The Threatful Self: Midbrain Functional Connectivity to Cortical Midline and Parietal Regions During Subliminal Trauma-Related Processing in PTSD

Abstract

Background The innate alarm system consists of a subcortical network of interconnected midbrain, lower brainstem, and thalamic nuclei, which together mediate the detection of evolutionarily-relevant stimuli. The periaqueductal gray is a midbrain structure innervated by the innate alarm system that coordinates the expression of defensive states following threat detection. In participants with post-traumatic stress disorder, the periaqueductal gray displays overactivation during the subliminal presentation of trauma-related stimuli as well as altered resting-state functional connectivity. Aberrant functional connectivity is also reported in post-traumatic stress disorder for the default-mode network, a large-scale brain network recruited during self-referential processing and autobiographical memory. Here, research lacks investigation on the extent to which functional interactions are displayed between the midbrain and the large-scale cortical networks in post-traumatic stress disorder. Methods Using a subliminal threat presentation paradigm, we investigated psycho-physiological interactions during functional neuroimaging in participants with post-traumatic stress disorder (n = 26) and healthy control subjects (n = 20). Functional connectivity of the periaqueductal gray was investigated across the whole-brain of each participant during subliminal exposure to trauma-related and neutral word stimuli. Results As compared to controls during subliminal threat presentation, the post-traumatic stress disorder group showed significantly greater periaqueductal gray functional connectivity with regions of the default-mode network (i.e., angular gyrus, precuneus, superior frontal gyrus). Moreover, multiple regression analyses revealed that the functional connectivity between the periaqueductal gray and the regions of the default-mode network correlated positively to symptoms of avoidance and state dissociation in post-traumatic stress disorder. Conclusion Given that the periaqueductal gray engages the expression of defensive states, stronger midbrain functional coupling with the default-mode network may have clinical implications to self-referential and trauma-related processing in participants with post-traumatic stress disorder.

The sense of self in the aftermath of trauma: lessons from the default mode network in posttraumatic stress disorder

“…Whereas resting-state functional connectivity is depicted in relation to the time series of the posterior cingulate cortex (PCC), trauma-related functional connectivity is depicted in relation to the time series of the periaqueductal grey (PAG). Figure 1 is an adaptation from two previous findings, where resting-state and threat-related functional connectivity are related to results by Bluhm et al ( 2009 ) and Terpou et al ( 2019a ), respectively…”

“…Here, DMN-related alterations may be developed during childhood and, in turn, act as a vulnerability factor towards the development of PTSD post-combat. Accordingly, we present the case where autobiographical memory-related processes may promote biases towards trauma-related processing among individuals with PTSD, which may assist to explain the stronger DMN functional connectivity during subliminal, trauma-related stimulus conditions reported by Terpou et al (2019a). Future research will also need to determine whether such biases towards trauma-related processing may provoke certain traumatic re-enactments, or automatic repetitions of the past -a phenomenon observed frequently among individuals with PTSD.…”

“…fight, flight, faint; De Oca, DeCola, Maren, & Fanselow, 1998;Brandão, Zanoveli, Ruiz-Martinez, Oliveira, & Landeira-Fernandez, 2008;Fenster, Lebois, Ressler, & Suh, 2018; for a review, see Keay & Bandler, 2014). Terpou et al (2019aTerpou et al ( , 2019b recently investigated the functional characteristics of the PAG during subliminal, trauma-related stimulus conditions in participants with PTSD as compared to healthy individuals. Initially, Terpou et al (2019b) assessed subcortical activity using improved spatial normalization procedures to attain greater resolution across brainstem, midbrain, and cerebellar brain structures (Diedrichsen, 2006).…”

“…Whereas the posterior cingulate cortex and the precuneus are associated more strongly with our experience of having an embodied self that exists in space, the medial prefrontal cortex is associated more strongly with our awareness of thoughts and emotions related to the self (for a review, Qin & Northoff, 2011 ). Critically, the DMN displays widespread functional alterations in individuals with PTSD during rest (Akiki et al, 2018 ; Brown et al, 2014 ; for a review, see Moore & Zoellner, 2007 ; St Jacques, Kragel, & Rubin, 2013 ; Nazarov et al, 2014 , 2015 ; Wang et al, 2016 ; Koch et al, 2016 ; Barredo et al, 2018 ; Akiki, Averill, & Abdallah, 2017 ) and during trauma-related stimulus conditions (Terpou et al, 2019a ; for a review, see St Jacques et al, 2013 ; Freeman, Hart, Kimbrell, & Ross, 2009 ), where these alterations are likely to mediate the clinical disturbances underlying self-related processes observed in PTSD.…”

“…Initially, Terpou et al ( 2019b ) assessed subcortical activity using improved spatial normalization procedures to attain greater resolution across brainstem, midbrain, and cerebellar brain structures (Diedrichsen, 2006 ). The approach revealed the PAG to display stronger activity in participants with PTSD as compared to healthy controls during subliminal, trauma-related stimulus conditions (Terpou et al, 2019a ). These findings are in keeping with a putative bias towards evolutionarily conserved defensive responses in PTSD, which may be expressed more actively in participants with PTSD than in healthy controls (for a review, see Fragkaki, Thomaes, & Sijbrandij, 2016 ; Kozlowska, Walker, McLean, & Carrive, 2015 ; Terpou et al, 2019c ).…”