Lower limb amputees undergo long-distance plasticity in sensorimotor functional connectivity.

Amputation in adults is associated with an extensive remapping of cortical topography in primary and secondary sensorimotor areas. Here, we used tactile residual limb stimulation and 3T functional magnetic resonance imaging in humans to investigate functional connectivity changes in the sensorimotor network of patients with long-term lower limb traumatic amputations with phantom sensation, but without pain. We found a pronounced reduction of inter-hemispheric functional connectivity between homologous sensorimotor cortical regions in amputees, including the primary (S1) and secondary (S2) somatosensory areas, and primary (M1) and secondary (M2) motor areas. We additionally observed an intra-hemispheric increased functional connectivity between primary and secondary somatosensory regions, and between the primary and premotor areas, contralateral to amputation. These functional connectivity changes in specialized small-scale sensory-motor networks improve our understanding of the functional impact of lower limb amputation in the brain. Our findings in a selective group of patients with phantom limb sensations, but without pain suggest that disinhibition of neural inputs following traumatic limb amputation disrupts sensorimotor topology, unbalancing functional brain network organization. These findings step up the description of brain plasticity related with phantom sensations by showing that pain is not critical for sensorimotor network changes after peripheral injury.

Functional expansion of sensorimotor representation and structural reorganization of callosal connections in lower limb amputees.

Previous studies have indicated that amputation or deafferentation of a limb induces functional changes in sensory (S1) and motor (M1) cortices, related to phantom limb pain. However, the extent of cortical reorganization after lower limb amputation in patients with nonpainful phantom phenomena remains uncertain. In this study, we combined functional magnetic resonance (fMRI) and diffusion tensor imaging (DTI) to investigate the existence and extent of cortical and callosal plasticity in these subjects. Nine "painless" patients with lower limb amputation and nine control subjects (sex- and age-matched) underwent a 3-T MRI protocol, including fMRI with somatosensory stimulation. In amputees, we observed an expansion of activation maps of the stump in S1 and M1 of the deafferented hemisphere, spreading to neighboring regions that represent the trunk and upper limbs. We also observed that tactile stimulation of the intact foot in amputees induced a greater activation of ipsilateral S1, when compared with controls. These results demonstrate a functional remapping of S1 in lower limb amputees. However, in contrast to previous studies, these neuroplastic changes do not appear to be dependent on phantom pain but do also occur in those who reported only the presence of phantom sensation without pain. In addition, our findings indicate that amputation of a limb also induces changes in the cortical representation of the intact limb. Finally, DTI analysis showed structural changes in the corpus callosum of amputees, compatible with the hypothesis that phantom sensations may depend on inhibitory release in the sensorimotor cortex.