Heterogeneity in PFC-amygdala connectivity in middle childhood, and concurrent interrelations with inhibitory control and anxiety symptoms

Abstract

The prefrontal cortex (PFC) is a key brain area in considering adaptive regulatory behaviors. This includes regulatory projections to regions of the limbic system such as the amygdala, where the nature of functional connections may confer lower risk for anxiety disorders. The PFC is also associated with behaviors like executive functioning. Inhibitory control is a behavior encompassed by executive functioning and is generally viewed favorably for adaptive socioemotional development. Yet, some research suggests that high levels of inhibitory control may actually be a risk factor for some maladaptive developmental outcomes, like anxiety disorders. In a sample of 51 children ranging from 7 to 9 years old, we examined resting state functional connectivity between regions of the PFC and the amygdala. We used Subgrouping Group Iterative Multiple Model Estimation (S-GIMME) to identify and characterize data-driven subgroups of individuals with similar networks of connectivity between these brain regions. Generated subgroups were collapsed into children characterized by the presence or absence of recovered connections between the PFC and amygdala. For subsets of children with available data (N = 38-44), we then tested whether inhibitory control, as measured by a stop signal task, moderated the relation between these subgroups and child-reported anxiety symptoms. We found an inverse relation between stop-signal reaction times and reported count of anxiety symptoms when covarying for connectivity group, suggesting that greater inhibitory control was actually related to greater anxiety symptoms, but only when accounting for patterns of PFC-amygdala connectivity. These data suggest that there is a great deal of heterogeneity in the nature of functional connections between the PFC and amygdala during this stage of development. The findings also provide support for the notion of high levels of inhibitory control as a risk factor for anxiety, but trait-level biopsychosocial factors may be important to consider in assessing the nature of risk.

Keywords: Anxiety; Inhibitory control; Resting state connectivity.