Spatial stability over time of brain areas generating fast ripples in the epileptic rat.

Abstract

Fast ripples (FRs) are interictal, pathological, high-frequency oscillations in the 200- to 600-Hz range, which can be recorded from limbic regions capable of generating spontaneous seizures in rodent models of epilepsy and in human mesial temporal lobe epilepsy. To evaluate the spatial stability of FR-generating brain areas over long periods, we monitored interictal FR oscillations in rats with chronic recurrent spontaneous seizures. After unilateral intrahippocampal injection of kainic acid, 22 rats were video monitored until spontaneous behavioral seizures occurred, and then implanted with multiple hippocampal, dentate gyrus, and entorhinal cortex microelectrodes. Electrophysiological monitoring of microelectrode sites was carried out during daily 8-h recordings for periods ranging from 6 to 98 days. Interictal FRs were recorded from discretely localized areas, adjacent to non-FR-generating areas in dentate gyrus and entorhinal cortex. The location of interictal FR oscillations remained fixed, and the electrophysiological pattern of FRs remained the same over the time of our study. For the duration of monitoring, sites initially recording interictal FRs continued to display FR oscillations, and sites that initially did not record FRs never demonstrated FR activity. A direct relation was seen between the total number of electrode contacts recording interictal FRs and the frequency of spontaneous seizure generation (p < 0.0001). These results suggest that interictal FRs reflect abnormal discharges from a fixed pathologic substrate imbedded within less-epileptogenic tissue, and that spontaneous seizure frequency is dependent on the extent and distribution of this pathologic substrate.