Auditory Neurophysiology publications

Spatial and nonspatial auditory processing is hypothesized to occur in parallel dorsal and ventral pathways, respectively. In this study, we tested the spatial and nonspatial sensitivity of auditory neurons in the ventrolateral prefrontal cortex (vPFC), a cortical area in the hypothetical nonspatial pathway. We found that vPFC neurons were modulated significantly by both the spatial and nonspatial attributes of an auditory stimulus. When comparing these responses with those in anterolateral belt region of the auditory cortex, which is hypothesized to be specialized for processing the nonspatial attributes of auditory stimuli, we found that the nonspatial sensitivity of vPFC neurons was poorer, whereas the spatial selectivity was better than anterolateral neurons. Also, the spatial and nonspatial sensitivity of vPFC neurons was comparable with that seen in the lateral intraparietal area, a cortical area that is a part of the dorsal pathway. These data suggest that substantial spatial and nonspatial processing occurs in both the dorsal and ventral pathways.

Neurons in primary auditory cortex (A1) of cats show strong stimulus-specific adaptation (SSA). In probabilistic settings, in which one stimulus is common and another is rare, responses to common sounds adapt more strongly than responses to rare sounds. This SSA could be a correlate of auditory sensory memory at the level of single A1 neurons. Here we studied adaptation in A1 neurons, using three different probabilistic designs. We showed that SSA has several time scales concurrently, spanning many orders of magnitude, from hundreds of milliseconds to tens of seconds. Similar time scales are known for the auditory memory span of humans, as measured both psychophysically and using evoked potentials. A simple model, with linear dependence on both short-term and long-term stimulus history, provided a good fit to A1 responses. Auditory thalamus neurons did not show SSA, and their responses were poorly fitted by the same model. In addition, SSA increased the proportion of failures in the responses of A1 neurons to the adapting stimulus. Finally, SSA caused a bias in the neuronal responses to unbiased stimuli, enhancing the responses to eccentric stimuli. Therefore, we propose that a major function of SSA in A1 neurons is to encode auditory sensory memory on multiple time scales. This SSA might play a role in stream segregation and in binding of auditory objects over many time scales, a property that is crucial for processing of natural auditory scenes in cats and of speech and music in humans.

Ion channels in the degenerin-epithelial sodium channel (DEG-ENaC) family perform diverse functions, including mechanosensation. Here we explored the role of the vertebrate DEG-ENaC protein, acid-sensing ion channel 2 (ASIC2), in auditory transduction. Contributions of ASIC2 to hearing were examined by comparing hearing threshold and noise sensitivity of wild-type and ASIC2 null mice. ASIC2 null mice showed no significant hearing loss, indicating that the ASIC2 was not directly involved in the mechanotransduction of the mammalian cochlea. However, we found that (1) ASIC2 was present in the spiral ganglion (SG) neurons in the adult cochlea and that externally applied protons induced amiloride-sensitive sodium currents and action potentials in SG neurons in vitro , (2) proton-induced responses were greatly reduced in SG neurons obtained from ASIC2 null mice, indicating that activations of ASIC2 contributed a major portion of the proton-induced excitatory response in SG neurons, and (3) ASIC2 null mice were considerably more resistant to noise-induced temporary, but not permanent, threshold shifts. Together, these data suggest that ASIC2 contributes to suprathreshold functions of the cochlea. The presence of ASIC2 in SG neurons could provide sensors to directly convert local acidosis to excitatory responses, therefore offering a cellular mechanism linking hearing losses caused by many enigmatic causes (e.g., ischemia or inflammation of the inner ear) to excitotoxicity.

This study examined the interactions between electrical stimuli presented through two channels of a cochlear implant. Experiments were conducted in anesthetized guinea pigs. Multiunit spike activity recorded from the auditory cortex reflected the cumulative effects of electric field interactions in the cochlea as well as any neural interactions along the ascending auditory pathway. The cochlea was stimulated electrically through a 6-electrode intracochlear array. The stimulus on each channel was a single 80- micro s/phase biphasic pulse. Channel interactions were quantified as changes in the thresholds for elevation of cortical spike rates. Experimental parameters were interchannel temporal offset (0 to +/-2000 micro s), interelectrode cochlear spacing (1.5 or 2.25 mm), electrode configuration (monopolar, bipolar, or tripolar), and relative polarity between channels (same or inverted). In most conditions, presentation of a subthreshold pulse on one channel reduced the threshold for a pulse on a second channel. Threshold shifts were greatest for simultaneous pulses, but appreciable threshold reductions could persist for temporal offsets up to 640 micro s. Channel interactions varied strongly with electrode configuration: threshold shifts increased in magnitude in the order tripolar, bipolar, monopolar. Channel interactions were greater for closer electrode spacing. The results have implications for design of speech processors for cochlear implants.

How do cortical neurons represent the acoustic environment? This question is often addressed by probing with simple stimuli such as clicks or tone pips. Such stimuli have the advantage of yielding easily interpreted answers, but have the disadvantage that they may fail to uncover complex or higher-order neuronal response properties. Here, we adopt an alternative approach, probing neuronal responses with complex acoustic stimuli, including animal vocalizations. We used in vivo whole-cell methods in the rat auditory cortex to record subthreshold membrane potential fluctuations elicited by these stimuli. Most neurons responded robustly and reliably to the complex stimuli in our ensemble. Using regularization techniques, we estimated the linear component, the spectrotemporal receptive field (STRF), of the transformation from the sound (as represented by its time-varying spectrogram) to the membrane potential of the neuron. We find that the STRF has a rich dynamical structure, including excitatory regions positioned in general accord with the prediction of the classical tuning curve. However, whereas the STRF successfully predicts the responses to some of the natural stimuli, it surprisingly fails completely to predict the responses to others; on average, only 11% of the response power could be predicted by the STRF. Therefore, most of the response of the neuron cannot be predicted by the linear component, although the response is deterministically related to the stimulus. Analysis of the systematic errors of the STRF model shows that this failure cannot be attributed to simple nonlinearities such as adaptation to mean intensity, rectification, or saturation. Rather, the highly nonlinear response properties of auditory cortical neurons must be attributable to nonlinear interactions between sound frequencies and time-varying properties of the neural encoder.

Focal excess sensory stimulation evokes reorganization of a sensory system. It is usually an expansion of the neural representation of that stimulus resulting from the shifts of the tuning curves (receptive fields) of neurons toward those of the stimulated neurons. The auditory cortex of the mustached bat has an area that is highly specialized for the processing of target-distance information carried by echo delays. In this area, however, reorganization is due to shifts of the delay-tuning curves of neurons away from those of the stimulated cortical neurons. Elimination of inhibition in the target-distance processing area in the auditory cortex by a drug reverses the direction of the shifts in neural tuning curves. Therefore, such unique reorganization in the time domain is due to strong lateral inhibition in the highly specialized area of the auditory cortex.

The hedgehog tenrec, Echinops telfairi, has certain basal mammalian features, like a cloaca and a sparsely differentiated brain with smooth cerebral hemispheres. The peripheral auditory capabilities of this species were investigated by means of distortion product otoacoustic emissions (DPOAE). For comparison, we determined auditory evoked potentials (AEP) in the inferior colliculus and the auditory cortex. Both methods show that the auditory range of E. telfairi extends well into ultrasonic frequencies, with a region of highest sensitivity at around 16 kHz. The total auditory range spans about 4 octaves at 40 dB SPL. The low-frequency limit of auditory processing is found at frequencies of about 2-3 kHz. The DPOAE and the AEP thresholds of E. telfairi do not run fully parallel in the high-frequency range. For a threshold value of 40 dB SPL, cochlear mechanical thresholds as measured with DPOAE extend up to 50 kHz, whereas neuronal thresholds reach the high-frequency limit at about 30 kHz. Frequency tuning, as assessed from DPOAE suppression tuning curves, was low to moderate with Q(10 dB) values ranging from 1.7 to 8. The lack of discontinuity in the group delay (derived from DPOAE measurements) reveals that cochlear frequency representation is tonotopic without any region of specialized mechanical tuning.

The voltage-gated potassium (Kv) channel subunit Kv1.1, encoded by the Kcna1 gene, is expressed strongly in the ventral cochlear nucleus (VCN) and the medial nucleus of the trapezoid body (MNTB) of the auditory pathway. To examine the contribution of the Kv1.1 subunit to the processing of auditory information, in vivo single-unit recordings were made from VCN neurons (bushy cells), axonal endings of bushy cells at MNTB cells (calyces of Held), and MNTB neurons of Kcna1 -null (-/-) mice and littermate control (+/+) mice. Thresholds and spontaneous firing rates of VCN and MNTB neurons were not different between genotypes. At higher sound intensities, however, evoked firing rates of VCN and MNTB neurons were significantly lower in -/- mice than +/+ mice. The SD of the first-spike latency (jitter) was increased in VCN neurons, calyces, and MNTB neurons of -/- mice compared with +/+ controls. Comparison along the ascending pathway suggests that the increased jitter found in -/- MNTB responses arises mostly in the axons of VCN bushy cells and/or their calyceal terminals rather than in the MNTB neurons themselves. At high rates of sinusoidal amplitude modulations, -/- MNTB neurons maintained high vector strength values but discharged on significantly fewer cycles of the amplitude-modulated stimulus than +/+ MNTB neurons. These results indicate that in Kcna1 -null mice the absence of the Kv1.1 subunit results in a loss of temporal fidelity (increased jitter) and the failure to follow high-frequency amplitude-modulated sound stimulation in vivo .

We evaluated the spatial selectivity of auditory cortical neurons in awake cats. Single- and multiunit activity was recorded in primary auditory cortex as the animals performed a nonspatial auditory discrimination or sat idly. Their heads were unrestrained, and head position was tracked. Broadband sounds were delivered from locations throughout 360° on the horizontal plane, and source locations were expressed in head-centered coordinates. As in anesthetized animals, the firing rates of most units were modulated by sound location, and most units responded best to sounds in the contralateral hemifield. Tuning was sharper than in anesthetized cats, in part because of suppression at nonoptimal locations. Nonetheless, spatial receptive fields typically spanned 150-180°. Units exhibited diverse temporal response patterns that often depended on sound location. An information-theoretic analysis showed that information transmission was reduced by ∼10% when the precision of spike timing was disrupted by 16-32 msec, and by ∼50% when all location-related variation of spike timing was removed. Spikes occurring within 60 msec of stimulus onset transmitted the most location-related information, but later spikes also carried information. The amount of information transmitted by ensembles of units increased with the number of units, indicating some degree of mutual independence in the spatial information transmitted by various units. Spatial tuning and information transmission were changed little by an increase in sound level of 20-30 dB. For the vast majority of units, receptive fields showed no significant change with the cat's head position or level of participation in the auditory task.

The Zwicker tone (ZT) is defined as an auditory negative afterimage, perceived after the presentation of an appropriate inducer. Typically, a notched noise (NN) with a notch width of 1/2 octave induces a ZT with a pitch falling in the frequency range of the notch. The aim of the present study was to find potential neural correlates of the ZT in the primary auditory cortex of ketamine-anesthetized cats. Responses of multiunits were recorded simultaneously with two 8-electrode arrays during 1 s and over 2 s after the presentation of a white noise (WN) and three NNs differing by the width of the notch, namely, 1/3 octave (NN1), 1/2 octave (NN2), and 2/3 octave (NN3). Both firing rate (FR) and peak cross-correlation coefficient (p) were evaluated for time windows of 500 ms. The cortical units were grouped according to whether their characteristic frequency (CF) was inside ("In" neurons) or outside ("Out" neurons) a 1-octave-wide frequency band centered on the notch center frequency. The ratios between the FRs and the rhos for each NN and the WN condition and for each group of neurons were then statistically evaluated. The ratios of FRs were significantly increased during and after the presentation of the NN for the "In" neurons. In contrast, the changes for the t" neurons were small and most often insignificant. The ratios of the p values differed significantly from 1 in the "In-In" and "In-Out" groups during stimulation as well as after it. We also found that the ps of "Out" neurons were dependent on the type of NN. Potentially, a combination of increased p and increased FR might be a neurophysiological correlate of the ZT.

Neurons are often assumed to operate in a highly unreliable manner: a neuron can signal the same stimulus with a variable number of action potentials. However, much of the experimental evidence supporting this view was obtained in the visual cortex. We have, therefore, assessed trial-to-trial variability in the auditory cortex of the rat. To ensure single-unit isolation, we used cell-attached recording. Tone-evoked responses were usually transient, often consisting of, on average, only a single spike per stimulus. Surprisingly, the majority of responses were not just transient, but were also binary, consisting of 0 or 1 action potentials, but not more, in response to each stimulus; several dramatic examples consisted of exactly one spike on 100% of trials, with no trial-to-trial variability in spike count. The variability of such binary responses differs from comparably transient responses recorded in visual cortical areas such as area MT, and represent the lowest trial-to-trial variability mathematically possible for responses of a given firing rate. Our study thus establishes for the first time that transient responses in auditory cortex can be described as a binary process, rather than as a highly variable Poisson process. These results demonstrate that cortical architecture can support a more precise control of spike number than was previously recognized, and they suggest a re-evaluation of models of cortical processing that assume noisiness to be an inevitable feature of cortical codes.

The prevailing hierarchical model of cortical sensory processing holds that early processing is specific to individual modalities and that combination of information from different modalities is deferred until higher-order stages of processing. In this paper, we present physiological evidence of multisensory convergence at an early stage of cortical auditory processing. We used multi-neuron cluster recordings, along with a limited sample of single-unit recordings, to determine whether neurons in the macaque auditory cortex respond to cutaneous stimulation. We found coextensive cutaneous and auditory responses in caudomedial auditory cortex, an area lying adjacent to A1, and at the second stage of the auditory cortical hierarchy. Somatosensory-auditory convergence in auditory cortex may underlie effects observed in human studies. Convergence of inputs from different sensory modalities at very early stages of cortical sensory processing has important implications for both our developing understanding of multisensory processing and established views of unisensory processing.

Neurons in the medial superior olive encode interaural temporal disparity, and their receptive fields indicate the location of a sound source in the azimuthal plane. It is often assumed that the projections of these neurons transmit the receptive field information about azimuth from point to point, much like the projections of the retina to the brain transmit the position of a visual stimulus. Yet this assumption has never been verified. Here, we use physiological and anatomical methods to examine the projections of the medial superior olive to the inferior colliculus for evidence of a spatial topography that would support transmission of azimuthal receptive fields. The results show that this projection does not follow a simple point-to-point topographical map of receptive field location. Thus, the representation of sound location along the azimuth in the inferior colliculus most likely relies on a complex, nonlinear map.

Contrary to findings in subcortical auditory nuclei, auditory cortex neurons have traditionally been described as spiking only at the onsets of simple sounds such as pure tones or bandpass noise and to acoustic transients in complex sounds. Furthermore, primary auditory cortex (A1) has traditionally been described as mostly tone responsive and the lateral belt area of primates as mostly noise responsive. The present study was designed to unify the study of these two cortical areas using random spectrum stimuli (RSS), a new class of parametric, wideband, stationary acoustic stimuli. We found that 60% of all neurons encountered in A1 and the lateral belt of awake marmoset monkeys (Callithrix jacchus) showed significant changes in firing rates in response to RSS. Of these, 89% showed sustained spiking in response to one or more individual RSS, a substantially greater percentage than would be expected from traditional studies, indicating that RSS are well suited for studying these two cortical areas. When firing rates elicited by RSS were used to construct linear estimates of frequency tuning for these sustained responders, the shape of the estimate function remained relatively constant throughout the stimulus interval and across the stimulus properties of mean sound level, spectral density, and spectral contrast. This finding indicates that frequency tuning computed from RSS reflects a robust estimate of the actual tuning of a neuron. Use of this estimate to predict rate responses to other RSS, however, yielded poor results, implying that auditory cortex neurons integrate information across frequency nonlinearly. No systematic difference in prediction quality between A1 and the lateral belt could be detected.

A direct commissural connection between cochlear nuclei provides a pathway by which binaural input can influence the processing of acoustic information through the ventral cochlear nucleus. Despite anatomical evidence to suggest the existence of such a pathway, its nature and behavior have not been investigated previously. This in vivo intracellular electrophysiological study provides direct evidence of monosynaptic (mean latency, 1.43 msec), inhibitory commissural input to T stellate cells. This inhibition is fast acting (duration, <10 msec), occurring with little synaptic delay (∼0.3 msec). Electrical stimulation also revealed the initiation of antidromic responses in the onset chopper population, signifying D stellate neurons as a source of commissural inputs. Activation of the commissural connection was most evident in response to broadband stimuli. These results provide the first compelling evidence of a fast, monosynaptic commissural pathway arising from contralateral D stellate neurons providing broadband inhibitory input to T stellate cells.

To localize sounds in space, humans heavily depend on minute interaural time differences (ITDs) generated by path-length differences to the two ears. Physiological studies of ITD sensitivity have mostly used deterministic, periodic sounds, in which either the waveform fine structure or a sinusoidal envelope is delayed interaurally. For natural broadband stimuli, however, auditory frequency selectivity causes individual channels to have their own envelopes; the temporal code in these channels is thus a mixture of fine structure and envelope. This study introduces a method to disentangle the contributions of fine structure and envelope in both binaural and monaural responses to broadband noise. In the inferior colliculus (IC) of the cat, a population of neurons was found in which envelope fluctuations dominate ITD sensitivity. This population extends over a surprisingly wide range of frequencies, including low frequencies for which fine-structure information is also available. A comparison with the auditory nerve suggests that an elaboration of envelope coding occurs between the nerve and the IC. These results suggest that internally generated envelopes play a more important role in binaural hearing than is commonly thought.

Synchronous envelope fluctuations in different frequency ranges of an acoustic background enhance the detection of signals in background noise. This effect, termed comodulation masking release (CMR), is attributed to both processing within one frequency channel of the auditory system and comparisons across separate frequency channels. Here we present data on CMR from a study in field L2 of the auditory forebrain of the European starling ( Sturnus vulgaris ) using two 25-Hz-wide bands of masking noise that provide the opportunity to distinguish between within-channel and across-channel effects. Acoustically evoked responses were recorded from unrestrained birds via radio telemetry. The signal was a 800 msec pure tone presented at the most sensitive frequency of the units in a previously determined frequency-tuning curve (FTC). One band of masking noise was centered on the signal frequency while the flanking band of noise was presented either within the limits of the excitatory FTC (i.e., within the same frequency channel as the on-frequency masker) or in the suppression area of the FTC (i.e., in a separate channel). For flanking bands inside the excitatory FTC, signal detection thresholds based on the rate code were lower in noise maskers with identical envelope fluctuations (comodulated) than in maskers with uncorrelated envelopes resulting in a neural CMR of ∼4–7 dB. For flanking bands inside the suppression areas, the neural CMR was reduced. Although the average neural CMR was below the behaviorally determined CMR, a subsample of between 11 and 26% of the recording sites resembled the behavioral performance.

Capsaicin, the vanilloid that selectively activates vanilloid receptors (VRs) on sensory neurons for noxious perception, has been reported to increase cochlear blood flow (CBF). VR-related receptors have also been found in the inner ear. This study aims to address the question as to whether VRs exist in the organ of Corti and play a role in cochlear physiology. Capsaicin or the more potent VR agonist, resiniferatoxin (RTX), was infused into the scala tympani of guinea pig cochlea, and their effects on cochlear sensitivity were investigated. Capsaicin (20 μM) elevated the threshold of auditory nerve compound action potential and reduced the magnitude of cochlear microphonic and electrically evoked otoacoustic emissions. These effects were reversible and could be blocked by a competitive antagonist, capsazepine. Application of 2 μM RTX resulted in cochlear sensitivity alterations similar to that by capsaicin, which could also be blocked by capsazepine. A desensitization phenomenon was observed in the case of prolonged perfusion with either capsaicin or RTX. Brief increase of CBF by capsaicin was confirmed, and the endocochlear potential was not decreased. Basilar membrane velocity (BM) growth functions near the best frequency and BM tuning were altered by capsaicin. Immunohistochemistry study revealed the presence of vanilloid receptor type 1 of the transient receptor potential channel family in the hair cells and supporting cells of the organ of Corti and the spiral ganglion cells of the cochlea. The results indicate that the main action of capsaicin is on outer hair cells and suggest that VRs in the cochlea play a role in cochlear homeostasis.