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Contents lists available at ScienceDirectNeuroImagejournal homepage: www.elsevier.com/locate/neuroimageAge-related functional brain changes in young childrenXiangyu Long a , Alina Benischek a , Deborah Dewey b,c , Catherine Lebel a, ?aDepartments of Radiology, University of Calgary, Alberta Children's Hospital Research Institute, Alberta Children's Hospital 2888 Shaganappi Trail, NW,Calgary, Alberta, Canada T3B 6A8bDepartments of Pediatrics, University of Calgary, Alberta Children's Hospital Research Institute, Calgary, Alberta, CanadacDepartments of Community Health Sciences, University of Calgary, Alberta Children's Hospital Research Institute, Calgary, Alberta, CanadaA R T I C L E I N F OKeywords:PreschoolBrain developmentfMRILocal activityGlobal connectivityAgeRegional homogeneityAmplitude of low frequency f l uctuationsDefault mode networkFrontoparietal networkA B S T R A C TBrain function and structure change signif i cantly during the toddler and preschool years. However, most studiesfocus on older or younger children, so the specif i c nature of these changes is unclear. In the present study, weanalyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2–6 years. We extractedmeasures of both local (amplitude of low frequency f l uctuation and regional homogeneity) and global(eigenvector centrality mapping) activity and connectivity, and examined their relationships with age usingrobust linear correlation analysis and strict control for head motion. Brain areas within the default modenetwork and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and theposterior cingulate cortex, showed increases in local and global functional features with age. Several brain areassuch as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories oflocal and global functional features, suggesting a shifting connectivity framework in early childhood. Thisdevelopment of functional connectivity in early childhood likely underlies major advances in cognitive abilities,including language and development of theory of mind. These f i ndings provide important insight into thedevelopment patterns of brain function during the preschool years, and lay the foundation for future studies ofaltered brain development in young children with brain disorders or injury.IntroductionEarly childhood is a period during which there is signif i cantdevelopment in cognitive functions, behavior, social abilities, andemotional maturity. Many neurodevelopmental disorders are f i rstrecognized and diagnosed during this time, and investigation of humanbrain development can provide insight into changes in cognitivefunctions, behavior, and emotional development (Brown andJernigan, 2012). Neurodevelopmental disorders are associated withfunctional and structural brain alterations in preschool children(Dinstein et al., 2011; Mahone et al., 2011). Developing a betterunderstanding of typical functional brain maturation during this timeis critical to fully understanding functional brain changes across thehuman lifespan (Zuo et al., 2017), and could inform early treatmentand intervention approaches for brain disorders.Magnetic resonance imaging (MRI) techniques have allowed us todevelop a better understanding of typical functional and structuralbrain changes from late childhood to adulthood (Fjell et al., 2009;Lebel et al., 2008; Lebel and Beaulieu, 2011). Throughout early life, thebrain undergoes structural changes; white matter volume, corticalthickness and myelination increase with age (Brain DevelopmentCooperative Group, 2012; Brown and Jernigan, 2012; Deoni et al.,2011), and likely underlie changes in functional brain network devel-opment. Changes in the ratio of blood–oxygen-level-dependent(BOLD) signal to cerebral blood f l ow that represent neurovascularcoupling in early childhood (Schmithorst et al., 2015) are likely relatedto brain changes observed in fMRI. Previous studies have shown thatbrain functional networks, such as the default mode network (DMN),follow a local-to-global pattern of development: younger children showa more focused, regional pattern of connections than adults who have alarger, more distributed network of connections, and this might be dueto synaptic growth and myelination during the early years (Fair et al.,2009, 2008; Lebel et al., 2008; Power et al., 2010; Sowell et al., 2002;Supekar et al., 2010; Uddin, 2010; Vogel et al., 2010). Key functionalnetworks associated with language-related brain areas are evident ininfants, and show signif i cant maturation during the f i rst two years oflife (Cao et al., 2016; Fransson et al., 2007; Gao, 2009; Gao et al., 2016,2015; Lin et al., 2008; Manning et al., 2013; Smyser et al., 2010).However, functional brain development in the preschool period (~2–6years) is very understudied due to the practical dif f i culties associatedhttp://dx.doi.org/10.1016/j.neuroimage.2017.04.059Received 2 November 2016; Accepted 25 April 2017? Corresponding author.E-mail address: clebel@ucalgary.ca (C. Lebel).NeuroImage 155 (2017) 322–330Available online 28 April 20171053-8119/ © 2017 Elsevier Inc. All rights reserved.MARK