Project Details
Projekt
Altered brain network interactions in antibody-mediated brain dysfunction in humans and mice
Subject Area
Molecular and Cellular Neurology and Neuropathology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 504745852
In this project, we aim to study antibody-mediated pathophysiologic mechanisms and to improve disease outcome prediction in autoimmune encephalitis using state-of-the-art translational neuroimaging approaches in human patients and murine disease models. Currently, the exact autoimmune mechanisms that impact brain structure and function and that lead to persistent long-term sequelae of the disease remain elusive. Furthermore, the lack of standardized MR imaging markers that can predict long-term functional status prevents prediction of disease outcome in individual encephalitis patients and therefore substantially limits current clinical decision-making (1). Here, we will first make use of advanced neuroimaging techniques (resting-state functional MRI, structural MRI, multiparameter mapping) to systematically assess translational structural and functional imaging changes in humans and rodent disease models (2–4). Second, we will investigate the histopathologic changes underlying those advanced brain imaging changes to identify the pathophysiological substrates of network alterations associated with clinical and cognitive symptoms. To this end, we will use empirical data and simulated data provided by biologically plausible computational models of brain network dynamics within the framework of the virtual brain (5). Third, we will use virtual brain-based model-inferred optimal parameters to train classification models for accurate prediction of disease class and cognitive outcome in the individual encephalitis patient after one year. Ultimately, our goal is to enhance prediction accuracy of NMDAR-ab and LGI1-ab encephalitis and functional outcome by combining multi-parameter neuroimaging with simulated virtual brain data to improve clinical decisions with regards to short- and long-term immunosuppressive therapy, and in identifying subgroups of patients who may benefit from novel salvage therapies in future clinical trials.
DFG Programme
Clinical Research Units
