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

Abstract

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.

Figure 1.

Activation maps during tactile stimulation. A, C, Amputees, corrected and uncorrected data (thresholded at p < 0.05 and p < 0.001, respectively). B, D, Healthy controls, corrected and uncorrected data (thresholded at p < 0.05 and p < 0.001, respectively). Note the expansion of stump representation in S1 contralaterally, and the appearance of a sizeable tactile activation in contralateral M1 and M2. ND, nondeafferented hemisphere; D, deafferented hemisphere.

Figure 2.

Comparisons between amputees and controls. A, C, Expanded sensorimotor cortical activations of the stump in amputees when compared with control homologue; B, D, Increased and bilateral activations in response to stimuli on the intact foot of amputees when compared with control foot. A, B, p < 0.001, uncorrected; C, D, p < 0.05, corrected). Abbreviations are as defined in the legend to Figure 1.

Figure 3.

Cortical activation overlays representing amputees stump (yellow/orange) and intact foot (blue). Note the overlap on the hemisphere contralateral to amputation on deafferented hemisphere (X, Y, Z are MNI coordinates; p < 0.001, uncorrected). Abbreviations are as defined in the legend to Figure 1.

Figure 4.

Microstructure integrity of the corpus callosum. A, B, DTI voxelwise analysis of the callosal body showed increased MD (blue/light blue) bilaterally, and reduced FA values (red/yellow) in amputees compared with controls (p < 0.01, uncorrected). This finding was specific, because voxelwise whole-brain analysis for FA showed a single region on the same topography. C, Whole-brain TBSS, p < 0.05, corrected.