Implantable cell-size ‘neural pixel’ device senses and blocks epileptic seizures

August 26, 2016

A biochemical system for reducing epileptic activity (experimentally generated chemically) in mice hippocampus brain tissue. The miniature “neural pixel” device (bottom) sensed the epileptic attack and then delivered the natural calming neurotransmitter GABA via PEDOT:PSS electrodes, which also  recorded the subsequent electrophysiological activity to confirm effectiveness. (credit: Amanda Jonsson et al./PNAS)

Researchers at Linköping University in Sweden and in France have developed a “neural pixel” device that when implanted in a mouse hippocampus brain slice detects the initial signal of an epileptic attack and also locally administers the exact dose of the natural neurotransmitter GABA needed to stop the attack.

The researchers used a conducting polymer called poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS) for electrodes. It has ten times better conductivity than gold, platinum, and iridium electrodes.  A tiny organic electronic ion pump* was used to pump the GABA neurotransmitter through a selective membrane, enabling high spatiotemporal delivery resolution (tiny and works fast) without requiring liquid flow (which is hard to control).

The idea is to have local, real-time measurement and precision delivery directly to specific neurons, which could pave the way in the future to closed-loop, fully automatic, miniature therapeutic devices. Combining electronic detection and release in the same electrode is a major advance, according to the researchers.

The development offers an alternative to drugs taken orally, which may be toxic outside the brain, may not cross the blood−brain barrier, or may have deleterious side effects when they penetrate the brain’s “healthy” regions, affecting physiological functions such as memory and learning. It also opens up a range of opportunities in basic neuroscience.

The research results have been published in the journal Proceedings of the National Academy of Sciences (PNAS).

* The implantable ion pump was developed at Linköping University’s Laboratory for Organic Electronics and announced in 2015. It was used initially to deliver exact dosages of painkiller GABA to the exact location where the pain signals reach the spinal cord for further transmission to the brain, and could be in clinical use in five to ten years, the researchers say.

The neural sensor for the initial signal of an epileptic attack was developed by the LiU researchers’ collaborators at the École Nationale Supérieure des Mines in Gardanne, France. The mouse experiments were performed at Aix-Marseille University. The entire device is manufactured from conductive, biocompatible plastic.

The Swedish part of the research was funded by Vinnova, the Swedish Research Council, and the Knut and Alice Wallenberg Foundation. The work took place at the OBOE center, under the leadership of Asst. Prof. Daniel Simon and Professor Magnus Berggren.

Abstract of Bioelectronic neural pixel: Chemical stimulation and electrical sensing at the same site

Local control of neuronal activity is central to many therapeutic strategies aiming to treat neurological disorders. Arguably, the best solution would make use of endogenous highly localized and specialized regulatory mechanisms of neuronal activity, and an ideal therapeutic technology should sense activity and deliver endogenous molecules at the same site for the most efficient feedback regulation. Here, we address this challenge with an organic electronic multifunctional device that is capable of chemical stimulation and electrical sensing at the same site, at the single-cell scale. Conducting polymer electrodes recorded epileptiform discharges induced in mouse hippocampal preparation. The inhibitory neurotransmitter, γ-aminobutyric acid (GABA), was then actively delivered through the recording electrodes via organic electronic ion pump technology. GABA delivery stopped epileptiform activity, recorded simultaneously and colocally. This multifunctional “neural pixel” creates a range of opportunities, including implantable therapeutic devices with automated feedback, where locally recorded signals regulate local release of specific therapeutic agents.