Whole-Brain Mapping of Structural Connectivity in Infants Reveals Altered Connection Strength Associated with Growth and Preterm Birth

: Cerebral white-matter injury is common in preterm-born infants and is associated with neurocognitive impairments. Identifying the pattern of connectivity changes in the brain following premature birth may provide a more comprehensive understanding of the neurobiology underlying these impairments. Here, we characterize whole-brain, macrostructural connectivity following preterm delivery and explore the influence of age and prematurity using a data-driven, nonsubjective analysis of diffusion magnetic resonance imaging data. T1- and T2-weighted and -diffusion MRI were obtained between 11 and 31 months postconceptional age in 49 infants, born between 25 and 35 weeks postconception. An optimized processing pipeline, combining anatomical, and tissue segmentations with probabilistic diffusion tractography, was used to map mean tract anisotropy. White-matter tracts where connection strength was related to age of delivery or imaging were identified using sparse-penalized regression and stability selection. Older children had stronger connections in tracts predominantly involving frontal lobe structures. Increasing prematurity at birth was related to widespread reductions in connection strength in tracts involving all cortical lobes and several subcortical structures. This nonsubjective approach to mapping whole-brain connectivity detected hypothesized changes in the strength of intracerebral connections during development and widespread reductions in connectivity strength associated with premature birth.