Functional connectivity of the irritative zone identified by electrical source imaging, and EEG-correlated fMRI analyses

Abstract

Objective: The irritative zone - the area generating epileptic spikes - can be studied non-invasively during the interictal period using Electrical Source Imaging (ESI) and simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI). Although the techniques yield results which may overlap spatially, differences in spatial localization of the irritative zone within the same patient are consistently observed. To investigate this discrepancy, we used Blood Oxygenation Level Dependent (BOLD) functional connectivity measures to examine the underlying relationship between ESI and EEG-fMRI findings.

Methods: Fifteen patients (age 20-54), who underwent presurgical epilepsy investigation, were scanned using a single-session resting-state EEG-fMRI protocol. Structural MRI was used to obtain the electrode localisation of a high-density 64-channel EEG cap. Electrical generators of interictal epileptiform discharges were obtained using a distributed local autoregressive average (LAURA) algorithm as implemented in Cartool EEG software. BOLD activations were obtained using both spike-related and voltage-map EEG-fMRI analysis. The global maxima of each method were used to investigate the temporal relationship of BOLD time courses and to assess the spatial similarity using the Dice similarity index between functional connectivity maps.

Results: ESI, voltage-map and spike-related EEG-fMRI methods identified peaks in 15 (100%), 13 (67%) and 8 (53%) of the 15 patients, respectively. For all methods, maxima were localised within the same lobe, but differed in sub-lobar localisation, with a median distance of 22.8 mm between the highest peak for each method. The functional connectivity analysis showed that the temporal correlation between maxima only explained 38% of the variance between the time course of the BOLD response at the maxima. The mean Dice similarity index between seed-voxel functional connectivity maps showed poor spatial agreement.

Significance: Non-invasive methods for the localisation of the irritative zone have distinct spatial and temporal sensitivity to different aspects of the local cortical network involved in the generation of interictal epileptiform discharges.

Keywords: EEG-fMRI; Electrical source imaging; Focal epilepsy; Functional connectivity; Irritative zone.

Fig. 1

Diagram representing the steps for the spatial and temporal comparison between non-invasive irritative zone localisation methods. Steps 1 to 3 show the acquisition and pre-processing steps using a single simultaneously acquired dataset. Step 4: Localisation of the irritative zone using spike-related, voltage-map EEG-fMRI and electrical source data. Step 5: Spatial maps were normalised to MNI space and the discrepancy between peaks was quantified at the lobar and sub-lobar levels. Step 6: Using each global maximum as seeds to assess the temporal correlation between BOLD timecourses and voxel-based functional connectivity analysis to investigate the spatial similarity between each functional network. BOLD: Blood-oxygen level-dependent;

Fig. 2

Graph showing the median (symbol) and interquartile range (bars) of all pairwise Euclidean distances between global maxima. ESI: Electrical Source Imaging, SR: Spike-related and VM: voltage map EEG-fMRI. * p < 0.05, ** p ≤ 0.01 One-sample Wilcoxon test.

Fig. 3

Functional connectivity analysis a) Bar graph showing the median Dice similarity value and interquartile range (bars) for ipsilateral peaks at each level. b) Violin plot showing the Dice similarity value comparison between ipsilateral and contralateral peak seeds. c) Temporal correlation between functional connectivity fMRI peaks in the ipsilateral and in their respective ROIs on the contralateral hemisphere (darker colours). Triangles and bars representing the mean and standard deviation, respectively. We found low temporal correlation across all ipsilateral BOLD peaks with no significant differences between techniques. The temporal correlation between ipsilateral peaks could not explain the majority of the variance observed between all methods. Contralateral ROIs, used as a control, showed significantly lower correlation values than their respective ipsilateral seed. (* p < 0.05, ** p < 0.01; *** p < 0.001, One-sample Wilcoxon test, ESI: Electrical Source Imaging, SR: Spike-related EEG-fMRI, VM: Voltage map EEG-fMRI, ipsilat.: ipsilateral seed, contralat.: contralateral seed).

Fig. 4

Patient 14 showed an epileptogenic lesion in the left temporal lobe. Interictal spikes were confined to the left posterior-quadrant region. a) Electrical Source Imaging maxima (ESI), Spike-related (ST) and Voltage-map EEG-fMRI BOLD co-localise its respective global maxima in the left parietal lobe, all adjacent to the structural lesion. However, peaks were all distant to each other (b) with a mean Euclidean distance of 22.8 ± 6.24 mm. (c) Seed-voxel functional connectivity maps (p > 0.05 FDR corr.) derived from seed ROIs (black dots) of each respective non-invasive localisation method. Clusters containing the peak are highlighted by the black arrow. The patient showed low spatial correlation between networks (d) with a mean DICE index of 0.6 ± 0.11 between peak clusters and (f) low correlation between BOLD time courses with a mean R² value of 0.29 ± 0.12 between all methods.