• M V Sysoeva, A Lüttjohann, G van Luijtelaar, and I V Sysoev.
• Yuri Gagarin State Technical University of Saratov, Saratov, Russia; Saratov Branch of Kotel'nikov Institute of Radio Engineering and Electronics of RAS, Saratov, Russia. Electronic address: bobrichek@mail.ru.
• Neuroscience. 2016 Feb 9; 314: 75-89.

PurposeSpike and wave discharges (SWDs), generated within cortico-thalamo-cortical networks, are the electroencephalographic biomarker of absence epilepsy. The current work aims to identify mechanisms of SWD initiation, maintenance and termination by the analyses of dynamics and directionality of mutual interactions between the neocortex and various functionally different thalamic nuclei.MethodsLocal-field potential recordings of 16 male Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats, equipped with electrodes targeting layer 4-6 of the somatosensory cortex, rostral and caudal reticular thalamic nuclei (rRTN and cRTN), ventro-posteromedial (VPM), anterior (ATN) and posterior (PO) thalamic nuclei, were obtained. 3s epochs prior to SWD onset, after SWD onset, prior to SWD offset and after SWD offset were analyzed with newly developed time-variant adapted nonlinear Granger causality.ResultsA gradual increase in coupling toward SWD onset between cortico-cortical pairs appears as early as 2s preictally. Next first unidirectional increase in coupling is noticed in a restricted number of cortico-thalamic and thalamo-cortical channel pairs, which turn into bidirectional coupling approaching SWD onset, and a gradual increase of intrathalamic coupling. Seizure onset is characterized by a coupling decrease for more than a second in a majority of channel pairs, only the cortex kept driving the cRTN. Intrathalamically the cRTN drives the PO, VPM and ATN. Most channel pairs no longer show differences in coupling with baseline during SWD maintenance, a major exception is the unidirectional coupling between cortex and cRTN. Toward the end of SWDs, more and more channel pairs show an increase in often bidirectional coupling, this increase suddenly vanishes at SWD offset.ConclusionThe initiation of SWD is due to a gradual increase in intracortical coupling, followed by a selective increase in first unidirectional and later bidirectional coupling between the cortex and thalamus and also intrathalamically. Once the network is oscillating, coupling decreases in most of the channel pairs, although the cortex keeps its influence on the cRTN. The SWD is dampened by a gradual increase in coupling strength and in the number of channel pairs that influence each other; the latter might represent an endogenous brake of SWDs.Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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