Authors
Eyre M, Fitzgibbon SP, Ciarrusta J, Cordero-Grande L, Price AN, Poppe T, Schuh A, Hughes E, O’Keefe C, Brandon J, Cromb D, Vecchiato K, Duff EP, Counsell SJ, Smith SM, Rueckert D, Hajnal JV, Arichi T, O’Muircheartaigh J, Batalle D, Edwards AD.

Institution(s)
Centre for the Developing Brain, King’s College London (KCL); Wellcome Centre for Integrative
Neuroimaging, University of Oxford; and the Biomedical Image Analysis Group, Imperial College London.

Introduction
The Developing Human Connectome Project (dHCP) represents the largest open source sample of neonatal functional MRI (fMRI) data ever collected. Using fMRI data collected at rest, the intrinsic functional connectivity of spatially distributed brain regions can be captured as distinct resting-state networks (RSNs). We hypothesised that (i) RSNs undergo active maturation from 37 to 43.5 weeks of postmenstrual age (PMA); and (ii) preterm birth is associated with reduced functional connectivity at normal term age.

Methods
Fifteen minutes of fMRI optimized for neonates was acquired in natural sleep. We first defined normative RSNs in 24 term-born infants scanned at 43.5-44.5 weeks PMA, using probabilistic independent component analysis. We then regressed data from 248 term-born and 65 preterm-born infants scanned at 37-43.5 weeks PMA against these normative networks to test for the effects of age, sex and preterm birth, using dual regression, general linear models and permutation testing. Family-wise error-rate corrected p values < 0.025 were regarded as significant. dHCP was approved by the UK National Research Ethics Authority (14/LO/1169). [Funding below]

Results
Five RSNs encompassing primary cortical areas (Fig. 1A) and six association RSNs (Fig. 1B) were identified. Primary RSNs showed adult-like topology at all ages, while four association RSNs showed areas of increasing functional connectivity with older PMA at scan. Female infants showed increased inferotemporal connectivity within the visual association network. Preterm birth was associated with strikingly reduced functional connectivity across all RSNs studied; conversely, connectivity of the superior parietal lobules within the lateral motor network was increased in preterm infants (Fig. 2).

Conclusions
We observed a primary-to-higher-order sequence of brain maturation. Preterm birth was associated with widespread impairments in functional connectivity and aberrant parieto-motor connectivity, with possible implications for understanding developmental coordination disorder and related problems in preterm children.

References
dHCP is funded by the European Research Council. Dr Eyre was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust / KCL.