Abstracts

Rationale: Deep brain stimulation has become a viable means to treat seizures in patients with medically intractable epilepsy. So far, however, the effectiveness of stimulation of the brain structures chosen as stimulation target to decrease or block seizure activity is low. Corpus callosum (CC) is one of the potential targets for deep brain stimulation and it has some advantages compared to other brain areas – it has a topographic organization, and stimulation of different parts of CC can control activity of different neocortical and other brain areas. In this study, we tested the hypothesis that corpus callosum could be a potential site for stimulation to stop epileptiform activity.Methods: Studies were performed in 3 naïve rats and 6 epileptic rats 3-4 months after status epilepticus induced by i.p. pilocarpine injection. Four stimulating electrodes were implanted into the corpus callosum 1 mm apart along the saggital axis. Recording electrodes were implanted bilaterally in the frontal, sensory motor, and occipital neocortex, as well as in the CA1-DG areas of hippocampus. Experiments were carried out under freely moving conditions starting one week after electrode implantation. Results: In both naïve and epileptic rats, a single electrical shock delivered to the electrodes implanted into the anterior parts of CC evoked mixed anti- and orthodromic responses in all areas of neocortex bilaterally. Electrical stimulation of the posterior part of the CC evoked the same responses as in the neocortex and the hippocampus. The responses in the hippocampus were due to the proximity of stimulating electrodes to the hippocampal commissure located just beneath the corpus callosum. During immobility initial short latency responses were followed by spindle oscillation. In the every epileptic rat delivery of 200 Hz stimulation for of 50-200 msec suppressed epileptiform activity (Fig. 1) at some electrode contacts but not others. The location of effective electrode contact was inconsistent across the animals. Tetanic stimulation longer than 500 msec evokes epileptiform afterdischarges. Electrodes located in the areas that evoke strong short latency response in the hippocampus did not suppress neocortical epileptiform activity but did suppress hippocampal epileptiform discharges. Conclusions: These data support the hypothesis that CC is a potential target for deep brain stimulation. For suppression of limbic seizures, stimulation of the hippocampal commissure would be more effective, while for suppression of neocortical seizures, the stimulation of corpus callosum would be more effective. Given to the rudimentary nature of hippocampal commissure in humans the effect seen here in rat hippocampus may not occur in patients. Closed-loop responsive stimulation studies in epileptic patients could test this hypothesis. Acknowledgements: This work was supported by Neuropace, Inc and ATP Cooperative Agreement No. 70NANB3H3044