Journal
BRAIN
Volume 144, Issue -, Pages 2199-2213Publisher
OXFORD UNIV PRESS
DOI: 10.1093/brain/awab118
Keywords
neonatology; brain development; functional connectivity; resting-state connectivity; neuroanatomy
Categories
Funding
- European Research Council under the European Union [319456]
- National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre (BRC) at South London, Maudsley NHS Foundation Trust, King's College London
- St Thomas' Hospitals NHS Foundation Trust (GSTFT)
- Wellcome Engineering and Physical Sciences Research Council (EPSRC) Centre for Medical Engineering at King's College London [WT 203148/Z/16/Z]
- Medical Research Council (UK) [MR/K006355/1, MR/L011530/1]
- Sackler Institute for Translational Neurodevelopment at King's College London
- European Autism Interventions (EU-AIMS)
- EU AIMS-2-TRIALS, a European Innovative Medicines Initiative Joint Undertaking [115300, 777394]
- European Union
- NIHR-BRC at GSTFT
- Medical Research Council (MRC) Clinician Scientist Fellowship [MR/P008712/1]
- Medical Research Council Centre for Neurodevelopmental Disorders, King's College London [MR/N026063/1]
- Wellcome Trust
- Royal Society [206675/Z/17/Z]
- Wellcome Trust Seed Award in Science [217316/Z/19/Z]
- Wellcome Trust [217316/Z/19/Z] Funding Source: Wellcome Trust
- MRC [MR/K006355/1, MR/N026063/1, MR/L011530/1] Funding Source: UKRI
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The Developing Human Connectome Project provides a framework to study brain development in humans at term-equivalent age, showing maturation of resting state networks and alterations in functional connectivity in preterm infants. Female infants exhibit increased connectivity in certain brain regions, while preterm birth leads to extensive disruptions in functional connectivity.
The Developing Human Connectome Project is an Open Science project that provides the first large sample of neonatal functional MRI data with high temporal and spatial resolution. These data enable mapping of intrinsic functional connectivity between spatially distributed brain regions under normal and adverse perinatal circumstances, offering a framework to study the ontogeny of large-scale brain organization in humans. Here, we characterize in unprecedented detail the maturation and integrity of resting state networks (RSNs) at term-equivalent age in 337 infants (including 65 born preterm). First, we applied group independent component analysis to define 11 RSNs in term-born infants scanned at 43.5-44.5 weeks postmenstrual age (PMA). Adult-like topography was observed in RSNs encompassing primary sensorimotor, visual and auditory cortices. Among six higher-order, association RSNs, analogues of the adult networks for language and ocular control were identified, but a complete default mode network precursor was not. Next, we regressed the subject-level datasets from an independent cohort of infants scanned at 37-43.5 weeks PMA against the group-level RSNs to test for the effects of age, sex and preterm birth. Brain mapping in term-born infants revealed areas of positive association with age across four of six association RSNs, indicating active maturation in functional connectivity from 37 to 43.5 weeks PMA. Female infants showed increased connectivity in inferotemporal regions of the visual association network. Preterm birth was associated with striking impairments of functional connectivity across all RSNs in a dose-dependent manner; conversely, connectivity of the superior parietal lobules within the lateral motor network was abnormally increased in preterm infants, suggesting a possible mechanism for specific difficulties such as developmental coordination disorder, which occur frequently in preterm children. Overall, we found a robust, modular, symmetrical functional brain organization at normal term age. A complete set of adult-equivalent primary RSNs is already instated, alongside emerging connectivity in immature association RSNs, consistent with a primary-to-higher order ontogenetic sequence of brain development. The early developmental disruption imposed by preterm birth is associated with extensive alterations in functional connectivity.
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