Dynamic causal modeling in PTSD and its dissociative subtype: Bottom-up versus top-down processing within fear and emotion regulation circuitry

Hum Brain Mapp. 2017 Nov;38(11):5551-5561. doi: 10.1002/hbm.23748. Epub 2017 Aug 24.

Abstract

Objective: Posttraumatic stress disorder (PTSD) is associated with decreased top-down emotion modulation from medial prefrontal cortex (mPFC) regions, a pathophysiology accompanied by hyperarousal and hyperactivation of the amygdala. By contrast, PTSD patients with the dissociative subtype (PTSD + DS) often exhibit increased mPFC top-down modulation and decreased amygdala activation associated with emotional detachment and hypoarousal. Crucially, PTSD and PTSD + DS display distinct functional connectivity within the PFC, amygdala complexes, and the periaqueductal gray (PAG), a region related to defensive responses/emotional coping. However, differences in directed connectivity between these regions have not been established in PTSD, PTSD + DS, or controls.

Methods: To examine directed (effective) connectivity among these nodes, as well as group differences, we conducted resting-state stochastic dynamic causal modeling (sDCM) pairwise analyses of coupling between the ventromedial (vm)PFC, the bilateral basolateral and centromedial (CMA) amygdala complexes, and the PAG, in 155 participants (PTSD [n = 62]; PTSD + DS [n = 41]; age-matched healthy trauma-unexposed controls [n = 52]).

Results: PTSD was characterized by a pattern of predominant bottom-up connectivity from the amygdala to the vmPFC and from the PAG to the vmPFC and amygdala. Conversely, PTSD + DS exhibited predominant top-down connectivity between all node pairs (from the vmPFC to the amygdala and PAG, and from the amygdala to the PAG). Interestingly, the PTSD + DS group displayed the strongest intrinsic inhibitory connections within the vmPFC.

Conclusions: These results suggest the contrasting symptom profiles of PTSD and its dissociative subtype (hyper- vs. hypo-emotionality, respectively) may be driven by complementary changes in directed connectivity corresponding to bottom-up defensive fear processing versus enhanced top-down regulation. Hum Brain Mapp 38:5551-5561, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: amygdala; connectivity; dynamic causal modeling; fMRI; periaqueductal gray; posttraumatic stress disorder; prefrontal cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adult Survivors of Child Adverse Events
  • Bayes Theorem
  • Brain / diagnostic imaging
  • Brain / physiopathology*
  • Brain Mapping / methods*
  • Dissociative Disorders / diagnostic imaging
  • Dissociative Disorders / physiopathology*
  • Fear / physiology
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Multivariate Analysis
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / physiopathology
  • Stress Disorders, Post-Traumatic / diagnostic imaging
  • Stress Disorders, Post-Traumatic / physiopathology*
  • Stress Disorders, Post-Traumatic / psychology

Grant support