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Neuronal growth in the brain may explain phantom limb syndrome

Vanderbilt University

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One of the most troubling aftereffects of an arm or leg amputation is the phantom limb syndrome, in which the person reports receiving sensations from the lost limb. Neuroscientists at Vanderbilt University report the first direct evidence that significant growth and reconnection of neurons in the brains of amputees may be at the root of this problem. The finding may ultimately lead to a treatment for phantom limb sensation. It also raises the hope that it may become possible to repair severed spinal cord injuries as scientists find ways to promote and regulate such growth.

For some time, neuroscientists have known that the phantom limb syndrome and its close companion, phantom limb pain, are an unpleasant side effect of the brain's attempt to reorganize itself following a serious disruption in the sensory information that it receives from the rest of the body. The specific regions of the brain in the cerebral cortex, thalamus and brainstem that process sensory information from the central nervous system-called somatosensory regions-are highly organized, and this organization begins to change after an amputation or major spinal cord injury.

Writing in the April 25 issue of the Proceedings of the National Academy of Science (PNAS), Assistant Professors of Psychology Neeraj Jain and Sherre L. Florence, Research Associate Hui-Xin Qi, and Psychology Professor Jon H. Kaas report that neurons in adult brains of monkeys grow and make new connections in somatosensory areas when they are massively deprived of sensory input. This strongly suggests that neuronal growth underlies the brain's reorganization following such injuries, they argue.

"We have suspected for some time that this is the case," says Jain. "But, until recently, the prevailing view has been that this kind of regenerative growth is unlikely to occur in adult brains. Hopefully, this new insight will suggest ways to stop or reverse phantom limb sensations, which tend to become more real over time."

Phantom limb syndrome is the most dramatic and mysterious example of a phenomenon called neuropathic pain, pain that does not seem to have a physical cause because it is produced by a malfunctioning nervous system. Neuropathic pain responds poorly to standard pain treatment and may get worse instead of better over time. For some people, it becomes a serious disability.

In the PNAS paper, the Vanderbilt researchers report on the results of a series of studies of the brains of adult monkeys who had sustained spinal cord injuries or had an arm amputated for therapeutic reasons.

The nerve endings in the hand, arm, face and other parts of the body are connected to the brain through the spinal cord. Sensory information from each part of the body is localized in specific areas of the brainstem, thalamus and cortex. These areas show up much more clearly in the cortex of monkeys than in those of humans because the monkey cortex is smooth, not highly convoluted like the human cortex. This has allowed researchers to map these somatosensory areas extensively and they have found that the areas connected to the face are adjacent to those connected to the hand and arm.

"The human brain is organized in much the same fashion. People who have lost an arm frequently report that when they are touched on the face they feel as if the sensation came from the missing limb," Jain says.

To determine how the brains of the monkeys with spinal cord injuries or amputated arms had changed as a result of their loss, the researchers first injected a tracer compound into their chins. When their brains were examined, the scientists found evidence for the tracer not only in the regions of the brain associated with the chin, but also in the areas associated with the hand and arm.

"This shows that the brain does not stay still, but it reacts to major changes," Jain says.

When the sensory input from part of the body suddenly vanishes, the brain reacts by reprogramming the area that is no longer serving a useful function. This is a very slow process, taking months to years. Also, the sensory loss has to be massive to trigger such changes: the brain has other ways of responding to smaller insults, such as the loss of a finger, the scientist says.

In order to determine if neuronal growth was involved in the reprogramming process, the researchers turned to the brainstem, where the somatosensory areas are much more compact. They hypothesized that even modest neuronal growth in this part of the brain would have significant consequences.

The researchers found clear evidence that neurons from the face area in the brainstem had extended axons and made a number of connections in the hand area. Although the number of such connections was limited there were enough to activate many of the neurons from the hand area, the researchers found.

"We conclude that the adult primate [central nervous system] is capable of extensive new growth and that the growth of even a few new connections can have a major impact on the functional organization of the brain," they conclude.


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