Abstracts

Rationale: Temporal lobe epilepsy is marked by focal seizures which are either complex, characterized by deficits in consciousness, or simple, involving no loss of consciousness. However, it is not understood how a seizure confined to the temporal lobe could cause loss of consciousness. In humans, complex partial seizures with loss of consciousness are characterized by slow waves across the neocortex concurrent with polyspike seizure activity in the temporal lobe. We have previously investigated a rodent model of hippocampal-stimulated seizures utilizing a single radio frequency surface coil to map dorsal brain structures involved in limbic seizures. The imaging data from the more ventral subcortical structures which may be crucial mechanistically for neocortical slow activity were limited by decreased signal-to-noise ratio (SNR). Methods: To obtain images with dramatically increased SNR in more ventral structures, we developed a new 2x1 quadrature coil, which acts as a transreciever. Using our newly developed coil, blood oxygen level dependent (BOLD) fMRI measurements were performed on a 9.4T system during seizures induced by brief hippocampal stimulation with a bipolar tungsten electrode. Results: FMRI increases were seen in the hippocampus, septal nuclei, anterior hypothalamus and mediodorsal thalamus. FMRI decreases were seen in cortical regions including the orbital frontal, cingulate and retrosplenial cortex, as well as in other neocortical areas to a lesser degree. FMRI decreases were also observed in subcortical regions such as the thalamic intralaminar and posterior nuclei, basal ganglia, and midbrain tegmentum. Conclusions: Together, these imaging findings suggest a possible mechanism for ictal neocortical slowing based on 3 overlapping networks. (1) Hippocampal seizures propagate to the structures of the limbic system such as the mediodorsal thalamus, anterior hypothalamus and septal nuclei, (2) inhibitory projections of the lateral septum, anterior hypothalamus or other regions suppress the forebrain arousal systems and (3) neuronal activity in central thalamic nuclei and the brainstem reticular formation are decreased which removes excitatory input to the neocortex. These new subcortical imaging data suggest new and potentially crucial nodes of the network responsible for neocortical dysfunction and impaired consciousness in temporal lobe seizures as well as provide targets for mechanistic studies in the future.