Abstracts

Partial seizures in patients with temporal lobe epilepsy (TLE) are often classified as either complex, characterized by deficits in consciousness, or simple, involving no loss of consciousness. Prior intracranial EEG studies of complex-partial seizures in TLE patients have shown large amplitude slow waves in the frontal and parietal cortices ictally, most prominent in the orbitofrontal cortex. This neocortical slowing is associated with decreased cerebral blood flow in these areas measured using single photon emission computed tomography (SPECT). It has been hypothesized that ictal neocortical slowing may reflect abnormal cortical and subcortical network interactions during temporal lobe seizures, responsible for the deficits in consciousness seen in TLE patients. However, an animal model is needed to further study the mechanisms and pathophysiology of neocortical slowing., Sprague-Dawley rats were implanted with a bipolar stimulating/recording electrode in the dorsal hippocampus, and a frontal recording electrode in the association (n=5), cingulate (n=6), or lateral orbital (n=5) cortex. After one week of recovery, animals were kindled with a daily 1s train of 1ms, 60Hz biphasic pulses at the threshold current necessary to produce an afterdischarges of [gt]3s duration. EEG recordings from the hippocampal and frontal electrodes were compared. Behavior was rated using the standard Racine scale., Hippocampal EEG showed seizure activity, consisting of polyspike discharges, during all events. While frontal recordings in the association and cingulate cortices showed rapidly propagating fast (polyspike or sharp) activity within 1-2s of hippocampal stimulation, large amplitude slow waves of approximately 3-4 Hz were seen ictally in the lateral orbital cortex. Behaviorally, these seizures did not involve motor convulsive activity. As daily stimulations proceeded, the slow rhythm in the lateral orbital cortex progressively converted to fast spike activity, suggesting seizure propagation., Our results show neocortical slowing in the lateral orbital cortex during hippocampal seizures in rats. These data suggest that hippocampal kindling may provide a good animal model of complex-partial seizures in patients with TLE, demonstrating neocortical slow activity outside the region of seizure initiation. Further studies into the fundamental mechanisms of neocortical slowing in this model may provide insight into pathophysiology of altered consciousness in complex-partial seizures, and may lead to improved treatments of TLE., (Supported by NIH R01 NS049307, the Betsy and Jonathan Blattmachr Family, and NIH Medical Scientist Training Program T32 GM07205.)