Phantom limb study rewires our understanding of the brain
NIH scientists and collaborators reveal the brain preserves its representation of lost limb in clinical study
NIH/Office of the Director
In a first-of-its-kind study, researchers found that the brain’s control center for a lost appendage can persist long after surgical amputation, which stands in stark contrast to longstanding theories about the brain’s ability to reorganize itself, also known as plasticity. Scientists from the National Institutes of Health (NIH) and their colleagues examined human brain activity before and after arm amputation and found that the loss of a limb does not prompt a large-scale cerebral overhaul. Published in the journal Nature Neuroscience, this study offers new insight into the mysterious phantom limb syndrome and could help guide the development of neuroprosthetics and pain treatments for people with limb loss.
A team of scientists from NIH and University College London acted on a unique window of opportunity, running MRI scans on three participants in the months prior to a planned amputation (performed for separate medical purposes) and then up to five years after.
“It’s not often you get the chance to conduct a study like this one, so we wanted to be exceedingly thorough,” said co-author Chris Baker, Ph.D., of NIH’s National Institute of Mental Health (NIMH). “We approached our data from a variety of angles and all of our results tell a consistent story.”
Different regions in the brain’s outermost layer, called the cortex, are responsible for managing specific body parts. A prevailing theory among neuroscientists has been that, when a body part is damaged or lost, the cortex will remap itself, with neighboring regions associated with intact body parts encroaching on the newly available real estate.
“For many decades, cortical remapping as a response to amputation has been a literal textbook example of brain plasticity,” Baker said.
This corner of neuroscience has not been without debate, however. One sticking point with this theory is the pervasive phantom limb syndrome, wherein a patient feels vivid, often painful, sensations in a now missing extremity.
Baker and his co-authors took this phenomenon as a hint that the brain may remember what it lost. To find out for sure, the researchers needed to do something unprecedented; compare individuals’ brain activity before and after their amputation.
After many years of actively searching for and screening patients that were already scheduled to undergo amputation, the researchers identified three participants who could help answer their questions.
Twice before the planned arm amputations, the scientists scanned participants using a special type of MRI, called functional MRI, to map brain activity triggered by the tapping of individual fingers. In the months and years following the surgeries, the researchers conducted three follow-up scans on the participants as they attempted to perform the same tasks, now with their phantom limb.
The researchers then compared brain activity in search of any major changes between pre- and post-amputation data, but it quickly became clear that there was little to no difference. Had the authors not already known when the data was collected, Baker explained, then they likely would not have been able to tell the difference between the brain maps.
The team’s analysis was not limited to human eyes, however. The authors found that a machine learning algorithm — trained to identify movements of the fingers from pre-amputation data —had no trouble distinguishing which phantom finger was being moved after amputation.
The researchers also learned that nearby brain circuits associated with lip and feet movement did not migrate into the phantom limb’s territory. Additional analyses comparing their data to scans of able-bodied controls, as well as to other studies entirely, only continued to bolster their initial impression; the brain’s representation of the lost limb endures.
These results potentially improve our understanding of how phantom limb syndrome manifests and suggest that standard phantom pain treatments — many of which assume cortical reorganization after limb loss — may be worth rethinking. According to the study’s lead author, Hunter Schone, Ph.D., who conducted this research while a graduate student at NIH, the findings could also be key in how we implement transformative brain-computer interface technologies.
"This study is a powerful reminder that even after limb loss, the brain holds onto the body, almost like it’s waiting to reconnect in some new way,” said Schone. “Now, rapidly developing brain-computer interface technologies can operate under the assumption that the brain's body map remains consistent over time. This allows us to move into the next frontier: accessing finer details of the hand map, like distinguishing the tip of the finger from the base, and restoring the rich, qualitative aspects of sensation, such as texture, shape and temperature.”
Reference: 'Stable cortical body maps before and after arm amputation.' Nature Neuroscience. 2025. DOI: 10.1038/s41593-025-02037-7.
###
About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit https://www.nimh.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit https://www.nih.gov.
Journal
Nature Neuroscience
Article Title
'Stable cortical body maps before and after arm amputation'
Article Publication Date
21-Aug-2025
Gone but not forgotten: the brain’s map of the body remains unchanged after amputation
University of Pittsburgh
image:
Brain activity maps for the hand (shown in red) and lips (blue) before the amputation (Pre1 and Pre2) and after amputation (3, 6 and 18 months post-amputation).
view moreCredit: Schone et al., Nature Neuroscience, 2025
PITTSBURGH, Aug. 21, 2025 – New research from the University of Pittsburgh School of Medicine and Cambridge University upends a long-standing belief about brain plasticity.
A study published today in Nature Neuroscience shows that the brain’s built-in “body map” remains stable even when the body undergoes drastic changes, such as the loss of a limb.
The findings have implications for the treatment of “phantom limb” pain and suggest that achieving reliable restoration of sensation and controlling robotic replacement limbs via brain-computer interfaces may be more viable in the long term than previously thought.
“This study is a powerful reminder that even after limb loss, the brain holds onto the body, waiting to reconnect,” said lead author Hunter Schone, Ph.D., postdoctoral research fellow at Pitt Rehab Neural Engineering Labs.
Foundational neuroscience research has shown that the somatosensory cortex – an area of the brain located just behind the frontal lobe – holds a rich and complex map of the body, with different regions corresponding to different body parts. The region corresponding to the hand and fingers, for example, lays next to the area representing lips, nose and eyes.
These maps are responsible for processing sensory information, such as touch, temperature and pain, as well as body position. For example, touching something hot with the hand activates a brain region just above the ear.
For decades, neuroscientists thought that losing a limb caused the brain’s body map to reorganize. Neighboring regions would invade and repurpose the brain area that previously represented the now amputated limb, the old thinking went. But this theory has long conflicted with patient experiences as many people continue to feel vivid sensations of their missing limbs. Adding to the puzzle, previous brain imaging studies have shown that when individuals who have had an amputation attempt to move their phantom limbs, their brain activation patterns closely resemble those of able-bodied individuals.
To investigate this contradiction, a team led by Tamar Makin, Ph.D., professor of cognitive neuroscience at the University of Cambridge, followed three individuals due to undergo amputation of one of their hands – the first time a study has looked at the hand and face maps of individuals both before and after amputation. Most of the work was carried out while Makin and Schone were at University College London.
Researchers asked study participants to move, or attempt moving, their fingers and purse their lips while lying in a magnetic resonance imaging (MRI) scanner. These functional MRI scans were taken prior to the planned hand amputation and then again three and six months after surgery. One participant was scanned again 18 months after amputation and a second participant five years after amputation.
Analysis of the ‘before’ and ‘after’ images revealed remarkable consistency: even with their hand now missing, the corresponding brain region activated in an almost identical manner.
“Because of our previous work, we suspected that the brain maps would be largely unchanged, but the extent to which the map of the missing limb remained intact was jaw-dropping,” Makin said. “Bearing in mind that the somatosensory cortex is responsible for interpreting what’s going on within the body, it seems astonishing that it doesn’t seem to know that the hand is no longer there.”
Researchers also confirmed that the region corresponding to the lips had not taken over the region representing the missing hand, disproving long-held assumptions that the body map can drastically reorganize.
The researchers think that the misconception comes from methodology flaws. While the brain does have a map of the body, each part of the map doesn’t support one body part exclusively – which is why activity from neighboring areas on the map could be misinterpreted as taking over.
Study findings also explain why treatment approaches focusing on restoring representation of the limb in the brain’s map have shown limited success for phantom limb pain – perhaps they tackled the wrong problem. The most promising therapies involve rethinking how the amputation surgery is performed, scientists say.
Reconnecting remaining parts of the nerves inside the residual limb to new muscle or skin could stop the nerves from sending signals that contribute to the feeling of pain back to the brain. Anecdotally, of the three participants, all of whom had substantial limb pain prior to amputation, one received a complex procedure to graft the nerves to new muscle. That participant is now pain-free.
Not only does the study challenge a long-held belief about brain plasticity, but it also suggests that restoring movement or sensation to a paralyzed limb or a prosthetic controlled by brain-computer interface – the kind of work spearheaded by researchers at Pitt Rehab Neural Engineering Labs -- is possible in the long-term.
“Now that we’ve shown these maps are stable, brain-computer interface technologies can operate under the assumption that the body map remains consistent over time,” said Schone. “This allows us to move into the next frontier: accessing finer details of the hand map, like distinguishing the tip of the finger from the base, and restoring the rich, qualitative aspects of sensation, such as texture, shape and temperature.”
Chris Baker, Ph.D., of the Laboratory of Brain & Cognition, National Institutes of Mental Health, and others contributed to this research.
Journal
Nature Neuroscience
Article Publication Date
21-Aug-2025
No comments:
Post a Comment