Neural and Cognitive Correlates of Adolescent Anxiety: Widespread Brain Network Alterations, Increased Control Costs, and Visuospatial Processing Deficits

Abstract

This study investigated the neural substrates and cognitive correlates of adolescent anxiety, which are currently incompletely understood, in N=3499 youth (~51.0% females) from the Adolescent Brain Cognitive Study, with median(IQR) age =12.0(1.1) years. Resting-state fMRI, structural MRI, anxiety (scores and related disorder diagnoses), and neurocognitive data were analyzed. Mixed effects regression models were used to examine associations between anxiety, brain characteristics (topological and morphometric properties, and regulatory (control) costs of intrinsic network dynamics), and cognitive outcomes. Females, older youth, and those with more parental mental health problems had higher anxiety (β=0.04-1.15, 95%CI=[0.01,2.18]). Higher resting-state connectivity and/or centrality (network importance) of the cerebellum, amygdala, and thalamus, and higher cerebellum-basal-ganglia-thalamus control costs were associated with higher anxiety (β=0.04-0.08, 95%CI=[0.01,0.11]). In contrast, temporoparietal and frontoparietal network efficiency and resilience (robustness) were protective for social and/or generalized anxiety disorders (adjusted odds ratio (aOR)=0.72-0.80, 95%CI=[0.62,0.98]). Higher cortical thickness and/or volume of the superior temporal gyrus, pars opercularis, precentral gyrus, and putamen were associated with higher odds of generalized or social anxiety disorder (aOR=1.28-1.44, 95%CI=[1.07,1.78]). Finally, anxiety was associated with lower response accuracy in the Little Man Task (β=-0.05, 95%CI=[-0.09,-0.01]), and attenuated positive brain-task performance associations. These findings suggest that adolescent anxiety is associated with widespread brain alterations, especially in the cerebellum-basal ganglia-thalamus, frontopariental and temporoparietal networks, which play key role in emotion regulation and social function. It is also associated with lower visuospatial processing and alterations in the networks that support it.