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.
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
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.
The research was supported
by the National Institutes of Health and the Christopher Reeve Paralysis
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