Key To Treating Neurological Damage Is Harnessing The Brain's Plasticity
With an aging population susceptible to stroke, Parkinson's disease
and other neurological conditions, and military personnel returning
from Iraq and Afghanistan with serious limb injuries, the need for
strategies that treat complex neurological impairments has never been
greater.
One tack being pursued by neuroscientists and
engineers is the development of "smart" neural prostheses. These
devices are intended to restore function, through electrical
stimulation, to damaged motor neural circuits - the long, slender
fibers that conduct neurochemical messages between nerve cells in the
brain and spinal cord.
It is the rapid-fire transmission of messages between nerve cells that
prompts the body's movements, leading the hand to whisk away a fly, the
leg to stretch, the head to turn. And it is disruption of these
messages that leads to impairment, including paralysis, staggered gaits
and other forms of motor dysfunction.
Simple forms of neural prostheses -- some external, some implantable --
have been developed over the last four decades to treat loss of
hearing, bladder control and respiration. And recent advances have led
to the development of some "smart" neural prostheses, which engage
higher levels of brain function.
However, significant challenges remain in developing ever-more precise
implanted neural interfaces that operate at the cellular level and that
will provide even greater precision and fidelity in restoring function.
Harnessing the brain's "plasticity"
To truly harness the capacity of neural prostheses to treat complex
damage of the nervous system, the devices must be designed to exploit
the brain's "plasticity," or capacity for change, says Michael
Merzenich, PhD, UCSF Francis A. Sooy Professor of Otolaryngology and a
member of the Keck Center for Integrative Neuroscience at UCSF.
Merzenich's pioneering studies over three decades have revealed the
capacity of the brain to rewire itself in response to new conditions,
even during adulthood and aging. And in developing the first neural
prosthesis - the cochlear implant, in the early 1980s -- and software
programs for language and learning disabilities in the mid 1990s - he
has demonstrated that the brain has the capacity to actively engage in
a remediation, or retraining, process.
"The brain is amazingly adaptive," says Merzenich. "Our early studies
developing the cochlear implant showed that the brain can take crude
electrical inputs and interpret them and create new constructs," he
says.
"But our studies showed that the brain wants to receive this
information in certain forms. Information delivered from the interface
of a device has to be adequate for the brain to extract enough
information to reestablish control."
As neural prosthetics involve extracting neurological information from
the higher levels of the brain, and transmitting it back to a critical
nerve center in an unfamiliar form, he says, they should engage the
brain in this process.
"The success with any complicated prosthetic device relates as much to
how the brain adjusts to it, accepts it and controls its use as it does
to the device itself. If we can figure out how to engage the brain to
do its part it can make a merely adequate neural prosthetic device work
marvelously."
Merzenich presented a talk, "The role of plasticity in the nervous
system in neural prosthetics," at the AAAS symposium "Smart
prosthetics: Interfaces to the nervous system help restore
independence" Friday, Feb. 16, 2007).
Neural prostheses can be "smart" in various ways, says Merzenich. They
can: be smart in and of themselves, by operating "intelligently" adapt
to the brain tissue environment in which they are introduced be
designed to grow in their utility as the brain is trained to take
advantage of them
In all cases, he says, devices should be organized to engage the brain
in ways that "enable plasticity and promote plasticity," such as by:
delivering plasticity-enabling chemicals providing a body/brain/device
interface that maximizes the potential for plastic adaptation applying
stimuli in forms that effectively induce plastic change enabling the
implementation of an intensive training program that makes the most out
of the device
Alternative forms of plasticity-based training
Notably, Merzenich's own current research focuses not on developing
neural prosthetics, but rather on developing intensive plasticity-based
mental and physical training programs. His targets are schizophrenia,
bipolar disorder, functional losses in normal aging, mild cognitive
impairment, Alzheimer's disease, acquired movement disorders, autism,
and learning, language and reading impairments in children.
"We are trying to see how far we can drive the brain in corrective directions by intensive training without a device," he says.
In these cases, the neural circuits at play are those that receive
sensory inputs - smell, touch, taste, sound and sight - support memory
and cognition, and orchestrate behaviors.
Merzenich's ongoing studies involving the use of software to accelerate
the speed at which children with language and learning disabilities
process sound suggest he's on track. (His patented findings led to his
founding in 1996, with Paula Tallal of Rutgers University, Scientific
Learning, a therapeutic software company in Oakland, California.)
And numerous clinical trials targeting the other neurological
conditions are producing encouraging results. A clinical trial for
schizophrenia, underway at UCSF and Yale, aims to drive misdirected
neural circuitry in a normal direction, though cognitive therapy,
perceptual training, movement control, response control.
The results of this trial (supported by a second therapeutic software
company that he has co-founded, Posit Science, in San Francisco) are
"outstanding," he says, far better than those produced by the standard
medication for the disease, but at this early stage in the development
of the strategy the regimen requires a burdensome 100 hours of work.
Other clinical trials under way at UCSF involve normal and infirm aging
populations, including mild cognitive impairment and Alzheimer's
patients.
The studies on autism are the least developed, he says. "We've trained
thousands of autistics with our child training programs, but our
training tools and their effective applications are still very limited.
We know that we can provide much better help for these individuals."
Merzenich is not currently collaborating with neural stem cell
scientists, but he talks with them, and thinks about their work. With
the establishment of new neurons in the brain, he says, "brain
plasticity will have to be a substantial and necessary part of
recovery."
"These are interesting stories," he reflects. "They do not involve
trying to substitute, compensate or work around a problem. In each
case, the work involves trying to correct the processing in the
machinery with the machinery being substantially intact."
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FOR MORE INFORMATION:
Merzenich laboratory
UCSF Magazine, Dec. 2004, "Grasping Autism"
UCSF Magazine, 2003, "Faculty Entrepreneur"
Contact: Jennifer O'Brien
University of California - San Francisco
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