In the 1990s researchers announced a series of discoveries that would upend
a bedrock tenet of neuroscience. For decades the mature brain was understood to
be incapable of growing new neurons. Once an individual reached adulthood, the
thinking went, the brain began losing neurons rather than gaining them. But
evidence was building that the adult brain could, in fact, generate new
neurons. 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 that is associated with memory. Since then,
other studies have established that exercise also has positive effects on the
brains of humans, especially as we age, and that it may even help reduce the
risk of Alzheimer’s disease and other neurodegenerative conditions. But the
research raised a key question: Why does exercise affect the brain at all?
Physical activity improves the function 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 the heart and building
new blood vessels. The cardiovascular changes are primarily a response to the
physical challenges of exercise, which can enhance endurance. But what
challenge elicits a response from the brain?
Answering this question requires that we rethink our views of exercise.
People often consider walking and running to be activities that the body is
able to perform on autopilot. But research carried out over the past decade by
us and others would indicate that this folk wisdom is wrong. Instead exercise
seems to be 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 hallmark traits of humankind. If we can better understand why and
how exercise engages the brain, perhaps we can leverage the relevant
physiological pathways to design novel exercise routines that will boost
people’s cognition as they age—work that we have begun to undertake.
To explore why exercise benefits the
brain, we need to first consider which aspects of brain structure and cognition
seem most responsive to it. When researchers at the Salk Institute for
Biological Studies in La Jolla, Calif., led by Fred Gage and Henriette Van
Praag, showed in the 1990s that running increased the birth of new hippocampal
neurons in mice, they noted that this process appeared to be tied to the
production of a protein called brain-derived neurotrophic factor (BDNF). 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. The results of these studies
were striking because atrophy of the hippocampus is widely linked to memory
difficulties during healthy human aging and occurs to a greater extent in
individuals with neurodegenerative diseases such as Alzheimer’s. The findings
in rodents provided an initial glimpse of how exercise could counter this
decline.
Following up on this work in animals, researchers carried out a series of
investigations that determined that in humans, just like in rodents, aerobic
exercise leads to the production of BDNF and augments the structure—that is,
the size and connectivity—of key areas of the brain, including the hippocampus.
In a randomized trial conducted at the University of Illinois at
Urbana-Champaign by Kirk Erickson and Arthur Kramer, 12 months of aerobic
exercise led to an increase in BDNF levels, an increase in the size of the hippocampus
and improvements in memory in older adults.
Other investigators have found associations between exercise and the
hippocampus in a variety of observational studies. In our own study of more
than 7,000 middle-aged to older adults in the U.K., published in 2019 in Brain
Imaging and Behavior, we demonstrated that people who spent more time
engaged in moderate to vigorous physical activity had larger hippocampal
volumes. Although it is not 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, together the results clearly
indicate that exercise can benefit the brain’s hippocampus and its cognitive
functions.
Researchers have also documented clear links between aerobic exercise and
benefits to other parts of the brain, including expansion of the prefrontal
cortex, which sits just behind the forehead. Such augmentation of this region
has been tied to sharper executive cognitive functions, which involve aspects
of planning, decision-making and multitasking—abilities that, like memory, 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.
With mounting evidence that aerobic exercise can boost brain health, especially
in older adults, the next step was to figure out exactly what cognitive
challenges physical activity poses that trigger this adaptive response. We
began to think that examining the evolutionary relation between the brain and
the body might be a good place to start. 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, between six million
and seven million years ago. 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 on
just their hind legs. This bipedal posture means that there are times when our
bodies are precariously balanced over one foot rather than two or more limbs
like in other apes. To accomplish this task, our brains must coordinate a great
deal of information and, in the process, make adjustments to muscle activity
throughout the body to maintain our balance. While coordinating these actions,
we must also watch out for any environmental obstacles. In other words, simply
because we are bipedal, our brains may be more cognitively challenged than
those of our quadrupedal ancestors.
Second, the hominin way of life changed to incorporate higher levels of
aerobic activity. Fossil evidence indicates that in the early stages of human
evolution, our ancestors were probably relatively 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, hunting animals and gathering plant foods. Hunting and
gathering dominated human subsistence strategies for nearly two million years
until the advent of farming and herding around 10,000 years ago. With Herman
Pontzer of Duke University and Brian Wood of the University of California, Los
Angeles, we have shown that because of the long distances traversed in search
of food, hunting and gathering involves much more aerobic activity than seen in
other apes.
Increased demands on the brain accompanied this shift toward a more
physically active routine. When out foraging afar, hunter-gatherers must survey
their surroundings to make sure they 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. In addition, they have to
scan the landscape for signs of food, using sensory information from their
visual and auditory systems. They must remember where they have been before and
when certain kinds of food were available. The brain uses this 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 also often forage in
groups, in which case 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 would make sense to have a brain 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, meaning that if we do not regularly make use
of this system, we are likely to lose these benefits.
This evolutionary neuroscience perspective on exercise and the brain, which
we detailed in an article published in 2017 in Trends in Neurosciences,
has profound implications for humans today. In our modern society, we do not
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 keeping brain decline at
bay. Indeed, our model suggests that even people who already get a lot of
aerobic activity may want to rethink their routines. It is possible that we
might not always exercise in ways that take full advantage of our evolved
mechanisms for sustaining brain performance.
Think
about the ways in which 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 might be deciding what channel to watch on the built-in
television. What is 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.
What if 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 augment the effects of exercise by including a cognitively demanding
activity, then perhaps we can increase the efficacy of exercise regimens aimed
at boosting cognition during aging and potentially even alter the course of
neurodegenerative diseases such as Alzheimer’s.
In fact, a growing body of research suggests that exercise that is
cognitively stimulating may indeed benefit the brain more than exercise that
does not make such cognitive demands. For example, Gerd Kempermann and his
colleagues at the Center for Regenerative Therapies Dresden in Germany explored
this possibility by comparing the growth and survival of new neurons in the
mouse hippocampus after exercise alone or after exercise combined with access
to 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, researchers have been exploring
combining exercise and cognitive challenges in individuals experiencing notable
cognitive decline. Cay Anderson-Hanley of Union College in Schenectady, N.Y.,
has tested simultaneous exercise and cognitive interventions in people with
mild cognitive impairment, a condition associated with increased risk for
Alzheimer’s. More work certainly needs to be done in populations such as this
one 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
elicit 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 have developed a
game designed to specifically challenge aspects of cognition that tend to
decline with age and that are probably needed during foraging. In the game,
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 are
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. In the near future, we will probably have a better idea of how
best to deploy them to support and enhance cognition in both healthy
individuals and those experiencing disease-related cognitive decline.
In addition to specially designed interventions similar to the ones
described here, it is possible that participation in sports that require
combinations of cognitive and aerobic tasks may be a way to activate these
brain benefits. For example, 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 with
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.
Much remains to be discovered. Although it is still too early to make
specific prescriptions for combining exercise and cognitive tasks, we can say
with certainty that exercise is a key player in preserving brain function as we
age. The U.S. Department of Health and Human Services guidelines suggest that
people should 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 efficacy of cognitively
engaged exercise—what kinds 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 we have so far, we believe
that with continued careful research we can 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 during exercise may help keep the mind sharp for
life.
