title: Sustained anxiety increases amygdala-dorsomedial prefrontal coupling: a mechanism for maintaining an anxious state in healthy adults.
abstract: BACKGROUND
  Neuroimaging research has traditionally explored fear and anxiety in response to discrete threat cues (e.g., during fear conditioning). However, anxiety is a sustained aversive state that can persist in the absence of discrete threats. Little is known about mechanisms that maintain anxiety states over a prolonged period. Here, we used a robust translational paradigm (threat of shock) to induce sustained anxiety. Recent translational work has implicated an amygdala-prefrontal cortex (PFC) circuit in the maintenance of anxiety in rodents. To explore the functional homologues of this circuitry in humans, we used a novel paradigm to examine the impact of sustained anticipatory anxiety on amygdala-PFC intrinsic connectivity.
  
  
  METHODS
  Task-independent fMRI data were collected in healthy participants during long-duration periods of shock anticipation and safety. We examined intrinsic functional connectivity.
  
  
  RESULTS
  Our study involved 20 healthy participants. During sustained anxiety, amygdala activity was positively coupled with dorsomedial PFC (DMPFC) activity. High trait anxiety was associated with increased amygdala-DMPFC coupling. In addition, induced anxiety was associated with positive coupling between regions involved in defensive responding, and decreased coupling between regions involved in emotional control and the default mode network.
  
  
  CONCLUSIONS
  Inferences regarding anxious pathology should be made with caution because this study was conducted in healthy participants.
  
  
  CONCLUSIONS
  Findings suggest that anticipatory anxiety increases intrinsic amygdala-DMPFC coupling and that the DMPFC may serve as a functional homologue for the rodent prefrontal regions by sustaining anxiety. Future research may use this defensive neural context to identify biomarkers of risk for anxious pathology and target these circuits for therapeutic intervention.
authors.affiliation: Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, NIH, Bethesda, MD, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Vytal
authors.affiliation: Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, NIH, Bethesda, MD, USA.
authors.forename: Cassie
authors.initials: C
authors.lastname: Overstreet
authors.affiliation: Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, NIH, Bethesda, MD, USA.
authors.forename: Danielle R
authors.initials: DR
authors.lastname: Charney
authors.affiliation: Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, NIH, Bethesda, MD, USA.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Robinson
authors.affiliation: Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, NIH, Bethesda, MD, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Grillon
mesh_terms: D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D059031:Anticipation, Psychological / Q000502:physiology; D001007:Anxiety / Q000503:physiopathology*; D001931:Brain Mapping; D004597:Electroshock; D005239:Fear / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D010551:Personality; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011601:Psychophysics; D055815:Young Adult