Predicting Successful Generation and Inhibition of Seizure-like Afterdischarges and Mapping Their Seizure Networks Using fMRI

Abstract

Summary: To understand the conditions necessary to initiate and terminate seizures, we investigate optogenetically induced hippocampal seizures with LFP, fMRI, and optogenetic inhibition. During afterdischarge induction using optogenetics, LFP recordings show that stimulations with earlier ictal onset times are more likely to result in afterdischarges and are more difficult to curtail with optogenetic inhibition. These results are generalizable across two initiation sites, the dorsal and ventral hippocampus. fMRI shows that afterdischarges initiated from the dorsal or ventral hippocampus exhibit distinct networks. Short-duration seizures initiated in the dorsal and ventral hippocampus are unilateral and bilateral, respectively, while longer-duration afterdischarges recruit broader, bilateral networks. When optogenetic inhibition is ineffective at stopping seizures, the network activity spreads more extensively but largely overlaps with the network activity associated with seizures that could be curtailed. These results provide insights into how seizures can be inhibited, which has implications for targeted seizure interventions. : Duffy et al. show that success in generating or curtailing seizures is related to their onset time, with inhibition proving less effective on earlier-onset afterdischarges. To identify downstream targets for intervention, fMRI is used to map the seizure network of afterdischarges initiated from the dorsal and ventral hippocampus. Keywords: seizure, epilepsy, hippocampus, fMRI, optogenetrics, generation, inhibition, stopping, network, afterdischarge