Patterns of Atypical Functional Connectivity and Behavioral Links in Autism Differ Between Default, Salience, and Executive Networks

Abstract

Autism spectrum disorder (ASD) is characterized by atypical brain network organization, but findings have been inconsistent. While methodological and maturational factors have been considered, the network specificity of connectivity abnormalities remains incompletely understood. We investigated intrinsic functional connectivity (iFC) for four "core" functional networks-default-mode (DMN), salience (SN), and left (lECN) and right executive control (rECN). Resting-state functional MRI data from 75 children and adolescents (37 ASD, 38 typically developing [TD]) were included. Functional connectivity within and between networks was analyzed for regions of interest (ROIs) and whole brain, compared between groups, and correlated with behavioral scores. ROI analyses showed overconnectivity (ASD > TD), especially between DMN and ECN. Whole-brain results were mixed. While predominant overconnectivity was found for DMN (posterior cingulate seed) and rECN (right inferior parietal seed), predominant underconnectivity was found for SN (right anterior insula seed) and lECN (left inferior parietal seed). In the ASD group, reduced SN integrity was associated with sensory and sociocommunicative symptoms. In conclusion, atypical connectivity in ASD is network-specific, ranging from extensive overconnectivity (DMN, rECN) to extensive underconnectivity (SN, lECN). Links between iFC and behavior differed between groups. Core symptomatology in the ASD group was predominantly related to connectivity within the salience network.

Keywords: autism spectrum disorder; default-mode network; executive control network; functional connectivity; salience network.

Figure 1.

Correlation matrices for all ROIs in ASD (upper right triangles) and TD groups (lower left) using (A) full sample and (B) low-motion subsample. Correlation matrices for networks (averaged across ROIs) using (C) full sample and (D) low-motion subsample. DMN, default-mode network; SN, salience network; rECN, right executive control network; lECN, left executive control network. +/−, significantly greater/weaker FC in ASD compared with TD group (P < 0.05, FDR-corrected); [+]/[−], analogous group differences at P < 0.05, uncorrected. For detailed statistical listing, see Supplementary Table 2. (E–H) Surface renderings of within-group functional connectivity (top) and between-group difference (bottom) for primary seeds of (E) default mode network, (F) salience network, as well as (G) right and (H) left executive control networks (all clusters P < 0.05, cluster-corrected).

Figure 2.

Correlations of demographic and behavioral measures with connectivity for TD (blue) and ASD groups (red): (A) DMN–lECN within-network connectivity by age, (B) SN within-network connectivity index by SRS Total, (C) SN within-network connectivity index by SP Sensory Avoidance, (D) DMN within-network connectivity index by BRIEF Global Executive Composite, (E) SN within-network connectivity index by BRIEF Shift, (F) SN–DMN connectivity index by SP Low Regulation, (G) SN-DMN connectivity index by BRIEF Working Memory, and (H) SN–DMN connectivity by BRIEF Global Executive Functioning. *P < 0.05, FDR-corrected.