The Hijacked Self: Disrupted Functional Connectivity between the Periaqueductal Gray and the Default Mode Network in Posttraumatic Stress Disorder using Dynamic Causal Modeling

Abstract Self-related processes define assorted self-relevant or social-cognitive functions that allow us to gather insight and to draw inferences related to our own mental conditions. Self-related processes are mediated by the default mode network (DMN), which, critically, shows altered functionality in participants with posttraumatic stress disorder (PTSD). In PTSD, the midbrain periaqueductal gray (PAG) demonstrates stronger functional connectivity with the DMN [i.e., precuneus (PCN), medial prefrontal cortex (mPFC)] as compared to healthy individuals during subliminal, trauma-related stimulus processing. Here, we analyzed the directed functional connectivity, or, effective connectivity, between the PAG and the PCN, as well as between the PAG and the mPFC to more explicitly characterize the functional connectivity observed among the same sample and paradigm we have reported on previously. We evaluated three models varying in regard to context-dependent modulatory directions (i.e., bi-directional, bottom-up, top-down) among individuals with PTSD (n = 26) and healthy participants (n = 20), where Bayesian model selection was used to identify the most optimal model for each group. We then compared the effective connectivity strength for each model parameter across the models and between groups using Bayesian model averaging. Bi-directional models were revealed to be favoured across both groups. In PTSD, we revealed the PAG to show stronger excitatory effective connectivity to the PCN, as well as to the mPFC as compared to controls. In PTSD, we revealed further that the PAG-mediated effective connectivity to the PCN, as well as to the mPFC were modulated more strongly during subliminal, trauma-related stimulus conditions as compared to controls. Clinical disturbances towards self-related processes are reported widely by participants with PTSD during trauma-related stimulus processing, where altered functional connectivity directed by the PAG to the DMN may assist to explain experiential links between self- and trauma-related processing in traumatized individuals.