Neural activity during self-referential working memory and the underlying role of the amygdala in social anxiety disorder

Self-referential processing, theory of mind, and working memory are distorted in social anxiety disorder (SAD). This study aimed to investigate characteristics of altered self-referential working memory processing and resting-state functional connectivity in patients with SAD. Twenty patients and 20 healthy controls underwent functional magnetic resonance imaging at resting-state and while performing a working memory task containing faces with self-referential positive or negative comments and three memory phases (encoding, maintenance, and retrieval). Task-related results were compared between groups and tested for correlations. Resting-state connectivity between amygdala subregions and regions showing a task-related difference was also compared between groups. Patients compared to controls showed augmented memory for the negative comments, hyperactivation of the dorsomedial prefrontal cortex and temporo-parietal junction during encoding, and hypoactivation of the dorsolateral prefrontal cortex and insula during retrieval. At resting-state, increased connectivity of amygdala subregions with multiple task-related regions was found in patients. These findings suggest that the encoding process in SAD is accompanied by altered involvement of self-referential processing and theory of mind, whereas the retrieval process reflects impaired cognitive control. These memory-related processing may be affected by predisposing resting-state hyperconnectivity with the amygdala, and may underlie a hypersensitivity to negative comments and post-event reflection in SAD.