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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, ,
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
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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