Revisiting Abnormalities in Brain Network Architecture Underlying Autism Using Topology-Inspired Statistical Inference

Abstract

A large body of evidence relates autism with abnormal structural and functional brain connectivity. Structural covariance magnetic resonance imaging (scMRI) is a technique that maps brain regions with covarying gray matter densities across subjects. It provides a way to probe the anatomical structure underlying intrinsic connectivity networks (ICNs) through analysis of gray matter signal covariance. In this article, we apply topological data analysis in conjunction with scMRI to explore network-specific differences in the gray matter structure in subjects with autism versus age-, gender-, and IQ-matched controls. Specifically, we investigate topological differences in gray matter structure captured by structural correlation graphs derived from three ICNs strongly implicated in autism, namely the salience network, default mode network, and executive control network. By combining topological data analysis with statistical inference, our results provide evidence of statistically significant network-specific structural abnormalities in autism.

Keywords: autism; brain networks; statistical inference; structural abnormalities; topological data analysis.

FIG. 1.

Structural covariance maps. (a) Structural covariance map with seed in right fronto-insular cortex anchoring SN. (b) Structural covariance map with seed in right dorsolateral prefrontal cortex anchoring ECN. (c) Structural covariance map with seed in right posterior cingulate cortex anchoring the default mode network. In all three subfigures, red represents the structural covariance map for the autism group and blue represents the structural covariance map for TDCs. ECN, executive control network; SN, salience network; TDC, typically developing control. Color images are available online.

FIG. 2.

Structural covariance maps further illustrated. (a) Structural covariance map with seed in right fronto-insular cortex anchoring SN. (b) Structural covariance map with seed in right dorsolateral prefrontal cortex anchoring ECN. (c) Structural covariance map with seed in right posterior cingulate cortex anchoring the default mode network. (d) Structural covariance map with seed in anterior part anchoring the default mode network. In all four subfigures, structural covariance maps are further illustrated here with red to yellow (autism) and dark blue to light blue (control) look-up tables. Color gradation indicates increasing statistical significance. Overlapping regions among autism and control groups are highlighted in green (c) and (d). Our data consist of subjects with an average age of about 13 years. The underlying structure of the default mode network is not fully developed at this age. We include two maps with different seeds to illustrate that the posterior part (c) is not yet integrated with the anterior part (d). In our analysis, we use the posterior covariance map (c), which corresponds to the most common seed for the default mode network in adults. Color images are available online.

FIG. 3.

β₀ curves. Top left: β₀ curves corresponding to whole-brain SCGs. Top right: β₀ curves corresponding to SCGs derived from SNs. Bottom left: β₀ curves corresponding to SCGs derived from ECNs. Bottom right: β₀ curves corresponding to SCGs derived from default mode networks. In all four subfigures, red represents the curve for the autism group and blue represents the curve for the control group. SCG, structural correlation graph. Color images are available online.

FIG. 4.

Comparative visualization of SN-SCG. SN-SCG at threshold , which corresponds to for both ASD (left) and TDC (right) groups. ROIs (4-mm spheres) are grouped by anatomical regions they are placed in as follows: S, SMA; SFG, superior frontal gyrus; FP, frontal pole; MFG, middle frontal gyrus; PF, postfusiform; AF, anterior fronto-insular; LO, lateral occipital; TP, temporal pole; MFC, medial frontal cortex; IFG, inferior frontal gyrus; ITG, inferior temporal gyrus; AP, anterior paracingulate; P, paracingulate; AC, anterior cingulate; MF, medial frontal (ventro-medial prefrontal cortex or VMPFC). Image courtesy of Yiliang Shi, University of Utah. Color images are available online.