Abstracts

Rationale: In temporal lobe epilepsy (TLE), complex-partial seizures result in a loss of consciousness despite confinement of seizure activity to temporal lobe regions not normally associated with consciousness. Data from prior human studies of TLE suggest that neocortical activity during complex-partial seizures may be impaired, leading to diminished consciousness. We have previously shown in rats that partial limbic seizures are associated with large-amplitude slow activity, decreased neuronal firing, and diminished cerebral metabolism in the frontal neocortex ictally, resembling a sleep-like state. However, the network mechanisms producing loss of consciousness and cortical deactivation during complex-partial seizures are poorly understood. Methods: We performed simultaneous functional magnetic resonance imaging (fMRI) and electrophysiology experiments in lightly-anesthetized rats during electrically-stimulated partial seizures. We also recorded local field potentials (LFP), multiunit activity (MUA), and cerebral blood flow (CBF) from the hippocampus, lateral septum, medial thalamus, and orbitofrontal cortex during seizures in parallel experiments. We then stimulated the hippocampus, lateral septum, or medial thalamus in awake-behaving animals to compare changes in behavior and frontal cortical activity during activation of each structure to changes seen during limbic seizures. Fimbria-fornix transection was used in some animals to prevent lateral septal involvement in seizure activity. Results: During partial limbic seizures, we observed decreases in fMRI signal, neuronal activity, and CBF in the frontal cortex, contrasting with increases in all parameters in the hippocampus, lateral septum, and medial thalamus. Furthermore, seizures were associated with behavioral arrest in awake-behaving animals. Stimulation of the lateral septum, but not the hippocampus or medial thalamus, produced neocortical and behavioral effects resembling those seen during limbic seizures. Septal involvement in limbic seizures was abated by fimbria-fornix transection, which also prevented cortical deactivation and behavioral arrest during the events. In fimbria-fornix lesioned animals, synchronous stimulation of the lateral septum during hippocampal seizures resulted in reemergence of negative cortical and behavioral effects ictally. Conclusions: Our results suggest that during partial limbic seizures in rats, excitatory seizure activity in the hippocampus, medial thalamus, and lateral septum is accompanied by frontal neocortical deactivation. Neocortical deactivation is i.) produced during both limbic seizures and lateral septal stimulation, ii.) associated with behavioral arrest, iii.) prevented by fimbria-fornix transection, and iv.) present in fimbria-fornix lesioned animals during seizures with synchronous septal stimulation. These findings imply that lateral septal involvement in complex-partial temporal lobe seizures may contribute to neocortical deactivation, and in turn, impaired consciousness in human TLE.