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

Abstract

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.

Keywords: S1M1; functional reorganization; lower-limb amputation; resting-state functional connectivity; subcortical nuclei; the sensorimotor network.

FIGURE 1

Visual depiction of the regions of interest (ROIs) within the subcortical and cortical sensorimotor network that were used in the analyses described in the text. BG, basal ganglia; THA, thalamus; S1M1, the primary sensorimotor cortex; SMA, the supplementary motor area; I indicates ipsilateral to the side of the amputation in the lower-limb amputees (LLAs); C indicates contralateral to the side of the amputation in the LLAs. I corresponds to the left brain in the healthy controls (HCs), and the C corresponds to the right brain in the HCs.

FIGURE 2

Significant between-group differences in the sensorimotor network in the intensity of the brain FC. The brain networks were visualized with the BrainNet Viewer. The thickness of the line represents the intensity of the between-group difference. BG, basal ganglia; THA, thalamus; S1M1, the primary sensorimotor cortex; SMA, the supplementary motor area; I indicate ipsilateral to the side of the amputation in the LLAs; C indicates contralateral to the side of the amputation in LLAs.

FIGURE 3

Decreased FC in patients with lower-limb amputation with the seed region in the contralateral S1M1, compared with connectivity in the HCs (p < 0.05, FDR corrected, voxels > 50). : Cerebellum VI; : Cerebellum Crus1; : Superior frontal gyrus (medial); : Thalamus; : Superior occipital Gyrus, Cuneus, and Middle occipital gyrus. All these brain regions located on the cerebral hemisphere ipsilateral to the side of the amputation. The blue-to-green patches show, on axial slices, the t statistic of the comparisons between FC in the LLAs and the HCs. Slice location (z) is displayed in Montreal Neurological Institute coordinates. I indicates ipsilateral to the side of the amputation; C indicates contralateral to the side of the amputation.

FIGURE 4

Scatter plots depicting the correlations between FC and time since amputation (p < 0.05). Partial correlation coefficients (r) were corrected for age, sex, and education. Scatter plots is fitted with regression line (black line). ^∗The correlations survived a critical FDR threshold. BG, basal ganglia; SMA, the supplementary motor area; S1M1, the primary sensorimotor cortex; I indicates ipsilateral to the side of the amputation; C indicates contralateral to the side of the amputation.