Significantly lateralized connections between each of the 20 hubs.

<p>Warm colors show significant left lateralization and cool colors show significant right lateralization. Color bar shows t-statistic for each connection. All colored squares were significant after correcting for multiple comparisons using a false discovery rate of q<0.05 among all possible connections between the hubs. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071275#pone-0071275-t002" target="_blank">Table 2</a> or <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071275#pone-0071275-g003" target="_blank">Figure 3</a> for the hubs’ two-letter abbreviations.</p

Connections between right-lateralized hubs that change in lateralization across development between the ages of 7 and 29.

<p>Connections between right-lateralized hubs that change in lateralization across development between the ages of 7 and 29.</p

Significant correlation of lateralized connections across subjects.

<p>Yellow nodes represent connections between left hubs and green nodes represent connections between right hubs. An edge is present if lateralization was found to significantly correlate across subjects between the two connections, with red edges showing positive correlation and blue edges negative correlation, after correcting for multiple comparisons using a false discovery rate of q<0.05 across all possible connection-to-connection pairs. Virtually all edges are between nodes with a hub in common. A Kamada-Kawai algorithm was implemented in Social Network Image Animator software (<a href="http://www.stanford.edu/group/sonia/" target="_blank">http://www.stanford.edu/group/sonia/</a>). The software was also used to visualize the relationship between connections. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071275#pone-0071275-t002" target="_blank">Table 2</a> or <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071275#pone-0071275-g003" target="_blank">Figure 3</a> for the hubs’ two-letter abbreviations.</p

Degree maps for significantly left- and right-lateralized connections after regression of structural laterality index from all connections.

<p>Significantly lateralized connections (after correcting for multiple comparisons using a false discovery rate of q <0.05, across all 14.1 million intrahemispheric connections) were used to construct a graph of significantly left-lateralized connections among left hemisphere ROIs and a separate graph of significantly right-lateralized connections among right hemisphere ROIs. Color scale shows graph-theoretical degree (i.e., sum of all significantly lateralized connections in which a given node is represented) for each ROI. Images are in radiologic format with subject left on image right.</p

Significant lateralization of gray matter density.

<p>Colored regions included ROIs that showed significantly greater left- or right-lateralization of gray matter density across 1011 subjects, correcting for multiple comparisons using a false discovery rate correction of q<0.05 across 7266 ROIs. Color bars show t-statistics for the left and right hemispheres, respectively. Images are in radiologic format with subject left on image right.</p

Reproducibility of lateralization.

<p><b>A</b>, Mean functional lateralization index for the 91 intrahemispheric connections (blue, connections involving right-lateralized hubs; red, connections involving left-lateralized hubs) is compared when averaging across all subjects except those from the Beijing site and when averaging across only subjects from the Beijing site. Pearson correlation coefficients and p-values are shown in both plots. <b>B</b>, Mean functional lateralization index for the 91 intrahemispheric connections (blue, connections involving right-lateralized hubs; red, connections involving left-lateralized hubs) is compared when averaging across all subjects and when averaging across all subjects except those that come from a site with less than 10 subjects.</p

Significantly lateralized connections to each hub.

<p>The hemispheric lateralization maps for the nine hubs of the left-lateralized network and 11 hubs of the right-lateralized network are shown in lateral and medial projections. Color scale (t-statistic) shows significantly left-lateralized (warm colors) or right-lateralized (cool colors) to the seed (i.e., hub). A black circle marks the position for each seed.</p

MNI coordinates of 20 lateralization hubs.

<p>MNI coordinates of 20 lateralization hubs.</p

Structural covariance maps of salience and default mode networks as a result of direct between-group contrasts.

<p>Statistical parametric maps depict brain regions in which gray matter intensity covaried with that of the seed ROI (right FI or PCC) differently between groups. (A) Structural covariance with right FI is greater in bilateral SMA in autistic subjects (hot colors; see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049172#pone-0049172-t003" target="_blank">Table 3</a>), whereas control subjects (cool colors) demonstrate more robust covariance in extensive frontal and temporal brain regions, in addition to insular cortex. Covariance outside of canonical SN boundaries is evidenced only in the autistic group. (B) Structural covariance with right PCC includes posterior cingulate, parieto-occipital, and temporal brain regions in autism (hot colors), whereas frontal covariance is absent. In contrast, control subjects demonstrate more robust covariance in frontal, lateral inferior parietal, and paracentral regions (cool colors; see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049172#pone-0049172-t003" target="_blank">Table 3</a>). Covariance outside of canonical DMN boundaries is evidenced only in the autistic group. scMRI data are T-statistic maps (p<0.05, inclusively masked to the network global map for both groups at p<0.01 FWE) displayed on the average anatomical template of all subjects. The left side of the image corresponds to the right side of the brain. DMN, default mode network; FI, frontoinsula; FWE, family-wise error; PCC, posterior cingulate cortex; ROI, region of interest; SN, salience network.</p

Structural covariance maps of the salience network in autism and controls.

<p>Statistical parametric maps depict brain regions in which gray matter intensity covaried with that of the seed ROI (right FI) in each group. (A) Structural covariance patterns appear substantially spatially restricted in autism (hot colors; see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049172#pone-0049172-t002" target="_blank">Table 2</a>). (B) Corresponding scMRI map in normal controls corresponds to a robust canonical SN (cool colors). (C) scMRI maps from both groups overlaid on a single anatomic volume. scMRI data are T-statistic maps (p<0.01, FWE-corrected) displayed on the average anatomical template of all subjects. The left side of the image corresponds to the right side of the brain. FI, frontoinsula; FWE, family-wise error; ROI, region of interest; scMRI, structural covariance MRI; SN, salience network.</p