Abstracts

Rationale: Functional magnetic resonance imaging (fMRI) studies show increases and decreases in the blood oxygenation level dependent (BOLD) response in selective neuronal networks. An increase in BOLD response has been shown to correspond with increase in neuronal activity and cerebral blood flow (CBF) using laser Doppler flowmetry (LDF) in rat somatosensory cortex. However, decreases in BOLD fMRI response are poorly understood. Therefore, an animal model is needed to study of the relationship and causes of the different hemodynamic response and corresponding neuronal signals. Aims of this study were two fold: i) to map various hemodynamic responses and to calculate neuro-energetics in whole brain during spike-wave discharges (SWD) in absence epilepsy using multimodal fMRI, and ii) to relate fMRI signals to electrophysiological changes during SWD within involved brain regions. Methods: We conducted combined electroencephalograph (EEG)- multimodal fMRI on anesthetized female WAG/Rij rats (n=9), an established model of human absence epilepsy at 9.4 Tesla. In parallel experiments, we conducted electrophysiology and CBF recordings using LDF under identical conditions. Results: Our results show increased BOLD fMRI response in the somatosensory and motor cortex, thalamus, and brainstem during SWD (n=9). Our electrophysiological and LDF recordings revealed increases in neuronal activity and CBF in the somatosensory cortex. Interestingly, our fMRI measurements also showed prominent decreases in BOLD response in the caudate-putamen and hippocampus during SWD. We can speculate that the observed BOLD decreases during SWD may be caused by three different mechanisms: 1) vascular steal; 2) decreases in BOLD response in the caudate-putamen may be due to net decrease in neuronal firing rate because of the combination of the distinctive alternation of increased activity during spikes and decreased activity during waves; 3) decreases in BOLD response in the hippocampus may be due to decrease in neuronal activity because hippocampus has been shown to be spared during absence seizures. We are currently conducting measurement of cerebral blood volume (CBV) by fMRI during absence seizures together with parallel experiments for electrophysiological and CBF measurement in regions of BOLD signal decreases to explain above findings. Conclusions: Based on our results, we can conclude that SWD in WAG/Rij rats can be used as a model to investigate the fundamental mechanisms of both BOLD fMRI increases and decreases during absence seizures. We found that BOLD fMRI increases are associated with regional increases in neuronal activity, and further investigations are continuing to see the physiological changes underlying fMRI decreases. Above findings may have an impact on the interpretation of various fMRI signals in human absence epilepsy. (Support: : NIH R01 NS049307 and The Betsy and Jonathan Blattmachr family.)