Neural dysregulation in posttraumatic stress disorder

Objective—Convergent neuroimaging and neuropsychological research demonstrates disrupted attention and heightened threat sensitivity in PTSD. This might be linked to aberrations in largescale networks subserving 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 who served in Iraq or Afghanistan with (n=15) and without PTSD (n=15) and in healthy community controls (n=15). Correlation coefficients were calculated between the time course of seed regions in key SN and DMN regions (posterior cingulate, ventromedial prefrontal cortex, and bilateral anterior insula) and all other voxels of the brain. Results—Compared to control groups, PTSD participants showed reduced functional connectivity within DMN (between DMN seeds and other DMN regions), including rostral ACC/ vmPFC (Z=3.31; p=.005, corrected) and hippocampus (Z=2.58; p=.005), and increased connectivity within SN (between insula seeds and other SN regions), including amygdala (Z=3.03; p=.01, corrected). PTSD participants also demonstrated increased cross-network connectivity. DMN seeds exhibited elevated connectivity with SN regions, including insula (Z=3.06; p=.03, corrected), putamen, and supplementary motor area (Z=4.14; Z=4.08; p<.001), and SN seeds exhibited elevated connectivity with DMN regions, including hippocampus (Z=3.10; p=.048, corrected). Conclusions—During resting state scanning, PTSD participants showed reduced coupling within DMN, greater coupling within SN, and increased coupling between DMN and SN. Our findings suggest a relative dominance of threat-sensitive circuitry in PTSD, even in task-freeconditions. Disequilibrium between large-scale networks subserving salience detection versus internally focused thought may be associated with PTSD pathophysiology