Deficient salience and default mode functional integration in high worry-proneness subject: a connectome-wide association study

Abstract

Worry has been conceptualized as a relatively uncontrollable chain of thought that increases the risk of mental problems, such as anxiety disorders. Here, we examined the link between individual variation in the functional connectome and worry proneness, which remains unclear. A total of 32 high worry-proneness (HWP) subjects and 25 low worry-proneness (LWP) subjects were recruited. We conducted multivariate distance-based matrix regression to identify phenotypic relationships in high-dimensional brain resting-state functional connectivity data from HWP subjects. Multiple hub regions, including key brain nodes of the salience network (SN) and default mode network (DMN), were identified in HWP subjects. Follow-up analyses revealed that a high worry-proneness score was dominated by functional connectivity between the SN and the DMN. Moreover, HWP subjects showed hypoconnectivity between the cerebellum and the SN and DMN compared with LWP subjects. This cross-sectional study could not fully measure the causal relationships between changes in functional networks and worry proneness in healthy subjects. Functional changes in the cerebellum-cortical region might affect the modulation of external stimuli processing. Together, our results provide new insight into the role of key networks, including the SN, DMN and cerebellum, in understanding the potential mechanism underlying the high worry dimension in healthy subjects.