March 27, 2006
Kerry A. Dolan

Aging minds can be made young again. New insights into the brain’s ability to rearrange itself, or “plasticity,” offer hope for fighting senility, Alzheimer’s and old age.

Give Michael Merzenich 40 hours and he’ll take ten years off your brain. He says.

Merzenich, a professor of neuroscience at the University of California at San Francisco, has spent nearly his entire 35-year career divining the intricate electrophysiology of the brain. When he started his work, the reigning experts believed that our gray matter was hardwired, that once a human reaches adulthood, the mind does little more than fade away. But in the mid-1980s Merzenich started to prove the opposite, that brains are “plastic,” malleable, reprogrammable, capable of steady improvement through carefully designed exercises.

Brain plasticity, the field that Merzenich helped pioneer, is now one of the hottest areas in medicine, one with hugely positive implications for an aging society. Six years ago 450 million people, or 7% of the world’s population, were over 65. By 2050, 16% of the world’s population, nearly 1.5 billion people, will have turned 65. Almost half of Americans older than 85 develop Alzheimer’s disease.

Merzenich, whose brain has been in use for 63 years, has wisely put his research work on sale. All he asks for is 40 hours of your time and $495 for the software from Posit Science, the company he cofounded in San Francisco three years ago.

You sit in front of a computer, listen and respond to Posit’s videogamelike program, which forces you to reconstruct stories and word sequences and distinguish between rising and falling tones. When the ear is attentive and working hard, it funnels clearer information to brain centers that handle memory and perception. Merzenich claims his software enables the brain, according to cognitive testing, to perform as if it were ten years younger. While Posit Science’s claims are not yet backed up by the Food & Drug Administration, Merzenich says that in some cases it can make a 75-year-old think and remember as clearly as someone who is 55. Fifty assisted-living homes in nine states and Canada offer their residents Posit’s brain-fitness software. Posit Science has raised $23 million in venture capital from investors, including Draper Fisher Jurvetson, and already has some $1 million in sales.

Even if the FDA says Merzenich’s listening game is bunk, demand for it could be enormous. (There’s no law against selling software, so long as you don’t attach medical claims.) Brain Age: Train Your Brain in Minutes a Day, for the Nintendo (other-otc: NTDOY.PK – news – people ) ds handheld player, was one of the hottest games in Japan last year, selling 1.7 million copies. It arrives soon in the U.S. Brain Age claims to sharpen noggins with math and word puzzles.

For Merzenich, improving memory and cognition among older people is just the beginning. Tweaked versions of his brain-fitness software serve as the basis for several clinical trials Posit has under way for treating neurological diseases such as Alzheimer’s and schizophrenia. “Most people think the solutions to the problems of aging will come from drugs, stem cells, genetic manipulation or medical devices,” says Merzenich. “I believe this [work we’re doing] is where the most benefit and the best answers will come from.”

Promising work on brain plasticity is spilling out of research labs. Randolph Nudo, a former postdoctoral student in Merzenich’s lab, runs the Landon Center on Aging at the University of Kansas Medical Center. From his work with animals Nudo has found that the brain is capable of spontaneously sprouting new pathways after injury, such as that caused by a stroke. His aim is to come up with a treatment combining drugs, electrical stimulation and plasticity-based therapy to help the 700,000 Americans each year who are left with some permanent impairment from a stroke. At the University of Konstanz in Germany, neuropsychology professor Thomas Elbert uses plasticity-based therapy with stroke patients who have lost the use of a limb or their ability to speak. Nine out of ten patients working on regaining speech improved significantly in two weeks with three hours a day of training. An intriguing result–although, to be sure, many aphasics improve either on their own or with old-fashioned therapies.

Merzenich’s colleague at UCSF, professor of physical therapy Nancy Byl, has worked with guitarists and pianists whose repetitive playing has rewired their brains to make them think that two fingers are fused into one, a syndrome known as focal hand dystonia. Through simple but increasingly challenging exercises, they gradually retrain their fingers to move separately again. Psychiatrist Jeffrey Schwartz at UCLA puts patients with obsessive-compulsive disorder through a series of exercises to focus their brains on, say, working or playing music, instead of on behaviors such as obsessive hand-washing. Of the 1,000 patients he has treated, 80% have significantly improved as measured by a clinical rating scale.

Plasticity studies have also revealed that the five senses, once thought to be isolated systems in the brain, may be interchangeable. Paul Bach-y-Rita, a neuroscientist at the University of Wisconsin, stunned his colleagues with a series of experiments that show how mild charges from a ribbon of electrodes on patients’ tongues can help restore some sight to the vision-impaired.

If brain research has proven anything, it is that one of the hoariest of clichés–use it or lose it–turns out to be scientific fact. Unless neural connections are constantly challenged with new information, they will gradually weaken with age. Synapses once relied on for learning and memory produce less of the chemical neuromodulators used to ferry cognitive messages. An 80-year-old produces one-fifth the dopamine, a chemical strongly tied to attentiveness and memory, that a 20-year-old does. Without as much chemical lubrication, older brains begin failing to parse sounds or parts of conversations as they come tumbling out.

Neurological decline makes for what Merzenich calls a “noisy” brain. It’s harder to hear and remember things. “All these things are going to hell because of disuse, unless you reenergize them by exercising the brain,” he says.

Reading, going to work and navigating a busy life may be enough to maintain brain health, but lifting performance takes massive amounts of practice–learning a new language, taking regular music lessons, doing complex jigsaw puzzles–to produce enough chemicals to make synapses stronger.

Merzenich first realized how malleable the brain is in a series of experiments in the mid-1980s. He decided to teach squirrel monkeys to pluck small pieces of food from inside a plastic cup. After 1,000 tries, with ever smaller cups, the monkeys mastered the challenge. Merzenich then recorded neural activity in the monkey’s cortex, the outer portion of the cerebrum that’s responsible for information processing (and in humans, for language). He compared that data to recordings made before the monkey’s first attempt. “Everywhere I looked in the brain, I saw the machinery was changed,” he says.

Merzenich built on that work to develop, with colleagues from UCSF, one of the first practical cochlear implants for the hearing-impaired, in the late 1980s. A cochlear implant is an external tiny microphone that transmits sound to surgically implanted electrodes that stimulate still-functioning auditory nerves in the inner ear. Patients who receive a cochlear implant need between 6 and 15 months to regain their hearing to the point where they say things sound normal. During that time, says Merzenich, as the patients listen to and repeat words they hear, their brains create new activity patterns to represent pieces of meaningful speech, thus teaching themselves to hear again. “I tried to tell the engineers the miracle is not the engineering, it is in the brain,” says Merzenich. “Ultimately, it’s as if the ear is replaced.”

The possibilities of what the brain can do to heal itself are tantalizing. Merzenich envisions a day when everyone over 40 will take a brain fitness course that will enable his brain to retain information as well as it did when he was 20. That, and a wrinkle remover, would be a fountain of youth.