MAPPING THE MOUSE BRAIN “CONNECTOME” WITH MULTI-LEVEL ANALYSIS OF STRUCTURAL AND FUNCTIONAL NETWORKS IN NEUROLOGICAL DISEASES
Relevant for Research Area
Prof. Dr. Jürgen Hennig (Contact PI)
This project aims at characterizing metabolic, structural and functional network changes associated with neurological diseases. Non-invasive MRI allows studying the longitudinal disease progression in animal models of mesial temporal lobe epilepsy (mTLE) and ischemic stroke as well as the dynamic changes of network activity caused by epileptic seizures. Having set up the methodological framework for MRI, electrophysiological and immunohistochemical analysis, we conducted a longitudinal study showing biomarkers of epileptogenesis in the mouse model of mTLE. By performing ex vivo measurements on sclerotic human hippocampal tissue we demonstrated the translational value of the discovered biomarkers in the clinic. In parallel we have performed a longitudinal study including MRI and transcranial direct current stimulation (tDCS) in the rat model of ischemic stroke. In contrast to the investigation of longitudinal and persistent alterations, current work focuses on dynamic network changes with respect to evoked epileptiform discharges. Combining MRI, optogenetic stimulation and EEG recordings, preliminary results indicate the possibility to monitor the origin and propagation of epileptic seizures. Once established we will apply multiple strategies tointerfere with and disrupt the epileptic activity, which is one of the main goals of the BLBT cluster.
We identified a complete, time-resolved set of MRI biomarkers during epileptogenesis allowing the early and non-invasive prediction of disease severity in experimental mTLE, which may help to identify patients at risk to develop mTLE, thus expanding the therapeutic window. Moreover, by combining optogenetic stimulation and simultaneous fMRI in mice we could describe the propagation dynamics of focal seizures at a whole-brain scale. Both results provide a clear benefits striving to explore and to develop novel therapeutic strategies for epilepsy intervention.