A time-variant processing approach for the analysis of alpha and gamma MEG oscillations during flicker stimulus generated entrainment

Repetitive flicker stimulation (photic driving) offers the possibility to study the properties and coupling characteristics of stimulation-sensitive neuronal oscillators by means of the MEG/EEG analysis. With flicker frequencies in the region of the individual alpha band frequency, the dynamics of the entrainment process of the alpha oscillation, as well as the dynamics of the accompanying gamma oscillations and the coupling between the oscillations, are investigated by means of an appropriate combination of time-variant analysis methods. The Hilbert and the Gabor transformation reveal time-variant properties (frequency entrainment, phase locking, and n:m synchronization) of the entrainment process in the whole frequency range. Additionally, time-variant partial directed coherence is applied to identify ocular saccadic interferences and to study the directed information transfer between the recording sites of the simultaneously derived MEG/EEG data during the entrainment. The MEG data is the focus of this methodological study as the entrainment effects of the alpha oscillation are stronger in MEG than in the EEG. The occipital brain region (visual cortex) was mainly investigated and the dynamics of the alpha entrainment quantified. It can be shown that at the beginning of this entrainment, a transient, strongly phase-locked "40-Hz" gamma oscillation occurs.     

A maximum-likelihood estimator for trial-to-trial variations in noisy MEG/EEG data sets

The standard procedure to determine the brain response from a multitrial evoked magnetoencephalography (MEG) or electroencephalography (EEG) data set is to average the individual trials of these data, time locked to the stimulus onset. When the brain responses vary from trial-to-trial this approach is false. In this paper, a maximum-likelihood estimator is derived for the case that the recorded data contain amplitude variations. The estimator accounts for spatially and temporally correlated background noise that is superimposed on the brain response. The model is applied to a series of 17 MEG data sets of normal subjects, obtained during median nerve stimulation. It appears that the amplitude of late component (30-120 ms) shows a systematic negative trend indicating a weakening response during stimulation time. For the early components (20-35 ms) no such a systematic effect was found. The model is furthermore applied on a MEG data set consisting of epileptic spikes of constant spatial distribution but varying polarity. For these data, the advantage of applying the model is that positive and negative spikes can be processed with a single model, thereby reducing the number of degrees of freedom and increasing the signal-to-noise ratio.     

Integration of amplitude and phase statistics for complete artifact removal in independent components of neuromagnetic recordings

In magnetoencephalography (MEG) and electroencephalography (EEG), independent component analysis is widely applied to separate brain signals from artifact components. A number of different methods have been proposed for the automatic or semiautomatic identification of artifact components. Most of the proposed methods are based on amplitude statistics of the decomposed MEG/EEG signal. We present a fully automated approach based on amplitude and phase statistics of decomposed MEG signals for the isolation of biological artifacts such as ocular, muscle, and cardiac artifacts (CAs). The performance of different artifact identification measures was investigated. In particular, we show that phase statistics is a robust and highly sensitive measure to identify strong and weak components that can be attributed to cardiac activity, whereas a combination of different measures is needed for the identification of artifacts caused by ocular and muscle activity. With the introduction of a rejection performance parameter, we are able to quantify the rejection quality for eye blinks and CAs. We demonstrate in a set of MEG data the good performance of the fully automated procedure for the removal of cardiac, ocular, and muscle artifacts. The new approach allows routine application to clinical measurements with small effect on the brain signal.      

Single-Trial Evoked Brain Responses Modeled by Multivariate Matching Pursuit

We present a new approach to the analysis of brain evoked electromagnetic potentials and fields. Multivariate version of the matching pursuit algorithm (MMP) performs an iterative, exhaustive search for waveforms, which optimally fit to signal structures, persistent in all the responses (trials) with the same time of occurrence, frequency, phase, and time width, but varying amplitude. The search is performed in a highly redundant time--frequency dictionary of Gabor functions, i.e., sines modulated by Gaussians. We present the feasibility of such a single-trial MMP analysis of the auditory M100 response, using an illustrative dataset acquired in a magnetoencephalographic (MEG) measurement with auditory stimulation with sinusoidal 1-kHz tones. We find that the morphology of the M100 estimate obtained from simple averaging of single trials can be very well explained by the average reconstruction with a few Gabor functions that parametrize those single trials. The M100 peak amplitude of single-trial reconstructions is observed to decrease with repetitions, which indicates habituation to the stimulus. This finding suggests that certain waveforms fitted by MMP could possibly be related to physiologically distinct components of evoked magnetic fields, which would allow tracing their dynamics on a single-trial level.      

Estimation of neural dynamics from MEG/EEG cortical current density maps: application to the reconstruction of large-scale cortical synchrony

There is a growing interest in elucidating the role of specific patterns of neural dynamics--such as transient synchronization between distant cell assemblies--in brain functions. Magnetoencephalography (MEG)/electroencephalography (EEG) recordings consist in the spatial integration of the activity from large and multiple remotely located populations of neurons. Massive diffusive effects and poor signal-to-noise ratio (SNR) preclude the proper estimation of indices related to cortical dynamics from nonaveraged MEG/EEG surface recordings. Source localization from MEG/EEG surface recordings with its excellent time resolution could contribute to a better understanding of the working brain. We propose a robust and original approach to the MEG/EEG distributed inverse problem to better estimate neural dynamics of cortical sources. For this, the surrogate data method is introduced in the MEG/EEG inverse problem framework. We apply this approach on nonaveraged data with poor SNR using the minimum norm estimator and find source localization results weakly sensitive to noise. Surrogates allow the reduction of the source space in order to reconstruct MEG/EEG data with reduced biases in both source localization and time-series dynamics. Monte Carlo simulations and results obtained from real MEG data indicate it is possible to estimate non invasively an important part of cortical source locations and dynamic and, therefore, to reveal brain functional networks.     

Phase-interpolated averaging for analyzing electroencephalography and magnetoencephalography epochs

Stimulus-locked averages of electroencephalography (EEG) and magnetoencephalography (MEG) epochs reveal characteristic waveforms. EEG/MEG generation models to have reconstruct such waveforms have been recently proposed. These models assume that evoked, phase-modulated, and amplitude-modulated activities occur solely or simultaneously. We propose a two-stage stimulus-locked averaging method, called phase-interpolated averaging, to investigate the EEG/MEG generation process. First, virtual EEG/MEG epochs, which would be obtained as if instantaneous phases for each time sampling point were on a phase-grid, are interpolated from actually measured EEG/MEG epochs. Then, the virtual EEG/MEG epochs are discrete Fourier transformed. A simulation revealed that the zeroth Fourier term revealed the evoked activity, the first Fourier term revealed the amplitude-modulated activity, and the condition number of the interpolation reflected the phase-modulated activity. On the basis of these facts, a preliminary EEG analysis implied that the evoked activity is much smaller than what would be expected by using conventional averaging, the evoked and phase-modulated activities simultaneously occur, and the amplitude-modulated activity occasionally associates with the evoked and phase-modulated activities. To the best of our knowledge, this is the first time that these three activities have been shown to coexist by actually separating them.     

Electromagnetic brain mapping

There has been tremendous advances in our ability to produce images of human brain function. Applications of functional brain imaging extend from improving our understanding of the basic mechanisms of cognitive processes to better characterization of pathologies that impair normal function. Magnetoencephalography (MEG) and electroencephalography (EEG) (MEG/EEG) localize neural electrical activity using noninvasive measurements of external electromagnetic signals. Among the available functional imaging techniques, MEG and EEG uniquely have temporal resolutions below 100 ms. This temporal precision allows us to explore the timing of basic neural processes at the level of cell assemblies. MEG/EEG source localization draws on a wide range of signal processing techniques including digital filtering, three-dimensional image analysis, array signal processing, image modeling and reconstruction, and, blind source separation and phase synchrony estimation. We describe the underlying models currently used in MEG/EEG source estimation and describe the various signal processing steps required to compute these sources. In particular we describe methods for computing the forward fields for known source distributions and parametric and imaging-based approaches to the inverse problem     

Spatio-temporal dynamics prior to neocortical seizures: amplitude versus phase couplings

The mechanisms underlying the transition of brain activity toward epileptic seizures remain unclear. Based on nonlinear analysis of both intracranial and scalp electroencephalographic (EEG) recordings, different research groups have recently reported dynamical smooth changes in epileptic brain activity several minutes before seizure onset. Such preictal states have been detected in populations of patients with mesial temporal lobe epilepsy (MTLE) and, more recently, with different neocortical partial epilepsies (NPEs). In this paper, we are particularly interested in the spatio-temporal organization of epileptogenic networks prior to seizures in neocortical epilepsies. For this, we characterize the network of two patients with NPE by means of two nonlinear measures of interdependencies. Since the synchronization of neuronal activity is an essential feature of the generation and propagation of epileptic activity, we have analyzed changes in phase synchrony between EEG time series. In order to compare the phase and amplitude dynamics, we have also studied the degree of association between pairs of signals by means of a nonlinear correlation coefficient. Recent findings have suggested changes prior to seizures in a wideband frequency range. Instead, for the examples of this study, we report a significant decrease of synchrony in the focal area several minutes before seizures (>30 min in both patients) in the frequency band of 10-25 Hz mainly. Furthermore, the spatio-temporal organization of this preictal activity seems to be specifically related to this frequency band. Measures of both amplitude and phase coupling yielded similar results in narrow-band analysis. These results may open new perspectives on the mechanisms of seizure emergence as well as the organization of neocortical epileptogenic networks. The possibility of forecasting the onset of seizures has important implications for a better understanding, diagnosis and a potential treatment of the epilepsy.     

Hierarchical clustering and filtering in half-inverse space for MEG and/or EEG hypothesis-free analysis

We propose hierarchical clustering and filtering methods for the analysis of spatio-temporal multidimensional time series, where both methods are based on a new pseudo distance. The pseudo distance is determined between orthogonal matrices, which are derived by eigenvalue decomposition of the variance-covariance matrix of the time series. Because the grouping algorithm is also important in clustering, a modified Ward method grouping criterion is used here. The filtering derives temporal similarity information between two time series, providing information that cannot be evaluated by the clustering. If the time series to be clustered and filtered cannot be obtained directly, different time series reflecting the original time series are used instead. There exists a transform between the time series, and hence, scaling distortion occurs. We also propose a scaling normalization method. As an application example, we present an analysis of a multichannel magnetoencephalography (MEG) and/or electroencephalography (EEG) time series. Each of the MEG and EEG generations is a transform from the same electrophysiological brain activity. We applied these methods to sound localization-related MEG time series and evaluated their effectiveness. These methods may be useful for discovering similarity among many multidimensional time series without a priori information and/or hypotheses.     

Spatiotemporal forward solution of the EEG and MEG using network modeling

Dynamic systems have proven to be well suited to describe a broad spectrum of human coordination behavior such synchronization with auditory stimuli. Simultaneous measurements of the spatiotemporal dynamics of electroencephalographic (EEG) and magnetoencephalographic (MEG) data reveals that the dynamics of the brain signals is highly ordered and also accessible by dynamic systems theory. However, models of EEG and MEG dynamics have typically been formulated only in terms of phenomenological modeling such as fixed-current dipoles or spatial EEG and MEG patterns. In this paper, it is our goal to connect three levels of organization, that is the level of coordination behavior, the level of patterns observed in the EEG and MEG and the level of neuronal network dynamics. To do so, we develop a methodological framework, which defines the spatiotemporal dynamics of neural ensembles, the neural field, on a sphere in three dimensions. Using magnetic resonance imaging we map the neural field dynamics from the sphere onto the folded cortical surface of a hemisphere. The neural field represents the current flow perpendicular to the cortex and, thus, allows for the calculation of the electric potentials on the surface of the skull and the magnetic fields outside the skull to be measured by EEG and MEG, respectively. For demonstration of the dynamics, we present the propagation of activation at a single cortical site resulting from a transient input. Finally, a mapping between finger movement profile and EEG/MEG patterns is obtained using Volterra integrals.     

Estimating evoked dipole responses in unknown spatially correlatednoise with EEG/MEG arrays

We present maximum likelihood (ML) methods for estimating evoked dipole responses using electroencephalography (EEG) and magnetoencephalography (MEG) arrays, which allow for spatially correlated noise between sensors with unknown covariance. The electric source is modeled as a collection of current dipoles at fixed locations and the head as a spherical conductor. We permit the dipoles' moments to vary with time by modeling them as linear combinations of parametric or nonparametric basis functions. We estimate the dipoles' locations and moments and derive the Cramer-Rao bound for the unknown parameters. We also propose an ML based method for scanning the brain response data, which can be used to initialize the multidimensional search required to obtain the true dipole location estimates. Numerical simulations demonstrate the performance of the proposed methods     

A nonstationary model of newborn EEG

The detection of seizure in the newborn is a critical aspect of neurological research. Current automatic detection techniques are difficult to assess due to the problems associated with acquiring and labelling newborn electroencephalogram (EEG) data. A realistic model for newborn EEG would allow confident development, assessment and comparison of these detection techniques. This paper presents a model for newborn EEG that accounts for its self-similar and nonstationary nature. The model consists of background and seizure submodels. The newborn EEG background model is based on the short-time power spectrum with a time-varying power law. The relationship between the fractal dimension and the power law of a power spectrum is utilized for accurate estimation of the short-time power law exponent. The newborn EEG seizure model is based on a well-known time-frequency signal model. This model addresses all significant time-frequency characteristics of newborn EEG seizure which include; multiple components or harmonics, piecewise linear instantaneous frequency laws and harmonic amplitude modulation. Estimates of the parameters of both models are shown to be random and are modelled using the data from a total of 500 background epochs and 204 seizure epochs. The newborn EEG background and seizure models are validated against real newborn EEG data using the correlation coefficient. The results show that the output of the proposed models have a higher correlation with real newborn EEG than currently accepted models (a 10% and 38% improvement for background and seizure models, respectively).     

基于精细化频带的脑磁信号跨频耦合特征分析

脑信号跨频耦合现象与人的意识活动密切相关。本文将精细化的频带划分方法和多种跨频耦合的度量方法相结合,研究不同类型手腕运动的脑磁信号跨频耦合特征。首先对四类手运动脑磁信号进行精细化的频带分解,采用了三种具有主次关系的耦合度量方法（相干、虚部相干、调制指数）,在高频耦合低频、低频耦合高频两种耦合形式下对某一运动方向类型信号显著区别于其它运动方向类型信号的频带数、通道对、频带对进行了统计分析,可以区分出不同方向手腕运动的MEG信号;进一步利用通道间的频带耦合关系以及源频带及其激励通道与响应通道等概念,采用相干耦合度量方法对上述两种耦合形式下的统计结果进行分析,获得相应的源频带、激励通道、响应通道,从而可以更加有效地区分不同方向手腕运动的MEG信号。      

Detection of seizure precursors from depth-EEG using a sign periodogram transform

Brief bursts of focal, low amplitude rhythmic activity have been observed on depth electroencephalogram (EEG) in the minutes before electrographic onset of seizures in human mesial temporal lobe epilepsy. We have found these periods to contain discrete, individualized synchronized activity in patient-specific frequency bands ranging from 20 to 40 Hz. We present a method for detecting and displaying these events using a periodogram of the sign-limited temporal derivative of the EEG signal, denoted joint sign periodogram event characterization transform (JSPECT). When applied to continuous 2-6 day depth-EEG recordings from ten patients with temporal lobe epilepsy, JSPECT demonstrated that these patient-specific EEG events reliably occurred 5-80 s prior to electrical onset of seizures in five patients with focal, unilateral seizure onsets. JSPECT did not reveal this type of activity prior to seizures in five other patients with bilateral, extratemporal or more diffuse seizure onsets on EEG. Patient-specific, localized rhythmic events may play an important role in seizure generation in temporal lobe epilepsy. The JSPECT method efficiently detects these events, and may be useful as part of an automated system for predicting electrical seizure onset in appropriate patients.     

Sensitivity distributions of EEG and MEG measurements

It is generally believed that because the skull has low conductivity to electric current but is transparent to magnetic fields, the measurement sensitivity of the magnetoencephalography (MEG) in the brain region should be more concentrated than that of the electroencephalography (EEG). It is also believed that the information recorded by these techniques is very different. If this were indeed the case, it might be possible to justify the cost of MEG instrumentation which is at least 25 times higher than that of EEG instrumentation. The localization of measurement sensitivity using these techniques was evaluated quantitatively in an inhomogeneous spherical head model using a new concept called half-sensitivity volume (HSV). It is shown that the planar gradiometer has a far smaller HSV than the axial gradiometer. However, using the EEG it is possible to achieve even smaller HSVs than with whole-head planar gradiometer MEG devices. The micro-superconducting quantum interference device (SQUID) MEG device does have HSVs comparable to those of the EEG. The sensitivity distribution of planar gradiometers, however, closely resembles that of dipolar EEG leads and, therefore, the MEG and EEG record the electric activity of the brain in a very similar way     

Three-Dimensional Imaging of Complex Neural Activation in Humans From EEG

Electro- or magnetoencephalography (EEG/MEG) are of utmost advantage in studying transient neuronal activity and its timing with respect to behavior in the working human brain. Direct localization of the neural substrates underlying EEG/MEG is commonly achieved by modeling neuronal activity as dipoles. However, the success of neural source localization with the dipole model has only been demonstrated in relatively simple localization tasks owing to the simplified model and its insufficiency in differentiating cortical sources with different extents. It would be of great interest to image complex neural activation with multiple sources of different cortical extensions directly from EEG/MEG. We have investigated this crucial issue by adding additional parameters to the dipole model, leading to the multipole model to better represent the extended sources confined to the convoluted cortical surface. The localization of multiple cortical sources is achieved by using the subspace source localization method with the multipole model. Its performance is evaluated with simulated data as compared with the dipole model, and further illustrated with the real data obtained during visual stimulations in human subjects. The interpretation of the localization results is fully supported by our knowledge about their anatomic locations and functional magnetic resonance imaging data in the same experimental setting. Methods for estimating multiple neuronal sources at cortical areas will facilitate our ability to characterize the cortical electrical activity from simple, early sensory components to more complex networks, such as in visual, motor, and cognitive tasks.     

Monitoring neuronal oscillations and signal transmission betweencortical regions using time-frequency analysis ofelectroencephalographic activity

Oscillatory states in the electroencephalogram (EEG) reflect the rhythmic synchronous activity in large networks of neurons. Time-frequency (TF) methods, which quantify the spectral content of the EEG as a function of time, are well suited as tools for the study of spontaneous and induced changes in oscillatory states. The use of these methods provides insights into the temporal dynamics of EEG activity in both humans and experimental animals, and aids the study of the neuronal mechanisms that generate rhythmic EEG activity. Further the use of TF coherence analysts, which quantifies the consistency of phase relationships in multichannel EEG recordings, may contribute to the understanding of signal transmission between neuronal populations in different parts of the brain. We have used TF techniques to analyze the flow of activity patterns between two strongly connected brain structures: the entorhinal cortex and the hippocampus. Both of these structures are believed to be involved in information storage. By applying various frequencies of stimulation, we have found a peak in the spectral power in both sites at around 18 Hz, but the coherence between the EEG signals recorded from these sites was found to increase monotonically up to about 35 Hz. We have also found that long-term potentiation, a strong increase in the efficacy of excitatory synapses between these sites, either had no effect or decreased coherence     

A statistical technique for measuring synchronism between cortical regions in the EEG during rhythmic stimulation

The coherence function has been widely applied in quantifying the degree of synchronism between electroencephalogram (EEG) signals obtained from different brain regions. However, when applied to investigating synchronization resulting from rhythmic stimulation, misleading results can arise from the high correlation of background EEG activity. We, thus propose a modified measure, which emphasizes the synchronized stimulus responses and reduces the influence of the spontaneous EEG activity. Critical values for this estimator are derived and tested in Monte Carlo simulations. The effectiveness of the method is illustrated on data recorded from 12 young normal subjects during rhythmic photic stimulation.     

EEG/MEC error bounds for a static dipole source with a realistichead model

We derive Cramer-Rao bounds (CRBs) on the errors of estimating the parameters (location and moment) of a static current dipole source using data from electro-encephalography (EEG), magneto-encephalography (MEG), or the combined EEG/MEG modality. We use a realistic head model based on knowledge of surfaces separating tissues of different conductivities obtained from magnetic resonance (MR) or computer tomography (CT) imaging systems. The electric potentials and magnetic field components at the respective sensors are functions of the source parameters through integral equations. These potentials and field are formulated for solving them by the boundary or the finite element method (BEM or FEM) with a weighted residuals technique. We present a unified framework for the measurements computed by these methods that enables the derivation of the bounds. The resulting bounds may be used, for instance, to choose the best configuration of the sensors for a given patient and region of expected source location. Numerical results are used to demonstrate an application for showing expected accuracies in estimating the source parameters as a function of its position in the brain, based on real EEG/MEG system and MR or CT images     

Automatic Detection of Spike and Wave Discharges in the EEG of Genetic Absence Epilepsy Rats From Strasbourg

Genetic absence epilepsy rats from Strasbourg are a strain of Wistar rats in which all animals exhibit spontaneous occurrences of spike and wave discharges (SWDs) in the EEG. In this paper, we propose a novel method for the detection of SWDs, based on the key observation that SWDs are quasi-periodic signals. The method consists of the following steps: 1) calculation of the spectrogram; 2) estimation of the background spectrum and detection of stimulation artifacts; 3) harmonic analysis with continuity analysis to estimate the fundamental frequency; and 4) classification based on the percentage of power in the harmonics to the total power of the spectrum. We evaluated the performance of the novel detection method and six SWD/seizure detection methods from literature on a large database of labeled EEG data consisting of two datasets running to a total duration of more than 26 days of recording. The method outperforms all tested SWD/seizure detection methods, showing a sensitivity and selectivity of 96% and 97%, respectively, on the first test set, and a sensitivity and selectivity of 94% and 92%, respectively, on the second test set. The detection performance is less satisfactory (as for all other methods) for EEG fragments showing more irregular and less periodic SWDs.