Coactivation pattern analysis reveals altered salience network dynamics in children with autism spectrum disorder.

Emily Marshall,Lucina Q Uddin,Lauren Kupis,Catie Chang,Celia Romero,Jason S Nomi,Bryce Dirks

doi:10.1162/netn_a_00163

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.

Highlights

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with central features of atypical social communication and restricted and repetitive behavioral patterns (American Psychiatric Association, 2013)
State 2 was characterized by coactivation with the posterior cingulate cortex (PCC) and medial prefrontal cortex of the medial fronto-parietal network (M-FPN), as well as bilateral regions of the lateral fronto-parietal network (L-FPN)
This pattern of coactivation was significantly more frequently observed in the typically developing (TD) children compared with ASD in both analyses (p = 0.0198, k = 0.0232) (Figure 6)

Summary

Introduction

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with central features of atypical social communication and restricted and repetitive behavioral patterns (American Psychiatric Association, 2013). Previous FC and activation studies of ASD have indicated that atypical functioning of the M-CIN, default mode/medial fronto-parietal (M-FPN), and central executive/lateral frontoparietal (L-FPN) is associated with the disorder (Abbott et al, 2016; Padmanabhan et al, 2017; Di Martino et al, 2009; Green et al, 2016). Because these brain networks support social and emotional behavior and executive functions, it is possible that altered relationships between them may underlie the social communication deficits and inflexible behaviors associated with ASD. Connectivity studies focusing on the anterior insula and the broader M-CIN in ASD have produced mixed findings, with some indicating that this network may be hyperconnected in children with the disorder (Uddin et al, 2013) while others report hypoconnectivity of this network (Abbott et al, 2016; Ebisch et al, 2011)

Objectives

Methods

Results

Discussion

Conclusion