Grant: Foundation Grant

<html> <body> <p> <strong><em>Overarching direction.</em></strong> Many patients with focal epilepsy are refractory to medical treatment. Surgical treatment is then the only option. Defining the region to resect is complex and far from fool proof. Some patients cannot be operated because the focus is not found; in operated patients, the success varies from 40 to 80% according to many factors, most of which are uncertain.<br>My research will center on the concept that human focal epilepsy is not a single uniform disease as most often considered today, but that it is possible to create a classification of focal epilepsies that will lead to improved treatment and a higher probability of finding different underlying mechanisms. Following recent results in experimental temporal lobe epilepsy, with initial confirmation in patients, I propose to define <em>different classes of focal epilepsy</em>, each corresponding to a cluster of features derived from seizure symptoms, imaging/pathological substrate, and functional imaging and electrophysiological signatures. These classes will be related to success/failure of different surgical resections as currently performed, allowing us to provide patients and physicians with critical information about future surgeries: likelihood of success, guidance for resection, and when surgery is not recommended. The classes of focal epilepsy will also define phenotypes that can be studied experimentally, possibly uncovering mechanisms specific to each.</p> <p> <strong><em>Methods</em>.</strong> <u>Electrophysiology</u> is the core investigation, reflecting directly the abnormal neuronal activity of epileptic discharges and seizures. We have been among pioneers discovering a new EEG activity, High Frequency Oscillations (HFOs), and demonstrated that HFOs provide better diagnostic information and help understand mechanisms of ictogenesis and epileptogenesis. We will now add single cell recordings combined with human EEG to discover the neural mechanisms likely to underlie epileptic discharges. <u>Structural MR imaging</u> provides the location and possible pathological substrate of the lesion that may cause the epilepsy, in patients showing a lesion. <u>Functional imaging</u>, principally EEG-fMRI, which we also pioneered, provides a unique view of the whole brain at the time of epileptic discharges, allowing the delineation of the epileptic focus as well as network abnormalities.</p> <p> <strong><em>Health outcome.</em></strong> This research should result in a better understanding of focal epilepsy, better outcome of surgery, and possibly investigation into specific mechanisms for the different classes of focal epilepsy that we will define.</p> <p> <strong><em>Core expertise.</em></strong> I have considerable experience in all the areas indicated above, as a pioneer in electrophysiological and functional imaging studies of human epilepsy. I have long-standing collaborations with Program Experts: F. Dubeau, senior epilepsy clinician and neurophysiologist with considerable experience in imaging; M. Avoli, senior neuroscientist and world leader in experimental epilepsy; C. Grova, young investigator specialized in the analysis of EEG and fMRI; and J. Hall, neurosurgeon active in the investigation and surgical treatment of epileptic patients.</p> <p> <strong><em>Mentoring</em>.</strong> I plan to continue the pattern of mentoring graduate students and research fellows in neuroscience, neurology and biomedical engineering. This mixture generates active collaborations between disciplines, enriches the training opportunity and has proven productive: all trainees generated peer-reviewed papers, several more than ten.</p> </body> </html>