Salience Network Disruption in US Army Soldiers with PTSD

Abstract

BACKGROUND: Better understanding of the neurobiology of posttraumatic stress disorder (PTSD) may be critical to developing novel, effective therapeutics. Here, we conducted a data-driven investigation using a well-established, graphbased topological measure of nodal strength to determine the extent of functional dysconnectivity in a cohort of active duty US Army soldiers with PTSD compared to controls.METHODS: 102 participants with (n=50) or without PTSD (n=52) completed functional magnetic resonance imaging (fMRI) at rest and during symptom provocation using subject-specific script imagery. Vertex/voxel global brain connectivity with global signal regression (GBCr), a measure of nodal strength, was calculated as the average of its functional connectivity with all other vertices/voxels in the brain gray matter. RESULTS:In contrast to during resting-state, where there were no group differences, we found a significantly higher GBCr, in PTSD participants compared to controls, in areas within the right hemisphere, including anterior insula, caudalventrolateral prefrontal, and rostral-ventrolateral parietal cortices. Overall, these clusters overlapped with the ventral and dorsal salience networks. Post hoc analysis showed increased GBCr in these salience clusters during symptom provocation compared to resting-state. In addition, resting-state GBCr in the salience clusters predicted GBCr during symptom provocation in PTSD participants but not in controls. CONCLUSION:In PTSD, increased connectivity within the salience network has been previously hypothesized, based primarily on seed-based connectivity findings. The current results strongly support this hypothesis using whole-brain network measure in a fully data-driven approach. It remains to be seen in future studies whether these identified salience disturbances would normalize following treatment.

A decennial review of psychotraumatology: what did we learn and where are we going?

“…Previous advances in pharmacological treatments for PTSD had relied mainly on clinical trials investigating the efficacy of compounds developed and marketed for commonly comorbid conditions, as it was the case for SSRIs and SNRIs or atypical antipsychotics. This was also the case more recently, with ketamine that has been shown to be efficacious for depression, with trials underway for PTSD (Abdallah et al, 2019).…”

Reduced Salience and Enhanced Central Executive Connectivity Following PTSD Treatment

“…This raises the question whether the level of symptoms during the scan may have increased the GBCr values in this subpopulation. Recently, this hypothesis was supported by a data-driven cross-sectional analysis demonstrating increased GBCr within the salience network during symptom provocation, but not at rest, in PTSD compared to trauma and non-trauma control 20 .…”

“…The clinical trial results for the PTSD treatment study were previously reported 21 were reported elsewhere (NCT01286415). The pretreatment GBCr data 20 . The posttreatment data and analyses are new and have not been reported previously.…”

“…The acquisition parameters were previously reported 20 . Briefly, each f MRI scan (voxel size = 2 × 2 × 3 mm; TR = 3000 ms; TE = 30 ms) included 10 minutes at rest and 12 minutes during symptom provocation – i.e., script imagery during which participants listened to recorded retelling of a personal event (alternating between trauma and neutral) over a 1-minute period, followed by a 1-minute period of thinking about the event and then a 1-minute break.…”

“…To investigate the salience ROI (Fig. 1A; based on 20 ), we constructed a general linear model (GLM) to determine the main effects of group (PCT vs. CPT vs. CC), task (rest vs. scripts), and time (pretreatment vs. posttreatment), as well as the interactions between the main effects, followed by post-hoc pairwise comparisons.…”