Structural connectivity at term equivalent age and language in preterm children at 2 years corrected

Abstract

We previously reported interhemispheric structural hyperconnectivity bypassing the corpus callosum in children born extremely preterm (EPT, <28 weeks) versus term children. This increased connectivity was positively associated with language performance at 4 to 6 years of age in our prior work. In the present study, we aim to investigate whether this extracallosal connectivity develops in EPT at term-equivalent age (TEA) by leveraging a prospective cohort study of 350 very and extremely preterm infants followed longitudinally in the Cincinnati Infant Neurodevelopment Early Prediction Study. For this secondary analysis, we included only children born EPT and without significant brain injury (n=95). We use higher-order diffusion modeling to assess the degree to which extracallosal pathways are present in EPT infants and predictive of later language scores at 22-26 months corrected age. We compare results obtained from two higher-order diffusion models: generalized q-sampling imaging (GQI) and constrained spherical deconvolution (CSD). Advanced magnetic resonance imaging was obtained at TEA (39-44 weeks post-menstrual age, PMA). For structural connectometry analysis, we assessed the level of correlation between white matter connectivity at the whole brain level at TEA and language scores at 2 years corrected age, controlling for PMA, sex, brain abnormality score, and social risk. For our CSD analyses, we performed connectivity-based fixel enhancement (CBFE), using probabilistic tractography to inform statistical testing of the hypothesis that fiber metrics at TEA relate to language scores at 2 years corrected age after adjusting for covariates. 95 infants were EPT with no significant brain injury. Of these, 53 had complete neurodevelopmental and imaging datasets that passed quality control. In the connectometry analyses adjusted for covariates and multiple comparisons (p<0.05), the following tracks were inversely correlated with language: bilateral cerebellar white matter and middle cerebellar peduncles, bilateral corticospinal tracks, posterior commissure, and the posterior inferior fronto-occipital fasciculus (IFOF). No tracks from the CSD/CBFE analyses remained significant after correction for multiple comparisons. Our findings provide critical information about the ontogeny of structural brain networks supporting language in EPT. Greater connectivity in more posterior tracks that include the cerebellum and connections to the regions of the temporal lobes at TEA appears to be disadvantageous for language development.