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Neuroimage. 2015 Apr 1;109:368-77. doi: 10.1016/j.neuroimage.2014.12.066. Epub 2015 Jan 3.

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

Author information

1
Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
2
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.
3
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.
4
Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
5
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.
6
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.

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.

KEYWORDS:

Absence seizures; Consciousness; Default mode network; EEG–fMRI; Epilepsy; Negative BOLD; Petit mal

PMID:
25562830
PMCID:
PMC4340775
DOI:
10.1016/j.neuroimage.2014.12.066
[Indexed for MEDLINE]
Free PMC Article
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