March 1, 2009
San Francisco Magazine
Gordy Slack

The brain-fitness revolution is now in full swing, thanks to a trailblazing UCSF neuroscientist and superachievers of all ages who will pay big money to pump up their cerebral cortexes. Science writer Gordy Slack travels to the west’s first brain gym to answer the question on everyone’s mind: Can you really train yourself to remember more and think smarter?

If a couple of creative thinkers could figure out how to take a drooping middle-aged brain and turn it back into something young and buff, they’d have themselves one golden goose. That’s exactly what Jan Zivic and Lisa Schoonerman are hoping to do with VibrantBrains, on Sacramento Street, a high-tech health club for people who want to tone the three pounds of fat that matter most-the ones between their ears.

The co-owners-San Francisco residents with brain-revitalization stories of their own to tell-envision VibrantBrains as a community center where people can hang out, exercise their gray matter, and learn how the latest neuroscience can translate into healthier practices. So far, several hundred people have joined, at $60 a month, and many regularly stop in several times a week. On a recent visit to the club, I met Bob, a typical member. He retired at 50 after much success in the financial real estate world, but he feels the need to get better at remembering names and matching them to faces. Dancing around the blank spots in his memory is putting a crimp in his social life, he says. Johann, age 32, who works in information technology at Visa, showed up at the club with his 34-year-old friend Cassandra: The two just want to strengthen their memories because “smarter is better,” they say.

I fit right in with this crowd. I’m not afraid of a falling butt, thinning hair, and lengthening teeth; I’m prepared to live with those indignities. What wakes me up in a cold sweat is the fear of losing the titles of my favorite movies and books, of forgetting my phone number, the name of the first girl I kissed, or the way to San Jose. Like so many of my boomerish friends, who will not go gently into that nursing-home night, I dread the prospect of losing my self.

“Vibrant brains are sexy brains” is a motto of the cheerful Pacific Heights storefront, which opened nearly 16 months ago in hopes of cashing in on what’s become known as the neuroplasticity revolution-a scientific sea change that was largely launched right here in the Bay Area and has altered the very idea of what it means to get old. Scientists used to think we were stuck for­ever with the brains we took out of childhood, and that mental decline was as inevitable as the sunset. But in the past couple of decades, with the help of advances in imaging technology and a slew of animal and human studies, they’ve learned that the brain is constantly changing, growing new neurons, and forging new connections among old neurons to improve its function. As a result, people who want to boost their chances of staying sharp into old age have been snarfing down blueberries, hitting the gym, and engaging in activities, like solving crossword puzzles or learning to dance, that have been shown to keep the brain well oiled and tuned.

If brain training is the new fitness craze, then the guru behind it-its Jack LaLanne, if you will-is Michael Merzenich, a neuroscientist at UCSF’s W.M. Keck Foundation Center for Integrative Neuroscience, which has become ground zero for neuroplasticity research. Merzenich didn’t exactly discover the brain’s ability to rewire, but he conducted some of the most influential early experiments to prove it beyond a doubt. Schoonerman, 41, a former publishing executive, came across his work about five years ago, when her mother was diagnosed with dementia and she was looking for ways to avoid a similar fate. Zivic, a 66-year-old former schoolteacher, had suffered from a head injury and benefited from brain-training exercises during her rehab. The idea behind VibrantBrains was to put Merzenich’s insights to work both for themselves and for a Bay Area clientele that seemed primed for the pitch: folks who are intellect-obsessed, as well as early adopters of all manner of self-improvement trends, from yoga and Zen to organic food and Botox. (Jack LaLanne, in fact, opened his first gym in Oakland in 1936, kicking off the physical-fitness boom.) Members attend classes and lectures, but two pieces of software developed by Merzenich’s company, Posit Science, form the centerpiece-or at least the most interesting part-of the VibrantBrains “workout.”

The Brain Fitness Program is a hearing-based regimen that may have come to your attention during a KQED pledge drive-viewers who donate $360 or more receive a copy of the software in return. InSight is a newer, visual workout, but both have been designed to stretch, realign, and tone specific cognitive functions. In Brain Fitness, for example, you listen to a series of sounds that turn either up (bweep) or down (bwoop) and try to distinguish between them-which apparently tunes up your brain’s ability to process audio input from the world. With InSight, you play a game in which you track the movements of birds around the screen, in theory raising your ability to process visual input. Members use other software as well, including Nintendo’s popular Brain Age games. But Merzenich’s programs lend VibrantBrains some scientific cachet-enough that people are willing to pay $350 to use each one for up to 50 hours, either in addition to their basic membership fee or on a drop-in basis.

It certainly sounds like a painless way to knock a few years off the old cortex. But the million-dollar question is: Does playing computer games, even scientifically designed ones, actually translate to better brain function in the real world? Merzenich says yes, and he has a lot to gain from getting the public to agree. With the success of his plasticity panacea would come fame, prestige, good karma, and potentially lots of money. In 2005, the hungry-for-market-share brain-fitness industry was already worth $100 million, and it more than doubled over the next two years. Riding this wave, Schoonerman and Zivic opened a second center in January, at the Peninsula Jewish Community Center in Foster City.

But many of Merzenich’s own colleagues at the Keck Center think he promises too much-or at least too much, too soon. The brain theories behind his software make a lot of sense, they say, but there just aren’t enough studies yet to show that it actually works in real people. And while it’s clear that they like and respect him a lot, they’re distinctly uncomfortable even discussing his role as a salesman/scientist. Frankly, it makes me uncomfortable, too: It is extraordinary for a scientist of Merzenich’s stature to be hawking product.

Those same colleagues, though, are doing research that makes you see the stunning potential of Merzenich’s basic ideas and the VibrantBrains venture. They mostly study animals, which is why they resist drawing specific conclusions about how to maintain and fix human brains. But they’re looking at some of the same neurological processes that Merzenich claims his software is juicing. So perhaps he’s just the ultimate early adopter, with VibrantBrains as his inadvertent lab.

Michael Merzenich has all the enthusiasm you’d want in the man who may offer the greatest hope for keeping us mentally spry into our golden years. He recently retired from UCSF, where he had been a professor since the early 1970s, but he still has a lab at the Keck Center and continues to work alongside its elite team of neuroscientists. At 66, he’s thick-bodied and white-haired, and he lumbers along a bit like a bear, but in many ways he remains the young Turk he was when he conducted his original plasticity experiments. He never skirts a good academic fight and is always spurring his ivory-tower colleagues to find real-world applications for their research-sooner rather than later. He rises early and retires late: In addition to putting in hours at his UCSF lab, Posit Science, and his other company, Scientific Learning (which makes brain-training software for kids), Merzenich writes a blog, keeps bees, makes wine, tends an orchard, and gardens at his Santa Rosa ranch.

When Merzenich first started doing brain research in the late ’60s, it was becoming well established that young, developing brains undergo a great deal of change during what are known as “critical periods.” By the end of these periods, the dogma held, brains would assume the structure they would keep for the rest of their lives-except, of course, when they traveled the one-way road of decline that comes with aging, disease, or traumatic injury. Merzenich didn’t set out to overthrow this paradigm. In fact, he assumed, as the rest of the neurobiology establishment did, that the adult brain is a fixed entity.

But then his experiments on monkeys changed everything. In the most famous one, Merzenich and two colleagues severed the nerves that brought information from the tips of the monkeys’ index fingers and thumbs to their somatosensory cortexes, the part of the brain that responds to touch. He then swapped those nerves and let them heal, so that the nerve going from the index finger went instead to the part of the brain assigned to the thumb, and vice versa. According to the old fixed-wiring model, the brain should have been very confused about where the information was coming from-and should have remained that way. But the monkeys’ brains quickly adapted, rededicating the parts of the cortex to reading information from the new spots on the ends of their fingers.

It was Merzenich’s eureka moment. “Suddenly, my whole landscape shifted,” he says. “Either this was unbelievable plasticity, or there were more nerves doing the same job-but that seemed impossibly redundant.” He spent the next few years testing these theories in other animals, too, and concluded that their brains were indeed rewiring neurons to restore an orderly map of their hands. Around this time, Merzenich was also doing work that convinced him of the human brain’s plasticity. He and a team were developing one of the first cochlear implants, a device that would transmit sound waves directly to the part of the brain that normally gets signals from the ear. When deaf patients received the implants, they were able to discern real words in what had formerly been incoherent sounds.

It’s hard now to appreciate how radical this idea was, says Merzenich, but consider that in 1981, the Swedish neuroscientist Torsten N. Wiesel won a Nobel Prize for his work on the brain’s critical periods. So the brain science establishment snubbed Merzenich’s research-and Merzenich himself-for as long as it could. “I was a lonely guy around then,” he says. He knew he was right, and he knew that the brain’s potential to radically rewire would be enormously significant. (He now calls it the most important neuroscientific discovery of the 20th century.)

The tide began to turn by the mid-’80s, though, as Merzenich produced a new generation of teachers and students who were not yet steeped in the fixed-brain dogma, and Wiesel and others conducted experiments of their own. Eventually, even Wiesel acknowledged that he had overstated his opposition to the notion of plasticity.

Thanks largely to Merzenich, the word neuroplasticity is everywhere these days. He has more than 200 scientific papers to his name, and his work has been touted in the New York Times, Newsweek, the Wall Street Journal, Time, Forbes, Discover, and Vogue. He appeared in two documentaries about neuroplasticity that have aired during the PBS fundraising drives (and he cowrote one of them); he was the celebrity guest on the programs’ pledge breaks; and he is utterly unabashed in his claims about the potential of neuroplasticity to address everything from garden-variety aging to Alzheimer’s disease, autism, depression, and even schizophrenia. One way his mental workout accomplishes this, Merzenich says, is by helping neurons develop the right links in the brain. There are a hundred billion of these neurological building blocks in your head, and their electrochemical business pretty much runs everything in your body and your brain. Neurons that fire at the same time form relationships, he explains, and under certain con­ditions, those relationships become long-lasting. In other words, neurons that fire together wire together.

Think of it as the reinforcing nature of simultaneous orgasm, multiplied billions of times every second. Neurons that “excite” together want to do it again, and with each simultaneous firing, they find it easier to do so. It’s how the brain keeps refining its processes over time. So, if you want to develop new skills, like learning to tango or speak Italian-or just remember the name of a new friend-you need to get new sets of neurons to orgasm together repeatedly.

But plasticity is a two-way street. “It can be good or it can be harmful,” Merzenich says. The emergence of an obsessive-compulsive behavior, like incessant hand washing, or even just a bad habit, like biting your nails or chain smoking, shows the negative side of plasticity in action. So does the loss of our powers of attention and memory, which people begin to experience around age 30 (yes, 30!). And assaults other than aging can accelerate that process. The person who eats poorly, never exercises, and spends all his spare time in front of the TV is turning himself into a mental couch potato, whatever his age.

Merzenich claims that both positive and negative plasticity can be encouraged. “I could destroy your ability to understand what I say by training you in a certain way,” he says, “or I could improve that ability and make you more intelligent.” The latter, of course, is exactly what Merzenich aims to do with Brain Fitness and InSight: coax the right neurons to fire together in a way that promotes better perception, faster recall, and sharper mental acuity. Schoonerman, of VibrantBrains, is so convinced that Merzenich is onto something that she exercises her own brain every day. She’s done both Brain Fitness and InSight, and she regularly participates in other VibrantBrains activities. “It’s not just about making myself smarter and sharper now,” she says. “It’s also about investing in my ‘cognitive reserve,’ which I can draw on in years to come.”

I, on the other hand, made it through about 10 hours of Brain Fitness, then gave up (you’re supposed to do 40). I found the production values as clunky as the aesthetic is corny, and trying to distinguish those low beeps from the high ones felt too much like lifting weights or running on a treadmill-that is, tedious as hell. And unlike weight lifting, where you start feeling stronger within a few sessions, I didn’t feel my mental muscles growing. I just got antsy and couldn’t stop thinking about everything else I had to do.

But others have felt smarter. A year and a half ago, Brain Fitness was the subject of a much touted study of 524 men and women, aged 65 and older, that was overseen by psychologists at three California universities and the Mayo Clinic in Minnesota. Half the group did the Brain Fitness program for at least an hour a day, five days a week; the other half watched educational DVDs. After 8 to 10 weeks, the groups took a variety of learning and memory tests, including one in which they were asked to recall details from a story or words from a list. The tests showed that the memories of those in the Brain Fitness group improved, on average, about a decade’s worth compared with those in the other group, who just did the watching. The people who did Brain Fitness also reported that they felt as if their memories were sharper by the end of the study. The study was designed and paid for by Merzenich’s company (though independent scientists administered it), an arrangement that suggests at least a hint of conflict of interest. You could also argue that the activities of the two groups weren’t similar enough to form an entirely fair point of comparison. Nevertheless, spending 40 to 50 hours playing challenging games convinced some it was worth the effort. And even if some of that effect was placebo, so what? says Carol Dweck, a psychologist at Stanford. She’s done studies designed specifically to test this placebo effect and found that people who truly believe they can improve their memories perform much better on most tasks than those who don’t.

Even if no actual physical change occurs in the brain, a decade’s worth of memory recovery seems like a bargain at $700 (the cost of using both Merzenich’s programs for up to 50 hours apiece at VibrantBrains). They can cost up to $900 on the open market, but once you have your own copies, you can use the software for as long as you want, since it adjusts and gets harder as you get better at it. (You can use it more often at VibrantBrains, too, though you’ll have to pay $350, minus a multiple-use discount, each time.)

But whatever you do, don’t expect medical miracles. Glenn Smith, a Mayo Clinic expert on Alzheimer’s disease and one of the Brain Fitness study’s principal investigators, is concerned that people are using such software as a hedge against Alzheimer’s. “There’s no scientific evidence that they delay the disease,” he says. On the other hand, he adds, “If you don’t have signs of early dementia, these activities may help you on specific memory tests.”

The last thing on the minds of the Keck Center neuroscientists is whether or not Merzenich’s software really works. In the lab, with nothing to sell and nothing in particular to prove, they’re hard at work studying the nuances of how the brain functions-what makes it rigid and what makes it plastic. For all of them, one factor is key: the power of mental focus. “Parts of your brain are engaged in a constant competition to see which ones can create lasting changes,” says Michael Stryker, another Keck scientist and a giant among plasticians. “And where you focus your attention,” he says, “helps determine where the positive plasticity takes hold.”

Stryker is a balding 61-year-old with a bushy, salt-and-pepper mustache and a defiant though not unfriendly face. On both his wall and his computer desktop are pictures of a remote valley in the California desert, where he spent two years at Deep Springs College. The day I met him, he was moving slowly and deliberately, somewhat like a tortoise from his former environment.

Stryker’s work builds on Merzenich’s studies about how neurons link up with other neurons, zeroing in on the role played by an animal’s ability to focus. “Studies suggest that about 5 percent of a neuron’s connections change each week,” he says. If these connections are reinforced, they become part of the neuron’s basic repertoire and represent opportunities for improvement. If they aren’t, they’re broken. Stryker has found that certain brain chemicals play a critical role in determining which outcome is more likely, and that they’re sparked by the act of paying attention.

My favorite experiments about this phenomenon took place just down the hall from Stryker, in the lab of Allison Doupe, a calm, attentive neuroscientist with a raspy voice that tends to speed up as she talks, betraying her excitement about her work. She studies the brains of adolescent and adult zebra finches-beautiful, finger-length Australian songbirds-looking specifically at the neurological processes that regulate how they learn songs: what makes them open to new ones, and what makes them stick with what they know.

Doupe describes what happens to the brains of finches that are first taught to sing by tape recorders. “Their songs are OK, and their development seems pretty normal on the surface,” says Doupe. “But when you take one of those recorder-trained birds and stick another bird in there singing a live song, the trained bird is highly stimulated and attentive, and his critical period can actually reopen.” In other words, when the bird’s attention is grabbed by something that matters-another living bird-he’s suddenly able to learn new things.

Michael Brainard also works with adult finches at the Keck Center, but his research focuses more on specific brain mechanisms that contribute to learning. (The name Michael is to the Keck lab what Bruce is to Monty Python’s philosophy department at the University of Walamaloo. “G’day, Michael.” “G’day, Michael. Have you met Allison?” “No, Michael, I haven’t, but will she mind if we call her Michael, just to avoid confusion?”) Birds flitter to and fro around Mount Sutro, which is visible through a bank of windows, but you won’t see any in the lab-until Brainard opens one of his 20 or so college refrigerator-size boxes and reveals a Bengalese finch. The chipper little guy is wearing earphones.

By fitting his birds with earbuds and distorting the way they hear their own voices, Brainard is able to condition the birds to change the songs they sing. “They practice the song they know, and then I introduce distortions that make it sound a little off,” he explains. “They respond by making the pitch a little higher or lower to match the distortion.”

But at a certain point, they stop responding. By way of illustration, Brainard plays recordings of weirdly errant songs that he has guided some of his finches to sing. If he distorts the pitch too much, the bird won’t deviate from its melody. As Doupe told me, the young brain, still at its peak of plasticity, can make broad changes in short periods of time. The older brain, on the other hand, can still make big changes, but “only one baby step at a time. Try for too big a step, and it just won’t move,” she says.

So here’s another brain-change principle: If you try to go too fast-say, by learning Vietnamese in a one-month immersion class when you’re 65, or trying to solve differential equations before you’ve mastered long division-you’re wasting your time. That’s a concept woven into his software, Merzenich claims, which is calibrated to encourage incremental change.

Across town, at the new Mission Bay annex of the Keck Center, is the only neuroscientist in this group, besides Merzenich, who actually studies human beings: Adam Gazzaley. Like Doupe, he examines the role of attention in the brain’s ability to form memories-and he is more willing to make a direct connection between insights from his lab and real-world treatments. Gazzaley recently compared the attention of two different age groups of big-brained bipeds. Members of the first group were 19 to 30 years old; the second, 60 to 77. Gazzaley showed all the volunteers two landscape pictures and two pictures of human faces, then instructed them to focus only on the faces. While they were looking, he took MRI scans of their brains. The young group’s MRIs revealed much more activity in the part of their brains that handles facial recognition than in the part that works on landscapes. But the older group was unable to ignore the landscapes and make the shift.

The ability to focus clearly on specific things, Gazzaley explains, is one reason why younger people have an easier time remembering details. He calls this “top-down modulation,” and it’s great for remembering things like where you parked your car in Chinatown before you sprinted to meet a friend for dinner. But the focused spotlight of top-down modulation is always competing with the diffusing houselights of “bottom-up modulation,” which casts a broader, gentler glow on all things in its reach. Both approaches have their advantages and their drawbacks. If you’re all top-down, says Gazzaley, you march past your friends on the street without even seeing them, lost in thought about where you’re headed; and if you’re all bottom-up, you just stand on the corner with your mouth agape as the world fills your consciousness with myriad details.

Merzenich sees older people’s shift away from top-down attention as a kind of negative plasticity, a product of disuse. Because these individuals don’t challenge themselves as much to learn new things, they grow less adept at achieving that kind of focus. One point that all the Keck scientists agree on is that the brain is plastic, and that even a muddled one can sharpen itself by strengthening its ability to focus. But do Brain Fitness and InSight encourage that more than, for example, learning to play chess or taking up haiku? “Certainly,” says Merzenich. “Perhaps,” replies Gazzaley. “Who knows?” asks Doupe. “Hmmm,” muses Brainard.

If Merzenich is frustrated with his circumspect colleagues, he doesn’t show it; he seems to reserve his fire for the neuroscience field in general. It pains him that the revolution he spurred has not been fully realized-that so few scientists are willing to turn lab results into prescription-even though plasticity studies generate thousands of papers each year, and members of the old guard of naysayers are either dead, retired, or full of crow. That’s partly why he takes his work to the public through his businesses, and why he is so supportive of a place like VibrantBrains, where owners Zivic and Schoonerman could not be more committed to the cause.

For Zivic, a form of brain training actually restored her ability to function. “Ten years ago, I was in a small car, and I was hit by a big truck,” she says. A brain hemorrhage caused strokelike symptoms, and before she knew it, Zivic couldn’t even find her way back to her own hospital room. It took her years of difficult brain rehab to get back to anything like her old mental self, she says-rehab that involved, among other things, rudimentary computer exercises that were similar to the ones used at VibrantBrains. “I’m here to tell you,” she declares, “this stuff works.”

But even if a snappier, sexier brain is all you’re after, VibrantBrains may well be worth a look. Sarah Young, a 35-year-old who works in financial real estate, has been a member since the club opened, and she loves the buzz she gets from her several-times-a-week visits. “I feel sharper, more energetic,” she says. “It’s the feeling you get after a good workout at the gym.” She also swears it’s become easier for her to remember the names of clients and to make a connection between two films by the same director.

Sooner or later, we may still have to consult the existentialists, the bible, our roshis, or our rabbis to deal with the inevitable system failure that occurs as we age. But in the meantime, it’s worth taking to heart the freedom that scientists say we have to influence the course of our neurological futures. We’re not just riding on a rudderless, paddleless raft down the river of mental decline. Even if we can’t change the river’s flow, Merzenich and his colleagues are telling us we can steer better and row harder. We can even paddle upstream against the current for a while, or seek out little backwaters to lengthen the trip.

What I love about this notion is its efficiency-the idea that what’s best for keeping our brains intact is, by and large, the same thing we’d want to do with our potent brains in the first place: learn new things, challenge ourselves, lead lives that allow us to stay engaged with the world around us. How does doing mental calisthenics on a computer factor into that? It could well work, as long as you’re doing it because it’s a challenge, not because you think it’s more effective than anything else.

For me, though, as the day grows longer, I think I’ll try learning zydeco dancing and Italian. Luckily for my brain, the new economy means retirement is out of the question, so I might also consider writing a book about neuroscience. Now, that would keep my neurons firing and hooking up.