Background: Phantom limb pain (PLP) is a common consequence of amputation and is difficult to treat. Mirror therapy (MT), a procedure utilizing the visual recreation of movement of a lost limb by moving the intact limb in front of a mirror, has been shown to be effective in reducing PLP. However, the neural correlates of this effect are not known. Methods:We investigated the effects of daily mirror training over 4 weeks in 13 chronic PLP patients after unilateral arm amputation. Eleven participants performed hand and lip movements during a functional magnetic resonance imaging (fMRI) measurement before and after MT. The location of neural activity in primary somatosensory cortex during these tasks was used to assess brain changes related to treatment. Results: The treatment caused a significant reduction of PLP (average decrease of 27%). Treatment effects were predicted by a telescopic distortion of the phantom, with those patients who experienced a telescope profiting less from treatment. fMRI data analyses revealed a relationship between change in pain after MT and a reversal of dysfunctional cortical reorganization in primary somatosensory cortex. Pain reduction after mirror training was also related to a decrease of activity in the inferior parietal cortex (IPC). Conclusions: Experienced body appearance seems to be an important predictor of mirror treatment effectiveness. Maladaptive changes in cortical organization are reversed during mirror treatment, which also alters activity in the IPC, a region involved in painful perceptions and in the perceived relatedness to an observed limb.

In the so-called rubber hand illusion, synchronous visuotactile stimulation of a visible rubber hand together with one's own hidden hand elicits ownership experiences for the artificial limb. Recently, advanced virtual reality setups were developed to induce a virtual hand illusion (VHI). Here, we present functional imaging data from a sample of 25 healthy participants using a new device to induce the VHI in the environment of a magnetic resonance imaging (MRI) system. In order to evaluate the neuronal robustness of the illusion, we varied the degree of synchrony between visual and tactile events in five steps: in two conditions, the tactile stimulation was applied prior to visual stimulation (asynchrony of −300 ms or −600 ms), whereas in another two conditions, the tactile stimulation was applied after visual stimulation (asynchrony of +300 ms or +600 ms). In the fifth condition, tactile and visual stimulation was applied synchronously. On a subjective level, the VHI was successfully induced by synchronous visuotactile stimulation. Asynchronies between visual and tactile input of ±300 ms did not significantly diminish the vividness of illusion, whereas asynchronies of ±600 ms did. The temporal order of visual and tactile stimulation had no effect on VHI vividness. Conjunction analyses of functional MRI data across all conditions revealed significant activation in bilateral ventral premotor cortex (PMv). Further characteristic activation patterns included bilateral activity in the motion-sensitive medial superior temporal area as well as in the bilateral Rolandic operculum, suggesting their involvement in the processing of bodily awareness through the integration of visual and tactile events. A comparison of the VHI-inducing conditions with asynchronous control conditions of ±600 ms yielded significant PMv activity only contralateral to the stimulation site. These results underline the temporal limits of the induction of limb ownership related to multisensory body-related input.