We investigated two important means for improving source reconstruction in presurgical epilepsy diagnosis. The first investigation is about the optimal choice of the number of epileptic spikes in averaging to (1) sufficiently reduce the noise bias for an accurate determination of the center of gravity of the epileptic activity and (2) still get an estimation of the extent of the irritative zone. The second study focuses on the differences in single modality EEG (80-electrodes) or MEG (275-gradiometers) and especially on the benefits of combined EEG/MEG (EMEG) source analysis. Both investigations were validated with simultaneous stereo-EEG (sEEG) (167-contacts) and low-density EEG (ldEEG) (21-electrodes). To account for the different sensitivity profiles of EEG and MEG, we constructed a six-compartment finite element head model with anisotropic white matter conductivity, and calibrated the skull conductivity via somatosensory evoked responses. Our results show that, unlike single modality EEG or MEG, combined EMEG uses the complementary information of both modalities and thereby allows accurate source reconstructions also at early instants in time (epileptic spike onset), i.e., time points with low SNR, which are not yet subject to propagation and thus supposed to be closer to the origin of the epileptic activity. EMEG is furthermore able to reveal the propagation pathway at later time points in agreement with sEEG, while EEG or MEG alone reconstructed only parts of it. Subaveraging provides important and accurate information about both the center of gravity and the extent of the epileptogenic tissue that neither single nor grand-averaged spike localizations can supply.

To increase the reliability for the non-invasive determination of the irritative zone in presurgical epilepsy diagnosis, we introduce here a new experimental and methodological source analysis pipeline that combines the complementary information in EEG and MEG, and apply it to data from a patient, suffering from refractory focal epilepsy. Skull conductivity parameters in a six compartment finite element head model with brain anisotropy, constructed from individual MRI data, are estimated in a calibration procedure using somatosensory evoked potential (SEP) and field (SEF) data. These data are measured in a single run before acquisition of further runs of spontaneous epileptic activity. Our results show that even for single interictal spikes, volume conduction effects dominate over noise and need to be taken into account for accurate source analysis. While cerebrospinal fluid and brain anisotropy influence both modalities, only EEG is sensitive to skull conductivity and conductivity calibration significantly reduces the difference in especially depth localization of both modalities, emphasizing its importance for combining EEG and MEG source analysis. On the other hand, localization differences which are due to the distinct sensitivity profiles of EEG and MEG persist. In case of a moderate error in skull conductivity, combined source analysis results can still profit from the different sensitivity profiles of EEG and MEG to accurately determine location, orientation and strength of the underlying sources. On the other side, significant errors in skull modeling are reflected in EEG reconstruction errors and could reduce the goodness of fit to combined datasets. For combined EEG and MEG source analysis, we therefore recommend calibrating skull conductivity using additionally acquired SEP/SEF data.