Lower limb amputees undergo long-distance plasticity in sensorimotor functional connectivity

Abstract

Amputation in adults is associated with an extensive remapping of cortical topography in primary and secondary sensorimotor areas. Here, we used tactile residual limb stimulation and 3T functional magnetic resonance imaging in humans to investigate functional connectivity changes in the sensorimotor network of patients with long-term lower limb traumatic amputations with phantom sensation, but without pain. We found a pronounced reduction of inter-hemispheric functional connectivity between homologous sensorimotor cortical regions in amputees, including the primary (S1) and secondary (S2) somatosensory areas, and primary (M1) and secondary (M2) motor areas. We additionally observed an intra-hemispheric increased functional connectivity between primary and secondary somatosensory regions, and between the primary and premotor areas, contralateral to amputation. These functional connectivity changes in specialized small-scale sensory-motor networks improve our understanding of the functional impact of lower limb amputation in the brain. Our findings in a selective group of patients with phantom limb sensations, but without pain suggest that disinhibition of neural inputs following traumatic limb amputation disrupts sensorimotor topology, unbalancing functional brain network organization. These findings step up the description of brain plasticity related with phantom sensations by showing that pain is not critical for sensorimotor network changes after peripheral injury.

Seven Properties of Self-Organization in the Human Brain

“…It is assumed that too much plasticity will result in previously learnt data being constantly forgotten, whereas too much stability will hinder self-reinforced learning at the synaptic level, yet, the exact functional relationship between changes in synaptic efficacy and structural plasticity is not entirely understood. It has been proposed that a continuum exists between the two, such that changes in synaptic efficacy precede and instruct structural changes, however, in other cases, structural changes may occur without any stimulation producing an initial change in local synaptic efficiency [55], which points towards the critical functional role of long-range connections [56] within the from-local-to-global functional organization of self-organizing systems.…”

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

“…For example, most studies defined S1 and M1 based on anatomical atlases (e.g. automated anatomical labelling 32 , MINC 33 , Harvard–Oxford 25 ). Other studies defined regions of interest (ROIs) for S1 and M1 based on overlap of functional activity ( conjunction ) between groups of controls and amputees 13 , 15 .…”

<p>Hyperalgesia and Reduced Offset Analgesia During Spinal Anesthesia</p>

“…Deafferentation or the traumatic or anesthetic disruption of afferent input from the peripheral to the central nervous system results in cortical, subcortical or brainstem reorganization and alters neuronal connectivity. [1][2][3][4][5][6][7] Using resting-state functional magnetic resonance imaging (fMRI), we previously showed that short-term spinal anesthesia-induced deafferentation is associated with functional connectivity changes in the thalamus in relation to the thalamocortical network and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. 5 In general, deafferentation causes adaptive plasticity, such as cortical expansion of brain areas adjacent to deafferentated areas, due to a rebalancing of excitatory and inhibitory neuronal modulators involved in plasticity.…”

“…While some studies show improved acuity of motor or sensory function related to cortical plasticity, 3,8 it is well known that deafferentation may additionally have negative behavioral effects related to maladaptive plasticity, as may occur in traumatic deafferentation, including phantom limb pain or pain after spinal cord injury. 1,2,6 Spinal and epidural anesthesia are forms of short-term deafferentation. There is evidence that both types of neuraxial blockade are associated with sensory distortions or pain.…”