Secret Life of the Grown-Up Brain (19 page)

So what exactly
are
they doing?

Through a complex system of math modeling, backed now with more animal data, Gage has recently developed a new and fascinating theory about newly generated brain cells. He believes that the cells are crucial for our entire lives, and are doing nothing less than “helping us make sense of the world.” In particular, he says, they “help us adapt to the new,” to fold new experiences into our existing view of the world.

“If we were spending our whole lives in this room, we would not need new brain cells,” Gage told me, gesturing toward the walls of his cluttered office. “But the new brain cells help us integrate the new with the old. Without them, we would never want anything to change because anything new would be too complicated.”

When sensory input first comes into the brain—to put all this in its simplest form—it goes to its outermost layer, the cortex. The input then travels to the hippocampus, which consolidates information, memories, and learning. The hippocampus binds the varied sensory experiences together into a sensible chunk—and then sends that back to the cortex for long-term memory storage.

But before the information even gets to the central hippocampus, it is first filtered by the gatekeeping dentate gyrus, which is thought to perform an opposite task—it breaks sensations into even smaller pieces. It is, as Gage puts it, “a pattern separator.” Brain cells in the dentate take note of subtle differences and similarities—a leaf a bit greener, tea slightly hotter. Mature brain cells in the dentate encode those minute differences and pass them on to the hippocampus.

So how do baby neurons fit into all that? Initially, Gage believed that the new cells—since they’re formed in the dentate—must somehow help it do its job, that is, break up information. But, Gage told me almost proudly, “I was really wrong.”

Instead, it now appears that new neurons may actually act to tie disparate information together—and place that information in a specific time frame. Gage now believes that new neurons help us make associations. If we hear a Beach Boys song and smell the salt from the beach, those two impressions—Beach Boys song and salt smell—will be forever tied together in time and place. In fact, the more neurogenesis you have, Gage says, “the more you link together things that are different” into a pattern that will hang together in your brain.

Our memories are notoriously unreliable, in part because we are constantly pulling up old memories and “retagging” them with new information, then restoring the memory in a modified form. Baby neurons, Gage believes, help us with that process, tying together different sensations that occur at the same time—and helping us fit the new with the old, the song we know with the sand we are sitting on.

With chronic stress, new neuron production is slowed or grinds to a halt. To explain this, Gage uses an example of a soldier in Iraq with post-traumatic stress disorder, PTSD. Imagine, Gage said, that “you have a soldier in Iraq and he is under chronic stress and therefore not producing new neurons. [Then there’s a] stark event, say, he sees his buddy’s head blown off.”

If neurogenesis were occurring, even that stark event would—when the soldier recalled it later—be
retagged
with new information and the soldier might be able to soften the memory by mixing it with more random—and gentler—everyday sensations and information before it is restored as a less upsetting memory.

“Neurogenesis links different things together and that helps us generalize experiences and rationalize them,” Gage explained. Without a stream of new neurons, Gage believes, such a memory would be stored only in mature brain cells and there it would stay—“the event would stay as the event,” as stark and real as it was.

Gage thinks this is one way that talk therapy might work. If we recall bad memories in a safer environment—and if we are not under stress and new neurons are being produced—those memories will be mingled with gentler thoughts—nice office, calm therapist, flowers on the table—and that may be what helps us make sense of—and live with—some of our most disturbing memories over time.

Gage has also developed a model of how all this might happen. In essence, when input comes into
mature
neurons, it’s encoded. But that encoding is then quickly halted by a neurotransmitter that inhibits brain activity, GABA. If the encoding were not stopped at some point, the older neuron would be constantly readjusting to new information.

But new baby neurons are set up quite differently. For the first seven days of their life, before they have formed connections with other neurons, Gage says, they are actually
excited
by GABA, rather than shut down. That means that as they are born, they will soak up some GABA from nearby mature neurons, and get excited at the very nanosecond that older neurons are both being activated and then shutting down.

As a result, the new baby neurons encode information from all their neighboring mature neurons—salt, sand, song—tying it all together in time in a mixed memory that stays with us until it resurfaces and is remixed and restored again. The new neurons have time-stamped memories.

This idea is still unproven, of course, but it is—perhaps not surprisingly, given its source—an elegant and compelling one.

Gage believes this may be the way that neurogenesis can alleviate depression, helping us maintain interest in our world. When we get sick we often become immobile, and with “that lethargy we stop producing new neurons, leaving us both less cognitively aware and depressed,” he says.

After all, he adds, “what is depression but a lack of interest in the new, the feeling ‘Is that all there is?’ We need new neurons to help us adapt to the new, to put it in context. Sometimes to get excited about things, you have to recognize how this cool new thing is like other cool things we knew about in the past. Neurogenesis helps us do that.”

In Gage’s view, in fact, the whole system might have developed to
allow
us to deal with the new. While this, he admits, is getting into the often fuzzy area of evolutionary theory, again, it is such an interesting thought that it seems worth mentioning.

“Just think about it,” Gage said. “As soon as the primitives walked out toward the savanna, the walking would have stimulated the production of new neurons that they would need to prepare for their new environment, to adapt to it and integrate it with their old environment.”

There is little question that in general neurogenesis declines with age, sometimes starting in middle age. But we also now know that, as Gage puts it, “the cells are there and we can reactivate” the process.

But we need to get up out of our chairs. Indeed, Gage is such a believer in the power of exercise to keep those baby brain cells blooming that he runs “a lot” so he will then be able to play squash “with the young guys” four or five times a week. He and his wife try to walk whenever they can. And he recommends we all at least try to do
something
for thirty minutes a day—to get that dentate gyrus up and pumping and get our dose of fresh new neurons.

“This is not about finding a drug,” he said. “This is a lifestyle thing. The drug companies don’t like to hear that, but we can affect what happens in our brains with what we do.”

There’s also emerging evidence that exercise helps the brain in more global ways as well. It’s still uncertain how much exercise a brain needs, or, as one scientist said to me: “In exercise, we don’t yet know the dosage.” By and large it appears that anything that increases your heart rate helps.

But that doesn’t mean you have to sign up for the New York City Marathon. And for that bit of good news, we can thank Art Kramer, the neuroscientist at the University of Illinois at Urbana-Champaign. Kramer is interested in the exercise-brain connection not only as a top scientist but also as a middle-aged man with a worrisome family history. Always a bit of a jock, Kramer boxed as a young man, then moved on to running and track, and now tries to get onto the stationary bike when he can. He also plays a game of squash that smashes twenty-year-olds.

Still, his father died young, and if he did not take drugs to control it, his cholesterol would be about 400. Like most of us reaching the middle of our lives, Kramer is concerned. Is he doing enough? Should he exercise more? Does any of this make any difference?

“It doesn’t matter how long we can live, it matters how long we can keep going functionally,” Kramer pointed out, quite logically, when I spoke with him recently. And so what are we to do to keep functioning well, and prove, with solid science, that what we’re doing really works? So far, Kramer, doing his part, has found encouraging news about fairly moderate levels of exercise.

In one of his latest studies, published in 2006, for instance, Kramer and his colleagues found that those over age sixty who did regular stints of aerobic exercise for six months had increased brain volumes in their frontal lobes’ gray matter, which includes the neurons, and in the white matter of their corpus callosum, the nerve bridge that connects right brain to left brain—and whose age-linked deterioration has been associated with slower thinking.

The exercise in this case was a fairly mundane program of brisk walking. Those who spent about an hour walking around a gym three times a week—at a pace of three miles an hour—had brain volumes of people three years younger.

“Significant increases in brain volume, in both gray and white matter regions, were found as a function of fitness training for the older adults who participated in the aerobic fitness training but not for the older adults who participated in the stretching and toning [nonaerobic] control group,” Kramer concluded in the study in the
Journal of Gerontology.

“These results suggest that cardiovascular fitness is associated with the sparing of brain tissue in aging humans. Furthermore, these results suggest a strong biological basis for the role of aerobic fitness in maintaining and enhancing central nervous system health and cognitive function in older adults.”

That impressive study came after a stream of similar research by Kramer and his colleagues. One study in 2003 found that those over age sixty who exercised regularly—again, that meant aerobic exercise such as running or walking quickly—had less brain tissue loss than non-exercisers. And in a study published in 1999 in the prominent science journal
Nature,
Kramer reported that a group of 124 relatively unfit people over age sixty, after walking rapidly (17.7 minutes per mile) for forty-five minutes three days a week (and especially those who managed to get up to a mile-long loop around the university at a good clip of 16 minutes per mile) were much better at complex tests, in particular those that involved “task switching,” the same frontal-lobe challenge that faced Mark Moss’s middle-aged monkeys. For the humans in Kramer’s study, this test also involved rapidly answering questions such as “Is this an odd or even number?”

The exercisers were also better at focusing and ignoring irrelevant information. Such frontal-lobe executive functions, as we’ve said, are crucial for a whole range of everyday activities, especially when we have to do two things at once.

Kramer’s studies also mirror solid tests in animals over recent years, including one at Oregon Health & Science University that found that monkeys that ran on a treadmill for five days a week for twenty weeks had much higher blood volume in their brains’ capillaries than sedentary monkeys—and it was the oldest and least fit monkeys that had the biggest gains. As Kramer says: “We know from all this research that there are a few good things for the brain—and one is exercise.”

Kramer says that he, too, is still not completely sure how all this happens in the brain and is now probing deeper to see if he can find more clues. It could be the dentate gyrus and it could be a combination of effects in the brain. “What all this precisely means on a molecular level we just don’t know but we can speculate,” Kramer says.

“We want to know what the nature of the volume change is,” he told me. “Is it the growth of blood vessels or the number of synapses or white matter or gray matter? We just don’t know yet.”

When I last spoke with him, he had decided to extend his human walkers’ study and then take their blood to see what genes are modulated and “who does better and why.” He will also check the participants’ blood for the presence of markers for inflammation linked to cardiovascular problems and possibly Alzheimer’s (a number of conditions, including obesity and smoking, are now thought to produce a kind of low level of chronic inflammation in the body, which over time may wear down cell defenses and lead to disease).

If he could, Kramer would love to do a spinal tap on volunteers and look for nerve growth factor, the Miracle-Gro, in the nervous system of study participants, but that’s not something one does with living humans. “We can’t get a slice of their hippocampuses, either,” he said, a bit sadly. Still, the thought that something as simple as exercise can have real benefits for our brains is just the kind of optimistic thought that may very well appeal to our positive-seeking middle-aged brains.

And it’s an idea that now makes perfect sense to people like Kevin Bukowski. Having ignored his brain for years—much like the rest of us—he is now giving it much more respect. Like most of us in middle age, Bukowski is busy. He has a demanding job, assisting and coordinating scientific trials at a major medical center. He has a seven-year-old daughter. He is taking care of his mother. But at age forty-seven, he feels somehow sharper and “calmer . . . there is a maturity factor there now.

“I just feel now at my age that I am doing a lot. But I feel I can really handle it all now and that makes me feel good. It is kind of surprising but here I am at middle age and it’s not bad; in fact, I feel more secure knowing I can deal with all this.”

But he is also now convinced that to maintain all that, he has to stay on the treadmill. And so he is setting out to do what he can. He is training his middle-aged body and brain—for a triathlon.