Spontaneous and artificial activation of neocortical seizures.

The aim of this study is to disclose the mechanisms underlying the recruitment of neocortical networks during slow-wave sleep oscillations evolving into spike-wave (SW) seizures. 1) We investigated the activation of SW seizures in a seizure-prone neocortex by means of electrical stimuli applied within the frequency range of spontaneous sleep oscillations. Stimuli were grouped in bursts of 10 Hz, similar to sleep spindles, and repeated every 2 s, to reproduce their rhythmic recurrence imposed by the slow (<1 Hz) sleep oscillation. Either cortical or thalamic stimuli, which were applied while the cortex displayed sleeplike activity, gradually induced paroxysmal responses in intracellularly recorded neocortical neurons, which were virtually identical to those of spontaneous seizures and consisted of a progressive buildup of paroxysmal depolarizing shifts (PDSs). 2) The ability of cortical networks to follow stimuli was tested at various stimulation frequencies (1-3 Hz) and quantified by calculating the entropy of the ensuing oscillation. Rhythmic PDSs were optimally induced, and the lowest entropy was generated, at a stimulation frequency around 1.5 Hz. Fast runs at 10-15 Hz, which often override PDSs, thus contributing to the polyspike-wave pattern of seizures, were induced by cortical stimuli, but were disturbed by thalamic stimuli. Spontaneous seizures generally evolved toward an accelerated discharge of PDSs. It is suggested that these accelerating trends during SW seizures act as protective mechanisms by provoking the uncoupling of cortical networks and eventually arresting the seizure.