Brain Functional Connectivity Plasticity Within and Beyond the Sensorimotor Network in Lower-Limb Amputees

Cerebral neuroplasticity after amputation has been elucidated by functional neuroimaging. However, little is known concerning how brain network-level functional reorganization of the sensorimotor system evolves following lower-limb amputation. We studied 32 unilateral lower-limb amputees (LLAs) and 32 matched healthy controls (HCs) using resting-state functional magnetic resonance imaging (rs-fMRI). A regions of interest (ROI)-wise connectivity analysis was performed with ROIs in eight brain regions in the sensorimotor network to investigate intra-network changes, and seed-based whole-brain functional connectivity (FC) with a seed in the contralateral primary sensorimotor cortex (S1M1) was used to study the FC reorganization between the sensorimotor region (S1M1) and other parts of the brain in the LLAs. The ROI-wise connectivity analysis showed that the LLAs had decreased FC, mainly between the subcortical nuclei and the contralateral S1M1 (p < 0.05, FDR corrected). Seed-based whole-brain FC analysis revealed that brain regions with decreased FC with the contralateral S1M1 extended beyond the sensorimotor network to the prefrontal and visual cortices (p < 0.05, FDR corrected). Moreover, correlation analysis showed that decreased FC between the subcortical and the cortical regions in the sensorimotor network progressively increased in relation to the time since amputation. These findings indicated a cascade of cortical reorganization at a more extensive network level following lower-limb amputation, and also showed promise for the development of a possible neurobiological marker of changes in FC related to motor function recovery in LLAs.