Prefrontal cortex, amygdala, and threat processing: implications for PTSD

Abstract

Posttraumatic stress disorder can be viewed as a disorder of fear dysregulation. An abundance of research suggests that the prefrontal cortex is central to fear processing-that is, how fears are acquired and strategies to regulate or diminish fear responses. The current review covers foundational research on threat or fear acquisition and extinction in nonhuman animals, healthy humans, and patients with posttraumatic stress disorder, through the lens of the involvement of the prefrontal cortex in these processes. Research harnessing advances in technology to further probe the role of the prefrontal cortex in these processes, such as the use of optogenetics in rodents and brain stimulation in humans, will be highlighted, as well other fear regulation approaches that are relevant to the treatment of posttraumatic stress disorder and involve the prefrontal cortex, namely cognitive regulation and avoidance/active coping. Despite the large body of translational research, many questions remain unanswered and posttraumatic stress disorder remains difficult to treat. We conclude by outlining future research directions related to the role of the prefrontal cortex in fear processing and implications for the treatment of posttraumatic stress disorder.

Fig. 1. Threat regulatory neurocircuitry across species.

a Rodent anatomy highlighting regions involved in threat learning, extinction, avoidance, and the contextual modulation of threat expression; b Human anatomy highlighting regions involved in threat learning, extinction, avoidance, cognitive regulation, and the contextual modulation of threat expression. PL = prelimbic cortex, IL = infralimbic cortex; dACC = dorsal anterior cingulate cortex, vmPFC = ventromedial prefrontal cortex, dlPFC = dorsolateral prefrontal cortex.

Fig. 2. Functional connections in threat circuitry in health and PTSD.

a Healthy Threat Circuit. Regions involved in threat learning and the control of threat reactions via extinction, context, avoidance, or cognitive regulation. In healthy individuals the coordination of this circuit enables adaptive threat expression. b PTSD Threat Circuit. The dlPFC, vmPFC/IL, and hippocampus show impaired functioning with PTSD, whereas the amygdala and dACC/PL are enhanced. Disrupted connections between regions are indicated by dashed lines. The disrupted threat circuit with PTSD results in maladaptive threat expression. Prefrontal cortex regions are highlighted within the beige circle. Terms for animal/human homologous regions are in the same circles. PL = prelimbic cortex, IL = infralimbic cortex, dACC = dorsal anterior cingulate cortex, vmPFC = ventromedial prefrontal cortex, dlPFC = dorsolateral prefrontal cortex.