Altered Amygdala Resting-State Functional Connectivity in Post-Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is often characterized by aberrant amygdala activation and functional abnormalities in corticolimbic circuitry, as elucidated by functional neuroimaging. These “activation” studies have primarily relied on tasks designed to induce region-specific, and task-dependent brain responses in limbic (e.g., amygdala) and paralimbic brain areas through the use of aversive evocative probes. It remains unknown if these corticolimbic circuit abnormalities exist at baseline or “at rest,” in the absence of fear/anxiety-related provocation and outside the context of task demands. Therefore the primary aim of the present experiment was to investigate aberrant amygdala functional connectivity patterns in combat-related PTSD patients during resting-state. Seventeen Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans with combat-related PTSD (PTSD group) and 17 combat-exposed OEF/OIF veterans without PTSD [combat-exposed control (CEC) group] underwent an 8-min resting-state functional magnetic resonance imaging scan. Using an anatomically derived amygdala “seed” region we observed stronger functional coupling between the amygdala and insula in the PTSD group compared to the CEC group, but did not find group differences in amygdala–prefrontal connectivity. These findings suggest that the aberrant amygdala and insula activation to fear-evocative probes previously characterized in PTSD may be driven by an underlying enhanced connectivity between the amygdala, a region known for perceiving threat and generating fear responses, and the insula, a region known for processing the meaning and prediction of aversive bodily states. This enhanced amygdala–insula connectivity may reflect an exaggerated, pervasive state of arousal that exists outside the presence of an overt actual threat/danger. Studying amygdala functional connectivity “at rest” extends our understanding of the pathophysiology of PTSD