Dynamic imaging of coherent sources reveals different network connectivity underlying the generation and perpetuation of epileptic seizures

The concept of focal epilepsies includes a seizure origin in brain regions with hyper synchronous activity (epileptogenic zone and seizure onset zone) and a complex epileptic network of different brain areas involved in the generation, propagation, and modulation of seizures. The purpose of this work was to study functional and effective connectivity between regions involved in networks of epileptic seizures. The beginning and middle part of focal seizures from ictal surface EEG data were analyzed using dynamic imaging of coherent sources (DICS), an inverse solution in the frequency domain which describes neuronal networks and coherences of oscillatory brain activities. The information flow (effective connectivity) between coherent sources was investigated using the renormalized partial directed coherence (RPDC) method. In 8/11 patients, the first and second source of epileptic activity as found by DICS were concordant with the operative resection site; these patients became seizure free after epilepsy surgery. In the remaining 3 patients, the results of DICS / RPDC calculations and the resection site were discordant; these patients had a poorer post-operative outcome. The first sources as found by DICS were located predominantly in cortical structures; subsequent sources included some subcortical structures: thalamus, Nucl. Subthalamicus and cerebellum. DICS seems to be a powerful tool to define the seizure onset zone and the epileptic networks involved. Seizure generation seems to be related to the propagation of epileptic activity from the primary source in the seizure onset zone, and maintenance of seizures is attributed to the perpetuation of epileptic activity between nodes in the epileptic network. Despite of these promising results, this proof of principle study needs further confirmation prior to the use of the described methods in the clinical praxis

Neuronal networks in children with continuous spikes and waves during slow sleep

Epileptic encephalopathy with continuous spikes and waves during slow sleep is an age-related disorder characterized by the presence of interictal epileptiform discharges during at least >85% of sleep and cognitive deficits associated with this electroencephalography pattern. The pathophysiological mechanisms of continuous spikes and waves during slow sleep and neuropsychological deficits associated with this condition are still poorly understood. Here, we investigated the haemodynamic changes associated with epileptic activity using simultaneous acquisitions of electroencephalography and functional magnetic resonance imaging in 12 children with symptomatic and cryptogenic continuous spikes and waves during slow sleep. We compared the results of magnetic resonance to electric source analysis carried out using a distributed linear inverse solution at two time points of the averaged epileptic spike. All patients demonstrated highly significant spike-related positive (activations) and negative (deactivations) blood oxygenation-level-dependent changes (P < 0.05, family-wise error corrected). The activations involved bilateral perisylvian region and cingulate gyrus in all cases, bilateral frontal cortex in five, bilateral parietal cortex in one and thalamus in five cases. Electrical source analysis demonstrated a similar involvement of the perisylvian brain regions in all patients, independent of the area of spike generation. The spike-related deactivations were found in structures of the default mode network (precuneus, parietal cortex and medial frontal cortex) in all patients and in caudate nucleus in four. Group analyses emphasized the described individual differences. Despite aetiological heterogeneity, patients with continuous spikes and waves during slow sleep were characterized by activation of the similar neuronal network: perisylvian region, insula and cingulate gyrus. Comparison with the electrical source analysis results suggests that the activations correspond to both initiation and propagation pathways. The deactivations in structures of the default mode network are consistent with the concept of epileptiform activity impacting on normal brain function by inducing repetitive interruptions of neurophysiological functio

With or without spikes: localization of focal epileptic activity by simultaneous electroencephalography and functional magnetic resonance imaging

In patients with medically refractory focal epilepsy who are candidates for epilepsy surgery, concordant non-invasive neuroimaging data are useful to guide invasive electroencephalographic recordings or surgical resection. Simultaneous electroencephalography and functional magnetic resonance imaging recordings can reveal regions of haemodynamic fluctuations related to epileptic activity and help localize its generators. However, many of these studies (40-70%) remain inconclusive, principally due to the absence of interictal epileptiform discharges during simultaneous recordings, or lack of haemodynamic changes correlated to interictal epileptiform discharges. We investigated whether the presence of epilepsy-specific voltage maps on scalp electroencephalography correlated with haemodynamic changes and could help localize the epileptic focus. In 23 patients with focal epilepsy, we built epilepsy-specific electroencephalographic voltage maps using averaged interictal epileptiform discharges recorded during long-term clinical monitoring outside the scanner and computed the correlation of this map with the electroencephalographic recordings in the scanner for each time frame. The time course of this correlation coefficient was used as a regressor for functional magnetic resonance imaging analysis to map haemodynamic changes related to these epilepsy-specific maps (topography-related haemodynamic changes). The method was first validated in five patients with significant haemodynamic changes correlated to interictal epileptiform discharges on conventional analysis. We then applied the method to 18 patients who had inconclusive simultaneous electroencephalography and functional magnetic resonance imaging studies due to the absence of interictal epileptiform discharges or absence of significant correlated haemodynamic changes. The concordance of the results with subsequent intracranial electroencephalography and/or resection area in patients who were seizure free after surgery was assessed. In the validation group, haemodynamic changes correlated to voltage maps were similar to those obtained with conventional analysis in 5/5 patients. In 14/18 patients (78%) with previously inconclusive studies, scalp maps related to epileptic activity had haemodynamic correlates even when no interictal epileptiform discharges were detected during simultaneous recordings. Haemodynamic changes correlated to voltage maps were spatially concordant with intracranial electroencephalography or with the resection area. We found better concordance in patients with lateral temporal and extratemporal neocortical epilepsy compared to medial/polar temporal lobe epilepsy, probably due to the fact that electroencephalographic voltage maps specific to lateral temporal and extratemporal epileptic activity are more dissimilar to maps of physiological activity. Our approach significantly increases the yield of simultaneous electroencephalography and functional magnetic resonance imaging to localize the epileptic focus non-invasively, allowing better targeting for surgical resection or implantation of intracranial electrode array

Causality within the Epileptic Network: An EEG-fMRI Study Validated by Intracranial EEG

Accurate localization of the Seizure Onset Zone (SOZ) is crucial in patients with drug-resistance focal epilepsy. EEG with fMRI recording (EEG-fMRI) has been proposed as a complementary non-invasive tool, which can give useful additional information in the pre-surgical work-up. However, fMRI maps related to interictal epileptiform activities (IED) often show multiple regions of signal change, or "networks," rather than highly focal ones. Effective connectivity approaches like Dynamic Causal Modeling (DCM) applied to fMRI data potentially offers a framework to address which brain regions drives the generation of seizures and IED within an epileptic network. Here, we present a first attempt to validate DCM on EEG-fMRI data in one patient affected by frontal lobe epilepsy. Pre-surgical EEG-fMRI demonstrated two distinct clusters of blood oxygenation level dependent (BOLD) signal increases linked to IED, one located in the left frontal pole and the other in the ipsilateral dorso-lateral frontal cortex. DCM of the IED-related BOLD signal favored a model corresponding to the left dorso-lateral frontal cortex as driver of changes in the fronto-polar region. The validity of DCM was supported by: (a) the results of two different non-invasive analysis obtained on the same dataset: EEG source imaging (ESI), and "psycho-physiological interaction" analysis; (b) the failure of a first surgical intervention limited to the fronto-polar region; (c) the results of the intracranial EEG monitoring performed after the first surgical intervention confirming a SOZ located over the dorso-lateral frontal cortex. These results add evidence that EEG-fMRI together with advanced methods of BOLD signal analysis is a promising tool that can give relevant information within the epilepsy surgery diagnostic work-up

Chapter Sleep Spindles – As a Biomarker of Brain Function and Plasticity

Alternative & renewable energy sources & technolog

Sleep Spindles – As a Biomarker of Brain Function and Plasticity

Alternative & renewable energy sources & technolog

Patient-specific detection of cerebral blood flow alterations as assessed by arterial spin labeling in drug-resistant epileptic patients

Electrophysiological and hemodynamic data can be integrated to accurately and precisely identify the generators of abnormal electrical activity in drug-resistant focal epilepsy. Arterial Spin Labeling (ASL), a magnetic resonance imaging (MRI) technique for quantitative noninvasive measurement of cerebral blood flow (CBF), can provide a direct measure of variations in cerebral perfusion associated with the epileptic focus. In this study, we aimed to confirm the ASL diagnostic value in the identification of the epileptogenic zone, as compared to electrical source imaging (ESI) results, and to apply a template-based approach to depict statistically significant CBF alterations. Standard video-electroencephalography (EEG), high-density EEG, and ASL were performed to identify clinical seizure semiology and noninvasively localize the epileptic focus in 12 drug-resistant focal epilepsy patients. The same ASL protocol was applied to a control group of 17 healthy volunteers from which a normal perfusion template was constructed using a mixed-effect approach. CBF maps of each patient were then statistically compared to the reference template to identify perfusion alterations. Significant hypo- and hyperperfused areas were identified in all cases, showing good agreement between ASL and ESI results. Interictal hypoperfusion was observed at the site of the seizure in 10/12 patients and early postictal hyperperfusion in 2/12. The epileptic focus was correctly identified within the surgical resection margins in the 5 patients who underwent lobectomy, all of which had good postsurgical outcomes. The combined use of ESI and ASL can aid in the noninvasive evaluation of drug-resistant epileptic patients

Electrophysiological correlates of the BOLD signal for EEG-informed fMRI

EEG and fMRI are important tools in cognitive and clinical neuroscience. Combined EEGfMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological-haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals, and proceed by reviewing EEG-informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (“EEG-fMRI mapping”), or exploring a range of EEGderived quantities to determine which best explain co-localised BOLD fluctuations (“local EEG-fMRI coupling”). While reviewing studies of different forms of brain activity (epileptic and non-epileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG-informed fMRI. Our review is focused on EEG-informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG-informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG-fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations

CPD – Education and Self-assessment: Functional imaging in epilepsy

AbstractFunctional imaging plays a growing role in the clinical assessment and research investigation of patients with epilepsy. This article reviews the literature on functional MRI (fMRI) investigation of EEG activity, fMRI evaluation of cognitive and motor functions, magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT) and positron emission tomography (PET) in epilepsy. The place of these techniques in clinical evaluation and their contribution to a better neurobiological understanding of epilepsy are discussed