Flexible graphene-based neural probes improve epilepsy detection

The results, published in the prestigious journal Nature Nanotechnology, were obtained by Graphene Flagship partners at the Catalan Institute of Nanoscience and Nanotechnology (ICN2) and the Institute of Microelectronics of Barcelona (IMB-CNM-CSIC), both in Spain, in collaboration with researchers at the Institute of Neurology, and the Nanomedicine Lab, based at Graphene Flagship partners University College London and the University of Manchester, UK, respectively.

Epilepsy is one of the most common serious brain disorders worldwide, with up to 30% of people unable to control their seizures using traditional anti-epileptic drugs. For drug-refractory patients, epilepsy surgery may be a viable option. Surgical removal of the area of the brain where the seizures first start can stop them. However, the success of surgery relies on accurately identifying the seizure onset zone (SOZ). 

The ability to record and map the full range of brain signals using electrophysiological probes will greatly advance our understanding of brain diseases and aid the clinical management of patients with diverse neurological disorders. However, current technologies are limited in their ability to accurately obtain with high spatial fidelity ultraslow brain signals.

Epileptic signals span a wide range of frequencies – much larger than those monitored in conventional electroencephalografy (EEG). Electrographic biomarkers of SOZ include very fast oscillations as well as infraslow activity and direct-current (DC) shifts. The latter provide important information associated with seizure onset, but are seldom used, due to the poor performance of current probes to record these types of slow brain signals. Thus, this new technology will allow researchers to investigate the role infraslow oscillations play in promoting susceptibility windows for the transition to seizure, as well as improving detection of clinically relevant electrophysiological biomarkers associated with epilepsy.

The graphene depth neural probe (gDNP) developed by the Graphene Flagship researchers consists of a millimetre-long linear array of micro-transistors embedded in a micrometre-thin polymeric flexible substrate. The flexible gDNP devices were chronically implanted in small animal models of seizures and epilepsy. The implanted devices provided outstanding spatial resolution and wide bandwidth recording of epileptic brain signals over weeks. Extensive chronic biocompatibility tests confirmed no significant tissue damage and neuro-inflammation, thanks to the biocompatibility of the used materials, including graphene, and the flexible nature of the gDNP device.

Clinical translation of this technology will offer the possibility to identify more precisely the zones of the brain responsible for seizure onset before or during surgery, leading to less extensive resections and better outcomes. This technology can also be applied to improve our understanding of other neurological disorders associated with ultraslow brain signals, such as traumatic brain injury, stroke and migraine.

Serge Picaud, Graphene Flagship Deputy Leader for Biomedical Technologies, says: “Precise diagnostic tools have improved patient care by improving the characterization of pathologies and by allowing assessment of new therapies. This novel graphene electrode technology enters in this category of great diagnostic tools for a fine assessment of brain states and a future improvement of patient care in many neurological diseases including epilepsy and all neurodegenerative diseases.”

Andrea Ferrari, Science and Technology Officer of the Graphene Flagship and Chair of its Management Panel, adds: “We are reaching the stage where medical applications of graphene and related materials become ever more relevant. This science and technology area is coming to the fore, as shown by these world leading results of the Graphene Flagship. This work also paves the way to new research directions, only possible thanks to the use of graphene”. 

Reference:

Full bandwidth electrophysiology of seizures and epileptiform activity enabled by flexible graphene micro-transistor depth neural probes. Nature Nanotechnology, 2021. DOI: 10.1038/s41565-021-01041-9.