Network dynamics of the electro-magnetic epileptic focus in patients with focal cortical dysplasia

• Applicants: Privatdozent Dr. Marcel Heers; Yiwen Li Hegner, Ph.D.
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 468174690

Focal cortical dysplasia (FCD) results from impaired neural migration during fetal brain development. It is one of the most common causes of drug-resistant epilepsy. Typically, epileptic activity and the occurrence of epileptic seizures in patients suffering from FCD-caused focal epilepsy depends on the state of their wakefulness: during sleep, the epileptic focus is prone to the occurrence of epileptic seizures, while when the patient is awake, epileptic seizures are rare. Biomarkers that differentiate between network states that are susceptible or not to epileptic seizures are crucial for identifying targets for effective neurostimulation treatment in focal epilepsy and may help identify patients with favourable postsurgical outcome in epilepsy surgery. In FCD different rates of fast epileptic activity (FEA > 14 Hz) and rates of spike-slow-waves in awake and asleep brain states indicate network effects related to wakefulness. We hypothesize that the spatial extent of epileptic spikes and slow waves, as well as spectral bandwidth of FEA are local markers of the dynamics of the epileptic focus to differentiate the interplay of neural network activities both within and between awake and asleep brain states. At the network level we assume, that classical functional connectivity measures, such as phase and amplitude coupling, will characterize local- and regional synchronization between the primarily epileptogenic and distant brain regions. Our aim is to identify and unify local as well as regional network markers of neural activity imbalance in patients with FCD from non-invasive simultaneous magnetoencephalography / electroencephalography (MEG/EEG) data to characterize the activity dynamics of the epileptic focus between awake and asleep states. Non-invasive simultaneous MEG/EEG with whole-head-coverage shows clear advantages in FCD patients because FCD typically occurs in neocortical brain areas near the surface of the head where MEG/EEG both have high signal sensitivity and high spatio-temporal resolution. To capture and differentiate multiple brain network configurations in these patients, we will use Hidden Markov Modelling (HMM) to statistically model the multiple network states that we believe underlie the organization of the epileptic focus during awake and asleep brain states. Combining all of our local and regional MEG/EEG network markers will allow a detailed characterization of the activity dynamics of the epileptic focus during the transition between awake and asleep brain states non-invasively with whole head coverage, and bring us closer towards targeted brain stimulation and identifying epilepsy surgery candidates with favourable prognosis.

• DFG Programme: Research Grants