The spatio-temporal mapping of epileptic networks: Combination of EEG–fMRI and EEG source imaging

Simultaneous EEG–fMRI acquisitions in patients with epilepsy often reveal distributed patterns of Blood Oxygen Level Dependant (BOLD) change correlated with epileptiform discharges. We investigated if electrical source imaging (ESI) performed on the interictal epileptiform discharges (IED) acquired during fMRI acquisition could be used to study the dynamics of the networks identified by the BOLD effect, thereby avoiding the limitations of combining results from separate recordings. Nine selected patients (13 IED types identified) with focal epilepsy underwent EEG–fMRI. Statistical analysis was performed using SPM5 to create BOLD maps. ESI was performed on the IED recorded during fMRI acquisition using a realistic head model (SMAC) and a distributed linear inverse solution (LAURA). ESI could not be performed in one case. In 10/12 remaining studies, ESI at IED onset (ESIo) was anatomically close to one BOLD cluster. Interestingly, ESIo was closest to the positive BOLD cluster with maximal statistical significance in only 4/12 cases and closest to negative BOLD responses in 4/12 cases. Very small BOLD clusters could also have clinical relevance in some cases. ESI at later time frame (ESIp) showed propagation to remote sources co-localised with other BOLD clusters in half of cases. In concordant cases, the distance between maxima of ESI and the closest EEG–fMRI cluster was less than 33 mm, in agreement with previous studies. We conclude that simultaneous ESI and EEG–fMRI analysis may be able to distinguish areas of BOLD response related to initiation of IED from propagation areas. This combination provides new opportunities for investigating epileptic networks

Network perspectives on epilepsy using EEG/MEG source connectivity

The evolution of EEG/MEG source connectivity is both, a promising, and controversial advance in the characterization of epileptic brain activity. In this narrative review we elucidate the potential of this technology to provide an intuitive view of the epileptic network at its origin, the different brain regions involved in the epilepsy, without the limitation of electrodes at the scalp level. Several studies have confirmed the added value of using source connectivity to localize the seizure onset zone and irritative zone or to quantify the propagation of epileptic activity over time. It has been shown in pilot studies that source connectivity has the potential to obtain prognostic correlates, to assist in the diagnosis of the epilepsy type even in the absence of visually noticeable epileptic activity in the EEG/MEG, and to predict treatment outcome. Nevertheless, prospective validation studies in large and heterogeneous patient cohorts are still lacking and are needed to bring these techniques into clinical use. Moreover, the methodological approach is challenging, with several poorly examined parameters that most likely impact the resulting network patterns. These fundamental challenges affect all potential applications of EEG/MEG source connectivity analysis, be it in a resting, spiking, or ictal state, and also its application to cognitive activation of the eloquent area in presurgical evaluation. However, such method can allow unique insights into physiological and pathological brain functions and have great potential in (clinical) neuroscience

Bayesian multi-modal model comparison: a case study on the generators of the spike and the wave in generalized spike–wave complexes

We present a novel approach to assess the networks involved in the generation of spontaneous pathological brain activity based on multi-modal imaging data. We propose to use probabilistic fMRI-constrained EEG source reconstruction as a complement to EEG-correlated fMRI analysis to disambiguate between networks that co-occur at the fMRI time resolution. The method is based on Bayesian model comparison, where the different models correspond to different combinations of fMRI-activated (or deactivated) cortical clusters. By computing the model evidence (or marginal likelihood) of each and every candidate source space partition, we can infer the most probable set of fMRI regions that has generated a given EEG scalp data window. We illustrate the method using EEG-correlated fMRI data acquired in a patient with ictal generalized spike–wave (GSW) discharges, to examine whether different networks are involved in the generation of the spike and the wave components, respectively. To this effect, we compared a family of 128 EEG source models, based on the combinations of seven regions haemodynamically involved (deactivated) during a prolonged ictal GSW discharge, namely: bilateral precuneus, bilateral medial frontal gyrus, bilateral middle temporal gyrus, and right cuneus. Bayesian model comparison has revealed the most likely model associated with the spike component to consist of a prefrontal region and bilateral temporal–parietal regions and the most likely model associated with the wave component to comprise the same temporal–parietal regions only. The result supports the hypothesis of different neurophysiological mechanisms underlying the generation of the spike versus wave components of GSW discharges

Simultaneous intracranial EEG and fMRI of interictal epileptic discharges in humans

Simultaneous scalp EEG–fMRI measurements allow the study of epileptic networks and more generally, of the coupling between neuronal activity and haemodynamic changes in the brain. Intracranial EEG (icEEG) has greater sensitivity and spatial specificity than scalp EEG but limited spatial sampling. We performed simultaneous icEEG and functional MRI recordings in epileptic patients to study the haemodynamic correlates of intracranial interictal epileptic discharges (IED). Two patients undergoing icEEG with subdural and depth electrodes as part of the presurgical assessment of their pharmaco-resistant epilepsy participated in the study. They were scanned on a 1.5 T MR scanner following a strict safety protocol. Simultaneous recordings of fMRI and icEEG were obtained at rest. IED were subsequently visually identified on icEEG and their fMRI correlates were mapped using a general linear model (GLM). On scalp EEG–fMRI recordings performed prior to the implantation, no IED were detected. icEEG–fMRI was well tolerated and no adverse health effect was observed. intra-MR icEEG was comparable to that obtained outside the scanner. In both cases, significant haemodynamic changes were revealed in relation to IED, both close to the most active electrode contacts and at distant sites. In one case, results showed an epileptic network including regions that could not be sampled by icEEG, in agreement with findings from magneto-encephalography, offering some explanation for the persistence of seizures after surgery. Hence, icEEG–fMRI allows the study of whole-brain human epileptic networks with unprecedented sensitivity and specificity. This could help improve our understanding of epileptic networks with possible implications for epilepsy surgery

Cost-Effectiveness of Advanced Imaging Technologies in the Presurgical Workup of Epilepsy.

The cost-effectiveness and benefit of many diagnostic tests used in the presurgical evaluation for persons with epilepsy is for the most part uncertain as is their influence on decision-making. The options we have at our disposal are ever increasing. Advanced imaging modalities aim to improve surgical candidacy by helping us better define the epileptogenic zone and optimize surgical planning. However, judicious use is important. Randomized controlled trials delineating which mode of investigation is superior are lacking. Presurgical tests do have incremental value by increasing surgical candidacy and refining surgical planning. The yield of additional imaging will increase with complex localization. However, every case must be tailored by hypothesis, cost, and accessibility. Future studies using a quantitative cost-benefit framework are needed to determine the cost-effectiveness of advanced diagnostic tests (beyond magnetic resonance imaging) in the presurgical evaluation of those with epilepsy

EEG source connectivity to localize the seizure onset zone in patients with drug resistant epilepsy

Visual inspection of the EEG to determine the seizure onset zone (SOZ) in the context of the presurgical evaluation in epilepsy is time-consuming and often challenging or impossible. We offer an approach that uses EEG source imaging (ESI) in combination with functional connectivity analysis (FC) to localize the SOZ from ictal EEG. Ictal low-density-scalp EEG from 111 seizures in 27 patients who were rendered-seizure free after surgery was analyzed. For every seizure, ESI (LORETA) was applied on an artifact-free epoch selected around the seizure onset. Additionally, FC was applied on the reconstructed sources. We estimated the SOZ in two ways: (i)the source with highest power after ESI and (ii)the source with the most outgoing connections after ESI and FC. For both approaches, the distance between the estimated SOZ and the resected zone (RZ) of the patient were calculated. Using ESI alone, the SOZ was estimated inside the RZ in 31% of the seizures and within 10mm from the border of the RZ in 42%. For 18.5% of the patients, all seizures were estimated within 10mm of the RZ. Using ESI and FC, 72% of the seizures were estimated inside the RZ, and 94% within 10mm. For 85% of the patients, all seizures were estimated within 10mm of the RZ. FC provided a significant added value to ESI alone (p<0.001). ESI combined with subsequent FC is able to localize the SOZ in a non-invasive way with high accuracy. Therefore it could be a valuable tool in the presurgical evaluation of epilepsy

Independent component analysis of interictal fMRI in focal epilepsy: comparison with general linear model-based EEG-correlated fMRI

The general linear model (GLM) has been used to analyze simultaneous EEG–fMRI to reveal BOLD changes linked to interictal epileptic discharges (IED) identified on scalp EEG. This approach is ineffective when IED are not evident in the EEG. Data-driven fMRI analysis techniques that do not require an EEG derived model may offer a solution in these circumstances. We compared the findings of independent components analysis (ICA) and EEG-based GLM analyses of fMRI data from eight patients with focal epilepsy. Spatial ICA was used to extract independent components (IC) which were automatically classified as either BOLD-related, motion artefacts, EPI-susceptibility artefacts, large blood vessels, noise at high spatial or temporal frequency. The classifier reduced the number of candidate IC by 78%, with an average of 16 BOLD-related IC. Concordance between the ICA and GLM-derived results was assessed based on spatio-temporal criteria. In each patient, one of the IC satisfied the criteria to correspond to IED-based GLM result. The remaining IC were consistent with BOLD patterns of spontaneous brain activity and may include epileptic activity that was not evident on the scalp EEG. In conclusion, ICA of fMRI is capable of revealing areas of epileptic activity in patients with focal epilepsy and may be useful for the analysis of EEG–fMRI data in which abnormalities are not apparent on scalp EEG

Seizure-onset mapping based on time-variant multivariate functional connectivity analysis of high-dimensional intracranial EEG : a Kalman filter approach

The visual interpretation of intracranial EEG (iEEG) is the standard method used in complex epilepsy surgery cases to map the regions of seizure onset targeted for resection. Still, visual iEEG analysis is labor-intensive and biased due to interpreter dependency. Multivariate parametric functional connectivity measures using adaptive autoregressive (AR) modeling of the iEEG signals based on the Kalman filter algorithm have been used successfully to localize the electrographic seizure onsets. Due to their high computational cost, these methods have been applied to a limited number of iEEG time-series (< 60). The aim of this study was to test two Kalman filter implementations, a well-known multivariate adaptive AR model (Arnold et al. 1998) and a simplified, computationally efficient derivation of it, for their potential application to connectivity analysis of high-dimensional (up to 192 channels) iEEG data. When used on simulated seizures together with a multivariate connectivity estimator, the partial directed coherence, the two AR models were compared for their ability to reconstitute the designed seizure signal connections from noisy data. Next, focal seizures from iEEG recordings (73-113 channels) in three patients rendered seizure-free after surgery were mapped with the outdegree, a graph-theory index of outward directed connectivity. Simulation results indicated high levels of mapping accuracy for the two models in the presence of low-to-moderate noise cross-correlation. Accordingly, both AR models correctly mapped the real seizure onset to the resection volume. This study supports the possibility of conducting fully data-driven multivariate connectivity estimations on high-dimensional iEEG datasets using the Kalman filter approach

Key lesion localization and pre-surgical planning using magnetoencephalography in patients with medically refractory epilepsy: three case reports.

Epilepsy is a common and debilitating disease affecting up to 50 million people worldwide. Nearly 30% of patients with epilepsy have disease refractory to treatment with medication alone. Even in medically refractory disease, neurosurgical resection can be curative when the epileptic focus is correctly identified. Several non-invasive techniques are available for epileptic focus localization and pre-surgical planning. These include electroencephalography (EEG), magnetic resonance imaging (MRI), and magnetoencephalography&nbsp;(MEG).Each of these techniques provides complementary information for precise lesion localization and targeted neurosurgical approach to minimize damage to important adjacent structures. We present three cases of medically refractory epilepsy. The cases show how the combination of EEG, MRI, and MEG allows for lesion localization and safe surgical planning in a variety of cases. They include epilepsy related to cortical dysplasia, grey matter heterotopia, and tumor recurrence. We emphasize the role of MEG and demonstrate how it can provide critical additional information which is not captured by conventional EEG and MRI alone