Dynamic reconfiguration of structural and functional connectivity across core neurocognitive brain networks with development

Abstract

Brain structural and functional development, throughout childhood and into adulthood, underlies the maturation of increasingly sophisticated cognitive abilities. High-level attentional and cognitive control processes rely on the integrity of, and dynamic interactions between, core neurocognitive networks. The right fronto-insular cortex (rFIC) is a critical component of a salience network (SN) that mediates interactions between large-scale brain networks involved in externally oriented attention [central executive network (CEN)] and internally oriented cognition [default mode network (DMN)]. How these systems reconfigure and mature with development is a critical question for cognitive neuroscience, with implications for neurodevelopmental pathologies affecting brain connectivity. Using functional and effective connectivity measures applied to fMRI data, we examine interactions within and between the SN, CEN, and DMN. We find that functional coupling between key network nodes is stronger in adults than in children, as are causal links emanating from the rFIC. Specifically, the causal influence of the rFIC on nodes of the SN and CEN was significantly greater in adults compared with children. Notably, these results were entirely replicated on an independent dataset of matched children and adults. Developmental changes in functional and effective connectivity were related to structural connectivity along these links. Diffusion tensor imaging tractography revealed increased structural integrity in adults compared with children along both within- and between-network pathways associated with the rFIC. These results suggest that structural and functional maturation of rFIC pathways is a critical component of the process by which human brain networks mature during development to support complex, flexible cognitive processes in adulthood.

Figure 1.

Identifying nodes of neurocognitive networks. SN, right CEN, and DMN identified from ICA of resting-state fMRI data. Network maps were derived by performing a combined group (adult + children) one-sample t test on individual best-fit network components. Network nodes for subsequent analyses were based on 8-mm-radius spheres created around peak voxels defined from this analysis.

Figure 2.

Functional connectivity between nodes of neurocognitive networks. A, Instantaneous (undirected) functional connectivity, as measured by partial correlation, of the six key nodes of the SN (blue), CEN (green), and DMN (yellow) in adults and children and results of a two-sample t test contrasting the functional connectivity in children versus adults (p < 0.01, FDR corrected). B, Results from analysis of left-hemisphere ROIs.

Figure 3.

Effective connectivity between nodes of neurocognitive networks. A, GCA of the six key nodes of the SN (blue), CEN (green), and DMN (yellow) in adults and children and results of a two-sample t test contrasting directed causal network interactions in children versus adults (p < 0.01, FDR corrected). B, Results from analysis of left-hemisphere ROIs.

Figure 4.

Replication analysis of functional and effective connectivity between nodes of neurocognitive networks. Using data from the publicly available NKI dataset (http://fcon_1000.projects.nitrc.org/indi/pro/nki.html), functional and effective connectivity analyses were conducted, replicating the original findings. A, Functional connectivity (partial correlation) between network nodes in children and adults. B, Effective connectivity (GCA) between network nodes in children and adults.

Figure 5.

Net outflow of effective connectivity between nodes of neurocognitive networks. Net causal outflow (out–in degree) in the key nodes of the SN (blue), DMN (yellow), and CEN (green) are shown for adults (A) and children (B). In both groups, the rFIC had significantly higher net causal outflow than the ACC, PCC, VMPFC, rDLPFC, and rPPC (p < 0.01, FDR corrected).

Figure 6.

Structural connectivity between nodes of SN: rFIC–ACC. DTI tractography identified white matter tracts along the uncinate fasciculus connecting the rFIC and ACC nodes of the SN. Fibers (blue) connecting rFIC (red) and ACC (green) in one representative individual child (A) and adult (B). C, Group differences in FA between rFIC–ACC (effect size, 0.46; p = 0.1). D, Group differences in fiber density between rFIC–ACC (effect size, 0.63; *p = 0.05).

Figure 7.

Structural connectivity between nodes of SN: rFIC–ACC in eight individuals. DTI tractography results show that tracts along the uncinate fasciculus can be reliably identified in individual subjects. Tracts were detected in 11 of 15 adults (73%) and 9 of 18 children (50%). Four children and adults are shown. The first row shows a sagittal slice viewed from the right, whereas the second row shows a coronal slice viewed anteriorly.

Figure 8.

Structural connectivity between nodes of SN and CEN: rFIC–rDLPFC. DTI tractography identified white matter tracts along the fronto-occipital fasciculus connecting rFIC and rDLPFC. Fibers (yellow) connecting rFIC (red) and rDLPFC (blue) in one representative individual child (A) and adult (B). C, Group differences in FA between rFIC–rDLPFC (effect size, 0.82; *p = 0.01). D, Group differences in fiber density between rFIC–rDLPFC (effect size, 0.33; p = 0.07).

Figure 9.

Structural connectivity between nodes of SN and CEN: rFIC–rDLPFC in eight individuals. DTI tractography results show that tracts along the fronto-occipital fasciculus can be reliably identified in individual subjects. Tracts were detected in 14 of 15 adults (93%) and 12 of 18 (67%) children. Four children and adults are shown. The first row shows a sagittal slice viewed from the right, whereas the second row show a sagittal slice viewed dorsally.

Figure 10.

Relationship between functional connectivity and structural connectivity. In adults, there was a significant correlation between functional connectivity (as measured by normalized partial correlation) and structural connectivity (as measured by FA) for the rFIC–rDLPFC link (r = 0.81, p = 0.0004). There were no other significant correlations between functional and structural connectivity in the adults or children.