Brain (re)organisation following amputation: Implications for phantom limb pain

Tamar R Makin,Herta Flor

doi:10.1016/j.neuroimage.2020.116943

Abstract

Following arm amputation the region that represented the missing hand in primary somatosensory cortex (S1) becomes deprived of its primary input, resulting in changed boundaries of the S1 body map. This remapping process has been termed ‘reorganisation’ and has been attributed to multiple mechanisms, including increased expression of previously masked inputs. In a maladaptive plasticity model, such reorganisation has been associated with phantom limb pain (PLP). Brain activity associated with phantom hand movements is also correlated with PLP, suggesting that preserved limb functional representation may serve as a complementary process. Here we review some of the most recent evidence for the potential drivers and consequences of brain (re)organisation following amputation, based on human neuroimaging. We emphasise other perceptual and behavioural factors consequential to arm amputation, such as non-painful phantom sensations, perceived limb ownership, intact hand compensatory behaviour or prosthesis use, which have also been related to both cortical changes and PLP. We also discuss new findings based on interventions designed to alter the brain representation of the phantom limb, including augmented/virtual reality applications and brain computer interfaces. These studies point to a close interaction of sensory changes and alterations in brain regions involved in body representation, pain processing and motor control. Finally, we review recent evidence based on methodological advances such as high field neuroimaging and multivariate techniques that provide new opportunities to interrogate somatosensory representations in the missing hand cortical territory. Collectively, this research highlights the need to consider potential contributions of additional brain mechanisms, beyond S1 remapping, and the dynamic interplay of contextual factors with brain changes for understanding and alleviating PLP.

Highlights

Three decades ago it was first demonstrated that the sensory and motor maps in the adult brain can change as a consequence of injury as well as in response to training and stimulation (Jenkins et al, 1990; Kaas et al, 1990; Merzenich et al, 1983; Rajan et al, 1993; Sanes et al, 1988), and that these organisational changes are not limited to early brain development
Alterations in the organisation of sensory maps have been associated with a number of perceptual and behavioural changes, with many of them viewed as maladaptive, ranging from tinnitus to focal dystonia and phantom limb pain (PLP)
Concluding remarks Our review shows that there is no simple relationship between somatosensory map reorganisation, PLP and preserved hand representation

Summary

Introduction

Three decades ago it was first demonstrated that the sensory and motor maps in the adult brain can change as a consequence of injury as well as in response to training and stimulation (Jenkins et al, 1990; Kaas et al, 1990; Merzenich et al, 1983; Rajan et al, 1993; Sanes et al, 1988), and that these organisational changes are not limited to early brain development. We review recent evidence on map changes in the primary somatosensory cortex (S1), and its association to PLP, based on neuroimaging studies in humans. Research characterising lower face representation in unilateral arm amputees has not identified clear facial activity in the missing hand cortex (Kikkert et al, 2018; Makin et al, 2013b) (Figure 2C).

Results

Conclusion