title: fMRI functional connectivity of the periaqueductal gray in PTSD and its dissociative subtype.
abstract: Posttraumatic stress disorder (PTSD) is associated with hyperarousal and active fight or flight defensive responses. By contrast, the dissociative subtype of PTSD, characterized by depersonalization and derealization symptoms, is frequently accompanied by additional passive or submissive defensive responses associated with autonomic blunting. Here, the periaqueductal gray (PAG) plays a central role in defensive responses, where the dorsolateral (DL-PAG) and ventrolateral PAG (VL-PAG) are thought to mediate active and passive defensive responses, respectively.
  
  
  
  We examined PAG subregion (dorsolateral and ventrolateral) resting-state functional connectivity in three groups: PTSD patients without the dissociative subtype (n= 60); PTSD patients with the dissociative subtype (n= 37); and healthy controls (n= 40) using a seed-based approach via PickAtlas and SPM12.
  
  
  
  All PTSD patients showed extensive DL- and VL-PAG functional connectivity at rest with areas associated with emotional reactivity and defensive action as compared to controls (n= 40). Although all PTSD patients demonstrated DL-PAG functional connectivity with areas associated with initiation of active coping strategies and hyperarousal (e.g., dorsal anterior cingulate; anterior insula), only dissociative PTSD patients exhibited greater VL-PAG functional connectivity with brain regions linked to passive coping strategies and increased levels of depersonalization (e.g., temporoparietal junction; rolandic operculum).
  
  
  
  These findings suggest greater defensive posturing in PTSD patients even at rest and demonstrate that those with the dissociative subtype show unique patterns of PAG functional connectivity when compared to those without the subtype. Taken together, these findings represent an important first step toward identifying neural and behavioral targets for therapeutic interventions that address defensive strategies in trauma-related disorders.
authors.affiliation: Department of Neuroscience University of Western Ontario London ON Canada.
authors.forename: Sherain
authors.initials: S
authors.lastname: Harricharan
authors.affiliation: Department of Psychiatry University of Western Ontario London ON Canada.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rabellino
authors.affiliation: Department of Psychiatry University of Western Ontario London ON Canada; Department of Psychology University of Western Ontario London ON Canada.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Frewen
authors.affiliation: Imaging Division Lawson Health Research Institute London ON Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Densmore
authors.affiliation: Imaging Division Lawson Health Research Institute London ON Canada; Departments of Medical Imaging and Medical Biophysics Western University London ON Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Théberge
authors.affiliation: Mood Disorders Program St. Joseph's Healthcare Hamilton ON Canada; Department of Psychiatry and Behavioural Neurosciences McMaster University Hamilton ON Canada; Homewood Research Institute Guelph ON Canada.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: McKinnon
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences University of California at Los Angeles Los Angeles CA USA.
authors.forename: Allan N
authors.initials: AN
authors.lastname: Schore
authors.affiliation: Department of Neuroscience University of Western Ontario London ON Canada; Department of Psychiatry University of Western Ontario London ON Canada; Imaging Division Lawson Health Research Institute London ON Canada.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Lanius
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D063132:Connectome; D004213:Dissociative Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000523:psychology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010487:Periaqueductal Gray / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013313:Stress Disorders, Post-Traumatic / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology
keywords: active defenses; autonomic blunting; cingulate gyrus; fight–flight; fusiform gyrus; hyperarousal; insula; passive defenses; periaqueductal gray; posttraumatic; temporoparietal junction