Fabrice Wendling, a Biomathematician at the Service of Epileptic Patients

At the Signal and Image Processing Laboratory in Rennes, Fabrice Wendling is analyzing and interpreting the brain’s electrical signals to understand how epileptic seizures are triggered and how they develop. After more than 25 years of research in the field, he and his two collaborators have obtained a 10-million-euro European Research Council Synergy Grant to develop an electrical treatment for drug-resistant epilepsy.

Fabrice Wendling has made epilepsy his combat. Head of the Epileptogenic Systems: Signals and Models (Sésame) team at the Signal and Image Processing Laboratory* in Rennes, the researcher has devoted himself to this disease for over 25 years so far thanks to his expertise in biomathematics. Day after day, he analyzes, deciphers, and interprets the brain’s electrical signals in patients to understand where and how seizures are triggered, what form they take, and what might worsen or – on the contrary – block them.

"It’s almost a vocation. I’d always wanted to work in medical research, he explains. So I enrolled in a biological and medical engineering school in Compiègne. This was in the 90s, it was the first of its kind," he recalls. His training took him to the USA where he spent two years as part of an exchange program with an equivalent school in Atlanta, gaining experience in an international setting. Then he returned to France to do his military service in the biomedical department of the Val-de-Grâce military hospital, where he specialized in electrophysiology. He completed his training with a dissertation on intracerebral signals in epileptic patients, which he defended in Rennes in 1996. Since then he has continued to develop this research topic in the same laboratory. "I had just the right profile for performing such analysis, he explains. Studying neural signals involves the integration of thousands of bits of information recorded using electrodes that are implanted or placed on the brain’s surface to make mathematical and computerized models."

Armed with his expertise, Wendling formed his own team (Sésame) in 2004, and was made research director four years later. His work means that his name will go down in history with the internationally renowned Wendling mathematical model of epileptogenic signals. An endeavor that earned him a French Academy of Science award in 2012. At present, there are some twenty people in his team, including ten researchers, teacher-researchers, and hospital neurologist practitioners.

"My team’s DNA is the analysis of neural signals to develop models inspired by the functioning of the brain, with its inhibitory and excitatory connections, its different types of neurons and neurotransmitters... It’s a difficult task – there’s an endless stream of new knowledge about the brain which needs to be taken into account. These models then make it possible to reproduce the data obtained, explain them, and make predictions. It’s thanks to this work that we have, for example, understood that epileptic seizures are triggered when the brain is no longer controlled by inhibitory processes", he explains.

Treating resistant and inoperable epilepsy

This year marks a new turning point in his career thanks to the 10-million-euro ERC Synergy Grant. This six-year funding has been awarded to the Galvani project, created with two longstanding collaborators and friends: Fabrice Bartolomei, neurology professor at La Timone hospital and researcher at Institute of System Neuroscience** in Marseille, and Giulio Ruffini, biophysicist in Barcelona. Its objective is to treat drug-resistant and inoperable epilepsy by transcranial stimulation. "Around 30% of patients respond poorly to drugs or not at all and suffer seizures that can come on at any time. These can be highly incapacitating and create problems when it comes to employment. Yet these inoperable drug-resistant forms of epilepsy represent around 19 million cases worldwide," he adds. During a previous study involving 17 patients, it was observed that applying a mild electrical current to the brain’s surface via a helmet reduced seizure frequency by 50% in half of them − and by up to 90% for one of them − despite the protocol not being optimized. "This first experiment showed that the technique can neuromodulate specific brain networks of epilepsy. Now we need to analyze the signals patient by patient, because each patient has their own epileptogenic network. We also need to clarify the interactions between the electrical fields emitted by the helmet and the neurons over the short and long term, and be able to predict the response to the electrical stimulation according to its intensity, frequency and location. The aim is to prevent the onset of seizures by developing 'tailor-made' stimulations for each patient", he explains. A clinical trial will then be conducted to validate the results of their models, including 120 patients recruited in some ten French centers.

Ultimately, the researchers hope that the influence of these findings will extend beyond epilepsy. "Our hope is not only to treat these patients but also for our predictive models to be used in other diseases eligible for transcranial stimulation, such as severe depression or certain psychiatric disorders," he envisages.

Soigner l'épilepsie humaine par stimulation transcrânienne : le défi du projet Galvani - interview - 5 min 10 - © Université de Rennes 1, 2019

Notes :
* unit 1099 Inserm/Université de Rennes 1, Signal and Image Processing Laboratory (LTSI), Rennes
** unit 1106 Inserm/Aix-Marseille Université, Institute of System Neuroscience (INS), team Dynamical Brain Mapping (DynaMap), Marseille