There is growing evidence for the benefits of simultaneous EEG-fMRI as a non-invasive localising tool in the presurgical evaluation of epilepsy. However, many EEG-fMRI studies fail due to the absence of interictal epileptic discharges (IEDs) on EEG. Here we present an algorithm which makes use of fMRI as sole modality to localise the epileptogenic zone (EZ). Recent studies using various model-based or data-driven fMRI analysis techniques showed that it is feasible to find activation maps which are helpful in the detection of the EZ. However, there is lack of evidence that these techniques can be used prospectively, due to (a) their low specificity, (b) selecting multiple activation maps, or (c) a widespread epileptic network indicated by the selected maps. In the current study we present a method based on independent component analysis and a cascade of classifiers that exclusively detects a single map related to interictal epileptic brain activity. In order to establish the sensitivity and specificity of the proposed method, it was evaluated on a group of 18 EEG-negative patients with a single well-defined EZ and 13 healthy controls. The results show that our method provides maps which correctly indicate the EZ in several (N=4) EEG-negative cases but at the same time maintaining a high specificity (92%). We conclude that our fMRI-based approach can be used in a prospective manner, and can extend the applicability of fMRI to EEG-negative cases.

SUMMARYObjective: Epilepsy is increasingly recognized as a network disorder, but the spatial relationship between ictal and interictal networks is still largely unexplored. In this work, we compared hemodynamic changes related to seizures and interictal spikes on a whole brain scale. Methods: Twenty-eight patients with refractory focal epilepsy (14 temporal and 14 extratemporal lobe) underwent both subtraction ictal single photon emission computed tomography (SPECT) coregistered to magnetic resonance imaging (MRI) (SISCOM) and spike-related electroencephalography (EEG-functional MRI (fMRI). SISCOM visualized relative perfusion changes during seizures, whereas EEG-fMRI mapped blood oxygen level-dependent (BOLD) changes related to spikes. Similarity between statistical maps of both modalities was analyzed per patient using the following two measures: (1) correlation between unthresholded statistical maps (Pearson's correlation coefficient) and (2) overlap between thresholded images (Dice coefficient). Overlap was evaluated at a regional level, for hyperperfusions and activations and for hypoperfusions and deactivations separately, using different thresholds. Nonparametric permutation tests were applied to assess statistical significance (p ≤ 0.05). Results: We found significant and positive correlations between hemodynamic changes related to seizures and spikes in 27 (96%) of 28 cases (median correlation coefficient 0.29 [range À0.12 to 0.62]). In 20 (71%) of 28 cases, spatial overlap between hyperperfusion on SISCOM and activation on EEG-fMRI was significantly larger than expected by chance. Congruent changes were not restricted to the territory of the presumed epileptogenic zone, but could be seen at distant sites (e.g., cerebellum and basal ganglia). Overlap between ictal hypoperfusion and interictal deactivation was statistically significant in 22 (79%) of 28 patients. Despite the high rate of congruence, discrepancies were observed for both modalities. Significance: We conclude that hemodynamic changes related to seizures and spikes varied spatially with the same sign and within a common network. Overlap was present in regions nearby and distant from discharge origin.

Simultaneous EEG-fMRI has proven to be useful in localizing interictal epileptic activity. However, the applicability of traditional GLM-based analysis is limited as interictal spikes are often not seen on the EEG inside the scanner. Therefore, we aim at extracting epileptic activity purely from the fMRI time series using independent component analysis (ICA). To our knowledge, we show for the first time that ICA can find sources related to epileptic activity in patients where no interictal spikes were recorded in the EEG. The epileptic components were identified retrospectively based on the known localization of the ictal onset zone (IOZ). We demonstrate that the selected components truly correspond to epileptic activity, as sources extracted from patients resemble significantly better the IOZ than sources found in healthy controls. Furthermore, we show that the epileptic components in patients with and without spikes recorded inside the scanner resemble the IOZ in the same degree. We conclude that ICA of fMRI has the potential to extend the applicability of EEG-fMRI for presurgical evaluation in epilepsy.