The Developing Human Connectome Project: typical and disrupted perinatal functional connectivity.

Michael Eyre ,Judit Ciarrusta ,Tomoki Arichi ,Daniel Cromb ,Jonathan O’muircheartaigh ,Dafnis Batalle ,Euguene Duff ,Jesper Andersson ,Joseph V Hajnal ,Anthony N Price ,Lucilio Cordero‐Grande ,Katy Vecchiato ,Jakki Brandon ,Serena J Counsell ,Camilla O’keeffe ,Daniel Rueckert ,Stephen M Smith ,Tanya Poppe ,Andreas Schuh ,Emer Hughes ,Sean P Fitzgibbon ,A David Edwards

doi:10.1093/brain/awab118

Abstract

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.

Highlights

The final study population consisted of 337 infants, divided into three groups: (i) term-born infants scanned at 43.5–44.5 weeks postmenstrual age (PMA), who were used to define the normative set of resting state networks (RSNs) and excluded from all subsequent subject-level analyses; and the remaining infants scanned at 37–43.5 weeks PMA, including both (ii) term-born; and (iii) preterm-born infants (Table 1)
Eleven RSNs were identified by group independent component analysis (ICA) in a subsample of termborn infants scanned between 43.5 and 44.5 weeks PMA (n = 24), who were excluded from any further analyses
The association of younger gesational age at birth with impaired functional connectivity was replicated across all networks in a separate analysis in which gesational age at birth was entered as a continuous variable, indicating a dose-dependent effect of prematurity on functional connectivity (Supplementary Figs 5 and 6, Bonferroni-corrected). In this large cohort of newborn infants we provide detailed characterization of the maturational trajectories of normal functional network development at term-equivalent age (TEA), and show that the early developmental disruption imposed by preterm birth is associated with significant and widespread alterations in functional connectivity

Summary

Introduction

This enables the characterization of 4D (three spatial dimensions and time) connectivity maps, which map the trajectories of human brain development to improve understanding of normal development and allow earlier detection and intervention for neurological and psychological disorders. Various alterations in the complexity, scope, strength and efficiency of functional connectivity in preterm-at-term infants have been reported[9,10,17,18,19]; the majority of studies lack the large numbers of control subjects required to characterize these effects with precision

Methods

Results

Discussion

Conclusion