Damage to the shortest structural paths between brain regions is associated with disruptions of restingstate functional connectivity after stroke Abstract   Focal brain lesions disrupt restingstate functional connectivity, but the underlying structural mechanisms are unclear. Here, we examined the direct and indirect effects of structural disconnections on restingstate functional connectivity in a large sample of subacute stroke patients with heterogeneous brain lesions. We estimated the impact of each patientu0027s lesion on the structural connectome by embedding the lesion in a diffusion MRI streamline tractography atlas constructed using data from healthy individuals. We defined direct disconnections as the loss of direct structural connections between two regions, and indirect disconnections as increases in the shortest structural path length between two regions that lack direct structural connections. We then tested the hypothesis that functional connectivity disruptions would be more severe for disconnected regions than for regions with spared connections. On average, nearly 20% of all region pairs were estimated to be either directly or indirectly disconnected by the lesions in our sample, and extensive disconnections were associated primarily with damage to deep white matter locations. Importantly, both directly and indirectly disconnected region pairs showed more severe functional connectivity disruptions than region pairs with spared direct and indirect connections, respectively, although functional connectivity disruptions tended to be most severe between region pairs that sustained direct structural disconnections. Together, these results emphasize the widespread impacts of focal brain lesions on the structural connectome and show that these impacts are reflected by disruptions of the functional connectome. Further, they indicate that in addition to direct structural disconnections, lesioninduced increases in the structural shortest path lengths between indirectly structurally connected region pairs provide information about the remote functional disruptions caused by focal brain lesions.

Spaceindependent community and hub structure of functional brain networks Abstract   Coordinated brain activity reflects underlying cognitive processes and can be modeled as a network of interregional functional connections. The most costly connections in the network are longdistance correlations that, in the absence of underlying structural connections, are maintained by sustained energetic inputs. Here, we present a spatial modeling approach that amplifies contributions made by longdistance functional connections to wholebrain network architecture, while simultaneously suppressing contributions made by shortrange connections. We use this method to characterize the longdistance architecture of functional networks and to identify aspects of community and hub structure that are driven by longdistance correlations and that, we argue, are of greater functional significance. We find that based only on patterns of longdistance connectivity, primary sensory cortices occupy increasingly central positions and appear more xe2x80x9chublikexe2x80x9d. Additionally, we show that the community structure of longdistance connections spans multiple topological levels and differs from the community structure detected in networks that include both shortrange and longdistance connections. In summary, these findings highlight the complex relationship between the brainxe2x80x99s physical layout and its functional architecture. The results presented here inform future analyses of community structure and network hubs in health, across development, and in the case of neuropsychiatric disorders.