Elsevier

NeuroImage

Volume 52, Issue 1, 1 August 2010, Pages 290-301
NeuroImage

Development of functional and structural connectivity within the default mode network in young children

https://doi.org/10.1016/j.neuroimage.2010.04.009Get rights and content

Abstract

Functional and structural maturation of networks comprised of discrete regions is an important aspect of brain development. The default-mode network (DMN) is a prominent network which includes the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), medial temporal lobes (MTL), and angular gyrus (AG). Despite increasing interest in DMN function, little is known about its maturation from childhood to adulthood. Here we examine developmental changes in DMN connectivity using a multimodal imaging approach by combining resting-state fMRI, voxel-based morphometry and diffusion tensor imaging-based tractography. We found that the DMN undergoes significant developmental changes in functional and structural connectivity, but these changes are not uniform across all DMN nodes. Convergent structural and functional connectivity analyses suggest that PCC-mPFC connectivity along the cingulum bundle is the most immature link in the DMN of children. Both PCC and mPFC also showed gray matter volume differences, as well as prominent macrostructural and microstructural differences in the dorsal cingulum bundle linking these regions. Notably, structural connectivity between PCC and left MTL was either weak or non-existent in children, even though functional connectivity did not differ from that of adults. These results imply that functional connectivity in children can reach adult-like levels despite weak structural connectivity. We propose that maturation of PCC-mPFC structural connectivity plays an important role in the development of self-related and social-cognitive functions that emerge during adolescence. More generally, our study demonstrates how quantitative multimodal analysis of anatomy and connectivity allows us to better characterize the heterogeneous development and maturation of brain networks.

Introduction

There is growing scientific interest in understanding large-scale brain networks that underlie higher-level cognition in humans. The default-mode network (DMN) is a prominent large-scale brain network that includes the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), medial temporal lobes (MTL), and angular gyrus (AG). The DMN is unique in terms of its high resting metabolism, deactivation profile during cognitively demanding tasks (Raichle et al., 2001, Shulman et al., 1997), and increased activity during high-level social cognitive tasks (Harrison et al., 2008). The precise functions collectively subserved by the DMN are still largely unknown, but the individual brain regions comprising it are involved in integration of autobiographical, self-monitoring and social cognitive functions (Spreng et al., 2009). The PCC is activated during tasks that involve autobiographical memory and self-referential processes (Buckner and Carroll, 2007), the mPFC is associated with social cognitive processes related to self and others (Amodio and Frith, 2006), the MTL is engaged in episodic memory (Milner, 2005), and the AG is implicated in semantic processing and attention (Binder et al., 2009, Chambers et al., 2004). Regardless of the specific functions subserved by each region of the DMN, it is noteworthy that dynamic suppression of this network during cognitively demanding tasks appears to be necessary for accurate behavioral performance (Kelly et al., 2008, Polli et al., 2005, Weissman et al., 2006).

Most of our knowledge about the DMN has been based on brain imaging studies in adults. In adults, the DMN can be reliably isolated in virtually every individual, presumably because interactions between the core brain regions that comprise it have led to a stable and mature network. Very little is currently known about the functional maturation of the DMN from childhood to adulthood, and less is known about structural changes that underlie the functional maturation of the DMN. Notably, no study has examined white matter within the DMN in children, using diffusion tensor imaging (DTI) tractography. As a result, the relationship between DMN structure and function in children is also not known. Examining the developmental trajectory of the DMN is important not only for understanding how structural brain changes during development impact development of key functional brain circuits, but also for understanding the ontogeny of cognitive processes subserved by the DMN. Additionally, the putative functions of the DMN, as well as the maturation of cognitive control mechanisms, are relatively late to develop in children, and are often compromised in neurodevelopmental disorders such as autism spectrum disorders and attention-deficit/hyperactivity disorder (Broyd et al., 2009).

Here we use resting-state fMRI in conjunction with DTI and optimized voxel-based morphometry (VBM) to characterize functional, white matter, and gray matter changes within the DMN from childhood to young adulthood. Specifically, we investigated developmental changes in functional and structural connectivity between key nodes within the DMN. We additionally examined the relationship between measures of functional and structural connectivity between DMN regions. Previous structural neuroimaging studies have shown that while gray matter volume follows a regionally specific inverted U-shaped trajectory, white matter volume shows protracted increases with development (Lenroot and Giedd, 2006). This principle suggests that connectivity between different cortical regions matures at different time points during development. We therefore hypothesized that DMN maturation would be characterized by heterogeneous changes in structural and functional connectivity with age. We further hypothesized that weak long-range structural connections between the PCC and the mPFC would have a significant impact on functional connectivity in children.

Section snippets

Participants

Twenty-three children and twenty-two IQ-matched young-adult subjects participated in this study after providing written informed consent. For those subjects who were unable to give informed consent, written informed consent was obtained from their legal guardian. The study protocol was approved by the Stanford University Institutional Review Board. The child subjects (10 males, 13 females) ranged in age from 7 to 9 (mean age 7.95) with an IQ range of 88 to 137 (mean IQ: 112). The young-adult

Results

Demographic data is shown in Table 1. Participant groups did not differ on IQ (p = 0.93) or gender distribution (p = 0.75).

Discussion

The human brain undergoes protracted structural and functional development (Barnea-Goraly et al., 2005, Sowell et al., 2003, Supekar et al., 2009). Most previous studies have focused on local changes in gray and white matter (Sowell et al., 2003), thus less is known about the maturation of functional circuits in the developing human brain. The DMN is a core network implicated in self-referential mental activity and social cognition, and understanding its developmental trajectory is important

Conclusion

Each of the major nodes (PCC, mPFC, AG, MTL) of the DMN could be consistently detected in 7- to 9-year-old children. We found that children had significantly weaker functional and structural connectivity between the anterior (mPFC) and posterior (PCC) nodes of the DMN. Both the PCC and the mPFC also showed gray volume differences, as well as prominent macrostructural and microstructural differences in the dorsal cingulum bundle that links these regions. Notably, functional connectivity was not

Acknowledgments

We thank Leeza Kondos and Jose Anguiano for their assistance with data acquisition. This work was supported by the National Institutes of Health (HD047520, HD059205, NS058899 to VM); the National Science Foundation (BCS-0449927 to VM) and the Children's Health Research Program of the Lucille Packard Children's Hospital.

References (67)

  • S. Pajevic et al.

    A continuous tensor field approximation of discrete DT-MRI data for extracting microstructural and architectural features of tissue

    J. Magn. Reson.

    (2002)
  • K. Shmueli et al.

    Low-frequency fluctuations in the cardiac rate as a source of variance in the resting-state fMRI BOLD signal

    NeuroImage

    (2007)
  • P. Skudlarski et al.

    Measuring brain connectivity: diffusion tensor imaging validates resting state temporal correlations

    NeuroImage

    (2008)
  • F.T. Sun et al.

    Measuring interregional functional connectivity using coherence and partial coherence analyses of fMRI data

    NeuroImage

    (2004)
  • P.M. Thompson et al.

    Structural MRI and brain development

    Int. Rev. Neurobiol.

    (2005)
  • D.C. Alexander et al.

    Spatial transformations of diffusion tensor magnetic resonance images

    IEEE Trans Med. Imaging

    (2001)
  • D.M. Amodio et al.

    Meeting of minds: the medial frontal cortex and social cognition

    Nat. Rev. Neurosci.

    (2006)
  • R. Bammer et al.

    Diffusion tensor imaging using single-shot SENSE-EPI

    Magn. Reson. Med.

    (2002)
  • N. Barnea-Goraly et al.

    White matter development during childhood and adolescence: a cross-sectional diffusion tensor imaging study

    Cereb. Cortex

    (2005)
  • P.J. Basser

    Inferring microstructural features and the physiological state of tissues from diffusion-weighted images

    NMR Biomed.

    (1995)
  • P.J. Basser et al.

    In vivo fiber tractography using DT-MRI data

    Magn. Reson. Med.

    (2000)
  • C. Beaulieu

    The basis of anisotropic water diffusion in the nervous system - a technical review

    NMR Biomed.

    (2002)
  • J.R. Binder et al.

    Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies

    Cereb. Cortex

    (2009)
  • B. Biswal et al.

    Functional connectivity in the motor cortex of resting human brain using echo-planar MRI

    Magn. Reson. Med.

    (1995)
  • C.D. Chambers et al.

    Fast and slow parietal pathways mediate spatial attention

    Nat. Neurosci.

    (2004)
  • T.E. Conturo et al.

    Tracking neuronal fiber pathways in the living human brain

    Proc. Natl. Acad. Sci. U. S. A.

    (1999)
  • D. Cordes et al.

    Frequencies contributing to functional connectivity in the cerebral cortex in “resting-state” data

    AJNR Am. J. Neuroradiol.

    (2001)
  • J.S. Damoiseaux et al.

    Greater than the sum of its parts: a review of studies combining structural connectivity and resting-state functional connectivity

    Brain Struct. Funct.

    (2009)
  • J.S. Damoiseaux et al.

    Consistent resting-state networks across healthy subjects

    Proc. Natl. Acad. Sci. U. S. A.

    (2006)
  • M. De Luca et al.

    Blood oxygenation level dependent contrast resting state networks are relevant to functional activity in the neocortical sensorimotor system

    Exp. Brain Res.

    (2005)
  • D.A. Fair et al.

    The maturing architecture of the brain's default network

    Proc. Natl. Acad. Sci. U. S. A.

    (2008)
  • D.A. Fair et al.

    Development of distinct control networks through segregation and integration

    Proc. Natl. Acad. Sci. U. S. A.

    (2007)
  • M.D. Fox et al.

    The human brain is intrinsically organized into dynamic, anticorrelated functional networks

    Proc. Natl. Acad. Sci. U. S. A.

    (2005)
  • Cited by (433)

    View all citing articles on Scopus
    View full text