RESEARCH Coactivation pattern analysis reveals altered salience network dynamics in children with autism spectrum disorder Emily Marshall 1* , Jason S. Nomi 1* , Bryce Dirks 1 , Celia Romero 1 , Lauren Kupis 1 , Catie Chang 2,3,4 , and Lucina Q. Uddin 1,5 1 Department of Psychology, University of Miami, Coral Gables, FL, USA 2 Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN, USA 3 Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA 4 Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA 5 Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL, USA * These authors contributed equally. Keywords: Anterior insula, Dynamic coactivation patterns, Functional connectivity, Lateral fronto-parietal network, Medial fronto-parietal network, Midcingulo-insular network ABSTRACT Brain connectivity studies of autism spectrum disorder (ASD) have historically relied on static measures of functional connectivity. Recent work has focused on identifying transient configurations of brain activity, yet several open questions remain regarding the nature of specific brain network dynamics in ASD. We used a dynamic coactivation pattern (CAP) approach to investigate the salience/midcingulo-insular (M-CIN) network, a locus of dysfunction in ASD, in a large multisite resting-state fMRI dataset collected from 172 children (ages 6–13 years; n = 75 ASD; n = 138 male). Following brain parcellation by using independent component analysis, dynamic CAP analyses were conducted and k-means clustering was used to determine transient activation patterns of the M-CIN. The frequency of occurrence of different dynamic CAP brain states was then compared between children with ASD and typically developing (TD) children. Dynamic brain configurations characterized by coactivation of the M-CIN with central executive/lateral fronto-parietal and default mode/medial fronto-parietal networks appeared less frequently in children with ASD compared with TD children. This study highlights the utility of time-varying approaches for studying altered M-CIN function in prevalent neurodevelopmental disorders. We speculate that altered M-CIN dynamics in ASD may underlie the inflexible behaviors commonly observed in children with the disorder. AUTHOR SUMMARY Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with altered patterns of functional brain connectivity. Little is currently known about how moment-to-moment brain dynamics differ in children with ASD and typically developing (TD) children. Altered functional integrity of the midcingulo-insular network (M-CIN) has been implicated in the neurobiology of ASD. Here we use a novel coactivation analysis approach applied to a large sample of resting-state fMRI data collected from children with ASD and TD children to demonstrate altered patterns of M-CIN dynamics in children with the disorder. We speculate that these atypical patterns of brain dynamics may underlie behavioral inflexibility in ASD. an open access journal Citation: Marshall, E., Nomi, J. S., Dirks, B., Romero, C., Kupis, L., Chang, C., & Uddin, L. Q. (2020). Coactivation pattern analysis reveals altered salience network dynamics in children with autism spectrum disorder. Network Neuroscience, 4(4), 1219–1234. https://doi.org/10.1162/netn_a_00163 DOI: https://doi.org/10.1162/netn_a_00163 Supporting Information: https://doi.org/10.1162/netn_a_00163 Received: 27 April 2020 Accepted: 29 July 2020 Competing Interests: The authors have declared that no competing interests exist. Corresponding Author: Lucina Q. Uddin l.uddin@miami.edu Handling Editor: Caterina Gratton Copyright: © 2020 Massachusetts Institute of Technology Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license The MIT Press Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/netn_a_00163 by guest on 03 September 2021