Dynamics of epileptic phenomena determined from statistics of ictal transitions

In this paper, we investigate the dynamical scenarios of transitions between normal and paroxysmal state in epilepsy. We assume that some epileptic neural network are bistable i.e., they feature two operational states, ictal and interictal that co-exist. The transitions between these two states may occur according to a Poisson process, a random walk process or as a result of deterministic time-dependent mechanisms. We analyze data from animal models of absence epilepsy, human epilepsies and in vitro models. The distributions of durations of ictal and interictal epochs are fitted with a gamma distribution. On the basis of qualitative features of the fits, we identify the dynamical processes that may have generated the underlying data. The analysis showed that the following hold. 1) The dynamics of ictal epochs differ from those of interictal states. 2) Seizure initiation can be accounted for by a random walk process while seizure termination is often mediated by deterministic mechanisms. 3) In certain cases, the transitions between ictal and interictal states can be modeled by a Poisson process operating in a bistable network. These results imply that exact prediction of seizure occurrence is not possible but termination of an ictal state by appropriate counter stimulation might be feasible.     

Directed differential connectivity graph of interictal epileptiform discharges

In this paper, we study temporal couplings between interictal events of spatially remote regions in order to localize the leading epileptic regions from intracerebral EEG (iEEG). We aim to assess whether quantitative epileptic graph analysis during interictal period may be helpful to predict the seizure onset zone of ictal iEEG. Using wavelet transform, cross-correlation coefficient, and multiple hypothesis test, we propose a differential connectivity graph (DCG) to represent the connections that change significantly between epileptic and nonepileptic states as defined by the interictal events. Postprocessings based on mutual information and multiobjective optimization are proposed to localize the leading epileptic regions through DCG. The suggested approach is applied on iEEG recordings of five patients suffering from focal epilepsy. Quantitative comparisons of the proposed epileptic regions within ictal onset zones detected by visual inspection and using electrically stimulated seizures, reveal good performance of the present method.     

A wavelet-chaos methodology for analysis of EEGs and EEG subbands to detect seizure and epilepsy

A wavelet-chaos methodology is presented for analysis of EEGs and delta, theta, alpha, beta, and gamma subbands of EEGs for detection of seizure and epilepsy. The nonlinear dynamics of the original EEGs are quantified in the form of the correlation dimension (CD, representing system complexity) and the largest Lyapunov exponent (LLE, representing system chaoticity). The new wavelet-based methodology isolates the changes in CD and LLE in specific subbands of the EEG. The methodology is applied to three different groups of EEG signals: 1) healthy subjects; 2) epileptic subjects during a seizure-free interval (interictal EEG); 3) epileptic subjects during a seizure (ictal EEG). The effectiveness of CD and LLE in differentiating between the three groups is investigated based on statistical significance of the differences. It is observed that while there may not be significant differences in the values of the parameters obtained from the original EEG, differences may be identified when the parameters are employed in conjunction with specific EEG subbands. Moreover, it is concluded that for the higher frequency beta and gamma subbands, the CD differentiates between the three groups, whereas for the lower frequency alpha subband, the LLE differentiates between the three groups.     

Modeling common dynamics in multichannel signals with applications to artifact and background removal in EEG recordings

Removing artifacts and background electroencephaloraphy (EEG) from multichannel interictal and ictal EEG has become a major research topic in EEG signal processing in recent years. We applied for this purpose a recently developed subspace-based method for modeling the common dynamics in multichannel signals. When the epileptiform activity is common in the majority of channels and the artifacts appear only in a few channels the proposed method can be used to remove the latter. The performance of the method was tested on simulated data for different noise levels. For high noise levels the method was still able to identify the common dynamics. In addition, the method was applied to real life EEG recordings containing interictal and ictal activity contaminated with muscle artifact. The muscle artifacts were removed successfully. For both the synthetic data and the analyzed real life data the results were compared with the results obtained with principal component analysis (PCA). In both cases, the proposed method performed better than PCA.     

Adaptive epileptic seizure prediction system

Current epileptic seizure "prediction" algorithms are generally based on the knowledge of seizure occurring time and analyze the electroencephalogram (EEG) recordings retrospectively. It is then obvious that, although these analyses provide evidence of brain activity changes prior to epileptic seizures, they cannot be applied to develop implantable devices for diagnostic and therapeutic purposes. In this paper, we describe an adaptive procedure to prospectively analyze continuous, long-term EEG recordings when only the occurring time of the first seizure is known. The algorithm is based on the convergence and divergence of short-term maximum Lyapunov exponents (STLmax) among critical electrode sites selected adaptively. A warning of an impending seizure is then issued. Global optimization techniques are applied for selecting the critical groups of electrode sites. The adaptive seizure prediction algorithm (ASPA) was tested in continuous 0.76 to 5.84 days intracranial EEG recordings from a group of five patients with refractory temporal lobe epilepsy. A fixed parameter setting applied to all cases predicted 82% of seizures with a false prediction rate of 0.16/h. Seizure warnings occurred an average of 71.7 min before ictal onset. Similar results were produced by dividing the available EEG recordings into half training and testing portions. Optimizing the parameters for individual patients improved sensitivity (84% overall) and reduced false prediction rate (0.12/h overall). These results indicate that ASPA can be applied to implantable devices for diagnostic and therapeutic purposes.     

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.     

Principal component analysis-enhanced cosine radial basis function neural network for robust epilepsy and seizure detection.

A novel principal component analysis (PCA)-enhanced cosine radial basis function neural network classifier is presented. The two-stage classifier is integrated with the mixed-band wavelet-chaos methodology, developed earlier by the authors, for accurate and robust classification of electroencephalogram (EEGs) into healthy, ictal, and interictal EEGs. A nine-parameter mixed-band feature space discovered in previous research for effective EEG representation is used as input to the two-stage classifier. In the first stage, PCA is employed for feature enhancement. The rearrangement of the input space along the principal components of the data improves the classification accuracy of the cosine radial basis function neural network (RBFNN) employed in the second stage significantly. The classification accuracy and robustness of the classifier are validated by extensive parametric and sensitivity analysis. The new wavelet-chaos-neural network methodology yields high EEG classification accuracy (96.6%) and is quite robust to changes in training data with a low standard deviation of 1.4%. For epilepsy diagnosis, when only normal and interictal EEGs are considered, the classification accuracy of the proposed model is 99.3%. This statistic is especially remarkable because even the most highly trained neurologists do not appear to be able to detect interictal EEGs more than 80% of the times.     

Prediction of PTZ-induced seizures using wavelet-based residual entropy of cortical and subcortical field potentials

Our proposed algorithm for seizure prediction is based on the principle that seizure build-up is always preceded by constantly changing bursting levels. We use a novel measure of residual subband wavelet entropy (RSWE) to directly estimate the entropy of bursts, which is otherwise obscured by the ongoing background activity. Our results are obtained using a slow infusion anesthetized pentylenetetrazol (PTZ) rat model in which we record field potentials (FPs) from frontal cortex and two thalamic areas (anterior and posterior nuclei). In each frequency band, except for the theta-delta frequency bands, we observed a significant build-up of RSWE from the preictal period to the first ictal event (p < or = 0.05) in cortex. Significant differences were observed between cortical and thalamic RSWE (p < or = 0.05) subsequent to seizure development. A key observation is the twofold increase in mean cortical RSWE from the preictal to interictal period. Exploiting this increase, we develop a slope change detector to discern early acceleration of entropy and predict the approaching seizure. We use multiple observations through sequential detection of slope changes to enhance the sensitivity of our prediction. Using the proposed method applied to a cohort of four rats subjected to PTZ infusion, we were able to predict the first seizure episode 28 min prior to its occurrence.     

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.     

On the tracking of rapid dynamic changes in seizure EEG

Estimation of autospectra and coherence and phase spectra of the seizure electroencephalograph (EEG), using the fast Fourier transform (FFT) technique, will cause smearing of the rapid dynamic changes which occur during the seizure. This is inherent to FFT spectral estimation, due to the averaging process which is necessary in order to get consistent spectral estimates. A different approach suggested in the present study is to carry out multivariate autoregressive modeling of the multichannel seizure EEG, combined with adaptive segmentation. In order to obtain good estimates in cases of short record length, the vectorial autoregressive (AR) modeling was based on residual energy ratios. The method has been tested on multichannel seizure EEG recordings from rats with focal epilepsy, caused by intracerebral administration of Kainic acid, and in-depth EEG recordings in patients with temporal lobe epilepsy     

Forecasting generalized epileptic seizures from the EEG signal bywavelet analysis and dynamic unsupervised fuzzy clustering

Dynamic state recognition and event-prediction are fundamental tasks in biomedical signal processing. The authors present a new, electroencephalogram (EEG)-based, brain-state identification method which could form the basis for forecasting a generalized epileptic seizure. The method relies on the existence in the EEG of a preseizure state, with extractable unique features, a priori undefined. The authors exposed 25 rats to hyperbaric oxygen until the appearance of a generalized EEG seizure. EEG segments from the preexposure, early exposure, and the period up to and including the seizure were processed by the fast wavelet transform. Features extracted from the wavelet coefficients were inputted to the unsupervised optimal fuzzy clustering (UOFC) algorithm. The UOFC is useful for classifying similar discontinuous temporal patterns in the semistationary EEG to a set of clusters which may represent brain-states. The unsupervised selection of the number of clusters overcomes the a priori unknown and variable number of states. The usually vague brain state transitions are naturally treated by assigning each temporal pattern to one or more fuzzy clusters. The classification succeeded in identifying several, behavior-backed, EEG states such as sleep, resting, alert and active wakefulness, as well as the seizure. In 16 instances a preseizure state, lasting between 0.7 and 4 min was defined. Considerable individual variability in the number and characteristics of the clusters may postpone the realization of an early universal epilepsy warning. Universality may not be crucial if using a dynamic version of the UOFC which has been taught the individual's normal vocabulary of EEG states and can be expected to detect unspecified new states     

Hilbert Transform and Statistical Analysis for Channel Selection and Epileptic Seizure Prediction

This paper is concerned with Electroencephalography (EEG) seizure prediction, which means the detection of the pre-ictal state prior to ictal activity occurrence. The basic idea of the proposed approach for EEG seizure prediction is to work on the signals in the Hilbert domain. The operation in the Hilbert domain guarantees working on the low-pass spectra of EEG signal segments to avoid artifacts. Signal attributes in the Hilbert domain including amplitude, derivative, local mean, local variance, and median are analyzed statistically to perform the channel selection and seizure prediction tasks. Pre-defined prediction and false-alarm probabilities are set to select the channels, the attributes, and bins of probability density functions (PDFs) that can be useful for seizure prediction. Due to the multi-channel nature of this process, there is a need for a majority voting strategy to take a decision for each signal segment. Simulation results reveal an average prediction rate of 96.46%, an average false-alarm rate of 0.028077/h and an average prediction time of 60.1595 min for a 90-min prediction horizon.

     

Analysis of Intracerebral EEG Recordings of Epileptic Spikes: Insights From a Neural Network Model

The pathophysiological interpretation of EEG signals recorded with depth electrodes [i.e., local field potentials (LFPs)] during interictal (between seizures) or ictal (during seizures) periods is fundamental in the presurgical evaluation of patients with drug-resistant epilepsy. Our objective was to explain specific shape features of interictal spikes in the hippocampus (observed in LFPs) in terms of cell- and network-related parameters of neuronal circuits that generate these events. We developed a neural network model based on “minimal” but biologically relevant neuron models interconnected through GABAergic and glutamatergic synapses that reproduce the main physiological features of the CA1 subfield. Simulated LFPs were obtained by solving the forward problem (dipole theory) from networks including a large number ($sim$3000) of cells. Insertion of appropriate parameters allowed the model to simulate events that closely resemble actual epileptic spikes. Moreover, the shape of the early fast component (``spike') and the late slow component (``negative wave') was linked to the relative contribution of glutamatergic and GABAergic synaptic currents in pyramidal cells. In addition, the model provides insights about the sensitivity of electrode localization with respect to recorded tissue volume and about the relationship between the LFP and the intracellular activity of principal cells and interneurons represented in the network.      

Enhancement of phase clustering in the EEG/MEG gamma frequency band anticipates transitions to paroxysmal epileptiform activity in epileptic patients with known visual sensitivity

A new analytical method for quantifying brain activity from magnetoelectroencephalogram (MEG) and electroencephalogram (EEG) recordings during periodic light stimulation is proposed. It consists in estimating the phase clustering of harmonically related frequency components of a subject's MEG/EEG responses evoked by the light stimulation. The method was developed to test the hypothesis that changes in the dynamics of brain systems in the course of intermittent photic stimulation (IPS) may precede the transition to seizure activity in photosensitive patients. We assumed that such changes would be reflected in the phase of harmonic components of the evoked responses. Thus, we determined the phase clustering for different harmonic components of these MEG/EEG signals. We found that the patients who develop epileptiform discharges during IPS present an enhancement of the phase clustering index at the gamma frequency band, compared with that at the driving frequency. We introduce a quantity--relative phase clustering index (rPCI)--by means of which this enhancement can be quantified. We argue that this quantity reflects the degree of excitability of the underlying dynamical system and it can indicate presence of nonlinear dynamics. rPCI can be applied to detect transitions to epileptic seizure activity in patients with known sensitivity to IPS.     

Extraction of spatio-temporal signatures from depth EEG seizuresignals based on objective matching in warped vectorialobservations

In the field of epilepsy, the analysis of stereoelectroencephalographic (SEEG) signals recorded with depth electrodes provides major information on interactions between brain structures during seizures. A comprehensive methodology of comparing SEEG seizure recordings is presented. It proceeds in three steps: 1) segmentation of SEEG signals; 2) characterization and labeling of segments; and 3) comparison of observations coded as sequences of symbol vectors. The third step reports a vectorial extension of the Wagner and Fischer's algorithm to first, quantify similarities between observations and second, extract invariant sequences of events, referred to as spatio-temporal signatures. The study shows that two observations of nonequal duration can be matched by deforming the first one to optimally fit the second, under cost constraints. Results show that the methodology allows to exhibit signatures occurring during epileptic seizures and to point out different types of seizure patterns. The study brings objective results on reproducible interactions between brain structures during ictal periods and may help in the understanding of epileptogenic networks     

Epileptic seizure detection using genetically programmed artificial features

Patient-specific epilepsy seizure detectors were designed based on the genetic programming artificial features algorithm, a general-purpose, methodic algorithm comprised by a genetic programming module and a k-nearest neighbor classifier to create synthetic features. Artificial features are an extension to conventional features, characterized by being computer-coded and may not have a known physical meaning. In this paper, artificial features are constructed from the reconstructed state-space trajectories of the intracranial EEG signals intended to reveal patterns indicative of epileptic seizure onset. The algorithm was evaluated in seven patients and validation experiments were carried out using 730.6 hr of EEG recordings. The results with the artificial features compare favorably with previous benchmark work that used a handcrafted feature. Among other results, 88 out of 92 seizures were detected yielding a low false negative rate of 4.35%.     

癫痫患者血清细胞因子水平与脑电图的相关性探讨

目的：探究癫痫患者血清细胞因子水平同脑电图之间存在的相关性。方法：将2015年4月~2016年4月期间我院收治的56例癫痫患者作为试验组,再选取同期在我院进行体检的56名健康人作为对照组,全部患者都给予常规脑电图检查。结果：试验组人员的血清肿瘤坏死因子、白细胞介素以及脑电图检测结果等都明显的比对照组高,差异具有统计学意义（P＜0.05）;其中癫痫患者的血清肿瘤坏死因子及白细胞介素之间具有显著的正相关（P＜0.05）。结论：癫痫患者一般具有细胞免疫功能紊乱的症状,免疫细胞CD8、CD4及肿瘤坏死因子（TNF）-α与白细胞介素（IL）-2等均为影响癫痫病情的关键介质。其中脑电图改变同免疫细胞CD8、CD4及TNF-α与IL-2水平等紧密相关,距离癫痫发作期越近,有关免疫细胞及细胞因子异常水平则越高,而同期脑电图异常率则越高。     

Estimation of time-varying connectivity patterns through the use of an adaptive directed transfer function

Frequency-derived identification of the propagation of information between brain regions has quickly become a popular area in the neurosciences. Of the various techniques used to study the propagation of activation within the central nervous system, the directed transfer function (DTF) has been well used to explore the functional connectivity during a variety of brain states and pathological conditions. However, the DTF method assumes the stationarity of the neural electrical signals and the time invariance of the connectivity among different channels over the investigated time window. Such assumptions may not be valid in the abnormal brain signals such as seizures and interictal spikes in epilepsy patients. In the present study, we have developed an adaptive DTF (ADTF) method through the use of a multivariate adaptive autoregressive model to study the time-variant propagation of seizures and interictal spikes in simulated electrocorticogram (ECoG) networks. The time-variant connectivity reconstruction is achieved by the Kalman filter algorithm, which can incorporate time-varying state equations. We study the performance of the proposed method through simulations with various propagation models using either sample seizures or interictal spikes as the source waveform. The present results suggest that the new ADTF method correctly captures the temporal dynamics of the propagation models, while the DTF method cannot, and even returns erroneous results in some cases. The present ADTF method was tested in real epileptiform ECoG data from an epilepsy patient, and the ADTF results are consistent with the clinical assessments performed by neurologists.      

Approximate entropy-based epileptic EEG detection using artificial neural networks.

The electroencephalogram (EEG) signal plays an important role in the diagnosis of epilepsy. The EEG recordings of the ambulatory recording systems generate very lengthy data and the detection of the epileptic activity requires a time-consuming analysis of the entire length of the EEG data by an expert. The traditional methods of analysis being tedious, many automated diagnostic systems for epilepsy have emerged in recent years. This paper proposes a neural-network-based automated epileptic EEG detection system that uses approximate entropy (ApEn) as the input feature. ApEn is a statistical parameter that measures the predictability of the current amplitude values of a physiological signal based on its previous amplitude values. It is known that the value of the ApEn drops sharply during an epileptic seizure and this fact is used in the proposed system. Two different types of neural networks, namely, Elman and probabilistic neural networks, are considered in this paper. ApEn is used for the first time in the proposed system for the detection of epilepsy using neural networks. It is shown that the overall accuracy values as high as 100% can be achieved by using the proposed system.     

Epileptic seizure prediction using hybrid feature selection over multiple intracranial EEG electrode contacts: a report of four patients

Epileptic seizure prediction has steadily evolved from its conception in the 1970s, to proof-of-principle experiments in the late 1980s and 1990s, to its current place as an area of vigorous, clinical and laboratory investigation. As a step toward practical implementation of this technology in humans, we present an individualized method for selecting electroencephalogram (EEG) features and electrode locations for seizure prediction focused on precursors that occur within ten minutes of electrographic seizure onset. This method applies an intelligent genetic search process to EEG signals simultaneously collected from multiple intracranial electrode contacts and multiple quantitative features derived from these signals. The algorithm is trained on a series of baseline and preseizure records and then validated on other, previously unseen data using split sample validation techniques. The performance of this method is demonstrated on multiday recordings obtained from four patients implanted with intracranial electrodes during evaluation for epilepsy surgery. An average probability of prediction (or block sensitivity) of 62.5% was achieved in this group, with an average block false positive (FP) rate of 0.2775 FP predictions/h, corresponding to 90.47% specificity. These findings are presented as an example of a method for training, testing and validating a seizure prediction system on data from individual patients. Given the heterogeneity of epilepsy, it is likely that methods of this type will be required to configure intelligent devices for treating epilepsy to each individual's neurophysiology prior to clinical deployment.