Following amputation brain reroutes the function to the remaining limb


Fans of the blockbuster movie “Iron Man 3” might remember the characters step inside the digital projection of a “big brain” and watch as groups of neurons are “lit up” along the brain’s neural “map” in response to physical touch.

Now, much like that scene, researchers at the University of Missouri have discovered a new insight into how the complex neural map of the human brain operates.

Similar findings have been previously reported in animal studies, but this is one of the first studies where such a result has been documented in people.

“When a person touches something with their right hand, a specific ‘hand area’ in the left side of the brain lights up,” said Scott Frey, the Miller Family Chair in Cognitive Neuroscience in the Department of Psychological Sciences.

“A similar, but opposite reaction happens with the left hand.

But when someone loses a hand, we found both ‘hand areas’ of the brain — left and right — become dedicated to the remaining healthy hand. This is a striking example of functional reorganization or the plasticity of the human brain.”

Researchers used functional MRI (fMRI) at the MU Brain Imaging Center to scan the brains of 48 people — 19 of whom had lost a hand.

They created a computer-controlled, air-based system to deliver light touch to the hands and face.

Functional MRI scans are similar to traditional MRI scans but are sensitive to tiny changes in blood oxygenation levels in the brain that occur when areas of the brain are processing information.

The researchers saw in their scans that when the brain is deprived of input from a lost hand, it reorganizes its neural map and reroutes those functions to the remaining hand.

this shows brain scans

These are results of a functional MRI on the whole brain. Areas of the brain exhibiting statistically significant effects are displayed in color. The image is credited to University of Missouri.

Frey said this discovery could help scientists and medical professionals better understand the underlying mechanisms behind the brain’s plasticity — the ability for the brain to adapt to changing conditions — when a traumatic bodily injury occurs, such as with veterans returning from injury on the military battlefield.

“We can think of the areas of the brain that process sensations from our bodies as being organized like a map with separate territories devoted to specific body regions such as the hands, face, or feet,” said Frey, who is also the director of the Rehabilitation Neuroscience Laboratory at MU, a joint venture between the MU College of Arts and Science and the MU School of Medicine.

“We have long known that injuries such amputation or spinal cord damage change the organization of this map.

If you lose a hand, for instance, then the associated ‘hand area’ may be partially taken over by neighboring functions in the map involved in processing sensations of the arm or face.

This is a form of ‘brain plasticity.’ This work demonstrates that such plasticity also occurs across great distances between the left and right hemispheres of the brain.”

Researchers said additional work is underway to determine how and whether these changes impact how amputees experience sensations, including pain.

The scientists hope their findings might also help inform efforts to develop prostheses that can provide users with the experience of touch.

Funding: Funding was provided by a grant from the National Institutes of Health and a grant from the U.S. Department of Defense. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

With increases in traffic accidents, malignant diseases and natural disasters, the number of lower-limb amputees (LLAs) is increasing (Barbosa et al., 2016).

LLAs have difficulties in motor control and coordination, especially in the early stages following amputation because of the major structural asymmetry arising from the amputation (Molina Rueda et al., 2013).

With a period of rehabilitation and the application of a prosthesis, the functional status of amputees is gradually restored (Soares et al., 2009Rusaw and Ramstrand, 2011), which could induce functional reorganization in the sensory and motor areas of the brain.

One of the most prominent consequences of limb amputation concerns the functional reorganization in the primary somatosensory and motor cortices.

Several studies in non-human primates have demonstrated that the loss of an upper limb results in functional reorganization of the primary sensorimotor cortex (S1M1) (Kaas et al., 1983Merzenich et al., 1983Pons et al., 1991Jain et al., 2008).

In humans, such reorganization after limb amputation has also been observed, and this has been interpreted as a form of maladaptive plasticity in these cortices that is triggered by the loss of sensory inputs (MacIver et al., 2008) or voluntary control (Raffin et al., 2016).

However, most of the studies dealing with cortical reorganization included only patients that have undergone upper-limb amputation.

The patterns of brain reorganization might vary significantly in LLAs due to differentiation in the functions and representations between the upper and lower limbs.

A remapping of the cortical topography was observed in LLAs, with an expansion of activation maps of the stump in the S1M1 of the deafferent hemisphere, spreading to neighboring regions that represent the trunk and upper limbs (Simões et al., 2012), which indicates that lower-limb amputation also induces neuroplastic changes in the S1M1.

Although emphasis has been given to the sensorimotor cortex in the functional reorganization following limb amputation, the contribution of subcortical structures cannot be overlooked (Curt et al., 2011).

The cerebellum and the basal ganglia are groups of subcortical nuclei with long-established roles in motor control (Hoshi et al., 2005Bostan and Strick, 2010Bostan et al., 2013).

Both of these structures are important subcortical structures in the motor circuit, and perform distinct functional operations such as the initiation and execution of voluntary movement (Groenewegen, 2003).

However, only a few studies have examined functional and structural alterations of these subcortical nuclei following lower-limb amputation. A fMRI study found increased activation in the contralateral basal ganglia during motor imagery of the amputated toes in LLAs (Romero-Romo et al., 2010).

A voxel-based morphometric (VBM) study found decreased gray matter volume in the bilateral cerebellum in LLAs (Di Vita et al., 2018). Structural and functional abnormalities of the thalamus have also been found following peripheral deafferentation.

 Garraghty and Kaas (1991) found functional reorganization in the thalamus of adult monkeys after peripheral nerve injury. Draganski et al., (2006) showed a significant decrease in the gray matter volume of the thalamus following limb amputation. Results from a study by Jones and Pons (1998) demonstrated that long-standing limb amputation can cause structural reorganization of the thalamus.

These findings implied that these movement-related subcortical structures are possibly involved in functional reorganization in LLAs. However, how these subcortical structures work during the process of functional reorganization following lower-limb amputation has not yet been elucidated.

In recent years, functional connectivity (FC) analyses have provided invaluable approaches for studying the human brain in healthy (Smith et al., 20092012Yeo et al., 2011) and diseased groups (Napadow et al., 2010Collignon et al., 2013Rocca et al., 2014) on the brain-network level. Among the varied functional neuroimaging techniques, resting-state fMRI (rs-fMRI) is a promising tool for mapping FC.

This method does not require the participants to accomplish complex sensorimotor task during functional neuroimaging acquisition. Resting-state FC analysis has been used in studying the network-level reorganization of FC following arm amputation and has found reduced FC between the cortex associated with the missing hand and the sensorimotor network in amputees (Makin et al., 2015).

Regarding lower-limb amputation, one diffusion tensor imaging (DTI) study observed that the mean fractional anisotropy (FA) value of the fibers in region II of the corpus callosum, which connects the premotor area and supplementary motor area (SMA), was significantly reduced, demonstrating that structural connectivity between the bilateral sensorimotor cortex was reorganized in LLAs (Li et al., 2017). To our knowledge, there have been no prior studies of changes in FC in LLAs. Thus, resting-state FC analysis may offer a new way to explore functional network reorganization in the brain after lower-limb amputation.

Besides the regions within the sensorimotor network, abnormal brain reorganization has been found in other regions (Preißler et al., 2013Jiang et al., 2015Makin et al., 2015). Specifically, Preißler et al. (2013) found that upper-limb amputees were associated with anatomical alterations in parts of the brain region that belong to dorsal visual stream.

Such plasticity was hypothesized to reflect a brain adaptation process to new movement and coordination patterns in operating hand prosthesis. Meanwhile, Jiang et al. (2015) found a significantly lower thickness in the motor-related visual cortex after lower-limb amputation which was presumably related to the degeneration of biological motion perception or tactile motion processing.

Additionally, Makin et al. (2015) found that in upper-limb amputees, the missing hand cortex gradually became functionally coupling with the default mode network (DMN) and decoupling with the sensorimotor network over the time since amputation. Such network-level cortical reorganization was supposed to be related to complex perceptual experiences of phantom sensations.

Thus we conclude that limb amputation may cause more extensive brain reorganization beyond the changes that occur in the sensorimotor network.

According to the research mentioned above, amputation may result in extensive structural and functional reorganization in the brain.

However, very little is known about large-scale network-level reorganization of FC following lower-limb amputation, which requires further investigation. Here, we take these ideas further by characterizing intra-network (within the sensorimotor network) and inter-network (between S1M1 and other parts of the brain) changes following lower-limb amputation using resting-state FC analysis.

We hypothesized that the LLAs would show abnormal FC within and beyond the sensorimotor network compared with the healthy controls (HCs); meanwhile, when considering the long duration of recovery for some amputees, we also hypothesized that FC in the LLAs may present progressive changes in relation to the time since amputation.

To test these hypotheses, we compared the regions of interest (ROI)-wise connectivity within the sensorimotor network and the seed-based whole-brain FC of the sensorimotor network between the LLAs and HCs. Further, we investigated the relationship between FC and time since amputation in LLAs.

University of Missouri-Columbia
Media Contacts:
Eric Stann – University of Missouri-Columbia
Image Source:
The image is credited to University of Missouri.

Original Research: Closed access
“Interhemispheric transfer of post-amputation cortical plasticity within the human somatosensory cortex”. Scott Frey et al.
NeuroImage doi:10.1016/j.neuroimage.2019.116291.


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