Finding the silent causes of seizure risk
EMERGING LEADER FELLOWSHIP
£300,000
Dr Robert Graham
UCL Queen Square Institute of Neurology
For many people with epilepsy, not knowing when a seizure is going to happen is a difficult aspect of the condition. Many people describe “seizure clusters” or periods where seizures seem more likely, and research has confirmed that seizure risk can vary over time. However, the reasons for this are unclear. EEG recordings don’t show strong warning signs before seizures, suggesting that deeper, slower changes in the brain may be involved. One possible factor is a chemical messenger in the brain called acetylcholine, which helps regulate brain activity but is very hard to measure over long periods – until now.
"Seizures occur in a manner that is very difficult to predict, but is not totally random. Importantly though, we don’t understand the molecular pressures in the brain that make seizure onset more or less likely. Characterising these pressures is a promising route both for understanding epilepsy and developing effective, light-touch treatments."
This study will use new florescent tools that can track acetylcholine (ACh) levels in real-time, across multiple days. The aim is to find out whether changes in ACh levels can explain when and why seizures start. The study will first record ACh activity in healthy animals, then in animals with epilepsy, and finally test how manipulating ACh affects seizure timing and spread.
By uncovering how brain chemistry changes before and during seizures, this research aims to explain why seizure risk goes up and down – something that could eventually help forecast seizures. The study will provide crucial insights into what makes the brain vulnerable to seizures. This knowledge could lead to new drug targets, especially for the 30% of people whose epilepsy does not respond to current medications.
