SAN FRANCISCO - 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.
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.
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"
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.
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.
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
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.
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
Merzenich will present 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" (8:30-11:30 a.m., Friday, Feb. 16, 2007).
Neural prostheses can be "smart" in various ways, says Merzenich. They can:
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
all cases, he says, devices should be organized to engage the brain in
ways that "enable plasticity and promote plasticity," such as by:
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
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.
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.
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."
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."
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."
University of California-San Francisco. February 2007.