A functional connectivity MRI study of network sculpting in autism spectrum disorders

摘要

There is increasing consensus that autism spectrum disorder (ASD) is a disorder involving distributed brain networks. Functional connectivity (fcMRI) studies have produced mixed findings, including underconnectivity and overconnectivity in ASD, implicating the default mode (DMN), salience (SN), mentalizing (Theory of Mind, ToM), and motor (MN) networks. Seemingly contradictory findings could reflect complementary aspects of impaired network sculpting, characterized by decreased connectivity within neurotypical networks and increased connectivity outside of these networks. The current study implemented a network sculpting index (NSI), a ratio of within-network and outside-network connectivity, to evaluate the efficiency of neurotypical networks (DMN, SN, ToM, MN) during rest in 39 ASD and 39 typically developing (TD) participants (7-18 y/o). Regions of interest (ROIs) were identified using 6mm-radius spheres centered on previously reported coordinates. Within-network masks were created for each ROI, including the seed and all other ROIs in the network (dilated to 12mm radius); outside-network masks excluded all network ROIs and non-cortical voxels. For each network, the number of significant voxels, weighted by z', was determined for within- and outside-network masks, and was then used to calculate the NSI using the formula: NSI = (WNC-ONC)/(WNC+ONC), with WNC and ONC being within and outside-of network connectivity, respectively. Marginally significant group differences were found in DMN and ToM, with reduced mean NSI in ASD group compared to TD group. A correlational analysis of NSI and three a priori social measures (ADI-Social, ADI-Communication, and ADOS Communication + Social (CS) scores) revealed negative relationships between NSI and ADI-Social scores for DMN and ToM, as well as between NSI and ADI-Communication scores for DMN and ToM networks. A post-hoc analysis was performed in a subset of ASD participants (n = 26) with highest level of social symptomatology (ADOS-CS scores ≥ 10). Direct group comparison of this ASD subsample and 26 TD participants yielded significant differences in mean NSI for DMN and ToM. Results suggest reduced functional sculpting in ASD for these networks, particularly pronounced in ASD participants with relatively high symptom severity. These findings are consistent with recent evidence of underconnectivity and overconnectivity in ASD, reflecting reduced network integration and differentiation or segregation.