Objective, early, and non-invasive assessment of brain function in high-risk newborns is critical to initiate timely interventions and to minimize long-term neurodevelopmental disabilities. A prerequisite to identifying deviations from normal, however, is the availability of baseline measures of brain function derived from healthy, full-term newborns. Recent advances in functional MRI combined with graph theoretic techniques may provide important, currently unavailable, quantitative markers of normal neurodevelopment. In the current study, we describe important properties of resting state networks in 60 healthy, full-term, unsedated newborns. The neonate brain exhibited an efficient and economical small world topology: densely connected nearby regions, sparse, but well integrated, distant connections, a small world index greater than 1, and global/local efficiency greater than network cost. These networks showed a heavy-tailed degree distribution, suggesting the presence of regions that are more richly connected to others (‘hubs’). These hubs, identified using degree and betweenness centrality measures, show a more mature hub organization than previously reported. Targeted attacks on hubs show that neonate networks are more resilient than simulated scale-free networks. Networks fragmented faster and global efficiency decreased faster when betweenness, as opposed to degree, hubs were attacked suggesting a more influential role of betweenness hub in the neonate network.

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IMPORTANCEMaternal psychological distress during pregnancy is associated with adverse obstetric outcomes and neuropsychiatric deficits in children. Currently unavailable in vivo interrogation of fetal brain function could provide critical insights into the onset and timing of altered neurodevelopmental trajectories. OBJECTIVE To investigate the association between prenatal maternal stress, anxiety, and depression and in vivo fetal brain resting state functional connectivity. DESIGN, SETTING, AND PARTICIPANTS This cohort study included pregnant women scanned between January 2016 and April 2019. A total of 50 pregnant women with healthy pregnancies were prospectively recruited from low-risk obstetric clinics in the Washington DC area and were scanned at Children's National in Washington DC. EXPOSURES Maternal stress, anxiety, and depression. MAIN OUTCOMES AND MEASURESThe association of prenatal maternal stress, anxiety, and depression with whole-brain connectivity was analyzed using multivariate distance matrix regression. Prenatal maternal stress, anxiety, and depression were assessed using the Perceived Stress Scale, Spielberger State Anxiety Inventory and Spielberger Trait Anxiety Inventory, and the Edinburgh Postnatal Depression Scale, respectively. Whole-brain connectivity was measured from 100 functionally defined regions of interest. RESULTSThis study analyzed 59 resting-state functional connectivity magnetic resonance image data sets from the fetuses (mean [SD] gestational age, 33.52 [4 weeks]) of 50 healthy pregnant women (mean [SD] age, 33.77 [5.51]). Mean (SD) scores for the questionnaires were as follows:

Newborns with congenital heart disease (CHD) requiring open heart surgery are at increased risk for neurodevelopmental disabilities. Recent quantitative MRI studies have reported disrupted growth, microstructure, and metabolism in fetuses and newborns with complex CHD. To date, no study has examined whether functional brain connectivity is altered in this high-risk population after birth, before surgery. Our objective was to compare whole-brain functional connectivity of resting state networks in healthy, term newborns (n = 82) and in term neonates with CHD before surgery (n = 30) using graph theory and network-based statistics. We report for the first time intact global network topology – efficient and economic small world networks – but reduced regional functional connectivity involving critical brain regions (i.e. network hubs and/or rich club nodes) in newborns with CHD before surgery. These findings suggest the presence of early-life brain dysfunction in CHD which may be associated with neurodevelopmental impairments in the years following cardiac surgery. Additional studies are needed to evaluate the prognostic, diagnostic and surveillance potential of these findings.

Brain structural changes in premature infants appear before term age. Functional differences between premature infants and healthy fetuses during this period have yet to be explored. Here, we examined brain connectivity using resting state functional MRI in 25 very premature infants (VPT; gestational age at birth <32 weeks) and 25 healthy fetuses with structurally normal brain MRIs. Resting state data were evaluated using seed-based correlation analysis and network-based statistics using 23 regions of interest (ROIs) per hemisphere. Functional connectivity strength, the Pearson correlation between blood oxygenation level dependent signals over time across all ROIs, was compared between groups. In both cohorts, connectivity between homotopic ROIs showed a decreasing medial to lateral gradient. The cingulate cortex, medial temporal lobe and the basal ganglia shared the strongest connections. In premature infants, connections involving superior temporal, hippocampal, and occipital areas, among others, were stronger compared to fetuses. Premature infants showed stronger connectivity in sensory input and stress-related areas suggesting that extra-uterine environment exposure alters the development of select neural networks in the absence of structural brain injury.