Abstract
Brain development is adversely affected by preterm birth. Magnetic resonance image analysis has revealed a complex fusion of structural alterations across all tissue compartments that are apparent by term-equivalent age, persistent into adolescence and adulthood, and associated with wide-ranging neurodevelopment disorders. Although functional MRI has revealed the relatively advanced organisational state of the neonatal brain, the full extent and nature of functional disruptions following preterm birth remain unclear.In this study, we apply machine-learning methods to compare whole-brain functional connectivity in preterm infants at term-equivalent age and healthy term-born neonates in order to test the hypothesis that preterm birth results in specific alterations to functional connectivity by term-equivalent age.Functional connectivity networks were estimated in 105 preterm infants and 26 term controls using group-independent component analysis and a graphical lasso model. A random forest–based feature selection method was used to identify discriminative edges within each network and a nonlinear support vector machine was used to classify subjects based on functional connectivity alone.We achieved 80% cross-validated classification accuracy informed by a small set of discriminative edges. These edges connected a number of functional nodes in subcortical and cortical grey matter, and most were stronger in term neonates compared to those born preterm. Half of the discriminative edges connected one or more nodes within the basal ganglia.These results demonstrate that functional connectivity in the preterm brain is significantly altered by term-equivalent age, confirming previous reports of altered connectivity between subcortical structures and higher-level association cortex following preterm birth.
Highlights
The incidence of preterm birth is increasing and, with improved survival rates, is linked to a wide-ranging set of neurodevelopmental, cognitive and behavioural disorders (Delobel-Ayoub et al, 2009; Marlow et al, 2005; Moore et al, 2012)
The deep grey matter structures in particular appear to be vulnerable following preterm birth: thalamic volume is significantly reduced in preterm infants, and linearly related to the degree of prematurity (Ball et al, 2012; Boardman et al, 2006)
After randomly selecting 27/2485 edges over 1000 permutations, we found that only the number of basal ganglia connections exceeded the expected number of connections given the number of nodes in each region
Summary
The incidence of preterm birth is increasing and, with improved survival rates, is linked to a wide-ranging set of neurodevelopmental, cognitive and behavioural disorders (Delobel-Ayoub et al, 2009; Marlow et al, 2005; Moore et al, 2012). Using MRI, studies have found significant alterations to the size, complexity and structure of cerebral white and grey matter in preterm infants compared to their term-born counterparts (Boardman et al, 2006; Dubois et al, 2010; Inder et al, 2005; Kapellou et al, 2006). Thalamo-cortical connections are disrupted by prematurity (Ball et al, 2013a), undermining the overall structural connectivity of the preterm brain (Ball et al, 2014) This evidence suggests that disruption of these systems may, in part, underlie subsequent adverse neurodevelopment in this population (Ball et al, 2015; Boardman et al, 2010; Fischi-Gómez et al, 2014; Volpe, 2009)
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