Learning and memory mechanisms involved in the processing of internal bodily sensations may be relevant for elucidating the pathophysiology of functional somatic disorders. We investigated brain processing during associative learning and modification of the learned response to visceral pain using a classical conditioning paradigm and mechanical oesophageal stimulation.
Twenty two healthy subjects (11 males) participated in an fMRI study. During acquisition, half of visual conditioning stimuli (coloured square: CS+) was paired with painful oesophageal distension as unconditioned stimuli (US) and different coloured square were presented as non-conditioned stimuli (CS-). First extinction phase immediately followed acquisition and CS+ and CS- were presented without US. Second extinction phase was conducted after 20 minutes of first extinction phase to study the spontaneous recovery of conditioning response (CR).
During acquisition phase, CS+ without pain compared to CS- induced greater activation in the visceral pain matrix including the thalamus, insula, caudate, midbrain, anterior cingulate cortex (ACC), supplementary motor area (SMA), inferior parietal lobule (IPL) and cerebellum. During first extinction phase, CS+ compared to CS- showed greater brain activity in the medial prefrontal cortex (mPFC) and dorsolateral prefrontal cortex (dlPFC) in addition to the visceral pain matrix. During second extinction phase, CS+ compared to CS- demonstrated greater activation in the hippocampus, mPFC, dlPFC, insula, ACC, IPL, SMA and cerebellum. All brain data was significant at least level p < 0.05 (corrected).
Conclusions: CR using visceral pain produced a neural response in the absence of physical visceral pain similar to that occurs during actual visceral pain. Frontal cortex activity including mPFC and dlPFC may play an important role in extinction learning to regulate acquired CR. The activation in the hippocampus may be associated with memory retrieval of CR after extinction.