Rhythmic 3–4 Hz discharge is insufficient to produce cortical BOLD fMRI decreases in generalized seizures

article i nfo Article history: Accepted 25 December 2014 Available online xxxx Absence seizures are transient episodes of impaired consciousness accompanied by 3- 4H z spike-wave discharge on electroencephalography (EEG). Human functional magnetic resonance imaging (fMRI) studies have demonstrated widespread cortical decreases in the blood oxygen-level dependent (BOLD) signal that may play an important role in the pathophysiology of these seizures. Animal models could provide an opportu- nity to investigate thefundamentalmechanismsofthese changes, however theyhavesofar failedtoconsistently replicate the cortical fMRI decreases observed in human patients. This may be due to important differences between human seizures and animal models, including a lack of cortical development in rodents or differences in the frequencies of rodent (7-8 Hz) and human (3- 4H z) spike-wave discharges. To examine the possible con- tributionsofthesedifferences,we developedaferretmodelthatexhibits3-4Hzspike-waveseizuresinthe pres- ence of a sulcated cortex. Measurements of BOLD fMRI and simultaneous EEG demonstrated cortical fMRI increases during and following spike-wave seizures in ferrets. However unlike human patients, significant fMRI decreases were not observed. The lack of fMRI decreases was consistent across seizures of different dura- tions, discharge frequencies, and anesthetic regimes, and using fMRI analysis models similar to human patients. In contrast, generalized tonic-clonic seizures under the same conditions elicited sustained postictal fMRI decreases, verifying that thelackof fMRI decreases with spike-wavewas not due totechnical factors.These find- ings demonstrate that 3-4 Hz spike-wave discharge in a sulcated animal model does not necessarily produce fMRI decreases, leaving the mechanism for this phenomenon open for further investigation.