In search of Fast Oscillations as Reliable markers of Cognition and Epilepsy – FORCE

Nearly 35% of epileptic patients do not respond to antiepileptic drugs, one fourth of whom can benefit from resective surgery. This represents in Europe around 250 000 patients. The identification of the cortical areas to be removed (the Epileptogenic Zone, EZ), and the evaluation of their functional integrity (the Functional Zone, FZ), is a difficult process which requires intracranial EEG (iEEG) recordings in 25-50% of the cases. However, even when using such iEEG information, epilepsy surgery still fails in a substantial ratio of patients, and post-operative cognitive/psychiatric deficits still exist in a significant number of the cases. This means that iEEG criteria used for identifying epileptogenic and functionally eloquent brain tissues are not clearly determined nor understood.
These recent years, emphasis has been put on High Frequency Oscillations (HFOs, 40-500Hz) as putative biomarkers of epileptogenicity or cognition in patients submitted to iEEG evaluation. Although very relevant, identification of HFOs require the use of signal analysis techniques and cognitive tasks that are mainly available as home-made softwares designed by researchers for their own line of research, without immediate clinical applications. Providing reliable HFOs-quantification tools in the clinical environment would undoubtedly have a large impact on the existing presurgical diagnostic procedures, and therefore on epileptic patient’s management.
The general objective of the FORCE project is precisely to develop methods and recording technologies into a professional-looking system for optimal recording, detection and characterization of epileptic and cognitive HFOs in clinical routine, in order to improve accuracy and safety of epilepsy surgery. To this aim, FORCE is established on a profoundly interdisciplinary consortium composed of 7 partners, including three industrial companies, all highly considered and renowned in their fields of interest and that together provide the full range of competencies in medicine, cognitive neuroscience, information processing and technology necessary to complete the project.
In practice, FORCE will start from the promising methods recently developed by our consortium, that allow to quantify fast activities at seizure onset (ictal HFOs) and between the seizures (interictal HFOs), as well as fast activities elicited by various cognitive tasks (Gamma Band Responses, GBRs). IEEG signals, visually analysed and validated by experts in a large cohort of epileptic patients (around 200), will be used to optimize the detection, quantification and visualization of HFOs and GBRs. Time-frequency methods will occupy a central place, and we will revisit the processing of iEEG signals for HFOs/GBRs visualization in a MRI-based environment. A new hybrid macro-microelectrode will be developed in order to assess the contribution of micro-electrodes for the recording of HFOs/GBRs. The validated tools will be integrated in a user-friendly software environment that will be incorporated in commercial EEG reviewing stations as readily-usable, CE-marked tools for the routine analysis of HFOs and GBRs. The clinical relevance of HFOs/GBRs quantification to localize the EZ and FZ will be evaluated by comparing these methods with the traditional ones (visual inspection, cortical electrical stimulation), with respect to surgical outcome.
Only a handful of clinical centers worldwide have the technology and human expertise to study in routine human epilepsy and human cognition based on intracranially-recorded HFOs/GBRs. FORCE represents a major advance in the field, that also will reinforce the leadership of industrial partners based on the newly developed products which extend the capabilities of their already-existing systems and devices.