Optical imaging of neocortical epileptic foci and inhibitory surround

Neocortical epileptic foci are becoming an increasingly recognized cause for medically intractable epilepsy. In order to understand the patterns of seizure propagation through the neocortex, optical imaging during visual stimulation was performed after the creation of an acute epileptic focus with bicuculline, a GAB A-A antagonist, in the primate striate cortex. Previous studies have shown that optical imaging of the intrinsic signal is able to identify both functional and epileptiform activity in human neocortex (Haglund et al., Nature 358:20, 1992). Prior work has also demonstrated apparent alternating patterns of positive (excitation) and negative (inhibition) intrinsic signal when seizures were triggered in primate visual cortex with full field visual stimulation (Haglund and Blasdel, Epilepsia 34:40, 1993). A simple receptive field of visual cortex (VI) was identified by electrophysiological extracellular single unii recording. In order to minimize the area of cortex stimulated, only this field was visually activated to trigger seizure activity. An acute epileptic focus was created at the mapped site by the local application (0.5 x 0.5mm) of bicuculline (ImM). Optical imaging of the intrinsic signal was performed both before and after the creation of the epileptic focus. Under epileptogenic conditions, the excitatory, positive intrinsic signal wave spread outward from the focus at 25 mm/min if no negative surrounding intrinsic signal was encountered, but if the a negative region of intrinsic signal was encountered by the spreading positive wave, the rate of spread was 2.8 mm/min. The spread of the seizure activity was halted in 30% of the cases when the negative wave was encountered. Single unit recordings in areas of negative intrinsic signal demonstrated reduced responsiveness to visual stimulation in the receptive field. The propagation of bicucullineinduced seizure activity across neocortex is greatly affected by the presence of an apparent inhibitory surround. The extent of effect of negative surround is in accordance with long range horizontal connections. This project funded by N1H K08-01828 and Sloan Foundation Fellowship to MMH.