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.

Placement of Deep Brain Electrodes in the Dog Using the Brainsight Frameless Stereotactic System: A Pilot Feasibility Study

“…Figure 5 shows the morphology of the averaged EPs over the experimental period together with variation in the time‐to‐peak amplitude on consecutive days. Averaged EPs displayed a wave with latency of approximately 40 ms and amplitude of 0.02 mV, consistent with activation of the Circuit of Papez as seen in sheep models 22. Interestingly, there was a slight decrease in EP amplitude that occurred approximately 1 hour after each dose of levetiracetam once this was initiated (Fig 5).…”

“…In all cases, the dogs recovered without adverse neurologic effects and showed no outward sign of the effects of the implantation or stimulation. In addition, stimulation and recording from the electrodes showed that stimulation of the ANT can produce evoked responses identical to those obtained in other large animal models in which similar studies have been performed 22. The shape and latency of the EPs was consistent with activation of the circuit of Papez, suggesting that the dog is a suitable model for the testing of DBS strategies in the treatment of epilepsy.…”

“…For this reason, large animal models such as the sheep and minipig are being developed that will allow better translation of DBS strategies into people. Recently, one such study has investigated the feasibility of implanting leads into the ANT and hippocampus of a sheep model as part of the evaluation of a novel device capable of both stimulating and recording from the brain 22, 23…”

Chronic Evaluation of a Clinical System for Deep Brain Stimulation and Recording of Neural Network Activity

“…This work was conducted in an ovine model recently developed in our laboratory to study DBS for epilepsy [18]. The prior study investigated stimulation and recording from nodes within the circuit of Papez, specifically the anterior nuclear (AN) region of the thalamus, and the hippocampus (HC).…”

Deep Brain Stimulation for the Treatment of Epilepsy: Circuits, Targets, and Trials

“…(Adapted from [23] and [46]) amongst other approaches, DBS. For example, theta band activity within the septo-hippocampal circuit has been associated with decreased seizures [119,120], and continuous multimicroelectrode electrical stimulation using theta frequencies in a rat model of temporal lobe epilepsy decreases seizures (Desai et al, in preparation). Conceivably, the RNS could be adapted to accomplish this.…”