Electrophysiology publications

Recognition of acoustic signals may be impeded by two factors: extrinsic noise, which degrades sounds before they arrive at the receiver's ears, and intrinsic neuronal noise, which reveals itself in the trial-to-trial variability of the responses to identical sounds. Here we analyzed how these two noise sources affect the recognition of acoustic signals from potential mates in grasshoppers. By progressively corrupting the envelope of a female song, we determined the critical degradation level at which males failed to recognize a courtship call in behavioral experiments. Using the same stimuli, we recorded intracellularly from auditory neurons at three different processing levels, and quantified the corresponding changes in spike train patterns by a spike train metric, which assigns a distance between spike trains. Unexpectedly, for most neurons, intrinsic variability accounted for the main part of the metric distance between spike trains, even at the strongest degradation levels. At consecutive levels of processing, intrinsic variability increased, while the sensitivity to external noise decreased. We followed two approaches to determine critical degradation levels from spike train dissimilarities, and compared the results with the limits of signal recognition measured in behaving animals.

The CBA/CaJ mouse strain is commonly used as a control as it has no known genetic mutations affecting the inner ear, maintains hearing sensitivity throughout life, and serves as a background for creating new genetic strains. The purpose of the present study was to characterize the effects of age and gender on gravity receptor function and compare functional changes between auditory and vestibular modalities. Vestibular-evoked potentials (VsEPs), auditory brainstem responses (ABRs), and distortion product otoacoustic emissions were measured in 131 mice. VsEP thresholds deteriorated an average of 0.39 dB re: 1.0 g/ms per month and at the oldest ages (18-23 months old) showed an average loss of 49% of VsEP dynamic range. No significant gender differences were found for VsEPs. ABR thresholds increased by an average of 1.35, 1.38, and 1.15 dB pe SPL per month for ABR stimulus frequencies of 8, 16, and 32 kHz, respectively, demonstrating an average decrease in auditory dynamic range of 25-35% at advanced ages. Both modalities declined with age. Age-related decreases in gravity receptor sensitivity should be considered when using the CBA/CaJ strain for vestibular studies.

The causes of dolphin and whale stranding can often be difficult to determine. Because toothed whales rely on echolocation for orientation and feeding, hearing deficits could lead to stranding. We report on the results of auditory evoked potential measurements from eight species of odontocete cetaceans that were found stranded or severely entangled in fishing gear during the period 2004 through 2009. Approximately 57% of the bottlenose dolphins and 36% of the rough-toothed dolphins had significant hearing deficits with a reduction in sensitivity equivalent to severe (70-90 dB) or profound (>90 dB) hearing loss in humans. The only stranded short-finned pilot whale examined had profound hearing loss. No impairments were detected in seven Risso's dolphins from three different stranding events, two pygmy killer whales, one Atlantic spotted dolphin, one spinner dolphin, or a juvenile Gervais' beaked whale. Hearing impairment could play a significant role in some cetacean stranding events, and the hearing of all cetaceans in rehabilitation should be tested.

The compromised abilities to localize sounds and to understand speech are two hallmark deficits in aged individuals. The auditory cortex is necessary for these processes, yet we know little about how normal aging affects these early cortical fields. In this study, we recorded the spatial tuning of single neurons in primary (auditory cortex, A1) and secondary (caudolateral field, CL) auditory cortical areas in young and aged alert rhesus macaques. We found that the neurons of aged animals had greater spontaneous and driven activity, and broader spatial tuning compared with those of younger animals. Importantly, spatial tuning was not sharpened between A1 and CL in aged monkeys as it is in younger monkeys. This implies that a major effect of normal aging is a degradation of the hierarchical processing between serially connected cortical areas, which could be a key contributing mechanism of the general cognitive decline that is commonly observed in normal aging.

Somatosensory evoked potentials (SSEPs) have been established as an electrophysiological tool for the prognostication of neurological outcome in patients with hypoxic-ischemic brain injury. The early and late responses in SSEPs reflect the sequential activation of neural structures along the somatosensory pathway. This study reports that the SSEP can be separated into early (short-latency, SL) and late (long-latency, LL) responses using independent component analysis (ICA), based on the assumption that these components are generated from different neural sources. Moreover, this source separation into the SL and LL components allows analysis of electrophysiological response to brain injury, even when the SSEPs are severely distorted and SL and LL components get mixed. With the help of ICA decomposition and corrected peak estimation, the latency of LL-SSEP is shown to be predictive of long-term neurological outcome. Further, it is shown that the recovery processes of SL- and LL-SSEPs follow different dynamics, with the SL-SSEP restored earlier than LL-SSEP. We predict that the SL- and LL-SSEPs reflect the timing of the progression of evoked response through the thalamocortical pathway and as such respond differently depending upon injury and recovery of the thalamic and cortical regions, respectively.

Human bilateral cochlear implant users do poorly on tasks involving interaural time differences (ITD), a cue that provides important benefits to the normal hearing, especially in challenging acoustic environments, yet the precision of neural ITD coding in acutely deafened, bilaterally implanted cats is essentially normal (Smith and Delgutte, 2007a). One explanation for this discrepancy is that the extended periods of binaural deprivation typically experienced by cochlear implant users degrades neural ITD sensitivity, by either impeding normal maturation of the neural circuitry or altering it later in life. To test this hypothesis, we recorded from single units in inferior colliculus of two groups of bilaterally implanted, anesthetized cats that contrast maximally in binaural experience: acutely deafened cats, which had normal binaural hearing until experimentation, and congenitally deaf white cats, which received no auditory inputs until the experiment. Rate responses of only half as many neurons showed significant ITD sensitivity to low-rate pulse trains in congenitally deaf cats compared with acutely deafened cats. For neurons that were ITD sensitive, ITD tuning was broader and best ITDs were more variable in congenitally deaf cats, leading to poorer ITD coding within the naturally occurring range. A signal detection model constrained by the observed physiology supports the idea that the degraded neural ITD coding resulting from deprivation of binaural experience contributes to poor ITD discrimination by human implantees.

The primary auditory cortex (A1) is organized tonotopically, with neurons sensitive to high and low frequencies arranged in a rostro-caudal gradient. We used laser scanning photostimulation in acute slices to study the organization of local excitatory connections onto layers 2 and 3 (L2/3) of the mouse A1. Consistent with the organization of other cortical regions, synaptic inputs along the isofrequency axis (orthogonal to the tonotopic axis) arose predominantly within a column. By contrast, we found that local connections along the tonotopic axis differed from those along the isofrequency axis: some input pathways to L3 (but not L2) arose predominantly out-of-column. In vivo cell-attached recordings revealed differences between the sound-responsiveness of neurons in L2 and L3. Our results are consistent with the hypothesis that auditory cortical microcircuitry is specialized to the one-dimensional representation of frequency in the auditory cortex.

Purpose: High‐frequency oscillations (HFOs) are an emerging biomarker for epileptic tissue. Yet the mechanism by which HFOs are produced is unknown, and their rarity makes them difficult to study. Our objective was to examine the occurrence of HFOs in relation to action potentials (APs) and the effect of microstimulation in the tetanus toxin (TT) model of epilepsy, a nonlesional model with a short latency to spontaneous seizures. Methods: Rats were injected with TT into dorsal hippocampus and implanted with a 16‐channel (8 × 2) multielectrode array, one row each in CA3 and CA1. After onset of spontaneous seizures (3–9 days), recordings were begun of APs and local field potentials, analyzed for the occurrence of interictal spikes and HFOs. Recordings were made during microstimulation of each electrode using customized, open‐source software. Results: Population bursts of APs during interictal spikes were phase‐locked with HFOs, which were observable almost exclusively with high‐amplitude interictal spikes. Furthermore, HFOs could reliably be produced by microstimulation of the hippocampus, providing evidence that these oscillations can be controlled temporally by external means. Discussion: We show for the first time the occurrence of HFOs in the TT epilepsy model, an attractive preparation for their experimental investigation and, importantly, one with a different etiology than that of status models, providing further evidence of the generality of HFOs. The ability to provoke HFOs with microstimulation may prove useful for better understanding of HFOs by directly evoking them in the lab, and designing high‐throughput techniques for presurgical localization of the epileptic focus.

The local field potential (LFP) and multiunit activity (MUA) are extracellularly recorded signals that describe local neuronal network dynamics. In our experiments, the LFP and MUA, recorded from the same electrode in macaque primary visual cortex V1 in response to drifting grating visual stimuli, were evaluated on coarse timescales (∼1–5 s) and fine timescales (<0.1 s). On coarse timescales, MUA and the LFP both produced sustained visual responses to optimal and non-optimal oriented visual stimuli. The sustainedness of the two signals across the population of recording sites was correlated (correlation coefficient, ∼0.4). At most recording sites, the MUA was at least as sustained as the LFP and significantly more sustained for optimal orientations. In previous literature, the blood oxygen level-dependent (BOLD) signal of functional magnetic resonance imaging studies was found to be more strongly correlated with the LFP than with the MUA as a result of the lack of sustained response in the MUA signal. Because we found that MUA was as sustained as the LFP, MUA may also be correlated with BOLD. On fine timescales, we computed the coherence between the LFP and MUA over the frequency range 10–150 Hz. The LFP and MUA were weakly but significantly coherent (∼0.14) in the gamma band (20–90 Hz). The amount of gamma-band coherence was correlated with the power in the gamma band of the LFP. The data were consistent with the proposal that the LFP and MUA are generated in a noisy, resonant cortical network.

In anurans, the temporal patterning of sound pulses is the primary information used for differentiating between spectrally similar calls. One class of midbrain neurons, referred to as 'interval-counting' cells, appears to be particularly important for discriminating among calls that differ in pulse repetition rate (PRR). These cells only respond after several pulses are presented with appropriate interpulse intervals. Here we show that the range of selectivity and sharpness of interval tuning vary considerably across neurons. Whole-cell recordings revealed that neurons showing temporally summating excitatory postsynaptic potentials (EPSPs) with little or no inhibition or activity-dependent enhancement of excitation exhibited low-pass or band-pass tuning to slow PRRs. Neurons that showed inhibition and rate-dependent enhancement of excitation, however, were band-pass or high-pass to intermediate or fast PRRs. Surprisingly, across cells, interval tuning based on membrane depolarization and spike rate measures were not significantly correlated. Neurons that lacked inhibition showed the greatest disparities between these two measures of interval tuning. Cells that showed broad membrane potential-based tuning, for example, varied considerably in their spike rate-based tuning; narrow spike rate-based tuning resulted from 'thresholding' processes, whereby only the largest depolarizations triggered spikes. The potential constraints associated with generating interval tuning in this manner are discussed.

Consistent with human perceptual data, we found many more black-dominant than white-dominant responses in layer 2/3 neurons of the macaque primary visual cortex (V1). Seeking the mechanism of this black dominance of layer 2/3 neurons, we measured the laminar pattern of population responses (multiunit activity and local field potential) and found that a small preference for black is observable in early responses in layer 4Cβ, the parvocellular-input layer, but not in the magnocellular-input layer 4Cα. Surprisingly, further analysis of the dynamics of black-white responses in layers 4Cβ and 2/3 suggested that black-dominant responses in layer 2/3 were not generated simply because of the weak black-dominant inputs from 4Cβ. Instead, our results indicated the neural circuitry in V1 is wired with a preference to strengthen black responses. We hypothesize that this selective wiring could be due to (1) feedforward connectivity from black-dominant neurons in layer 4C to cells in layer 2/3 or (2) recurrent interactions between black-dominant neurons in layer 2/3, or a combination of both.

A popular model of binaural processing, proposed by Jeffress (1948), states that external interaural time delays (ITDs) are compensated by internal axonal delays allowing ITD to be spatially represented by a population of coincidence detectors in the medial superior olive (MSO). Isolating single-neuron responses in MSO is difficult because of the presence of a strong extracellular field potential known as the neurophonic, so that few studies have tested Jeffress's key prediction. Phase delays in the nucleus laminaris neurophonic in owls have been observed and are consistent with a Jeffress-like model. Here, we recorded neurophonic responses in cat MSO to monaural tones at locations along its dendritic axis. Fourier analysis of the neurophonic was used to extract amplitude and phase at the stimulus frequency. Amplitude, as a function of depth, showed two peaks separated by a dip. A half-cycle phase shift was observed at depths close to the dip, over a wide frequency range. Current source density analysis for contralateral (ipsilateral) stimulation shows a current source close to the neurophonic amplitude peak and a sink a few hundred micrometers ventromedially (dorsolaterally). These results are consistent with a dipole configuration: contralateral (ipsilateral) excitation causes a current sink at the ventromedial (dorsolateral) dendrites and a source at the soma and dorsolateral (ventromedial) dendrites. Incorporating these results in a dipole model explains the phase and amplitude patterns observed. We conclude that the half-cycle phase shift is consistent with a current dipole, making it difficult to derive measurements of axonal delays from the neurophonic.

Distinct pathways carry monaural and binaural information from the lower auditory brainstem to the central nucleus of the inferior colliculus (ICC). Previous anatomical and physiological studies suggest that differential ascending inputs to regions of the ICC create functionally distinct zones. Here, we provide direct evidence of this relationship by combining recordings of single unit responses to sound in the ICC with focal, iontophoretic injections of the retrograde tracer Fluoro-Gold at the physiologically characterized sites. Three main patterns of anatomical inputs were observed. One pattern was identified by inputs from the cochlear nucleus and ventral nucleus of the lateral lemniscus in isolation, and these injection sites were correlated with monaural responses. The second pattern had inputs only from the ipsilateral medial and lateral superior olive, and these sites were correlated with interaural time difference (ITD)-sensitive responses to low frequency (<500 Hz). A third pattern had inputs from a variety of olivary and lemniscal sources, notably the contralateral lateral superior olive and dorsal nucleus of the lateral lemniscus. These were correlated with high-frequency ITD sensitivity to complex acoustic stimuli. These data support the notion of anatomical regions formed by specific patterns of anatomical inputs to the ICC. Such synaptic domains may represent functional zones in ICC.

Speech perception requires the rapid and effortless extraction of meaningful phonetic information from a highly variable acoustic signal. A powerful example of this phenomenon is categorical speech perception, in which a continuum of acoustically varying sounds is transformed into perceptually distinct phoneme categories. We found that the neural representation of speech sounds is categorically organized in the human posterior superior temporal gyrus. Using intracranial high-density cortical surface arrays, we found that listening to synthesized speech stimuli varying in small and acoustically equal steps evoked distinct and invariant cortical population response patterns that were organized by their sensitivities to critical acoustic features. Phonetic category boundaries were similar between neurometric and psychometric functions. Although speech-sound responses were distributed, spatially discrete cortical loci were found to underlie specific phonetic discrimination. Our results provide direct evidence for acoustic-to-higher order phonetic level encoding of speech sounds in human language receptive cortex.

In humans, horizontal sound localization of low-frequency sounds is mainly based on interaural time differences (ITDs). Traditionally, it was assumed that ITDs are converted into a topographic (or rate-place) code, supported by an array of neurons with parametric tuning to ITDs within the behaviorally relevant range. Although this topographic model has been confirmed in owls, its applicability to mammals has been challenged by recent physiological results suggesting that, at least in small-headed species, ITDs are represented by a nontopographic population rate code, which involves only two opponent (left and right) channels, broadly tuned to ITDs from the two auditory hemifields. The current study investigates which of these two models of ITD processing is more likely to apply to humans. For that, evoked responses to abrupt changes in the ITDs of otherwise continuous sounds were measured with electroencephalography. The ITD change was either away from (“outward” change) or toward the midline (“inward” change). According to the opponent-channel model, the response to an outward ITD change should be larger than the response to the corresponding inward change, whereas the topographic model would predict similar response sizes for both conditions. The measured response sizes were highly consistent with the predictions of the opponent-channel model and contravened the predictions of the topographic model, suggesting that, in humans, ITDs are coded nontopographically. The hemispheric distributions of the ITD change responses suggest that the majority of ITD-sensitive neurons in each hemisphere are tuned to ITDs from the contralateral hemifield.

The neurophonic is a sound-evoked, frequency-following potential that can be recorded extracellularly in nucleus laminaris of the barn owl. The origin of the neurophonic, and thus the mechanisms that give rise to its exceptional temporal precision, has not yet been identified. Putative generators of the neurophonic are the activity of afferent axons, synaptic activation of laminaris neurons, or action potentials in laminaris neurons. To identify the generators, we analyzed the neurophonic in the high-frequency (>2.5 kHz) region of nucleus laminaris in response to monaural pure-tone stimulation. The amplitude of the neurophonic is typically in the millivolt range. The signal-to-noise ratio reaches values beyond 30 dB. To assess which generators could give rise to these large, synchronous extracellular potentials, we developed a computational model. Spike trains were produced by an inhomogeneous Poisson process and convolved with a spike waveform. The model explained the dependence of the simulated neurophonic on parameters such as the mean rate, the vector strength of phase locking, the number of statistically independent sources, and why the signal-to-noise ratio is independent of the spike waveform and subsequent filtering of the signal. We found that several hundred sources are needed to reach the observed signal-to-noise ratio. The summed coherent signal from the densely packed afferent axons and activation of their synapses on laminaris neurons are alone sufficient to explain the measured properties of the neurophonic.

Belgian Waterslager (BW) canaries have an inherited hearing loss due to missing and abnormal hair cells, but it is unclear whether the loss is congenital or developmental. We used auditory brainstem responses and scanning electron microscopy to describe the development of auditory sensitivity and hair cell abnormalities in BW and non-BW canaries. In both strains, adult ABR thresholds were higher than behavioral thresholds, but BW canaries exhibited higher thresholds than non-BW canaries across all frequencies. Immediately post-hatch, ABR thresholds and hair cell numbers were similar in both strains. Two weeks later, thresholds were significantly higher in BW canaries, and hair cell number progressively decreased as the birds aged. These data show that in BW canaries: the peripheral auditory system is functionally similar to non-BW canary from hatch to 2 weeks, ABR thresholds improve during this developmental period, actually becoming better than those of adults, but then worsen as the bird continues to age. Hair cell number and appearance is similar to non-BW canaries at hatch but progressively declines after 30 days of age. These data show that the hearing loss characteristic of BW canaries is, at least in part, developmental and is established by the time song learning begins.

Purpose: CO₂ has been long recognized for its anticonvulsant properties. We aimed to determine whether inhaling 5% CO₂ can be used to suppress seizures in epilepsy patients. The effect of CO₂ on cortical epileptic activity accompanying behavioral seizures was studied in rats and nonhuman primates, and based on these data, preliminary tests were carried out in humans. Methods: In freely moving rats, cortical afterdischarges paralleled by myoclonic convulsions were evoked by sensorimotor cortex stimulation. Five percent CO₂ was applied for 5 min, 3 min before stimulation. In macaque monkeys, hypercarbia was induced by hypoventilation while seizure activity was electrically or chemically evoked in the sensorimotor cortex. Seven patients with drug-resistant partial epilepsy were examined with video-EEG (electroencephalography) and received 5% CO₂ in medical carbogen shortly after electrographic seizure onset. Results: In rats, 5% CO₂ strongly suppressed cortical afterdischarges, by approximately 75%, whereas responses to single-pulse stimulation were reduced by about 15% only. In macaques, increasing pCO₂) from 37 to 44-45 mm Hg (corresponding to inhalation of 5% CO₂ or less) suppressed stimulation-induced cortical afterdischarges by about 70% and single, bicuculline-induced epileptiform spikes by approximately 25%. In a pilot trial carried out in seven patients, a rapid termination of electrographic seizures was seen despite the fact that the application of 5% CO₂ was started after seizure generalization. Conclusions: Five percent CO₂ has a fast and potent anticonvulsant action. The present data suggest that medical carbogen with 5% CO₂ can be used for acute treatment to suppress seizures in epilepsy patients.

Connectional anatomical evidence suggests that the auditory core, containing the tonotopic areas A1, R, and RT, constitutes the first stage of auditory cortical processing, with feedforward projections from core outward, first to the surrounding auditory belt and then to the parabelt. Connectional evidence also raises the possibility that the core itself is serially organized, with feedforward projections from A1 to R and with additional projections, although of unknown feed direction, from R to RT. We hypothesized that area RT together with more rostral parts of the supratemporal plane (rSTP) form the anterior extension of a rostrally directed stimulus quality processing stream originating in the auditory core area A1. Here, we analyzed auditory responses of single neurons in three different sectors distributed caudorostrally along the supratemporal plane (STP): sector I, mainly area A1; sector II, mainly area RT; and sector III, principally RTp (the rostrotemporal polar area), including cortex located 3 mm from the temporal tip. Mean onset latency of excitation responses and stimulus selectivity to monkey calls and other sounds, both simple and complex, increased progressively from sector I to III. Also, whereas cells in sector I responded with significantly higher firing rates to the “other” sounds than to monkey calls, those in sectors II and III responded at the same rate to both stimulus types. The pattern of results supports the proposal that the STP contains a rostrally directed, hierarchically organized auditory processing stream, with gradually increasing stimulus selectivity, and that this stream extends from the primary auditory area to the temporal pole.

Using modulation transfer functions (MTF), we investigated how sound patterns are processed within the auditory pathway of grasshoppers. Spike rates of auditory receptors and primary-like local neurons did not depend on modulation frequencies while other local and ascending neurons had lowpass, bandpass or bandstop properties. Local neurons exhibited broader dynamic ranges of their rate MTF that extended to higher modulation frequencies than those of most ascending neurons. We found no indication that a filter bank for modulation frequencies may exist in grasshoppers as has been proposed for the auditory system of mammals. The filter properties of half of the neurons changed to an allpass type with a 50% reduction of modulation depths. Contrasting to reports for mammals, the sensitivity to small modulation depths was not enhanced at higher processing stages. In ascending neurons, a focus on the range of low modulation frequencies was visible in the temporal MTFs, which describe the temporal locking of spikes to the signal envelope. To investigate the influence of stimulus rise time, we used rectangularly modulated stimuli instead of sinusoidally modulated ones. Unexpectedly, steep stimulus onsets had only small influence on the shape of MTF curves of 70% of neurons in our sample.