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Carbamazepine and GABA have distinct effects on seizure onset dynamics in mouse brain slices

Dakota N. Crisp, Rachel Parent, Mitsuyoshi Nakatani, Geoffrey G. MurphyiD, William C. StaceyiD

Abstract

Optimizing antiepileptic drug therapy is very challenging due to the absence of a reliable method to assess how brain activity changes between seizures. This work uses the Taxonomy of Seizure Dynamics (Saggio et al., 2020) to investigate how anticonvulsants influence seizure onset dynamotypes. The no Mg2+ /high K+ mouse brain-slice seizure model (N = 92) was used to generate consistent epileptiform onsets. We compared the onset bifurcations of controls with slices treated with either GABA or carbamazepine. Each anticonvulsant uniquely changed the types of bifurcations in the slices. This experiment provides proof-of-concept evidence that brain states exist on a "map" of seizure dynamics, and that antiepileptic drugs with different mechanisms can change the positioning of the brain states on the map. Impact statementAntiepileptic drugs modify underlying brain states and influence the pathway into seizure onset in brain slices.

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