WASHINGTON, D.C.—Rapid changes unfold in the brain after a person's hand is amputated. Within days—and possibly even hours—neurons that once processed sensations from the palm and fingers start to shift their allegiances, beginning to fire in response to sensations in other body parts, such as the face. But a hand transplant can bring these neurons back into the fold, restoring the sense of touch nearly back to normal, according to a study presented here this week at the annual conference of the Society for Neuroscience.
To date, roughly 85 people worldwide have undergone hand replant or transplant surgery, an 8- to 10-hour procedure in which surgeons reattach the bones, muscles, nerves, blood vessels, and soft tissue between the patient's severed wrist and their own hand or one from a donor, often using a needle finer than a human hair. After surgery, studies have shown that it takes about 2 years for the peripheral nerves to regenerate, with sensation slowly creeping through the palm and into the fingertips at a rate of roughly 2 mm per day, says Scott Frey, a cognitive neuroscientist at the University of Missouri, Columbia.
Even once the nerves have regrown, the surgically attached hand remains far less sensitive to touch than the original hand once was. One potential explanation is that the brain's sensory "map" of the body—a series of cortical ridges and folds devoted to processing touch in different body parts—loses its ability to respond to the missing hand in the absence of sensory input, Frey says. If that's true, the brain may need to reorganize that sensory map once again in order to fully restore sensation.
To test that hypothesis, Frey's group and collaborators at the Christine M. Kleinert Institute in Louisville, Kentucky, recruited eight former amputees, four of whom had their own hands immediately reattached after amputation and four of whom, between 2 and 14 years after being injured, had received transplants of hands from recently deceased people. The research team measured hand recipients’ sensitivity to touch in a systematic manner. Using a plastic filament no thicker than a fishing line, the scientists gently prodded each participant’s palm on the transplanted hand in many different places, following a series of red dots previously placed on the hand by the team. The participants were not allowed to watch and wore red goggles that made it impossible to see the red ink. After each poke, they were asked to mark where they thought they had been touched with a fine yellow pen. To measure participants' accuracy, the team then measured the distance between the red and yellow dots.
Of the eight participants, four were able to locate where they had been touched almost as accurately as healthy people, who can perform this task with no more than a few millimeters of error, Frey says. The longer each patient had their transplanted or replanted hands, the more precisely they could pinpoint the sensation, showing steady progress long after the nerves in the hand had healed, Frey says. This long trajectory of improvement suggests that the brain, and not just the severed appendage, must adapt to restore sensation, he says.
Brain imaging data from prior studies, as well as new functional magnetic resonance imaging data from one of Frey's patients, a man who lost one of his hands in 1998 at age 23 and received a hand transplant 13 years later, support that hypothesis, says Francesco Petrini, a neuroengineer at the Swiss Federal Institute of Technology in Lausanne. In another new study, also presented at the meeting, Frey and colleagues found over the course of 27 months that the male patient, now 39, transitioned from abnormal, disorganized patterns of brain activity associated with the movement of his transplanted hand to more typical patterns as his control over the hand improved. The shift suggests that the brain can indeed recover from "aberrant" patterns of activity established after a severe injury, Petrini says. The work could also shed light on the neural basis of phantom limb pain—the sensation of pain in an appendage that's no longer there, he notes. In at least one transplant recipient in Frey's lab, phantom limb pain disappeared after a new hand was reattached.
Unraveling just what changes in the brain after amputation and transplant surgery will require detailed, long-term imaging studies beginning immediately after amputation, Frey notes. The fact that a person can learn to use and feel using a new hand after more than 10 years is an "extreme example" of what's possible, he says. Although damage directly to the brain is likely trickier to repair, Frey says, the new work suggests that people who have experienced spinal cord injury and stroke "may have more potential to recover than we ever thought."