Abstracts

Generalized seizures are assumed to show a pattern of overall increased neuronal activity affecting the whole brain. Recent experiments have shown that the brain shows a rather heterogeneous pattern of increased and decreased activity during generalized seizures. While some consensus exists about increases, decreased neuronal activity during generalized seizures is still a matter of debate. Here we investigate increased and decreased activities during absence- and generalized tonic-clonic (T/C) seizures by combined EEG/fMRI measurements. We used WAG/Rij rats, because rats of this strain develop spontaneous absence epilepsy. T/C-seizures were induced by bicuculline injections. Rats were equipped with carbon filament electrodes for EEG recordings and placed inside a 9.4T horizontal bore spectrometer. During recordings rats were anesthetized with fentanyl/haloperidol and received D-tubocurarine for neuromuscular blockade. BOLD fMRI signals were analyzed by comparing images acquired during seizures to baseline images, and by comparing images acquired during different phases of seizure activity (T/C only). Our recordings revealed widespread increases of the BOLD signal throughout the cortex, basal ganglia, thalamus, septum and hypothalamus and also decreased BOLD responses throughout the cortex and septum for both seizure types, but in slightly different locations from the increases. However, increased and decreased activity was generally more intense and widespread in T/C compared to absence seizures that showed a more fronto-parietal dominance. Compared to absence, T/C-seizures also showed mixed increases/decreases in the basal ganglia and hypothalamus, and decreases in the ventral pallidum and ncl. accumbens. Interestingly, the hippocampus consistently displayed signal decreases for both seizure types. Our results suggest that during generalized seizures the brain is not homogenously affected, but rather shows increased/decreased BOLD activities in distinct networks. Furthermore, activation/inactivation patterns are different, dependent on seizure type. In particular the decreases in BOLD activity, especially in the hippocampus, are interesting and deserve further investigation. While decreases in hippocampus during absence seizure might correspond to the non-involvement of this structure in this seizure type, its cause in T/C-seizures (vascular steal, increased O2 consumption exceeding compensatory blood flow, or other mechanisms) remains to be elucidated. Our results encourage further studies of the mechanisms of increased/decreased activity during generalized seizures which may lead to new therapeutic interventions in epilepsy. (Supported by NIH R01 NS049307 and the Blattmacher Fund (HB); NIH R01 MH67528 and DC03710 (FH).)