Dynamics of networks during absence seizure's on- and offset in rodents and man

Abstract

Network mechanisms relevant for the generation, maintenance and termination of spike-wave discharges (SWD), the neurophysiological hallmark of absence epilepsy, are still enigmatic and widely discussed. Within the last years, however, improvements in signal analytical techniques, applied to both animal and human fMRI, EEG, MEG, and ECoG data, greatly increased our understanding and challenged several, dogmatic concepts of SWD. This review will summarize these recent data, demonstrating that SWD are not primary generalized, are not sudden and unpredictable events. It will disentangle different functional contributions of structures within the cortico-thalamo-cortical system, relevant for the generation, generalization, maintenance, and termination of SWD and will present a new “network based” scenario for these oscillations. Similarities and differences between rodent and human data are presented demonstrating that in both species a local cortical onset zone of SWD exists, although with different locations; that in both some forms of cortical and thalamic precursor activity can be found, and that SWD occur through repetitive cyclic activity between cortex and thalamus. The focal onset zone in human data could differ between patients with varying spatial and temporal dynamics; in rats the latter is still poorly investigated.

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

“…the cortex was found to interact differently with the caudal and rostral part of the NRT) during SWDs and in a short period immediately prior to SWD onset, where the network already seems to prepare towards SWD generation. Based on these findings, different functional contributions of the different thalamic nuclei for SWD preparation, generation and maintenance, as well as a temporal SWD generation scenario was proposed (for review see (Luttjohann and van Luijtelaar, 2015)). …”

CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy

“…As a fairly common form of generalized seizure, the network mechanisms of SWDs have been extensively investigated for more than seven decades (Avoli 2012;Luttjohann and van Luijtelaar 2015). Accumulating evidence indicates that SWDs are generated within the corticothalamocortical circuitry and that the dynamic interaction of local microcircuits within this neuronal network leads to the "full-blown" SWDs associated with absence epilepsy (McCormick and Contreras 2001;Steriade 2005;Huguenard and McCormick 2007;Luttjohann and van Luijtelaar 2015).…”

“…Accumulating evidence indicates that SWDs are generated within the corticothalamocortical circuitry and that the dynamic interaction of local microcircuits within this neuronal network leads to the "full-blown" SWDs associated with absence epilepsy (McCormick and Contreras 2001;Steriade 2005;Huguenard and McCormick 2007;Luttjohann and van Luijtelaar 2015). The very early studies of absence epilepsy (also known as petit mal epilepsy) reported that SWDs, as in human absence epilepsy, could initiate and sustain after a brief electric stimulation in the thalamus in animals (Lewy and Gammon 1940;Lindsley et al 1949).…”

“…In the most recent studies, investigators employed the simultaneous EEG and/or functional magnetic resonance imaging (fMRI) recordings at multiple cortical and thalamic sites and saw the precursor activity in specific cortical areas prior to SWD onset in animal models (Meeren et al 2002;David et al 2008) as well as in human patients (Tyvaert et al 2009;Bai et al 2010). These findings provide the most compelling evidence supporting that the cortex is actually the initiator of SWDs, although technical limitations prevented the simultaneous monitoring of every thalamic and cortical area or subareas potentially involved in SWDs in these studies (Luttjohann and van Luijtelaar 2015). Here, we introduced an alternative genetic approach that may address network mechanisms in a complementary way.…”

Identification of Focal Epileptogenic Networks in Generalized Epilepsy Using Brain Functional Connectivity Analysis of Bilateral Intracranial EEG Signals

“…Studies of GSWD using magnetoencephalography also revealed focal source in absence seizures (Tenney et al 2013;Westmijse et al 2009). These evidences suggest the possibility that some generalized seizures could be developed by a complex epileptogenic network involving both local and global brain networks (Blumenfeld et al 2003;Lüttjohann and van Luijtelaar 2015;McNally and Blumenfeld 2004). Furthermore, by interrupting the global network through corpus callosotomy (CC), several clinical studies have demonstrated the possibility of revealing focal seizure onset in scalp EEG (Clarke et al 2007;Hur et al 2011;Iwasaki et al 2011;Lin et al 2011;Ono et al 2011).…”