Mar. 17, 1998 The schoolchild's fantasy of learning without really paying attention might not be so farfetched after all, although recovering stroke patients, not schoolchildren, may be the most likely to ultimately benefit from a technique that could potentially make such learning possible.
In a study appearing in the March 13 issue of Science, researchers with the W. M. Keck Center for Integrative Neuroscience at the University of California San Francisco used mild electrical stimulation in mature rats to quickly bulk up brain regions that perceive and interpret sounds. They suggest that a similar strategy might help stroke patients recover lost brain functions such as speech, accurate hearing, and movement.
Michael Merzenich, PhD, the Francis A. Sooy Professor of Otolaryngology at UCSF, has for almost two decades studied the ability of the brain to learn and in so doing to form new networks of nerve connections. Merzenich pioneered the new idea, now well accepted, that adults as well as growing children exhibit these brain changes. In his research into this phenomenon, termed "brain plasticity," Merzenich has concentrated on refining maps of the brain regions that represent sensory and motor stimuli.
Both children and adults rely on plasticity to remodel the detailed connections in the brain during learning. Brain plasticity underlies the progressive development of all of our behavioral skills and abilities, Merzenich explains, and it contributes critically to the maintenance of our abilities to recognize and discriminate among incoming stimuli and to respond appropriately. Brain plasticity also contributes to progressive recovery from brain trauma such as stroke.
Thanks to brain plasticity, stroke patients often regain a substantial amount of the brain function lost after brain cells die. Exercises to regain control over movements or to recover the ability to speak or to understand language, for example, often lead to significant post-stroke recovery.
However, for psychological and neurological reasons, stroke patients often lack the will to participate vigorously in rehabilitation programs. And because brain resources are more limited after a stroke, it is often difficult for a patient to voluntarily and reliably produce normal movements or speech.
Experiments conducted by Merzenich and graduate student Michael Kilgard on the auditory cortex, the brain region responsible for sound processing, now have revealed a greater degree of brain reorganization than has ever previously been observed in mammals.
To spur accelerated brain reorganization in normal adult rats, Kilgard and Merzenich electrically stimulated an area called the nucleus basalis, which is located at the front of the brain below the cerebral cortex.
"Just as direct electrical stimulation in the basal ganglia now is used as a treatment for Parkinson's disease, stimulation of the nucleus basalis to coincide with an important-to-remember stimulus or movement might serve as a means to overcome motivational problems in the early epoch of stroke recovery," Merzenich says. "In extension, this strategy could quickly maximize the full potential for recovery of function in a damaged brain," he adds.
If we regarded all incoming stimuli as equally important, we would not learn successfully to adapt and respond to our surroundings, and normal mental development would not be possible, Merzenich points out. In a person engaged in learning, brain structures, including the relatively primitive limbus and paralimbus, help weigh the importance of stimuli to the more evolved cerebral cortex, the "thinking" brain that must further process stimuli during learning. If stimuli are deemed important, these brain structures activate the nucleus basalis.
The nucleus basalis is a gatekeeper. To bring about brain reorganization, it relays commands to the auditory cortex or other brain regions by secreting the neurotransmitter acetylcholine. The amount of this vital signaling molecule released corresponds to the speed of learning and the strength of memory, Merzenich says. Indeed, in Alzheimer's disease, treatment aims to boost the supply of acetylcholine available within the brain, without focusing on a particular brain region.
Although paying close attention to stimuli and the brain's recognition of the stimuli's behavioral importance play a critical role in activating brain regions during learning, direct stimulation of the nucleus basalis may bypass this requirement, according to Merzenich.
"Our strategy has been to trick the brain into sending a message that says 'save this,' and thereby to maximize and accelerate brain plasticity. In our experiments, electrical stimuli of the nucleus basalis clearly magnified and accelerated plasticity changes in the brain related to the progression of learning.
"These changes closely paralleled those that we previously recorded in skill-learning, except that in this case changes were especially large and rapid, and were achieved in a non-attending brain. These changes are similar to some of those that must occur during successful recovery from brain injury," he says.
To explore and map out in detail the learning-related changes in the auditory cortex, Kilgard exposed normal rats to sounds of assorted frequencies and bandwidths, about 300 times a day for 20 days.
The experimental group of 21 rats received auditory stimuli coinciding with mild electrical stimulation of the nucleus basalis. Another group received the auditory stimuli but no electrical stimulation. In the electrically stimulated rats, the auditory cortex became dramatically rearranged to respond to the specific frequencies used as sound stimuli. The researchers recorded no changes in rats that were not electrically stimulated.
Brains of humans and other mammalian species have been trained to distinguish sound frequencies, but according to Merzenich, "The extent of reorganization in the auditory cortex generated by activating the nucleus basalis that we saw in the rats is substantially larger than the reorganization that is typically observed after several months of intensive behavioral training."
The brain is a highly sophisticated, self-organizing system, but additional experiments similar to those described in the Science article should lead to much more precise brain maps and to better models for explaining how reorganization of nerve networks occurs, Merzenich says.
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