Abstracts

Rationale: While simple partial seizures in patients with temporal lobe epilepsy (TLE) do not cause a loss of consciousness, complex partial limbic seizures do produce deficits in consciousness. Previously, we found that in TLE patients, loss of consciousness during (ictal) and following (postictal) complex partial seizures is associated with: 1) large amplitude slow oscillations in the frontal and parietal neocortex on intracranial EEG, and 2) decreased cerebral blood flow (CBF) in the frontoparietal association cortex measured using single position emission computerized tomography (SPECT). However, the long-range network mechanisms of ictal neocortical slowing are not known. Thus, we studied a rodent model of ictal neocortical slowing to determine whether this phenomenon represents propagation of seizure activity to the neocortex, or if it more closely resembles cortical UP and DOWN states present during slow-wave sleep and anesthesia.Methods: Using a bipolar stainless steel electrode, we electrically stimulated the dorsal hippocampus in lightly-anesthetized Sprague-Dawley rats (n=27), inducing partial limbic seizures. During seizures, local field potentials (LFP) and multiunit activity (MUA) were recorded in the hippocampus and the lateral orbital frontal cortex with high impedance microelectrodes, and CBF was recorded using laser Doppler flowmetry probes. Hippocampal and frontal cortical recordings were also collected under deep ketamine/xylazine anesthesia. In a few experiments (n=4), LFP recordings were collected in the mediodorsal thalamus during limbic seizures, as this region contains considerable connectivity to both the frontal cortex and hippocampus.Results: Limbic seizures were associated with large amplitude 1-2 Hz slow oscillations in the orbital frontal cortex, characterized by decreased MUA and decreased CBF. Ictal neocortical slowing was starkly contrasted with fast poly-spike activity seen in the hippocampus ictally, associated with dramatically increased MUA and CBF. Ictal slowing in the frontal cortex persisted postictally and closely resembled UP and DOWN states of neuronal firing observed when animals were placed under deep anesthesia. Thalamic recordings revealed propagation of fast poly-spike activity during intense portions of the seizure, resembling ictal hippocampal rhythms. However, thalamic slow oscillations were occasionally seen during less intense seizure activity, more closely resembling frontal slowing. Conclusions: Our results suggest that ictal neocortical slowing may represent depressed neocortical function during seizures resembling natural sleep, and does not represent the spread of seizure activity. The mediodorsal thalamus may play a role in mediating neocortical slowing during limbic seizures, and future studies should examine this possibility.