Absence seizures are the most pure form of generalized epilepsy. They are characterized in the electroencephalogram by widespread bilaterally synchronous spike-wave discharges (SWDs), which are the reflections of highly synchronized oscillations in thalamocortical networks. To reveal network mechanisms responsible for the initiation and generalization of the discharges, we studied the interrelationships between multisite cortical and thalamic field potentials recorded during spontaneous SWDs in the freely moving WAG/Rij rat, a genetic model of absence epilepsy.Nonlinear association analysis revealed a consistent cortical "focus" within the peri-oral region of the somatosensory cortex.The SWDs recorded at other cortical sites consistently lagged this focal site, with time delays that increased with electrode distance (corresponding to a mean propagation velocity of 1.4 m/sec). Intra-thalamic relationships were more complex and could not account for the observed cortical propagation pattern. Cortical and thalamic sites interacted bi-directionally, whereas the direction of this coupling could vary throughout one seizure. However, during the first 500 msec, the cortical focus was consistently found to lead the thalamus.These findings argue against the existence of one common subcortical pacemaker for the generation of generalized spikewave discharges characteristic for absence seizures in the rat. Instead, the results suggest that a cortical focus is the dominant factor in initiating the paroxysmal oscillation within the corticothalamic loops, and that the large-scale synchronization is mediated by ways of an extremely fast intracortical spread of seizure activity. Analogous mechanisms may underlie the pathophysiology of human absence epilepsy.

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Pijn, J.P.; Velis, D.N.; van der Heyden, M.; de Goede, J.; van Veelen, C.W.M. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Signal analysis methods derived from the theory of nonlinear dynamics provide new tools to characterize the behavior of such networks, and are particularly relevant for the analysis of epileptiform activity. Methods: We calculated the correlation dimension, tested for irreversibility, and made recurrence plots of EEG signals recorded intracranially both during interictal and ictal states in temporal lobe epilepsy patients who were surgical candidates. Results: Epileptic seizure activity often, but not always, emerges as a low-dimensional oscillation. In general, the seizure behaves as a nonstationary phenomenon during which both phases of low and high complexity may occur. Nevertheless a low dimension may be found mainly in the zone of ietal onset and nearby structures. Both the zone of ictal onset and the pattern of propagation of seizure activity in the brain could be identified using this type of analysis. Furthermore, the results obtained were in close agreement with visual inspection of the EEG records. Conclusions: Application of these mathematical tools provides novel insights into the spatio-temporal dynamics of "epileptic brain states". In this way it may be of practical use in the localization of an epileptogenic region in the brain, and thus be of assistance in the presurgical evaluation of patients with localization-related epilepsy.

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