Abstract

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.

Highlights

  • Post-traumatic stress disorder (PTSD) is characterized by various altered emotional responses as a result of trauma exposure

  • 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

  • Follow-up ROI analyses on the extracted Z -scores of the strength of connectivity from the insula revealed that both groups exhibited positive amygdala–insula coupling, the extent of connectivity between the amygdala and insula was greater in the PTSD group than the combat-exposed control (CEC) group (Figure 1)

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Summary

Introduction

Post-traumatic stress disorder (PTSD) is characterized by various altered emotional responses as a result of trauma exposure (e.g., combat, assault, and disasters). Functional neuroimaging techniques have focused primarily on the study of brain function related to fear perception and response, and have consistently implicated aberrant amygdala reactivity to fear-relevant probes and other abnormalities in a broad aberrant amygdala-linked circuitry involving the medial prefrontal cortex (mPFC), insula, anterior cingulate cortex (ACC), and hippocampus (Rauch and Shin, 1997; Pitman et al, 2001; Nemeroff et al, 2006; Rauch et al, 2006; Etkin and Wager, 2007; Liberzon and Sripada, 2008; Shin, 2009; Shin and Liberzon, 2010) Together these interconnected regions form a disrupted functional network thought to be responsible for impaired regulation of fear responses, enhanced attention to threat-related stimuli, and biased memory for adverse events (Shin, 2009). These dysfunctional networks have been implicated in mediating several characteristics of PTSD, such as, hyperarousal, abnormal reactivity to emotional stimuli, and avoidance of emotionally distressing memories (Nemeroff et al, 2006; Shin and Liberzon, 2010), little is known about how these regions may interact dynamically within individual subjects

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