Altered Topography of Intrinsic Functional Connectivity in Childhood Risk for Social Anxiety.

BACKGROUND Extreme shyness in childhood arising from behavioral inhibition (BI) is among the strongest risk factors for developing social anxiety. Although no imaging studies of intrinsic brain networks in children with BI have been reported, adults with a history of BI exhibit altered functioning of frontolimbic circuits and enhanced processing of salient, personally relevant information. BI in childhood may be marked by increased coupling of salience (insula) and default (ventromedial prefrontal cortex [vmPFC]) network hubs. METHODS We tested this potential relation in 42 children ages 9-12, oversampled for high BI. Participants provided resting-state functional magnetic resonance imaging. A novel topographical pattern analysis of salience network intrinsic functional connectivity was conducted, and the impact of salience-default coupling on the relation between BI and social anxiety symptoms was assessed via moderation analysis. RESULTS Children with high BI exhibit altered salience network topography, marked by reduced insula connectivity to dorsal anterior cingulate and increased insula connectivity to vmPFC. Whole-brain analyses revealed increased connectivity of salience, executive, and sensory networks with default network hubs in children higher in BI. Finally, the relation between insula-ventromedial prefrontal connectivity and social anxiety symptoms was strongest among the children highest in BI. CONCLUSIONS BI is associated with an increase in connectivity to default network hubs that may bias processing toward personally relevant information during development. These altered patterns of connectivity point to potential biomarkers of the neural profile of risk for anxiety in childhood.