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In this work we apply the network physiology paradigm to retrieve information from central and autonomic nervous systems before focal epileptic seizure, represented respectively by electroencephalogram (EEG) signals and R-R intervals (RRI), and investigate on the presence and strength of brain-heart interactions by computing mutual information (MI) measures. Statistical significance of MI values was tested through surrogate time series generated with the random shuffle approach. Our results suggest that the proposed method for aligning signals representing brain and heart activity measured with different sampling rates, is capable of revealing coupling between RRI representing heart system, and aligned averaged power spectrum of brain processes, measured with EEG, resulting in significant MI. For electrodes C3, Fp2, Cz, and T4 in correspondingly α, β, γ, and total frequency bands, we obtain significantly smaller values of MI in the pre-ictal period in comparison with baseline period, as well as general decrease of significant and all estimated MI values before the focal seizure can be observed.

Scalp electroencephalographic (EEG) signals are influenced by several factors, including volume conduction and low spatial resolution, which can jeopardize the validity of brain connectivity analysis performed on the raw recordings. One possible solution is to identify, starting from scalp EEG signals, the underlying cortical source activations, and to apply connectivity metrics on the reconstructed source time series. In this work, the dynamics of information flow between cortical EEG signals obtained after source reconstruction were assessed in children suffering from focal epilepsy. In a group of 10 children with focal seizures, 5-second windows of the 19-channel EEG were obtained in the baseline, pre-ictal, and post-ictal phases. After filtering and artifact removal, 19 baseline, 19 pre-ictal, and 12 post-ictal stationary trials were selected for the analysis. Source reconstruction was performed combining a common spatial pattern algorithm with linear modeling and Indiapendent component analysis. Finally, linear measures of functional connectivity (information storage, total and conditional information transfer) were obtained from vector autoregressive models of the source signals. While the average information stored in the nodes of the source EEG network did not change significantly across conditions, the total information transferred to each node increased significantly just before the seizure onset (p=0.001) and remained high after the seizure (p=0.009). The number of directed links in the network (statistically significant values of the conditional information transfer) also increased comparing the pre-ictal and post-ictal phases with the baseline period (p=0.134, p=0.109). These results indicate that a reorganization of the source EEG network, characterized by dense topology and increased information transfer, occurs before the onset of focal seizures, which is promising for seizure prediction algorithms.

Network physiology is a recent approach describing the human body as an integrated network composed of several organ systems which continuously interact to produce healthy and diseased states. In this work, we apply the network physiology paradigm to study dynamical interactions between EEG activity and heart rate variability in children suffering from focal epilepsy. We aim to study the characteristics of brainheart coupling between, before, and after seizures to better understand the physiological mechanisms underlying seizure onset in the pre-ictal phase and the recovery of normal autonomic function in the post-ictal phase. In perspective, linking the dynamic information of brain-heart can provide useful information for a better seizure prediction. EEG and ECG data were recorded in 10 patients with focal epilepsy. After removal of baseline drift and muscle artifacts, the variability of heart rate and brain activity were measured extracting R-R intervals from the ECG and computing the spectral power of the EEG. 143 synchronous time series of 300 points were obtained in 4 different time windows (10 min and 10 sec before and after the seizure) and analyzed computing the cross-correlation coefficient (CC) and the mutual information (MI). A statistically significant increase of MI was observed just after seizure episodes (pvalue equal to 0.04, 10s before vs 10s after distributions, electrode O2), while a recovery of the baseline value was obtained 10 minutes after the episodes. This trend was found for several other EEG electrodes (Fp2, F3, F8, T3, C4, T4). On the contrary, CC did not change significantly across time windows. These results suggest that focal seizures are associated with an increased brain-heart coupling which is noticeable after seizure termination only in terms of mutual information. We conclude that focal epilepsy in childhood is associated with nonlinear brain-heart interaction mechanisms.

To evaluate the interaction between epilepsy-related brain activities and heart rate dynamics, we analyze electroencephalogram (EEG) and heart rate variability (HRV) using detrended moving-average cross-correlation analysis (DMCA) for pre- and postictal periods in subjects with focal epilepsy. The DMCA was applied to the 5 min. long periods of heart beat-to-beat intervals and power spectral density time series, located 5 and 10 min. before and after seizures. Statistically significant differences were found in the cross-correlation in δ (0.5–4 Hz) band for the periods before and after seizure, which shows the correlative coupling between RR intervals that δ band activity is changing while approaching to and after the epileptic seizure, that suggests the presence of nonlinear mechanisms of interactions between low-band EEG and RR intervals in observed periods of brain and heart activity in epilepsy. In contrast, no statistically significant changes could be observed while comparing brain-heart coupling in preictal periods. The wide scatter of distributions of all frequency bands in periods before epileptic seizure suggests that the multiscale cross-correlation coefficient is highly subject dependent and needs further subject-specific analysis for this particular period with longer time series.

This study introduces a framework for the information-theoretic analysis of brain functional connectivity performed at the level of electroencephalogram (EEG) sources. The framework combines the use of common spatial patterns to select the EEG components which maximize the variance between two experimental conditions, simultaneous implementation of vector autoregressive modeling (VAR) with independent component analysis to describe the joint source dynamics and their projection to the scalp, and computation of information dynamics measures (information storage, information transfer, statistically significant network links) from the source VAR parameters. The proposed framework was tested on simulated EEGs obtained mixing source signals generated under different coupling conditions, showing its ability to retrieve source information dynamics from the scalp signals. Then, it was applied to investigate scalp and source brain connectivity in a group of children manifesting episodes of focal and generalized epilepsy, the analysis was performed on EEG signals lasting 5 s, collected in two consecutive windows preceding and one window following each ictal episode. Our results show that generalized seizures are associated with a significant decrease from pre-ictal to post-ictal periods of the information stored in the signals and of the information transferred among them, reflecting reduced self-predictability and causal connectivity at the level of both scalp and source brain dynamics. On the contrary, in the case of focal seizures the scalp EEG activity was not discriminated across conditions by any information measure, while source analysis revealed a tendency of the measures of information transfer to increase just before seizures and to decrease just after seizures. These results suggest that focal epileptic seizures are associated with a reorganization of the topology of EEG brain networks which is only visible analyzing connectivity among the brain sources. Our findings emphasize the importance of EEG modeling approaches able to deal with the adverse effects of volume conduction on brain connectivity analysis, and their potential relevance to the development of strategies for prediction and clinical treatment of epilepsy.

In this work, partial information decomposition (PID) was applied to the time series of heart rate and EEG amplitude variability to investigate the dynamical interactions in brain-heart coupling before and after epileptic seizures. From ECG and EEG signals collected on 23 children suffering from focal epilepsy, the RR intervals and the EEG variance at ipsilateral and contralateral temporal electrodes were computed in four different time windows before and after the seizures. Static PID was used to obtain redundant, unique and synergistic components of the total information shared between the series of RR and EEG variance. Results highlight, in the progression from preictal to postictal states, a statistically significant change of mutual information at the ipsilateral electrode and of the synergy between brain locations.

In this work, we analyze the information content of the multiple time scale components of heart rate variability (HRV) in children with focal epilepsy. HRV components are extracted from 30 pediatric patients, monitored 10 min and 10 s before and after focal epileptic seizures, using wavelet multiscale decomposition (with 5, 15, 30, 60, 120, 180 s time scale), and then characterized computing Entropy (E), permutation entropy (PE), conditional entropy (CE) and information storage (IS). Moving from preictal to postictal windows, we find statistically significant differences in the CE and IS values of HRV components at short time scales, which reflect autonomic imbalance and appear as potential candidates of descriptive features for HRV monitoring in epilepsy.

Introduction. Brain electrical activity signals (or EEG) by their very nature are non-stationary time series. This basically allows applying a set of mathematical-statistical analysis methods to them. One of the most common methods for signal analyzing is the construction of autoregressive mathematical models and analysis of their parameters in order to obtain additional information about the signal itself or causality between signals. In multivariate autoregressive (MVAR) modeling of EEG, the main issue is the optimal choice of model order. In this work, the approach for selecting the optimal order of MVAR models of brain electrical activity signals of subjects diagnosed with epilepsy is proposed. MVAR modeling. The autoregressive model assumes that the current sample of the discrete signal can be linearly predicted as a weighted sum of its previous samples. MVAR model extends this assumption to multiple time series so that the vector of current samples of all signals is modeled as a linear sum of their previous samples. MVAR models of EEG signals essentially are formed by solving systems of linear equations. The Yule-Walker method of linear equations systems solving is used in this paper. The accuracy of EEG modeling depends on the order of model. Each model order influenced by the amount of delay between current samples and last previous samples used to generate the model. To assess the order and quality of models the Schwarz-Bayes information criterion (SBC) is used in this work taking into account the covariance matrix of the residuals. Additionally, the quality is assessed by Pearson's correlation coefficient between the real and simulated data. In this paper, the MVAR modeling and statistical analysis of the models' optimal orders of the input signal periods before, during and after an epileptic seizure is carried out. Experimental results. Two sets of EEG data with generalized and focal epileptic seizures are used. The first group of patients with focal seizures consists of 26 people and more than 100 epileptic seizures. The second group with generalized seizures consists of 11 people and about 50 epileptic seizures. For EEG signals modeling, values of orders in a range from 1 to 22 are used. Consequently, for each investigated period of signal (before, during and after a seizure), 22 different MVAR models are constructed and compared. After modeling, the obtained models for each order value are evaluated using the SBC criterion. Conclusions. According to the results, it is recommended to choose the order of MVAR models of EEG signals in the predefined range of orders from 11 to 13. Since the sampling rate of the signals used in these experiments is 250 Hz, the specified range of order values indicates that MVAR-modelling of one signal includes information that contains all other signals with a delay of 44-52 ms. Therefore, theoretically, it is possible to allocate functional characteristics of brain electrical activity for patients with epilepsy that occur synchronously in different parts of the brain and spread at an average of 50 ms. Moreover, the ways of further research of electrical brain activity and functional connections of brain regions during epileptic activity are indicated.

OBJECTIVE In this work we explore the potential of combining standard time and frequency domain indexes with novel information measures, to characterize pre- and post-ictal heart rate variability (HRV) in epileptic children, with the aim of differentiating focal and generalized epilepsy regarding the autonomic control mechanisms. APPROACH We analyze short-term HRV in 37 children suffering from generalized or focal epilepsy, monitored 10 s, 300 s, 600 s and 1800 s both before and after seizure episodes. Nine indexes are computed in time (mean, standard deviation of normal-to-normal intervals, root mean square of the successive differences (RMSSD)), frequency (low-to-high frequency power ratio LF/HF, normalized LF and HF power) and information (entropy, conditional entropy and self-entropy) domains. Focal and generalized epilepsy are compared through statistical analysis of the indexes and using linear discriminant analysis (LDA). MAIN RESULTS In children with focal epilepsy, early post-ictal phase is characterized by significant tachycardia, depressed HRV, increased LF power and LF/HF, and decreased complexity, progressively recovered across time windows after the episodes. Children with generalized seizures instead show significant tachycardia, lower RMSSD, higher LF power and LF/HF ratio before the seizure. These different behaviors are exploited by LDA analysis to separate focal and generalized epilepsy up to an accuracy of 75%. Results suggest a shift of the sympatho-vagal balance towards sympathetic dominance and vagal withdrawal, noticeable just after the termination of seizure episodes and then reverted in focal epilepsy, and persistent during inter-ictal and pre-ictal periods in generalized epilepsy. SIGNIFICANCE Our analysis helps in elucidating the pathophysiology of inter-ictal HRV autonomic control and the differential diagnosis of generalized and focal epilepsy. These findings may have clinical relevance since altered sympatho-vagal control can be related to a higher danger of morbidity and mortality, may reduce thresholds for life-threatening arrhythmias, and could be a biomarker of risk for sudden unexpected death in epilepsy.

In this research, the study of functional connectivity between sources of electroencephalogram (EEG) activity assessed for different classes (well before seizure, preictal and post-ictal) was performed. EEG recordings were acquired from 12 subjects with focal epilepsy. Then, ten common spatial patterns (CSP) were obtained for EEG segments describing 95% of Riemannian distance between pairs of classes, followed by estimation of multivariate autoregressive (MVAR) models’ coefficients. The MVAR models were further used to extract coherence as a functional connectivity measures. Our results show that the coherence between CSP sources differs between baseline and pre-ictal segments: it has the larger values in low and high frequency ranges during pre-ictal segment. This might correspond to increased coupling of slow and fast oscillations just before the seizure onset which poses a defining attribute of epileptiform activity. Our results indicate that a reorganization of EEG source activations occurs before the onset of focal seizures, which is promising for seizure prediction algorithms.