閉ループ脳深部刺激によるてんかん発作の制御

抄録

Temporal lobe epilepsy with distributed hippocampal seizure foci is oftenintractable and its secondary generalization might lead to sudden death. Earlytermination through spatially extensive hippocampal intervention is not feasibledirectly, due to the large size and irregular shape of the hippocampus. Incontrast, the medial septum (MS) is a promising target to govern hippocampaloscillations through its divergent connections to both hippocampi. Combiningthis ‘proxy intervention’ concept and precisely timed stimulation, we reporthere that closed-loop MS electrical stimulation can quickly terminateintrahippocampal seizures and suppress secondary generalization in a ratkindling model. Precise stimulus timing governed by internal seizure rhythms wasessential. Cell-type-specific stimulation revealed that the precisely timedactivation of MS GABAergic neurons underlaid the effects. Our concept oftime-targeted proxy stimulation for intervening pathological oscillations can beextrapolated to other neurological and psychiatric disorders, and has potentialfor clinical translation.