Abstracts

Rationale: The mechanism governing loss of consciousness during temporal lobe seizures is unknown. In epilepsy patients, slow cortical oscillations are correlated with loss of consciousness during complex-partial seizures. In a rodent model of complex-partial limbic seizures, blood oxygen level dependent (BOLD) signal is increased in the hippocampus, septal nuclei, and anterior hypothalamus while BOLD signal is decreased in the neocortex, central thalamus, and midbrain tegmentum. The neuronal changes underlying these BOLD signal changes and the mechanistic importance of these changes have not been explored.Methods: We measured multiunit activity, single unit (juxtacellular) activity, and local field potential to determine the neuronal activity underlying BOLD fMRI changes in a rat limbic seizure model. Seizures were generated with a 2 second electrical stimulus in the hippocampus. The hippocampal stimulating electrode also recorded local field potential. At the same time, multiunit activity and local field potential were recorded in the lateral orbital frontal cortex and either the anterior hypothalamus or brainstem. In separate experiments, the anterior hypothalamic/brainstem electrode was replaced with a glass electrode for juxtacellular single unit activity recordings in the brainstem. We used juxtacellular recording methods and histology to verify nuclei and individual neurons.Results: Multiunit activity in the anterior hypothalamus was increased during seizures suggesting seizure propagation and a possible role in ictal neocortical slow wave generation. To support this hypothesis, we electrically stimulated the anterior hypothalamus and induced slow waves oscillations in the orbital frontal cortex. Conversely, multiunit and single unit activity in the brainstem were decreased during seizures, suggesting that brainstem firing may be important to maintaining activated cortical EEG during seizures. To support this hypothesis, we stimulated the brainstem and converted ictal cortical slow wave activity to desynchronous EEG in the orbital frontal cortex similar to the awake state.Conclusions: These findings as well our previously presented fMRI data suggest ictal neocortical slowing is caused by (1) seizure activity within limbic structures such as the hippocampus, anterior hypothalamus and septal nuclei, (2) increased activity in GABAergic projections from the lateral septum and anterior hypothalamus, which inhibit the ascending arousal systems and (3) decreased neuronal activity in the ascending arousal system and intralaminar thalamic nuclei. These results suggest a novel mechanism for neocortical slow oscillations and impaired consciousness in temporal lobe epilepsy.