Anxiety sensitivity and intolerance of uncertainty track distinct neurobehavioral dimensions of avoidance in anxiety-related psychopathology

Avoidance behavior is a prominent and impairing feature of anxiety, obsessive-compulsive, and trauma-related disorders (AD). A transdiagnostic approach to identifying the neural basis of avoidance is a promising avenue to elucidate the heterogeneity of AD. In this cross-sectional study, 58 adults with AD and 77 healthy comparisons (HC) completed self-report measures of anxiety sensitivity (i.e., “fear of fear”) and intolerance of uncertainty (i.e., “fear of the unknown”), two transdiagnostic correlates of anxiety-related psychopathology. Participants then completed an avoidance task during functional magnetic resonance imaging (fMRI), involving a threat-cue paired with shock, safety-cues, and safe generalization stimuli with varying resemblance to the threat-cue. We examined neural activity preceding avoidance decisions in two phases: a) initial stimulus presentation (i.e., Pavlovian response) and b) decision contemplation. Pavlovian activity in anterior insula and dorsomedial prefrontal cortex tracked threat-relevance of stimuli, as expected. AD status and anxiety sensitivity both strengthened the relationship between Pavlovian neural activity and avoidance to safe generalization stimuli. We then applied multi-voxel pattern analysis (MVPA) to decode avoidance behavior from neural activity during decision contemplation. For those with higher intolerance of uncertainty, neural activity in motor cortex and intraparietal sulcus was less predictive of avoidance. Our results suggest that anxiety sensitivity and intolerance of uncertainty differentially contribute to avoidance behavior in anxiety-related psychopathology.