Epilepsia 44 Suppl. 9 :175, 2003
COMBINED BOLD fMRI AND EEG RECORDINGS DURING SPONTANEOUS SPIKE-WAVE SEIZURES AND BICUCULLINE-INDUCED GENERALIZED TONIC-CLONIC SEIZURES IN WAG/Rij RATS
Authors: Hrachya Nersesyan, Sohil Patel, Maritza Rivera, Douglas L. Rothman, Fahmeed Hyder, Hal Blumenfeld Neurology, Yale University School of Medicine, New Haven, CT; Diagnostic Radiology, Yale University School of Medicine, New Haven, CT; Neurobiology, Yale University School of Medicine, New Haven, CT
Functional magnetic resonance imaging (fMRI) using blood oxygen level dependent (BOLD) contrast has become a popular tool to investigate brain function. It is known that the BOLD signal depends on cerebral blood flow (CBF), oxidative metabolism and blood volume. However, the relationship between neuronal activity and the BOLD signal is not fully understood yet, particularly in abnormal conditions such as epileptic seizures. Our previous studies have shown that during somatosensory stimulation there is a direct relationship between the rate of neuronal spiking and oxidative metabolism derived from the BOLD signal. In addition, as we report in another presentation at this meeting, increases in neuronal firing during spike-wave discharges (SWD) and generalized tonic-clonic seizures in WAG/Rij rats are accompanied by commensurate increases in CBF. Here we sought to determine whether BOLD signals changes during SWD and generalized tonic-clonic seizures are similar to or differ from the observed increases in neuronal firing and CBF.
In vivo BOLD fMRI measurements were performed in a 7T horizontal bore spectrometer in WAG/Rij rats during spontaneous SWDs and bicuculline-induced generalized tonic-clonic seizures under fentanyl/haloperidol anesthesia and neuromuscular blockade. EEG was recorded simultaneously with carbon filament radio-translucent electrodes to determine the timing of seizures. BOLD fMRI signals were then analyzed by comparing images acquired during seizures to baseline images, and superimposed on high resolution anatomical images in the coronal plane.
Comparison of ictal and interictal epochs revealed bilateral increases in BOLD fMRI signals in cortical and subcortical structures during both SWDs and bicuculline-induced generalized tonic-clonic seizures. However, unlike generalized tonic-clonic seizures, SWD-induced increases in BOLD signal were less intense and more localized, mainly involving primary somatosensory cortex and corresponding thalamic nuclei. Interestingly, the BOLD fMRI signal changes during generalized tonic-clonic seizures were also not uniform throughout the brain, but had very intense areas of activation interrupted by relatively "silent" symmetrical cortical areas.
BOLD fMRI signals increase during both SWDs and generalized tonic-clonic seizures in parallel with increases in neuronal spiking and regional CBF. During both SWDs and generalized tonic-clonic seizures the whole brain is not involved uniformly, rather selective networks particularly in the anterior brain regions are most intensely involved.
[Supported by: NIH NS02060, NIH MH067528, NIH NS037203, and the Patterson Trust]
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