Primary cortical folding in the human newborn: an early marker of later functional development

TLDR

Cortical folding patterns, which develop early in life, vary among individuals and may signal developmental or neuropsychiatric disorders, yet the mechanisms driving these early structural changes remain poorly understood. The study used MRI and specialized post‑processing to compare anatomical and functional brain development in 45 premature newborns—including singletons, twins, and IUGR infants—during the 26–36‑week gestational window to identify early sulcal endophenotypes. Twins displayed delayed yet coordinated maturation with lower surface area and sulcation index, whereas IUGR infants showed discordant gyrification and a greater surface reduction relative to sulcation index, and birth‑time cortical metrics predicted term‑equivalent cerebral volumes and neurobehavioural outcomes measured by APIB.

Abstract

In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26–36 weeks of gestational age), and defined early 'endophenotypes' of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants' outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infant's behaviour (APIB).