title: Rhythmic 3-4Hz discharge is insufficient to produce cortical BOLD fMRI decreases in generalized seizures.
abstract: Absence seizures are transient episodes of impaired consciousness accompanied by 3-4 Hz 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 opportunity to investigate the fundamental mechanisms of these changes, however they have so far failed to consistently 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 (3-4 Hz) spike-wave discharges. To examine the possible contributions of these differences, we developed a ferret model that exhibits 3-4 Hz spike-wave seizures in the presence 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 durations, 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 the lack of fMRI decreases with spike-wave was not due to technical factors. These findings 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.
authors.affiliation: Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Youngblood
authors.affiliation: Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Core Center for Quantitative Neuroscience with Magnetic Resonance (QNMR), New Haven, CT 06520, USA.
authors.forename: Asht M
authors.initials: AM
authors.lastname: Mishra
authors.affiliation: Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Enamandram
authors.affiliation: Core Center for Quantitative Neuroscience with Magnetic Resonance (QNMR), New Haven, CT 06520, USA; Department of Diagnostic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Basavaraju G
authors.initials: BG
authors.lastname: Sanganahalli
authors.affiliation: Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Motelow
authors.affiliation: Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Harrison X
authors.initials: HX
authors.lastname: Bai
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Flavio
authors.initials: F
authors.lastname: Frohlich
authors.affiliation: Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gribizis
authors.affiliation: Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Lighten
authors.affiliation: Core Center for Quantitative Neuroscience with Magnetic Resonance (QNMR), New Haven, CT 06520, USA; Department of Diagnostic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Biomedical Engineering, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Fahmeed
authors.initials: F
authors.lastname: Hyder
authors.affiliation: Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Core Center for Quantitative Neuroscience with Magnetic Resonance (QNMR), New Haven, CT 06520, USA; Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: hal.blumenfeld@yale.edu.
authors.forename: Hal
authors.initials: H
authors.lastname: Blumenfeld
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000503:physiopathology*; D005260:Female; D005289:Ferrets; D008279:Magnetic Resonance Imaging; D012640:Seizures / Q000503:physiopathology*
keywords: Absence seizures; Consciousness; Default mode network; EEG–fMRI; Epilepsy; Negative BOLD; Petit mal