It’s All About the Networks

Abstract

Interictal stereotactic-EEG functional connectivity in refractory focal epilepsies Lagarde S, Roehri N, Lambert I, et al. Brain. 2018;141(10):2966-2980. 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 magnetic resonance imaging (MRI)-based functional connectivity. Few studies have used electrophysiology, despite its high-temporal capacities. In particular, stereotactic-electroencephalogram (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 toward 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 postsurgical 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 nonlinear correlation. We focused on 3 zones defined by stereotactic-EEG ictal activity: the epileptogenic zone (EZ), the propagation zone (PZ), and the noninvolved zone. First, we compared within-zone and between-zones functional connectivity. Second, we analyzed the directionality of functional connectivity between these zones. Third, we measured the associations between functional connectivity measures and clinical variables, especially postsurgical prognosis. Our study confirms that functional connectivity differs according to the zone under investigation. We found: (1) a gradual decrease in the within-zone functional connectivity with higher values for EZ and PZ, and lower for noninvolved zones; (2) preferential coupling between structures of the EZ; (3) preferential coupling between EZ and PZ; and (4) poorer postsurgical outcome in patients with higher functional connectivity of non-involved zone (within-noninvolved zone, between noninvolved zone, and PZ functional connectivity). Our work suggests that, even during the interictal state, functional connectivity is reinforced within epileptic cortices (EZ and PZ) with a gradual organization. Moreover, larger functional connectivity alterations, suggesting more diffuse disease, are associated with poorer postsurgical prognosis. This is consistent with computational studies suggesting that connectivity is crucial in order to model the spatiotemporal dynamics of seizures. Dynamic brain network states in human generalized spike-wave discharges Tangwiriyasakul C, Perani S, Centeno M, et al. Brain. 2018;141(10):2981-2994. Generalized spike-wave discharges in idiopathic generalized epilepsy are conventionally assumed to have abrupt onset and offset. However, in rodent models, discharges emerge during a dynamic evolution of brain network states, extending several seconds before and after the discharge. In human idiopathic generalized epilepsy, simultaneous EEG and functional MRI shows cortical regions may be active before discharges, and network connectivity around discharges may not be normal. Here, in human idiopathic generalized epilepsy, we investigated whether generalized spike-wave discharges emerge during a dynamic evolution of brain network states. Using EEG-functional MRI, we studied 43 patients and 34 healthy control subjects. We obtained 95 discharges from 20 patients. We compared data from patients with discharges with data from patients without discharges and healthy controls. Changes in MRI (blood oxygenation level dependent) signal amplitude in discharge epochs were observed only at and after EEG onset, involving a sequence of parietal and frontal cortical regions then thalamus (P < .01, across all regions and measurement time points). Examining MRI signal phase synchrony as a measure of functional connectivity between each pair of 90 brain regions, we found significant connections (P < .01, across all connections and measurement time points) involving frontal, parietal and occipital cortex during discharges, and for 20 seconds after EEG offset. This network prominent during discharges showed significantly low synchrony (below 99% confidence interval for synchrony in this network in nondischarge epochs in patients) from 16 seconds to 10 seconds before discharges, then ramped up steeply to a significantly high level of synchrony 2 seconds before discharge onset. Significant connections were seen in a sensorimotor network in the minute before discharge onset. This network also showed elevated synchrony in patients without discharges compared to healthy controls (P = .004). During 6 seconds prior to discharges, additional significant connections to this sensorimotor network were observed, involving prefrontal, and precuneus regions. In healthy subjects, significant connections involved a posterior cortical network. In patients with discharges, this posterior network showed significantly low synchrony during the minute prior to discharge onset. In patients without discharges, this network showed the same level of synchrony as in healthy controls. Our findings suggest persistently high sensorimotor network synchrony, coupled with transiently (at least 1 minute) low posterior network synchrony, may be a state predisposing to generalized spike-wave discharge onset. Our findings also show that EEG onset and associated MRI signal amplitude change is embedded in a considerably longer period of evolving brain network states before and after discharge events.