EEGNET: An Open Source Tool for Analyzing and Visualizing M/EEG Connectome

The brain is a large-scale complex network often referred to as the “connectome”. Exploring the dynamic behavior of the connectome is a challenging issue as both excellent time and space resolution is required. In this context Magneto/Electroencephalography (M/EEG) are effective neuroimaging techniques allowing for analysis of the dynamics of functional brain networks at scalp level and/or at reconstructed sources. However, a tool that can cover all the processing steps of identifying brain networks from M/EEG data is still missing. In this paper, we report a novel software package, called EEGNET, running under MATLAB (Math works, inc), and allowing for analysis and visualization of functional brain networks from M/EEG recordings. EEGNET is developed to analyze networks either at the level of scalp electrodes or at the level of reconstructed cortical sources. It includes i) Basic steps in preprocessing M/EEG signals, ii) the solution of the inverse problem to localize / reconstruct the cortical sources, iii) the computation of functional connectivity among signals collected at surface electrodes or/and time courses of reconstructed sources and iv) the computation of the network measures based on graph theory analysis. EEGNET is the unique tool that combines the M/EEG functional connectivity analysis and the computation of network measures derived from the graph theory. The first version of EEGNET is easy to use, flexible and user friendly. EEGNET is an open source tool and can be freely downloaded from this webpage: https://sites.google.com/site/eegnetworks/.     

Effects of Spatial Pattern Scale of Brain Activity on the Sensitivity of DOT,fMRI, EEG and MEG

The objective of this work is to quantify how patterns of cortical activity at different spatial scales are measured by noninvasive functional neuroimaging sensors. We simulated cortical activation patterns at nine different spatial scales in a realistic head model and propagated this activity to magnetoencephalography (MEG), electroencephalography (EEG), diffuse optical tomography (DOT), and functional magnetic resonance imaging (fMRI) sensors in arrangements that are typically used in functional neuroimaging studies. We estimated contrast transfer functions (CTF), correlation distances in sensor space, and the minimum resolvable spatial scale of cortical activity for each modality. We found that CTF decreases as the spatial extent of cortical activity decreases, and that correlations between nearby sensors depend on the spatial extent of cortical activity. For cortical activity on the intermediate spatial scale of 6.7 cm², the correlation distances (r>0.5) were 1.0 cm for fMRI, 2.0 cm for DOT, 12.8 for EEG, 9.5 cm for MEG magnetometers and 9.7 cm for MEG gradiometers. The resolvable spatial pattern scale was found to be 1.43 cm² for MEG magnetometers, 0.88 cm² for MEG gradiometers, 376 cm² for EEG, 0.75 cm² for DOT, and 0.072 cm² for fMRI. These findings show that sensitivity to cortical activity varies substantially as a function of spatial scale within and between the different imaging modalities. This information should be taken into account when interpreting neuroimaging data and when choosing the number of nodes for network analyses in sensor space.     

Mapping Cortical Dynamics Using Simultaneous MEG/EEG and Anatomically-constrained Minimum-norm Estimates: an Auditory Attention Example

Magneto- and electroencephalography (MEG/EEG) are neuroimaging techniques that provide a high temporal resolution particularly suitable to investigate the cortical networks involved in dynamical perceptual and cognitive tasks, such as attending to different sounds in a cocktail party. Many past studies have employed data recorded at the sensor level only, i.e., the magnetic fields or the electric potentials recorded outside and on the scalp, and have usually focused on activity that is time-locked to the stimulus presentation. This type of event-related field / potential analysis is particularly useful when there are only a small number of distinct dipolar patterns that can be isolated and identified in space and time. Alternatively, by utilizing anatomical information, these distinct field patterns can be localized as current sources on the cortex. However, for a more sustained response that may not be time-locked to a specific stimulus (e.g., in preparation for listening to one of the two simultaneously presented spoken digits based on the cued auditory feature) or may be distributed across multiple spatial locations unknown a priori, the recruitment of a distributed cortical network may not be adequately captured by using a limited number of focal sources.Here, we describe a procedure that employs individual anatomical MRI data to establish a relationship between the sensor information and the dipole activation on the cortex through the use of minimum-norm estimates (MNE). This inverse imaging approach provides us a tool for distributed source analysis. For illustrative purposes, we will describe all procedures using FreeSurfer and MNE software, both freely available. We will summarize the MRI sequences and analysis steps required to produce a forward model that enables us to relate the expected field pattern caused by the dipoles distributed on the cortex onto the M/EEG sensors. Next, we will step through the necessary processes that facilitate us in denoising the sensor data from environmental and physiological contaminants. We will then outline the procedure for combining and mapping MEG/EEG sensor data onto the cortical space, thereby producing a family of time-series of cortical dipole activation on the brain surface (or "brain movies") related to each experimental condition. Finally, we will highlight a few statistical techniques that enable us to make scientific inference across a subject population (i.e., perform group-level analysis) based on a common cortical coordinate space.     

Electric Field Encephalography as a Tool for Functional Brain Research: A Modeling Study

We introduce the notion of Electric Field Encephalography (EFEG) based on measuring electric fields of the brain and demonstrate, using computer modeling, that given the appropriate electric field sensors this technique may have significant advantages over the current EEG technique. Unlike EEG, EFEG can be used to measure brain activity in a contactless and reference-free manner at significant distances from the head surface. Principal component analysis using simulated cortical sources demonstrated that electric field sensors positioned 3 cm away from the scalp and characterized by the same signal-to-noise ratio as EEG sensors provided the same number of uncorrelated signals as scalp EEG. When positioned on the scalp, EFEG sensors provided 2–3 times more uncorrelated signals. This significant increase in the number of uncorrelated signals can be used for more accurate assessment of brain states for non-invasive brain-computer interfaces and neurofeedback applications. It also may lead to major improvements in source localization precision. Source localization simulations for the spherical and Boundary Element Method (BEM) head models demonstrated that the localization errors are reduced two-fold when using electric fields instead of electric potentials. We have identified several techniques that could be adapted for the measurement of the electric field vector required for EFEG and anticipate that this study will stimulate new experimental approaches to utilize this new tool for functional brain research.     

Complexity of Multi-Channel Electroencephalogram Signal Analysis in Childhood Absence Epilepsy

Absence epilepsy is an important epileptic syndrome in children. Multiscale entropy (MSE), an entropy-based method to measure dynamic complexity at multiple temporal scales, is helpful to disclose the information of brain connectivity. This study investigated the complexity of electroencephalogram (EEG) signals using MSE in children with absence epilepsy. In this research, EEG signals from 19 channels of the entire brain in 21 children aged 5-12 years with absence epilepsy were analyzed. The EEG signals of pre-ictal (before seizure) and ictal states (during seizure) were analyzed by sample entropy (SamEn) and MSE methods. Variations of complexity index (CI), which was calculated from MSE, from the pre-ictal to the ictal states were also analyzed. The entropy values in the pre-ictal state were significantly higher than those in the ictal state. The MSE revealed more differences in analysis compared to the SamEn. The occurrence of absence seizures decreased the CI in all channels. Changes in CI were also significantly greater in the frontal and central parts of the brain, indicating fronto-central cortical involvement of “cortico-thalamo-cortical network” in the occurrence of generalized spike and wave discharges during absence seizures. Moreover, higher sampling frequency was more sensitive in detecting functional changes in the ictal state. There was significantly higher correlation in ictal states in the same patient in different seizures but there were great differences in CI among different patients, indicating that CI changes were consistent in different absence seizures in the same patient but not from patient to patient. This implies that the brain stays in a homogeneous activation state during the absence seizures. In conclusion, MSE analysis is better than SamEn analysis to analyze complexity of EEG, and CI can be used to investigate the functional brain changes during absence seizures.     

Des sources neuronales aux signaux EEG : modèle et interprétation des activités épileptiques

This work deals with the interpretation of electrophysiological patients recorded in epileptic patients candidate to surgery. This issue is addressed through a physiologically relevant model for the generation of scalp and intracerebral electroencephalographic (EEG) signals. The proposed model is based on a spatiotemporal representation of the sources of brain activity, which combines a distributed dipole source model and a model of coupled neuronal populations. Signals recorded by sensors (scalp and intracerebral) are then computed by solving the forward problem in the head volume conductor. In this paper, the EEG generation model is used to study the influence of some source-related parameters (spatial extent, position, synchronization) on simulated signals, during epileptic transient activity (interictal spikes). Results show that the model allows for studying, on the one hand, the relationship between the spatiotemporal organization of neuronal sources and the properties of the observed signals and, on the other hand, the relationship between surface and depth EEG signals.     

Electroencephalographic imaging of higher brain function.

High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. Electroencephalography (EEG) provides temporal resolution in the millisecond range. However, traditional EEG technology and practice provide insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. Recent advances help to overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical images, and by correcting the distortion caused by volume conduction of EEG signals through the skull and scalp. In addition, statistical measurements of sub-second interdependences between EEG time-series recorded from different locations can help to generate hypotheses about the instantaneous functional networks that form between different cortical regions during perception, thought and action. Example applications are presented from studies of language, attention and working memory. Along with its unique ability to monitor brain function as people perform everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.     

Linear correlation between fractal dimension of EEG signal and handgrip force

Fractal dimension (FD) has been proved useful in quantifying the complexity of dynamical signals in biology and medicine. In this study, we measured FDs of human electroencephalographic (EEG) signals at different levels of handgrip forces. EEG signals were recorded from five major motor-related cortical areas in eight normal healthy subjects. FDs were calculated using three different methods. The three physiological periods of handgrip (command preparation, movement and holding periods) were analyzed and compared. The results showed that FDs of the EEG signals during the movement and holding periods increased linearly with handgrip force, whereas FD during the preparation period had no correlation with force. The results also demonstrated that one method (Katz’s) gave greater changes in FD, and thus, had more power in capturing the dynamic changes in the signal. The linear increase of FD, together with results from other EEG and neuroimaging studies, suggest that under normal conditions the brain recruits motor neurons at a linear progress when increasing the force.     

A probabilistic framework for a physiological representation of dynamically evolving sleep state

This work presents a probabilistic method for mapping human sleep electroencephalogram (EEG) signals onto a state space based on a biologically plausible mathematical model of the cortex. From a noninvasive EEG signal, this method produces physiologically meaningful pathways of the cortical state over a night of sleep. We propose ways in which these pathways offer insights into sleep-related conditions, functions, and complex pathologies. To address explicitly the noisiness of the EEG signal and the stochastic nature of the mathematical model, we use a probabilistic Bayesian framework to map each EEG epoch to a distribution of likelihoods over all model sleep states. We show that the mapping produced from human data robustly separates rapid eye movement sleep (REM) from slow wave sleep (SWS). A Hidden Markov Model (HMM) is incorporated to improve the path results using the prior knowledge that cortical physiology has temporal continuity.     

Seizure source localization using a hybrid second order blind identification and extended rival penalized competitive learning algorithm

Localization of seizure sources prior to neurosurgery is crucial. In this paper, a new method is proposed to localize the seizure sources from multi-channel electroencephalogram (EEG) signals. Blind source separation based on second order blind identification (SOBI) is primarily applied to estimate the brain source signals in each window of the EEG signals. A new clustering method based on rival penalized competitive learning (RPCL) is then developed to cluster the rows of the estimated unmixing matrices in all the windows. The algorithm also includes pre and post-processing stages. By multiplying each cluster center to the EEG signals, the brain signal sources are approximated. According to a complexity value measure, the main seizure source signal is separated from the others. This signal is projected back to the electrodes’ space and is subjected to the dipole source localization using a single dipole model. The simulation results verify the accuracy of the system. In addition, correct localization of the seizure source is consistent with the clinical tests derived using the simultaneous intracranial recordings.     

Modelling and detecting deep brain activity with MEG and EEG

We introduce an anatomical and electrophysiological model of deep brain structures dedicated to magnetoencephalography (MEG) and electroencephalography (EEG) source imaging. So far, most imaging inverse models considered that MEG/EEG surface signals were predominantly produced by cortical, hence superficial, neural currents. Here we question whether crucial deep brain structures such as the basal ganglia and the hippocampus may also contribute to distant, scalp MEG and EEG measurements. We first design a realistic anatomical and electrophysiological model of these structures and subsequently run Monte-Carlo experiments to evaluate the respective sensitivity of the MEG and EEG to signals from deeper origins. Results indicate that MEG/EEG may indeed localize these deeper generators, which is confirmed here from experimental MEG data reporting on the modulation of alpha (10–12 Hz) brain waves.     

Effects of RF‐EMF on the Human Resting‐State EEG—the Inconsistencies in the Consistency. Part 1: Non‐Exposure‐Related Limitations of Comparability Between Studies

The results of studies on possible effects of radiofrequency electromagnetic fields (RF‐EMFs) on human waking electroencephalography (EEG) have been quite heterogeneous. In the majority of studies, changes in the alpha‐frequency range in subjects who were exposed to different signals of mobile phone‐related EMF sources were observed, whereas other studies did not report any effects. In this review, possible reasons for these inconsistencies are presented and recommendations for future waking EEG studies are made. The physiological basis of underlying brain activity, and the technical requirements and framework conditions for conducting and analyzing the human resting‐state EEG are discussed. Peer‐reviewed articles on possible effects of EMF on waking EEG were evaluated with regard to non‐exposure‐related confounding factors. Recommendations derived from international guidelines on the analysis and reporting of findings are proposed to achieve comparability in future studies. In total, 22 peer‐reviewed studies on possible RF‐EMF effects on human resting‐state EEG were analyzed. EEG power in the alpha frequency range was reported to be increased in 10, decreased in four, and not affected in eight studies. All reviewed studies differ in several ways in terms of the methodologies applied, which might contribute to different results and conclusions about the impact of EMF on human resting‐state EEG. A discussion of various study protocols and different outcome parameters prevents a scientifically sound statement on the impact of RF‐EMF on human brain activity in resting‐state EEG. Further studies which apply comparable, standardized study protocols are recommended. Bioelectromagnetics. 2019;40:291–318. © 2019 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.     

Use of a neural mass model for the analysis of effective connectivity among cortical regions based on high resolution EEG recordings

Assessment of brain connectivity among different brain areas during cognitive or motor tasks is a crucial problem in neuroscience today. Aim of this work is to use a neural mass model to assess the effect of various connectivity patterns in cortical electroencephalogram (EEG) power spectral density, and investigate the possibility to derive connectivity circuits from EEG data. To this end, a model of an individual region of interest (ROI) has been built as the parallel arrangement of three populations, each described as in Wendling et al. (Eur J Neurosci 15:1499–1508, 2002). Connectivity among ROIs includes three parameters, which specify the strength of connection in the different frequency bands. The following main steps have been followed: (1) we analyzed how the power spectral density (PSD) is significantly modified by the kind of coupling hypothesized among the ROIs; (2) with the model, and using an automatic fitting procedure, we looked for a simple connectivity circuit able to reproduce PSD of cortical EEG in three ROIs during a finger-movement task. The estimated parameters represent the strength of connections among the ROIs in the different frequency bands. Cortical EEGs were computed with an inverse propagation algorithm, starting from measurement performed with 96 electrodes on the scalp. The present study suggests that the model can be used as a simulation tool, able to mimic the effect of connectivity on EEG. Moreover, it can be used to look for simple connectivity circuits, able to explain the main features of observed cortical PSD. These results may open new prospectives in the use of neurophysiological models, instead of empirical models, to assess effective connectivity from neuroimaging information.     

Nonlinear analysis of EEG signals: Surrogate data analysis

ObjectivesThe electroencephalogram (EEG) signal contains information about the state and condition of the brain. The aim of the study is to conduct a nonlinear analysis of the EEG signals and to compare the differences in the nonlinear characteristics of the EEG during normal state and the epileptic state.DataThe EEG data used for this study – which consisted of epileptic EEG and normal EEG – were obtained from the EEG database available with the Bonn University, Germany.ResultsThe attractors seen in normal and epileptic human brain dynamics were studied and compared. Surrogate data analyses were conducted on two nonlinear measures, namely the largest Lyapunov exponent and the correlation dimension, to test the hypothesis whether EEG signals were in accordance with linear stochastic models.DiscussionsThe existence of deterministic chaos in brain activity is confirmed by the existence of a chaotic attractor; also, saturation of the correlation dimension towards a definite value is the manifestation of a deterministic dynamics. Also a reduction is observed between the dimensionalities of the brain attractors from normal state to the epileptic state. The evaluation of the largest Lyapunov exponent also confirms the lowering of complexity during an episode of seizure.ConclusionIn case of Lyapunov exponent of EEG data, the change due to surrogating is small suggesting that it is not representing the system complexity properly but there is a marked change in the case of correlation dimension value due to surrogating.     

The multifactor method of EEG separation into the cortical and deep components

A new method of separation of multichannel brain electrical activity into cortical and subcortical components with the help of multifactor analysis is proposed. The method provides a means for isolation and, consequently, more reliable localization of sources of electrical activity not only in deep brain structures (on the basis of the dipole model) but also on the cortical surface. The proposed method does not depend on the rotation and interpretation of factors, and no data losses occur. The mufasel algorithm is based on integration of all selected factors (within a particular EEG or EP time segment) in two groups using a statistical criterion, which defines general and specific factors. It is assumed that general factors loaded with highly correlated derivations predominantly describe the electrical activity of deep brain structures, whereas specific factors loaded by the dynamics of electrical activity in individual derivations, reflect the integrated activity of cortical brain structures.     

Functional Connectivity Alterations in Epilepsy from Resting-State Functional MRI

The study of functional brain connectivity alterations induced by neurological disorders and their analysis from resting state functional Magnetic Resonance Imaging (rfMRI) is generally considered to be a challenging task. The main challenge lies in determining and interpreting the large-scale connectivity of brain regions when studying neurological disorders such as epilepsy. We tackle this challenging task by studying the cortical region connectivity using a novel approach for clustering the rfMRI time series signals and by identifying discriminant functional connections using a novel difference statistic measure. The proposed approach is then used in conjunction with the difference statistic to conduct automatic classification experiments for epileptic and healthy subjects using the rfMRI data. Our results show that the proposed difference statistic measure has the potential to extract promising discriminant neuroimaging markers. The extracted neuroimaging markers yield 93.08% classification accuracy on unseen data as compared to 80.20% accuracy on the same dataset by a recent state-of-the-art algorithm. The results demonstrate that for epilepsy the proposed approach confirms known functional connectivity alterations between cortical regions, reveals some new connectivity alterations, suggests potential neuroimaging markers, and predicts epilepsy with high accuracy from rfMRI scans.     

From Oscillatory Transcranial Current Stimulation to Scalp EEG Changes: A Biophysical and Physiological Modeling Study

Both biophysical and neurophysiological aspects need to be considered to assess the impact of electric fields induced by transcranial current stimulation (tCS) on the cerebral cortex and the subsequent effects occurring on scalp EEG. The objective of this work was to elaborate a global model allowing for the simulation of scalp EEG signals under tCS. In our integrated modeling approach, realistic meshes of the head tissues and of the stimulation electrodes were first built to map the generated electric field distribution on the cortical surface. Secondly, source activities at various cortical macro-regions were generated by means of a computational model of neuronal populations. The model parameters were adjusted so that populations generated an oscillating activity around 10 Hz resembling typical EEG alpha activity. In order to account for tCS effects and following current biophysical models, the calculated component of the electric field normal to the cortex was used to locally influence the activity of neuronal populations. Lastly, EEG under both spontaneous and tACS-stimulated (transcranial sinunoidal tCS from 4 to 16 Hz) brain activity was simulated at the level of scalp electrodes by solving the forward problem in the aforementioned realistic head model. Under the 10 Hz-tACS condition, a significant increase in alpha power occurred in simulated scalp EEG signals as compared to the no-stimulation condition. This increase involved most channels bilaterally, was more pronounced on posterior electrodes and was only significant for tACS frequencies from 8 to 12 Hz. The immediate effects of tACS in the model agreed with the post-tACS results previously reported in real subjects. Moreover, additional information was also brought by the model at other electrode positions or stimulation frequency. This suggests that our modeling approach can be used to compare, interpret and predict changes occurring on EEG with respect to parameters used in specific stimulation configurations.     

Relating Alpha Power and Phase to Population Firing and Hemodynamic Activity Using a Thalamo-cortical Neural Mass Model

Oscillations are ubiquitous phenomena in the animal and human brain. Among them, the alpha rhythm in human EEG is one of the most prominent examples. However, its precise mechanisms of generation are still poorly understood. It was mainly this lack of knowledge that motivated a number of simultaneous electroencephalography (EEG) – functional magnetic resonance imaging (fMRI) studies. This approach revealed how oscillatory neuronal signatures such as the alpha rhythm are paralleled by changes of the blood oxygenation level dependent (BOLD) signal. Several such studies revealed a negative correlation between the alpha rhythm and the hemodynamic BOLD signal in visual cortex and a positive correlation in the thalamus. In this study we explore the potential generative mechanisms that lead to those observations. We use a bursting capable Stefanescu-Jirsa 3D (SJ3D) neural-mass model that reproduces a wide repertoire of prominent features of local neuronal-population dynamics. We construct a thalamo-cortical network of coupled SJ3D nodes considering excitatory and inhibitory directed connections. The model suggests that an inverse correlation between cortical multi-unit activity, i.e. the firing of neuronal populations, and narrow band local field potential oscillations in the alpha band underlies the empirically observed negative correlation between alpha-rhythm power and fMRI signal in visual cortex. Furthermore the model suggests that the interplay between tonic and bursting mode in thalamus and cortex is critical for this relation. This demonstrates how biophysically meaningful modelling can generate precise and testable hypotheses about the underpinnings of large-scale neuroimaging signals.     

Coherence and phase locking in the scalp EEG and between LORETA model sources, and microstates as putative mechanisms of brain temporo-spatial functional organization.

Brain electric mechanisms of temporary, functional binding between brain regions are studied using computation of scalp EEG coherence and phase locking, sensitive to time differences of few milliseconds. However, such results if computed from scalp data are ambiguous since electric sources are spatially oriented. Non-ambiguous results can be obtained using calculated time series of strength of intracerebral model sources. This is illustrated applying LORETA modeling to EEG during resting and meditation. During meditation, time series of LORETA model sources revealed a tendency to decreased left-right intracerebral coherence in the delta band, and to increased anterior-posterior intracerebral coherence in the theta band. An alternate conceptualization of functional binding is based on the observation that brain electric activity is discontinuous, i.e., that it occurs in chunks of up to about 100 ms duration that are detectable as quasi-stable scalp field configurations of brain electric activity, called microstates. Their functional significance is illustrated in spontaneous and event-related paradigms, where microstates associated with imagery- versus abstract-type mentation, or while reading positive versus negative emotion words showed clearly different regions of cortical activation in LORETA tomography. These data support the concept that complete brain functions of higher order such as a momentary thought might be incorporated in temporal chunks of processing in the range of tens to about 100 ms as quasi-stable brain states; during these time windows, subprocesses would be accepted as members of the ongoing chunk of processing.