Developmental neuroplasticity of the white matter connectome in children with perinatal stroke

Abstract

Objective: To employ diffusion imaging connectome methods to explore network development in the contralesional hemisphere of children with perinatal stroke and its relationship to clinical function. We hypothesized alterations in global efficiency of the intact hemisphere would correlate with clinical disability.

Methods: Children with unilateral perinatal arterial (n = 26) or venous (n = 27) stroke and typically developing controls (n = 32) underwent 3T diffusion and T1 anatomical MRI and completed established motor assessments. A validated atlas coregistered to whole-brain tractography for each individual was used to estimate connectivity between 47 regions. Graph theory metrics (assortativity, hierarchical coefficient of regression, global and local efficiency, and small worldness) were calculated for the left hemisphere of controls and the intact contralesioned hemisphere of both stroke groups. Validated clinical motor assessments were then correlated with connectivity outcomes.

Results: Global efficiency was higher in arterial strokes compared to venous strokes (p < 0.001) and controls (p < 0.001) and was inversely associated with all motor assessments (all p < 0.012). Additional graph theory metrics including assortativity, hierarchical coefficient of regression, and local efficiency also demonstrated consistent differences in the intact hemisphere associated with clinical function.

Conclusions: The structural connectome of the contralesional hemisphere is altered after perinatal stroke and correlates with clinical function. Connectomics represents a powerful tool to understand whole brain developmental plasticity in children with disease-specific cerebral palsy.

Figure 1. Neuroimaging pipeline

Image processing steps employed a combination of SPM12, FSL, and MRtrix to optimize results in brains with larger lesions. AAL2 = automated anatomic labeling 2; CSD = constrained spherical deconvolution.

Figure 2. Global graph theory differences between stroke groups and controls

(A) Assortativity in arterial ischemic stroke (AIS) was significantly higher than in periventricular venous infarction (PVI) and typically developing controls (TDCs) and PVI assortativity was higher than in TDCs. (B) AIS values for hierarchical coefficient of regression (HCR) were higher than in PVI and TDCs, and PVI derived HCR was higher than in TDCs. (C) Global efficiency in AIS was higher than in PVI and TDCs. PVI global efficiency was higher than in TDC. The orange circles in the depictions represent nodes and the black lines represent the edges, where thicker lines represent higher weighting.

Figure 3. Visual representation of the weighted, undirected networks for a random child selected from the arterial ischemic stroke (AIS), periventricular venous infarction (PVI), and typically developing control (TDC) groups

The weighted, undirected networks for each child is presented as both a composite graph (far left column) and segregated subnetworks based on network degree. Each subnetwork is displayed for node degrees n_degree = 10^x for x = 0,1,…,5. Exponential steps between node degrees provide an appropriate visualization across the total number of streamlines representing each graph.

Figure 4. Global graph theory metrics of the contralesional hemisphere relate to clinical function

Global efficiency was inversely related to Assisting Hand Assessment (AHA) and Melbourne Assessment (MA) (A and B, respectively). The hierarchical coefficient of regression (HCR) was inversely related to the Box and Block Test of the affected hand (BBTA) (C). Assortativity was inversely related to AHA and MA (D and E, respectively) and positively related to Jebsen Taylor Hand Function test of the affected hand (JTHFA) (F). AIS = arterial ischemic stroke; PVI = periventricular venous infarction.