To better understand the underlying mechanisms of SUDEP, we are carrying out a translational project which will investigate the role that spreading depolarisation (SD), and subsequent spreading depression, plays in these processes.
But, what is spreading depolarisation (SD)?
SD is a brain signal associated with seizures which shows a sudden wave of hyperactivity, followed by a wave of suppression of brain activity. This is like a power surge followed by a power cut, which causes normal brain activity to shut down. SD can last a relatively long time – tens of seconds – and can, worryingly, affect the areas of the brain that are required for breathing, or other areas of the brain associated with arousal and restoration of breathing.
Although SDs have been known about for decades, their involvement in epilepsy has only recently been considered. Around 10 years ago, ERUK-funded research carried out in our lab was among the first to show the presence of a post-seizure SD by using imaging methods in experimental models of epilepsy. Although a powerful research tool, these imaging experiments require sophisticated equipment that is not readily available, nor suitable for humans. A major reason why the involvement of SDs in epilepsy is still a relatively understudied area given its potential importance, is that the electrographic tools epilepsy researchers commonly use to study seizures are poorly suited to detect SDs.
Since 2018, the Wykes lab has been developing electrographic probes based on graphene with partners on the European Union Graphene Flagship Project. Graphene has several advantages over traditional metal-based electrodes that are more commonly used for recording brain activity. Importantly they can record a wide range of brain signals. Graphene micro-transistors (devices used to amplify electrical activity) can detect the abnormal slow brain signals that result from an SD, at the same time as capturing higher frequency activity associated with a seizure.
Our preliminary data applying these probes to epilepsy research indicates that they can map seizure and SD propagation over and through large areas of the brain. This gives us the ability to determine what happens to brain activity and respiration when an SD invades a particular area of the brain. We also plan to investigate whether localised brain stimulation can prevent SD invasion and shutting down of crucial brain regions or hasten their recovery from suppression.
At the same time, my collaborator Dr Beate Diehl will examine EEG recordings from patients at high-risk of SUDEP to determine whether the very slow brain signals that can be detected in clinical EEG relate to PGES and respiratory abnormalities. We will also implement a specialised research amplifier that improves detection of very slow brain signals in our patients undergoing presurgical telemetry monitoring to further investigate the role SD plays in human PGES. This could provide vital information on why certain people with epilepsy are at increased risk of SUDEP.
In the final stage of this project, we will plan interventions to prevent SUDEP based on stimulation of specific brain regions after a seizure. This neurostimulation may disrupt the developing EEG suppression, thus reducing SUDEP risk. Our hope is that this research could one day make preventing SUDEP a reality, so that fewer people with epilepsy and their families are impacted by this devastating occurrence.
Read more about Dr Rob Wykes’ research here.
