This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (45)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Epilepsy  • Neuropathology  • Seizures, Nonepileptic  • Alert me on articles by topic

The Cortical Focus Theory

Hanneke Meeren, PhD; Gilles van Luijtelaar, PhD; Fernando Lopes da Silva, MD; Anton Coenen, PhD

Arch Neurol. 2005;62:371-376.

Four main theories on the pathophysiology of generalized absence seizures have been proposed. The "centrencephalic" theory, proposed in 1954, suggested that discharges originate from a deep-seated diffusely projecting subcortical pacemaker in the midline thalamus. This concept was refined in 1991 with the "thalamic clock" theory, implying that the reticular thalamic nucleus contains the pacemaker cells for the thalamic clock, imposing its rhythm to the cortex. According to other investigators, however, the cortex seems to play a leading role. They suggested that spike-wave discharges have a focal onset in the cortex and are generalized through a rapid propagation. In the "corticoreticular" theory, postulated in 1968, spike-wave discharges are linked to the thalamocortical mechanisms that generate spindles. Rhythmic spindle oscillations generated in the thalamus are transformed into spike-wave discharges when the cortex is hyperexcitable. A 2002 study confirmed in epileptic rats that a functionally intact thalamocortical network is required for the generation of spike-wave discharges. The corticothalamic interrelationships were investigated by means of nonlinear association signal analyses of multiple spike-wave discharges. This showed a consistent focus within the perioral region of the somatosensory cortex. From this focus, seizure activity generalizes rapidly over the cortex. During the first cycles of the seizure the cortex drives the thalamus, while thereafter cortex and thalamus drive each other, thus amplifying and maintaining the rhythmic discharge. In this way the "cortical focus" theory for generalized absence epilepsy bridges cortical and thalamic theories.

Author Affiliations: F. C. Donders Centre for Cognitive Neuroimaging (Dr Meeren) and Department of Biological Psychology, Nijmegen Institute for Cognition and Information (Drs van Luijtelaar and Coenen), Radboud University Nijmegen, Nijmegen, the Netherlands; and Neurobiology Section, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands (Dr Lopes da Silva).

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Absence seizures in C3H/HeJ and knockout mice caused by mutation of the AMPA receptor subunit Gria4
Beyer et al.
Hum Mol Genet 2008;17:1738-1749.
ABSTRACT | FULL TEXT  

Deep Layer Somatosensory Cortical Neurons Initiate Spike-and-Wave Discharges in a Genetic Model of Absence Seizures
Polack et al.
J. Neurosci. 2007;27:6590-6599.
ABSTRACT | FULL TEXT  

Spreading photoparoxysmal EEG response is associated with an abnormal cortical excitability pattern
Siniatchkin et al.
Brain 2007;130:78-87.
ABSTRACT | FULL TEXT  

Recurrent Absence Status Epilepticus (Spike-and-Wave Stupor) Associated With Lamotrigine Therapy
Hasan et al.
J Child Neurol 2006;21:807-809.
ABSTRACT  

Functional stabilization of weakened thalamic pacemaker channel regulation in rat absence epilepsy
Kuisle et al.
J. Physiol. 2006;575:83-100.
ABSTRACT | FULL TEXT  

Voltage-gated calcium channels and idiopathic generalized epilepsies.
Khosravani and Zamponi
Physiol. Rev. 2006;86:941-966.
ABSTRACT | FULL TEXT