecific manner, leaving the process of SSA intact. Together, our results suggest that auditory novelty detection as indexed by the MMN is dissociable from SSA at the level of activity encoded by auditory cortex neurons. Further, the NMDA sensitivity reported for the MMN, which models the disruption of MMN observed in schizophrenia, may occur at a mechanistic locus outside of SSA.

The human auditory cortex is engaged in monitoring the speech of interlocutors as well as self-generated speech. During vocalization, auditory cortex activity is reported to be suppressed, an effect often attributed to the influence of an efference copy from motor cortex. Single-unit studies in non-human primates have demonstrated a rich dynamic range of single-trial auditory responses to self-speech consisting of suppressed, nonsuppressed and excited auditory neurons. However, human research using noninvasive methods has only reported suppression of averaged auditory cortex responses to self-generated speech. We addressed this discrepancy by recording electrocorticographic activity from neurosurgical subjects performing auditory repetition tasks. We observed that the degree of suppression varied across different regions of auditory cortex, revealing a variety of suppressed and nonsuppressed responses during vocalization. Importantly, single-trial high-gamma power (γ High , 70–150 Hz) robustly tracked individual auditory events and exhibited stable responses across trials for suppressed and nonsuppressed regions.

Multisensory stimuli can improve performance, facilitating RTs on sensorimotor tasks. This benefit is referred to as the redundant signals effect (RSE) and can exceed predictions on the basis of probability summation, indicative of integrative processes. Although an RSE exceeding probability summation has been repeatedly observed in humans and nonprimate animals, there are scant and inconsistent data from nonhuman primates performing similar protocols. Rather, existing paradigms have instead focused on saccadic eye movements. Moreover, the extant results in monkeys leave unresolved how stimulus synchronicity and intensity impact performance. Two trained monkeys performed a simple detection task involving arm movements to auditory, visual, or synchronous auditory–visual multisensory pairs. RSEs in excess of predictions on the basis of probability summation were observed and thus forcibly follow from neural response interactions. Parametric variation of auditory stimulus intensity revealed that in both animals, RT facilitation was limited to situations where the auditory stimulus intensity was below or up to 20 dB above perceptual threshold, despite the visual stimulus always being suprathreshold. No RT facilitation or even behavioral costs were obtained with auditory intensities 30–40 dB above threshold. The present study demonstrates the feasibility and the suitability of behaving monkeys for investigating links between psychophysical and neurophysiologic instantiations of multisensory interactions.

The purpose of this experiment was to determine whether the normalized interaural cross-correlation (CC) model or a model based on interaural phase and level differences can better describe incoherence detection data. The ability to detect interaural incoherence in three sets of reproducible dichotic noises was tested in six listeners. The first set contained noises with a constrained value of the CC and the CC including signal compression. The second set contained noises with a constrained value of the CC including signal compression. The third set contained noises with constrained values in the fluctuations in the interaural differences. Modeling showed that neither the CC model nor the model using the interaural differences could account for the data in any set. Examination of the statistical properties of the stimuli showed that including compression before the calculation of the interaural CC causes a substantial correlation of this metric to the fluctuations in the interaural phase difference. This finding implies that it may be more difficult to discriminate between the common types of binaural models than previously thought.

An important question in auditory neuroscience concerns how the neural representation of sound features changes from the periphery to the cortex. Here we focused on the encoding of sound onsets and we used a modeling approach to explore the degree to which auditory cortical neurons follow a similar envelope integration mechanism found at the auditory periphery. Our “forward” model was able to predict relatively accurately the timing of first spikes evoked by natural communication calls in the auditory cortex of awake, head-restrained mice, but only for a subset of cortical neurons. These neurons were systematically different in their encoding of the calls, exhibiting less call selectivity, shorter latency, greater precision, and more transient spiking compared with the same factors of their poorly predicted counterparts. Importantly, neurons that fell into this best-predicted group all had thin spike waveforms, suggestive of suspected interneurons conveying feedforward inhibition. Indeed, our population of call-excited thin spike neurons had significantly higher spontaneous rates and larger frequency tuning bandwidths than those of thick spike neurons. Thus the fidelity of our model's first spike predictions segregated neurons into one earlier responding subset, potentially dominated by suspected interneurons, which preserved a peripheral mechanism for encoding sound onsets and another longer latency subset that reflected higher, likely centrally constructed nonlinearities. These results therefore provide support for the hypothesis that physiologically distinct subclasses of neurons in the auditory cortex may contribute hierarchically to the representation of natural stimuli.

Loss of central inhibition has been hypothesized to underpin tinnitus and impact auditory acuity. Taurine, a partial agonist at inhibitory glycine and γ-amino butyric acid receptors, was added to the daily diet of rats to examine its effects on chronic tinnitus and normal auditory discrimination. Eight rats were unilaterally exposed once to a loud sound to induce tinnitus. The rats were trained and tested in an operant task shown to be sensitive to tinnitus. An equivalent unexposed control group was run in parallel. Months after exposure, 6 of the exposed rats showed significant evidence of chronic tinnitus. Two concentrations of taurine in drinking water were given over several weeks (attaining average daily doses of 67 mg/kg and 294 mg/kg). Water consumption was unaffected. Three main effects were obtained: (1) The high taurine dose significantly attenuated tinnitus, which returned to near pre-treatment levels following washout. (2) Auditory discrimination was significantly improved in unexposed control rats at both doses. (3) As indicated by lever pressing, taurine at both doses had a significant group-equivalent stimulant effect. These results are consistent with the hypothesis that taurine attenuates tinnitus and improves auditory discrimination by increasing inhibitory tone and decreasing noise in the auditory pathway.

This study examines patterns of neural activity in response to single biphasic electrical pulses, presented alone or following a forward masking pulse train, delivered by a cochlear implant. Recordings were made along the tonotopic axis of the central nucleus of the inferior colliculus (ICC) in ketamine/xylazine anesthetized guinea pigs. The partial tripolar electrode configuration was used, which provided a systematic way to vary the tonotopic extent of ICC activation between monopolar (broad) and tripolar (narrow) extremes while maintaining the same peak of activation. The forward masking paradigm consisted of a 200 ms masker pulse train (1017 pulses per second) followed 10 ms later by a single-pulse probe stimulus; the current fraction of the probe was set to 0 (monopolar), 1 (tripolar), or 0.5 (hybrid), and the fraction of the masker was fixed at 0.5. Forward masking tuning profiles were derived from the amount of masking current required to just suppress the activity produced by a fixed-level probe. These profiles were sharper for more focused probe configurations, approximating the pattern of neural activity elicited by single (non-masked) pulses. The result helps to bridge the gap between previous findings in animals and recent psychophysical data.

The middle ear transmits sound efficiently from the air in the ear canal (EC) to the fluid filled cochlea. In gerbil, middle ear transmission produces a constant pressure gain between the EC and the cochlea of ∼25 dB from 2 to 40 kHz, and a delay-like phase corresponding to a ∼25-30 μs delay. The mechanisms by which the air-born signal is collected and delivered to the cochlea are not thoroughly understood, and the source of the delay is controversial. We investigated these issues by observing ossicular motion along a single line of sight, roughly parallel to the EC and perpendicular to the stapes footplate. Measurements were made at the umbo, the long process of the manubrium, across the malleus-incus joint, at the long process of the incus, and the stapes head. While the overall delay between EC pressure and stapes velocity was fairly constant with frequency, subcomponents of the delay were frequency dependent. Up to ∼17 kHz, most of the overall delay was between the EC and umbo with a much smaller contribution along the ossicles, whereas in the range from ∼17 to 30 kHz, more of the overall delay was along the ossicles.

Progeny from the Harwell N-ethyl-N-nitrosourea (ENU) recessive mutagenesis screen were assessed for auditory defects. A pedigree was identified with multiple progeny lacking response to a clickbox test. Auditory brainstem response (ABR) analysis showed that homozygous mutant mice were profoundly deaf and the line was named melody. We subsequently mapped this mutation to a 6-Mb region on chromosome 8 and identified a point mutation in melody that results in a C163S substitution in the catalytic site of Caspase 3, a cysteine protease involved in apoptosis. Melody fails to complement a null Caspase-3 mutant. Scanning electron microscopy (SEM) has revealed disorganised sensory hair cells and hair cell loss. Histological analysis of melody has shown degeneration of spiral ganglion cells in homozygote mice, with a gradient of severity from apical to basal turns. Melody heterozygotes also show evidence of loss of spiral ganglion neurons, suggesting that the C163S mutation may show dominant negative effects by binding and sequestering proteins at the active site. The melody line provides a new model for studying the role of Caspase 3 in deafness and a number of other pathways and systems.