Abstract
We assess and compare the effects of both closedloop and open-loop neurostimulation of the rat hippocampus by means of a custom low-power programmable therapeutic neurostimulation device on the suppression of spontaneous seizures in a rodent model of epilepsy. Chronic seizures were induced by intraperitoneal kainic acid injection. Two bipolar electrodes were implanted into the CA1 regions of both hippocampi. The electrodes were connected to the custom-built programmable therapeutic neurostimulation device that can trigger an electrical stimulation either in a periodic manner or upon detection of the intracerebral electroencephalographic (icEEE) seizure onset. This device includes a microchip consisting of a 256-channel icEEG recording system and a 64-channel stimulator, and a programmable seizure detector implemented in a field-programmable gate array (FPGA). The neurostimulator was used to evaluate seizure suppression efficacy in 10 epileptic rats for a total of 240 subject-days (5760 subject-hours). For this purpose, all rats were randomly divided into two groups: the nostimulation group and the stimulation group. The no-stimulation group did not receive stimulation. The stimulation group received, first, closed-loop stimulation and, next, open-loop stimulation. The no-stimulation and stimulation groups had a similar seizure frequency baseline, averaging five seizures per day. Closed-loop stimulation reduced seizure frequency by 90% and open-loop stimulation reduced seizure frequency by 17%, both in the stimulation group as compared to the no-stimulation group.
VI. CONCLUSION
This study demonstrates engineering aspects associated with the effective epileptic seizure control and proposes a therapeutic neurostimulation device for the treatment of refractory epilepsy. The results of this study using a custombuilt therapeutic neurostimulation device reveal a greater efficiency at reducing ictal events (90% seizure frequency suppression) using a closed-loop stimulation method, whereas the open-loop resulted in a 17% reduction. This seizure suppression efficacy is achieved as a result of triggering a stimulation just before a seizure development, in response to an abnormal icEEG pattern detection; whereas the open-loop system delivers stimulations periodically. Thus, the closedloop strategy increases efficiency of the stimulations, while reducing the possible side effects using the minimum number of stimulations as required. Therefore, an effective alternative to the open-loop neurostimulator is the closedloop neurostimulator, in which the involvement of the deep brain stimulation is minimal. As an extension of the work on epilepsy, the new era of deep brain stimulation strategies based on closed-loop paradigms may be able to target different pathological aspects of brain activity for the treatment of various neurological disorders.
