PNAS

Handy. Years after a double hand transplant, this patient can perform complex tasks, including repairing an electrical wire.

Double Amputees Shed Light on Brain's Flexibility

How does the brain cope when, several years after having both hands amputated, a person suddenly receives two new hands? Surprisingly well, it seems. In a study out today, researchers provide the most detailed picture yet of how the brain reorganizes itself to accommodate foreign appendages. And in a result that they are still trying to explain, the scientists found that in two such double-hand transplants, the left hand reconnected with the brain more quickly than did the right.

A group of French and Australian doctors performed the world's first hand transplant in 1998, and the same team repeated the feat on both hands 2 years later. Studies carried out since then indicate that the brain reorganizes itself in response to these new appendages. However, the work looked only at coarse hand movements that mainly used nontransplanted muscles.

Wanting to learn more about how the brain copes with donor hands, cognitive neuroscientist Angela Sirigu of the French National Research Agency in Lyon and colleagues looked at two right-handed men, one age 20 and the other 42, who recently had left and right hand transplants to replace hands amputated following work injuries 3 to 4 years ago. After extensive training, both men are now able to perform a range of complex tasks with the foreign appendages, from dialing a phone number to using tools such as screwdrivers and pliers to rewire an electrical outlet.

The researchers found that both men's motor cortexes--the region of the brain responsible for carrying out muscle movement--had reorganized themselves in response to the new hands. After a person loses a hand, the region of the motor cortex that controls hand movement shrinks and rewires itself to control the upper arm, a property called plasticity. But when Sirigu and colleagues used transcranial magnetic stimulation--a technique that employs magnetic fields to excite neurons in the brain--to stimulate specific fragments of the motor cortex, they found that the "hand areas" in the motor cortex of both men had reassumed their original "wiring." The finding, reported online today in the Proceedings of the National Academy of Sciences, shows that the brain is capable of reorganizing in quite a dramatic way in response to hand transplants, says Sirigu.

But one result baffled Sirigu's team: In both men, the left donor hand was able to connect with the brain more quickly than was the right. In the younger patient, the left hand took 10 months, and the right 26 months, to work efficiently with the brain, leaving the patient with the left as his dominant hand when performing complex tasks after transplantation. In the other patient, the left hand was able to perform complex tasks after 51 months, whereas the right still lagged behind. The results could mean that because the right hand is more dominant in these men, its representation in the brain is more rigid than the left--and thus the brain is less able to rewire control of it--says co-author Claudia Vargas, a neuroscientist who recently moved to the Federal University of Rio de Janeiro in Brazil.

Still, Sirigu cautions that it's too soon to make any concrete conclusions. The difference could result from something as simple as the way in which the surgeon reattached each hand, she says, noting that a different surgeon worked on each hand. In addition, both patients had been using advanced prosthetic right hands controlled by the nerves in the amputation stump. The motor cortex may have reorganized to accommodate the prosthetic, and this may have slowed its ability to then accept the new donor hand, says Sirigu.

Neuroscientists hail the new work as yet another demonstration of the brain's remarkable plasticity. "The results are important because they show that even after several years without a hand to control, the brain retrains the circuits necessary to control one," says neurophysiologist John Rothwell of the Institute of Neurology at University College London. And that could have "important clinical applications for rehabilitation," says neuroscientist Vilayanur Ramachandran of the University of California, San Diego.

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