Global and focal aspects of absence epilepsy: the contribution of genetic models.

The cortico-reticular theory of absence epilepsy explains the origin of the bilateral generalized spike-wave discharges (SWDs) characterizing absence seizures via a subcortical pacemaker that is responsible for both normal sleep spindles and pathological SWDs. This pacemaker is the reticular thalamic nucleus (RTN); it produces spontaneous oscillations together with thalamic relay cells and the cortex in an assembled thalamo-cortico-thalamic network. Recently, Meeren et al. [2002. Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. Journal of Neuroscience 22, 1480-1495.] proposed a focal theory of absence epilepsy based on experimental findings in the WAG/Rij rat, a genetic model of absence epilepsy: the somatosensory cortex contains a focus that initiates a cascade of events that ultimately leads to the occurrence of the bilateral and generalized SWDs if the state of the thalamo-cortical circuitry is favorable. Pharmacological, neurochemical, and neurophysiological data are presented and reviewed here that suggest SWDs might emerge from spontaneous oscillating neurons in the somatosensory cortex during both wakefulness and drowsiness. There is evidence for a variety of neurobiological changes, including a deficient global (parvalbumin) and local GABA-ergic (neurophysiological) system in the neocortex, which may explain why specifically the perioral region of the somatosensory cortex is hyperexcitable and the initiation site of 10Hz oscillations. The neuronal cortical and subcortical circuitry that produces SWDs is part of a large oscillatory system involved in generating cerebral rhythms associated with vibrissal movements. It needs to be established whether similar or comparable pathophysiological processes are also present in humans. Our hypothesis can be readily tested in other models and in humans considering that it is very specific and can be subjected to experimental verification.