title: Ventromedial prefrontal cortex is critical for the regulation of amygdala activity in humans.
abstract: BACKGROUND
  Dysfunction in the ventromedial prefrontal cortex (vmPFC) is believed to play a pivotal role in the pathogenesis of mood and anxiety disorders. Leading neurocircuitry models of these disorders propose that hypoactivity in the vmPFC engenders disinhibited activity of the amygdala and, consequently, pathologically elevated levels of negative affect. This model predicts that a selective loss or diminution of function of the vmPFC would result in heightened activity of the amygdala. Although this prediction has been borne out in rodent lesion and electrophysiologic studies using fear conditioning and extinction paradigms, there has not yet been a definitive test of this prediction in humans.
  
  
  METHODS
  We tested this prediction through a novel use of functional magnetic resonance imaging in four neurosurgical patients with focal, bilateral vmPFC damage.
  
  
  RESULTS
  Relative to neurologically healthy comparison subjects, the patients with vmPFC lesions exhibited potentiated amygdala responses to aversive images and elevated resting-state amygdala functional connectivity. No comparable group differences were observed for activity in other brain regions.
  
  
  CONCLUSIONS
  These results provide unique evidence for the critical role of the vmPFC in regulating activity of the amygdala in humans and help elucidate the causal neural interactions that underlie mental illness.
authors.affiliation: Departments of Psychiatry (JCM, CLP, RCW, MK), University of Wisconsin-Madison, Madison, Wisconsin; Neuroscience Training Program (JCM, RCW) University of Wisconsin-Madison, Madison, Wisconsin; Medical Scientist Training Program (JCM), University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Julian C
authors.initials: JC
authors.lastname: Motzkin
authors.affiliation: Departments of Psychiatry (JCM, CLP, RCW, MK), University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Carissa L
authors.initials: CL
authors.lastname: Philippi
authors.affiliation: Departments of Psychiatry (JCM, CLP, RCW, MK), University of Wisconsin-Madison, Madison, Wisconsin; Neuroscience Training Program (JCM, RCW) University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Wolf
authors.affiliation: Neurological Surgery (MKB) University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Mustafa K
authors.initials: MK
authors.lastname: Baskaya
authors.affiliation: Departments of Psychiatry (JCM, CLP, RCW, MK), University of Wisconsin-Madison, Madison, Wisconsin. Electronic address: mrkoenigs@wisc.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Koenigs
mesh_terms: D000679:Amygdala / Q000502:physiology*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D004644:Emotions / Q000502:physiology; D005260:Female; D006339:Heart Rate; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D017156:Photoplethysmography; D017397:Prefrontal Cortex / Q000503:physiopathology* / Q000601:surgery; D012146:Rest; D014796:Visual Perception / Q000502:physiology
chemical_list: D010100:Oxygen
keywords: Amygdala; Anxiety; Emotion; Lesion; Prefrontal cortex; fMRI