Andrew A Nicholson1,2,3, Karl J Friston4, Peter Zeidman4, Sherain Harricharan1,2,3, Margaret C McKinnon5,6,7, Maria Densmore3, Richard W J Neufeld1,2,8, Jean Théberge2,3,9,10,11, Frank Corrigan12, Rakesh Jetly13, David Spiegel14, Ruth A Lanius1,2,3. 1. Departments of Neuroscience, Western University, London, Ontario, Canada. 2. Departments of Psychiatry, Western University, London, Ontario, Canada. 3. Imaging department, Lawson Health Research Institute, London, Ontario, Canada. 4. Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, United Kingdom. 5. Mood Disorders Program, St. Joseph's Healthcare, Hamilton, Ontario, Canada. 6. Department of Psychiatry and Behavioural Neuroscience, McMaster University, Hamilton, Ontario, Canada. 7. Department of psychiatry, Homewood Research Institute, Guelph, Ontario, Canada. 8. Departments of Psychology, Western University, London, Ontario, Canada. 9. Departments of Medical Imaging, Western University, London, Ontario, Canada. 10. Departments of Medial Biophysics, Western University, London, Ontario, Canada. 11. Department of Diagnostic Imaging, St. Joseph's Healthcare, London, Ontario, Canada. 12. Department of Psychiatry, Argyll & Bute Hospital, Lochgilphead, Argyll, United Kingdom. 13. Department of National Defence, Canadian Forces, Health Services, Ottawa, Ontario, Canada. 14. Department of Psychiatry, Stanford University School of Medicine, Stanford, California.
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.
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, PTSDpatients 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.
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