Reduced white matter fractional anisotropy mediates cortical thickening in adults born preterm with very low birthweight

ABSTRACT Development of the cerebral cortex may be affected by aberrant white matter development. Preterm birth with very low birth weight (VLBW) has been associated with reduced fractional anisotropy of white matter and changes in cortical thickness and surface area. We use a new methodological approach to combine white and gray matter data and test the hypothesis that white matter injury is primary, and acts as a mediating factor for concomitant gray matter aberrations, in the developing VLBW brain. T1 and dMRI data were obtained from 47 young adults born preterm with VLBW and 73 term‐born peers (mean age=26). Cortical thickness was measured across the cortical mantle and compared between the groups, using the FreeSurfer software suite. White matter pathways were reconstructed with the TRACULA software and projected to their cortical end regions, where cortical thickness was averaged. In the VLBW group, cortical thickness was increased in anteromedial frontal, orbitofrontal, and occipital regions, and fractional anisotropy (FA) was reduced in frontal lobe pathways, indicating compromised white matter integrity. Statistical mediation analyses demonstrated that increased cortical thickness in the frontal regions was mediated by reduced FA in the corpus callosum forceps minor, consistent with the notion that white matter injury can disrupt frontal lobe cortical development. Combining statistical mediation analysis with pathway projection onto the cortical surface offers a powerful novel tool to investigate how cortical regions are differentially affected by white matter injury. HIGHLIGHTSDevelopment of the cerebral cortex may be affected by white matter injury in individuals born preterm with very low birth weight (VLBW).White and gray matter MRI data from 26 year‐olds born with VLBW were combined to test if white matter injury mediates gray matter aberrations in VLBW.White matter pathways were reconstructed and projected to their cortical end regions, where cortical thickness was measured.Cortical thickness was increased in frontal and occipital regions in VLBW relative to a term‐born control group.Increased thickness in the frontal lobe was statistically mediated by reduced FA in the corpus callosum forceps minor.

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