Spark

by John J. Ratey

WE ALL KNOW that exercise makes us feel better, but most of us have no idea why. We assume it’s because we’re burning off stress or reducing muscle tension or boosting endorphins, and we leave it at that. But the real reason we feel so good when we get our blood pumping is that it makes the brain function at its best, and in my view, this benefit of physical activity is far more important—and fascinating—than what it does for the body. Building muscles and conditioning the heart and lungs are essentially side effects. I often tell my patients that the point of exercise is to build and condition the brain.

To keep our brains at peak performance, our bodies need to work hard. In Spark, I’ll demonstrate how and why physical activity is crucial to the way we think and feel. I’ll explain the science of how exercise cues the building blocks of learning in the brain; how it affects mood, anxiety, and attention; how it guards against stress and reverses some of the effects of aging in the brain; and how in women it can help stave off the sometimes tumultuous effects of hormonal changes. I’m not talking about the fuzzy notion of runner’s high. I’m not talking about a notion at all. These are tangible changes, measured in lab rats and identified in people.

What I aim to do here is to deliver in plain English the inspiring science connecting exercise and the brain and to demonstrate how it plays out in the lives of real people. I want to cement the idea that exercise has a profound impact on cognitive abilities and mental health. It is simply one of the best treatments we have for most psychiatric problems.

This is not good old gym class. This is Zero Hour PE, the latest in a long line of educational experiments conducted by a group of maverick physical education teachers who have turned the nineteen thousand students in Naperville District 203 into the fittest in the nation—and also some of the smartest. (The name of the class refers to its scheduled time before first period.) The objective of Zero Hour is to determine whether working out before school gives these kids a boost in reading ability and in the rest of their subjects. The notion that it might is supported by emerging research showing that physical activity sparks biological changes that encourage brain cells to bind to one another. For the brain to learn, these connections must be made; they reflect the brain’s fundamental ability to adapt to challenges. The more neuroscientists discover about this process, the clearer it becomes that exercise provides an unparalleled stimulus, creating an environment in which the brain is ready, willing, and able to learn. Aerobic activity has a dramatic effect on adaptation, regulating systems that might be out of balance and optimizing those that are not—it’s an indispensable tool for anyone who wants to reach his or her full potential.

The kids in Zero Hour, hearty volunteers from a group of freshmen required to take a literacy class to bring their reading comprehension up to par, work out at a higher intensity than Central’s other PE students. They’re required to stay between 80 and 90 percent of their maximum heart rate. “What we’re really doing is trying to get them prepared to learn, through rigorous exercise,” says Duncan. “Basically, we’re getting them to that state of heightened awareness and then sending them off to class.” How do they feel about being Mr. Duncan’s guinea pigs? “I guess it’s OK,” says Michelle. “Besides getting up early and being all sweaty and gross, I’m more awake during the day. I mean, I was cranky all the time last year.” Beyond improving her mood, it will turn out, Michelle is also doing much better with her reading. And so are her Zero Hour classmates: at the end of the semester, they’ll show a 17 percent improvement in reading and comprehension, compared with a 10.7 percent improvement among the other literacy students who opted to sleep in and take standard phys ed. The administration is so impressed that it incorporates Zero Hour into the high school curriculum as a first-period literacy class called Learning Readiness PE. And the experiment continues. The literacy students are split into two classes: one second period, when they’re still feeling the effects of the exercise, and one eighth period. As expected, the second-period literacy class performs best. The strategy...

FIRST-CLASS PERFORMANCE Zero Hour grew out of Naperville District 203’s unique approach to physical education, which has gained national attention and become the model for a type of gym class that I suspect would be unrecognizable to any adult reading this. No getting nailed in dodgeball, no flunking for not showering, no living in fear of being the last kid picked. The essence of physical education in Naperville 203 is teaching fitness instead of sports. The underlying philosophy is that if physical education class can be used to instruct kids how to monitor and maintain their own health and fitness, then the lessons they learn will serve them for life. And probably a longer and happier life at that. What’s being taught, really, is a lifestyle. The students are developing healthy habits, skills, and a sense of fun, along with a knowledge of how their bodies work. Naperville’s gym teachers are opening up new vistas for their students by exposing them to such a wide range of activities that they can’t help but find something they enjoy. They’re getting kids hooked on moving instead of sitting in front of the television. This couldn’t be more important, particularly since statistics show that children who exercise regularly are likely to do the same as adults.

During the weekly mile, he tested the device on a sixth-grade girl who was thin but not the least bit athletic. When Lawler downloaded her stats, he couldn’t believe what he found. “Her average heart rate was 187!” he exclaims. As an eleven-year-old, her maximum heart rate would have been roughly 209, meaning she was plugging away pretty close to full tilt. “When she crossed the finish line, she went up to 207,” Lawler continues. “Ding, ding, ding! I said, You gotta be kidding me! Normally, I would have gone to that girl and said, You need to get your ass in gear, little lady! It was really that moment that caused dramatic changes in our overall program. The heart rate monitors were a springboard for everything. I started thinking back to all the kids we must have turned off to exercise because we weren’t able to give them credit. I didn’t have an athlete in class who knew how to work as hard as that little girl.” He realized that being fast didn’t necessarily have anything to do with being fit. One of Lawler’s favorite statistics is that less than 3 percent of adults over the age of twenty-four stay in shape through playing team sports, and this underscores the failings of traditional gym class. But he knew he couldn’t have the students run the mile every day, so he set up a program of what they have termed “small-sided sports”—three-on-three basketball or four-on-four soccer—where the students are constantly moving. “We still play sports,” Lawler says. “We just do them w...

But what, exactly, do we know about the effect of gym on GPA? Few researchers have tackled the question, although one study from Virginia Tech showed that cutting gym class and allocating more time to math, science, and reading did not improve test scores, as so many school administrators assume it will. Because gym class can mean so many things, research in this area has focused on the correlation between physical fitness and academic achievement. The most telling studies come from the California Department of Education (CDE). Over the past five years, the CDE has consistently shown that students with higher fitness scores also have higher test scores.

The California studies don’t stand alone. In 2004 a panel of thirteen noted researchers in fields ranging from kinesiology to pediatrics conducted a massive review of more than 850 studies about the effects of physical activity on school-age children. Most of the studies measured the effects of thirty to forty-five minutes of moderate to vigorous physical activity three to five days a week. They covered a wide range of issues, such as obesity, cardiovascular fitness, blood pressure, depression, anxiety, self-concept, bone density, and academic performance. Based on strong evidence in a number of these categories, the panel issued a recommendation that schoolchildren should participate in one hour (or more) of moderate to vigorous physical activity a day. Looking specifically at academic performance, the panel found enough evidence to support the findings of the California studies, and it also reported that physical activity has a positive influence on memory, concentration, and classroom behavior. It didn’t specify gym class, but you can see how the students in Naperville are getting a healthy jump start.

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.

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 ...

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 ...

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 growt...

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.”

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.

“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.

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 throu...

So if you have an important afternoon brainstorming session scheduled, going for a short, intense run during lunchtime is a smart idea.

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.”

INOCULATE YOURSELF How the body and brain respond to stress depends on many factors, not the least of which is your own genetic background and personal experience. Today there is an ever-widening gap between the evolution of our biology and our society. We don’t have to run from lions, but we’re stuck with the instinct, and the fight-or-flight response doesn’t exactly fly in the boardroom. If you get stressed at work, would you slap your boss? Or turn and run? The trick is how you respond. The way you choose to cope with stress can change not only how you feel, but also how it transforms the brain. If you react passively or if there is simply no way out, stress can become damaging. Like most psychiatric issues, chronic stress results from the brain getting locked into the same pattern, typically one marked by pessimism, fear, and retreat. Active coping moves you out of this territory. Instincts aside, you do have some control over how stress affects you. And, as Susan would agree, control is key. Exercise controls the emotional and physical feelings of stress, and it also works at the cellular level. But how can that be, if exercise itself is a form of stress? The brain activity caused by exercise generates molecular by-products that can damage cells, but under normal circumstances, repair mechanisms leave cells hardier for future challenges. Neurons get broken down and built up just like muscles—stressing them makes them more resilient. This is how exercise forces the bod...

The amygdala connects to many parts of the brain and thus receives a wide array of input—some of it routed through the high-level processing center of the prefrontal cortex, and some of it wired indirectly, bypassing the cortex, which explains how even a subconscious perception or memory can trigger a stress response. Within ten milliseconds of sounding the alarm, the amygdala fires off messages that cause the adrenal gland to release different hormones at different stages. First, norepinephrine triggers lightning-fast electrical impulses that travel through the sympathetic nervous system activate the adrenal gland to dump the hormone epinephrine, or adrenaline, into the bloodstream. Heart rate, blood pressure, and breathing increase, contributing to the physical agitation we feel under stress. At the same time, signals carried by norepinephrine and corticotropin-releasing factor (CRF) travel from the amygdala to the hypothalamus, where they are handed off to messengers that take the slow train through the bloodstream. These messengers prompt the pituitary gland to activate another part of the adrenal gland, which releases the second major hormone of the stress response: cortisol. This relay from the hypothalamus to the pituitary to the adrenal gland is known as the HPA axis, and its role in summoning cortisol and in turning off the response makes it a key player in the story of stress. Meanwhile, the amygdala has signaled the hippocampus to start recording memories and an...

The overarching principle of the fight-or-flight response is marshaling resources for immediate needs in lieu of building for the future—act now, ask questions later. The hormonal rush of epinephrine focuses the body, increasing heart rate and blood pressure and dilating the bronchial tubes of the lungs to carry more oxygen to the muscles. Epinephrine binds to muscle spindles, and this ratchets up the muscles’ resting tension so they’re ready to explode into action. Blood vessels in the skin constrict to limit bleeding in the event of a wound. Endorphins are released in the body to blunt pain. In this scenario, biological imperatives like eating and reproduction are put on the back burner. The digestive system shuts down; the muscles used to contract the bladder relax so as not to waste glucose; and saliva stops flowing. If you’ve ever faced a nerve-racking public-speaking situation, you’ve experienced this shift in the form of a racing heart and cotton mouth. Your muscles and your brain get stiff, and you lose all hope of being flexible and engaging. Or, if the processed signal from the cortex to the amygdala breaks up, you can’t think and you freeze. Technically, the full-blown stress response should be called “freeze or fight or flight.” None of this is particularly helpful when you’re up at the podium, but the body responds in essentially the same way whether you’re staring down a hungry lion or a restless audience. Two neurotransmitters put the brain on alert: norepin...

FUEL To fuel the anticipated activity of the muscles and the brain, epinephrine immediately begins converting glycogen and fatty acids into glucose. Traveling through the bloodstream, cortisol works more slowly than epinephrine, but its effects are incredibly widespread. Cortisol wears a number of different hats during the stress response, one of which is that of traffic cop for metabolism. Cortisol takes over for epinephrine and signals the liver to make more glucose available in the bloodstream, while at the same time blocking insulin receptors at nonessential tissues and organs and shutting down certain intersections so the fuel flows only to areas important to fight-or-flight. The strategy is to make the body insulin-resistant so the brain has enough glucose. Cortisol also begins restocking the shelves, so to speak, replenishing energy stores depleted by the action of epinephrine. It converts protein into glycogen and begins the process of storing fat. If this process continues unabated, as in chronic stress, the action of cortisol amasses a surplus fuel supply around the abdomen in the form of belly fat. (Unrelenting cortisol also explains why some marathon runners carry a slight paunch despite all their training—their bodies never get a chance to adequately recover.) The problem with our inherited stress response is that it mobilizes energy stores that don’t get used. More on that later.

FIGHTING OUR INSTINCTS The stress response is elegantly adaptive behavior, but because it doesn’t get you very far in today’s world, there’s no outlet for all that energy buildup. You have to make a conscious effort to initiate the physical component of fight or flight. The human body is built for regular physical activity, but how much? In a 2002 article in the Journal of Applied Physiology, researchers studied this very question, by looking at our ancestors’ pattern of physical activity, which they call the Paleolithic rhythm. From the time Homo sapiens emerged two million years ago, until the agricultural revolution, ten thousand years ago, everyone was a hunter-gatherer, and life was marked by periods of intense physical activity followed by days of rest. It was feast or famine. By calculating how much our forebears “exercised” and comparing it to figures from today, it’s easy to see where the problem lies: Our average energy expenditure per unit of body mass is less than 38 percent of that of our Stone Age ancestors. And I think it’s fair to say that our calorie intake has increased quite a bit. The kicker is that even if we followed the most demanding governmental recommendations for exercise and logged thirty minutes of physical activity a day, we’d still be at less than half the energy expenditure for which our genes are encoded. Paleolithic man had to walk five to ten miles on an average day, just to be able to eat.

Regular aerobic activity calms the body, so that it can handle more stress before the serious response involving heart rate and stress hormones kicks in. It raises the trigger point of the physical reaction. In the brain, the mild stress of exercise fortifies the infrastructure of our nerve cells by activating genes to produce certain proteins that protect the cells against damage and disease. So it also raises our neurons’ stress threshold.

The cellular stress-and-recovery dynamic takes place on three fronts: oxidation, metabolism, and excitation. When a nerve cell is called into action, its metabolic machinery switches on like the pilot light in a furnace. As glucose is absorbed into the cell, mitochondria turn it into adenosine triphosphate (ATP)—the main type of fuel a cell can burn—and just as with any energy conversion process, waste by-products are produced. This is oxidative stress. Under normal circumstances, the cell also produces enzymes whose job it is to mop up waste such as free radicals, molecules with a rogue electron that rupture the cell structure while careening around trying to neutralize the electron. These protective enzymes are our internal antioxidants. Metabolic stress happens when the cells can’t produce adequate ATP, either because glucose can’t get into the cell or because there’s not enough of it to go around. Excitotoxic stress occurs when there is so much glutamate activity that there isn’t enough ATP to keep up with the energy demand of the increased information flow. If this continues for too long without recovery, there’s a problem. The cell is on a death march—forced to work without food or resources to repair the damage. The dendrites begin to shrink back and eventually cause the cell to die. This is neurodegeneration, the mechanism underlying diseases such as Alzheimer’s, Parkinson’s, and even aging itself. It’s largely through intensive study of these diseases that scienti...

Mattson’s latest work will change the way we look at some of our healthiest foods. An enormous industry has sprung up to promote the cancer-fighting properties of foods and products that contain antioxidants. Eat more antioxidant-rich broccoli, the logic goes, and you’ll live a longer and healthier life. True, perhaps, but not for the reasons the marketing folks would have you believe. It turns out that these foods are particularly beneficial not only because they contain antioxidants but also because they contain toxins. “Many of the beneficial chemicals in plants—vegetables and fruits—have evolved as toxins to dissuade insects and other animals from eating them,” Mattson explains. “What they’re doing is inducing a mild, adaptive stress response in the cells. For example, in broccoli, there’s a chemical called sulforaphane, and it clearly activates stress response pathways in cells that upregulate antioxidant enzymes. Broccoli has antioxidants, but at the level you could get from your diet, they’re not going to function as antioxidants.” Just as with the nuclear shipyard workers, a mild toxin generates an adaptive stress response that bolsters cells. It’s the same process generated by dietary restriction and exercise. The title of one of Mattson’s journal articles says it all: “Neuroprotective signaling and the aging brain: Take away my food and let me run.”

Resilience is the buildup of these waste-disposing enzymes, neuroprotective factors, and proteins that prevent the naturally programmed death of cells. I like to think of these elements as armies that remain on duty to take on the next stress. The best way to build them up is by bringing mild stress on yourself: using the brain to learn, restricting calories, exercising, and, as Mattson and your mother would remind you, eating your vegetables. All these activities challenge the cells and create waste products that can be just stressful enough. The paradox is that our wonderful ability to adapt and grow doesn’t happen without stress—we can’t have the good without a bit of the bad.

When you suffer from chronic stress, you lose the capacity to compare the situation to other memories or to recall that you can grab a jump rope and immediately relieve the stress or that you have friends to talk to or that it’s not the end of the world. Positive and realistic thoughts become less accessible, and eventually brain chemistry can shift toward anxiety or depression.

One of the ways exercise optimizes energy usage is by triggering the production of more receptors for insulin. In the body, having more receptors means better use of blood glucose and stronger cells. Best of all, the receptors stay there, which means the newfound efficiency gets built in. If you exercise regularly, and the population of insulin receptors increases if there is a drop in blood sugar or blood flow, the cell will still be able to squeeze enough glucose out of the bloodstream to keep working. Also, exercise increases IGF-1, which helps insulin manage glucose levels. In the brain, IGF-1 doesn’t have as much to do with getting energy into the cells as it does with regulating glucose throughout the body. What’s fascinating is that in the hippocampus, IGF-1 increases LTP, neuroplasticity, and neurogenesis. It’s another way exercise helps our neurons bind. Exercise also produces FGF-2 and VEGF, which build new capillaries and expand the vascular system in the brain. More and bigger highways means more efficient blood flow. At the same time, aerobic exercise increases BDNF production. Taken all together, these factors combine forces to make the brain bloom and prevent the damaging effects of chronic stress from taking hold. In addition to cranking up the cellular repair mechanisms, they also keep cortisol in check and increase the levels of our regulatory neurotransmitters serotonin, norepinephrine, and dopamine.

On a mechanical level, exercise relaxes the resting tension of muscle spindles, which breaks the stress-feedback loop to the brain. If the body isn’t stressed, the brain figures maybe it can relax too. Over time, regular exercise also increases the efficiency of the cardiovascular system, lowering blood pressure. Cardiologists have recently discovered that a hormone called atrial natriuretic peptide (ANP), which is produced by muscle tissue in the heart, directly tempers the body’s stress response by putting the brakes on the HPA axis and quelling noise in the brain. What’s so interesting about ANP is that it increases as the heart rate increases during exercise, thus illustrating another pathway by which physical activity relieves both the feeling of stress and the body’s response to it. The stress of exercise is predictable and controllable because you’re initiating the action, and these two variables are key to psychology. With exercise, you gain a sense of mastery and self-confidence. As you develop awareness of your own ability to manage stress and not rely on negative coping mechanisms, you increase your ability to “snap out of it,” so to speak.

Panic doesn’t cause heart failure, but it sure feels that way. Muscle tension and hyperventilation cause severe chest pains. Then, because the rapid, shallow breathing expels too much carbon dioxide, the blood’s pH level drops, triggering an alarm from the brain stem that causes muscles to constrict even more. (This is why breathing into a paper bag stops us from hyperventilating: it forces us to rebreathe the carbon dioxide.)

It teaches a different outcome. One aspect of anxiety that makes it so different from other disorders is the physical symptoms. Because anxiety brings the sympathetic nervous system into play, when you sense your heart rate and breathing picking up, that awareness can trigger anxiety or a panic attack. But those same symptoms are inherent to aerobic exercise—and that’s a good thing. If you begin to associate the physical symptoms of anxiety with something positive, something that you initiated and can control, the fear memory fades in contrast to the fresh one taking shape. Think of it as a biological bait and switch—your mind is expecting a panic attack, but instead it ends up with a positive association with the symptoms.

We still don’t know what causes depression, but we’ve made great strides in describing the brain activity underlying emotions. And the more we’ve learned about the biology of mood, the more we’ve come to understand how aerobic exercise alters it. In fact, it’s largely through depression research that we know as much as we do about what exercise does for the brain. It counteracts depression at almost every level. In Britain, doctors now use exercise as a first-line treatment for depression, but it’s vastly underutilized in the United States, and that’s a shame. According to the World Health Organization, depression is the leading cause of disability in the United States and Canada, ahead of coronary heart disease, any given cancer, and AIDS. About 17 percent of American adults experience depression at some point in their lives, to the tune of $26.1 billion in health care costs each year. It’s impossible to know how many people try to commit suicide, but, tragically, in the United States someone succeeds about every seventeen minutes. For this reason, and also because 74 percent of depression patients experience some other disorder—including anxiety, substance abuse, and dementia—it’s an urgent problem. Unfortunately, it’s not getting any better.

Several other sweeping studies have looked at the correlation from slightly different angles, and all of them came to the same conclusion. A massive Dutch study of 19,288 twins and their families published in 2006 showed that exercisers are less anxious, less depressed, less neurotic, and also more socially outgoing. A Finnish study of 3,403 people in 1999 showed that those who exercise at least two to three times a week experience significantly less depression, anger, stress, and “cynical distrust” than those who exercise less or not at all. This was a cardiovascular risk factor survey that included questions about mood, which is to say they were talking about a broader range of symptoms than clinical depression. Another study, from the epidemiology department at Columbia University published in 2003, surveyed 8,098 people and found the same inverse relationship between exercise and depression.

Aside from elevating endorphins, exercise regulates all of the neurotransmitters targeted by antidepressants. For starters, exercise immediately elevates levels of Schildkraut’s favorite neurotransmitter, norepinephrine, in certain areas of the brain. It wakes up the brain and gets it going and improves self-esteem, which is one component of depression. Exercise also boosts dopamine, which improves mood and feelings of wellness and jump-starts the attention system. Dopamine is all about motivation and attention. Studies have shown that chronic exercise increases dopamine storage in the brain and also triggers the production of enzymes that create dopamine receptors in the reward center of the brain, and this provides a feeling of satisfaction when we have accomplished something. If the demand is there, the dopamine genes get activated to produce more, and the overall effect is a more stable regulation of these pathways, which are important to controlling addictions. Serotonin is equally affected by exercise, and it’s important for mood, impulse control, and self-esteem. It also helps stave off stress by counteracting cortisol, and it primes the cellular connections in the cortex and hippocampus that are important for learning.

High levels of the stress hormone cortisol kill neurons in the hippocampus. If you put a neuron in a petri dish and flood it with cortisol, its vital connections to other cells retract. Fewer synapses develop and the dendrites wither. This causes a communication breakdown, which, in the hippocampus of a depressed brain, could partly explain why it gets locked into thinking negative thoughts—it’s recycling a negative memory, perhaps because it can’t branch out to form alternative connections.

Our understanding hasn’t junked the old theory, just expanded it. Now we see depression as a physical alteration of the brain’s emotional circuitry. Norepinephrine, dopamine, and serotonin are essential messengers that ferry information across the synapses, but without enough good connections in place, these neurotransmitters can only do so much. As far as the brain is concerned, it’s job is to transfer information and constantly rewire itself to help us adapt and survive. In depression, it seems that in certain areas, the brain’s ability to adapt grinds to a halt. The shutdown in depression is a shutdown of learning at the cellular level. Not only is the brain locked into a negative loop of self-hate, but it also loses the flexibility to work its way out of the hole. Redefining depression as a connectivity issue helps explain the wide range of symptoms people experience. It’s not just a matter of feeling empty, helpless, and hopeless. It affects learning, attention, energy, and motivation—disparate systems that involve different parts of the thinking brain. Depression also affects the body, shutting down the drive to sleep, eat, have sex, and generally look after ourselves on a primitive level. Psychiatrist Alexander Niculescu sees depression as a survival instinct to conserve resources in an environment void of hope—“to keep still and stay out of harm’s way,” he wrote in a 2005 article in Genome Biology. It’s a form of hibernation: When the emotional landscape turns wint...

As with norepinephrine in the 1960s, BDNF may be the tip of the iceberg. Today, research focuses on BDNF as well as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF-2), insulin-like growth factor (IGF-1), and all the related chemicals involved in encouraging neuroplasticity and neurogenesis. At the same time, pharmaceutical companies are funding research to mark and measure all these factors, and to map the genes affected by them, so they can figure out how to mimic their actions. BDNF and its neurotrophic brethren are much farther upstream in the neurochemical cascade than serotonin, closer to the source. Ultimately, the genes have to turn on the flow. The shift from the neurotransmitter hypothesis to the connectivity theory is a move from outside to inside the nerve cell. In addition to working at the synapse, as serotonin does, BDNF turns on genes to produce more neurotransmitters and neurotrophins, puts the brakes on self-destructive cellular activity, releases antioxidants, and provides the proteins used as building material for axons and dendrites. These gene-regulated adaptations of BDNF might go a long way toward explaining the delayed effect of antidepressants. It can often take three weeks for antidepressants to work. Is it merely a coincidence that the process of neurogenesis—from the time a stem cell is born in the hippocampus until it plugs into the network—takes approximately the same amount of time? Many researchers think not. The lat...

Mayberg would be the first to say that executive function is still only part of the story. In comparing PET scans of patients who responded to antidepressants against others who responded to cognitive behavior therapy, she found that the two approaches change activity levels of the limbic system from opposite directions. Antidepressants seem to work through a bottom-up chain of events, meaning the activity begins in the brain stem and ripples through the limbic system until it reaches the prefrontal cortex. This might explain why antidepressants relieve the physical effects first—we feel more energetic before we feel less sad. With cognitive behavioral therapy and psychotherapy, we feel better about ourselves before we feel better physically. Therapy works from the prefrontal cortex down, to modify our thinking so we can challenge the learned helplessness and spring ourselves out of the hopeless spiral. The beauty of exercise is that it attacks the problem from both directions at the same time. It gets us moving, naturally, which stimulates the brain stem and gives us more energy, passion, interest, and motivation. We feel more vigorous. From above, in the prefrontal cortex, exercise shifts our self-concept by adjusting all the chemicals I’ve mentioned, including serotonin, dopamine, norepinephrine, BDNF, VEGF, and so on. And unlike many anti-depressants, exercise doesn’t selectively influence anything—it adjusts the chemistry of the entire brain to restore normal signalin...

OUT OF THE TUNNEL Science has come a long way since our search for the single culprit began, and the decades’ worth of research generated from the monoamine hypothesis has taught us volumes about the biology of emotions. The closer we get to the cause of depression, the more complex it appears. When we began, everyone was fairly certain that the problem was an imbalance of neurotransmitters at the synapses. Now we know for certain that it’s not so simple. Ironically, I think this is precisely why exercise has yet to be embraced as a medical treatment. It doesn’t simply raise serotonin or dopamine or norepinephrine. It adjusts all of them, to levels that, we can only presume, have been optimally programmed by evolution. The same goes for exercise’s effect on BDNF, IGF-1, VEGF, and FGF-2, which provide the building material and oversight for the construction of new connections and neurons. In short, exercise affects so many variables in the brain that its nigh impossible to isolate its effect as we’d like—in the name of hard science. But the evidence is there, from the action of microscopic molecules to massive surveys of tens of thousands of people over the years. Yes, exercise is an antidepressant. But it is also much more.

It’s not simply a matter of whether the signals get through to capture our attention, but how fluidly that information travels. This is where the attention system ties in with movement and thus exercise: the areas of the brain that control physical movement also coordinate the flow of information. The cerebellum is a primitive part of the brain that for decades was assumed to be involved only with governing and refining movement. When we learn how to do something physical, whether it’s a karate kick or snapping our fingers, the cerebellum is hard at work. The cerebellum takes up just 10 percent of the brain’s volume, but it contains half of our neurons, which means it’s a densely packed area constantly buzzing with activity. But it keeps rhythm for more than just motor movements: it regulates certain brain systems so they run smoothly, updating and managing the flow of information to keep it moving seamlessly. In patients with ADHD, parts of the cerebellum are smaller in volume and don’t function properly, so it makes sense that this could cause disjointed attention. The cerebellum sends information to the prefrontal and motor cortices—the centers for thinking and movement—but along the route is an important cluster of nerve cells called the basal ganglia, which acts as a sort of automatic transmission, subconsciously shifting attentional resources as the cortex demands. It’s modulated by dopamine signals stemming from the substantia nigra. Dopamine works like transmission...

Typically, when we learn something, the connections stabilize and the levels of dopamine tail off over time. With addiction, especially drug addiction, dopamine floods the system with each drug use, reinforcing the memory and pushing other stimuli further into the background. Animal studies show that drugs such as cocaine and amphetamine make the dendrites in the nucleus accumbens bloom, thus increasing their synaptic connections. The changes can remain months and maybe even years after the drugs are stopped, which is why it’s so easy to relapse. One way to look at addiction is that the brain has learned something too well. These adaptations lead to a vicious cycle in which the basal ganglia goes on autopilot whenever you smell fried chicken, and the prefrontal cortex can’t override your actions even though you may know better. One of the responsibilities of the prefrontal cortex is to assess risk versus reward and to decide whether to inhibit behavior that may cause harm. With addicts, it’s not so much that they make bad choices as that they fail to inhibit behavior that has become reflexive. We know from studies in animals and humans that cocaine, for one, damages nerve cells in the prefrontal cortex and even reduces gray matter. And in recent years, imaging studies have shown that the prefrontal cortex doesn’t fully develop until we are well into our twenties, which could explain why most people who experiment with drugs and get hooked do so as teenagers or during early...

Scientists discovered the endocannabinoids in the early 1990s after realizing that THC binds to specialized receptors in the brain. These receptors didn’t evolve for us to enjoy marijuana, obviously, so there had to be some natural substance the body produces for them. What they found were the neurotransmitters anandamide and 2-arachidonoylglycerol (2-AG). It turns out that marijuana, exercise, and chocolate all activate these same receptors in the brain. Both of these endocannabinoids are produced in the body and the brain when we exercise. They travel through the bloodstream to activate receptors in the spinal cord, and this blocks pain signals from getting to the brain (not unlike morphine). They also move throughout the reward system and the prefrontal cortex, where they have a direct effect on dopamine. When the endocannabinoid receptors are strongly activated, they produce all the euphoric feelings of marijuana, and, along with endorphins, they act as the body’s extra-strength aspirin. Doctors are starting to use anandamide to treat pain syndromes such as chronic fatigue and fibromyalgia, and a number of studies have shown that gradually increasing exercise can relieve the pain and fatigue associated with these syndromes. The link between exercise and these natural pain killers makes perfect sense: they evolved to help us deal with the inevitable pain of straining muscles and joints during the hunt.

I can think of no better example of somebody with an exercise dependence than ultramarathoner Dean Karnazes, the forty-four-year-old Californian who has appeared on 60 Minutes, The Tonight Show, and countless magazine covers for his mind-bending feat of running fifty marathons in fifty days (in fifty different states). He also ran 350 miles without stopping. Only slightly less impressive to me is that over the past fifteen years, the longest period he has gone without exercising is three days. “I had the flu,” Karnazes recalls. “I was still sick, but I finally said, Screw it, I need to bust out a run.” For starters, his streak says something about the formidable strength of his immune system. Karnazes was drunk at a bar on his thirtieth birthday when he decided to make a change in his life—at that very moment. He stumbled home, grabbed an old pair of sneakers, and ran thirty miles into the night. He was no alcoholic and has never been into drugs, but the question remains: does this guy have a problem? “Maybe 10 to 20 percent of the time I do think of running as an addiction,” he says. “What I really long for is the feeling of bliss or satiety that I get after exercise. It makes me feel complete. I’m most tuned into this when I can’t exercise. If I’m traveling or I’m in meetings all day, I can feel it pulling at me. I’ll think, Why am I ready to implode? I’m crawling out of my skin here! And then I realize my body needs to move. It’s almost a feeling of being trapped.” Ther...

One of the connections I see here is between learning and overall mental strength. If the brain is flexible, the mind is stronger, and this gets at a concept known as self-efficacy. It’s difficult to measure, but it relates to confidence in our ability to change ourselves. For most addicts, if they stop to consider how they may be destroying their lives, they suddenly feel like they can’t handle anything, let alone their self-control over their addiction. Exercise, though, can have a powerful impact on the way an addict feels about himself. If he’s engaged in a new pursuit such as exercise, which involves work and commitment, and he’s able to follow through and be persistent with it, that sense of self-control spreads to other areas of his life. A group of Australian researchers recently put this idea to the test. Using twenty-four students as subjects, they measured the effect of a two-month exercise program on self-regulation, which is a slightly different characterization of self-efficacy. Every two weeks, the students were given two psychological tests, and they kept diaries of their daily habits. The results, published in 2006 in the British Journal of Health and Psychology, are profound. Aside from improving on the two tests, which measured intellectual inhibition (control), the participants reported that an entire range of behavior related to self-regulation took a turn for the better. Not only did they steadily increase their visits to the gym, they reported that t...

How much exercise you need depends, of course, on how severe the habit is. But I would say thirty minutes of vigorous aerobic exercise five days a week is the bare minimum if you want to root out an addiction. To begin, however, it’s best if you can do something every day, because the exercise will keep you occupied and focused on something positive. I have seen a lot of people who bury themselves in addiction when they lose their jobs, so if you are unemployed, having exercise in place is essential. And while I often suggest that people exercise in the morning, if your goal is to break a habit such as having a drink every night when you come home, exercising in the evening is probably a better strategy. You can use the aerobic shot for a different kind of buzz.

HORMONES HAVE A powerful influence on how our brains develop as well as on our feelings and behaviors and personality traits throughout life. After adolescence, hormone levels remain fairly steady in men, but in women, they fluctuate like clockwork. The constant shifting affects every woman differently, and this must be factored in to any discussion of brain health. Exercise is particularly important for women because it tones down the negative consequences of hormonal changes that some experience, and for others, it enhances the positive. Overall, exercise balances the system, on a monthly basis as well as during each stage of life, including pregnancy and menopause. The average woman has four hundred to five hundred menstrual cycles in her lifetime, each one lasting four to seven days. If you add them all up, it comes out to more than nine years—a long time for women who suffer premenstrual syndrome (PMS). “You can’t be bitchy and agitated and short-tempered and have a decent life,” says a thirty-eight-year-old colleague I’ll call Patty. “I know the feminists hate it when you say this, but some of us do go crazy.”

One explanation, certainly, is that physical activity increases levels of tryptophan in the bloodstream and thus concentrations of serotonin in the brain. It also balances dopamine, norepinephrine, and synaptic mediators such as BDNF. By stabilizing such a broad number of variables, exercise helps to tone down the ripple effects of shifting hormones. Exercise also ties into a more nuanced theory of PMS that is just developing. Estrogen and progesterone both get transformed into dozens of hormonal derivatives, some of which are of great interest to neuroscientists because they regulate the brain’s major excitatory and inhibitory neurotransmitters—glutamate and gamma-aminobutyric acid (GABA). During the hormonal fluctuations of the premenstrual phase, the levels of these derivatives relative to one another can get out of whack, which can lead to too much excitement of the nerve cells in the brain’s emotional circuitry. This could happen because too much glutamate is being produced or not enough GABA, but either way, the runaway activity can lead to mood changes, anxiety attacks, aggression, and even seizures. One recent study found that while hormone levels were the same in women with and without PMS symptoms, their GABA levels were different. Exercise has widespread effects on the GABA system, which puts the brakes on excessive cellular activity as Xanax does. Studies in rats have shown that just one bout of exercise turns on the genes that produce GABA, for instance. Exerc...