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Comparative Study
. 2010 Aug 1;52(1):290-301.
doi: 10.1016/j.neuroimage.2010.04.009. Epub 2010 Apr 10.

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

Kaustubh Supekar  1 , Lucina Q Uddin, Katherine Prater, Hitha Amin, Michael D Greicius, Vinod Menon
Affiliations
Comparative Study

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

Kaustubh Supekar et al. Neuroimage. .

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.

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Figures

Figure 1
Figure 1. Weaker DMN activity in children
Default mode network (DMN) in (A) children, and (B) young adults. (C) shows results of a two-sample t test contrasting the DMN in young adults vs. children. Both groups show activity in posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), medial temporal lobe (MTL), and angular gyrus (AG). Compared to young adults, children showed reduced activity in the mPFC (p < 0.01). Compared to young adults, children did not show greater DMN activity in any brain region.
Figure 2
Figure 2. Maturation of DMN: PCC-mPFC connectivity
(A) Functional connectivity between PCC and mPFC was significantly weaker in children, compared to young adults (p < 0.01, indicated by **). Functional connectivity was assessed using partial correlation between specific nodes of the default mode network (DMN) after controlling for the influence of other nodes of the DMN and five non-DMN brain networks. (B) Greater gray matter volume in the PCC and mPFC was observed in children, compared to young adults. (C) Lower white matter volume was observed in children within the cingulum (cingulate gyrus), which connects the PCC and mPFC. (D) DTI tractography of fiber tracts connecting PCC to mPFC (blue tracts). Fiber density, the number of fibers per unit area between the PCC to mPFC, was significantly lower in children, compared to young adults (p < 0.001, indicated by **). The mean FA of the PCC-mPFC fibers was significantly lower in children compared to young adults (p << 0.0001, indicated by **). (E) Functional connectivity, assessed using partial correlations between the PCC and mPFC, and structural connectivity, assessed using DTI-based measures of fiber density showed positive correlation in young adults (r = 0.57; p < 0.05, indicated by **) but not in children (r = 0.21; p = 0.4). A similar relationship between PCC-mPFC functional connectivity and structural connectivity was observed when mean FA was used as a measure of structural connectivity instead of fiber density (data not shown).
Figure 3
Figure 3. Maturation of DMN: PCC-left MTL connectivity
(A) No significant group difference in functional connectivity between PCC and left MTL was observed. Functional connectivity was assessed using partial correlation between specific nodes of the default mode network (DMN) after controlling for the influence of other nodes of the DMN and five non-DMN brain networks. (B) Greater gray matter volume in the PCC but not the left MTL was observed in children, compared to young adults. (C) Lower white matter volume was observed in children within the left cingulum (hippocampus), which connects the PCC and left MTL. (D) DTI tractography of fiber tracts connecting PCC to left MTL (yellow tracts). Fiber density, the number of fibers per unit area between the PCC to left MTL, was significantly lower in children, compared to young adults (p < 0.001, indicated by **). The mean FA of the PCC-leftMTL fibers was significantly lower in children compared to young adults (p < 0.001, indicated by **). (E) No significant correlation between functional connectivity, assessed using partial correlations and structural connectivity, assessed using DTI-based measures of fiber density between the PCC and left MTL was observed in either group. A similar relationship between PCC-left MTL functional connectivity and structural connectivity was observed when mean FA was used as a measure of structural connectivity instead of fiber density (data not shown).
Figure 4
Figure 4. Maturation of DMN: PCC-right MTL connectivity
(A) No significant group difference in functional connectivity between PCC and right MTL was observed. Functional connectivity was assessed using partial correlation between specific nodes of the default mode network (DMN) after controlling for the influence of other nodes of the DMN and five non-DMN brain networks. (B) Greater gray matter volume in the PCC but not the right MTL was observed in children, compared to young adults. (C) No white matter volume group differences were found in the right cingulum (hippocampus), which connects the PCC and right MTL. (D) DTI tractography of fiber tracts connecting PCC to right MTL (yellow tracts). No significant group differences in the density of fibers connecting PCC to right MTL were observed. No significant group differences in the mean FA of PCC-rightMTL fibers were observed (E) No significant correlation between functional connectivity, assessed using partial correlations and structural connectivity, assessed using DTI-based measures of fiber density between the PCC and right MTL was observed in either group. A similar relationship between PCC-rightMTL functional connectivity and structural connectivity was observed when mean FA was used as a measure of structural connectivity instead of fiber density (data not shown)
Figure 5
Figure 5. Individual subject fiber tracts between DMN regions in children and young adults
Representative single-subject DTI tractography in four children and four young adults showing fiber tracts linking the PCC (shown in red), mPFC, and left (purple) and right MTL (green). Both children and adults showed fiber tracts from the mPFC that enter the more rostral aspect of the PCC (shown in blue), and tracts from the MTL that enter the more caudal aspect of the PCC (shown in yellow). Only half of the children showed tracts between PCC and left MTL. There were no tracts connecting the mPFC to the MTL.
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