title: Amygdala activity and prefrontal cortex-amygdala effective connectivity to emerging emotional faces distinguish remitted and depressed mood states in bipolar disorder.
abstract: OBJECTIVE
  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 = 32 years], 21 adults with BD in a depressed episode [(depressed BD), mean age = 33 years], and 25 healthy control participants [(HC), mean age = 31 years] 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. perlmansb2@upmc.edu
authors.forename: Susan B
authors.initials: SB
authors.lastname: Perlman
authors.forename: Jorge R C
authors.initials: JR
authors.lastname: Almeida
authors.forename: Dina M
authors.initials: DM
authors.lastname: Kronhaus
authors.forename: Amelia
authors.initials: A
authors.lastname: Versace
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Labarbara
authors.forename: Crystal R
authors.initials: CR
authors.lastname: Klein
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping; D004644:Emotions; D005145:Face; D005149:Facial Expression; D005260:Female; D007839:Functional Laterality; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D010775:Photic Stimulation; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011930:Reaction Time; D055815:Young Adult