Phantom Limb Study Challenges Long-Held Views of Brain Plasticity

A groundbreaking study from the National Institutes of Health (NIH) and collaborators reveals that the brain retains its representation of a lost limb long after amputation—challenging decades of assumptions about neural plasticity. Published in Nature Neuroscience, the findings could reshape understanding of phantom limb syndrome and inform future development of neuroprosthetics and pain therapies for individuals with limb loss.

Traditionally, neuroscientists believed that when a body part is lost, the cortex—the brain’s outer layer responsible for controlling movement—reorganizes itself. The prevailing theory suggested that surrounding brain regions, such as those controlling lips or feet, would migrate into the cortical space left vacant by the missing limb.

“For many decades, cortical remapping as a response to amputation has been a literal textbook example of brain plasticity,” said study co-author Chris Baker, Ph.D., of NIH’s National Institute of Mental Health (NIMH).

But this new research paints a different picture. Instead of widespread reorganization, the brain’s map of the missing limb appears to persist largely unchanged—possibly explaining why many amputees experience vivid sensations in their absent limb, a phenomenon known as phantom limb syndrome.

The team, led by Graeme Woodworth, MD, of the University of Maryland School of Medicine, and colleagues at University College London, had a rare opportunity to test this hypothesis. Over several years, they identified three participants scheduled for medical amputations and conducted MRI scans both before and after surgery.

Prior to amputation, each participant underwent two functional MRI (fMRI) sessions where finger tapping was used to map cortical activity. After surgery, the participants returned for up to three follow-up scans over a five-year period, this time attempting the same movements using their phantom hand.

The results were striking. Brain activity maps taken after amputation were nearly indistinguishable from those recorded beforehand. “Had we not already known when the data was collected, we likely would not have been able to tell the difference,” Baker explained.

The consistency was further validated using machine learning. An algorithm trained on pre-amputation data successfully identified which phantom finger participants attempted to move in the post-amputation scans, demonstrating that the neural code for finger movement remained intact.

Moreover, neighboring circuits controlling lips or feet did not encroach on the phantom hand’s cortical territory. Comparisons with healthy controls and other published studies reinforced the conclusion: the brain’s representation of the missing limb endures over time.

“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 lead author Hunter Schone, Ph.D., who conducted the work while at NIH. He noted that the findings could accelerate the development of brain-computer interfaces (BCIs), which could exploit the preserved limb maps to restore movement and even nuanced sensations such as texture, shape, and temperature.

The discovery also raises questions about current treatments for phantom pain, many of which are based on the assumption that cortical reorganization drives the condition. Rethinking those approaches in light of this study could open new therapeutic possibilities.

“We approached our data from a variety of angles and all of our results tell a consistent story,” Baker said. “The brain’s body map is more stable than we once believed.”