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For decades, the mature brain was understood to be incapable of growing new neurons. Once an individual reached adulthood, researchers thought, the brain actually began to lose neurons. But then, in the 1990s, a series of discoveries shook this bedrock tenet of neuroscience.
In one particularly striking experiment with mice, scientists found that simply running on a wheel led to the birth of new neurons in the hippocampus, a brain structure associated with memory. Since then, other studies have established that exercise has positive effects on the brains of humans, too.
It’s well-known that physical activity improves the functioning of many organ systems in the body. But the effects are usually linked to better athletic performance. For example, when you walk or run, your muscles demand more oxygen, and over time your cardiovascular system responds by increasing the size of your heart and building new blood vessels. The physical challenges of exercise enhance endurance. But what challenges elicit a response from the brain?
Answering this question requires us to rethink our understanding of exercise. While many people consider walking and running to be something the body does on autopilot, research over the past decade indicates that exercise is as much a cognitive activity as a physical one. In fact, this link between physical activity and brain health may trace back millions of years to the origin of certain hallmark traits of humankind.
If we can better understand why and how exercise engages the brain, we might be able to design new workout routines that boost people’s cognition as they age.
Flexing the Brain
First, we need to consider which aspects of brain structure and cognition are most responsive to exercise.
When researchers at the Salk Institute for Biological Studies in California showed that running increased the generation of new hippocampal neurons in mice, they noted that this appeared to be tied to a protein called brain-derived neurotrophic factor. BDNF is produced throughout the body and in the brain, and it promotes both the growth and the survival of nascent neurons.
The Salk group and others went on to demonstrate that exercise-induced neurogenesis is associated with improved performance on memory-related tasks in rodents. These results were striking because atrophy of the hippocampus is widely linked to memory difficulties during healthy human aging, and it occurs to a greater extent in people with neurodegenerative diseases such as Alzheimer’s.
Following up on this work in animals, a further series of investigations determined that aerobic exercise leads to the production of BDNF in humans, too. In a randomized trial conducted by Kirk Erickson and Arthur Kramer at the University of Illinois at Urbana-Champaign, 12 months of aerobic exercise led to a rise in BDNF levels, an increase in the size of the hippocampus, and improvements in memory in older adults.
In our own study of more than 7,000 middle-aged to older adults in the UK, published in 2019, we demonstrated that people who spent more time engaged in moderate to vigorous physical activity had larger hippocampal volumes.
It isn’t yet possible to say whether these effects in humans are related to neurogenesis or other forms of brain plasticity, such as increasing connections among existing neurons. But together the results clearly indicate that exercise can benefit the hippocampus and its cognitive functions.
Researchers have also found clear links between aerobic exercise and benefits to other parts of the brain, including expansion of the prefrontal cortex. Growth of this region is tied to sharper executive cognitive functions, which involve planning, decision-making and multitasking. Like memory, these abilities tend to decline with healthy aging and are further degraded in the presence of Alzheimer’s.
Scientists suspect that increased connections between existing neurons, rather than the birth of new neurons, are responsible for the beneficial effects of exercise on the prefrontal cortex and other brain regions outside the hippocampus.
Upright and Active
Our next step was to figure out exactly which cognitive challenges involved in physical activity trigger this adaptive response. We thought examining the evolutionary relation between the brain and the body might be a good place to start.
Between six million and seven million years ago, hominins (the group that includes modern humans and our close extinct relatives) split from the lineage leading to our closest living relatives, chimpanzees and bonobos. In that time, hominins evolved a number of anatomical and behavioral adaptations that distinguish us from other primates. We think two of these evolutionary changes in particular bound exercise to brain function in ways that people can make use of today.
First, our ancestors shifted from walking on all fours to walking upright. Our bipedal posture means there are times when our bodies are precariously balanced over just one foot instead of two or more limbs like other apes. Our brains must coordinate a great deal of information and make adjustments to muscle activity throughout the body to maintain our balance. At the same time, we also have to watch out for any environmental obstacles. In other words, because we’re bipedal, our brains may be more cognitively challenged than those of our quadrupedal ancestors.
Second, fossil evidence suggests that early in human evolution, our ancestors were sedentary bipedal apes who ate mainly plants. By some two million years ago, however, as habitats dried out under a cooling climate, at least one group of ancestral humans began to forage in a new way: by hunting animals and gathering plant foods.
Hunting and gathering dominated human subsistence strategies for nearly two million years before the advent of farming and herding around 10,000 years ago. And because of the long distances traversed in search of food, hunting and gathering involves much more aerobic activity than a sedentary lifestyle.
Increased demands on the brain accompanied this shift toward a more physically active routine. When out foraging, hunter-gatherers must survey their surroundings to know where they are. This kind of spatial navigation relies on the hippocampus, the same brain region that benefits from exercise and that tends to atrophy as we get older.
Hunter-gatherers must also scan the landscape for signs of food, using sensory information from their visual and auditory systems. They have to remember where they’ve been before and when certain kinds of food were available. To do all this, the brain uses information from both short- and long-term memory, allowing people to make decisions and plan their routes—cognitive tasks that are supported by the hippocampus and the prefrontal cortex, among other regions.
Hunter-gatherers often forage in groups, too, which means they may have conversations while their brains are maintaining their balance and keeping them spatially located in their environment. All of this multitasking is controlled, in part, by the prefrontal cortex, which also tends to diminish with age.
Although any foraging animal must navigate and figure out where to find food, hunter-gatherers have to perform these functions during fast-paced treks that can extend over more than 20 kilometers. At high speeds, multitasking becomes even more difficult and requires faster information processing.
From an evolutionary perspective, it makes sense to have a brain that’s ready to respond to an array of challenges during and after foraging to maximize the chances of success in finding food. But the physiological resources required to build and maintain such a brain—including those that support the birth and survival of new neurons—cost the body energy. So if we don’t regularly make use of this system, we’re likely to lose these benefits.
This evolutionary neuroscience perspective on exercise and the brain has profound implications for humans today. In our modern society, we don’t need to engage in aerobic physical activity to find food for survival. The brain atrophy and attendant cognitive declines that commonly occur during aging may be partly related to our sedentary habits.
But simply exercising more may not realize the full potential of physical activity for impeding brain decline. Indeed, our model suggests that even people who already get a lot of aerobic activity may want to rethink their routines. It’s possible we’re not always exercising in ways that take full advantage of our evolved mechanisms for sustaining brain performance.
Think about how many of us get our aerobic exercise. Often we go to gyms and use a stationary exercise machine. The most cognitively demanding task in such a workout is deciding which channel to watch on the built-in television. What’s more, these machines remove some of the demands of maintaining balance and adjusting speed, among many other intrinsic cognitive challenges of movement through a changing environment. So is this form of exercise is shortchanging us?
Our ancestors evolved in an unpredictable world. What if we could modify our exercise routines to include cognitive challenges like those faced by our hunter-gatherer forebears? If we can boost the effects of exercise by including a cognitively demanding activity, then maybe we can increase the effectiveness of exercise regimens aimed at improving cognition during aging. We might even be able to alter the course of neurodegenerative diseases such as Alzheimer’s.
Move and Think
A growing body of research suggests that cognitively stimulating exercise may indeed benefit the brain more than exercise without such cognitive demands.
Gerd Kempermann and his colleagues at the Center for Regenerative Therapies in Dresden, Germany, explored this possibility by comparing the growth and survival of new neurons in the mouse hippocampus after exercise alone and after exercise in a cognitively enriched environment.
They found an additive effect: exercise alone was good for the hippocampus. But combining physical activity with cognitive demands in a stimulating environment was even better, leading to even more new neurons. Using the brain during and after exercise seemed to trigger enhanced neuron survival.
We and others have recently begun to extend these studies from animals to humans—with encouraging results. For example, Cay Anderson-Hanley of Union College has tested simultaneous exercise and cognitive interventions in people with mild cognitive impairment, a condition associated with increased risk for Alzheimer’s.
More work needs to be done in such populations before we can draw any firm conclusions, but the results so far suggest that people who are already experiencing some cognitive decline may benefit from exercising while playing a mentally demanding video game.
In studies of healthy adults, Anderson-Hanley and her colleagues have also shown that simultaneously exercising and playing a cognitive challenging video game may lead to a greater increase in circulating BDNF than exercise alone. These findings further bolster the idea that BDNF is instrumental in bringing about exercise-induced brain benefits.
In our own work, we’ve developed a game specifically designed to challenge aspects of cognition that tend to decline with age and that are probably needed during foraging. Players spatially navigate and complete attention and memory tasks while cycling at a moderate aerobic intensity level. To evaluate the potential of this approach to boost cognitive performance in healthy older adults, we’re comparing a group exercising while playing the game with a group exercising without the game, a group playing the game without exercising, and a control group that only watches nature videos. The results to date are promising.
Many other research groups are testing combinations of exercise and cognitive tasks. Soon, we’ll likely have a better idea of how best to use them to support and enhance cognition in both healthy people and those experiencing disease-related cognitive decline.
In addition to the specially designed interventions already mentioned, it’s possible that playing sports that require combinations of cognitive and aerobic tasks may also activate these brain benefits. In fact, we recently showed that collegiate cross-country runners who train extensively on outdoor trails have increased connectivity among brain regions associated with executive cognitive functions compared to healthy but more sedentary young adults. Future work will help us understand whether these benefits are also greater than those seen in runners who train in less complex settings—on a treadmill, for instance.
Although it’s still too early to make specific prescriptions for combining exercise and cognitive tasks, we can say with certainty that exercise is a key factor in preserving brain function as we age.
The U.S. Department of Health and Human Services guidelines advise people to engage in aerobic exercise for at least 150 minutes a week at a moderate intensity or at least 75 minutes a week at a vigorous intensity (or an equivalent combination of the two). Meeting or exceeding these exercise recommendations is good for the body and may improve brain health.
Clinical trials will tell us much more about the effectiveness of cognitively engaged exercise—which sorts of mental and physical activities are most impactful, for example, and the optimal intensity and duration of exercise for augmenting cognition. But in light of the evidence so far, we believe that with continued research we’ll be able to target physiological pathways linking the brain and the body and exploit our brain’s evolved adaptive capacity for exercise-induced plasticity during aging.
In the end, working out both the body and the brain may help keep the mind sharp for life.
Reference: Why Your Brain Needs Exercise. David A. Raichlen and Gene E. Alexander in Scientific American Vol. 322, No. 1, 26-31; January 2020. doi:10.1038/scientificamerican0120-26
