Frequency-dependent dynamics of steady-state visual evoked potentials under sustained flicker stimulation.

Steady-state visual evoked potentials (SSVEP) are electroencephalographic signals elicited when the brain is exposed to a visual stimulus with a steady frequency. We analyzed the temporal dynamics of SSVEP during sustained flicker stimulation at 5, 10, 15, 20 and 40 Hz. We found that the amplitudes of the responses were not stable over time. For a 5 Hz stimulus, the responses progressively increased, while, for higher flicker frequencies, the amplitude increased during the first few seconds and often showed a continuous decline afterward. We hypothesize that these two distinct sets of frequency-dependent SSVEP signal properties reflect the contribution of parvocellular and magnocellular visual pathways generating sustained and transient responses, respectively. These results may have important applications for SSVEP signals used in research and brain-computer interface technology and may contribute to a better understanding of the frequency-dependent temporal mechanisms involved in the processing of prolonged periodic visual stimuli.

Brain activity during meditation in first-time meditators.

AIM OF THE STUDY: The electrophysiological correlates of meditation states in both short and long-term meditators have been increasingly documented; however, little is known about the brain activity associated with first-time meditation experiences. The goal of this study was to investigate the electrophysiological correlates of a single guided mindfulness meditation session in subjects with no previous meditation experience. MATERIALS AND METHODS: We analyzed electroencephalogram (EEG) changes in signal power, hemispheric asymmetry, and information flow between EEG channels, in 16 healthy subjects who were new to meditation practice. RESULTS: Our results show that information flow decreases in the theta (4-8 Hz) and alpha ranges (8-13 Hz) during mindfulness meditation exercise as compared to control: a passive listening condition. These changes are accompanied by a general trend in the decrease of alpha power over the whole scalp. One possible interpretation of these results is that there is an increased level of alertness/vigilance associated with the meditation task rather than reaching the target state. CONCLUSIONS: Our study expands on the existing body of knowledge concerning neural oscillations during breathing meditation practice by showing that in participants with no previous meditation training, EEG correlates are different from the electrophysiological signatures of mindfulness meditation found in studies of more advanced practitioners.

Focal seizures are organized by feedback between neural activity and ion concentration changes.

Human and animal EEG data demonstrate that focal seizures start with low-voltage fast activity, evolve into rhythmic burst discharges and are followed by a period of suppressed background activity. This suggests that processes with dynamics in the range of tens of seconds govern focal seizure evolution. We investigate the processes associated with seizure dynamics by complementing the Hodgkin-Huxley mathematical model with the physical laws that dictate ion movement and maintain ionic gradients. Our biophysically realistic computational model closely replicates the electrographic pattern of a typical human focal seizure characterized by low voltage fast activity onset, tonic phase, clonic phase and postictal suppression. Our study demonstrates, for the first time in silico, the potential mechanism of seizure initiation by inhibitory interneurons via the initial build-up of extracellular K+ due to intense interneuronal spiking. The model also identifies ionic mechanisms that may underlie a key feature in seizure dynamics, that is, progressive slowing down of ictal discharges towards the end of seizure. Our model prediction of specific scaling of inter-burst intervals is confirmed by seizure data recorded in the whole guinea pig brain in vitro and in humans, suggesting that the observed termination pattern may hold across different species. Our results emphasize ionic dynamics as elementary processes behind seizure generation and indicate targets for new therapeutic strategies.

Epilepsy as a manifestation of a multistate network of oscillatory systems.

The human brain, largely accepted as the most complex biological system known, is still far from being understood in its parts or as a whole. More specifically, biological mechanisms of epileptic states and state transitions are not well understood. Here, we explore the concept of the epilepsy as a manifestation of a multistate network composed of coupled oscillatory units. We also propose that functional coupling between neuroglial elements is a dynamic process, characterized by temporal changes both at short and long time scales. We review various experimental and modelling data suggesting that epilepsy is a pathological manifestation of such a multistate network - both when viewed as a coupled oscillatory network, and as a system of multistate stable state attractors. Based on a coupled oscillators model, we propose a significant role for glial cells in modulating hyperexcitability of the neuroglial networks of the brain. Also, using these concepts, we explain a number of observable phenomena such as propagation patterns of bursts within a seizure in the isolated intact hippocampus in vitro, postictal generalized suppression in human encephalographic seizure data, and changes in seizure susceptibility in epileptic patients. Based on our conceptual model we propose potential clinical applications to estimate brain closeness to ictal transition by means of active perturbations and passive measures during on-going activity.

Lateral Inhibition Organizes Beta Attentional Modulation in the Primary Visual Cortex.

We have previously shown that during top-down attentional modulation (stimulus expectation) correlations of the beta signals across the primary visual cortex were uniform, while during bottom-up attentional processing (visual stimulation) their values were heterogeneous. These different patterns of attentional beta modulation may be caused by feed-forward lateral inhibitory interactions in the visual cortex, activated solely during stimulus processing. To test this hypothesis, we developed a large-scale computational model of the cortical network. We first identified the parameter range needed to support beta rhythm generation, and next, simulated the different activity states corresponding to experimental paradigms. The model matched our experimental data in terms of spatial organization of beta correlations during different attentional states and provided a computational confirmation of the hypothesis that the paradigm-specific beta activation spatial maps depend on the lateral inhibitory mechanism. The model also generated testable predictions that cross-correlation values depend on the distance between the activated columns and on their spatial position with respect to the location of the sensory inputs from the thalamus.

Temporal Modulation of Steady-State Visual Evoked Potentials.

Electroencephalographic responses to periodic stimulation are termed steady-state visual evoked potentials (SSVEP). Their characteristics in terms of amplitude, frequency and phase are commonly assumed to be stationary. In this work, we tested this assumption in 30 healthy participants submitted to 50 trials of 60 s flicker stimulation at 15 Hz frequency. We showed that the amplitude of the first and second harmonic frequency components of SSVEP signals were in general not stable over time. The power (squared amplitude) of the fundamental component was stationary only in 30% the subjects, while the power at the second harmonic frequency was stationary in 66.7% of the group. The phases of both SSVEP frequency components were more stable over time, but could exhibit small drifts. The observed temporal changes were heterogeneous across the subjects, implying that averaging results over participants should be performed carefully. These results may contribute to improved design and analysis of experiments employing prolonged visual stimulation. Our findings offer a novel characterization of the temporal changes of SSVEP that may help to identify their physiological basis.

Integrated trimodal SSEP experimental setup for visual, auditory and tactile stimulation.

OBJECTIVE: Steady-state evoked potentials (SSEPs), the brain responses to repetitive stimulation, are commonly used in both clinical practice and scientific research. Particular brain mechanisms underlying SSEPs in different modalities (i.e. visual, auditory and tactile) are very complex and still not completely understood. Each response has distinct resonant frequencies and exhibits a particular brain topography. Moreover, the topography can be frequency-dependent, as in case of auditory potentials. However, to study each modality separately and also to investigate multisensory interactions through multimodal experiments, a proper experimental setup appears to be of critical importance. The aim of this study was to design and evaluate a novel SSEP experimental setup providing a repetitive stimulation in three different modalities (visual, tactile and auditory) with a precise control of stimuli parameters. Results from a pilot study with a stimulation in a particular modality and in two modalities simultaneously prove the feasibility of the device to study SSEP phenomenon. APPROACH: We developed a setup of three separate stimulators that allows for a precise generation of repetitive stimuli. Besides sequential stimulation in a particular modality, parallel stimulation in up to three different modalities can be delivered. Stimulus in each modality is characterized by a stimulation frequency and a waveform (sine or square wave). We also present a novel methodology for the analysis of SSEPs. MAIN RESULTS: Apart from constructing the experimental setup, we conducted a pilot study with both sequential and simultaneous stimulation paradigms. EEG signals recorded during this study were analyzed with advanced methodology based on spatial filtering and adaptive approximation, followed by statistical evaluation. SIGNIFICANCE: We developed a novel experimental setup for performing SSEP experiments. In this sense our study continues the ongoing research in this field. On the other hand, the described setup along with the presented methodology is a considerable improvement and an extension of methods constituting the state-of-the-art in the related field. Device flexibility both with developed analysis methodology can lead to further development of diagnostic methods and provide deeper insight into information processing in the human brain.

Changes of Ionic Concentrations During Seizure Transitions - A Modeling Study.

Traditionally, it is considered that neuronal synchronization in epilepsy is caused by a chain reaction of synaptic excitation. However, it has been shown that synchronous epileptiform activity may also arise without synaptic transmission. In order to investigate the respective roles of synaptic interactions and nonsynaptic mechanisms in seizure transitions, we developed a computational model of hippocampal cells, involving the extracellular space, realistic dynamics of [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] ions, glial uptake and extracellular diffusion mechanisms. We show that the network behavior with fixed ionic concentrations may be quite different from the neurons' behavior when more detailed modeling of ionic dynamics is included. In particular, we show that in the extended model strong discharge of inhibitory interneurons may result in long lasting accumulation of extracellular [Formula: see text], which sustains the depolarization of the principal cells and causes their pathological discharges. This effect is not present in a reduced, purely synaptic network. These results point to the importance of nonsynaptic mechanisms in the transition to seizure.

Seizures Start without Common Signatures of Critical Transition.

Complex dynamical systems may exhibit sudden autonomous changes from one state to another. Such changes that occur rapidly in comparison to the regular dynamics have been termed critical transitions. Examples of such phenomena can be found in many complex systems: changes in climate and ocean circulation, changes in wildlife populations, financial crashes, as well as in medical conditions like asthma attacks and depression. It has been recognized that critical transitions, even if they arise in completely different contexts and situations, share several common attributes and also generic early-warning signals that indicate that a critical transition is approaching. In the present study, we review briefly the general characteristics that have been observed in systems prior to critical transitions and apply these general indicators to nearly 300 epileptic seizures collected from human subjects using invasive EEG. Only in about 8% of the patients was evidence of critical transitions found. In the remaining majority of cases no early warning signals that behaved consistently prior to seizures were observed. These results do not rule out the possibility of critical transitions to seizure but point to limited relevance of their early warning signals in the context of human epilepsy observed using intracranial EEG recordings.

Nonlinear Origin of SSVEP Spectra-A Combined Experimental and Modeling Study.

Steady state visual evoked potentials (SSVEPs) are steady state oscillatory potentials elicited in the electroencephalogram (EEG) by flicker stimulation. The frequency of these responses maches the frequency of the stimulation and of its harmonics and subharmonics. In this study, we investigated the origin of the harmonic and subharmonic components of SSVEPs, which are not well understood. We applied both sine and square wave visual stimulation at 5 and 15 Hz to human subjects and analyzed the properties of the fundamental responses and harmonically related components. In order to interpret the results, we used the well-established neural mass model that consists of interacting populations of excitatory and inhibitory cortical neurons. In our study, this model provided a simple explanation for the origin of SSVEP spectra, and showed that their harmonic and subharmonic components are a natural consequence of the nonlinear properties of neuronal populations and the resonant properties of the modeled network. The model also predicted multiples of subharmonic responses, which were subsequently confirmed using experimental data.

Towards an optimization of stimulus parameters for brain-computer interfaces based on steady state visual evoked potentials.

Efforts to construct an effective brain-computer interface (BCI) system based on Steady State Visual Evoked Potentials (SSVEP) commonly focus on sophisticated mathematical methods for data analysis. The role of different stimulus features in evoking strong SSVEP is less often considered and the knowledge on the optimal stimulus properties is still fragmentary. The goal of this study was to provide insight into the influence of stimulus characteristics on the magnitude of SSVEP response. Five stimuli parameters were tested: size, distance, colour, shape, and presence of a fixation point in the middle of each flickering field. The stimuli were presented on four squares on LCD screen, with each square highlighted by LEDs flickering with different frequencies. Brighter colours and larger dimensions of flickering fields resulted in a significantly stronger SSVEP response. The distance between stimulation fields and the presence or absence of the fixation point had no significant effect on the response. Contrary to a popular belief, these results suggest that absence of the fixation point does not reduce the magnitude of SSVEP response. However, some parameters of the stimuli such as colour and the size of the flickering field play an important role in evoking SSVEP response, which indicates that stimuli rendering is an important factor in building effective SSVEP based BCI systems.

Afferent inputs to cortical fast-spiking interneurons organize pyramidal cell network oscillations at high-gamma frequencies (60-200 Hz).

High-gamma activity, ranging in frequency between ∼60 Hz and 200 Hz, has been observed in local field potential, electrocorticography, EEG and magnetoencephalography signals during cortical activation, in a variety of functional brain systems. The origin of these signals is yet unknown. Using computational modeling, we show that a cortical network model receiving thalamic input generates high-gamma responses comparable to those observed in local field potential recorded in monkey somatosensory cortex during vibrotactile stimulation. These high-gamma oscillations appear to be mediated mostly by an excited population of inhibitory fast-spiking interneurons firing at high-gamma frequencies and pacing excitatory regular-spiking pyramidal cells, which fire at lower rates but in phase with the population rhythm. The physiological correlates of high-gamma activity, in this model of local cortical circuits, appear to be similar to those proposed for hippocampal ripples generated by subsets of interneurons that regulate the discharge of principal cells.

On the quantification of SSVEP frequency responses in human EEG in realistic BCI conditions.

This article concerns one of the most important problems of brain-computer interfaces (BCI) based on Steady State Visual Evoked Potentials (SSVEP), that is the selection of the a-priori most suitable frequencies for stimulation. Previous works related to this problem were done either with measuring systems that have little in common with actual BCI systems (e.g., single flashing LED) or were presented on a small number of subjects, or the tested frequency range did not cover a broad spectrum. Their results indicate a strong SSVEP response around 10 Hz, in the range 13-25 Hz, and at high frequencies in the band of 40-60 Hz. In the case of BCI interfaces, stimulation with frequencies from various ranges are used. The frequencies are often adapted for each user separately. The selection of these frequencies, however, was not yet justified in quantitative group-level study with proper statistical account for inter-subject variability. The aim of this study is to determine the SSVEP response curve, that is, the magnitude of the evoked signal as a function of frequency. The SSVEP response was induced in conditions as close as possible to the actual BCI system, using a wide range of frequencies (5-30 Hz, in step of 1 Hz). The data were obtained for 10 subjects. SSVEP curves for individual subjects and the population curve was determined. Statistical analysis were conducted both on the level of individual subjects and for the group. The main result of the study is the identification of the optimal range of frequencies, which is 12-18 Hz, for the registration of SSVEP phenomena. The applied criterion of optimality was: to find the largest contiguous range of frequencies yielding the strong and constant-level SSVEP response.

Statistical analysis of sleep spindle occurrences.

Spindles - a hallmark of stage II sleep - are a transient oscillatory phenomenon in the EEG believed to reflect thalamocortical activity contributing to unresponsiveness during sleep. Currently spindles are often classified into two classes: fast spindles, with a frequency of around 14 Hz, occurring in the centro-parietal region; and slow spindles, with a frequency of around 12 Hz, prevalent in the frontal region. Here we aim to establish whether the spindle generation process also exhibits spatial heterogeneity. Electroencephalographic recordings from 20 subjects were automatically scanned to detect spindles and the time occurrences of spindles were used for statistical analysis. Gamma distribution parameters were fit to each inter-spindle interval distribution, and a modified Wald-Wolfowitz lag-1 correlation test was applied. Results indicate that not all spindles are generated by the same statistical process, but this dissociation is not spindle-type specific. Although this dissociation is not topographically specific, a single generator for all spindle types appears unlikely.

Event-related desynchronization and synchronization in evoked K-complexes.

K-complexes - phenomena occurring in sleep EEG - pose severe challenges in terms of detection as well as finding their physiological origin. In this study, K-complexes (KCs) were evoked by auditory stimuli delivered during sleep. The use of evoked KCs enables testing the sleeping nervous system under good experimental control. This paradigm allowed us to adopt into the KC studies a method of signal analysis that provides time-frequency maps of statistically significant changes in signal energy density. Our results indicate that KCs and sleep spindles may be organized by a slow oscillation. Accordingly, KCs might be evoked only if the stimulus occurs in a certain phase of the slow oscillation. We also observed middle-latency evoked responses following auditory stimulation in the last sleep cycle. This effect was revealed only by the time-frequency maps and was not visible in standard averages.

Derivation and analysis of an ordinary differential equation mean-field model for studying clinically recorded epilepsy dynamics.

In this paper we describe how an ordinary differential equation model of corticothalamic interactions may be obtained from a more general system of delay differential equations. We demonstrate that transitions to epileptic dynamics via changes in system parameters are qualitatively the same as in the original model with delay, as well as demonstrating that the onset of epileptic activity may arise due to regions of bistability. Hence, the model presents in one unique framework, two competing theories for the genesis of epileptiform activity. Similarities between model transitions and clinical data are presented and we argue that statistics obtained from, and a parameter estimation of this model may be a potential means of classifying and predicting the onset and offset of seizure activity.

Active paradigms of seizure anticipation: computer model evidence for necessity of stimulation.

It has been shown that the analysis of electroencephalographic (EEG) signals submitted to an appropriate external stimulation (active paradigm) is efficient with respect to anticipating epileptic seizures [S. Kalitzin, Clin. Neurophysiol. 116, 718 (2005)]. To better understand how an active paradigm is able to detect properties of EEG signals by means of which proictal states can be identified, we performed a simulation study using a computational model of seizure generation of a hippocampal network. Applying the active stimulation methodology, we investigated (i) how changes in model parameters that lead to a transition from the normal ongoing EEG to an ictal pattern are reflected in the properties of the simulated EEG output signals and (ii) how the evolution of neuronal excitability towards seizures can be reconstructed from EEG data using an active paradigm, rather than passively, using only ongoing EEG signals. The simulations indicate that a stimulation paradigm combined with appropriate analytical tools, as proposed here, may yield information about the change in excitability that precedes the transition to a seizure. Such information is apparently not fully reflected in the ongoing EEG activity. These findings give strong support to the development and application of active paradigms with the aim of predicting the occurrence of a transition to an epileptic seizure.

The effects of vigabatrin on spike and wave discharges in WAG/Rij rats.

The effects of vigabatrin, which increases GABA concentrations by inhibiting GABA transaminase, on spike and wave discharges (SWDs) in the electroencephalogram of WAG/Rij rats were studied. Vigabatrin increased the incidence and duration of the SWDs, suggesting a quantitative GABA(A)ergic involvement in the mechanism(s) underlying the starting and stopping of an ongoing SWD. Also, vigabatrin decreased the SWD peak frequency, suggesting an important role of GABA(B) in the mechanism(s) underlying the peak frequency of the SWDs. Vigabatrin gradually changed the course of the hazard rates of the SWD durations, suggesting a qualitative GABAergic role in the mechanism(s) underlying the stopping of an ongoing SWD.

GABAergic mechanisms in absence epilepsy: a computational model of absence epilepsy simulating spike and wave discharges after vigabatrin in WAG/Rij rats.

In this study, the effects of vigabatrin on spike-and-wave discharges (SWDs) were measured in WAG/Rij rats, an animal model of absence epilepsy. Vigabatrin was used with the aim of enhancing GABAergic neurotransmission, and in this way to investigate the role of this process in the properties of SWDs. The study was carried out both in the rat, in vivo, and also using a computational model, in order to test different mechanisms that may account for the changes in SWDs after vigabatrin. The model parameters, representing GABA levels, were changed according to the known, and assumed, mechanism of action of the drug. The results show that the computational model can most adequately simulate the data obtained in vivo on the assumption that the enhancement of GABAergic neurotransmission due to application of vigabatrin is most pronounced at the level of the thalamic relay nuclei (TC cells). Furthermore, vigabatrin was shown to affect both the SWD starting and stopping mechanisms, as reflected by hazard rates. Based on these results, we suggest that GABAergic neurotransmission in TC cells is actively involved in the SWD termination.