Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Neuroscience

Supervisor

Dr. Ruth Lanius

Abstract

In post-traumatic stress disorder (PTSD), self-related processing disturbances are demonstrated commonly and have been linked to the default mode network (DMN), a large-scale, neural network altered significantly after trauma. However, emerging evidence suggests the midbrain may be underlying self-related processing disturbances as well, yet midbrain systems remain poorly characterized in PTSD. Here, we evaluated midbrain activity and functional connectivity during subliminal, trauma-related stimulus processing (Chapters 2–4), as well as during moral injury-related (MI) memory recall (Chapter 5) in participants with PTSD as compared to healthy controls. Initially, during subliminal, trauma-related stimulus processing, we revealed stronger midbrain periaqueductal gray (PAG) activity among participants with PTSD as compared to healthy controls (Chapter 2). Afterward, we evaluated the functional connectivity exhibited by the PAG, where we revealed stronger functional connectivity between the PAG and the medial prefrontal cortex (mPFC), as well as between the PAG and the precuneus (PCN) among participants with PTSD as compared to healthy controls (Chapter 3). Critically, the mPFC and the PCN are both DMN hubs, which we did not expect to covary functionally with the PAG. Next, we evaluated directionality, where we revealed stronger excitatory functional connectivity directed by the PAG toward the mPFC and toward the PCN among participants with PTSD as compared to healthy controls (Chapter 4). Lastly, during script-driven, MI-related memory recall, we revealed convergent evidence to the above using an independent component analysis (ICA) across participants with civilian-related PTSD, participants with military- or public safety-related PTSD, and MI-exposed, healthy controls. Here, we evaluated the functional network connectivity across the IC correlated most strongly to the DMN. In PTSD, we revealed stronger functional network connectivity exhibited by the PAG across the DMN IC as compared to MI-exposed, healthy controls (Chapter 5). Taken together, these findings suggest the midbrain may be related functionally to the DMN. In PTSD, critically, the DMN appears to be recruited during trauma- and MI-related memory processing, which assists to explain the clinical significance trauma has toward self-related processing and self-identity more generally. Lastly, these findings highlight the importance the midbrain has toward large-scale, neural networks, a long-overlooked dynamic in psychopathology.

Summary for Lay Audience

Trauma may profoundly alter self-related thoughts and self-identity more generally. In post-traumatic stress disorder (PTSD), self-related thoughts tend to be very self-critical, and self-identity appears to shift to be more trauma-related, highlighting how tightly linked self- and trauma-related processing seem to be post-trauma. Self-related thoughts are mediated by a large-scale, neural network called the default mode network (DMN), which, critically, has been revealed to be altered in PTSD, especially while at rest. During task-based, trauma-related processing (e.g., trauma-related images, script-driven imagery), the DMN has been analyzed much less and limbic and extended brainstem and midbrain systems are analyzed more commonly, where they are revealed to be altered in PTSD as well. Since self- and trauma-related processing seem to be tightly linked in PTSD, limbic and extended brainstem and midbrain systems may serve a critical role underlying DMN-related processing. Here, we revealed a midbrain structure called the periaqueductal gray (PAG) to be more strongly active during subliminal (i.e., non-conscious), trauma-related stimulus processing in participants with PTSD as compared to healthy controls. Moreover, we revealed the PAG to be linked functionally to the DMN during subliminal, trauma-related stimulus processing, as well as during script-driven, trauma-related memory recall in PTSD. These findings support the link between self- and trauma-related processing during a trauma-related images paradigm (i.e., subliminal, trauma-related stimulus processing), as well as during a script-driven imagery paradigm. Critically, the PAG has been suggested to be involved in defense- and avoidance-related behaviour, which are demonstrated commonly in PTSD and vary based on arousal symptomatology. These findings assist to explain the clinical significance trauma seems to have toward self-related thoughts and self-identity more generally, as well as highlight the contribution midbrain systems have toward large-scale, neural networks, a long-overlooked dynamic in mental health research.

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