Abstracts

Recently, fMRI became an important tool to study brain activity in epilepsy by investigating increases/decreases in the blood oxygenation level dependent (BOLD) response, known to be associated with changes in cerebral blood flow (CBF) and -volume (CBV). Although increases in the BOLD response have been linked to increases in neuronal activity, decreases of the signal, although often present, are generally neglected and still poorly understood. A detailed understanding of the relationship and causes of the different hemodynamic and neuronal signals is however essential for interpreting neuroimaging data in epilepsy and also has important implications for its treatment., 26 Wistar rats were injected with bicuculline (0.5mg/kg, iv) to induce generalized tonic-clonic seizures. Increased/decreased brain activity during seizures were investigated by combining fMRI and CBV imaging with neurophysiological recordings (field and unit activity), and local CBF measurements using laser Doppler flowmetry., The fMRI showed widespread BOLD and CBV increases throughout the cortex, basal ganglia and thalamus during seizures. Neurophysiological recordings, likewise, showed increased CBF, local field potential power and neuronal firing rate in cortical areas. Surprisingly, however, most of the rats had a decreased BOLD response in the hippocampus, which was accompanied by increased CBF and neuronal activity., Our results show that during generalized seizures the brain shows rather heterogeneous BOLD activity with increases/decreases in distinct networks. While our data confirm that increases in the BOLD signal during seizures correlate with increases in CBF, CBV and neuronal activity, we found that in the hippocampus increases in the latter three variables are associated with a decreased BOLD response. This observation argues against the hypothesis of a vascular steal phenomenon as cause for a decreased BOLD signal. Although the cause for the local dissociation of the signals is not known, one possibility is that the neuronal oxygen consumption in the hippocampus during seizures exceeds its supply; which is currently under investigation in our laboratory. In conclusion, our data show that fMRI can reveal important information about the pathophysiology of epilepsy and its treatment, but that the interpretation of the neuroimaging signals during seizures should proceed with caution, and might be different depending on brain region., (Supported by NIH R01 NS049307 and the Blattmachr Fund (HB); NIH R01 MH67528 and DC03710 (FH).)