Resting‐state functional connectivity of the bed nucleus of the stria terminalis in post‐traumatic stress disorder and its dissociative subtype

Abstract

The bed nucleus of the stria terminals (BNST) is a subcortical structure involved in anticipatory and sustained reactivity to threat and is thus essential to the understanding of anxiety and stress responses. Although chronic stress and anxiety represent a hallmark of post-traumatic stress disorder (PTSD), to date, few studies have examined the functional connectivity of the BNST in PTSD. Here, we used resting state functional Magnetic Resonance Imaging (fMRI) to investigate the functional connectivity of the BNST in PTSD (n = 70), its dissociative subtype (PTSD + DS) (n = 41), and healthy controls (n = 50). In comparison to controls, PTSD showed increased functional connectivity of the BNST with regions of the reward system (ventral and dorsal striatum), possibly underlying stress-induced reward-seeking behaviors in PTSD. By contrast, comparing PTSD + DS to controls, we observed increased functional connectivity of the BNST with the claustrum, a brain region implicated in consciousness and a primary site of kappa-opioid receptors, which are critical to the dynorphin-mediated dysphoric stress response. Moreover, PTSD + DS showed increased functional connectivity of the BNST with brain regions involved in attention and salience detection (anterior insula and caudate nucleus) as compared to PTSD and controls. Finally, BNST functional connectivity positively correlated with default-mode network regions as a function of state identity dissociation, suggesting a role of BNST networks in the disruption of self-relevant processing characterizing the dissociative subtype. These findings represent an important first step in elucidating the role of the BNST in aberrant functional networks underlying PTSD and its dissociative subtype.

PTSD and its dissociative subtype through the lens of the insula: Anterior and posterior insula resting‐state functional connectivity and its predictive validity using machine learning

“…Although the Brainnetome atlas was used to parcellate the insula into its subregions (not captured in the Automated Anatomical Labeling [AAL] atlas and MNI2 Talairich [MNI2Tal] atlas), brain regions from the results of the seed‐based analysis were identified using the AAL atlas (Tzourio‐Mazoyer et al, ) via xjview software (https://www.nitrc.org/projects/xjview), the MNI2Tal atlas (https://bioimagesuite.yale.edu/mni2tal; Lacadie, Fulbright, Constable, & Papademetris, ), and visual inspection using an additional anatomical atlas (Montemurro & Bruni, ). This approach is consistent with our previous studies (Harricharan et al, ; Rabellino et al ; Terpou et al, ).…”

“…Seedbased analysis correlations with self-reported psychological measures used to assess state symptoms at the time of scanning (RSDI, STAI, CADSS) and trait symptoms prior to scanning (CAPS, CTQ, MDI, BDI) were performed in both the PTSD and PTSD+DS groups (significant peak coordinates were evaluated at the same voxel-wise pFWE < .05, k = 10 threshold and visual inspection using an additional anatomical atlas (Montemurro & Bruni, 1988). This approach is consistent with our previous studies (Harricharan et al, 2016;Rabellino et al 2018;Terpou et al, 2018).…”

“…A primary PTSD diagnosis was determined using the Clinician‐Administered PTSD Scale (CAPS), versions IV (for 156 participants) and 5 (for 28 participants)—CAPS IV: cutoff score > 50 (Blake et al, ); CAPS‐5: no cutoff score is used for the DSM‐5 version (Weathers et al, ). Individuals meeting the criteria for the dissociative subtype scored at least 2 in frequency and intensity on the CAPS‐IV scale or at least 2 in symptom severity on the CAPS‐5 scale for depersonalization and/or derealization symptoms as per previous studies (Harricharan et al, ; Rabellino et al, ; Terpou et al, ). For all participants, the SCID (Structured Clinical Interview for DSM‐IV Axis I disorders; First, Spitzer, Gibbon, & Williams, ) was administered, along with a battery of questionnaires: Beck Depression Inventory (BDI; Beck, Guth, Steer, & Ball, ), Child Trauma Questionnaire (CTQ; 87% of all PTSD patients had histories of childhood trauma, confirmed if patient scored above the none/minimal threshold for any trauma category according to the CTQ scoring manual; Bernstein & Fink, ), as well as the Multiscale Dissociation Inventory (MDI; Briere, Weathers, & Runtz, ).…”

Stria terminalis, amygdala, and temporoparietal junction networks facilitate efficient emotion processing under expectations

“…In psychosis, for example, there is a deficit in recognising threatening emotions (Behere, 2015;Mandal, Pandey, & Prasad, 1998;van't Wout et al, 2007) and also misattribution of threat (Premkumar et al, 2008). These abnormalities in threat processing have strong links to neurobiological factors; specifically, abnormal activation and connectivity in similar brain regions as those identified in the current study (i.e., amygdala, temporoparietal junction, BNST, ACC, and hippocampus) (Bitsch, Berger, Nagels, Falkenberg, & Straube, 2018;Bryant et al, 2008;Buff et al, 2017;Felmingham et al, 2008;Rabellino et al, 2015;Rabellino et al, 2018;Underwood, Kumari, & Peters, 2016;Underwood, Peters, & Kumari, 2015). These abnormalities in threat processing have strong links to neurobiological factors; specifically, abnormal activation and connectivity in similar brain regions as those identified in the current study (i.e., amygdala, temporoparietal junction, BNST, ACC, and hippocampus) (Bitsch, Berger, Nagels, Falkenberg, & Straube, 2018;Bryant et al, 2008;Buff et al, 2017;Felmingham et al, 2008;Rabellino et al, 2015;Rabellino et al, 2018;Underwood, Kumari, & Peters, 2016;Underwood, Peters, & Kumari, 2015).…”

The cerebellum after trauma: Resting‐state functional connectivity of the cerebellum in posttraumatic stress disorder and its dissociative subtype

“…The sample consisted of 149 subjects, including 65 individuals with a diagnosis of PTSD, 37 individuals diagnosed with the dissociative subtype of PTSD (PTSD + DS), and 47 healthy non‐trauma exposed controls (HC). A subset of the current sample has been utilized in previous resting state studies from our group investigating other regions of the brain (Harricharan et al, ; Nicholson et al, ; Olivé et al, ; Rabellino et al, ; Thome et al, ).…”