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Brain Advance Access published online on June 28, 2008

Brain, doi:10.1093/brain/awn137
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© The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

J. Dubois1, M. Benders1,2, C. Borradori-Tolsa1, A. Cachia3,4, F. Lazeyras5, R. Ha-Vinh Leuchter1, S. V. Sizonenko1, S. K. Warfield6, J. F. Mangin4,7 and P. S. Hüppi1,8

1Department of Pediatrics, Geneva University Hospitals, Geneva, Switzerland, 2Department of Pediatrics, Wilhemina Children's Hospital, Utrecht, Netherlands, 3INSERM-CEA, U797, CEA/DSV/I2BM/Service Hospitalier Frédéric Joliot, Orsay and University Paris-Sud, Orsay France and University Paris Descartes, 4IFR49, Paris, France, 5Department of Radiology – CIBM, Geneva University Hospitals, Geneva, Switzerland, 6Department of Radiology, Computational Radiology Laboratory, Children's Hospital, Harvard Medical School, Boston, MA, USA, 7CEA, Laboratoire de neuroimagerie assistée par ordinateur, CEA/SAC/DSV/I2BM/NeuroSpin, Saclay, France and 8Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA, USA

Correspondence to: Jessica Dubois, Department of Pediatrics, Division of Development and Growth, Geneva University Hospitals, 6 rue Willy Donzé, 1211 Geneva, Switzerland E-mail: jessica.dubois{at}centraliens.net

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).

Key Words: cortex; development; gyrification; newborn; premature; twin; IUGR; MRI; APIB

Abbreviations: IUGR, intrauterine growth restriction; APIB, assessment of preterm infant's behaviour; MRI, magnetic resonance imaging; ADHD, attention deficit hyperactivity disorder

Received December 18, 2007. Revised May 27, 2008. Accepted June 4, 2008.


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