PTSD and cognitive symptoms relate to inhibition-related prefrontal activation and functional connectivity

Abstract

Background Posttraumatic stress disorder (PTSD) is associated with reduced executive functioning and verbal memory performance, as well as abnormal task-specific activity in prefrontal (PFC) and anterior cingulate cortices (ACC). The current study examined how PTSD symptoms and neuropsychological performance in combat veterans relates to 1) medial PFC and ACC activity during cognitive inhibition, and 2) task-independent PFC functional connectivity. Methods Thirty-nine male combat veterans with varying levels of PTSD symptoms completed the multisource interference task during functional magnetic resonance imaging. Robust regression analyses were used to assess relationships between percent signal change (PSC: Incongruent-Congruent) and both PTSD severity and neuropsychological performance. Analyses were conducted voxel-wise and for PSC extracted from medial PFC and ACC regions of interest. Resting state scans were available for veterans with PTSD. Regions identified via task-based analyses were used as seeds for resting state connectivity analyses. Results Worse PTSD severity and neuropsychological performance related to less medial PFC and rostral ACC activity during interference processing, driven partly by increased activation to congruent trials. Worse PTSD severity related to reduced functional connectivity between these regions and bilateral, lateral PFC (Brodmann area 10). Worse neuropsychological performance related to reduced functional connectivity between these regions and the inferior frontal gyrus. Conclusions PTSD and associated neuropsychological deficits may result from difficulties regulating medial PFC regions associated with “default mode”, or self-referential processing. Further clarification of functional coupling deficits between default mode and executive control networks in PTSD may enhance understanding of neuropsychological and emotional symptoms and provide novel treatment targets.

Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study

“…The differences in cognitive function align with the fronto-limbic hypothesis of PTSD, which postulates that PTSD symptoms, including impaired cognition, may result from alterations in the structure and function of brain regions comprising this circuit (e.g., prefrontal cortex, hippocampus, amygdala;Clausen et al, 2017;Polak, Witteveen, Reitsma, & Olff, 2012;Scott et al, 2015;Wrocklage et al, 2016).…”

“…The differences in cognitive function align with the fronto‐limbic hypothesis of PTSD, which postulates that PTSD symptoms, including impaired cognition, may result from alterations in the structure and function of brain regions comprising this circuit (e.g., prefrontal cortex, hippocampus, amygdala; Clausen et al, ; Polak, Witteveen, Reitsma, & Olff, ; Scott et al, ; Wrocklage et al, ). Further, the reduced hippocampal volume is a relatively consistent finding in individuals with PTSD (Karl et al, ; Kitayama, Vaccarino, Kutner, Weiss, & Bremner, ; Woon, Sood, & Hedges, ).…”

White matter integrity alterations in post‐traumatic stress disorder

“…In general, it is found that amygdala response is exaggerated in PTSD subjects, and is more pronounced when PTSD symptoms are more severe (Brunetti et al, ; Dickie, Brunet, Akerib, & Armony, ; Shin et al, ; Zhong et al, ). Modulation/extinction of the fear response is postulated to involve an inhibitory role of medial prefrontal structures, particularly the ACC, over the amygdala (Clausen et al, ; Shin et al, ; Stevens et al, ). In PTSD diagnosed subjects, correlational analyses from the current study identified associations between FA/RD/AD/MD values and PTSD symptoms (as measured by CAPS subscores) in WM tracts connecting the amygdala and ACC.…”

Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man

“…Alternatively, it could reflect a compensatory mechanism for maintaining focus during sustained attention tasks that stops working with more difficult inhibition tasks 80 . Another interpretation is that this pattern of activity reflects a decreased ability to regulate midline cortical self-referential processing activity during attentional tasks 84 . It is yet to be determined how these changes in PFC engagement might also alter the hippocampal-related declarative memory processes discussed above.…”