Whole-brain structural connectivity in dyskinetic cerebral palsy and its association with motor and cognitive function

Abstract

Dyskinetic cerebral palsy (CP) has long been associated with basal ganglia and thalamus lesions. Recent evidence further points at white matter (WM) damage. This study aims to identify altered WM pathways in dyskinetic CP from a standardized, connectome-based approach, and to assess structure-function relationship in WM pathways for clinical outcomes. Individual connectome maps of 25 subjects with dyskinetic CP and 24 healthy controls were obtained combining a structural parcellation scheme with whole-brain deterministic tractography. Graph theoretical metrics and the network-based statistic were applied to compare groups and to correlate WM state with motor and cognitive performance. Results showed a widespread reduction of WM volume in CP subjects compared to controls and a more localized decrease in degree (number of links per node) and fractional anisotropy (FA), comprising parieto-occipital regions and the hippocampus. However, supramarginal gyrus showed a significantly higher degree. At the network level, CP subjects showed a bilateral pathway with reduced FA, comprising sensorimotor, intraparietal and fronto-parietal connections. Gross and fine motor functions correlated with FA in a pathway comprising the sensorimotor system, but gross motor also correlated with prefrontal, temporal and occipital connections. Intelligence correlated with FA in a network with fronto-striatal and parieto-frontal connections, and visuoperception was related to right occipital connections. These findings demonstrate a disruption in structural brain connectivity in dyskinetic CP, revealing general involvement of posterior brain regions with relative preservation of prefrontal areas. We identified pathways in which WM integrity is related to clinical features, including but not limited to the sensorimotor system. Hum Brain Mapp 38:4594-4612, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: cerebral palsy; cognition; diffusion MRI; fractional anisotropy; graph theory; motor function; network-based statistic; structural connectome; white matter injury.

Figure 1

Results of the comparison of node‐level graph metrics between CP subjects and healthy controls (HC). The size of the nodes indicates the absolute difference among CP subjects and controls; warm colors indicate CP < HC and cold colors CP > HC; high‐intensity color indicates significant differences and low‐intensity color indicates non‐significant differences after applying FDR correction for multiple comparisons (P < 0.05); CP: Cerebral palsy; FA: Fractional anisotropy; HC: Healthy controls; L: Left; NOS: Number of streamlines; R: Right. BrainNet Viewer was used to create these figures [Xia et al., 2013]. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Results of the network‐based statistic analysis (NBS). Node and edge color indicates network membership; red indicates significance and gray indicates tendency (0.05 < P ≤ 0.1); the size of the nodes indicates the number of connections of this node that are included in the component. BFRT: Benton's Facial Recognition Test; CP: Cerebral palsy; FA: Fractional anisotropy; GMFCS: Gross Motor Function Classification System; HC: Healthy controls; IQ: Intelligence quotient; L: Left; MACS: Manual Ability Classification System; R: Right. BrainNet Viewer was used to create these figures [Xia et al., 2013]. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Circular graph of the results of the network‐based statistic analysis (NBS). Lines indicate significant connections for every kind of analysis. Edge colors separate intrahemispheric connections (dark green for the left hemisphere; soft green for the right hemisphere) and interhemispheric connections (green‐yellow). The color of the circle nodes indicates the number of connections of this node that are included in the component: the brighter means more connections. CP: Cerebral palsy; FA: Fractional anisotropy; GMFCS: Gross Motor Function Classification System; HC: Healthy controls; IQ: Intelligence quotient; L: Left; MACS: Manual Ability Classification System; R: Right. Schemaball was used to create this figure [Komarov, 2013]. [Color figure can be viewed at http://wileyonlinelibrary.com]