Rewiring the extremely preterm brain: Altered structural connectivity relates to language function.

Children born preterm are at increased risk for cognitive impairment, with higher-order functions such as language being especially vulnerable. Previously, we and others have reported increased interhemispheric functional connectivity in children born extremely preterm; the finding appears at odds with literature showing decreased integrity of the corpus callosum, the primary commissural bundle, in preterm children. We address the apparent discrepancy by obtaining advanced measures of structural connectivity in twelve school-aged children born extremely preterm (<28 weeks) and ten term controls. We hypothesize increased extracallosal structural connectivity might support the functional hyperconnectivity we had previously observed. Participants were aged four to six years at time of study and groups did not differ in age, sex, race, ethnicity, or socioeconomic status. Whole-brain and language-network-specific (functionally-constrained) connectometry analyses were performed. At the whole-brain level, preterm children had decreased connectivity in the corpus callosum and increased connectivity in the cerebellum versus controls. Functionally-constrained analyses revealed significantly increased extracallosal connectivity between bilateral temporal regions in preterm children (FDRq <0.05). Connectivity within these extracallosal pathways was positively correlated with performance on standardized language assessments in children born preterm (FDRq <0.001), but unrelated to performance in controls. This is the first study to identify anatomical substrates for increased interhemispheric functional connectivity in children born preterm; increased reliance on an extracallosal pathway may represent a biomarker for resiliency following extremely preterm birth.