title: Amygdala and orbitofrontal reactivity to social threat in individuals with impulsive aggression.
abstract: BACKGROUND
  Converging evidence from animal and human lesion studies implicates the amygdala and orbitofrontal cortex (OFC) in emotional regulation and aggressive behavior. However, it remains unknown if functional deficits exist in these specific brain regions in clinical populations in which the cardinal symptom is impulsive aggression. We have previously shown that subjects diagnosed with intermittent explosive disorder (IED), a psychiatric disorder characterized by reactive aggressive behavior, perform poorly on facial emotion recognition tasks. In this study we employed a social-emotional probe of amygdala-OFC function in individuals with impulsive aggression.
  
  
  METHODS
  Ten unmedicated subjects with IED and 10 healthy, matched comparison subjects (HC) underwent functional magnetic resonance imaging while viewing blocks of emotionally salient faces. We compared amygdala and OFC reactivity to faces between IED and HC subjects, and examined the relationship between the extent of activation in these regions and extent of prior history of aggressive behavior.
  
  
  RESULTS
  Relative to controls, individuals with IED exhibited exaggerated amygdala reactivity and diminished OFC activation to faces expressing anger. Extent of amygdala and OFC activation to angry faces were differentially related to prior aggressive behavior across subjects. Unlike controls, aggressive subjects failed to demonstrate amygdala-OFC coupling during responses to angry faces.
  
  
  CONCLUSIONS
  These findings provide evidence of amygdala-OFC dysfunction in response to an ecologically-valid social threat signal (processing angry faces) in individuals with a history of impulsive aggressive behavior, and further substantiate a link between a dysfunctional cortico-limbic network and aggression.
authors.affiliation: Department of Psychiatry, Biological Sciences Division and the Pritzker School of Medicine, The University of Chicago, Chicago, Illinois 60637-1470, USA. ecoccaro@yoda.bsd.uchicago.edu
authors.forename: Emil F
authors.initials: EF
authors.lastname: Coccaro
authors.forename: Michael S
authors.initials: MS
authors.lastname: McCloskey
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Fitzgerald
authors.forename: K Luan
authors.initials: KL
authors.lastname: Phan
mesh_terms: D000328:Adult; D000374:Aggression / Q000502:physiology*; D000679:Amygdala / Q000503:physiopathology*; D000786:Anger / Q000502:physiology; D001921:Brain / Q000503:physiopathology; D001931:Brain Mapping; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000175:diagnosis* / Q000503:physiopathology*; D004644:Emotions; D005149:Facial Expression; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D021641:Recognition, Psychology; D012737:Sex Factors; D012938:Social Perception