A Systems-Level Approach to Human Epileptic Seizures

Abstract

Epileptic seizures are due to the pathological collective activity of large cellular assemblies. A better understanding of this collective activity is integral to the development of novel diagnostic and therapeutic procedures. In contrast to reductionist analyses, which focus solely on small-scale characteristics of ictogenesis, here we follow a systems-level approach, which combines both small-scale and larger-scale analyses. Peri-ictal dynamics of epileptic networks are assessed by studying correlation within and between different spatial scales of intracranial electroencephalographic recordings (iEEG) of a heterogeneous group of patients suffering from pharmaco-resistant epilepsy. Epileptiform activity as recorded by a single iEEG electrode is determined objectively by the signal derivative and then subjected to a multivariate analysis of correlation between all iEEG channels. We find that during seizure, synchrony increases on the smallest and largest spatial scales probed by iEEG. In addition, a dynamic reorganization of spatial correlation is observed on intermediate scales, which persists after seizure termination. It is proposed that this reorganization may indicate a balancing mechanism that decreases high local correlation. Our findings are consistent with the hypothesis that during epileptic seizures hypercorrelated and therefore functionally segregated brain areas are re-integrated into more collective brain dynamics. In addition, except for a special sub-group, a highly significant association is found between the location of ictal iEEG activity and the location of areas of relative decrease of localised EEG correlation. The latter could serve as a clinically important quantitative marker of the seizure onset zone (SOZ).

Virtual Cortical Resection Reveals Push-Pull Network Control Preceding Seizure Evolution

“…Prior work has explored differences in seizure semiology to describe primary and secondary zones of dysfunction (Nair et al, 2004; Rosenow and Luders, 2001). Others have identified strong, tightly connected network hubs localized in areas outside of the seizure-generating region that indicate a wider extent of network damage (Rummel et al, 2013; Schevon et al, 2007; Zaveri et al, 2009). Our results support the view that tissue surrounding the seizure-generating area displays abnormalities that support seizure evolution.…”

“…Recent work at the cellular level indicates that seizure generation is complex, involving interactions between many neuronal subtypes both within and surrounding seizure-generating regions (Toyoda et al, 2015; Truccolo et al, 2011). Studies establishing a link between macroscale network structure and microscale neuroarchitectonics have demonstrated that heterogeneity of macroscale structure, such as regions of high and low node strengths often associated with the seizure-onset zone (Khambhati et al, 2015; Rummel et al, 2013; Schevon et al, 2007; Warren et al, 2010; Zaveri et al, 2009), is related to increasing complexity in the morphological structure of pyramidal neurons, a common post-synaptic site of excitatory neural activity (Scholtens et al, 2014; van den Heuvel et al, 2015). Prior work has demonstrated that strong γ-band activity at the site of interneurons can transition to β-band activity that is mediated by excitatory, pyramidal neuron activity through changes in excitatory synapses and potassium conductance (Kopell et al, 2000).…”

“…The prospect of patient-centric algorithms that modulate brain state to abort seizures is exciting to clinicians and researchers alike (Afshar et al, 2013; Stacey & Litt, 2008; Stanslaski et al, 2012). However, the best targets for chronic devices remain elusive, partly because functional brain networks, including the epileptic network, reorganize dynamically (Bassett et al, 2011; Bassett et al, 2006; Burns et al, 2014; Khambhati et al, 2015; Rummel et al, 2013). Such reorganization appears to follow a specific progression through network states unique to the patient's seizures (Burns et al, 2014; Khambhati et al, 2015; Wulsin et al, 2013).…”

Sleep-related epileptic behaviors and non-REM-related parasomnias: Insights from stereo-EEG

“…Accordingly, it is the presence of functional heterogeneity in the cortical networks, represented by the lack of spatial slow wave homogeneity,[50,149] that seems to represent the necessary condition for seizure initiation during sleep (Figure 5-B and -C) [139,141]. Altogether, these findings suggests that from circumscribed bursts of low voltage fast activity inside the FCD only propagates and develop into a full blown seizure when the EZ (re)integrates collective brain dynamics during periods of functional heterogeneity [7,124,150]. Of note, such a state occurs spontaneously every night (phase A of the CAP)[115] and can also be triggered…”

Neurological Diseases from a Systems Medicine Point of View

“…Here, the disturbance of these mapped circuits may be assessed using the technique of recording neuronal activity in local brain areas, called electroencephalography ( EEG) . EEG allows to obtain a good temporal resolution when measuring brain activity during epileptic seizures [ 167 ], or permits longitudinal tracking of the disruption of disease-relevant brain circuits, as shown for PD [ 168 ].…”