Mapping the epileptic brain with EEG dynamical connectivity: established methods and novel approaches

Several algorithms rooted in statistical physics, mathematics and machine learning are used to analyze neuroimaging data from patients suffering from epilepsy, with the main goals of localizing the brain region where the seizure originates from and of detecting upcoming seizure activity in order to trigger therapeutic neurostimulation devices. Some of these methods explore the dynamical connections between brain regions, exploiting the high temporal resolution of the electroencephalographic signals recorded at the scalp or directly from the cortical surface or in deeper brain areas. In this paper we describe this specific class of algorithms and their clinical application, by reviewing the state of the art and reporting their application on EEG data from an epileptic patient

Oscillatory Network Activity in Brain Functions and Dysfunctions

Recent experimental studies point to the notion that the brain is a complex dynamical system whose behaviors relating to brain functions and dysfunctions can be described by the physics of network phenomena. The brain consists of anatomical axonal connections among neurons and neuronal populations in various spatial scales. Neuronal interactions and synchrony of neuronal oscillations are central to normal brain functions. Breakdowns in interactions and modifications in synchronization behaviors are usual hallmarks of brain dysfunctions. Here, in this dissertation for PhD degree in physics, we report discoveries of brain oscillatory network activity from two separate studies. These studies investigated the large-scale brain activity during tactile perceptual decision-making and epileptic seizures. In the perceptual decision-making study, using scalp electroencephalography (EEG) recordings of brain potentials, we investigated how oscillatory activity functionally organizes different neocortical regions as a network during a tactile discrimination task. While undergoing EEG recordings, blindfolded healthy participants felt a linear three-dot array presented electromechanically, under computer control, and reported whether the central dot was offset to the left or right. Based on the current dipole modeling in the brain, we found that the source-level peak activity appeared in the left primary somatosensory cortex (SI), right lateral occipital complex (LOC), right posterior intraparietal sulcus (pIPS) and finally left dorsolateral prefrontal cortex (dlPFC) at 45, 130, 160 and 175 ms respectively. Spectral interdependency analysis showed that fine tactile discrimination is mediated by distinct but overlapping ~15 Hz beta and ~80 Hz gamma band large-scale oscillatory networks. The beta-network that included all four nodes was dominantly feedforward, similar to the propagation of peak cortical activity, implying its role in accumulating and maintaining relevant sensory information and mapping to action. The gamma-network activity, occurring in a recurrent loop linked SI, pIPS and dlPFC, likely carrying out attentional selection of task-relevant sensory signals. Behavioral measure of task performance was correlated with the network activity in both bands. In the study of epileptic seizures, we investigated high-frequency (\u3e 50 Hz) oscillatory network activity from intracranial EEG (IEEG) recordings of patients who were the candidates for epilepsy surgery. The traditional approach of identifying brain regions for epilepsy surgery usually referred as seizure onset zones (SOZs) has not always produced clarity on SOZs. Here, we investigated directed network activity in the frequency domain and found that the high frequency (\u3e80 Hz) network activities occur before the onset of any visible ictal activity, andcausal relationships involve the recording electrodes where clinically identifiable seizures later develop. These findings suggest that high-frequency network activities and their causal relationships can assist in precise delineation of SOZs for surgical resection

Thalamocortical relationship in epileptic patients with generalized spike and wave discharges — A multimodal neuroimaging study

AbstractUnlike focal or partial epilepsy, which has a confined range of influence, idiopathic generalized epilepsy (IGE) often affects the whole or a larger portion of the brain without obvious, known cause. It is important to understand the underlying network which generates epileptic activity and through which epileptic activity propagates. The aim of the present study was to investigate the thalamocortical relationship using non-invasive imaging modalities in a group of IGE patients. We specifically investigated the roles of the mediodorsal nuclei in the thalami and the medial frontal cortex in generating and spreading IGE activities. We hypothesized that the connectivity between these two structures is key in understanding the generation and propagation of epileptic activity in brains affected by IGE. Using three imaging techniques of EEG, fMRI and EEG-informed fMRI, we identified important players in generation and propagation of generalized spike-and-wave discharges (GSWDs). EEG-informed fMRI suggested multiple regions including the medial frontal area near to the anterior cingulate cortex, mediodorsal nuclei of the thalamus, caudate nucleus among others that related to the GSWDs. The subsequent seed-based fMRI analysis revealed a reciprocal cortical and bi-thalamic functional connection. Through EEG-based Granger Causality analysis using (DTF) and adaptive DTF, within the reciprocal thalamocortical circuitry, thalamus seems to serve as a stronger source in driving cortical activity from initiation to the propagation of a GSWD. Such connectivity change starts before the GSWDs and continues till the end of the slow wave discharge. Thalamus, especially the mediodorsal nuclei, may serve as potential targets for deep brain stimulation to provide more effective treatment options for patients with drug-resistant generalized epilepsy

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

Generalized Partial Directed Coherence and centrality measures in brain networks for epileptogenic focus localization

Accurate epileptogenic focus localization is required prior to surgical resection of brain tissue for treatment of patients with intractable temporal lobe epilepsy, a clinical need that is partially fulfilled to date through a subjective, and at times inconclusive, evaluation of the recorded electroencephalogram (EEG). Using brain connectivity analysis, patterns of causal interactions between brain regions were derived from multichannel EEG of 127 seizures in nine patients with focal, temporal lobe epilepsy (TLE). The statistically significant directed interactions in the reconstructed brain networks were estimated from three second intracranial multi-electrode EEG segments using the Generalized Partial Directed Coherence (GPDC) and validated by surrogate data analysis. A set of centralities per network node were then estimated. Compared to extra-focal brain regions, regions located anatomically within the epileptogenic focus (focal regions) were found to be associated with enhanced inward directed centrality values at high frequencies (y band) during the initial segments of seizures (within nine seconds from seizures onset) and led to correct localization of the epileptogenic focus in all nine patients. Therefore, an immediate application of the employed novel network framework of analysis to intracranial EEG recordings may lead to a computerized, accurate and objective localization of the epileptogenic focus from ictal periods. The proposed framework could also pave the way for studies into network dynamics of the epileptogenic focus peri-ictally and interictally, which may have a significant impact on current automated seizure prediction and control applications

Estimating EEG Source Dipole Orientation Based on Singular-value Decomposition for Connectivity Analysis.

In the last decade, the use of high-density electrode arrays for EEG recordings combined with the improvements of source reconstruction algorithms has allowed the investigation of brain networks dynamics at a sub-second scale. One powerful tool for investigating large-scale functional brain networks with EEG is time-varying effective connectivity applied to source signals obtained from electric source imaging. Due to computational and interpretation limitations, the brain is usually parcelled into a limited number of regions of interests (ROIs) before computing EEG connectivity. One specific need and still open problem is how to represent the time- and frequency-content carried by hundreds of dipoles with diverging orientation in each ROI with one unique representative time-series. The main aim of this paper is to provide a method to compute a signal that explains most of the variability of the data contained in each ROI before computing, for instance, time-varying connectivity. As the representative time-series for a ROI, we propose to use the first singular vector computed by a singular-value decomposition of all dipoles belonging to the same ROI. We applied this method to two real datasets (visual evoked potentials and epileptic spikes) and evaluated the time-course and the frequency content of the obtained signals. For each ROI, both the time-course and the frequency content of the proposed method reflected the expected time-course and the scalp-EEG frequency content, representing most of the variability of the sources (~ 80%) and improving connectivity results in comparison to other procedures used so far. We also confirm these results in a simulated dataset with a known ground truth

Hippocampal Sleep Features: Relations to Human Memory Function

The recent spread of intracranial electroencephalographic (EEG) recording techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific patterns of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, non-REM sleep) in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples) that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate sleep function