title: Neural dysregulation in posttraumatic stress disorder: evidence for disrupted equilibrium between salience and default mode brain networks.
abstract: OBJECTIVE
  Convergent research demonstrates disrupted attention and heightened threat sensitivity in posttraumatic stress disorder (PTSD). This might be linked to aberrations in large-scale networks subserving the detection of salient stimuli (i.e., the salience network [SN]) and stimulus-independent, internally focused thought (i.e., the default mode network [DMN]).
  
  
  METHODS
  Resting-state brain activity was measured in returning veterans with and without PTSD (n = 15 in each group) and in healthy community controls (n = 15). Correlation coefficients were calculated between the time course of seed regions in key SN and DMN regions and all other voxels of the brain.
  
  
  RESULTS
  Compared with control groups, participants with PTSD showed reduced functional connectivity within the DMN (between DMN seeds and other DMN regions) including the rostral anterior cingulate cortex/ventromedial prefrontal cortex (z = 3.31; p = .005, corrected) and increased connectivity within the SN (between insula seeds and other SN regions) including the amygdala (z = 3.03; p = .01, corrected). Participants with PTSD also demonstrated increased cross-network connectivity. DMN seeds exhibited elevated connectivity with SN regions including the insula (z = 3.06; p = .03, corrected), and SN seeds exhibited elevated connectivity with DMN regions including the hippocampus (z = 3.10; p = .048, corrected).
  
  
  CONCLUSIONS
  During resting-state scanning, participants with PTSD showed reduced coupling within the DMN, greater coupling within the SN, and increased coupling between the DMN and the SN. Our findings suggest a relative dominance of threat-sensitive circuitry in PTSD, even in task-free conditions. Disequilibrium between large-scale networks subserving salience detection versus internally focused thought may be associated with PTSD pathophysiology.
authors.affiliation: Departments of Psychology, University of Michigan, Ann Arbor, Michigan, USA. rekaufma@umich.edu
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Sripada
authors.forename: Anthony P
authors.initials: AP
authors.lastname: King
authors.forename: Robert C
authors.initials: RC
authors.lastname: Welsh
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Garfinkel
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Sripada
authors.forename: Israel
authors.initials: I
authors.lastname: Liberzon
mesh_terms: D000328:Adult; D055826:Afghan Campaign 2001-; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology; D003130:Combat Disorders / Q000503:physiopathology* / Q000523:psychology*; D003213:Conditioning, Psychological / Q000502:physiology; D004292:Dominance, Cerebral / Q000502:physiology; D004644:Emotions / Q000502:physiology; D006179:Gyrus Cinguli / Q000503:physiopathology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D021621:Imaging, Three-Dimensional; D054542:Iraq War, 2003-2011; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology; D012016:Reference Values; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology* / Q000523:psychology*; D014728:Veterans / Q000523:psychology*