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Mild traumatic brain injury (mTBI) disrupts the integrity of white matter microstructure, which affects brain functional connectivity supporting cognitive function. Although the relationship between structural and functional connectivity (SC and FC), here called SC–FC coupling, has been studied on global level in brain disorders, the long-term disruption of SC–FC coupling in mTBI at regional scale was still unclear. The current study investigated the alteration pattern of regional SC–FC coupling in 104 acute mTBI patients (41 with 6–12 months of follow-up) and 56 healthy controls (HCs). SC and FC networks were constructed to measure regional, intra-network, and inter-network SC–FC coupling. Compared with HCs, acute mTBI exhibited altered SC–FC coupling of the sensorimotor network (SMN). The coupling laterality indicators of the SMN can identify mTBI from controls. The persistent SC–FC decoupling of the SMN and the additional decoupling of the default mode network (DMN) were observed in chronic mTBI. Crucially, decoupling of the SMN and DMN predicted better cognitive outcomes. The findings revealed the SC–FC coupling alternations exhibited hierarchical trend originating from the sensorimotor cortex to high-order cognitive regions with the progression of mTBI. The regional and hierarchical SC–FC coupling may be a prognostic biomarker to provide insights into the pathophysiology mechanism of mTBI.

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