Phantom Limbs and Brain Plasticity in Amputees

Abstract

Phantom sensations are experienced by almost every person who has lost their hand in adulthood. This mysterious phenomenon spans the full range of bodily sensations, including the sense of touch, temperature, movement, and even the sense of wetness. For a majority of upper-limb amputees, these sensations will also be at times unpleasant, painful, and for some even excruciating to the point of debilitating, causing a serious clinical problem, termed phantom limb pain (PLP). Considering the sensory organs (the receptors in the skin, muscle or tendon) are physically missing, in order to understand the origins of phantom sensations and pain the potential causes must be studied at the level of the nervous system, and the brain in particular. This raises the question of what happens to a fully developed part of the brain that becomes functionally redundant (e.g. the sensorimotor hand area after arm amputation). Relatedly, what happens to the brain representation of a body part that becomes overused (e.g. the intact hand, on which most amputees heavily rely for completing daily tasks)? Classical studies in animals show that the brain territory in primary somatosensory cortex (S1) that was “freed up” due to input loss (hereafter deprivation) becomes activated by other body part representations, those neighboring the deprived cortex. If neural resources in the deprived hand area get redistributed to facilitate the representation of other body parts following amputation, how does this process relate to persistent phantom sensation arising from the amputated hand? Subsequent work in humans, mostly with noninvasive neuroimaging and brain stimulation techniques, have expanded on the initial observations of cortical remapping in two important ways. First, research with humans allows us to study the perceptual consequence of remapping, particularly with regards to phantom sensations and pain. Second, by considering the various compensatory strategies amputees adopt in order to account for their disability, including overuse of their intact hand and learning to use an artificial limb, use-dependent plasticity can also be studied in amputees, as well as its relationship to deprivation-triggered plasticity. Both of these topics are of great clinical value, as these could inform clinicians how to treat PLP, and how to facilitate rehabilitation and prosthesis usage in particular. Moreover, research in humans provides new insight into the role of remapping and persistent representation in facilitating (or hindering) the realization of emerging technologies for artificial limb devices, with special emphasis on the role of embodiment. Together, this research affords a more comprehensive outlook at the functional consequences of cortical remapping in amputees’ primary sensorimotor cortex.

Transcutaneous Spinal Cord Stimulation to Reduce Phantom Limb Pain in People with a Transtibial Amputation

“…Following peripheral nerve injury or limb amputation, the primary sensory and motor cortices undergo remapping, where the affected regions have persistent but suppressed cortical representation (Makin et al, 2020; Wesselink et al, 2019). The extent of this cortical remapping correlates with the intensity of PLP, where more severe PLP results in more extensive remapping (Gunduz et al, 2020).…”

“…Several mechanisms have been proposed to explain cortical remapping, including axonal sprouting in the primary somatosensory cortex (Florence et al, 1998), thalamus, and brainstem (Jones and Pons, 1998), the expansion of the receptive field in the thalamus (Davis et al, 1998;Jain et al, 2008), unmasking or disinhibition of inhibitory connections between somatotopic regions (Li et al, 2014), or unmasking of overlapping receptive fields in the primary somatosensory cortex (Wesselink et al, 2022). Evidence to support the preservation, but suppression, of the canonical topographic cortical map following a limb amputation stems from studies where the nervous system was stimulated and sensory percepts were evoked (Makin et al, 2020). Sensory percepts have been evoked in the missing limbs of people with amputations using electrical stimulation of the peripheral nerves, (Anani and Körner, 1979;Charkhkar et al, 2018;Clippinger et al, 1982;D'Anna et al, 2017;Raspopovic et al, 2014), spinal cord (Chandrasekaran et al, 2020;Nanivadekar et al, 2022aNanivadekar et al, , 2022b, and thalamus (Davis et al, 1998), as well as magnetic stimulation of the contralateral primary motor cortex (Bestmann et al, 2006;Reilly and Sirigu, 2008).…”

Identifying Users’ Needs to Design and Manufacture 3D-Printed Upper Limb Sockets: A Survey-Based Study

“…This reported breathability problem is in accordance with previous observations made by several authors [6,47], who claimed that more attention must be paid by researchers, clinicians and manufacturers of prosthetic components to the heat-related biomechanics of soft tissues, a proper fabrication technique, better material selection and the introduction of efficient thermoregulatory systems [6]. Nevertheless, it must be taken into account that wetness may sometimes be altered by phantom pain, which has a high prevalence in adult upper limb amputees and implies sensations like an altered sense of touch, altered temperature and even the sense of wetness [48].…”

Neural Bypasses: Literature Review and Future Directions in Developing Artificial Neural Connections

“…Studies of humans with prosthetic limbs have shown neural representations that are specific to their prosthetic rather than biological limb, as seen when the prosthetic differs from an actual limb in form (such as a hook for a hand) [97]. Studies of primate amputations have shown that the primary motor representation of body parts are plastic following finger amputations, as neural regions are redistributed to non-amputated fingers [98]. This neuroplasticity within neural regions has thus far limited rather than facilitated the advancement of neural bypasses.…”