Drug-refractory focal epilepsies are network diseases associated with functional connectivity alterations both during ictal and interictal periods. A large majority of studies on the interictal/resting state have focused on functional MRI-based functional connectivity. Few studies have used electrophysiology, despite its high temporal capacities. In particular, stereotactic-EEG is highly suitable to study functional connectivity because it permits direct intracranial electrophysiological recordings with relative large-scale sampling. Most previous studies in stereotactic-EEG have been directed towards temporal lobe epilepsy, which does not represent the whole spectrum of drug-refractory epilepsies. The present study aims at filling this gap, investigating interictal functional connectivity alterations behind cortical epileptic organization and its association with post-surgical prognosis. To this purpose, we studied a large cohort of 59 patients with malformation of cortical development explored by stereotactic-EEG with a wide spatial sampling (76 distinct brain areas were recorded, median of 13.2 per patient). We computed functional connectivity using non-linear correlation. We focused on three zones defined by stereotactic-EEG ictal activity: the epileptogenic zone, the propagation zone and the non-involved zone. First, we compared within-zone and between-zones functional connectivity. Second, we analysed the directionality of functional connectivity between these zones. Third, we measured the associations between functional connectivity measures and clinical variables, especially post-surgical prognosis. Our study confirms that functional connectivity differs according to the zone under investigation. We found: (i) a gradual decrease of the within-zone functional connectivity with higher values for epileptogenic zone and propagation zone, and lower for non-involved zones; (ii) preferential coupling between structures of the epileptogenic zone; (iii) preferential coupling between epileptogenic zone and propagation zone; and (iv) poorer post-surgical outcome in patients with higher functional connectivity of non-involved zone (within- non-involved zone, between non-involved zone and propagation zone functional connectivity). Our work suggests that, even during the interictal state, functional connectivity is reinforced within epileptic cortices (epileptogenic zone and propagation zone) with a gradual organization. Moreover, larger functional connectivity alterations, suggesting more diffuse disease, are associated with poorer post-surgical prognosis. This is consistent with computational studies suggesting that connectivity is crucial in order to model the spatiotemporal dynamics of seizures.10.1093/brain/awy214_video1awy214media15833456182001.

The hippocampus and amygdala are key brain structures of the medial temporal lobe, involved in cognitive and emotional processes as well as pathological states such as epilepsy. Despite their importance, it is still unclear whether their  neural activity can be recorded non-invasively. Here, using simultaneous intracerebral and magnetoencephalography (MEG) recordings in patients with focal drug-resistant epilepsy, we demonstrate a direct contribution of amygdala and hippocampal activity to surface MEG recordings. In particular, a method of blind source separation, independent component analysis, enabled activity arising from large neocortical networks to be disentangled from that of deeper structures, whose amplitude at the surface was small but significant. This finding is highly relevant for our understanding of hippocampal and amygdala brain activity as it implies that their activity could potentially be measured non-invasively.