GAT: Graph Analysis Toolbox for Brain Networks Figure 9. Between-group differences in network resilience to random failure and targeted attack. Changes in the size of the largest component of the networks after cascading random failure (A) and targeted attack (B). Stars show where the difference in the size of the largest remaining components between groups is significant. The ALL network shows less tolerance to random failure and targeted attack. The AUC analysis revealed a significantly lower tolerance to random failure in the ALL network compared to CON. doi:10.1371/journal.pone.0040709.g009 Compared to the CON network, the ALL network showed smaller normalized clustering and larger normalized path length that led to a significant smaller small-world index across several densities in the ALL network. In addition, the area under the small-worldness curve was also significantly smaller in the ALL network suggesting the consistency of the findings irrespective of the threshold. These findings suggest that the structural networks of ALL patients tend to have a more regularized configuration relative to CON group; a configuration that is more segregated but less integrated compared to random networks. This configuration in the ALL network is thus less optimal for information processing compared to CON network. Our results corroborate previous structural neuroimaging findings that have demonstrated a diffuse pattern of atrophy in white matter and gray matter structure in ALL survivors [34–38]. One potential mechanism underlying this network-level alter- ation is white matter damage. A large body of evidence suggests that global gray matter atrophy is associated with focal and global white matter damage due in part to the transection of axons and subsequent retrograde neuronal loss [82,83]. Animal studies show that chemotherapy suppresses neural progenitor cell proliferation responsible for white-matter tract integrity and cortico-cortical connections [84–88]. Thus, the observed network-level alteration in structural correlation network of ALL patients might arise from neurotoxic effects of chemotherapy on cortico-cortical connec- tions. This idea is also supported by previous diffusion weighted Figure 10. Between-group differences in network modularity. The 95% confidence intervals and between-group differences in network modularity (A). The + marker shows the difference between CON vs. ALL networks; the + signs falling out of the confidence intervals indicate the densities in which the difference in global modularity is significant. The positive values indicate CON . ALL and negative values indicate CON , ALL. The modular structures of the CON and ALL networks are also shown (B). While both the networks had the same number of modules (five modules color-coded for each network separately), the degree of modularity is significantly lower in the ALL group in various network densities relative to CON group. doi:10.1371/journal.pone.0040709.g010 PLoS ONE | www.plosone.org 12 July 2012 | Volume 7 | Issue 7 | e40709