LFP publications

Here we propose a methodology to analyze volumetric electrical activity of neuronal masses in the somatosensory barrel field of Wistar rats. The key elements of the proposed methodology are a three-dimensional microelectrode array, which was customized by our group to observe extracellular recordings from an extended area of the barrel field, and a novel method for the current source density analysis. By means of this methodology, we were able to localize single barrels from their event-related responses to single whisker deflection. It was also possible to assess the spatiotemporal dynamics of neuronal aggregates in several barrels at the same time with the resolution of single neurons. We used simulations to study the robustness of our methodology to unavoidable physiological noise and electrode configuration. We compared the accuracy to reconstruct neocortical current sources with that obtained with a previous method. This constitutes a type of electrophysiological microscopy with high spatial and temporal resolution, which could change the way we analyze the activity of cortical neurons in the future.

Ongoing clinical studies on patients recently implanted with the auditory midbrain implant (AMI) into the inferior colliculus (IC) for hearing restoration have shown that these patients do not achieve performance levels comparable to cochlear implant patients. The AMI consists of a single-shank array (20 electrodes) for stimulation along the tonotopic axis of the IC. Recent findings suggest that one major limitation in AMI performance is the inability to sufficiently activate neurons across the three-dimensional (3-D) IC. Unfortunately, there are no currently available 3-D array technologies that can be used for clinical applications. More recently, there has been a new initiative by the European Commission to fund and develop 3-D chronic electrode arrays for science and clinical applications through the NeuroProbes project that can overcome the bulkiness and limited 3-D configurations of currently available array technologies. As part of the NeuroProbes initiative, we investigated whether their new array technology could be potentially used for future AMI patients. Since the NeuroProbes technology had not yet been tested for electrical stimulation in an in vivo animal preparation, we performed experiments in ketamine-anesthetized guinea pigs in which we inserted and stimulated a NeuroProbes array within the IC and recorded the corresponding neural activation within the auditory cortex. We used 2-D arrays for this initial feasibility study since they were already available and were sufficient to access the IC and also demonstrate effective activation of the central auditory system. Based on these encouraging results and the ability to develop customized 3-D arrays with the NeuroProbes technology, we can further investigate different stimulation patterns across the ICC to improve AMI performance.

Background: Noise induced injury of the cochlea causes shifts in activation thresholds and changes of frequency response in the inferior colliculus (IC). Noise overexposure also induces pathological changes in the cochlea, and is highly correlated to hearing loss. However, the underlying mechanism has not been fully elucidated. In this study, we hypothesized that overexposure to noise induces substantial electrophysiological changes in the IC of guinea pigs. Results: During the noise exposure experiment, the animals were undergoing a bilateral exposure to noise. Additionally, various techniques were employed including confocal microscopy for the detection of cochlea hair cells and single neuron recording for spontaneous firing activity measurement. There were alterations among three types of frequency response area (FRA) from sound pressure levels, including V-, M-, and N-types. Our results indicate that overexposure to noise generates different patterns in the FRAs. Following a short recovery (one day after the noise treatment), the percentage of V-type FRAs considerably decreased, whereas the percentage of M-types increased. This was often caused by a notch in the frequency response that occurred at 4 kHz (noise frequency). Following a long recovery from noise exposure (11-21 days), the percentage of V-types resumed to a normal level, but the portion of M-types remained high. Interestingly, the spontaneous firing in the IC was enhanced in both short and long recovery groups. Conclusion: Our data suggest that noise overexposure changes the pattern of the FRAs and stimulates spontaneous firing in the IC in a unique way, which may likely relate to the mechanism of tinnitus.

The study of mouse hearing impairment mutants has led to the identification of a number of human hearing impairment genes and has greatly furthered our understanding of the physiology of hearing. The novel mouse mutant neurological/sensory 5 (nse5) demonstrates a significantly reduced or absent startle response to sound and is therefore a potential murine model of human hearing impairment. Genetic analysis of 500 intercross progeny localized the mutant locus to a 524 kilobase (kb) interval on mouse chromosome 15. A missense mutation in a highly-conserved amino acid was found in the asparagine-linked glycosylation 10B gene (Alg10b), which is within the critical interval for the nse5 mutation. A 20.4 kb transgene containing a wildtype copy of the Alg10b gene rescued the mutant phenotype in nse5/nse5 homozygous animals, confirming that the mutation in Alg10b is responsible for the nse5/nse5 mutant phenotype. Homozygous nse5/nse5 mutants had abnormal auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and cochlear microphonics (CMs). Endocochlear potentials (EPs), on the other hand, were normal. ABRs and DPOAEs also confirmed the rescue of the mutant nse5/nse5 phenotype by the wildtype Alg10b transgene. These results suggested a defect in the outer hair cells of mutant animals, which was confirmed by histologic analysis. This is the first report of mutation in a gene involved in the asparagine (N)-linked glycosylation pathway causing nonsyndromic hearing impairment, and it suggests that the hearing apparatus, and the outer hair cells in particular, are exquisitely sensitive to perturbations of the N-linked glycosylation pathway.

Successful categorization of phonemes in speech requires that the brain analyze the acoustic signal along both spectral and temporal dimensions. Neural encoding of the stimulus amplitude envelope is critical for parsing the speech stream into syllabic units. Encoding of voice onset time (VOT) and place of articulation (POA), cues necessary for determining phonemic identity, occurs within shorter time frames. An unresolved question is whether the neural representation of speech is based on processing mechanisms that are unique to humans and shaped by learning and experience, or is based on rules governing general auditory processing that are also present in non-human animals. This question was examined by comparing the neural activity elicited by speech and other complex vocalizations in primary auditory cortex of macaques, who are limited vocal learners, with that in Heschl's gyrus, the putative location of primary auditory cortex in humans. Entrainment to the amplitude envelope is neither specific to humans nor to human speech. VOT is represented by responses time-locked to consonant release and voicing onset in both humans and monkeys. Temporal representation of VOT is observed both for isolated syllables and for syllables embedded in the more naturalistic context of running speech. The fundamental frequency of male speakers is represented by more rapid neural activity phase-locked to the glottal pulsation rate in both humans and monkeys. In both species, the differential representation of stop consonants varying in their POA can be predicted by the relationship between the frequency selectivity of neurons and the onset spectra of the speech sounds. These findings indicate that the neurophysiology of primary auditory cortex is similar in monkeys and humans despite their vastly different experience with human speech, and that Heschl's gyrus is engaged in general auditory, and not language-specific, processing. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives".

Interaural time differences (ITDs) are a major cue for localizing low-frequency (<1.5 kHz) sounds. Sensitivity to this cue first occurs in the medial superior olive (MSO), which is thought to perform a coincidence analysis on its monaural inputs. Extracellular single-neuron recordings in MSO are difficult to obtain because (1) MSO action potentials are small and (2) a large field potential locked to the stimulus waveform hampers spike isolation. Consequently, only a limited number of studies report MSO data, and even in these studies data are limited in the variety of stimuli used, in the number of neurons studied, and in spike isolation. More high-quality data are needed to better understand the mechanisms underlying neuronal ITD-sensitivity. We circumvented these difficulties by recording from the axons of MSO neurons in the lateral lemniscus (LL) of the chinchilla, a species with pronounced low-frequency sensitivity. Employing sharp glass electrodes we successfully recorded from neurons with ITD sensitivity: the location, response properties, latency, and spike shape were consistent with an MSO axonal origin. The main difficulty encountered was mechanical stability. We obtained responses to binaural beats and dichotic noise bursts to characterize the best delay versus characteristic frequency distribution, and compared the data to recordings we obtained in the inferior colliculus (IC). In contrast to most reports in other rodents, many best delays were close to zero ITD, both in MSO and IC, with a majority of the neurons recorded in the LL firing maximally within the presumed ethological ITD range.

The basal forebrain provides the primary source of cholinergic input to the cortex, and it has a crucial function in promoting wakefulness and arousal. However, whether rapid changes in basal forebrain neuron spiking in awake animals can dynamically influence sensory perception is unclear. Here we show that basal forebrain cholinergic neurons rapidly regulate cortical activity and visual perception in awake, behaving mice. Optogenetic activation of the cholinergic neurons or their V1 axon terminals improved performance of a visual discrimination task on a trial-by-trial basis. In V1, basal forebrain activation enhanced visual responses and desynchronized neuronal spiking; these changes could partly account for the behavioral improvement. Conversely, optogenetic basal forebrain inactivation decreased behavioral performance, synchronized cortical activity and impaired visual responses, indicating the importance of cholinergic activity in normal visual processing. These results underscore the causal role of basal forebrain cholinergic neurons in fast, bidirectional modulation of cortical processing and sensory perception.

In this report we describe how common brain networks within the medial frontal cortex (MFC) facilitate adaptive behavioral control in rodents and humans. We demonstrate that after errors, low-frequency oscillations below 12 Hz are modulated over the midfrontal cortex in humans and within the prelimbic and anterior cingulate regions of the MFC in rats. These oscillations were phase locked between the MFC and motor areas in both rats and humans. In rats, single neurons that encoded prior behavioral outcomes were phase coherent with low-frequency field oscillations, particularly after errors. Inactivating the medial frontal regions in rats led to impaired behavioral adjustments after errors, eliminated the differential expression of low-frequency oscillations after errors and increased low-frequency spike-field coupling within the motor cortex. Our results describe a new mechanism for behavioral adaptation through low-frequency oscillations and elucidate how medial frontal networks synchronize brain activity to guide performance.

Background: Human magneto/electrophysiology studies suggest that the phantom sound of tinnitus arises from spontaneous oscillatory neural activity in auditory cortex; however, in animal models, behavioral techniques suitable for testing this hypothesis in combination with electrophysiology recordings have yet to be evaluated. While electrophysiological studies of tinnitus have been reported in passive, awake animals, these studies fail to control for attentional mechanisms likely to play a role in the perception of tinnitus. New method: A novel appetitive operant conditioning, two-alternative identification task was developed for detecting acute tinnitus in rats. The procedure optimizes conditions for simultaneously recording oscillatory neural activity while controlling for the attentional state of the animal. Results: Tinnitus was detected in six of seven rats following systemic injection with sodium salicylate (200mg/kg IP), a known inducer of tinnitus. Analysis of ongoing local field potentials recorded from chronically implanted electrodes in auditory cortex of a rat reporting tinnitus revealed changes in the spectrum of ongoing neural activity. Comparison with existing method(s): Existing tinnitus-detection methods were not explicitly designed for the simultaneous recording of neural activity. The behavioral method reported here is the first to provide the conditions necessary for obtaining these recordings in chronically implanted rats. Conclusions: The behavioral assay presented here will facilitate research into the neural mechanisms of tinnitus by allowing researchers to compare the electrophysiological data in animals with confirmed tinnitus.

Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior.

A growing interest in sensory system plasticity in the natural context of motherhood has created the need to investigate how intrinsic physiological state (e.g., hormonal, motivational, etc.) interacts with sensory experience to drive adaptive cortical plasticity for behaviorally relevant stimuli. Using a maternal mouse model of auditory cortical inhibitory plasticity for ultrasonic pup calls, we examined the role of pup care versus maternal physiological state in the long-term retention of this plasticity. Very recent experience caring for pups by Early Cocarers, which are virgins, produced stronger call-evoked lateral-band inhibition in auditory cortex. However, this plasticity was absent when measured post-weaning in Cocarers, even though it was present at the same time point in Mothers, whose pup experience occurred under a maternal physiological state. A two-alternative choice phonotaxis task revealed that the same animal groups (Early Cocarers and Mothers) demonstrating stronger lateral-band inhibition also preferred pup calls over a neutral sound, a correlation consistent with the hypothesis that this inhibitory mechanism may play a mnemonic role and is engaged to process sounds that are particularly salient. Our electrophysiological data hint at a possible mechanism through which the maternal physiological state may act to preserve the cortical plasticity: selectively suppressing detrimental spontaneous activity in neurons that are responsive to calls, an effect observed only in Mothers. Taken together, the maternal physiological state during the care of pups may help maintain the memory trace of behaviorally salient infant cues within core auditory cortex, potentially ensuring a more rapid induction of future maternal behavior.

The neurophonic potential is a synchronized frequency-following extracellular field potential that can be recorded in the nucleus laminaris (NL) in the brainstem of the barn owl. Putative generators of the neurophonic are the afferent axons from the nucleus magnocellularis, synapses onto NL neurons, and spikes of NL neurons. The outputs of NL, i.e., action potentials of NL neurons, are only weakly represented in the neurophonic. Instead, the inputs to NL, i.e., afferent axons and their synaptic potentials, are the predominant origin of the neurophonic (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J Neurophysiol 104: 2274–2290, 2010). Thus in NL the monaural inputs from the two brain sides converge and create a binaural neurophonic. If these monaural inputs contribute independently to the extracellular field, the response to binaural stimulation can be predicted from the sum of the responses to ipsi- and contralateral stimulation. We found that a linear summation model explains the dependence of the responses on interaural time difference as measured experimentally with binaural stimulation. The fit between model predictions and data was excellent, even without taking into account the nonlinear responses of NL coincidence detector neurons, although their firing rate and synchrony strongly depend on the interaural time difference. These results are consistent with the view that the afferent axons and their synaptic potentials in NL are the primary origin of the neurophonic.

Primary motor-cortex multi-unit activity (MUA) and local-field potentials (LFPs) have both been suggested as potential control signals for brain-computer interfaces (BCIs) aimed at movement restoration. Some studies report that LFP-based decoding is comparable to spiking-based decoding, while others offer contradicting evidence. Differences in experimental paradigms, tuning models and decoding techniques make it hard to directly compare these results. Here, we use regression and mutual information analyses to study how MUA and LFP encode various kinematic parameters during reaching movements. We find that in addition to previously reported directional tuning, MUA also contains prominent speed tuning. LFP activity in low-frequency bands (15-40Hz, LFPL) is primarily speed tuned, and contains more speed information than both high-frequency LFP (100-300Hz, LFPH) and MUA. LFPH contains more directional information compared to LFPL, but less information when compared with MUA. Our results suggest that a velocity and speed encoding model is most appropriate for both MUA and LFPH, whereas a speed only encoding model is adequate for LFPL.

Cardiac Arrest (CA) leads to a global hypoxic-ischemic injury in the brain leading to a poor neurological outcome. Understanding the mechanisms of functional disruption in various regions of the brain may be essential for the development of improved diagnostic and therapeutic solutions. Using controlled laboratory experiment with animal models of CA, our primary focus here is on understanding the functional changes in the thalamus and the cortex, associated with the injury and acute recovery upon resuscitation. Specifically, to study the changes in thalamocortical synchrony through these periods, we acquired local field potentials (LFPs) from the ventroposterior lateral (VPL) nucleus of the thalamus and the forelimb somatosensory cortex (S1FL) in rats after asphyxial CA. Band-specific relative Hilbert phases were used to analyze synchrony between the LFPs. We observed that the CA induced global ischemia changes the local phase-relationships by introducing a phase-lag in both the thalamus and the cortex, while the synchrony between the two regions is nearly completely lost after CA.

Inputs from the two eyes are first combined in simple cells in the primary visual cortex. Consequently, visual cortical neurons need to have the flexibility to encode visual features under both monocular and binocular situations. Here we show that binocular orientation selectivity of mouse simple cells is nearly identical to monocular orientation selectivity in both anaesthetized and awake conditions. In vivo whole-cell recordings reveal that the binocular integration of membrane potential responses is sublinear. The sublinear integration keeps binocularly evoked depolarizations below threshold at non-preferred orientations, thus preserving orientation selectivity. Computational simulations based on measured synaptic conductances indicate that inhibition promotes sublinear binocular integration, which are further confirmed by experiments using genetic and pharmacological manipulations. Our findings therefore reveal a cellular mechanism for how visual system can switch effortlessly between monocular and binocular conditions. The same mechanism may apply to other sensory systems that also integrate multiple channels of inputs.

Background The basal forebrain (BF) regulates cortical activity by the action of cholinergic projections to the cortex. At the same time, it also sends substantial GABAergic projections to both cortex and thalamus, whose functional role has received far less attention. We used deep brain stimulation (DBS) in the BF, which is thought to activate both types of projections, to investigate the impact of BF activation on V1 neural activity. Results BF stimulation robustly increased V1 single and multi-unit activity, led to moderate decreases in orientation selectivity and a remarkable increase in contrast sensitivity as demonstrated by a reduced semi-saturation contrast. The spontaneous V1 local field potential often exhibited spectral peaks centered at 40 and 70 Hz as well as reliably showed a broad γ-band (30-90 Hz) increase following BF stimulation, whereas effects in a low frequency band (1-10 Hz) were less consistent. The broad γ-band, rather than low frequency activity or spectral peaks was the best predictor of both the firing rate increase and contrast sensitivity increase of V1 unit activity. Conclusions We conclude that BF activation has a strong influence on contrast sensitivity in V1. We suggest that, in addition to cholinergic modulation, the BF GABAergic projections play a crucial role in the impact of BF DBS on cortical activity.

In primary visual cortex, spiking activity that evoked by stimulus confined in receptive field can be modulated by surround stimulus. This center-surround interaction is hypothesized to be the basis of visual feature integration and segregation. Spiking output has been extensively reported to be surround suppressive. However, less is known about the modulation properties of the local field potential (LFP), which generally reflects synaptic inputs. We simultaneously recorded spiking activity and LFP in the area 17 of anesthetized cats to examine and compare their modulation characteristics. When the stimulus went beyond the classical receptive field, LFP exhibited decreased power along the gamma band (30-100 Hz) in most of our recording sites. Further investigation revealed that suppression of the LFP gamma mean power (gLFP) depended on the angle between the center and surround orientations. The strongest suppression was induced when center and surround orientations were parallel. Moreover, the surround influence of the gLFP exhibited an asymmetric spatial organization. These results demonstrate that the gLFP has similar but not identical surround modulation properties, as compared to the spiking activity. The spatiotemporal integration of LFP implies that the oscillation and synchronization of local synaptic inputs may have important functions in surround modulation.

Objective: Our goal was to identify spatial filtering methods that would improve decoding of continuous arm movements from epidural field potentials as well as demonstrate the use of the epidural signals in a closed-loop brain-machine interface (BMI) system in monkeys. Approach: Eleven spatial filtering options were compared offline using field potentials collected from 64-channel high-density epidural arrays in monkeys. Arrays were placed over arm/hand motor cortex in which intracortical microelectrodes had previously been implanted and removed leaving focal cortical damage but no lasting motor deficits. Spatial filters tested included: no filtering, common average referencing (CAR), principle component analysis, and eight novel modifications of the common spatial pattern (CSP) algorithm. The spatial filtering method and decoder combination that performed the best offline was then used online where monkeys controlled cursor velocity using continuous wrist position decoded from epidural field potentials in real time. Main results: Optimized CSP methods improved continuous wrist position decoding accuracy by 69% over CAR and by 80% compared to no filtering. Kalman decoders performed better than linear regression decoders and benefitted from including more spatially-filtered signals but not from pre-smoothing the calculated power spectra. Conversely, linear regression decoders required fewer spatially-filtered signals and were improved by pre-smoothing the power values. The 'position-to-velocity' transformation used during online control enabled the animals to generate smooth closed-loop movement trajectories using the somewhat limited position information available in the epidural signals. The monkeys' online performance significantly improved across days of closed-loop training. Significance: Most published BMI studies that use electrocorticographic signals to decode continuous limb movements either use no spatial filtering or CAR. This study suggests a substantial improvement in decoding accuracy could be attained by using our new version of the CSP algorithm that extends the traditional CSP method for use with continuous limb movement data.

The cerebellum is an essential structure for the control of movement. It sends abundant ascending projections to the cerebral cortex via the thalamus, but its contribution to cortical activity remains largely unknown. Here we studied its influence on cortical neuronal activity in freely moving rats. We demonstrate an excitatory action of the cerebellum on the motor thalamus and the motor cortex. We also show that cerebellar inactivation disrupts the gamma-band coherence of local field potential between the sensory and motor cortices during whisking. In contrast, phase locking of neuronal activities to local gamma oscillations was preserved in the sensory and motor cortices by cerebellar inactivation. These results indicate that the cerebellum contributes to coordinated sensorimotor cortical activities during motor activation and thus participates in the multiregional cortical processing of information.

Learning alters the responses of neurons in the neocortex, typically strengthening their encoding of behaviorally relevant stimuli. These enhancements are studied extensively in the auditory cortex by characterizing changes in firing rates and evoked potentials. However, synchronous activity is also important for the processing of stimuli, especially the relationship between gamma oscillations in the local field potential and spiking. We investigated whether tone/shock fear conditioning in rats, a task known to alter responses in auditory cortex, also modified the relationship between gamma and unit activity. A boost in gamma oscillations developed, especially at sites tuned near the tone, and strengthened across multiple conditioning sessions. Unit activity became increasingly phase-locked to gamma, with sites tuned near the tone developing enhanced phase-locking during the tone, whereas those tuned away maintained a tendency to decrease their phase-locking. Enhancements in the coordination of spiking between sites tuned near the tone developed within the first conditioning session and remained throughout the rest of training. Enhanced cross-covariances in unit activity were strongest for subjects that exhibited robust conditioned fear. These results illustrate that changes in sensory cortex during associative learning extend to the coordination of neurons encoding the relevant stimulus, with implications for how it is processed downstream.