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Figures
- Figure 1
In GIFT, independent component 3 (shown above) was correlated very strongly with the DMN mask. Independent component 3 included key DMN-related hubs, such as the mPFC, the PCC and the precuneus. It also included supplementary DMN-related areas, such as the middle cingulate cortex and the bilateral temporal lobes, but these areas revealed less functional network connectivity than the hubs. We also observed clusters in the insula, midbrain and cerebellum, which are not generally thought to be involved in the DMN (indicated by an asterisk). DMN = default mode network; fMRI = functional MRI; GIFT = Group ICA of fMRI Toolbox; ICA = independent component analysis; mPFC = medial prefrontal cortex; PAG = periaqueductal grey; PCC = posterior cingulate cortex.
- Figure 2
(A) Top: the whole-brain image shows a thresholded independent component 3 (k > 35 cut-off) and the DMN-related spatial correlation value. Bottom: midbrain PAG functional network connectivity clusters that were more strongly involved in the DMN in participants with civilian-related PTSD versus healthy controls exposed to moral injury have been superimposed onto the cropped brainstem and cerebellum mask from the SUIT toolbox. (B) This summary image interprets the functional connectivity revealed in the present study and the study by Terpou and colleagues.43 In PTSD, we suspect that the DMN-related hubs — namely the mPFC, PCC and precuneus — reveal strong functional connectivity during DMN-mediated processing, similar to healthy controls. However, Terpou and colleagues43 found stronger PAG-directed functional connectivity to DMN-related hubs in PTSD, a finding that converges with the stronger PAG functional network connectivity we found in the present study. Taking these findings together, we suggest that the PAG may be driving the DMN in people with PTSD, primarily in a bottom–up manner; functional connectivity is mediated by the insula and directed toward the DMN. DMN = default mode network; FWE = family-wise error; mPFC = medial prefrontal cortex; PAG = periaqueductal grey; PCC = posterior cingulate cortex; PCUN = precuneus; PTSD = posttraumatic stress disorder; ROI = region of interest; SUIT = Spatially Unbiased Infratentorial Template.
Tables
Characteristic* Military- and law-enforcement-related PTSD Civilian-related PTSD Healthy controls exposed to a moral injury event Participants, n 28 28 18 M/F, n 25/3 9/19 7/11 Age, yr 49 ± 8 49 ± 8 33 ± 11 Clinician-Administered PTSD Scale, total score 40.9 ± 7.9† 41.7 ± 6.6† 0 ± 0 Clinician-Administered PTSD Scale, criterion D 15.4 ± 3.5† 15.4 ± 3.2† 0 ± 0 Childhood Trauma Questionnaire, total score 52.8 ± 24.2† 65.7 ± 23.4† 30.3 ± 8.4 Multiscale Dissociation Inventory, total score 60.3 ± 16.3† 68.0 ± 17.8† 35.6 ± 5.2 Moral Injury Events Scale, total score 39.9 ± 6.9† 39.3 ± 7.7† 25.9 ± 9.6 World Health Organization Disability Assessment Schedule 2.0, total score 30.3 ± 9.3† 31.6 ± 8.7† 12.9 ± 1.7 Major depressive disorder, recurrent, n Current: 9
Past: 0Current: 21
Past: 0Current: 0
Past: 0Major depressive disorder, single episode, n Current: 4
Past: 1Current: 0
Past: 0Current: 0
Past: 0Prescribed psychotropic medication, n‡ 23 10 0 F = female; M = male; PTSD = posttraumatic stress disorder.
↵* Values are mean ± standard deviation, unless otherwise indicated.
↵† Significantly higher clinical symptom values relative to healthy controls, based on 1-way analysis of variance and follow-up t tests (p < 0.05).
↵‡ See Appendix 1 for a full breakdown of the psychotropic medications prescribed, the class they belonged to, and how many past and present prescriptions were recorded in each group.
Independent component Contrast Brain region Cluster, k MNI coordinates, x, y, z t statistic Z score pFDR (peak) Independent component 3: DMN (whole brain) Civilian-related PTSD > military- and law-enforcement-related PTSD Precuneus 43 14, −46, 54 5.67 5.38 0.009 Independent component 3: DMN (region of interest) Civilian-related PTSD > healthy controls Periaqueductal grey 39 0, −32, −8 4.95 4.75 0.028 Cerebellar lobule VII 49 10, −66, −40 4.44 4.29 0.046 Military- and law-enforcement-related PTSD > healthy controls Periaqueductal grey 60 4, −30, −2 4.22 4.09 0.076† DMN = default mode network; FDR = false discovery rate; MNI = Montreal Neurological Institute; PTSD = posttraumatic stress disorder.
↵* Group-level functional network connectivity across the independent component correlated to the DMN is displayed for whole-brain and region-of-interest analyses; t contrasts were evaluated at a significance threshold of pFDR < 0.05, k > 10 (peak-corrected).
↵† Denotes a group difference approaching significance.
Independent component Group Clinical score (direction) Brain region Cluster, k MNI coordinates, x, y, z t statistic Z score pFDR (peak) Independent component 3: DMN (whole brain) Military- and law-enforcement-related PTSD State: shame (−) Precentral gyrus 24 −36, −28, 40 8.29 5.18 0.049 Independent component 3: DMN (region of interest) Military- and law-enforcement-related PTSD State: shame (+) Cerebellar lobule IX 24 2, −56, −24 8.10 5.12 0.006 PTSD Clinician-Administered
PTSD Scale, total score (+)Cerebellar lobule VII 28 42, −60, −34 5.10 4.58 0.041 Clinician-Administered
PTSD Scale, total score (−)Brainstem 19 14, −16, −18 4.96 4.48 0.049 DMN = default mode network; FDR = false discovery rate; MNI = Montreal Neurological Institute; PTSD = posttraumatic stress disorder.
Clinical correlations across group-level functional network connectivity are displayed; t contrasts were evaluated at a significance threshold of pFDR < 0.05, k > 10 (peak-corrected).
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