Identification of functional network nodes in temporal lobe epilepsy

• Applicants: Professor Dr. Dominik von Elverfeldt, since 2/2020; Professorin Dr. Carola A. Haas
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Human Cognitive and Systems Neuroscience
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 431990881

Mesial temporal lobe epilepsy (MTLE) is the most frequent form of drug-resistant epilepsy in adults. In MTLE, seizures typically originate from brain areas located deep within the temporal lobe (e.g. the hippocampus or the amygdala). Surgical resection of the epileptic brain areas often represents the only way to control seizures. However, only about one third of patients that have undergone curative surgery remain seizure free, indicating that epileptic regions may extend well beyond the operated areas and demonstrating the urgent need for new therapeutic strategies. One promising approach relies in deep brain stimulation with electrical currents, which is also applied successfully in neurological disorders such as Parkinson’s disease or depression. In MTLE typically the hippocampus is stimulated with short electrical pulses delivered at 100-190 Hz, which is believed to desynchronize the epileptic network and has been shown to reduce seizures by 50% - 90% in about 75% of patients. However, particularly in MTLE with hippocampal sclerosis (characterized by neuronal cell loss and glial scarring) the efficacy of hippocampal stimulation is remarkably low, again suggesting that brain areas other than the hippocampus might be better targets.In the proposed project we aim at identifying brain-wide networks critically involved in seizure spread, and thus, facilitate targeted therapeutic intervention. Therefore, we will perform functional magnetic resonance imaging (fMRI) during optogenetically-induced seizures and during epileptogenesis in a mouse model for MTLE with hippocampal sclerosis, which closely reflects the human pathology. State-of-the-art analytical tools for fMRI data will enable us to describe the activity dynamics and the causal interactions of hyperactive brain areas, and to identify central network hubs during seizures on a whole-brain scale. We will also use local field potential recordings in order to validate and to further investigate neuronal activity dynamics observed with fMRI. In a second step, we will perform chemogenetic and optogenetic silencing of epileptic network hubs to test their functional role in seizure propagation and generalization using both fMRI and video-EEG measurements. Our project will largely extend the current knowledge regarding network interactions in MTLE, and therefore, could disclose new circuit targets for effective therapeutic interventions.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Pierre LeVan, until 2/2020