FMRI of generalized absence status epilepticus in conscious marmoset monkeys reveals corticothalamic activation

Abstract

Purpose: A nonhuman primate model of generalized absence status epilepticus was developed for use in functional magnetic resonance imaging (/MRI) experiments to elucidate the brain mechanisms underlying this disorder. Methods: Adult male marmoset monkeys (Callithrix jacchus) were treated with γ-butyrolactone (GBL) to induce prolonged absence seizures, and the resulting spike-wave discharges (SWDs) were analyzed to determine the similarity to the 3-Hz SWDs that characterize the disorder. In addition, blood-oxygenation-level-dependent (BOLD) fMRI was measured at 4.7 Tesla after absence seizure induction with GBL. Results: Electroencephalographic recordings during imaging showed 3-Hz SWDs typical of human absence seizures. This synchronized EEG pattern started within 15 to 20 min of drug administration and persisted for >60 min. In addition, pretreatment with the antiepileptic drug, ethosuximide (ESM), blocked the behavioral and EEG changes caused by GBL. Changes in BOLD signal intensity in the thalamus and sensorimotor cortex correlated with the onset of 3-Hz SWDs. The change in BOLD signal intensity was bilateral but heterogeneous, affecting some brain areas more than others. No significant negative BOLD changes were seen. Conclusions: The BOLDfMRI data obtained in this marmoset monkey model of absence status epilepticus shows activation within the thalamus and cortex.