A Sheep Model for the Study of Focal Epilepsy with Concurrent Intracranial EEG and Functional MRI


Address correspondence and reprint requests to Dr. G. D. Jackson at Brain Research Institute, Neurosciences Building, ARMC, Banksia Street, West Heidelberg, Victoria, Australia 3081. E-mail: BRI@brain.org.au


Summary:  Purpose: We describe a sheep model of penicillin-induced seizure activity using electroencephalography (EEG) and functional MRI (fMRI).

Methods: Ten adult sheep were used. Spikes and seizures were generated by instillation of 8,000–10,000 IU of penicillin into the right prefrontal cortex via a specially designed port. Bilateral intracranial EEG was acquired by using carbon fiber electrodes. Animals had behavioral characterization of their seizures and were then anesthetized for fMRI studies. Functional MRI was performed at 1.5 and 3 Tesla by measuring blood oxygen level–dependent (BOLD) weighted signal intensity at different times during the evolution of seizures.

Results: Behavioral seizures were associated with electrographic seizures. Intracranial EEG obtained in the MR scanner was of high quality. Focal spiking and seizures were seen in all animals and developed 11.3 ± 11.2 s and 17.3 ± 12.1 min after penicillin administration, respectively. An average of 13 ± 4.8 seizures were seen per animal, each lasting 27.3 ± 12.3 s. Functional MR images with little parenchymal artefact were obtained. Regional BOLD signal-intensity changes were observed during seizures at the seizure focus and ipsilateral amygdala.

Conclusions: We have developed an animal model of partial epilepsy in which seizures can be reliably elicited with concurrent fMRI and intracranial EEG. During unilateral electrographic seizures, focal BOLD signal changes occurred at the seizure focus and ipsilateral amygdala, suggesting the presence of a cortico–subcortical loop. This observation illustrates the potential of the model for understanding seizure generation, spread, and possibly the consequences of repeated seizures on the brain.