Physiological basis of pathophysiological brain rhythms

Focal epilepsy may be induced acutely in the brain in vivo by measures whic h reduce inhibition or enhance excitation. Athough the various models invol ve different mechanisms causing the epilepsy, their epileptiform discharge patterns vary only little. Intracellular analyses in vivo and in vitro reve al that the cellular hallmark of epileptic discharge, the paroxysmal depola rization shift, is followed by a giant hyperpolarization. The latter is com prised of several, overlapping, components with different durations, includ ing calcium dependent potassium currents and GABA dependent inhibitions. Re lative reduction of one inhibitory component is compensated by other inhibi tory components. In epilepsy caused by reduction of GABAergic inhibition, t he absolute duration and amplitude of GABAergic inhibition may even be incr eased in comparison to the responses following afferent stimulation under c ontrol conditions since the excitatory drive of the paroxysmal discharges o n the interneurons is strongly increased. In some interictal discharge patt erns, the enhanced inhibitions within the focus determine the refractory pe riods of the focus. The latter is paced by neurons from the perifocal area which show a shorter inibition associated with the interictal epileptic eve nt. The discharge pattern of the focus may switch to other patterns, either spontaneously, or as entrained by external stimulation. Such changes are c aused e.g. by progressive potassium accumulations in the extracellular spac e with critically small intervals of the epileptic events. It is concluded that the epileptiform discharge patterns reflect intrinsic properties of th e brain, and do not very well reflect the mechanism of action of the epilep togenic model. The brain is thus equipped with inherent mechanisms which fa vor rhythmic epileptiform discharges under certain conditions.