Amygdala activity and prefrontal cortex-amygdala effective connectivity to emerging emotional faces distinguish remitted and depressed mood states in bipolar disorder

Objectives: Few studies have employed effective connectivity (EC) to examine the functional integrity of neural circuitry supporting abnormal emotion processing in bipolar disorder (BD), a key feature of the illness. We used Granger Causality Mapping (GCM) to map EC between the prefrontal cortex (PFC) and bilateral amygdala and a novel paradigm to assess emotion processing in adults with BD. Methods: Thirty-one remitted adults with BD [(remitted BD), mean age = 32years], 21 adults with BD in a depressed episode [(depressed BD), mean age = 33years], and 25 healthy control participants [(HC), mean age = 31years] performed a block-design emotion processing task requiring color-labeling of a color flash superimposed on a task-irrelevant face morphing from neutral to emotional (happy, sad, angry, or fearful). GCM measured EC preceding (top-down) and following (bottom-up) activity between the PFC and the left and right amygdalae. Results: Our findings indicated patterns of abnormally elevated bilateral amygdala activity in response to emerging fearful, sad, and angry facial expressions in remitted-BD subjects versus HC, and abnormally elevated right amygdala activity to emerging fearful faces in depressed-BD subjects versus HC. We also showed distinguishable patterns of abnormal EC between the amygdala and dorsomedial and ventrolateral PFC, especially to emerging happy and sad facial expressions in remitted-BD and depressed-BD subjects. Discussion: EC measures of neural system level functioning can further understanding of neural mechanisms associated with abnormal emotion processing and regulation in BD. Our findings suggest major differences in recruitment of amygdala-PFC circuitry, supporting implicit emotion processing between remitted-BD and depressed-BD subjects, which may underlie changes from remission to depression in BD.