Motor Function and White Matter Connectivity in Children Treated with Therapeutic Hypothermia for Neonatal Encephalopathy

Therapeutic hypothermia reduces the incidence of severe motor disability, such as cerebral palsy, following neonatal hypoxic-ischemic encephalopathy. However, cooled children without cerebral palsy at school-age demonstrate motor deficits and altered white matter connectivity. In this study, we used diffusion-weighted imaging to investigate the relationship between white matter connectivity and motor performance, measured using the Movement Assessment Battery for Children-2, in school-age children treated with therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy at birth, who did not develop cerebral palsy (cases), and matched controls. Analysis of tract-level microstructure (33 cases, 36 controls) revealed correlations between total motor scores and fractional anisotropy, in cases but not controls, in the anterior thalamic radiation bilaterally, the inferior fronto-occipital fasciculus bilaterally and both the hippocampal and cingulate gyrus parts of the left cingulum. Analysis of structural brain networks (22 cases, 32 controls), in which edges were determined by probabilistic tractography and weighted by fractional anisotropy, revealed correlations between total motor scores and several whole-brain network metrics in cases but not controls. We then investigated edge-level association with motor function using the network-based statistic. This revealed subnetworks which exhibited group differences in the association between motor outcome and edge weights, for total motor scores as well as for balance and manual dexterity domain scores. All three of these subnetworks comprised numerous frontal lobe regions known to be associated with motor function, including the superior frontal gyrus and middle frontal gyrus. These findings demonstrate an association between impaired motor function and brain organisation in case children.