Dynamic causal modeling in PTSD and its dissociative subtype: Bottom–up versus top–down processing within fear and emotion regulation circuitry. Issue 11 (24th August 2017)

• Record Type: Journal Article
• Authors: Nicholson, Andrew A.; Friston, Karl J.; Zeidman, Peter; Harricharan, Sherain; McKinnon, Margaret C.; Densmore, Maria; Neufeld, Richard W.J.; Théberge, Jean; Corrigan, Frank; Jetly, Rakesh; Spiegel, David; Lanius, Ruth A.
• Is Part Of: Human brain mapping. Volume 38:Issue 11(2017)
• Page Start: 5551
• Page End: 5561
• Publication Date: 2017-08-24
• Subjects: posttraumatic stress disorder -- dynamic causal modeling -- amygdala -- prefrontal cortex -- periaqueductal gray -- fMRI -- connectivity; Brain mapping -- Periodicals; 611.81
• DOI: 10.1002/hbm.23748
• Languages: English
• ISSNs: 1065-9471

Abstract

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.