What Is a Seizure Network? Very Fast Oscillations at the Interface Between Normal and Epileptic Brain

Abstract

Although there is a great multiplicity of normal brain electrical activities, one can observe defined, relatively abrupt, transitions between apparently normal rhythms and clearly abnormal, higher amplitude, "epileptic" signals; transitions occur over tens of ms to many seconds. Transitional activity typically consists of low-amplitude very fast oscillations (VFO). Examination of this VFO provides insight into system parameters that differentiate the "normal" from the "epileptic." Remarkably, VFO in vitro is generated by principal neuron gap junctions, and occurs readily when chemical synapses are suppressed, tissue pH is elevated, and [Ca(2+)]o is low. Because VFO originates in principal cell axons that fire at high frequencies, excitatory synapses may experience short-term plasticity. If the latter takes the form of potentiation of recurrent synapses on principal cells, and depression of these on inhibitory interneurons, then the stage is set for synchronized bursting - if [Ca(2+)]o recovers sufficiently. Our hypothesis can be tested (in part) in patients, once it is possible to measure brain tissue parameters (pH, [Ca(2+)]o) simultaneously with ECoG.