Aberrant Spontaneous and Task-Dependent Functional Connections in the Anxious Brain

A number of brain regions have been implicated in anxiety disorders, yet none of these regions in isolation has been distinguished as the sole or discrete site responsible for anxiety disorder pathology. Therefore, the identification of dysfunctional neural networks as represented by alterations in the temporal correlation of blood oxygen level-dependent signal across several brain regions in anxiety disorders has been increasingly pursued in the past decade. Here, we review task-independent (e.g., resting-state) and task-induced functional connectivity magnetic resonance imaging (fcMRI) studies in adult anxiety disorders (including trauma- and stressor-related and obsessive-compulsive disorders). The results of this review suggest that anxiety disorder pathophysiology involves aberrant connectivity between amygdala-frontal and frontal-striatal regions, as well as within and between canonical intrinsic brain networks-the default mode and salience networks-and suggests that evidence of these aberrations may help inform findings of regional activation abnormalities observed in anxiety disorders. Nonetheless, significant challenges remain, including the need to better understand mixed findings observed using different methods (e.g., resting-state and task-based approaches); the need for more developmental work; the need to delineate disorder-specific and transdiagnostic fcMRI aberrations in anxiety disorders; and the need to better understand the clinical significance of fcMRI abnormalities. In meeting these challenges, future work has the potential to elucidate aberrant neural networks as intermediate, brain-based phenotypes to predict disease onset and progression, refine diagnostic nosology, and ascertain treatment mechanisms and predictors of treatment response across anxiety, trauma-related, and obsessive-compulsive disorders.