Assessment of cortical reorganization and preserved function in phantom limb pain: a methodological perspective

Jamila Andoh,Martin Diers,Susanne Becker,Christopher Milde,Simon Desch,Robin Bekrater-Bodmann,Herta Flor,Xaver Fuchs,Jörg Trojan

doi:10.1038/s41598-020-68206-9

Abstract

Phantom limb pain (PLP) has been associated with reorganization in primary somatosensory cortex (S1) and preserved S1 function. Here we examined if methodological differences in the assessment of cortical representations might explain these findings. We used functional magnetic resonance imaging during a virtual reality movement task, analogous to the classical mirror box task, in twenty amputees with and without PLP and twenty matched healthy controls. We assessed the relationship between task-related activation maxima and PLP intensity in S1 and motor cortex (M1) in individually-defined or group-conjoint regions of interest (ROI) (overlap of task-related activation between the groups). We also measured cortical distances between both locations and correlated them with PLP intensity. Amputees compared to controls showed significantly increased activation in M1, S1 and S1M1 unrelated to PLP. Neural activity in M1 was positively related to PLP intensity in amputees with PLP when a group-conjoint ROI was chosen. The location of activation maxima differed between groups in S1 and M1. Cortical distance measures were unrelated to PLP. These findings suggest that sensory and motor maps differentially relate to PLP and that methodological differences might explain discrepant findings in the literature.

Highlights

Phantom limb pain (PLP) has been associated with reorganization in primary somatosensory cortex (S1) and preserved S1 function
Examining the PLP group only, we found a significant positive relationship between PLP intensity and %BSC based on ROIconj in S1M1 (r = 0.75, p = 0.01, pFDR = 0.03, 95% CI [0.23, 0.94]) as well as M1 (r = 0.78, p = 0.006, pFDR = 0.03, 95% CI [0.33, 0.95]), but not for S1 (r = 0.54, p = 0.11, 95% CI [− 0.13, 0.87]), see Fig. 2b
We found that the consideration of individual variability in the location of S1M1 dispersed the correlation between S1M1 activity and PLP intensity, emphasizing the importance of considering inter-individual variability in the representation of the phantom limb

Summary

Introduction

Phantom limb pain (PLP) has been associated with reorganization in primary somatosensory cortex (S1) and preserved S1 function. Flor et al.[10] applied tactile stimuli to the lips and the fingers of unilateral upper limb amputees and found a displacement of the lip representation towards the hand representation in S1, which was related to the magnitude of PLP, such that the closer the lip was to the hand somatosensory area, the more intense the PLP. This finding was replicated using tasks in the motor domain implementing either executed or imagined phantom hand movements. These findings seem in opposition to those reported by Makin et al.[13], who found a positive association between PLP and activation in the sensorimotor (S1M1) phantom cortex

Methods

Results

Discussion

Conclusion