Surgical resection or ablation of the anterior hippocampus is the standard of care for drug-resistant mesial temporal lobe epilepsy (TLE). However, seizures persist in about one-third of patients post-surgery. This study identified the fasciola cinereum (FC) neurons of the posterior hippocampal tail as a critical seizure node in both mice and humans with epilepsy. Optogenetic inhibition of FC neurons in epileptic mice significantly reduced seizure duration. In humans, sEEG recordings showed prominent FC involvement during seizures, and targeted FC lesioning in one patient reduced seizure burden after anterior mesial temporal structure ablation. The FC emerges as a promising interventional target for epilepsy.

Ryan M. Jamiolkowski, Quynh-Anh Nguyen, Jordan S. Farrell, Ryan J. McGinn, David A. Hartmann, Jeff J. Nirschl, Mateo I. Sanchez, Vivek P. Buch, Ivan Soltesz