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| Vanderbilt University http://www.vanderbilt.edu/
Neuronal growth in the brain may explain phantom limb syndrome
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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