## 4 Discussion
HGG is considered a 'whole-brain' disease, showing widespread involvement of distant regions even from early stages [24]. The right-hemispheric network in HGG was characterized by decreased cost and degree, which are measures of network centrality expressing the degree of local connectedness of each node (Supplementary Table S1). To a certain extent, these network modifications highlight an effect on brain connectivity which may be characteristic of HGG. Fast-growing tumors may act in a similar way to acute insults such as stroke, leading to the phenomenon of diaschisis. This phenomenon was originally described as a loss of excitability, reduced metabolism and/or blood flow in areas remote to the original lesion [25]. Connectomal diaschisis has been recently described in stroke as changes in the structural and functional connectome, including disconnections between and reorganization of subgraphs, involving areas distant from the original lesion [25]. Our results seem to support a similar effect on functional connectivity driven by the rapid growth of HGG. On the other hand, our findings may also point to a certain degree of inter-hemispheric reorganization in HGG. Although plastic changes have been more extensively described in LGG [26], previous studies reported functional reorganization in HGG (e.g., in the cerebral-cerebellar circuits) [27]. Inter-hemispheric language reorganization has been shown in HGG, including translocation of eloquent language areas [28; 29; 30]. In fact, the median age of glioblastomas at diagnosis is approximately 330 days [31], while brain modifications related to learning new functions can develop within months [32]. This time window may be enough to develop significant network modifications. The effect of tumor location on brain plasticity is rarely investigated. From our dedicated analysis, tumor location appears to be crucial for network changes. While frontal and temporal tumors showed bilateral functional modifications, parietal and insular tumors appeared to display only local effects (i.e., functional changes in the left hemisphere). Notably, essential functions such as language are primarily lateralized to the left frontal and temporal lobes [33], while the parietal and insular lobes host secondary language areas [34]. [PERSON] et al. showed that unilateral tumors are associated with inter-hemispheric reorganization and that the proximity of tumor location is more linked to distributed network deterioration than anatomical distance [35]. Eleoquent regions may act as connectors in the functional network [8], whose damage leads to deeper and wider modifications of the network organization than peripheral areas, as supported by neuro-computational models [36]. Interestingly, while frontal tumors showed mixed connectivity changes, temporal tumors led to a decrease in all graph metrics in both LGG and HGG of both hemispheres (Table 4). [PERSON] et al. reported a stronger decrease in left hemispheric connectivity in posterior vs. anterior tumors by studying the language network with a pseudo-resting state [37]. These results may suggest that lesions in the left temporal lobe have a more detrimental effect on connectivity than other locations and that beneficial plastic changes may be more likely to occur with a frontal than a temporal tumor. The presence of a tumor in the left frontal lobe was associated with significant modification of connectivity at the level of the right SFG in both LGG and HGG patients vs. HC (Figure 4). However, while the node had increased global efficiency, local efficiency, degree and decreased average path length in LGG vs. HC, the opposite was true for HGG vs. HC. As a consequence, the node was more integrated into LGG than HGG. This finding may support the idea that such right-sided network modification was more favorable in LGG than in HGG. Despite this promising finding, connectivity changes in other nodes were less indicative of a specific pattern (Table 4).