Extended viewing of movements of the intact hand in a mirror as well as motor imagery has been shown to decrease pain in phantom pain patients. We used functional magnetic resonance imaging to assess the neural correlates of mirrored, imagined and executed hand movements in 14 upper extremity amputees - 7 with phantom limb pain (PLP) and 7 without phantom limb pain (non-PLP) and 9 healthy controls (HC). Executed movement activated the contralateral sensorimotor area in all three groups but ipsilateral cortex was only activated in the non-PLP and HC group. Mirrored movements activated the sensorimotor cortex contralateral to the hand seen in the mirror in the non-PLP and the HC but not in the PLP. Imagined movement activated the supplementary motor area in all groups and the contralateral primary sensorimotor cortex in the non-PLP and HC but not in the PLP. Mirror- and movement-related activation in the bilateral sensorimotor cortex in the mirror movement condition and activation in the sensorimotor cortex ipsilateral to the moved hand in the executed movement condition were significantly negatively correlated with the magnitude of phantom limb pain in the amputee group. Further research must identify the causal mechanisms related to mirror treatment, imagined movements or movements of the other hand and associated changes in pain perception.

Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS) was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS) in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context-specificity of extinction learning.

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