An fMRI study of unconditioned responses in post-traumatic stress disorder

Whereas responses to the conditioned stimulus (CS) were similar in PTSD and TENC, the former displayed higher putamen, insula, caudate and amygdala responses to the US. Reactivity to the US in the anterior insula correlated with PTSD symptom severity. Functional connectivity analyses using the putamen as a seed region indicated that TENC subjects had increased amygdala-putamen connectivity during US delivery; this connection was disengaged in PTSD.Our results indicate that although neural processing of fear learning in people with PTSD seems to be comparable with controls, neural responses to unconditioned aversive stimuli in PTSD seem to be increased.In classic fear conditioning, an initially neutral, and later conditioned stimulus (CS+) is paired with an aversive unconditioned stimulus (US) such as an electric shock. After pairing, the neutral stimulus is able to elicit fear on its own. Much has been learned about the neural responses induced by the CS+ presentation. In healthy people, conditioned stimuli activate the amygdala, brainstem, insula and parts of anterior cingulate cortex (ACC) [1]. Less is known about changes occurring in response to the presentation of the more biologically relevant US [2]. Responses to a US in healthy subjects are accompanied by increased activity in the brainstem, thalamus, and cingulate, sensory and insular cortices [3-5], structures also known to respond to noxious stimuli [6].Understanding the neural mechanisms that mediate aversive unconditioned responses may be clinically relevant. Brain regions involved in fear learning, such as the amygdala and the ACC, are implicated in the pathophysiology of several anxiety disorders such as post-traumatic stress disorder (PTSD). Other intrinsically aversive stimuli such as trauma reminders, aversive images and fearful faces also elicit increased responses in several brain regions in PTSD, such as the amygdala and the ACC [7]. The unconditioned response represents a specific exemplar of a