Abstract
BackgroundBoth fear and pain processing are altered in post-traumatic stress disorder (PTSD), as evidenced by functional neuroimaging studies showing increased amygdala responses to threats, and increased insula, putamen and caudate activity in response to heat pain. Using psychophysiology and functional magnetic resonance imaging, we studied conditioned and unconditioned autonomic and neuronal responses in subjects with PTSD versus trauma-exposed non-PTSD control (TENC) subjects. A design using an electric shock selected by subjects to be 'highly annoying but not painful' as an unconditioned stimulus (US) with partially reinforced cues allowed us to partly disentangle the expectancy- and prediction-error components from sensory components of the unconditioned response.ResultsWhereas 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.ConclusionsOur 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.
Highlights
Both fear and pain processing are altered in post-traumatic stress disorder (PTSD), as evidenced by functional neuroimaging studies showing increased amygdala responses to threats, and increased insula, putamen and caudate activity in response to heat pain
Responses to a unconditioned stimulus (US) in healthy subjects are accompanied by increased activity in the brainstem, thalamus, and cingulate, sensory and insular cortices [3,4,5], structures known to respond to noxious stimuli [6]
Based on the univariate results, we investigated whether the delivery of the US modulated the inter-regional functional connectivity between seed regions and targets elsewhere in the brain differently in PTSD and trauma-exposed non-PTSD control (TENC) subjects
Summary
Both fear and pain processing are altered in post-traumatic stress disorder (PTSD), as evidenced by functional neuroimaging studies showing increased amygdala responses to threats, and increased insula, putamen and caudate activity in response to heat pain. A design using an electric shock selected by subjects to be ‘highly annoying but not painful’ as an unconditioned stimulus (US) with partially reinforced cues allowed us to partly disentangle the expectancy- and prediction-error components from sensory components of the unconditioned response. An initially neutral, and later conditioned stimulus (CS+) is paired with an aversive unconditioned stimulus (US) such as an electric shock. In healthy people, conditioned stimuli activate the amygdala, brainstem, insula and parts of anterior cingulate cortex (ACC) [1]. Responses to a US in healthy subjects are accompanied by increased activity in the brainstem, thalamus, and cingulate, sensory and insular cortices [3,4,5], structures known to respond to noxious stimuli [6]
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