Network-level reorganisation of functional connectivity following arm amputation

AbstractOne of the most striking demonstrations of plasticity in the adult human brain follows peripheral injury, such as amputation. In the primary sensorimotor cortex, arm amputation results in massive local remapping of the missing hands' cortical territory. However, little is known about the consequences of sensorimotor deprivation on global brain organisation. Here, we used resting-state fMRI to identify large-scale reorganisation beyond the primary sensorimotor cortex in arm amputees, compared with two-handed controls. Specifically, we characterised changes in functional connectivity between the cortical territory of the missing hand in the primary sensorimotor cortex (‘missing hand cortex’) and two networks of interest: the sensorimotor network, which is typically strongly associated with the hand cortex, and the default mode network (DMN), which is normally dissociated from it. Functional connectivity values between the missing hand cortex and the sensorimotor network were reduced in amputees, and connectivity was weaker in individuals amputated for longer periods. Lower levels of functional coupling between the missing hand cortex and the sensorimotor network were also associated with emerged coupling of this cortex with the DMN. Our results demonstrate that plasticity following arm amputation is not restricted to local remapping occurring within the sensorimotor homunculus of the missing hand but rather produces a cascade of cortical reorganisation at a network-level scale. These findings may provide a new framework for understanding how local deprivation following amputation could elicit complex perceptual experiences of phantom sensations, such as phantom pain

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

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

Representation of Multiple Body Parts in the Missing-Hand Territory of Congenital One-Handers.

Individuals born without one hand (congenital one-handers) provide a unique model for understanding the relationship between focal reorganization in the sensorimotor cortex and everyday behavior. We previously reported that the missing hand\u27s territory of one-handers becomes utilized by its cortical neighbor (residual arm representation), depending on residual arm usage in daily life to substitute for the missing hand\u27s function [1, 2]. However, the repertoire of compensatory behaviors may involve utilization of other body parts that do not cortically neighbor the hand territory. Accordingly, the pattern of brain reorganization may be more extensive [3]. Here we studied unconstrained compensatory strategies under ecological conditions in one-handers, as well as changes in activation, connectivity, and neurochemical profile in their missing hand\u27s cortical territory. We found that compensatory behaviors in one-handers involved multiple body parts (residual arm, lips, and feet). This diversified compensatory profile was associated with large-scale cortical reorganization, regardless of cortical proximity to the hand territory. Representations of those body parts used to substitute hand function all mapped onto the cortical territory of the missing hand, as evidenced by task-based and resting-state fMRI. The missing-hand territory also exhibited reduced GABA levels, suggesting a reduction in connectional selectivity to enable the expression of diverse cortical inputs. Because the same body parts used for compensatory purposes are those showing increased representation in the missing hand\u27s territory, we suggest that the typical hand territory may not necessarily represent the hand per se, but rather any other body part that shares the functionality of the missing hand [4]

The role of peripheral input and its contribution to phantom limb pain

Following amputation, nearly all amputees report non-painful phantom phenomena and many of them suffer from chronic phantom limb pain (PLP) and residual limb pain (RLP). The etiology of PLP remains elusive and there is an ongoing debate on the role of peripheral and central mechanisms. Few studies have examined the entire somatosensory pathway from the truncated nerves to the cortex in amputees with PLP compared to those without PLP. The relationship between afferent input, somatosensory responses and the change in PLP remains unclear. The present thesis aimed at identifying whether peripheral afferent input can induce PLP and how it interacts with somatosensory processing and postamputation pain. Transcutaneous electrical nerve stimulation was applied on the truncated median nerve, the skin of the residual limb and the contralateral homologous nerve in twenty-two traumatic upper-limb amputees (12 with and 10 without PLP). Using somatosensory event-related potentials, the ascending volley was monitored through the brachial plexus, the spinal cord, the brainstem and the thalamus to the primary somatosensory cortex. There were no significant differences in the electrical potentials generated by the stimulation from the truncated nerve or the skin of the residual limb in amputees with and without PLP. Peripheral input could evoke PLP in amputees with chronic PLP (7/12), but not in amputees without a history of PLP (0/10). In addition, peripherally induced potentials through the spinal-subcortical segment were significantly positively associated with evoked RLP, but not PLP. Peripheral input can enhance PLP but seems insufficient to cause it. These findings indicate the multifactorial complexity of PLP and also suggest different mechanisms for PLP and RLP

Progressive Thinning of Visual Motion Area in Lower Limb Amputees

Accumulating evidence has indicated that amputation or deafferentation of a limb induces functional or structural reorganization in the visual areas. However, the extent of the visual areas involved after lower limb amputation remains uncertain. In this investigation, we studied 48 adult patients with unilateral lower limb amputation and 48 matched healthy controls using T1-weighted magnetic resonance imaging. Template-based regions of interest analysis was implemented to detect the changes of cortical thickness in the specific visual areas. Compared with normal controls, amputees exhibited significantly lower thickness in the V5/middle temporal (V5/MT+) visual area, as well as a trend of cortical thinning in the V3d. There was no significant difference in the other visual areas between the two groups. In addition, no significant difference of cortical thickness was found between patients with amputation at different levels. Across all amputees, correlation analyses revealed that the cortical thickness of the V5/MT+ was negatively correlated to the time since amputation. In conclusion, our findings indicate that the amputation of unilateral lower limb could induce changes in the motor-related visual cortex, and provide an update on the plasticity of the human brain after limb injury

Plasticity in the Brain after a Traumatic Brachial Plexus Injury in Adults

In this chapter, we aim to discuss the neurophysiological basis of the brain reorganization (also called plasticity) that associates with a traumatic brachial plexus injury (TBPI), as well as following the brachial plexus surgical reconstruction and its physical rehabilitation. We start by reviewing core aspects of plasticity following peripheral injuries such as amputation and TBPI as well as those associated with chronic pain conditions. Then, we present recent results collected by our team centered on physiological measurements of plasticity after TBPI. Finally, we discuss that an important limitation in the field is the lack of systematic measurement of TBPI clinical features. We finish by proposing possible future venues in the domain of brain plasticity following a TBPI

Intracortical and interhemispheric excitability changes in arm amputees: A TMS study

Objective: To evaluate cortical circuits and excitability of the motor cortex in the hemisphere contralateral to the affected (AH) and to the unaffected arm (UH), in upper limb amputees. Methods: Motor evoked potentials (MEP) were recorded in 17 subjects who had upper limb amputation: 11 trans-radial (TR) and 6 trans-humeral (TH). Motor thresholds (MT), short interval intracortical inhibition (SICI), and interhemispheric inhibition (IHI) in the available arm muscles of the stump were evaluated. Results: There was no significant difference in MT between hemispheres. SICI was preserved in TR but not in TH group. Additionally, in the TR group, the MEP amplitudes in AH were higher than in UH. A significant IHI was observed in the whole sample but not in each hemisphere or patient group. Conclusions: In our population of TR amputees, we found increased corticospinal excitability in the AH with preserved intracortical inhibition. This finding was not observed in the TH population. Significance: Understanding the changes in intracortical excitability in amputees may enhance knowledge of the functional reorganization of the brain in the post-amputation phase, bringing useful information for prosthetic rehabilitation

A neurally-interfaced hand prosthesis tuned inter-hemispheric communication

Purpose: This work investigates how a direct bidirectional connection between brain and hand prosthesis modifies the bi-hemispheric sensorimotor system devoted to the movement control of the lost limb. Hand prostheses are often unable to satisfy users' expectations, mostly due to the poor performance of their interfacing system. Neural Interfaces implanted inside nerves of the stump offer the advantage of using the bidirectional neural pathways 'naturally' dispatching signals to control proper hand actions and feed-back sensations. Learning to control a neurally-interfaced hand prosthesis and decode sensory information was previously observed to reduce the inter-hemispheric asymmetry of cortical motor maps and the clinical symptoms of phantom limb syndrome. Methods: Electroencephalographic (EEG) data was analysed using Functional Source Separation (FSS), a semi-blind method that incorporates prior knowledge about the signal of interest into data decomposition to give access to cortical patch activities. Results: Bi-hemispheric cortices showed normalization of their activity (topographical and spectral patterns) and of functional connectivity between homologous hand controlling areas, during the delivery of the motor command to the cybernetic prosthesis. Conclusions: The re-establishment of central-peripheral communication with the lost limb induced by a neurally-interfaced hand prosthesis produces beneficial plastic reorganization, not only restructuring contralateral directly-connected control areas, but also their functional balance within the bi-hemispheric system necessary for motor control