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