Neural dysregulation in posttraumatic stress disorder: evidence for disrupted equilibrium between salience and default mode brain networks

Abstract

Objective: Convergent research demonstrates disrupted attention and heightened threat sensitivity in posttraumatic stress disorder (PTSD). This might be linked to aberrations in large-scale networks subserving the detection of salient stimuli (i.e., the salience network [SN]) and stimulus-independent, internally focused thought (i.e., the default mode network [DMN]).

Methods: Resting-state brain activity was measured in returning veterans with and without PTSD (n = 15 in each group) and in healthy community controls (n = 15). Correlation coefficients were calculated between the time course of seed regions in key SN and DMN regions and all other voxels of the brain.

Results: Compared with control groups, participants with PTSD showed reduced functional connectivity within the DMN (between DMN seeds and other DMN regions) including the rostral anterior cingulate cortex/ventromedial prefrontal cortex (z = 3.31; p = .005, corrected) and increased connectivity within the SN (between insula seeds and other SN regions) including the amygdala (z = 3.03; p = .01, corrected). Participants with PTSD also demonstrated increased cross-network connectivity. DMN seeds exhibited elevated connectivity with SN regions including the insula (z = 3.06; p = .03, corrected), and SN seeds exhibited elevated connectivity with DMN regions including the hippocampus (z = 3.10; p = .048, corrected).

Conclusions: During resting-state scanning, participants with PTSD showed reduced coupling within the DMN, greater coupling within the SN, and increased coupling between the DMN and the SN. Our findings suggest a relative dominance of threat-sensitive circuitry in PTSD, even in task-free conditions. Disequilibrium between large-scale networks subserving salience detection versus internally focused thought may be associated with PTSD pathophysiology.

Figure 1. Functional connectivity analysis

Statistical significance (color-coded t score) of resting-state functional connectivity patterns for Default Mode Network (PCC seed and vmPFC seed) and Salience Network (left anterior insula seed and right anterior insula seed) for 15 PTSD participants and 30 Controls (15 combat-exposed controls and 15 healthy community controls). PCC: posterior cingulate cortex; vmPFC: ventromedial prefrontal cortex.

Figure 2. Group Comparison

(A) Compared to controls, PTSD participants showed greater connectivity between posterior cingulate cortex (PCC; seed region shown in A) and right putamen (column 2; y = −4) and right insula (column 3; z = 2) and a trend for less connectivity between PCC seed and left hippocampus (column 4; x = −27). (B) Compared to controls, PTSD participants showed greater connectivity between ventromedial prefrontal cortex (vmPFC; seed region shown in B) and supplementary motor area (column 2; x = 5) and bilateral superior temporal sulcus (column 3; z = 11) and less connectivity between vmPFC seed and rostral anterior cingulate cortex (column 4; x = −10). (C) Compared to controls, PTSD participants showed greater connectivity between left anterior insula (=seed region shown in C) and right amygdala (column 2; y = 8), left peri-insula (column 3; z = 21) and right hippocampus (column 4; x = 37).