fMRI of generalized absence status epilepticus in conscious marmoset monkeys reveals corticothalamic activation.
OBJECTIVE
A nonhuman primate model of generalized absence status epilepticus was developed for use in functional magnetic resonance imaging (fMRI) experiments to elucidate the brain mechanisms underlying this disorder.


METHODS
Adult male marmoset monkeys (Callithrix jacchus) were treated with gamma-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 BOLD fMRI data obtained in this marmoset monkey model of absence status epilepticus shows activation within the thalamus and cortex.
Center for Comparative Neuroimaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts, USA. jeffrey.tenney@umassmed.edu
Jeffrey R
JR
Tenney
Paul C
PC
Marshall
Jean A
JA
King
Craig F
CF
Ferris
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002144:Callithrix; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D003243:Consciousness / Q000502:physiology; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D013226:Status Epilepticus / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology*; D013788:Thalamus / Q000187:drug effects / Q000503:physiopathology*
D015107:4-Butyrolactone; D010100:Oxygen