Interictal stereotactic-EEG functional connectivity in refractory focal epilepsies

Brain. 2018 Oct 1;141(10):2966-2980. doi: 10.1093/brain/awy214.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / physiopathology*
  • Child
  • Child, Preschool
  • Drug Resistant Epilepsy / etiology
  • Drug Resistant Epilepsy / physiopathology*
  • Electroencephalography
  • Epilepsies, Partial / etiology
  • Epilepsies, Partial / physiopathology*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Malformations of Cortical Development / complications
  • Malformations of Cortical Development / physiopathology
  • Nerve Net / physiopathology
  • Neural Pathways / physiopathology*
  • Stereotaxic Techniques
  • Young Adult