title: Amygdala perfusion is predicted by its functional connectivity with the ventromedial prefrontal cortex and negative affect.
abstract: BACKGROUND
  Previous studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect). It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1) amygdala over-activity and 2) reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states.
  
  
  METHODS
  Here we used resting-state arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF) and functional connectivity (correlated fluctuations in the BOLD signal) of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA), and subsyndromal anxiety levels in 38 healthy subjects.
  
  
  RESULTS
  BLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety.
  
  
  CONCLUSIONS
  These results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach.
authors.affiliation: The Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, United States of America; The MGH/HST/MIT Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, United States of America; Center for Brain Science, Department of Psychology, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Garth
authors.initials: G
authors.lastname: Coombs
authors.affiliation: The Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, United States of America; The MGH/HST/MIT Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Marco L
authors.initials: ML
authors.lastname: Loggia
authors.affiliation: The MGH/HST/MIT Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America; The Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Greve
authors.affiliation: The Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, United States of America; The MGH/HST/MIT Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Daphne J
authors.initials: DJ
authors.lastname: Holt
mesh_terms: D000339:Affect / Q000502:physiology*; D000679:Amygdala / Q000502:physiology*; D063132:Connectome; D003863:Depression / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008954:Models, Biological; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000502:physiology*; D013113:Spin Labels
chemical_list: D013113:Spin Labels; D010100:Oxygen