A multimodal, implantable sensor array and measurement system to investigate the suppression of focal epileptic seizure using hypothermia

Objective. Local cooling of the brain as a therapeutic intervention is a promising alternative for patients with epilepsy who do not respond to medication. In vitro and in vivo studies have demonstrated the seizure-suppressing effect of local cooling in various animal models. In our work, focal brain cooling in a bicuculline induced epilepsy model in rats is demonstrated and evaluated using a multimodal micro-electrocorticography (microECoG) device. Approach. We designed and experimentally tested a novel polyimide-based sensor array capable of recording microECoG and temperature signals concurrently from the cortical surface of rats. The effect of cortical cooling after seizure onset was evaluated using 32 electrophysiological sites and eight temperature sensing elements covering the brain hemisphere, where injection of the epileptic drug was performed. The focal cooling of the cortex right above the injection site was accomplished using a miniaturized Peltier chip combined with a heat pipe to transfer heat. Control of cooling and collection of sensor data was provided by a custom designed Arduino based electronic board. We tested the experimental setup using an agar gel model in vitro, and then in vivo in Wistar rats. Main results. Spatial variation of temperature during the Peltier controlled cooling was evaluated through calibrated, on-chip platinum temperature sensors. We found that frequency of epileptic discharges was not substantially reduced by cooling the cortical surface to 30 degrees C, but was suppressed efficiently at temperature values around 20 degrees C. The multimodal array revealed that seizure-like ictal events far from the focus and not exposed to high drop in temperature can be also inhibited at an extent like the directly cooled area. Significance. Our results imply that not only the absolute drop in temperature determines the efficacy of seizure suppression, and distant cortical areas not directly cooled can be influenced.

Automated summary

The study demonstrated that cooling the cortical surface to around 20 degrees Celsius efficiently suppresses epileptic discharges, with distant cortical areas also being influenced. This suggests that the efficacy of seizure suppression is not solely determined by the absolute drop in temperature.