Abstracts

The topographical relationship between interictal spikes and ictal onsets in human neocortical epilepsy is variable and involves shifting populations of highly interconnected networks. Previous investigations in acute models have not shown this variability. We investigated the shifting topography of epileptiform events in a lesional and nonlesional model of chronic rodent neocortical epilepsy with optical mapping of intrinsic signals. We injected 200-400 mM/2.5-5 [mu]l of FeCl[sub]2[/sub] (lesional; n=3) or 50 ng/0.5 [mu]l of tetanus toxin (nonlesional; n=3) into the somatosensory cortex of adult Sprague-Dawley rats. Video-EEG monitoring was performed via an implanted telemetry device (DSI). Average seizure frequency was calculated using a custom seizure detection algorithm (Matlab). After two-month of EEG monitoring, the animals were placed in a stereotactic frame and underwent a craniotomy with general anesthesia (Urethane). Field potential electrodes were inserted into the neocortex near the injection site. A CCD camera was focused 500 [mu]m below the brain surface that was illuminated by filtering a halogen lamp at different wavelengths (546 [plusmn] 10 nm, 605 [plusmn] 10 nm, 630 [plusmn] 10 nm and 700 [plusmn] 10 nm) and images were acquired at 100-600 ms/frame. Animals were sacrificed for histology. Both models induced frequent but stable epileptiform events in all rats during the two-month monitoring period (lesional: 3.75[plusmn]1.66 sz/hr; nonlesional: 3.85[plusmn]1.2 sz/hr). Even under general anesthesia, a variety of epileptiform events persisted, including single interictal spikes (IIS), poly-spikes, and ictal events. Optical epilepsy maps, revealed that the IISs arose from a variety of locations surrounding the injection site. Likewise, ictal onsets were variable in location but always arose from adjacent regions of cortex with occasional secondary generalization and cross callosal spread. Inverted optical signals were recorded from surrounding cortex with a dynamic relationship with the epileptiform events. This is the first report of optical imaging of spontaneous epileptiform events in a chronic model of rodent neocortical epilepsy. We report that, unlike in acute models, the relationship between ictal onsets and interictal spikes is dynamic and spatially variable in relation to both nonlesional and lesional cortical irritation. (Supported by NIH)