Abstract

In recent years, coordinated variations in brain morphology (e.g., volume, thickness) have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks. Recent evidence suggests that brain networks constructed in this manner are inherently more clustered than random networks of the same size and degree. Thus, null networks constructed by randomizing topology are not a good choice for benchmarking small-world parameters of these networks. In the present report, we investigated the influence of choice of null networks on small-world parameters of gray matter correlation networks in healthy individuals and survivors of acute lymphoblastic leukemia. Three types of null networks were studied: 1) networks constructed by topology randomization (TOP), 2) networks matched to the distributional properties of the observed covariance matrix (HQS), and 3) networks generated from correlation of randomized input data (COR). The results revealed that the choice of null network not only influences the estimated small-world parameters, it also influences the results of between-group differences in small-world parameters. In addition, at higher network densities, the choice of null network influences the direction of group differences in network measures. Our data suggest that the choice of null network is quite crucial for interpretation of group differences in small-world parameters of structural correlation networks. We argue that none of the available null models is perfect for estimation of small-world parameters for correlation networks and the relative strengths and weaknesses of the selected model should be carefully considered with respect to obtained network measures.

Highlights

  • The results of cumulative functional data analysis (FDA) analysis in the density range [0.22:0.02:0.5] and nonparametric permutation test for dependent samples showed that the cumulative FDA of normalized clustering coefficient, normalized path length, and small-world index in healthy controls (HC) network are significantly different between all three choices of null networks (p,0.01) after correction for multiple comparisons (Bonferroni correction)

  • We investigated the influence of choice of null networks on small-world parameters of gray matter correlation networks in healthy individuals (HC) and survivors of acute lymphoblastic leukemia (ALL)

  • We investigated the influence of choice of null networks on small-world properties of structural correlation networks

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Summary

Introduction

In recent years, coordinated variations in brain morphology (e.g. volume, thickness, surface area) have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. Structural correlation networks constructed in this manner are usually represented by a set of nodes that correspond to brain regions and a set of edges (connections) that correspond to statistical correlations in morphometric values between regions, across individuals [5,11]. The small-worldness index of a network is obtained as SW = [C/Cnull]/[L/Lnull] where Cnull and Lnull are the mean clustering coefficient and the characteristic path length of the m null random networks, respectively [22]. The smallworld index of a network is largely affected by the choice of null network [32,33]

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