Simple SummaryGliomas are known to impact on large-scale networks beyond the tumor location, but it is unknown how the tumor affects controllability and robustness of neural networks. We applied advanced control theory algorithms on connectivity data of structural and functional networks of prognostically differing glioma patients and healthy controls. We determined the driver nodes of the default-mode network (DMN), which are receptive to outside signals, and critical nodes as the most important elements for network controllability. Patients showed decreased network controllability and robustness mainly in the isocitratedehydrogenase (IDH) wildtype group, while additional topological shifts of driver and critical nodes were observed mainly in the prognostically more favourable IDH mutated patients. We hereby suggest a novel approach for elucidating disease evolution in brain cancer, which may aid in defining potential treatment targets under the aspects of network controllability and robustness in glioma patients.AbstractPrevious studies suggest that the topological properties of structural and functional neural networks in glioma patients are altered beyond the tumor location. These alterations are due to the dynamic interactions with large-scale neural circuits. Understanding and describing these interactions may be an important step towards deciphering glioma disease evolution. In this study, we analyze structural and functional brain networks in terms of determining the correlation between network robustness and topological features regarding the default-mode network (DMN), comparing prognostically differing patient groups to healthy controls. We determine the driver nodes of these networks, which are receptive to outside signals, and the critical nodes as the most important elements for controllability since their removal will dramatically affect network controllability. Our results suggest that network controllability and robustness of the DMN is decreased in glioma patients. We found losses of driver and critical nodes in patients, especially in the prognostically less favorable IDH wildtype (IDHwt) patients, which might reflect lesion-induced network disintegration. On the other hand, topological shifts of driver and critical nodes, and even increases in the number of critical nodes, were observed mainly in IDH mutated (IDHmut) patients, which might relate to varying degrees of network plasticity accompanying the chronic disease course in some of the patients, depending on tumor growth dynamics. We hereby implement a novel approach for further exploring disease evolution in brain cancer under the aspects of neural network controllability and robustness in glioma patients.