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Cited by 30Posttraumatic Stress Disorder ResearchFunctional Brain Connectivity StudiesTraumatic Brain Injury Research

Moral wounds run deep: exaggerated midbrain functional network connectivity across the default mode network in posttraumatic stress disorder

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Terpou, Braeden A., Lloyd, Chantelle S., Densmore, Maria, McKinnon, Margaret C., Théberge, Jean, Neufeld, Richard W. J., Jetly, Rakesh, Lanius, Ruth A.·2022·Journal of Psychiatry and Neuroscience
DOI 10.1503/jpn.210117PMC PMC8865964
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Abstract

Background: A moral injury occurs when a deeply held moral code has been violated, and it can lead to the development of symptoms of posttraumatic stress disorder (PTSD). However, the neural correlates that differentiate moral injury and PTSD remain largely unknown. Intrinsic connectivity networks such as the default mode network (DMN) appear to be altered in people with PTSD who have experienced moral injury. However, brainstem, midbrain and cerebellar systems are rarely integrated into the intrinsic connectivity networks; this is a critical oversight, because these systems display marked differences in people with PTSD and are thought to underlie strong moral emotions such as shame, guilt and betrayal. Methods: We conducted an independent component analysis on data generated during script-driven memory recall of moral injury in participants with military- or law enforcement–related PTSD ( n = 28), participants with civilian-related PTSD ( n = 28) and healthy controls exposed to a potentially morally injurious event ( n = 18). We conducted group-wise comparisons of functional network connectivity differences across a DMN-correlated independent component, with a particular focus on brainstem, midbrain and cerebellar systems. Results: We found stronger functional network connectivity in the midbrain periaqueductal grey ( t 71 = 4.95, p FDR = 0.028, k = 39) and cerebellar lobule IX ( t 71 = 4.44, p FDR = 0.046, k = 49) in participants with civilian-related PTSD as compared to healthy controls. We also found a trend toward stronger functional network connectivity in the midbrain periaqueductal grey ( t 71 = 4.22, p FDR = 0.076, k = 60) in participants with military- or law enforcement–related PTSD as compared to healthy controls. Limitations: The significant clusters were large, but resolution is generally lower for subcortical structures. Conclusion: In PTSD, the DMN appears to be biased toward lower-level, midbrain systems, which may drive toxic shame and related moral emotions that are common in PTSD, highlighting the depth at which moral injuries are represented neurobiologically.

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  • Investigations of morally salient autobiographical recall report atypical posterior DMN activation, altered connectivity with sensorimotor and midbrain regions, and associations between shame intensity and dorsomedial prefrontal activity.

    “Investigations of morally salient autobiographical recall report atypical posterior DMN activation, altered connectivity with sensorimotor and midbrain regions, and associations between shame intensity and dorsomedial prefrontal activity—patterns broadly consistent with intensified moral self-focus and difficulties integrating emotionally charged experiences into coherent narratives (40, 41, 52).”

    From The therapeutic role of self-transcendence in moral injury recovery: theory, mechanisms, and clinical implications (2026) · cites this paper as [41]

    The Discussion (Midbrain functional network connectivity; page unavailable) reports greater midbrain–DMN connectivity during moral injury–related recall in participants with PTSD. The Introduction reports an association between shame scores and dorsomedial prefrontal activity from a study the paper reviews. This paper does not establish atypical posterior DMN activation or altered connectivity with sensorimotor regions as phrased: its Results describe precuneus connectivity differences between PTSD groups, not posterior DMN activation. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Emerging studies associate moral injury with altered activity in large-scale brain networks supporting self-referential thought, particularly the Default Mode Network.

    “Emerging studies associate moral injury with altered activity in large-scale brain networks supporting self-referential thought, particularly the Default Mode Network (DMN) (40, 41, 51, 52).”

    From The therapeutic role of self-transcendence in moral injury recovery: theory, mechanisms, and clinical implications (2026) · cites this paper as [41]

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Authors
Terpou, B. A., Lloyd, C. S., Densmore, M., McKinnon, M. C., Théberge, J., Neufeld, R. W. J., Jetly, R., & Lanius, R. A.
Affiliations
Western University (CA)
Corresponding author
Lanius, Ruth A.
ORCID
Venue
Journal of Psychiatry and Neuroscience
Publisher
Canadian Science Publishing
Published
2022-02-23
Volume
47
Issue
1
Pages
E56-E66
ISSN
  • 1180-4882 (ISSN-L)
  • 1488-2434
DOI
10.1503/jpn.210117
PMC
PMC8865964
OpenAlex
W4212764706
Cited by
30
References
67
Citations by year
2026: 8 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 3
FWCI
5.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Psychiatry and Neuroscience (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Scholarship@Western (Western University) (submittedVersion)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
moral injury, post-traumatic stress disorder, default mode network, periaqueductal gray, brainstem, shame, guilt, betrayal, resting-state networks, moral emotions
MeSH terms
Default Mode Network, Brain, Humans, Magnetic Resonance Imaging, Mesencephalon, Morals, Stress Disorders, Post-Traumatic

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