Abstracts

Rationale: If a partial seizure propagates, or secondarily generalizes, then remote brain regions can also be disrupted by abnormally intense neuronal firing. What happens to the function of remote regions during a partial seizure that does not propagate from its region of onset? Human partial temporal lobe seizures are associated with remote changes including slow oscillations on electroencephalography (EEG) and decreased cerebral blood flow (CBF) in the neocortex. While ictal neocortical slow activity has traditionally been interpreted as seizure propagation, we hypothesize that it reflects a depressed cortical state resembling sleep or coma. To elucidate this hypothesis, we performed a multi-modal study using video/EEG, electrophysiology, and neuroimaging techniques to study both partial and secondarily-generalized limbic seizures in rats. Methods: We first used 24-hr continuous video/EEG monitoring to study spontaneous partial and secondarily-generalized limbic seizures in awake-behaving pilocarpine treated rats. Next, we investigated neuronal firing and physiology in partial and secondarily-generalized seizures induced by hippocampal stimulation using: 1) electrophysiology, 2) direct CBF measurements, and 3) functional magnetic resonance imaging (fMRI) weighted for blood oxygenation (BOLD) and blood volume (CBV). Finally, using these data, we calculated the cerebral metabolic rate of oxygen consumption (CMRO2) in both the hippocampus and frontal cortex during seizures. Results: Partial hippocampal seizures were associated with neocortical slow activity characterized by Up and Down states of neuronal firing, as well as decreased neuronal activity, reduced fMRI signals, and decreased CMRO2 in the frontal cortex. This activity differed markedly from seizure propagation observed in the neocortex during secondarily-generalized seizures, which was characterized by fast poly-spike activity, increased neuronal activity, elevated fMRI signals, and increased CMRO2. Other regions showing increased neuroimaging signals during both seizure types included the thalamus and septal nuclei. In awake-behaving rats, behaviorally mild seizures were more likely than behaviorally severe seizures to be associated with ictal neocortical slow oscillations, which closely resembled cortical rhythms during natural sleep or deep anesthesia. Conclusions: These findings suggest that ictal neocortical slow waves represent an altered cortical state of depressed function, not propagation of seizure activity. It is likely that in humans with TLE, ictal neocortical slow waves represent a pathophysiological consequence of limbic seizure activity, resulting in aberration of normal cortical function. This may cause loss of consciousness during complex-partial seizures. Our current results also provide preliminary insight into brain regions which may play an important role in mediating this phenomenon, including the septal nuclei and the thalamus. Understanding the long-range effects of limbic seizures may lead to improved therapies geared at disrupting the cortical effects of partial epilepsy.