Seizure Suppression Efficacy of Closed-Loop Versus Open-Loop Deep Brain Stimulation in a Rodent Model of Epilepsy

Abstract

We assess and compare the effects of both closed-loop 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 ten epileptic rats for a total of 240 subject-days (5760 subject-hours). For this purpose, all rats were randomly divided into two groups: the no-stimulation 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.

Dynamiceuticals: The Next Stage in Personalized Medicine

“…If we ignore the analytical results and try to control epileptiform activity using, instead of the aforementioned dynamically-guided closed-loop method to stop seizure generation, an open-loop protocol—which is the normal paradigm in most of clinical DBS applications (but see Morrell, 2011)—we will find that same stimulation protocol (5 seconds at 5 Hz) reduces seizure frequency by 17%, compared with the ~90% reduction using the closed-loop system (Salam et al, 2016). It is fair to note that other studies using periodic pacing without a closed-loop approach found greater success rate at stopping seizures, even though in these cases the stimulation was applied for longer times (Barbarosie and Avoli, 1997; Panuccio et al, 2013).…”

“…The reason that such a short stimulation in the previous studies (5 seconds) was efficient at preventing seizure generation is probably due to the typical extreme sensitivity to perturbations when a system is close to a dynamical bifurcation, as was elaborated in our publications. Such a short precisely-timed stimulus has the added advantage of these closed-loop methods in that they deliver less energy than conventional open-loop stimulation (Salam et al, 2016; Cagnan et al, 2017). …”

A framework for seizure detection using effective connectivity, graph theory, and multi-level modular network

“…Seizure detection is another application of FBC and EBC [26][27][28][29][30][31][32][33][34][35][36]. In [26,27], total information outflow based on the DTF and PDC considered as feature and SVM is a classifier, respectively.…”

N‐of‐1 Trials for Closed‐Loop Deep Brain Stimulation Devices

“…Said differently, these closed‐loop DBS systems could record and use the neural states of a patient to influence the device's stimulatory behavior. This change in stimulation pattern was an improvement over the traditionally constant stimulation patterns of open‐loop DBS devices in that the closed‐loop devices provide stimulation only when needed and simultaneously save battery power 4 . If the stimulation pattern of an open‐loop device needed adjustment, then a health care provider or consult programmer would have to change it manually.…”

“…This change in stimulation pattern was an improvement over the traditionally constant stimulation patterns of open-loop DBS devices in that the closed-loop devices provide stimulation only when needed and simultaneously save battery power. 4 If the stimulation pattern of an open-loop device needed adjustment, then a health care provider or consult programmer would have to change it manually. By contrast, closed-loop DBS stimulation patterns are the result of a personalized algorithm within the device that interprets the neural data and systematically determines when stimulation is needed.…”