Graph analysis of epileptogenic networks in human partial epilepsy

Historically, the epileptogenic zone in human partial epilepsy has been conceptually thought to consist of one or more discrete focal sources (Luders & Comair, 2001). Recently, alternative views of epileptic brain and ictogenesis (seizure generation) have been proposed, in that the ictal activity is thought to arise from the activity of epileptogenic cortical networks (Franaszczuk et al., 1994; Franaszczuk & Bergey, 1998; Baccala et al., 2004; Worrell et al., 2004; Jirsch et al., 2006; Kramer et al., 2008; Worrell et al., 2008). It is hypothesized that the activity of these networks, rather than a single focal “pacemaker,” is responsible for the initiation and propagation of the ictal activity. As a result, this has opened the door for potential novel therapies for medically intractable epilepsy through the disruption or inhibition of these epileptogenic networks. Techniques by which to identify and characterize these networks would, therefore, have a significant impact upon the medical treatment of these patients. The application of network topology measures has revolutionized the study of brain function in both physiologic and pathologic states (Stam & Reijneveld, 2007; Bullmore & Sporns, 2009). Through this work, a clearer picture has emerged regarding the basic properties underlying these brain networks, which are highly conserved among a variety of scales (Bullmore & Sporns, 2009). Disruptions of these networks have further been shown to exist in a range of neurologic disorders (Montoya et al., 2006; Stoffers et al., 2008; Hashimoto et al., 2009; Magnee, et al. 2009). In the study of epilepsy, graph theory techniques have been applied to the identification and characterization of the cortical networks giving rise to the ictal activity (Franaszczuk et al., 1994; Franaszczuk & Bergey, 1998; Baccala et al., 2004). Analysis of network connectivity in patients with epilepsy has been performed using functional data garnered from ECoG (Ortega et al., 2008a,b; Van Dellen et al., 2009), electroencephalography (EEG) (Ponten et al., 2009; Horstmann et al., 2010), magnetoencephalography (MEG) (Chavez et al., 2010), and functional magnetic resonance imaging (fMRI) (Zhang et al., 2009) measurements. These studies have demonstrated the existence of highly interconnected “hubs,” which may play a role in the initiation and propagation of the ictal activity by the epileptogenic networks (Morgan & Soltesz, 2008). Selective modulation of these hubs could, theoretically, prevent or abolish seizure activity without the need for removal of the entire network, which in turn could lead to better preoperative planning and more focused interventions. In this study, graph theoretic measures were applied to evaluate the local and global connectivity within the network. Examination of the network properties was performed during resting interictal periods as well as during interictal spikes, in order to determine whether the network properties observed during the ictal periods could also be observed during the interictal intervals. It was observed that the functional changes in the connectivity were correlated with the seizure onset zone (SOZ) and the activity of the cortical networks affiliated with these regions was also enhanced during interictal periods as well.