Electrophysiology publications

A “ventral” auditory pathway in nonhuman primates that originates in the core auditory cortex and ends in the prefrontal cortex is thought to be involved in components of nonspatial auditory processing. Previous work from our laboratory has indicated that neurons in the prefrontal cortex reflect monkeys' decisions during categorical judgments. Here, we tested the role of the superior temporal gyrus (STG), a region of the secondary auditory cortex that is part of this ventral pathway, during similar categorical judgments. While monkeys participated in a match-to-category task and reported whether two consecutive auditory stimuli belonged to the same category or to different categories, we recorded spiking activity from STG neurons. The auditory stimuli were morphs of two human-speech sounds ( bad and dad). We found that STG neurons represented auditory categories. However, unlike activity in the prefrontal cortex, STG activity was not modulated by the monkeys' behavioral reports (choices). This finding is consistent with the anterolateral STG's role as a part of functional circuit involved in the coding, representation, and perception of the nonspatial features of an auditory stimulus.

The human temporal lobe is well known to be critical for language comprehension. Previous physiological research has focused mainly on non-invasive neuroimaging and electrophysiological techniques with each approach requiring averaging across many trials and subjects. The results of these studies have implicated extended anatomical regions in peri-sylvian cortex in speech perception. These non-invasive studies typically report a spatially homogenous functional pattern of activity across several centimeters of cortex. We examined the spatiotemporal dynamics of word processing using electrophysiological signals acquired from high-density electrode arrays (4mm spacing) placed directly on the human temporal lobe. Electrocorticographic (ECoG) activity revealed a rich mosaic of language activity, which was functionally distinct at four mm separation. Cortical sites responding specifically to word and not phoneme stimuli were surrounded by sites that responded to both words and phonemes. Other sub-regions of the temporal lobe responded robustly to self-produced speech and minimally to external stimuli while surrounding sites at 4mm distance exhibited an inverse pattern of activation. These data provide evidence for temporal lobe specificity to words as well as self-produced speech. Furthermore, the results provide evidence that cortical processing in the temporal lobe is not spatially homogenous over centimeters of cortex. Rather, language processing is supported by independent and spatially distinct functional sub-regions of cortex at a resolution of at least 4mm.

The auditory system must represent sounds with a wide range of statistical properties. One important property is the spectrotemporal contrast in the acoustic environment: the variation in sound pressure in each frequency band, relative to the mean pressure. We show that neurons in ferret auditory cortex rescale their gain to partially compensate for the spectrotemporal contrast of recent stimulation. When contrast is low, neurons increase their gain, becoming more sensitive to small changes in the stimulus, although the effectiveness of contrast gain control is reduced at low mean levels. Gain is primarily determined by contrast near each neuron's preferred frequency, but there is also a contribution from contrast in more distant frequency bands. Neural responses are modulated by contrast over timescales of ∼100 ms. By using contrast gain control to expand or compress the representation of its inputs, the auditory system may be seeking an efficient coding of natural sounds.

The perception of sensory stimuli by an animal requires several steps, commencing with the capture of stimulus energy by an antenna that, as the interface between the physical world and the nervous system, modifies the stimulus in ways that enhance the animal's perception. The mammalian external ear, for example, collects sound and spectrally alters it to increase sensitivity and improve the detection of directionality. In view of the morphological diversity of the lateral-line system across species and its accessibility to observation and experimental intervention, we sought to investigate the role of antennal structures on the response characteristics of the lateral line. The surface-feeding killifish Aplocheilus lineatus is able to hunt in darkness by detecting surface capillary waves with the lateral-line system atop its head. This cephalic lateral line consists of a stereotyped array of 18 mechanosensitive neuromasts bordered by fleshy ridges. By recording microphonic potentials, we found that each neuromast has a unique receptive field defined by its sensitivity to stimulation of the water's surface. The ridges help determine these receptive fields by altering the flow of water over each neuromast. Modification of the hydrodynamic environment by the addition of a supplemental ridge changes the pattern of water movement, perturbs the receptive fields of adjacent neuromasts and impairs the fish's localization ability. On the basis of electrophysiological, hydrodynamic and behavioral evidence, we propose that the ridges constitute a hydrodynamic antenna for the cephalic lateral line.

As the information bottleneck of nearly all auditory input that reaches the cortex, the auditory thalamus serves as the basis for establishing auditory cortical processing streams. The functional organization of the primary and nonprimary subdivisions of the auditory thalamus is not well characterized, particularly in awake primates. We have recorded from neurons in the auditory thalamus of awake marmoset monkeys and tested their responses to tones, band-pass noise, and temporally modulated stimuli. We analyzed the spectral and temporal response properties of recorded neurons and correlated those properties with their locations in the auditory thalamus, thereby forming the basis for parallel output channels. Three medial geniculate body (MGB) subdivisions were identified and studied physiologically and anatomically, although other medial subdivisions were also identified anatomically. Neurons in the ventral subdivision (MGV) were sharply tuned for frequency, preferred narrowband stimuli, and were able to synchronize to rapid temporal modulations. Anterodorsal subdivision (MGAD) neurons appeared well suited for temporal processing, responding similarly to tone or noise stimuli but able to synchronize to the highest modulation frequencies and with the highest temporal precision among MGB subdivisions. Posterodorsal subdivision (MGPD) neurons differed substantially from the other two subdivisions, with many neurons preferring broadband stimuli and signaling changes in modulation frequency with nonsynchronized changes in firing rate. Most neurons in all subdivisions responded to increases in tone sound level with nonmonotonic changes in firing rate. MGV and MGAD neurons exhibited responses consistent with provision of thalamocortical input to core regions, whereas MGPD neurons were consistent with provision of input to belt regions.

Direct recording from sequential processing stations within the brain has provided opportunity for enhancing understanding of important neural circuits, such as the corticothalamic loops underlying auditory, visual, and somatosensory processing. However, the common reliance upon microwire-based electrodes to perform such recordings often necessitates complex surgeries and increases trauma to neural tissues. This paper reports the development of titanium-based, microfabricated, microelectrode devices designed to address these limitations by allowing acute recording from the thalamic nuclei and associated cortical sites simultaneously in a minimally invasive manner. In particular, devices were designed to simultaneously probe rat auditory cortex and auditory thalamus, with the intent of recording auditory response latencies and isolated action potentials within the separate anatomical sites. Details regarding the design, fabrication, and characterization of these devices are presented, as are preliminary results from acute in vivo recording.

Movement-assist devices such as neuromuscular stimulation systems can be used to generate movements in people with chronic hand paralysis due to stroke. If detectable, motor planning activity in the cortex could be used in real time to trigger a movement-assist device and restore a person's ability to perform many of the activities of daily living. Additionally, re-coupling motor planning in the cortex with assisted movement generation in the periphery may provide an even greater benefit-strengthening relevant synaptic connections over time to promote natural motor recovery. This study examined the potential for using electroencephalograms (EEGs) as a means of rapidly detecting the intent to open the hand during movement planning in individuals with moderate chronic hand paralysis following a subcortical ischemic stroke. On average, attempts to open the hand could be detected from EEGs approximately 100-500 ms prior to the first signs of movement onset. This earlier detection would minimize device activation delays and allow for tighter coupling between initial formation of the motor plan in the cortex and augmentation of that plan in the periphery by a movement-assist device. This tight temporal coupling may be important or even essential for strengthening synaptic connections and enhancing natural motor recovery.

Growing evidence from electrophysiological data in animal and human studies suggests that multisensory interaction is not exclusively a higher-order process, but also takes place in primary sensory cortices. Such early multisensory interaction is thought to be mediated by means of phase resetting. The presentation of a stimulus to one sensory modality resets the phase of ongoing oscillations in another modality such that processing in the latter modality is modulated. In humans, evidence for such a mechanism is still sparse. In the current study, the influence of an auditory stimulus on visual processing was investigated by measuring the electroencephalogram (EEG) and behavioral responses of humans to visual, auditory, and audiovisual stimulation with varying stimulus-onset asynchrony (SOA). We observed three distinct oscillatory EEG responses in our data. An initial gamma-band response around 50 Hz was followed by a beta-band response around 25 Hz, and a theta response around 6 Hz. The latter was enhanced in response to cross-modal stimuli as compared to either unimodal stimuli. Interestingly, the beta response to unimodal auditory stimuli was dominant in electrodes over visual areas. The SOA between auditory and visual stimuli—albeit not consciously perceived—had a modulatory impact on the multisensory evoked beta-band responses; i.e., the amplitude depended on SOA in a sinusoidal fashion, suggesting a phase reset. These findings further support the notion that parameters of brain oscillations such as amplitude and phase are essential predictors of subsequent brain responses and might be one of the mechanisms underlying multisensory integration.

Multi-electrode array recordings of spike and local field potential (LFP) activity were made from primary auditory cortex of 12 normal hearing, ketamine-anesthetized cats. We evaluated 259 spectro-temporal receptive fields (STRFs) and 492 frequency-tuning curves (FTCs) based on LFPs and spikes simultaneously recorded on the same electrode. We compared their characteristic frequency (CF) gradients and their cross-correlation distances. The CF gradient for spike-based FTCs was about twice that for 2-40 Hz-filtered LFP-based FTCs, indicating greatly reduced frequency selectivity for LFPs. We also present comparisons for LFPs band-pass filtered between 4-8 Hz, 8-16 Hz and 16-40 Hz, with spike-based STRFs, on the basis of their marginal frequency distributions. We find on average a significantly larger correlation between the spike based marginal frequency distributions and those based on the 16-40 Hz filtered LFP, compared to those based on the 4-8 Hz, 8-16 Hz and 2-40 Hz filtered LFP. This suggests greater frequency specificity for the 16-40 Hz LFPs compared to those of lower frequency content. For spontaneous LFP and spike activity we evaluated 1373 pair correlations for pairs with >200 spikes in 900 s per electrode. Peak correlation-coefficient space constants were similar for the 2-40 Hz filtered LFP (5.5 mm) and the 16-40 Hz LFP (7.4 mm), whereas for spike-pair correlations it was about half that, at 3.2 mm. Comparing spike-pairs with 2-40 Hz (and 16-40 Hz) LFP-pair correlations showed that about 16% (9%) of the variance in the spike-pair correlations could be explained from LFP-pair correlations recorded on the same electrodes within the same electrode array. This larger correlation distance combined with the reduced CF gradient and much broader frequency selectivity suggests that LFPs are not a substitute for spike activity in primary auditory cortex.

We hypothesize that a visual prosthesis capable of evoking high-resolution visual perceptions can be produced using high-electrode-count arrays of penetrating microelectrodes implanted into the primary visual cortex of a blind human subject. To explore this hypothesis, and as a prelude to human psychophysical experiments, we have conducted a set of experiments in primary visual cortex (V1) of non-human primates using chronically implanted Utah Electrode Arrays (UEAs). The electrical and recording properties of implanted electrodes, the high-resolution visuotopic organization of V1, and the stimulation levels required to evoke behavioural responses were measured. The impedances of stimulated electrodes were found to drop significantly immediately following stimulation sessions, but these post-stimulation impedances returned to pre-stimulation values by the next experimental session. Two months of periodic microstimulation at currents of up to 96 µA did not impair the mapping of receptive fields from local field potentials or multi-unit activity, or impact behavioural visual thresholds of light stimuli that excited regions of V1 that were implanted with UEAs. These results demonstrate that microstimulation at the levels used did not cause functional impairment of the electrode array or the neural tissue. However, microstimulation with current levels ranging from 18 to 76 µA (46 ± 19 µA, mean ± std) was able to elicit behavioural responses on eight out of 82 systematically stimulated electrodes. We suggest that the ability of microstimulation to evoke phosphenes and elicit a subsequent behavioural response may depend on several factors: the location of the electrode tips within the cortical layers of V1, distance of the electrode tips to neuronal somata, and the inability of nonhuman primates to recognize and respond to a generalized set of evoked percepts.

The development of the auditory system has received increasing attention since the mechanisms of patterned, spontaneous activity in prehearing mammals were discovered. This early activity originates in the cochlea and is assumed to be of importance for the establishment and refinement of synaptic connections in the auditory system. In the present study we investigate synaptic transmission and its interplay with spontaneous discharges in the developing auditory system. We used the calyx of Held as a model system, where this question can be investigated in vivo over a broad range of ages [postnatal day 8 (P8)–P28]. To precisely quantify the timing and reliability of synaptic transmission, we developed a novel fitting approach which decomposes the extracellularly recorded signal into its presynaptic and postsynaptic components. In prehearing mice, we found signal transmission to be unreliable, with high variability in the transmission delay and in the amplitude of postsynaptic components. These timing and amplitude changes were strongly correlated with the preceding activity. Around hearing onset (P12–P14), the properties of signal transmission converged to the adult-like state which was characterized by high transmission reliability as well as high consistency in timing and amplitude. Although activity-dependent depression was still found in action potentials, EPSP depression no longer played a prominent role. In conclusion, the maturation of synaptic transmission at the calyx of Held seems to be precisely timed to achieve its adult potential by the time acoustically evoked signal processing commences.

The planning and control of sensory-guided movements requires the integration of multiple sensory streams. Although the information conveyed by different sensory modalities is often overlapping, the shared information is represented differently across modalities during the early stages of cortical processing. We ask how these diverse sensory signals are represented in multimodal sensorimotor areas of cortex in macaque monkeys. Although a common modality-independent representation might facilitate downstream readout, previous studies have found that modality-specific representations in multimodal cortex reflect upstream spatial representations. For example, visual signals have a more eye-centered representation. We recorded neural activity from two parietal areas involved in reach planning, area 5 and the medial intraparietal area (MIP), as animals reached to visual, combined visual and proprioceptive, and proprioceptive targets while fixing their gaze on another location. In contrast to other multimodal cortical areas, the same spatial representations are used to represent visual and proprioceptive signals in both area 5 and MIP. However, these representations are heterogeneous. Although we observed a posterior-to-anterior gradient in population responses in parietal cortex, from more eye-centered to more hand- or body-centered representations, we do not observe the simple and discrete reference frame representations suggested by studies that focused on identifying the “best-match” reference frame for a given cortical area. In summary, we find modality-independent representations of spatial information in parietal cortex, although these representations are complex and heterogeneous.

Gamma-band (25–140 Hz) oscillations of the local field potential (LFP) are evoked by sensory stimuli in the mammalian forebrain and may be strongly modulated in amplitude when animals attend to these stimuli. The optic tectum (OT) is a midbrain structure known to contribute to multimodal sensory processing, gaze control, and attention. We found that presentation of spatially localized stimuli, either visual or auditory, evoked robust gamma oscillations with distinctive properties in the superficial (visual) layers and in the deep (multimodal) layers of the owl's OT. Across layers, gamma power was tuned sharply for stimulus location and represented space topographically. In the superficial layers, induced LFP power peaked strongly in the low-gamma band (25–90 Hz) and increased gradually with visual contrast across a wide range of contrasts. Spikes recorded in these layers included presumptive axonal (input) spikes that encoded stimulus properties nearly identically with gamma oscillations and were tightly phase locked with the oscillations, suggesting that they contribute to the LFP oscillations. In the deep layers, induced LFP power was distributed across the low and high (90–140 Hz) gamma-bands and tended to reach its maximum value at relatively low visual contrasts. In these layers, gamma power was more sharply tuned for stimulus location, on average, than were somatic spike rates, and somatic spikes synchronized with gamma oscillations. Such gamma synchronized discharges of deep-layer neurons could provide a high-resolution temporal code for signaling the location of salient sensory stimuli.

The inferior colliculus has been well studied for its role of transmitting information from the brainstem to the thalamocortical system. However, it is also the source of a major pathway to the cerebellum, via the pontine gray (PG). We compared auditory responses from single neurons in the medial geniculate body (MGB) and PG of the awake big brown bat. MGB neurons were selective for a variety of stimulus types whereas PG neurons only responded to pure tones or simple FM sweeps. Best frequencies (BF) in MGB ranged from 8 kHz to > 80 kHz. BFs of PG neurons were all above 20 kHz with a high proportion above 60 kHz. The mean response latency was 19 ms for MGB neurons and 11 ms for PG neurons. MGB and PG contained neurons with a variety of discharge patterns but the most striking difference was the proportion of neurons with responses that lasted longer than the stimulus duration (MGB 13%, PG 58%). Both nuclei contained duration-sensitive neurons; the majority of those in MGB were band pass whereas in the PG they were long pass. Over half of the neurons in both nuclei were binaural. Differences between these nuclei are consistent with the idea that the thalamocortical pathway performs integration over time for cognitive analysis, thereby increasing selectivity and lengthening latency, while the colliculo-pontine pathway, which is more concerned with sensory-motor control, provides rapid input and a lasting trace of an auditory event.

The superior olivary nucleus (SON) is the primary source of inhibition in the avian auditory brainstem. While much is known about the role of inhibition at the SON's target nuclei, little is known about how the SON itself processes auditory information or how inhibition modulates these properties. Additionally, the synaptic physiology of inhibitory inputs within the SON has not been described. We investigated these questions using in vivo and in vitro electrophysiological techniques in combination with immunohistochemistry in the chicken, an organism for which the auditory brainstem has otherwise been well characterized. We provide a thorough characterization of monaural response properties in the SON and the influence of inhibitory input in shaping these features. We found that the SON contains a heterogeneous mixture of response patterns to acoustic stimulation and that in most neurons these responses are modulated by both GABAergic and glycinergic inhibitory inputs. Interestingly, many SON neurons tuned to low frequencies have robust phase-locking capability and the precision of this phase locking is enhanced by inhibitory inputs. On the synaptic level, we found that evoked and spontaneous inhibitory postsynaptic currents (IPSCs) within the SON are also mediated by both GABAergic and glycinergic inhibition in all neurons tested. Analysis of spontaneous IPSCs suggests that most SON cells receive a mixture of both purely GABAergic terminals, as well as terminals from which GABA and glycine are coreleased. Evidence for glycinergic signaling within the SON is a novel result that has important implications for understanding inhibitory function in the auditory brainstem.

Vocalizations emitted within a social context can trigger call-specific changes in the emotional and physiological/autonomic state of the receiver. The amygdala is implicated in mediating these changes, but its role in call perception remains relatively unexplored. We examined call and pitch selectivity of single neurons within the basolateral amygdala (BLA) by recording spiking activity in response to 5 pitch variants of each of 14 species-specific calls presented to awake, head-restrained mustached bats, Pteronotus parnellii. A response-wise analysis across neurons revealed seven types of temporal response patterns based on the timing and duration of spiking. Roughly half of the responses to different call types were significantly affected by changes in call pitch. A neuron-wise analysis revealed that ∼12% (8/69) of the neurons preferred the same pitch across all call types. Ninety-three percent (93/100) of neurons were excited by at least one call type and 76% exhibited either complete or transient suppression to one or more call types. The majority of neurons preferred fewer than half of the 14 different simple-syllabic calls. A call-wise analysis of spiking activity revealed that call types signaling either threat or fear most consistently evoked increases in the spike rate. In contrast, calls emitted during appeasement tended to evoke spike suppression. Our data suggest that BLA neurons participate in the processing of multiple call types and exhibit a rich variety of temporal response patterns that are neither neuron nor call specific.

Cortical responses can vary greatly between repeated presentations of an identical stimulus. Here we report that both trial-to-trial variability and faithfulness of auditory cortical stimulus representations depend critically on brain state. A frozen amplitude-modulated white noise stimulus was repeatedly presented while recording neuronal populations and local field potentials (LFPs) in auditory cortex of urethane-anesthetized rats. An information-theoretic measure was used to predict neuronal spiking activity from either the stimulus envelope or simultaneously recorded LFP. Evoked LFPs and spiking more faithfully followed high-frequency temporal modulations when the cortex was in a desynchronized state. In the synchronized state, neural activity was poorly predictable from the stimulus envelope, but the spiking of individual neurons could still be predicted from the ongoing LFP. Our results suggest that although auditory cortical activity remains coordinated as a population in the synchronized state, the ability of continuous auditory stimuli to control this activity is greatly diminished.

Brain-machine interfaces (BMIs) use signals from the brain to control a device such as a computer cursor. Various types of signals have been used as BMI inputs, from single-unit action potentials to scalp potentials. Recently, intermediate-level signals such as subdural field potentials have also shown promise. These different signal types are likely to provide different amounts of information, but we do not yet know what signal types are necessary to enable a particular BMI function, such as identification of reach target location, control of a two-dimensional cursor or the dynamics of limb movement. Here we evaluated the performance of field potentials, measured either intracortically (local field potentials, LFPs) or epidurally (epidural field potential, EFPs), in terms of the ability to decode reach direction. We trained rats to move a joystick with their forepaw to control the motion of a sipper tube to one of the four targets in two dimensions. We decoded the forelimb reach direction from the field potentials using linear discriminant analysis. We achieved a mean accuracy of 69 ± 3% with EFPs and 57 ± 2% with LFPs, both much better than chance. Signal quality remained good up to 13 months after implantation. This suggests that using epidural signals could provide BMI inputs of high quality with less risk to the patient than using intracortical recordings.

In a natural scene, multiple stimuli compete for the control of gaze direction and attention. The nucleus isthmi pars parvocellularis (Ipc) is a cholinergic, midbrain nucleus that is reciprocally interconnected to the optic tectum, a structure known to be involved in the control of gaze and attention. Previous research has shown that the responses of many Ipc units to a visual stimulus presented inside the classical receptive field (RF) can be powerfully inhibited when the strength of a distant, competing stimulus becomes the stronger stimulus. This study investigated further the nature of competitive interactions in the Ipc of owls by using two complementary protocols: in the first protocol, we measured the effects of a distant stimulus on responses to an RF stimulus located at different positions inside the RF; in the second protocol, we measured the effects of a distant stimulus on responses to RF stimuli of different strengths. The first protocol demonstrated that the effect of a competing stimulus is purely divisive: the competitor caused a proportional reduction in responses to the RF stimulus that did not alter either the location or sharpness of spatial tuning. The second protocol demonstrated that, for most units, the strength of this divisive inhibition is regulated powerfully by the relative strengths of the competing stimuli: inhibition was strong when the competitor was the stronger stimulus and weak when the competitor was the weaker stimulus. The data indicate that competitive interactions in the Ipc depend on feedback and a globally divisive inhibitory network.

Objective: There is interest in using cortical auditory evoked potentials (CAEPs) to evaluate hearing aid fittings and experience-related plasticity associated with amplification; however, little is known about hearing aid signal processing effects on these responses. The purpose of this study was to determine the effect of clinically relevant hearing aid gain settings, and the resulting in-the-canal signal-to-noise ratios (SNRs), on the latency and amplitude of P1, N1, and P2 waves. DESIGN & SAMPLE: Evoked potentials and in-the-canal acoustic measures were recorded in nine normal-hearing adults in unaided and aided conditions. In the aided condition, a 40-dB signal was delivered to a hearing aid programmed to provide four levels of gain (0, 10, 20, and 30 dB). As a control, unaided stimulus levels were matched to aided condition outputs (i.e. 40, 50, 60, and 70 dB) for comparison purposes. Results: When signal levels are defined in terms of output level, aided CAEPs were surprisingly smaller and delayed relative to unaided CAEPs, probably resulting from increases to noise levels caused by the hearing aid. Discussion: These results reinforce the notion that hearing aids modify stimulus characteristics such as SNR, which in turn affects the CAEP in a way that does not reliably reflect hearing aid gain.