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

Abstract

Electrical source imaging (ESI) from interictal scalp EEG is increasingly validated and used as a valuable tool in the presurgical evaluation of epilepsy as a reflection of the irritative zone. ESI of ictal scalp EEG to localize the seizure onset zone (SOZ) remains challenging. We investigated the value of an approach for ictal imaging using ESI and functional connectivity analysis (FC). Ictal scalp EEG from 111 seizures in 27 patients who had Engel class I outcome at least 1 year following resective surgery was analyzed. For every seizure, an artifact-free epoch close to the seizure onset was selected and ESI using LORETA was applied. In addition, the reconstructed sources underwent FC using the spectrum-weighted Adaptive Directed Transfer Function. This resulted in the estimation of the SOZ in two ways: (i) the source with maximal power after ESI, (ii) the source with the strongest outgoing connections after combined ESI and FC. Next, we calculated the distance between the estimated SOZ and the border of the resected zone (RZ) for both approaches and called this the localization error ((i) LE_pow and (ii) LE_conn respectively). By comparing LE_pow and LE_conn, we assessed the added value of FC. The source with maximal power after ESI was inside the RZ (LE_pow = 0 mm) in 31% of the seizures and estimated within 10 mm from the border of the RZ (LE_pow ≤ 10 mm) in 42%. Using ESI and FC, these numbers increased to 72% for LE_conn = 0 mm and 94% for LE_conn ≤ 10 mm. 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.

Keywords: Clinical EEG; EEG source imaging; Functional connectivity; Granger causality; Ictal imaging.

Fig. 1

A) Boxplot of the localization errors of all analyzed seizures, B) percentage of correct localized seizures per patient, for both methods and both limits (LE = 0 mm and LE ≤ 10 mm).

Fig. 2

Three examples of the spatial dispersion of the estimated SOZs for ESI + connectivity (blue circle) and ESI power (red circle). The dot represents the centroid, whereas the circle represents the standard distance. The resected zone is highlighted in green. Both ESI + connectivity and ESI power gave a good indication of the SOZ in PAT 17, respectively 100% and 67% of the seizures were localized correctly. The spatial dispersion of ESI + connectivity points directly to the RZ with a standard distance equal to zero. However, the spatial dispersion of ESI power also gives a good indication where to look for the true SOZ, but less precise. In PAT 12, the standard distance for ESI + connectivity larger than zero, but the spatial dispersion is still informative, remaining mainly in the temporal lobe. The spatial dispersion based on ESI power, however, crosses lobe and even hemisphere borders and could be more difficult to interpret. For PAT 8, the spatial dispersion based on ESI + connectivity contains the RZ, whereas the spatial dispersion based on ESI power does not. Although, ESI + connectivity correctly localized 67% of the seizures, the standard distance is very high due to two completely wrong localizations, rendering the spatial dispersion less informative. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Distribution of the standard distance to the geometrical centroid within the patients who had more than one seizure during recording.

Fig. 4

A) The resected volumes for every patient, sorted from small to large and B) boxplot of the localization errors corresponding to small and large resected volumes, for both methods.

Fig. 5

Distance to the center of the RZ for small and large resected volumes, for both methods.