Figure 6.

Two-step seizure progression model. Top panel: Depicted is a 40 s pre-ictal period before electrographic seizure onset, and initial 20 s of a full ictal event. LFP (black), and corresponding intrafocal (red) and extrafocal (blue) avg. population Ca²⁺ transient. Note how during the pre-ictal period, increasingly escalating population Ca²⁺ events are only detected inside the seizure initiation site, not in extrafocal territories. Bottom, Corresponding to the population avg. signals shown above, 3-D surface Ca²⁺ activity plots of imaged fields of view inside the seizure initiation site (red), and in extrafocal territory (blue). The gray layer schematically represents local interneuron population activity. During intrafocal micro-epileptic build-up in the pre-ictal period, inhibition fails at the level of local ensembles only inside the seizure initiation site. Small patches of excitatory ensemble activity break through the layer of local inhibition. Microepileptic expansion over the 40 s pre-ictal period occurs in a saltatory fashion taking over increasingly large areas where inhibition has failed to restrain epileptic activity. Due to the yet highly spatially confined epileptic build-up, it is at first electrographically silent, and not detected even by nearby LFP microelectrodes. Once a local threshold is reached (whose nature remains unclear), seizures spread into neighboring territories outside the seizure initiation site in a continuous fashion, and become detectable by microelectrodes and macroelectrodes across wider portions of the brain. Before this ictal expansion, little population activity can be detected in surround cortex, as opposed to intrafocal territories. This is likely due to increased feedforward inhibition in extrafocal areas that is driven by locally confined pathological activity inside the seizure initiation site. Thus, seizure progression consists of at least two consecutive steps, and may display differential spatiotemporal local network and subpopulation dynamics highly depending on the localization of recording.