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What if the shape of the early brain sulci could predict certain pathologies?

Researchers from UNIACT and BAOBAB (NeuroSpin department), in collaboration with the UMC Utrecht, conducted a longitudinal brain imaging study in very premature infants to analyze the variability of the shape of the central sulcus early in its development and its functional implications. 

Published on 20 May 2022

​Variations on the same theme

In mammals, the brain folds in relation to its size, so that the mouse brain is smooth while the human brain shows a complex folding, which sets up during fetal development. With a fixed cranial volume, this folding allows for a larger cortical surface. It results in numerous circumvolutions made up of hollows, called sulci.

 Although its "patterns" are similar from one individual to another, this folding is in fact unique to each individual. Also, some variations in the shape of the sulci are correlated with pathologies, one of the most explicit being lissencephaly, a disease that gives the brain a smooth appearance, with diminished or absent convolutions, and that is linked to mental retardation and epilepsy, among others. Other more subtle variations in folding are related to functional differences in healthy subjects. For example, the shape of the sulci in the anterior cingulate cortex, which appears in-utero and remains stable throughout life, may predict to some extent the performance of cognitive control; that is, our ability to respond to stimuli in a context-sensitive manner. 

So, is it possible to differentiate normal variability in folding patterns from pathological variability and what might be the functional implications of this variability? The brain of an infant born at term is more or less similar to that of an adult, and even if the shape of the folds may continue to evolve later on, these changes remain subtle compared to the patterns observed at the end of pregnancy. So, when do these folding patterns appear before birth and are they predictive of our future sensorimotor and cognitive functions?

OBSERVing the sulci during their development

To find out, researchers from UNIACT and BAOBAB (NeuroSpin department), in collaboration with UMC Utrecht, have been interested in the formation of the central sulcus: a convolution of interest since it appears relatively early in pregnancy, from the twentieth week, and is therefore already developing during the disruptive event of very premature birth. This sulcus is also located between two brain regions associated with the sensory-motor system, which have been functionally mapped in detail. Thus, certain sub-regions of this fold are linked to already known parts of the body, such as the "elbow" linked to the functional region of the hand. 

To overcome the technical and ethical difficulties of longitudinal imaging in the healthy fetus, the researchers chose to study the shape of the central sulcus in premature newborns followed during childhood, including an imaging performed before the age equivalent to a full-term birth and one at that age. Thus, the longitudinal study, published in the journal Neuroimage, included a cohort of 71 very premature infants, born between 24 and 28 weeks of amenorrhea, who were "imaged" twice shortly after birth: the first time at around 30 weeks post-menstrual age, when the central sulcus was already present, but at a rough stage, and the second time at around 40 weeks, equivalent to a full-term birth, when the central sulcus was well developed. The laterality of the children was then assessed at around five years of age, as well as their fine motor performance, measured in a psychometric test. 

Using elaborate analyses of brain images, the researchers first showed that the majority of the shape characteristics of the central sulcus are already encoded around 30 weeks post-menstrual age, and that they evolve mostly in accordance with this primitive shape. They also revealed novel hemispheric asymmetries at each age, as well as unresolved links between the perinatal shape of the central sulcus and the manual laterality and fine motor skills of these preterm infants. In the future, further studies will allow a better understanding of the functional implications of the early variability of the sulcus shape, but also potentially the identification of early biomarkers to improve the diagnosis in order to lead to a more personalized support of these infants at risk of neurodevelopmental disorders.

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