Abstracts

RATIONALE: Penicillin-induced seizures in animal models of epilepsy have been evaluated electrophysiologically in the past. Activation of subcortical structures such as the thalamus have been demonstrated in these studies. Whether other subcortical structures are routinely activated in cortical models of focal epilepsy is not known. We sought to non-invasively evaluate these structures using fMRI techniques.
METHODS: Three adult merino sheep were used. Surgery was performed one week prior to the fMRI study to implant a custom made penicillin infusion port and intracranial EEG electrode strips over both hemispheres. On the day of the experiment, animals were anaesthetised using opiate and histamine anaesthesia. This has been previously shown to produce adequate anaesthesia while preserving fMRI responses to penicillin-induced seizures. Epileptiform spike and wave activity as well as electrographic seizures were then generated by unilateral instillation of 8,000 to 10,000 IU of sodium penicillin into the right prefrontal cortex. Functional MRI was performed at 1.5 Tesla with concurrent bilateral intracranial EEG. Blood oxygen level dependant (BOLD) weighted signals were measured. Subcortical structures were evaluated by 5 coronal slices with data points sampled every 10 seconds throughout the course of the experiment.
RESULTS: In all three animals, focal electrographic seizures were seen within 17 minutes after penicillin infusion. There was an average of 13 seizures per animal, each lasting up to 30 seconds. The bold fMRI signal intensity was evaluated during each of these seizures. Areas that showed large variance in subcortical sites were determined. In all three animals, dramatic signal BOLD signal increases where seen which occurred at a frequency consistent with the frequency of seizures was seen in the amygdala ipsilateral to the site of penicillin injection. There was also a high signal change in the region of the ipsilateral hypothalamus, most consistent with the mamillary body.
CONCLUSIONS: BOLD signals were seen in the ipsilateral amygdala and mamillary body during electrographic seizures in frontal lobe penicillin-induced seizures in sheep. No consistent activation was seen in the thalamus. These results suggest that the amygdala and mamillary body are key subcortical structures involved in maintenance or propagation of seizures in this experimental model.
[Supported by: National Health and Medical Research Council of Australia (Grant # 135400), Brain Imaging Research Foundation, Canadian Institutes of Health Research, and Alberta Heritage Foundation for Medical Research.]