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Learning

Grow Your Brain Cells

WHEN THE STUDENTS in Titusville or in Naperville go for a mile run in gym, they are more prepared to learn in their other classes: their senses are heightened; their focus and mood are improved; they’re less fidgety and tense; and they feel more motivated and invigorated. The same goes for adults, in the classroom of life. What allows us to absorb the material is where the revolutionary new science comes into play. In addition to priming our state of mind, exercise influences learning directly, at the cellular level, improving the brain’s potential to log in and process new information.

Darwin taught us that learning is the survival mechanism we use to adapt to constantly changing environments. Inside the microenvironment of the brain, that means forging new connections between cells to relay information. When we learn something, whether it’s a French word or a salsa step, cells morph in order to encode that information; the memory physically becomes part of the brain. As a theory, this idea has been around for more than a century, but only recently has it been borne out in the lab. What we now know is that the brain is flexible, or plastic in the parlance of neuroscientists — more Play-Doh than porcelain. It is an adaptable organ that can be molded by input in much the same way as a muscle can be sculpted by lifting barbells. The more you use it, the stronger and more flexible it becomes.

The concept of plasticity is fundamental to understanding how the brain works and how exercise optimizes brain function by fostering that quality. Everything we do and think and feel is governed by how our brain cells, or neurons, connect to one another. What most people think of as psychological makeup is rooted in the biology of these connections. Likewise, our thoughts and behavior and environment reflect back on our neurons, influencing the pattern of connections. Far from being hardwired, as scientists once envisioned it, the brain is constantly being rewired. I’m here to teach you how to be your own electrician.

THE MEDIUM IS THE MESSENGER

It’s all about communication. The brain is made up of one hundred billion neurons of various types that chat with one another by way of hundreds of different chemicals, to govern our every thought and action. Each brain cell might receive input from a hundred thousand others before firing off its own signal. The junction between cell branches is the synapse, and this is where the rubber meets the road. Synapses don’t actually touch, which is a little confusing because neuroscientists talk about synapses “wiring together” when they establish a connection. The way it works is that an electrical signal shoots down the axon, the outgoing branch, until it reaches the synapse, where a neurotransmitter carries the message across the synaptic gap in chemical form. On the other side, at the dendrite, or the receiving branch, the neurotransmitter plugs into a receptor — like a key into a lock — and this opens ion channels in the cell membrane to turn the signal back into electricity. If the electrical charge at the receiving neuron builds up beyond a certain threshold, that nerve cell fires a signal along its own axon, and the entire process repeats.

About 80 percent of the signaling in the brain is carried out by two neurotransmitters that balance each other’s effect: glutamate stirs up activity to begin the signaling cascade, and gamma-aminobutyric acid (GABA) clamps down on activity. When glutamate delivers a signal between two neurons that haven’t spoken before, the activity primes the pump. The more often the connection is activated, the stronger the attraction becomes, which is what neuroscientists mean when they talk about binding. As the saying goes, neurons that fire together wire together. Which makes glutamate a crucial ingredient in learning.

Glutamate is a workhorse, but psychiatry focuses more on a group of neurotransmitters that act as regulators — of the signaling process and of everything else the brain does. These are serotonin, norepinephrine, and dopamine. And although the neurons that produce them account for only 1 percent of the brain’s hundred billion cells, these neurotransmitters wield powerful influence. They might instruct a neuron to make more glutamate, or they might make the neuron more efficient or alter the sensitivity of its receptors. They can override other signals coming into the synapse, thus lowering the “noise” in the brain, or, conversely, amplify those signals. They can deliver signals directly, like glutamate and GABA, but their primary role is in adjusting the flow of information in order to fine-tune the overall balance of neurochemicals.

Serotonin, which you’ll hear a lot more about in later chapters, is often called the policeman of the brain because it helps keep brain activity under control. It influences mood, impulsivity, anger, and aggressiveness. We use serotonin drugs such as fluoxetine (Prozac), for instance, because they help modify runaway brain activity that can lead to depression, anxiety, and obsessive-compulsiveness.

Norepinephrine, which was the first neurotransmitter scientists studied to understand mood, often amplifies signals that influence attention, perception, motivation, and arousal.

Dopamine, which is thought of as the learning, reward (satisfaction), attention, and movement neurotransmitter, takes on sometimes contradictory roles in different parts of the brain. Methylphenidate (Ritalin) eases attention-deficit/hyperactivity disorder (ADHD) by raising dopamine, thus calming the mind.

Most of the drugs we use to improve mental health target one or more of these three neurotransmitters. But as I hope to make abundantly clear, simply raising or lowering the level of a neurotransmitter doesn’t elicit a crisp one-to-one result because the system is so complex. Manipulating just one neurotransmitter creates a ripple effect that takes different paths in different brains.

I tell people that going for a run is like taking a little bit of Prozac and a little bit of Ritalin because, like the drugs, exercise elevates these neurotransmitters. It’s a handy metaphor to get the point across, but the deeper explanation is that exercise balances neurotransmitters — along with the rest of the neurochemicals in the brain. And as you’ll see, keeping your brain in balance can change your life.

TO LEARN IS TO GROW

As fundamental as the neurotransmitters are, there’s another class of master molecules that over the past fifteen years or so has dramatically changed our understanding of connections in the brain, specifically, how they develop and grow. I’m talking about a family of proteins loosely termed factors, the most prominent of which is brain-derived neurotrophic factor (BDNF). Whereas neurotransmitters carry out signaling, neurotrophins such as BDNF build and maintain the cell circuitry — the infrastructure itself.

During the 1990s, as neuroscientists began to pin down the cellular mechanism of memory, BDNF became the focus of a whole new field of research. About a dozen papers on BDNF were published before 1990, the year scientists discovered that it exists in the brain and nourishes neurons like fertilizer. Then, “a tsunami of labs and pharma companies” joined the fray, says Eero Castrén, a neuroscientist involved in the early work on BDNF at Sweden’s Karolinska Institute. Today the research literature shows more than fifty-four hundred papers on BDNF. Once it became clear that BDNF was present in the hippocampus, an area of the brain related to memory and learning, researchers set out to test whether it’s a necessary ingredient in the process.

Learning requires strengthening the affinity between neurons through a dynamic mechanism called long-term potentiation (LTP). When the brain is called on to take in information, the demand naturally causes activity between neurons. The more activity, the stronger the attraction becomes, and the easier it is for the signal to fire and make the connection. The initial activity marshals existing stores of glutamate in the axon to be sent across the synapse and reconfigures receptors on the receiving side to accept the signal. The voltage on the receiving side of the synapse becomes stronger in its resting state, thereby attracting the glutamate signal like a magnet. If the firing continues, genes inside the neuron’s cell nucleus are turned on to produce more building material for the synapses, and it is this bolstering of the infrastructure that allows the new information to stick as a memory.

Say you’re learning a French word. The first time you hear it, nerve cells recruited for a new circuit fire a glutamate signal between each other. If you never practice the word again, the attraction between the synapses involved naturally diminishes, weakening the signal. You forget. The discovery that astonished memory researchers — and earned Columbia University neuroscientist Eric Kandel a share of the 2000 Nobel Prize — is that repeated activation, or practice, causes the synapses themselves to swell and make stronger connections. A neuron is like a tree that instead of leaves has synapses along its dendritic branches; eventually new branches sprout, providing more synapses to further solidify the connections. These changes are a form of cellular adaptation called synaptic plasticity, which is where BDNF takes center stage.

Early on, researchers found that if they sprinkled BDNF onto neurons in a petri dish, the cells automatically sprouted new branches, producing the same structural growth required for learning — and causing me to think of BDNF as Miracle-Gro for the brain.

BDNF also binds to receptors at the synapse, unleashing the flow of ions to increase the voltage and immediately improve the signal strength. Inside the cell, BDNF activates genes that call for the production of more BDNF as well as serotonin and proteins that build up the synapses. BDNF directs traffic and engineers the roads as well. Overall, it improves the function of neurons, encourages their growth, and strengthens and protects them against the natural process of cell death. And — as I hope to make clear throughout this book — BDNF is a crucial biological link between thought, emotions, and movement.

THE MIND-BODY CONNECTION

Only a mobile creature needs a brain, points out New York University neurophysiologist Rodolfo Llinás in his 2002 book, I of the Vortex: From Neurons to Self. To illustrate, he uses the example of a tiny jellyfish-like animal called a sea squirt: Born with a simple spinal cord and a three hundred–neuron “brain,” the larva motors around in the shallows until it finds a nice patch of coral on which to put down its roots. It has about twelve hours to do so, or it will die. Once safely attached, however, the sea squirt simply eats its brain. For most of its life, it looks much more like a plant than an animal, and since it’s not moving, it has no use for its brain. Llinás’s interpretation: “That which we call thinking is the evolutionary internalization of movement.”

As our species has evolved, our physical skills have developed into abstract abilities to predict, sequence, estimate, plan, rehearse, observe ourselves, judge, correct mistakes, shift tactics, and then remember everything we did in order to survive. The brain circuits that our ancient ancestors used to start a fire are the same ones we use today to learn French.

Take the cerebellum, which coordinates motor movements and allows us to do everything from returning a tennis serve to resisting the pull of gravity. Starting with evidence that the trunk of nerve cells connecting the cerebellum to the prefrontal cortex are proportionally thicker in humans than in monkeys, it now appears that this motor center also coordinates thoughts, attention, emotions, and even social skills. I call it the rhythm and blues center. When we exercise, particularly if the exercise requires complex motor movement, we’re also exercising the areas of the brain involved in the full suite of cognitive functions. We’re causing the brain to fire signals along the same network of cells, which solidifies their connections.

When we learn something, a wide array of connected brain areas are called into action. The hippocampus doesn’t do much without oversight from the prefrontal cortex. Broadly speaking, the prefrontal cortex organizes activity, both mental and physical, receiving input and issuing instructions through the brain’s most extensive network of connections. The prefrontal cortex is the boss. As such, it is responsible for, among other things, keeping tabs on our current situation through so-called working memory, inhibiting stimuli and initiating action, judging, planning, predicting — all executive functions. As the CEO of the brain, the prefrontal cortex has to stay in close contact with the COO — the motor cortex — as well as many other areas.

The hippocampus is something like the cartographer, receiving new input from working memory, cross-referencing that information with existing memories for the sake of comparison and to form new associations, and reporting back to the boss. A memory, scientists believe, is a collection of information fragments dispersed throughout the brain. The hippocampus serves as a way station, receiving the fragments from the cortex, and then bundling them together and sending them back up as a map of a unique new pattern of connections.

Brain scans show that when we learn a new word, for example, the prefrontal cortex lights up with activity (as does the hippocampus and other pertinent areas, such as the auditory cortex). Once the circuit has been established by the firing of glutamate, and the word is learned, the prefrontal cortex goes dark. It has overseen the initial stages of the project, and now it can leave the responsibility to a team of capable employees while it moves on to new challenges.

This is how we come to know things and how activities like riding a bike become second nature. Patterns of thinking and movement that are automatic get stored in the basal ganglia, cerebellum, and brain stem — primitive areas that until recently scientists thought related only to movement. Delegating fundamental knowledge and skills to these subconscious areas frees up the rest of the brain to continue adapting, a crucial arrangement. Imagine if we had to stop and think to process every thought and to remember how to perform every action. We’d collapse in a heap of exhaustion before we could pour our first cup of morning coffee. Which is why a morning run is so important.

THE FIRST SPARK

In 1995 I was in the process of researching my book A User’s Guide to the Brain, when I came across a one-page article in the journal Nature about exercise and BDNF in mice. There was scarcely more than a column of text, yet it said everything. Namely, that exercise elevates Miracle-Gro throughout the brain.

“I expected the big changes to occur in motor-sensory areas of the brain — the motor cortex, the cerebellum, the sensory cortex, maybe even the basal ganglia a little bit — because they’re all involved with movement,” recalls Carl Cotman, director of the Institute for Brain Aging and Dementia at the University of California, Irvine, who designed the study. “We developed the first films and, son of a gun, it showed up in the hippocampus. Well, the significance is that the hippocampus is an area of the brain that is extremely vulnerable to degenerative disease and that is needed for learning. Instantly I said, This changes the game completely.”

The news certainly came out of left field for me. For years, I had been a vocal proponent of using exercise for ADHD and many other psychological issues, based on what I’d seen with my own patients and what I knew about exercise’s effect on neurotransmitters. But this was different. By showing that exercise sparks the master molecule of the learning process, Cotman nailed down a direct biological connection between movement and cognitive function. In doing so, he blazed the trail for the study of exercise in neuroscience.

Cotman conducted this experiment not long after BDNF was discovered in the brain, and there was nothing to suggest that exercise had anything to do with it; his hypothesis was an act of sheer creativity. He’d just finished working on a long-term aging study designed to see if the people whose minds hold up best share anything in common. Among those with the least cognitive decline over a four-year period, three factors turned up: education, self-efficacy, and exercise. The first two weren’t so surprising, but Cotman was curious about the last. “I got to thinking about what the heck was really going on,” he says. “The assumption was that exercise didn’t act on the brain, but my take on it was that somehow it had to be the brain.”

At the time, if you’d asked what variable might underlie overall brain health, most scientists would have said neurotrophic factors because they were “kind of the in thing,” says Cotman, and everyone knew that BDNF helped neurons in culture survive. It was a bit of a leap, but if Cotman could tie exercise to BDNF, he’d at least have a plausible explanation for why it turned up in the aging study.

He set up an experiment to measure the levels of BDNF in the brains of mice that exercise. It was important that the exercise be voluntary because if he forced the mice to run on treadmills, he feared his peers might say the effect was from the stress of being handled. No problem: he’d use running wheels. As an indication of how new this territory was, finding rodent equipment that the university would approve for lab use was an ordeal in itself — Cotman had to pay $1,000 apiece for stainless steel running wheels that would pass protocol. “I remember signing the purchase order and thinking, This is painful; I just hope it doesn’t not work,” he jokes. On top of that, none of his postdoctoral students wanted anything to do with this research, and he had to go through a number of graduate students before finding a physical therapy major who liked the idea.

Unlike humans, rodents seem to inherently enjoy physical activity, and Cotman’s mice ran several kilometers a night. They were divided into four groups: mice running for two, four, or seven nights, and one control group with no running wheel. When their brains were injected with a molecule that binds to BDNF and scanned, not only did the scans of the running rodents show an increase in BDNF over controls, but the farther each mouse ran, the higher the levels were. When Cotman saw the results — that the spike occurred in the hippocampus — he didn’t believe them himself: “I said, No, c’mon guys, we did something wrong; the darn hippocampus is lit up. We had to repeat the experiment — it was too far out. And so we did, and we got the same results.”

As the stories of BDNF and exercise developed in parallel, it became clear that BDNF was important not merely for the survival of neurons but also for their growth (sprouting new branches) and thus for learning. Eero Castrén, as well as Susan Patterson from Kandel’s lab at Columbia, found that if you stimulate LTP in mice by making them learn, BDNF levels increase. Looking inside their brains, researchers determined that mice without BDNF lose their capacity for LTP; conversely, injecting BDNF directly into the brains of rats encouraged LTP. Then one of Cotman’s former postdoctoral students, neurosurgeon Fernando Gomez-Pinilla, showed that if you neutralize BDNF in mice, they are slow to find their way out of a pool having a hidden platform. It all adds up to solid evidence of how exercise helps the brain learn.

“One of the prominent features of exercise, which is sometimes not appreciated in studies, is an improvement in the rate of learning, and I think that’s a really cool take-home message,” Cotman says. “Because it suggests that if you’re in good shape, you may be able to learn and function more efficiently.”

Indeed, in a 2007 study of humans, German researchers found that people learn vocabulary words 20 percent faster following exercise than they did before exercise, and that the rate of learning correlated directly with levels of BDNF. Along with that, people with a gene variation that robs them of BDNF are more likely to have learning deficiencies. Without Miracle-Gro, the brain closes itself off to the world.

Psychiatry had grudgingly accepted the idea that exercise could help improve our state of mind by creating a conducive environment for learning. But Cotman’s work laid the foundation for proving that exercise strengthens the cellular machinery of learning. BDNF gives the synapses the tools they need to take in information, process it, associate it, remember it, and put it in context. Which isn’t to say that going for a run will turn you into a genius. “You can’t just inject BDNF and be smarter,” Cotman points out. “With learning, you have to respond to something in a different way. But the something has to be there.”

And without question, what that something is matters.

THE NATURE OF NURTURE

Scientists all the way back to Ramón y Cajal — who won the Nobel Prize in 1906 for proposing that the central nervous system was made up of individual neurons that communicate at what he termed polarized junctions — have theorized that learning involves changes at the synapses. Despite the accolades, most scientists didn’t buy it. And it wasn’t until 1945 that a psychologist from McGill University named Donald Hebb stumbled onto the first hint of evidence. The lab rules were loose in those days, and apparently Hebb thought it would be fine if he brought some lab rats home as temporary pets for his children. The arrangement turned out to be mutually beneficial: When he returned the rats to the lab, Hebb noticed that compared to their cage-bound peers, they excelled in learning tests. The novel experience of being handled and toyed with somehow improved their learning ability, which Hebb interpreted to mean that it changed their brains. In his acclaimed textbook, The Organization of Behavior: A Neuropsychological Theory, he described the phenomenon as “use-dependent plasticity.” The theory was that the synapses rearrange themselves under the stimulation of learning.

Hebb’s work ties in with exercise because physical activity counts as novel experience, at least as far as the brain is concerned. In the 1960s a group of psychologists at Berkeley formalized an experimental model called environmental enrichment as a way to test use-dependent plasticity. Rather than take rodents home, the researchers outfitted their cages with toys, obstacles, hidden food, and running wheels. They also grouped the animals together, so they could socialize and play.

It wasn’t all peace and love, though, and eventually the rodents’ brains were dissected. Living in an environment with more sensory and social stimuli, the lab tests showed, altered the structure and function of the brain. Not only did the rats fare better on learning tasks, but their brains weighed more compared to those housed alone in bare cages. Hebb’s definition of plasticity hadn’t included growth. “This was at a time when it was almost heresy to say that the brain could actually change,” says neuroscientist William Greenough — who, as a young graduate student during that period, was keenly interested in the Berkeley work — “especially in a physical way, through experience.”

Greenough wanted to investigate environmental enrichment, but was warned off from that line of inquiry. “My adviser essentially said, If you pick that as your thesis, you’ll be in Vietnam for sure,” Greenough recalls. But as the Berkeley findings were replicated, the notion that experience could impact the brain gained a foothold. In a parallel line of research, a group from Harvard proved the converse — that environmental deprivation could shrink the brain. In examining cats raised with one eye sewn shut, they found that the visual cortex was significantly smaller. All this work established the metaphor of the brain as a muscle, and the notion of use it or lose it.

Aside from challenging the long-standing separation between biology and psychology, the social implications of environmental enrichment were radical. The Berkeley studies led to the creation of Head Start, the federal education program that provides funding to send disadvantaged children to preschool. Why should poor kids be left in bare cages? The field took off, and neuroscientists began to investigate different ways to stimulate brain growth.

Once Greenough was safely ensconced as a faculty member, at the University of Illinois, he turned back to this line of research. In a seminal study in the early 1970s, he used an electron microscope to show that environmental enrichment made the neurons sprout new dendrites. The branching caused by the environmental stimulation of learning, exercise, and social contact caused the synapses to form more connections, and those connections had thicker myelin sheaths, which allowed them to fire signals more efficiently. Now we know that such growth requires BDNF. This remodeling of the synapses has a huge impact on the circuits’ capacity to process information, which is profoundly good news. What it means is that you have the power to change your brain. All you have to do is lace up your running shoes.

STRETCHING PLASTICITY

As the concept of synaptic plasticity took hold in neuroscience, an even more radical notion of growth was gaining credence. For the better part of the twentieth century, scientific dogma held that the brain was hardwired once fully developed in adolescence, meaning we’re born with all the neurons we’re going to get. We can rearrange synapses all we like, but we can only lose neurons. Certainly, we can speed up the decline, a point that your eighth-grade biology teacher may have made to scare you away from underage drinking. “Now, remember: alcohol kills brain cells, and they never grow back.”

But guess what? They do grow back — by the thousands. Not until scientists became handy with advanced imaging tools that enabled them to peer into the brain did they find conclusive evidence, which was published in a seminal 1998 paper. It came from an unlikely source. Cancer patients are sometimes injected with a dye that shows up in proliferating cells so that the spread of the disease can be tracked. Researchers looked at the brains of terminally ill patients who had donated their bodies to science and found that their hippocampi were packed with the dye marker, proof that neurons were dividing and propagating — a process called neurogenesis — just like cells in the rest of the body. With that, they formalized one of the biggest discoveries in neuroscience.

Ever since, from Stockholm to Southern California to Princeton, New Jersey, neuroscientists have been scrambling to figure out what our new brain cells actually do. The implications are wide-ranging, given that the fundamental cause of degenerative diseases such as Parkinson’s and Alzheimer’s is dying and damaged cells. Aging itself is a matter of cells dying, and suddenly we learned that the brain has a built-in countermeasure, at least in certain areas. Figure out how to kick-start neurogenesis, and maybe we could make replacement parts for the brain.

And what does this mean for healthy brains? One of the early clues about neurogenesis had come from studies of chickadees, which learn new songs every spring and also show a significant burst of new cells in the hippocampus. Coincidence? The fledgling cells hinted at some role in learning, but proof has been hard to come by. Like synaptic plasticity, “neurogenesis is clearly involved in our interactions with our environment, both emotionally and cognitively,” says neuroscientist Fred Gage, of the Salk Institute in La Jolla, California. Gage was one of the researchers, along with Peter Eriksson of Sweden, who conducted the linchpin study in 1998. “Trying to figure out what exactly [neurogenesis] is doing is a real interesting problem.”

Neurons are born as blank-slate stem cells, and they go through a development process in which they need to find something to do in order to survive. Most of them don’t. It takes about twenty-eight days for a fledgling cell to plug into a network, and, as with existing neurons, Hebb’s concept of activity-dependent learning would apply: if we don’t use the newborn neurons, we lose them. Gage went back to the environmental enrichment model to test this idea in rodents. “When we first did our experiments, we had all sorts of things going on,” Gage explains. “We needed to tease that out, and to our surprise, just putting a running wheel in a cage had a profound effect on the number of cells that were born. Ironically, with running, the same percentage of cells die as in the control group — it’s just that you have a bigger starting pool. But in order for a cell to survive and integrate, it has to fire its axon.” Exercise spawns neurons, and the stimulation of environmental enrichment helps those cells survive.

The first solid link between neurogenesis and learning came from one of Gage’s colleagues, Henrietta van Praag. They used a rodent-size pool filled with opaque water to hide a platform just beneath the surface in one quadrant. Mice don’t like water, so the experiment was designed to test how well they remember, from an earlier dip, the location of the platform — their escape route. When comparing inactive mice with others that hit the running wheel four to five kilometers a night, the results showed that the runners remembered where to find safety more quickly. Both groups swam at the same rate, but the exercised animals made a beeline for the platform, while the sedentary ones floundered about before figuring it out. When the mice were dissected, the active mice had twice as many new stem cells in the hippocampus as the inactive ones. Speaking generally about what they found, Gage says: “There is a significant correlation between the total number of cells and [a mouse’s] ability to perform a complex task. And if you block neurogenesis, mice can’t recall information.”

Although all this research is in rodents, you can see how it might relate back to the kids in Naperville: Gym class provides the brain with the right tools to learn, and the stimulation in the kids’ classes encourages those newly developing cells to plug into the network, where they become valuable members of the signaling community. The neurons are given a mission. And it seems that cells spawned during exercise are better equipped to spark LTP. They are plastic phenoms, which led Princeton neuroscientist Elizabeth Gould to suggest that perhaps our new neurons play a role in hanging onto our conscious thoughts, while the prefrontal cortex decides if they should be wired in as long-term memories. Gould is the researcher who first showed that primates grow new neurons, paving the way for experiments on human neurogenesis.

She and everyone else in the field of neuroscience are still unpacking the relationship between neurogenesis and learning, and exercise has been a crucial lab tool. What I find interesting, though, is that relatively few scientists are studying exercise because they’re interested in exercise. Rather, they make the mice run because it “massively increases neurogenesis,” as the title of a 2006 study in Hippocampus proclaimed, and thus allows researchers to deconstruct the chain of signals behind the process. That’s what the pharmaceutical companies need to create drugs. They dream of an anti-Alzheimer’s pill that regenerates neurons to keep memory intact. “There has to be some kind of chemical stuff in the [hippocampus] that is sensing exercise and saying, OK, let’s start cranking out new cells,” says Columbia University neurologist Scott Small, who recently used a novel MRI technique to track neurogenesis in live human subjects. “If we can identify those molecular pathways, we might be able to think of clever ways to induce neurogenesis biochemically.”

Just imagine if they could put exercise in a bottle.

THE BODY-MIND CONNECTION

If we’re going to have new cells, we’ll need fertilizer for them, and from the get-go, neurogenesis researchers have been onto BDNF. They already knew that without Miracle Gro our brains can’t take in new information, and now they’ve seen that BDNF is also a necessary ingredient for making new cells.

BDNF gathers in reserve pools near the synapses and is unleashed when we get our blood pumping. In the process, a number of hormones from the body are called into action to help, which brings us to a new list of initialisms: IGF-1 (insulin-like growth factor), VEGF (vascular endothelial growth factor), and FGF-2 (fibroblast growth factor). During exercise, these factors push through the blood-brain barrier, a web of capillaries with tightly packed cells that screen out bulky intruders such as bacteria. Scientists have just recently learned that once inside the brain, these factors work with BDNF to crank up the molecular machinery of learning. They are also produced within the brain and promote stem-cell division, especially during exercise. The broader importance is that these factors trace a direct link from the body to the brain.

Take IGF-1, a hormone released by the muscles when they sense the need for more fuel during activity. Glucose is the major energy source for the muscles and the sole energy source for the brain, and IGF-1 works with insulin to deliver it to your cells. What’s interesting is that the role of IGF-1 in the brain isn’t related to fuel management, but to learning — presumably so we can remember where to locate food in the environment. During exercise, BDNF helps the brain increase the uptake of IGF-1, and it activates neurons to produce the signaling neurotransmitters, serotonin and glutamate. It then spurs the production of more BDNF receptors, beefing up connections to solidify memories. In particular, BDNF seems to be important for long-term memories.

Which makes perfect sense in light of evolution. If we strip everything else away, the reason we need an ability to learn is to help us find and obtain and store food. We need fuel to learn, and we need learning to find a source of fuel — and all these messengers from the body keep this process going and keep us adapting and surviving.

To pipe fuel to new cells, we need new blood vessels. When our body’s cells run short of oxygen, as they can when our muscles contract during exercise, VEGF gets to work building more capillaries in the body and the brain. Researchers suspect that one way VEGF is vital to neurogenesis is its role in changing the permeability of the blood-brain barrier, prying back the fence to let other factors through during exercise.

Another important element from the body that makes its way to the brain is FGF-2, which, like IGF-1 and VEGF, is increased during exercise and is necessary for neurogenesis. In the body, FGF-2 helps tissue grow, and in the brain it’s important to the process of LTP.

As we age, production of all three of these factors and BDNF naturally tails off, bringing down neurogenesis with it. Even before we get old, however, a drop in these factors and in neurogenesis can show up in stress and depression, as we’ll see later. To me, this is actually encouraging news, because if moving the body increases BDNF, IGF-1, VEGF, and FGF-2, it means we have some control over the situation.

It’s about growth versus decay, activity versus inactivity. The body was designed to be pushed, and in pushing our bodies we push our brains too. Learning and memory evolved in concert with the motor functions that allowed our ancestors to track down food, so as far as our brains are concerned, if we’re not moving, there’s no real need to learn anything.

EXERCISE YOUR OPTIONS

Now you know how exercise improves learning on three levels: first, it optimizes your mind-set to improve alertness, attention, and motivation; second, it prepares and encourages nerve cells to bind to one another, which is the cellular basis for logging in new information; and third, it spurs the development of new nerve cells from stem cells in the hippocampus. OK, but now you want to know what the best exercise plan is. I wish there were an ideal type and amount of activity to suggest for building your brain, but scientists are only beginning to tackle such questions. “Nobody’s done that research yet,” says William Greenough. “But I suspect in five years we’ll know a lot more.”

Still, we can draw certain conclusions from the existing re-search. One thing scientists know for sure is that you can’t learn difficult material while you’re exercising at high intensity because blood is shunted away from the prefrontal cortex, and this hampers your executive function. For example, while working out on the treadmill or the stationary bike for twenty minutes at a high intensity of 70 to 80 percent of their maximum heart rate, college students perform poorly on tests of complex learning. (So don’t study for the Law School Admission Test with the elliptical machine on full-tilt.) However, blood flow shifts back almost immediately after you finish exercising, and this is the perfect time to focus on a project that demands sharp thinking and complex analysis.

A notable experiment in 2007 showed that cognitive flexibility improves after just one thirty-five-minute treadmill session at either 60 percent or 70 percent of maximum heart rate. The forty adults in the study (age fifty to sixty-four) were asked to rattle off alternative uses for common objects, like a newspaper — it’s meant for reading, but it can be used to wrap fish, line a birdcage, pack dishes, and so forth. Half of them watched a movie and the other half exercised, and they were tested before the session, immediately after, and again twenty minutes later. The movie watchers showed no change, but the runners improved their processing speed and cognitive flexibility after just one workout. Cognitive flexibility is an important executive function that reflects our ability to shift thinking and to produce a steady flow of creative thoughts and answers as opposed to a regurgitation of the usual responses. The trait correlates with high-performance levels in intellectually demanding jobs. So if you have an important afternoon brainstorming session scheduled, going for a short, intense run during lunchtime is a smart idea.

A lot of the research I’ve mentioned in this chapter revolves around exercise’s effect on the hippocampus, because its role in forming memories makes it vital to learning. But the hippocampus isn’t off by itself somewhere, stamping out new circuits on its own accord. The learning process calls on a lot of areas, under the direction of the prefrontal cortex. The brain has to be aware of the incoming stimulus, hold it in working memory, give it emotional weight, associate it with past experience, and relate all this back to the hippocampus. The prefrontal cortex analyzes the information, sequences it, and ties everything together. It works with the cerebellum and the basal ganglia, which keep these functions on track by maintaining rhythm for the back-and-forth of information. Improving plasticity in the hippocampus strengthens a crucial link in the chain, but learning creates bushier, healthier, better connected neurons throughout the brain. The more we build these networks and enrich our stores of memory and experience, the easier it is to learn, because what we already know serves as a foundation for forming increasingly complex thoughts.

As for how much aerobic exercise you need to stay sharp, one small but scientifically sound study from Japan found that jogging thirty minutes just two or three times a week for twelve weeks improved executive function. But it’s important to mix in some form of activity that demands coordination beyond putting one foot in front of the other. Greenough worked on an experiment several years ago in which running rats were compared to others that were taught complex motor skills, such as walking across balance beams, unstable objects, and elastic rope ladders. After two weeks of training, the acrobatic rats had a 35 percent increase of BDNF in the cerebellum, whereas the running rats had none in that area. This extends what we know from the neurogenesis research: that aerobic exercise and complex activity have different beneficial effects on the brain. The good news is they’re complementary. “It’s important to take both into account,” says Greenough. “The evidence isn’t perfect, but really, your regimen has to include skill acquisition and aerobic exercise.”

What I would suggest, then, is to either choose a sport that simultaneously taxes the cardiovascular system and the brain — tennis is a good example — or do a ten-minute aerobic warm-up before something nonaerobic and skill-based, such as rock climbing or balance drills. While aerobic exercise elevates neurotransmitters, creates new blood vessels that pipe in growth factors, and spawns new cells, complex activities put all that material to use by strengthening and expanding networks. The more complex the movements, the more complex the synaptic connections. And even though these circuits are created through movement, they can be recruited by other areas and used for thinking. This is why learning how to play the piano makes it easier for kids to learn math. The prefrontal cortex will co-opt the mental power of the physical skills and apply it to other situations.

Learning the asanas of yoga, the positions of ballet, the skills of gymnastics, the elements of figure skating, the contortions of Pilates, the forms of karate — all these practices engage nerve cells throughout the brain. Studies of dancers, for example, show that moving to an irregular rhythm versus a regular one improves brain plasticity. Because the skills involved in these activities are unnatural forms of movement, they serve as activity-dependent learning of the sort that made Hebb’s rats smarter and that Greenough showed made synapses bushier.

Any motor skill more complicated than walking has to be learned, and thus it challenges the brain. At first you’re awkward and flail a little bit, but then as the circuits linking the cerebellum, basal ganglia, and prefrontal cortex get humming, your movements become more precise. With the repetition, you’re also creating thicker myelin around the nerve fibers, which improves the quality and the speed of the signals and, in turn, the circuit’s efficiency. To take the example of karate, as you perfect certain forms, you can incorporate them into more complicated movements, and before long you have new responses to new situations. The same would hold true for learning tango. The fact that you have to react to another person puts further demands on your attention, judgment, and precision of movement, exponentially increasing the complexity of the situation. Add in the fun and social aspect, and you’re activating the brain and the muscles all the way down through the system. And then you’re primed and ready to move on to the next challenge, which is what it’s all about.