Abstracts

Rationale: Characterization of seizure propagation from an acute experimental epileptic focus and involvement of other brain areas in the ictal discharge. Methods: The experiments were performed on 17 adult Sprague-Dawley male rats. 16 tungsten microelectrodes were implanted into ipsilateral and contralateral anterior hippocampus, posterior hippocampus, entorhinal cortex and piriform cortex. Baseline recordings of electrical activity were performed over 3 days under freely moving conditions. Kainic acid was then injected into the posterior CA3 region followed by electrophysiological recording for 5 hours. Data analysis was performed to characterize (1) the propagation of seizure activity from the area of injection, which was considered as the seizure onset zone (SOZ), estimated by measurement of the latency to seizure occurrence in other recorded brain areas; and (2) generation of individual ictal discharges in different structures during the onset of seizure activity, which was estimated by calculating the temporal relationship among individual epileptiform events recorded from the SOZ and other brain areas. Results: A positive correlation of latencies of seizures propagated to other brain areas with the distance to these areas were observed. The closest brain areas located at a physical distance of 3mm showed the shortest latency (9.80 + 9.93s), while the long-distance (10-12mm) showed the largest latencies (19.43s + 17.55s). Large-scale measurements showed an overall increase in latency for each consecutive seizure propagated from the SOZ. Specifically, the shortest latencies (11.60 + 9.77s) were observed during the first seizure, while the longest during the fifth seizure (18.44 + 18.46s). At the level of micro-intervals, we observed, that at the beginning of the recruitment process into ictal activity, there was a high dispersion of LFP peaks in other brain areas in relation to the peak of the epileptiform event amplitudes recorded in the SOZ. However, later when the seizure developed, the dispersion of epileptiform event amplitudes decreased and events in other brain areas located within 3-12 mm distance from the SOZ occurred simultaneously, and at time before events recorded in the SOZ. Conclusions: Our results illustrate that the speed of propagation of seizures from an acute experimental focus to other brain areas is similar to what was described for spontaneous seizures in animal models of chronic epilepsy and in patients with temporal lobe epilepsy. This speed is slow and suggests the existence of mechanisms preventing involvement of target brain areas into pathological discharges. At present, it is not clear whether these homeostatic mechanisms involve feed forward inhibition. Involvement of target brain areas into ictal activity does not appear to be driven, necessarily, by the seizure onset zone, but rather there is initial instability concerning which brain structure drives individual epileptiform event; eventually one structure, not necessarily the SOZ, becomes the generator. Analysis of mechanisms of this phenomenon is in progress. Funding: NIH grants, NS065877 and NS033310