Decoupling of Structural and Functional Connectivity in Hubs and Cognitive Impairment After Mild Traumatic Brain Injury

Introduction: Mild traumatic brain injury (mild TBI) exhibited abnormal brain network topologies associated with cognitive dysfunction. However, it was still unclear which aspects of network organization were critical underlying the key pathology of mild TBI. Here, a multi-imaging strategy was applied to capture dynamic topological features of both structural and functional connectivity networks (SCNs and FCNs), to provide more sensitive detection of altered FCN from its anatomical backbone and identify novel biomarkers of mild TBI outcomes. Methods: A total of 62 mild TBI patients (30 subjects as an original sample with 3–12 months of follow-up, 32 subjects as independent replicated sample) and 37 healthy controls were recruited. Both diffusion tensor imaging and resting-state functional magnetic resonance imaging were used to create global connectivity matrices in the same individuals. Global and regional network analyses were applied to identify group differences and correlations with clinical assessments. Results: Most global network properties were conserved in both SCNs and FCNs in subacute mild TBI, whereas SCNs presented decreased global efficiency and characteristic path length at follow-up. Specifically, some hubs in healthy brain networks typically became nonhubs in patients and vice versa , such as the medial prefrontal cortex, superior temporal gyrus, and middle frontal gyrus. The relationship between structural and functional connectivity (SC and FC) in patients also showed salient decoupling as a function of time, primarily located in the hubs. Conclusions: These results suggested mild TBI influences the relationship between SCN and FCN, and the SC–FC coupling strength may be used as a potential biomarker to predict long-term outcomes after injury. Impact statement The current study was the first study to explore the coupling of structural–functional connectivity (SC–FC) from large-scale whole-brain networks in patients with mild traumatic brain injury. The results showed that the global properties homeostatically conserved in functional connectivity networks while altered in structural connectivity networks. The SC–FC coupling strength showed salient decoupling as a function of time and primarily occurred in hub regions.