Abstracts

Rationale: Increases in the blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) response in corticothalamic networks studies have been reported in absence epilepsy. However, decreases of the BOLD fMRI response also occur, but are not properly understood. An animal model can provide a detailed understanding of the causes and relationship of the different fMRI and neuronal signals. The aim of this study was to map various hemodynamic responses and neuro-energetics in whole brain during spike-wave discharges (SWD) using multimodal fMRI. The study was further designed to relate fMRI signals to electrophysiological changes during SWD in involved brain regions. Methods: Combined EEG-fMRI at 9.4 Tesla, cerebral blood volume (CBV)-weighted and BOLD fMRI, parallel electrophysiology and cerebral blood flow (CBF) recordings using laser Doppler flowmetry (LDF) under identical conditions were performed. Female WAG/Rij rats, an established model of human absence epilepsy were used to conduct this study. Results: An increase in BOLD fMRI signal was observed in the somatosensory and motor cortex, anterior cingulate cortex, retrosplenial cortex, thalamus, brainstem, and superior colliculi during absence seizures (n= 15). Increased fMRI and CBV signals in the somatosensory cortex and thalamus were associated with increases in neuronal activity and CBF as revealed by electrophysiological and LDF recordings, respectively. Our fMRI results also showed prominent decreases in BOLD (n= 15) and CBV (n= 9) signals in the caudate-putamen during SWD. We propose that the observed BOLD decreases in associated brain regions may be caused by a net decrease in neuronal firing rate. This may possibly be due to the combination of the distinctive alternation of increased activity during spikes and decreased activity during waves. Conclusions: Our data show that SWD in WAG/Rij rats can be used as a model to investigate the fundamental mechanisms of both fMRI increases and decreases during absence seizures. BOLD fMRI and CBV increases are associated with regional increases in neuronal activity and increase in relative CBF. Further studies are underway to unravel the physiological changes underlying fMRI and CBV decreases. These findings will be important for the interpretation of various fMRI signals in human absence epilepsy. (Grant/Other Support: NIH R01 NS049307 AND The Betsy and Jonathan Blattmachr family)