Abstracts

Rationale: The generalized spike-and-wave discharges (GSWDs) are the result of irregular coupling between thalamic oscillations and cortical rhythms. However, the varying contribution of each cortical region to its clinical manifestations have not been well studied. This study is aimed to characterize the hemodynamic changes during GSWDs over time in order to better understand the dynamic processes that lead to the development of various clinical manifestations of absence seizures. Methods: A pharmacological animal model was used. Animals were anesthetized using 1% isoflurane. Following 10 min simultaneous baseline scalp-EEG and 9.4 T fMRI recordings, GSWDs were generated in 8 Long-Evans rats using an intraperitoneal injection of ?-butyrolactone (GBL; 200 mg/kg). fMRI recordings were made for 60 min post-injection. EEG recordings were used to demonstrate the temporal occurrence of spiking and seizure activity, while general linear modeling, independent component analysis and dynamic causal modeling were implemented to characterize the hemodynamic changes and functional network abnormalities recorded using BOLD-fMRI. Results: GBL produced bilaterally synchronous GSWDs within 2-5 min of its administration. We observed hemodynamic changes following GSWD onset in which there were unique patterns of activity specific to each brain area. The cerebral cortex showed a gradual and sustained increase in blood oxygenation in response to GBL injection preceding GSWD onset. A lesser effect was observed in the thalamic nuclei. Cortical hemodynamic spiking was also observed in some rats during SWDs. Conclusions: Using simultaneous EEG-fMRI, we demonstrated robust hemodynamic signal changes in brain areas that have been electrophysiologically implicated in the generation of GSWDs. Hemodynamic spiking superimposed on the rise in the blood flow to the crebreal cortex was a novel finding that requires further studies.