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The Journal of Neuroscience, February 15, 2002, 22(4):1480-1495

Cortical Focus Drives Widespread Corticothalamic Networks during Spontaneous Absence Seizures in Rats

Hanneke K. M. Meeren1, 2, Jan Pieter M. Pijn3, dagger , Egidius L. J. M. Van Luijtelaar1, Anton M. L. Coenen1, and Fernando H. Lopes da Silva3, 4

1 Department of Comparative and Physiological Psychology, Nijmegen Institute of Cognition and Information, University of Nijmegen, 6500 HE Nijmegen, The Netherlands, 2 Centre for Magnetoencephalography, Vrije Universiteit Medical Centre, 1081 HV Amsterdam, The Netherlands, 3 Dutch Epilepsy Clinics Foundation, Location "Meer en Bosch," 2100 AA Heemstede, The Netherlands, and 4 Section Neurobiology, Swammerdam Institute of Life Sciences, University of Amsterdam, 1090 GB Amsterdam, The Netherlands

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 spike-wave 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.

Key words: generalized spike-wave discharges; absence epilepsy; cortical focus; thalamus; synchronized oscillations; nonlinear association analysis


dagger Deceased, December, 1998.

Correspondence should be addressed to Hanneke K. M. Meeren, MEG Centre Amsterdam, Vrije Universiteit Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. E-mail: h.meeren{at}vumc.nl.


Copyright © 2002 Society for Neuroscience  0270-6474/02/2241480-16$05.00/0


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