Interhemispheric transfer of post-amputation cortical plasticity within the human somatosensory cortex

Abstract

Animal models reveal that deafferenting forelimb injuries precipitate reorganization in both contralateral and ipsilateral somatosensory cortices. The functional significance and duration of these effects are unknown, and it is unclear whether they also occur in injured humans. We delivered cutaneous stimulation during functional magnetic resonance imaging (fMRI) to map the sensory cortical representation of the intact hand and lower face in a group of chronic, unilateral, upper extremity amputees (N = 19) and healthy matched controls (N = 29). Amputees exhibited greater activity than controls within the deafferented former sensory hand territory (S1f) during stimulation of the intact hand, but not of the lower face. Despite this cortical reorganization, amputees did not differ from controls in tactile acuity on their intact hands. S1f responses during hand stimulation were unrelated to tactile acuity, pain, prosthesis usage, or time since amputation. These effects appeared specific to the deafferented somatosensory modality, as fMRI visual mapping paradigm failed to detect any differences between groups. We conclude that S1f becomes responsive to cutaneous stimulation of the intact hand of amputees, and that this modality-specific reorganizational change persists for many years, if not indefinitely. The functional relevance of these changes, if any, remains unknown.

Figure 1.. Apparatus and design.

Cutaneous stimulation was applied to the left or right lower face (A) or tips of the second and fourth digits of the left or right hand (B). These digits were selected to include median, radial and ulnar nerve distributions. Sample timeline of events from a single run for controls (C) and amputees (D).

Figure 2.. Results of whole-brain fMRI analyses.

Areas exhibiting statistically significant effects are displayed on semi-inflated surface rendering (left) and accompanying axial slices (right): (A) Areas exhibiting significant increases for stimulation of the intact “left” hand in amputees relative to baseline. (B) Areas exhibiting significant increases for stimulation of the “left” hand in controls relative to baseline. (C) Areas exhibiting significantly greater activity during stimulation of the intact “left” hand in amputees compared to the comparable hand in controls. This difference includes S1f and extends caudally across the lateral convexity of the postcentral sulcus, and into the supramarginal gyrus. See text for details.

Figure 3.. ROI results.

L-S1 (A) and R-S1 (B) hand ROIs are functionally defined by data from controls. Slices show ROI locations and MNI coordinates. L-S1 is the estimated former sensory hand area of amputees (S1_f). Boxplots show percent BOLD signal change (%-BSC) values per condition per ROI for amputees and controls, with individual-level data as open circles. Filled circles indicate left-hand amputees (after these data are left-right flipped). The line within boxplots indicates the median, the upper and lower edges indicate the third and first quartiles, respectively, and the error bars indicate the maximum and minimum data points. Grey shading indicates the 95% confidence intervals of the group mean. The * indicates a statistically significant group difference, p < 0.001.

Figure 4.. ROI activity and tactile acuity, phantom limb pain, and years since amputation.

GOT thresholds (A/B), average phantom limb pain (C/D), and years since amputation (E/F) are shown as a function of percent BOLD signal change (%-BSC) per S1f and S1i ROIs during stimulation of the intact hand of amputees, and for comparison, the left hand of controls (A/B only). Regression lines are shown with 95% confidence intervals.

Figure 5.. ROI results by amputation level.

Boxplots show percent BOLD signal change (%-BSC) values corresponding to stimulation of the intact hand per ROI (A/B) for above and below elbow amputees, respectively, with individual-level data as open circles. The line within boxplots indicates the median, the upper and lower edges indicate the third and first quartiles, respectively, and the error bars indicate the maximum and minimum data points. The * indicates a statistically significant group difference, p < 0.05.