Interictal Functional Connectivity of Human Epileptic Networks Assessed by Intracerebral EEG and BOLD Signal Fluctuations

In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal derived from resting state functional magnetic resonance imaging (fMRI) reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG) and resting-state functional MRI (fMRI) in 5 patients suffering from intractable temporal lobe epilepsy (TLE). Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions) during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband) and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal). This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional connectivity measured by iEEG and BOLD signals give complementary but sometimes inconsistent information in TLE.