Development of a large animal model for investigation of deep brain stimulation for epilepsy

Abstract

Background/objectives: To better understand the mechanism of action of deep brain stimulation (DBS) for epilepsy and to investigate implantable device features, it is desirable to have a large animal model to evaluate clinical-grade systems. This study assessed the suitability of an ovine model of epilepsy for this purpose.

Methods: Animals were anesthetized for surgery and 1.5 T MRIs collected. Unilateral anterior thalamic DBS leads, hippocampal depth electrodes and catheters were implanted using a frameless stereotactic system. Evoked responses and local field potentials were collected and stored for off-line analysis.

Results: Despite limited neuroanatomic information for this species, it was possible to reliably implant leads into the target structures using MR-guided techniques. Stimulation of these regions produced robust evoked potentials within this circuit that were dependent on stimulus location and parameters. High-frequency thalamic DBS produced a clear inhibition of both spontaneous and penicillin-induced ictal activity in the hippocampus which far outlasted the duration of the stimulation.

Conclusions: These preliminary results suggest that the sheep model may be useful for further investigation of DBS for epilepsy. The demonstration of marked suppression of network excitability with high-frequency stimulation supports a potential therapeutic mechanism for this DBS therapy.