Abstract
Some studies identified hypo-connectivity, while others showed hyper-connectivity of the insula in the autism spectrum disorders (ASD). These contradictory findings leave open the question of whether and to what extent functional connectivity of the insula is altered and how functional connectivity of the insula is associated with the severity of ASD. A newly emerging insular atlas that comprises multiple functionally differentiated subregions provides a new framework to interpret the functional significance of insular findings and uncover the mechanisms underlying the severity of ASD. Using the new insular atlas, the present study aimed to investigate the distinct functional connectivity of the insular subregions and their associations with ASD severity in a cohort of 49 children with ASD and 33 typically developing (TD) subjects. We found that compared with TD group, the ASD group showed different connectivity patterns in the left ventral agranular insula, right ventral dysgranular and granular insula, and dorsal dysgranular insula, characterized by significant hyper-connectivity and/or hypo-connectivity with special brain regions. Furthermore, both the hypo-connectivity and hyper-connectivity patterns of the insular subregions were significantly associated with the severity of ASD symptoms. Our research demonstrated distinct functional connectivity patterns of the insular subregions and emphasized the importance of the subdivisions within the insula to the potential impact of functional difference in children with ASD. Moreover, these results might help us to better understand the mechanisms underlying the symptoms in children with ASD and might elucidate potential biomarkers for clinical applications.
Highlights
Autism spectrum disorders (ASD) are prevalent neurodevelopmental disorders characterized by deficits in social interaction; verbal and nonverbal communication; and restricted and stereotyped patterns of behavior, interests, and activities (Minshew and Williams, 2007)
resting-state functional connectivity (RSFC) analyses based on the insular subregions resulted in distinct connectivity maps in the typically developing (TD) and autism spectrum disorders (ASD) groups (Figure 1)
The hypo-connectivity between the left ventral agranular insula and PCUN.R was negatively correlated with the Autism Diagnostic Observation Schedule (ADOS) total/social scores in the ASD group
Summary
Autism spectrum disorders (ASD) are prevalent neurodevelopmental disorders characterized by deficits in social interaction; verbal and nonverbal communication; and restricted and stereotyped patterns of behavior, interests, and activities (Minshew and Williams, 2007). Regarding functional connectivity, reduced functional connectivity of the anterior, middle, and posterior insula with specific brain regions involved in different brain networks was identified in adolescent and adult ASD (Ebisch et al, 2011; Von Dem Hagen et al, 2013; Di Martino et al, 2014). These results all confirmed the hypo-connectivity of the insula and strongly supported the hypo-connectivity theory of the ASD. It is noteworthy that the insula is comprised of separate subregions, only assessing it as a whole region may obscure individual differences of functional connectivity with insula in ASD
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