The importance of modeling epileptic seizure dynamics as spatio-temporal patterns.

Published onlineJournal ArticleThis is the final version of the article. Available from Frontiers Media via the DOI in this record.The occurrence of seizures is the common feature across the spectrum of epileptic disorders. We describe how the use of mechanistic neural population models leads to novel insight into the dynamic mechanisms underlying two important types of epileptic seizures. We specifically stress the need for a spatio-temporal description of the rhythms to deal with the complexity of the pathophenotype. Adapted to functional and structural patient data, the macroscopic models may allow a patient-specific description of seizures and prediction of treatment outcome.We thank British research councils EPSRC and BBSRC and the University of Manchester for financial support. We thank Kaspar Schindler, Ulrich Stephani, Hiltrud Muhle, Rainer Boor, Michael Siniatchkin, Fernando Lopes da Silva, and Gilles van Luijtelaar for discussions. EEG data are from the University Hospital Inselspital, Bern, Switzerland

Localization of extended brain sources from EEG/MEG: The ExSo-MUSIC approach.

International audienceWe propose a new MUSIC-like method, called 2q-ExSo-MUSIC (q≥1). This method is an extension of the 2q-MUSIC (q≥1) approach for solving the EEG/MEG inverse problem, when spatially-extended neocortical sources ("ExSo") are considered. It introduces a novel ExSo-MUSIC principle. The novelty is two-fold: i) the parameterization of the spatial source distribution that leads to an appropriate metric in the context of distributed brain sources and ii) the introduction of an original, efficient and low-cost way of optimizing this metric. In 2q-ExSo-MUSIC, the possible use of higher order statistics (q≥2) offers a better robustness with respect to Gaussian noise of unknown spatial coherence and modeling errors. As a result we reduced the penalizing effects of both the background cerebral activity that can be seen as a Gaussian and spatially correlated noise, and the modeling errors induced by the non-exact resolution of the forward problem. Computer results on simulated EEG signals obtained with physiologically-relevant models of both the sources and the volume conductor show a highly increased performance of our 2q-ExSo-MUSIC method as compared to the classical 2q-MUSIC algorithms

Interictal Functional Connectivity of Human Epileptic Networks Assessed by Intracerebral EEG and BOLD Signal Fluctuations

In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal derived from resting state functional magnetic resonance imaging (fMRI) reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG) and resting-state functional MRI (fMRI) in 5 patients suffering from intractable temporal lobe epilepsy (TLE). Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions) during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband) and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal). This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional connectivity measured by iEEG and BOLD signals give complementary but sometimes inconsistent information in TLE

Blind Source Separation Methods Applied to Muscle Artefacts Removing from Epileptic Eeg Recording: A Comparative Study.

International audienceElectroencephalogram (EEG) recordings are often contaminated with muscle artifacts. These artifacts obscure the EEG and complicate its interpretation or even make the interpretation unfeasible. In this paper, realistic spike EEG signals are simulated from the activation of a 5 cm2 epileptic patch in the left superior temporal gyrus. Background activities and real muscle artifacts are then added to the simulated data. We compare the efficiency of Empirical Mode Decomposition (EMD), Independent Component Analysis (ICA) and Blind Source Separation based on Canonical Correlation Analysis (BSS-CCA) to remove muscle artifacts from the EEG signals. The quantitative comparison indicates that the EMD approach exhibits a better performance than ICA and BSS-CCA, especially in the case of very low Signal to Noise Ratio (SNR)

Epileptic neuronal networks: methods of identification and clinical relevance

The main objective of this paper is to examine evidence for the concept that epileptic activity should be envisaged in terms of functional connectivity and dynamics of neuronal networks. Basic concepts regarding structure and dynamics of neuronal networks are briefly described. Particular attention is given to approaches that are derived, or related, to the concept of causality, as formulated by Granger. Linear and non-linear methodologies aiming at characterizing the dynamics of neuronal networks applied to EEG/MEG and combined EEG/fMRI signals in epilepsy are critically reviewed. The relevance of functional dynamical analysis of neuronal networks with respect to clinical queries in focal cortical dysplasias, temporal lobe epilepsies, and “generalized” epilepsies is emphasized. In the light of the concepts of epileptic neuronal networks, and recent experimental findings, the dichotomic classification in focal and generalized epilepsy is re-evaluated. It is proposed that so-called “generalized epilepsies,” such as absence seizures, are actually fast spreading epilepsies, the onset of which can be tracked down to particular neuronal networks using appropriate network analysis. Finally new approaches to delineate epileptogenic networks are discussed

Modèle de génération simultanée des signaux EEG de surface et de profondeur

Ce travail porte sur l'interprétation des signaux électroencéphalographiques (EEG) et stéréo-électroencéphalographiques (SEEG) acquis chez des patients épileptiques candidats à la chirurgie. Cette question est abordée au travers d'une modélisation réaliste des signaux EEG et SEEG, qui repose sur une représentation physiologiquement pertinente des sources de l'activité cérébrale associant un modèle biophysique de sources dipolaires et un modèle biomathématique de populations neuronales. Les signaux induits sur les capteurs de surface et de profondeur sont ensuite obtenus par la résolution du problème direct dans le volume conducteur de la tête. Le modèle complet permet d'étudier les relations existant entre la configuration spatio-temporelle des sources d'activité et les propriétés des signaux observés en surface et en profondeur

Analysis and Enhancements of a Prolific Macroscopic Model of Epilepsy

Macroscopic models of epilepsy can deliver surprisingly realistic EEG simulations. In the present study, a prolific series of models is evaluated with regard to theoretical and computational concerns, and enhancements are developed. Specifically, we analyze three aspects of the models: (1) Using dynamical systems analysis, we demonstrate and explain the presence of direct current potentials in the simulated EEG that were previously undocumented. (2) We explain how the system was not ideally formulated for numerical integration of stochastic differential equations. A reformulated system is developed to support proper methodology. (3) We explain an unreported contradiction in the published model specification regarding the use of a mathematical reduction method. We then use the method to reduce the number of equations and further improve the computational efficiency. The intent of our critique is to enhance the evolution of macroscopic modeling of epilepsy and assist others who wish to explore this exciting class of models further

Spatio-temporal modelling and analysis of epileptiform EEG

In this thesis we investigate the mechanisms underlying the generation of abnormal EEG rhythms in epilepsy, which is a crucial step towards better treatment of this disorder in the future. To this end, macroscopic scale mathematical models of the interactions between neuronal populations are examined. In particular, the role of interactions between neural masses that are spatially distributed in cortical networks are explored. In addition, two other important aspects of the modelling process are addressed, namely the conversion of macroscopic model variables into EEG output and the comparison of multivariate, spatio-temporal data. For the latter, we adopt a vectorisation of the correlation matrix of windowed data and subsequent comparison of data by vector distance measures. Our modelling studies indicate that excitatory connectivity between neural masses facilitates self-organised dynamics. In particular, we report for the first time the production of complex rhythmic transients and the generation of intermittent periods of 'abnormal' rhythmic activity in two different models of epileptogenic tissue. These models therefore provide novel accounts of the spontaneous, intermittent transition between normal and pathological rhythms in primarily generalised epilepsies and the evocation of complex, self-terminating, spatio-temporal dynamics by brief stimulation in focal epilepsies. Two key properties of these models are excitability at the macroscopic level and the presence of spatial heterogeneities. The identification of neural mass excitability as an important processes in spatially extended brain networks is a step towards uncovering the multi-scale nature of the pathological mechanisms of epilepsy. A direct consequence of this work is therefore that novel experimental investigations are proposed, which in itself is a validation of our modelling approach. In addition, new considerations regarding the nature of dynamical systems as applied to problems of transitions between rhythmic states are proposed and will prompt future investigations of complex transients in spatio-temporal excitable systems.EThOS - Electronic Theses Online ServiceGBUnited Kingdo