Abstracts

Amygdala kindled seizures are a standard rodent model of epileptogenesis, however, the spread of limbic seizures to the neocortex has not been extensively studied. Involvement of the neocortex and subcortical structures such as the thalamus may play an important role in behavioral manifestations, including convulsive motor activity. Therefore, we investigated relationships between electrical activity in limbic, medial thalamic, and neocortical structures during the progression from limbic to neocortical seizures induced by kindling. Male Sprague-Dawley rats were implanted with electrodes in the basolateral amygdala, ipsilateral mediodorsal nucleus of the thalamus, and the frontal cingulate cortex. Afterdischarge threshold was determined for each animal, and kindling performed twice daily with stimulus current set at the afterdischarge threshold. Kindling was continued until animals had 3 consecutive class 5 seizures by the Racine scale. EEG power analysis and cross correlation analyses were performed using Spike2 software. Seizure duration increased progressively during kindling, and was linearly related to the behavioral Racine rating (r=0.994, p=0.001). EEG power during the first 30s of seizures compared to preictal baseline did not change significantly in the amygdala between class 1 and class 5 seizures. However, the frontal cortex showed a significant increase in EEG power between class 1 and class 5 seizures (n=24; p=0.0003, two tailed t-test). EEG power in the medial thalamus showed a similar dramatic increase between class 1 and class 5 seizures (p[lt]0.00001). Cross correlation analysis revealed a striking change in cortical-subcortical relationships during kindling. Thus, during class 1 seizures there was a low correlation between amygdala and frontal EEG (mean peak correlation = 0.16[plusmn]0.05) which increased significantly during class 5 seizures (0.40[plusmn]0.06; p=0.015). In contrast, correlation between frontal and medial thalamic EEG was relatively high during class 1 seizures (0.47[plusmn]0.17) and tended to decrease during class 5 seizures (0.22[plusmn]0.11). Correlation between amygdala and medial thalamic EEG did not change significantly between class 1 and class 5 seizures. Kindling produces a change in limbic and neocortical networks resulting in increased seizure duration and more dramatic motor convulsive activity. Even when analyses are confined to the initial 30s of seizures, kindling produces increased EEG power in the frontal neocortex and medial thalamus. Meanwhile, there is a switch in frontal networks from high fronto-thalamic correlation to high fronto-amygdalar correlation. These results suggest that during kindling, connections between the amygdala and neocortex are strengthened, facilitating spread of seizures from limbic to neocortical networks, and producing more dramatic motor convulsions. (Supported by NIH NS02060 and the Patterson Trust (to H.B.).)