Structural and functional connectivity of the human brain in autism spectrum disorders and attention-deficit/hyperactivity disorder: A rich club-organization study

Abstract

Attention-deficit/hyperactive disorder (ADHD) and autism spectrum disorders (ASD) are two of the most common and vexing neurodevelopmental disorders among children. Although the two disorders share many behavioral and neuropsychological characteristics, most MRI studies examine only one of the disorders at a time. Using graph theory combined with structural and functional connectivity, we examined the large-scale network organization among three groups of children: a group with ADHD (8-12 years, n = 20), a group with ASD (7-13 years, n = 16), and typically developing controls (TD) (8-12 years, n = 20). We apply the concept of the rich-club organization, whereby central, highly connected hub regions are also highly connected to themselves. We examine the brain into two different network domains: (1) inside a rich-club network phenomena and (2) outside a rich-club network phenomena. The ASD and ADHD groups had markedly different patterns of rich club and non rich-club connections in both functional and structural data. The ASD group exhibited higher connectivity in structural and functional networks but only inside the rich-club networks. These findings were replicated using the autism brain imaging data exchange dataset with ASD (n = 85) and TD (n = 101). The ADHD group exhibited a lower generalized fractional anisotropy and functional connectivity inside the rich-club networks, but a higher number of axonal fibers and correlation coefficient values outside the rich club. Despite some shared biological features and frequent comorbity, these data suggest ADHD and ASD exhibit distinct large-scale connectivity patterns in middle childhood.

Keywords: DW-MRI; attention-deficit/hyperactivity disorder; autism spectrum disorders; connectivity; diffusion tensor imaging; high angular resolution diffusion imaging; rich-club organization; rs-fMRI.

© 2014 Wiley Periodicals, Inc.

Figures

Figure 1

Rich‐club organization in structural group networks of ASD, TD, and ADHD. Rich‐club coefficients normalized relative to random are shown in blue (ASD), green (controls), and red (ADHD) colors. The coefficients are plotted against degree, between 1 and 20. Shaded regions shows the significant (p < 0.05) higher coefficients.

Figure 2

Spatial topography and spring embedded graphs of structural rich club in ASD, control, and ADHD (top–bottom). Rich‐club regions at k ≥ 13 are shown for all the three groups. Regions are colored based on their degree distribution (yellow to red). On the right‐hand side are the corresponding spring embedded graphs for each group where regions are depicted as circles and links between them are the solid lines between them.

Figure 3

Connectedness coefficients (unweighted and weighted) between structural networks of ASD, controls, and ADHD for networks inside and outside the rich‐club organization. Graphs on the left‐hand side show the unweighted connectedness coefficients and weighted coefficients comparison between groups inside the rich club (13 ≤ k ≤ 20), while right‐hand side graphs shows these comparison for networks outside the rich club (5 ≤ k ≤ 13). Significant differences between ASD‐controls are marked with “+” sign, ADHD‐controls are marked with “o” sign, ASD‐ADHD are marked with “^” sign.

Figure 4

GFA and number of streamlines comparison between ASD, TD, and ADHD for networks inside and outside the rich‐club organization. Graphs on the top row shows the GFA‐mean comparison between ASD (colored blue), controls (colored green), and ADHD group (colored red) inside and outside rich club, respectively. Graphs on the bottom row show mean of number of fiber streamlines comparison between the TD, the ASD, and the ADHD groups inside and outside the rich‐club organization. Significant differences between ASD‐controls are marked with “+” sign, ADHD‐controls are marked with “o” sign, ASD‐ADHD are marked with “^” sign and between all three groups are marked with “*” sign.

Figure 5

Rich‐club organization in functional group networks of ASD, controls, and ADHD. Rich‐club coefficients normalized relative to random are shown in blue (ASD), green (controls), and red (ADHD) colors. The coefficients are plotted against degree, between 1 and 17. Shaded regions show the significant (p < 0.05) higher coefficients.

Figure 6

Spatial topography and spring embedded graphs of functional rich club in ASD, control, and ADHD (top–bottom). Rich‐club regions at k ≥ 11 are shown for all three groups. Regions are colored based on their degree distribution (yellow to red). On the right‐hand side are the spring embedded graphs for each group where regions are depicted as circles and links between them are the solid lines between them.

Figure 7

Connectedness coefficients comparison between functional networks of ASD, controls, and ADHD for networks inside and outside the rich‐club organization. Graphs on left‐hand side shows the unweighted connectedness coefficients, weighted coefficients, and number stream lines comparison between groups inside the rich club (11 ≤ k ≤ 17), whereas right‐hand side graphs shows these comparison for networks outside the rich club (3 ≤ k ≤ 11). Significant differences between ASD‐controls are marked with “+” sign, ADHD‐controls are marked with “o” sign, ASD‐ADHD are marked with “^” sign.

Figure 8

Connectedness coefficients comparison between functional networks of ASD and controls (ABIDE data) for networks inside and outside the rich‐club organization. The left‐hand side graphs shows the unweighted connectedness coefficients and weighted coefficients comparison between groups inside the rich club (11 ≤ k ≤ 17), the right‐hand side graphs shows these comparison for networks outside the rich club (3 ≤ k ≤ 11). Significant differences between ASD‐controls are marked with “+” sign.

Figure 9

Correlation values comparison between ASD, TD, and ADHD group inside and outside rich‐club organization. Average of correlation values across various degree levels are compared between ASD (blue), TD (green), and ADHD (red). Significant difference, from ANOVA, are marked using “*”. Significant differences between ASD‐controls are marked with “+” sign, ADHD‐controls are marked with “o” sign, ASD‐ADHD are marked with “^” sign.