Auditory Neurophysiology publications

Rodent studies using cortical removal techniques, ranging from transient deactivation to surgical ablation of cortex, reveal the importance of auditory cortical integrity in detecting short silent gaps in white noise (2-15 ms). Processing limits for longer gaps under decorticate conditions in rats remain unknown. Determining the temporal threshold for subcortical resolution of gaps in noise could, however, shed light on both normal hierarchical processing of acoustic temporal stimuli, as well as the etiology of processing anomalies following developmental cortical disruption. To address these important issues, we assessed whether intact rats, as well as those with induced developmental cortical disruptions (microgyria) could resolve silent gaps of 20-100 ms in duration when embedded in white noise, during functional deactivation of auditory cortex. Results showed that both intact rats, as well as those with cortical malformations resulting from early focal disruptions of neuronal migration could resolve silent gaps of 100-ms duration under cortical deactivation (KCl). However, only intact rats could reliably detect 75-ms gaps, suggesting possible subcortical anomalies in subjects with early cortical disturbances.

We investigated encoding properties of identified auditory interneurons in two not closely related grasshopper species (Acrididae). The neurons can be homologized on the basis of their similar morphologies and physiologies. As test stimuli, we used the species-specific stridulation signals of Chorthippus biguttulus , which evidently are not relevant for the other species, Locusta migratoria . We recorded spike trains produced in response to these signals from several neuron types at the first levels of the auditory pathway in both species. Using a spike train metric to quantify differences between neuronal responses, we found a high similarity in the responses of homologous neurons: interspecific differences between the responses of homologous neurons in the two species were not significantly larger than intraspecific differences (between several specimens of a neuron in one species). These results suggest that the elements of the thoracic auditory pathway have been strongly conserved during the evolutionary divergence of these species. According to the ‘efficient coding’ hypothesis, an adaptation of the thoracic auditory pathway to the specific needs of acoustic communication could be expected. We conclude that there must have been stabilizing selective forces at work that conserved coding characteristics and prevented such an adaptation.

The auditory center in the cerebrum, the auditory cortex, consists of multiple interconnected areas. The functional role of these interconnections is poorly understood. The auditory cortex of the mustached bat consists of at least nine areas, including the frequency modulation–frequency modulation (FF) and dorsal fringe (DF) areas. The FF and DF areas consist of neurons tuned to specific echo delays carrying target-distance information. The DF area is hierarchically at a higher level than the FF area. Here, we show that the feedback projection from the DF area to the FF area shifts the delay-tuning of FF neurons toward that of the stimulated DF neurons. In contrast, the feed-forward projection from the FF area to the DF area shifts the delay-tuning of DF neurons away from that of the stimulated FF neurons. The lateral projection within the DF area shifts the delay-tuning of DF neurons toward that of the stimulated DF neurons. In contrast, the lateral projection within the FF area shifts the delay-tuning of FF neurons away from that of the stimulated FF neurons. The delay-tuning shift evoked by the DF stimulation was 2.5 times larger than that evoked by the FF stimulation. Our data indicate that the FF–DF feed-forward and FF–FF lateral projections shape the highly selective neural representation of the tuning of the excited DF neurons, whereas the DF–FF feedback and DF–DF lateral projections enhance the representation of the selected tuning, perhaps, for focal processing of information carried by the excited FF neurons.

The transformation of auditory information from the cochlea to the cortex is a highly nonlinear process. Studies using tone stimuli have revealed that changes in even the most basic parameters of the auditory stimulus can alter neural response properties; for example, a change in stimulus intensity can cause a shift in a neuron's preferred frequency. However, it is not yet clear how such nonlinearities contribute to the processing of spectrotemporal features in complex sounds. Here, we use spectrotemporal receptive fields (STRFs) to characterize the effects of stimulus intensity on feature selectivity in the mammalian inferior colliculus (IC). At low intensities, we find that STRFs are relatively simple, typically consisting of a single excitatory region, indicating that the neural response is simply a reflection of the stimulus amplitude at the preferred frequency. In contrast, we find that STRFs at high intensities typically consist of a combination of an excitatory region and one or more inhibitory regions, often in a spectrotemporally inseparable arrangement, indicating selectivity for complex auditory features. We show that a linear–nonlinear model with the appropriate STRF can predict neural responses to stimuli with a fixed intensity, and we demonstrate that a simple extension of the model with an intensity-dependent STRF can predict responses to stimuli with varying intensity. These results illustrate the complexity of auditory feature selectivity in the IC, but also provide encouraging evidence that the prediction of nonlinear responses to complex stimuli is a tractable problem.

Sound duration can play a pivotal role in the reproductive behavior of anuran amphibians. Here, we report the first whole-cell recordings from duration-selective neurons in the anuran torus semicircularis, in vivo . We show that most short-pass duration-selective cells exhibited short-latency inhibition and delayed excitation. The duration of the inhibition increased with tone burst duration. Hence, for long-duration tone bursts, inhibition overlapped with excitation, reducing or eliminating spikes; no postinhibitory rebound was present. Other short-pass cells, however, showed inhibition only for long-duration tone bursts. Bandpass duration selectivity also involved interplay between inhibition and excitation; inhibition negated excitation with tone bursts that exceeded the optimum duration. Additionally, however, bandpass selectivity arose from stimulus-dependent excitation; tone bursts of sufficiently long duration were required to elicit excitation. Similarly, long-pass neurons showed inhibition and duration-dependent enhancement of excitation; long-pass selectivity resulted from enhanced excitation outlasting the transient inhibition or, in some cases, excitation overriding concurrent inhibition. Last, we evaluated the stimulus specificity of duration-selective neurons to variations in pulse repetition rate. We show that (1) most neurons that exhibited long-pass selectivity for tone-burst duration nonetheless responded to short-duration pulses when repeated at particular rates, and (2) some neurons that showed selectivity for tone burst duration also showed selectivity for pulse train duration. These novel response profiles appear to result from interplay between inhibition and time- and activity-dependent changes in excitation strength. These findings are discussed in the context of prevailing models of duration selectivity and acoustic communication in anurans.

Animals, including humans, use interaural time differences (ITDs) that arise from different sound path lengths to the two ears as a cue of horizontal sound source location. The nature of the neural code for ITD is still controversial. Current models differentiate between two population codes: either a map-like rate-place code of ITD along an array of neurons, consistent with a large body of data in the barn owl, or a population rate code, consistent with data from small mammals. Recently, it was proposed that these different codes reflect optimal coding strategies that depend on head size and sound frequency. The chicken makes an excellent test case of this proposal because its physical prerequisites are similar to small mammals, yet it shares a more recent common ancestry with the owl. We show here that, like in the barn owl, the brainstem nucleus laminaris in mature chickens displayed the major features of a place code of ITD. ITD was topographically represented in the maximal responses of neurons along each isofrequency band, covering approximately the contralateral acoustic hemisphere. Furthermore, the represented ITD range appeared to change with frequency, consistent with a pressure gradient receiver mechanism in the avian middle ear. At very low frequencies, below 400 Hz, maximal neural responses were symmetrically distributed around zero ITD and it remained unclear whether there was a topographic representation. These findings do not agree with the above predictions for optimal coding and thus revive the discussion as to what determines the neural coding strategies for ITDs.

The lateral superior olive (LSO) is one of the earliest sites in the auditory pathway that is involved in processing acoustical cues to sound location. Here, we tested the hypothesis that LSO neurons can signal small changes in interaural level differences (ILDs), a cue to horizontal sound location, of pure tones based on discharge rate consistent with psychophysical performance in the discrimination of ILDs. Neural thresholds for ILD discrimination were determined from the discharge rates and associated response variability of single units in response to 300 ms tones in the LSO of barbiturate-anesthetized cats using detection theory. Neural response variability was well described by a power function of the mean rate, both in individual neurons and collectively; LSO neurons were less variable than expected from a Poisson process. Compared with psychophysical data, the best-threshold ILDs of single LSO neurons were comparable with or better than behavior over the full range of frequencies (0.3–35 kHz) and pedestal ILDs (±25 dB) explored in this study. With a pedestal ILD of 0 dB, ILD increments of 1 dB could be discriminated by some neurons, with a median of 4.35 dB across neurons. For pedestal ILDs away from 0 dB, the best-threshold ILDs were as low as 0.5 dB, with a median of 2.3 dB. These findings support the hypothesis that the LSO plays a role in the extraction of ILD, and that the representation of ILD by LSO neurons may set a lower bound on the behavioral sensitivity to ILDs.

Application of ouabain to the round window membrane of the gerbil selectively induces the death of most spiral ganglion neurons and thus provides an excellent model for investigating the survival and differentiation of embryonic stem cells (ESCs) introduced into the inner ear. In this study, mouse ESCs were pretreated with a neural-induction protocol and transplanted into Rosenthal's canal (RC), perilymph, or endolymph of Mongolian gerbils either 1-3 days (early post-injury transplant group) or 7 days or longer (late post-injury transplant group) after ouabain injury. Overall, ESC survival in RC and perilymphatic spaces was significantly greater in the early post-injury microenvironment as compared to the later post-injury condition. Viable clusters of ESCs within RC and perilymphatic spaces appeared to be associated with neovascularization in the early post-injury group. A small number of ESCs transplanted within RC stained for mature neuronal or glial cell markers. ESCs introduced into perilymph survived in several locations, but most differentiated into glia-like cells. ESCs transplanted into endolymph survived poorly if at all. These experiments demonstrate that there is an optimal time window for engraftment and survival of ESCs that occurs in the early post-injury period.

The primate auditory cortex contains three interconnected regions (core, belt, parabelt), which are further subdivided into discrete areas. The caudomedial area (CM) is one of about seven areas in the belt region that has been the subject of recent anatomical and physiological studies conducted to define the functional organization of auditory cortex. The main goal of the present study was to examine temporal coding in area CM of marmoset monkeys using two related classes of acoustic stimuli: (1) marmoset twitter calls; and (2) frequency-modulated (FM) sweep trains modeled after the twitter call. The FM sweep trains were presented at repetition rates between 1 and 24 Hz, overlapping the natural phrase frequency of the twitter call (6-8 Hz). Multiunit recordings in CM revealed robust phase-locked responses to twitter calls and FM sweep trains. For the latter, phase-locking quantified by vector strength (VS) was best at repetition rates between 2 and 8 Hz, with a mean of about 5 Hz. Temporal response patterns were not strictly phase-locked, but exhibited dynamic features that varied with the repetition rate. To examine these properties, classification of the repetition rate from the temporal response pattern evoked by twitter calls and FM sweep trains was examined by Fisher's linear discrimination analysis (LDA). Response classification by LDA revealed that information was encoded not only by phase-locking, but also other components of the temporal response pattern. For FM sweep trains, classification was best for repetition rates from 2 to 8 Hz. Thus, the majority of neurons in CM can accurately encode the envelopes of temporally complex stimuli over the behaviorally-relevant range of the twitter call. This suggests that CM could be engaged in processing that requires relatively precise temporal envelope discrimination, and supports the hypothesis that CM is positioned at an early stage of processing in the auditory cortex of primates.

Audible frequencies of sound are encoded in a continuous manner along the length of the cochlea, and frequency is transmitted to the brain as a representation of place on the basilar membrane. The resulting tonotopic map has been assumed to be a continuous smooth progression from low to high frequency throughout the central auditory system. Here, physiological and anatomical data show that best frequency is represented in a discontinuous manner in the inferior colliculus, the major auditory structure of the midbrain. Multiunit maps demonstrate a distinct stepwise organization in the order of best frequency progression. Furthermore, independent data from single neurons show that best frequencies at octave intervals of approximately one-third are more prevalent than others. These data suggest that, in the inferior colliculus, there is a defined space of tissue devoted to a given frequency, and input within this frequency band may be pooled for higher-level processing.

A young male zebra finch (Taeniopygia guttata) learns to sing by copying the vocalizations of an older tutor in a process that parallels human speech acquisition. Brain pathways that control song production are well defined, but little is known about the sites and mechanisms of tutor song memorization. Here we test the hypothesis that molecular signaling in a sensory brain area outside of the song system is required for developmental song learning. Using controlled tutoring and a pharmacological inhibitor, we transiently suppressed the extracellular signal-regulated kinase signaling pathway in a portion of the auditory forebrain specifically during tutor song exposure. On maturation, treated birds produced poor copies of tutor song, whereas controls copied the tutor song effectively. Thus the foundation of normal song learning, the formation of a sensory memory of tutor song, requires a conserved molecular pathway in a brain area that is distinct from the circuit for song motor control.

Determining the spatial direction of sound sources is one of the major computations performed by the auditory system. The anterior ectosylvian sulcus (AES) of cat cortex is known to be important for sound localization. However, there are contradicting reports as to the spatial response properties of neurons in AES: whereas some studies found narrowly tuned neurons, others reported mostly spatially widely tuned neurons. We hypothesized that this is the result of a nonhomogenous distribution of the auditory neurons in this area. To test this possibility, we recorded neuronal activity along the AES, together with a sample of neurons from primary auditory cortex (A1) of cats in response to pure tones and to virtual acoustic space stimuli. In all areas, most neurons responded to both types of stimuli. Neurons located in posterior AES (pAES) showed special response properties that distinguished them from neurons in A1 and from neurons in anterior AES (aAES). The proportion of space-selective neurons among auditory neurons was significantly higher in pAES (82%) than in A1 (72%) and in aAES (60%). Furthermore, whereas the large majority of A1 neurons responded preferentially to contralateral sounds, neurons in pAES (and to a lesser extent in aAES) had their spatial selectivity distributed more homogenously. In particular, 28% of the space-selective neurons in pAES had highly modulated frontal receptive fields, against 8% in A1 and 17% in aAES. We conclude that in cats, pAES contains a secondary auditory cortical field which is specialized for spatial processing, in particular for the representation of frontal space.

We used optical imaging of intrinsic signals to study the large-scale organization of ferret auditory cortex in response to complex sounds. Cortical responses were collected during continuous stimulation by sequences of sounds with varying frequency, period, or interaural level differences. We used a set of stimuli that differ in spectral structure, but have the same periodicity and therefore evoke the same pitch percept (click trains, sinusoidally amplitude modulated tones, and iterated ripple noise). These stimuli failed to reveal a consistent periodotopic map across the auditory fields imaged. Rather, gradients of period sensitivity differed for the different types of periodic stimuli. Binaural interactions were studied both with single contralateral, ipsilateral, and diotic broadband noise bursts and with sequences of broadband noise bursts with varying level presented contralaterally, ipsilaterally, or in opposite phase to both ears. Contralateral responses were generally largest and ipsilateral responses were smallest when using single noise bursts, but the extent of the activated area was large and comparable in all three aural configurations. Modulating the amplitude in counter phase to the two ears generally produced weaker modulation of the optical signals than the modulation produced by the monaural stimuli. These results suggest that binaural interactions seen in cortex are most likely predominantly due to subcortical processing. Thus our optical imaging data do not support the theory that the primary or nonprimary cortical fields imaged are topographically organized to form consistent maps of systematically varying sensitivity either to stimulus pitch or to simple binaural properties of the acoustic stimuli.

Averaged auditory evoked potentials (AEPs) to bilaterally presented 100 Hz click trains were recorded from multiple sites simultaneously within Heschl's gyrus (HG) and on the posterolateral surface of the superior temporal gyrus (STG) in epilepsy-surgery patients. Three auditory fields were identified based on AEP waveforms and their distribution. Primary (core) auditory cortex was localized to posteromedial HG. Here the AEP was characterized by a robust polyphasic low-frequency field potential having a short onset latency and on which was superimposed a smaller frequency-following response to the click train. Core AEPs exhibited the lowest response threshold and highest response amplitude at one HG site with threshold rising and amplitude declining systematically on either side of it. The AEPs recorded anterolateral to the core, if present, were typically of low amplitude, with little or no evidence of short-latency waves or the frequency-following response that characterized core AEPs. We suggest that this area is part of a lateral auditory belt system. Robust AEPs, with waveforms demonstrably different from those of the core or lateral belt, were localized to the posterolateral surface of the STG and conform to previously described field PLST.

It is well established that the responses of binaural auditory neurons can adapt and change dramatically depending on the nature of a preceding sound. Examples of how the effects of ensuing stimuli play a functional role in auditory processing include motion sensitivity and precedence-like effects. To date, these types of effects have been documented at the level of the midbrain and above. Little is known about sensitivity to ensuing stimuli below in the superior olivary nuclei where binaural response properties are first established. Here we report on single cell responses in the gerbil lateral superior olive, the initial site where sensitivity to interaural level differences is established. In contrast to our expectations we found a robust sensitivity to ensuing stimuli. The majority of the cells we tested (86%), showed substantial suppression and/or enhancement to a designated target stimulus, depending on the nature of a preceding stimulus. Hence, sensitivity to ensuing stimuli is already established at the first synaptic station of binaural processing.

Studies have shown that acoustic experiences significantly contribute to the functional shaping of the structural organization and signal processing capacities of the mammalian auditory system during postnatal development. Here, we show how an early epoch of exposure to structured noise influences temporal processing in the rat primary auditory cortex documented immediately after exposure and again in adulthood. Pups were continuously exposed to broadband-pulsed noise across the critical period for auditory system development. Immediately after cessation of exposure at postnatal day ≈35 (P35) or ≈55 days later (i.e., P90) in other rats, the temporal modulation-transfer functions of cortical neurons were documented. We found that pulsed noise exposure at a low modulation rate significantly decreased cortical responses to repetitive stimuli presented across a range of higher modulation rates. The highest temporal rate at which temporal modulation-transfer function was at half of its maximum was reduced when compared with naïve rats. Low-rate pulsed noise exposure also decreased cortical response synchronization at higher stimulus rates, as shown by vector strength and Rayleigh statistic measures. These postexposure changes endured into adulthood. These findings bear significant implications for the role of early sound experiences as contributors to the ontogeny of human auditory and language-related abilities and impairments.

Anatomical and physiological studies have shown that anteroventral cochlear nucleus (AVCN) neurons receive glycinergic and GABAergic inhibitory inputs. In this study, changes in the temporal responses of AVCN neurons to pure tones and complex sounds after blocking inhibition were analyzed. Blocking inhibition influenced the temporal responses of each type of AVCN neuron. Choppers showed more chopping peaks and shortened chopping cycles after blocking inhibition. Sustained and slowly adapting choppers showed increased regularity throughout the response duration after blocking inhibition, whereas most transient choppers showed increased regularity in the early part of the response. Diverse changes in temporal response patterns were observed in neurons with primary-like and unusual responses, with several neurons showing a large decrease in the first-spike latency after blocking inhibition. This result disagreed with previous findings that onset responses are less affected than sustained responses by manipulating inhibition. Although blocking inhibition had a greater effect on spontaneous activity than that on tone-evoked activity, the change in spontaneous activity was less significant because of larger variability. In addition, for relatively high level masker noises, blocking inhibition had similar effects on responses to noise-alone and noise-plus-tone stimuli, in contrast with previous studies with low-level background noise. In general, inhibition had an enhancing effect on temporal contrast only for responses to amplitude-modulated tones, for which envelope synchrony was enhanced. Results of this study contribute new information about the characteristics, functional roles, and possible sources of inhibitory inputs received by AVCN neurons.

In this study, we investigate the ability of the mammalian auditory pathway to adapt its strategy for temporal processing under natural stimulus conditions. We derive temporal receptive fields from the responses of neurons in the inferior colliculus to vocalization stimuli with and without additional ambient noise. We find that the onset of ambient noise evokes a change in receptive field dynamics that corresponds to a change from bandpass to lowpass temporal filtering. We show that these changes occur within a few hundred milliseconds of the onset of the noise and are evident across a range of overall stimulus intensities. Using a simple model, we illustrate how these changes in temporal processing exploit differences in the statistical properties of vocalizations and ambient noises to increase the information in the neural response in a manner consistent with the principles of efficient coding.

The mammalian auditory system is the temporally most precise sensory modality: To localize low-frequency sounds in space, the binaural system can resolve time differences between the ears with microsecond precision. In contrast, the binaural system appears sluggish in tracking changing interaural time differences as they arise from a low-frequency sound source moving along the horizontal plane. For a combined psychophysical and electrophysiological approach, we created a binaural stimulus, called “Phasewarp,” that can transmit rapid changes in interaural timing. Using this stimulus, the binaural performance in humans is significantly better than reported previously and comparable with the monaural performance revealed with amplitude-modulated stimuli. Parallel, electrophysiological recordings of binaural brainstem neurons in the gerbil show fast temporal processing of monaural and different types of binaural modulations. In a refined electrophysiological approach that was matched to the psychophysics, the seemingly faster binaural processing of the Phasewarp was confirmed. The current data provide both psychophysical and physiological evidence against a general, hard-wired binaural sluggishness and reconcile previous contradictions of electrophysiological and psychophysical estimates of temporal binaural performance.

Abrupt orientation to novel stimuli is a critical, memory-dependent task performed by the brain. In the present study, we examined two gaze control centers of the barn owl: the optic tectum (OT) and the arcopallium gaze fields (AGFs). Responses of neurons to long sequences of dichotic sound bursts comprised of two sounds differing in the probability of appearance were analyzed. We report that auditory neurons in the OT and in the AGFs tend to respond stronger to rarely presented sounds (novel sounds) than to the same sounds when presented frequently. This history-dependent phenomenon, known as stimulus-specific adaptation (SSA), was demonstrated for rare sound frequencies, binaural localization cues [interaural time difference (ITD) and level difference (ILD)] and sound amplitudes. The manifestation of SSA in such a variety of independent acoustic features, in the midbrain and in the forebrain, supports the notion that SSA is involved in sensory memory and novelty detection. To track the origin of SSA, we analyzed responses of neurons in the external nucleus of the inferior colliculus (ICX; the source of auditory input to the OT) to similar sequences of sound bursts. Neurons in the ICX responded stronger to rare sound frequencies, but did not respond differently to rare ITDs, ILDs, or sound amplitudes. We hypothesize that part of the SSA reported here is computed in high-level networks, giving rise to novelty signals that modulate tectal responses in a context-dependent manner.