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Cited by 187Functional Brain Connectivity StudiesAdvanced Neuroimaging Techniques and ApplicationsComplex Network Analysis Techniques

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Structural and Functional Rich Club Organization of the Brain in Children and Adults

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Grayson, David S., Ray, Siddharth, Carpenter, Samuel, Iyer, Swathi, Dias, Taciana G. Costa, Stevens, Corinne, Nigg, Joel T., Fair, Damien A.·2014·PLoS ONE
DOI 10.1371/journal.pone.0088297PMC PMC3915050
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Abstract

Recent studies using Magnetic Resonance Imaging (MRI) have proposed that the brain's white matter is organized as a rich club, whereby the most highly connected regions of the brain are also highly connected to each other. Here we use both functional and diffusion-weighted MRI in the human brain to investigate whether the rich club phenomena is present with functional connectivity, and how this organization relates to the structural phenomena. We also examine whether rich club regions serve to integrate information between distinct brain systems, and conclude with a brief investigation of the developmental trajectory of rich-club phenomena. In agreement with prior work, both adults and children showed robust structural rich club organization, comprising regions of the superior medial frontal/dACC, medial parietal/PCC, insula, and inferior temporal cortex. We also show that these regions were highly integrated across the brain's major networks. Functional brain networks were found to have rich club phenomena in a similar spatial layout, but a high level of segregation between systems. While no significant differences between adults and children were found structurally, adults showed significantly greater functional rich club organization. This difference appeared to be driven by a specific set of connections between superior parietal, insula, and supramarginal cortex. In sum, this work highlights the existence of both a structural and functional rich club in adult and child populations with some functional changes over development. It also offers a potential target in examining atypical network organization in common developmental brain disorders, such as ADHD and Autism.

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Figure 1 Overview of processing pipeline for each subject. Region Selection: T1-weighted image segmentation and parcellation resulted in a white matter mask for further diffusion data processing, as well as 219 cortical regions of interest (ROIs) covering the whole brain (the same ROIs were used for functional and structural analyses). Structural Connections: High-angular diffusion weighted MRI was acquired, and deterministic fiber tractography was performed throughout the white matter mask using a qball scheme. For each unique pair of ROIs, a connection weight was computed as the number of fibers with ends terminating upon them (see Materials and Methods). This resulted in a weighted network of structural connectivity across the whole brain. Functional Connections: Resting-state BOLD data (rs-fcMRI) was acquired, and timecourses were generated by averaging signal intensity across all voxels within a given region. Cross-correlations between regions were then used to generate the functional connectivity network.
Figure 1 Overview of processing pipeline for each subject. Region Selection: T1-weighted image segmentation and parcellation resulted in a white matter mask for further diffusion data processing, as well as 219 cortical regions of interest (ROIs) covering the whole brain (the same ROIs were used for functional and structural analyses). Structural Connections: High-angular diffusion weighted MRI was acquired, and deterministic fiber tractography was performed throughout the white matter mask using a qball scheme. For each unique pair of ROIs, a connection weight was computed as the number of fibers with ends terminating upon them (see Materials and Methods). This resulted in a weighted network of structural connectivity across the whole brain. Functional Connections: Resting-state BOLD data (rs-fcMRI) was acquired, and timecourses were generated by averaging signal intensity across all voxels within a given region. Cross-correlations between regions were then used to generate the functional connectivity network.CC BY · PubMed Central
Figure 2 Community detection in functional and structural group networks from healthy adults. Brain regions are colored according to which community they belong to. In the functional network (left), six predominant communities were identified, comprising the Default Mode (red), Cingulo-opercular (pink), Fronto-parietal (yellow), Visual (blue), Orbitofrontal/Limbic (dark red), and Somatosensory (light blue) systems. Communities resembling analogues of the functional systems were identified in the structural network as well (right).
Figure 2 Community detection in functional and structural group networks from healthy adults. Brain regions are colored according to which community they belong to. In the functional network (left), six predominant communities were identified, comprising the Default Mode (red), Cingulo-opercular (pink), Fronto-parietal (yellow), Visual (blue), Orbitofrontal/Limbic (dark red), and Somatosensory (light blue) systems. Communities resembling analogues of the functional systems were identified in the structural network as well (right).CC BY · PubMed Central
Figure 3 Rich club phenomena in structural group network of adults. (a) Regions comprising the structural rich club are displayed on an average brain surface. Degree k> = 14 was used to define rich club nodes, reflecting the peak value observed in the weighted rich club coefficient curve in (b). Results highlight the involvement of medial parietal/PCC, superior frontal/ACC, insula, and inferior temporal cortex. (b) Rich club coefficients relative to random are shown as weighted in red and as unweighted in dark red. Significant values (p<.05) are signified with an asterisk. (c) Rich club regions from (a) are colored according to community assignments. Below, a spring embedded graph shows rich club nodes and links between them, reflecting a high level of integration between systems. (d, e) Rich club regions with a high Community Index (C > = 3) and a high Distribution Index (D> = 10) are colored. A large proportion of regions are colored, reflecting high levels of integration.
Figure 3 Rich club phenomena in structural group network of adults. (a) Regions comprising the structural rich club are displayed on an average brain surface. Degree k> = 14 was used to define rich club nodes, reflecting the peak value observed in the weighted rich club coefficient curve in (b). Results highlight the involvement of medial parietal/PCC, superior frontal/ACC, insula, and inferior temporal cortex. (b) Rich club coefficients relative to random are shown as weighted in red and as unweighted in dark red. Significant values (p<.05) are signified with an asterisk. (c) Rich club regions from (a) are colored according to community assignments. Below, a spring embedded graph shows rich club nodes and links between them, reflecting a high level of integration between systems. (d, e) Rich club regions with a high Community Index (C > = 3) and a high Distribution Index (D> = 10) are colored. A large proportion of regions are colored, reflecting high levels of integration.CC BY · PubMed Central
Figure 4 Rich club phenomena in functional group network of adults. (a) Functional rich club regions were defined as having degree k> = 14, equal to the degree threshold for the structural rich club. In agreement with prior research, these results highlight the involvement of medial parietal/PCC, medial frontal/ACC, and insula cortex. (b) Rich club coefficients relative to random are shown as weighted in red and as unweighted in dark red (*where both curves are significant, p<.05). (c) Rich club regions are colored according to which community they belong to. Below, spring embedded graph of rich club nodes and links between them, reflecting a low level of integration between systems. (d, e) Rich club regions with a high Community Index (C > = 3) and regions with a high Distribution Index (D> = 10) are colored. Nearly all regions are subthreshold, indicating very low levels of integration.
Figure 4 Rich club phenomena in functional group network of adults. (a) Functional rich club regions were defined as having degree k> = 14, equal to the degree threshold for the structural rich club. In agreement with prior research, these results highlight the involvement of medial parietal/PCC, medial frontal/ACC, and insula cortex. (b) Rich club coefficients relative to random are shown as weighted in red and as unweighted in dark red (*where both curves are significant, p<.05). (c) Rich club regions are colored according to which community they belong to. Below, spring embedded graph of rich club nodes and links between them, reflecting a low level of integration between systems. (d, e) Rich club regions with a high Community Index (C > = 3) and regions with a high Distribution Index (D> = 10) are colored. Nearly all regions are subthreshold, indicating very low levels of integration.CC BY · PubMed Central
Figure 5 Regions that overlap between functional and structural rich clubs in adults. Overlapping regions, colored in yellow, defined as having degree k> = 14 in both the structural and functional group networks (the rich clubs). Structural-only and functional-only rich nodes are colred in green and red, respectively.
Figure 5 Regions that overlap between functional and structural rich clubs in adults. Overlapping regions, colored in yellow, defined as having degree k> = 14 in both the structural and functional group networks (the rich clubs). Structural-only and functional-only rich nodes are colred in green and red, respectively.CC BY · PubMed Central
Figure 6 Comparison of structural rich club organization in adults versus in children. (Left) Normalized rich club coefficients for structural data are shown for weighted (adults = red, solid; children = pink, solid), and unweighted (adults = brown, dashed; children = tan, dashed) networks. No significant differences were observed for weighted or unweighted coefficients. (Right) Regions with degree k> = 14 are shown, to facilitate direct comparison with adults. Results indicate substantial overlap in spatial layout with adults (Fig. 1a).
Figure 6 Comparison of structural rich club organization in adults versus in children. (Left) Normalized rich club coefficients for structural data are shown for weighted (adults = red, solid; children = pink, solid), and unweighted (adults = brown, dashed; children = tan, dashed) networks. No significant differences were observed for weighted or unweighted coefficients. (Right) Regions with degree k> = 14 are shown, to facilitate direct comparison with adults. Results indicate substantial overlap in spatial layout with adults (Fig. 1a).CC BY · PubMed Central
Figure 7 Comparison of functional rich club phenomena and network organization in adults versus in children. (a) Normalized rich club coefficients for functional data are shown for weighted (adults = red, solid; children = pink, solid), and unweighted (adults = brown, dashed; children = tan, dashed) networks. Significant differences are indicated with an asterisk at the top of the graph for weighted networks, and at the bottom for unweighted. Significant differences are observed (adults>children) across a wide range of k. (b) Rich club regions are displayed for the point of maximal difference in rich club coefficients that was significant (k> = 19). While many regions overlap (red arrows, for example), there are bilateral regions that appear only in adults (blue arrows, for example). (c) Rich club connections (k> = 19) are depicted for adults and for children. (d) Comparisons of the full, unfiltered matrices for adult vs. children subjects (non-group-averaged) using the Network-Based Statistic shows a single bilateral cluster of connections between regions of the insula, supramarginal, and superior parietal cortex. Cluster size was significantly greater in number than what we would expect at random (p<.01, one-tailed, T>4.5; significant clusters centered around the same nodes were also observed at T>4 and T>5 thresholds (p<.05, data not shown)). These connections primarily linked regions of the adult functional rich club as seen in (b) (k > = 19; lightly colored).
Figure 7 Comparison of functional rich club phenomena and network organization in adults versus in children. (a) Normalized rich club coefficients for functional data are shown for weighted (adults = red, solid; children = pink, solid), and unweighted (adults = brown, dashed; children = tan, dashed) networks. Significant differences are indicated with an asterisk at the top of the graph for weighted networks, and at the bottom for unweighted. Significant differences are observed (adults>children) across a wide range of k. (b) Rich club regions are displayed for the point of maximal difference in rich club coefficients that was significant (k> = 19). While many regions overlap (red arrows, for example), there are bilateral regions that appear only in adults (blue arrows, for example). (c) Rich club connections (k> = 19) are depicted for adults and for children. (d) Comparisons of the full, unfiltered matrices for adult vs. children subjects (non-group-averaged) using the Network-Based Statistic shows a single bilateral cluster of connections between regions of the insula, supramarginal, and superior parietal cortex. Cluster size was significantly greater in number than what we would expect at random (p<.01, one-tailed, T>4.5; significant clusters centered around the same nodes were also observed at T>4 and T>5 thresholds (p<.05, data not shown)). These connections primarily linked regions of the adult functional rich club as seen in (b) (k > = 19; lightly colored).CC BY · PubMed Central

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Metadata

Authors
Grayson, D. S., Ray, S., Carpenter, S., Iyer, S., Dias, T. G. C., Stevens, C., Nigg, J. T., & Fair, D. A.
Affiliations
Oregon Health & Science University (US)
Corresponding author
  • Grayson, David S.
  • Fair, Damien A.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-02-05
Volume
9
Issue
2
Pages
e88297
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0088297
PMC
PMC3915050
OpenAlex
W2063751901
Cited by
187
References
59
Citations by year
2026: 4 · 2025: 9 · 2024: 12 · 2023: 14 · 2022: 14 · 2021: 14 · 2020: 13 · 2019: 26 · 2018: 19 · 2017: 14 · 2016: 19 · 2015: 18 · 2014: 11
FWCI
11.52
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • James S. McDonnell Foundation (R01 MH096773)
  • National Institutes of Health (MH091238, MH086654)
  • Oregon Clinical and Translational Research Institute
  • National Institute of Mental Health (MH086654, MH091238, R01MH115357, R00MH091238, R01MH096773, MH096773, R01MH086654)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › Complex Network Analysis Techniques
Keywords
rich club, brain network organization, functional connectivity, structural connectivity, white matter, brain development, children, adults, default mode network, dorsal anterior cingulate cortex, posterior cingulate cortex, insula, inferior temporal cortex, supramarginal cortex, functional segregation, attention deficit hyperactivity disorder, autism spectrum disorder
MeSH terms
Adult, Brain, Brain Mapping, Child, Female, Humans, Magnetic Resonance Imaging, Male, Models, Anatomic, Models, Neurological, Nerve Net, Neural Pathways, Young Adult, Diffusion Tensor Imaging

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