Moral wounds run deep: exaggerated midbrain functional network connectivity across the default mode network in
Braeden A Terpou1, Chantelle S Lloyd1, Maria Densmore1
1From the Department of Neuroscience (Terpou, Neufeld), the Department of Psychiatry (Lloyd, Densmore, Théberge, Neufeld, Lanius), the Department of Medical Biophysics (Théberge), the Department of Psychology (Neufeld), Western University, London, Ont.; the Imaging Division, Lawson Health Research Institute (Densmore, Lanius), the Department of Psychology, Neuroscience, and Behaviour (Lloyd), the Department of Psychiatry and Behavioural Neurosciences (McKinnon), McMaster University, Hamilton, Ont.; Mood Disorders Program, St. Joseph's Healthcare (McKinnon), Hamilton, Ont.; Homewood Research Institute (McKinnon, Lanius), Guelph, Ont.; Canadian Forces, Health Services (Jetly), Ottawa, Ont.
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.


