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

Abstract

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 8 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 °C, but was suppressed efficiently at temperature values around 20 °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.

Focal Cooling for Drug-Resistant Epilepsy

“…Recent studies in rats have investigated these temperature thresholds. In a recent article, one group built a novel device to cool the cortex, remove excess heat, and monitor electroencephalography (EEG) activity in a rat epilepsy model . Their work reproduced earlier findings, showing that epileptiform discharges were not significantly reduced at 30 °C but were suppressed efficiently at 20 °C .…”

“…In a recent article, one group built a novel device to cool the cortex, remove excess heat, and monitor electroencephalography (EEG) activity in a rat epilepsy model . Their work reproduced earlier findings, showing that epileptiform discharges were not significantly reduced at 30 °C but were suppressed efficiently at 20 °C . A separate study tested focal cooling with different temperatures, also in anesthetized rats, and analyzed the effect on IEDs stratified by power spectrum band .…”

“…One solution described by Tanaka et al is to combine the cooling device with a convective heat sink made of copper wire mesh. An alternative is a heat pipe . Any of these devices could be paired with a seizure detection mechanism that would allow the implanted device to remain dormant and turn on only when ictal changes are detected and turn off once the electrical activity returns to the interictal baseline .…”

“…In animals, there has been significant progress made in developing small thermoelectric devices capable of delivering the necessary cooling for the necessary amount of time, displacing corresponding heat, measuring temperature and EEG, and remaining implanted without long term damage to the host . In humans, these device barriers must still be addressed, but investigations continue to deliver promising results …”

Dimensionality Reduction and Prediction of Impedance Data of Biointerface

“…Thirty-two recording sites with a 4 × 8 matrix configuration was used to record the ECoG signals. This device has shown outstanding performances in in vivo and in vitro applications [22]. A 32-channel microelectrode array (Figure 1B) was formed usi substrate and indium-tin-oxide (ITO) metallization eight micron (PI2611, HD Microsystems GmbH, Heidelberg, Germany) was spin-co wafer.…”