A CLOSED-LOOP PROXY-INTERVENTION OF EPILEPTIC SEIZURES
Yuichi Takeuchi1, 2, Márk Harangozó1, Lizeth Pedraza1, Tamás Földi1, Gábor Kozák1, and Antal Berényi1, 3
1 MTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged, Szeged H-6720, Hungary; 2Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Aichi 467-8603, Japan; 3Neuroscience Institute, New York University, New York, New York 10016, USA
Temporal lobe epilepsy with distributed hippocampal seizure foci is often intractable and secondary generalization of its seizures might lead to sudden death. Early termination of the seizures through spatially extensive hippocampal intervention is not feasible directly, due to its large size and irregular shape. In contrast, the medial septum (MS) is a promising target to govern hippocampal oscillations through its divergent connections to both hippocampi. Combining this ‘proxy intervention’ concept and precisely-timed stimulation, we report here that closed-loop MS electrical stimulation can quickly terminate intrahippocampal seizures and suppress secondary generalization in a rat kindling model. Precise stimulus timing governed by internal seizure rhythms in a closed-loop manner was essential for the seizure terminating effect. Cell-type-specific optogenetic stimulation revealed that alternating activation of MS GABAergic and glutamatergic neurons within the internal seizure rhythms can underlie the seizure terminating effect. This seizure rhythm congruent MS electrical stimulation can be directly translated into clinical application. Furthermore, combined with the transcranial focused electrical stimulation technology we developed recently the concept of phase-targeted proxy stimulation for intervening pathological oscillations could be extrapolated to other neurological and psychiatric disorders.