26 Why Your Brain Needs Exercise, SCIENTIFIC AMERICAN

 JANUARY 2020

VOLUME 322, NUMBER 1

SCIENTIFIC AMERICAN

48

W

TO

EVOLUTION

26 Why Your Brain Needs Exercise

The evolutionary history of humans may explain why physical activity can slow brain aging. By David A. Raichlen and Gene E. Alexander

SPACE 32 The Galactic Archipelago

Even if the Milky Way is crawling with spacefaring aliens, we should not be surprised that they haven't visited Earth. By Caleb Scharf

HEALTH 40 Unbound from Opioids

More than seven million chronic pain patients continue to take risky painkillers. Researchers

Photograph by Tim Flach

are finding better ways to wean people off them while keeping distress low. By Claudia Wallis

ANIMAL COGNITION

The Surprising Power of the Avian Mind

Some bird species use tools and can recognize them selves in the mirror. How do tiny brains pull off such big feats?

By Onur Güntürkün

PHYSICS

56 The Triple-Slit Experiment

An update to a classic experiment establishes new quantum-mechanical truths and paves the way toward a novel strategy for quantum computing. By Urbasi Sinha

INNOVATIONS IN

The DNA Drug Revolution

By manipulating life's master molecule, scientists are treat ing the root causes of disease.

The Power of Spheres New arrangments of DNA and RNA can treat illnesses conventional drugs cannot. By Chad A. Mirkin, Christine Laramy and

Kacper Skakuj

23 and Baby

Should newborns receive genetic screening? By Tanya Lewis

Gene Therapy Arrives What's in the pipeline. By Jim Daley

S1

SCIENTIFIC 75 AMERICAN

ACTIVE BODY ACTIVE BRAIN

ON THE COVER

Exercise is well

known to have positive effects on the aging brain. New research hints at why this is the case and suggests that combining cognitive tasks with physical acti vity can enhance those benefits. Illustration by Bryan Christie Design.

48

S3

S8

S12

S14 All of Us

Fixing bias in DNA medicine. By Stephanie Devaney

January 2020, ScientificAmerican.com 14 From the Editor

6 Letters

10 Science Agenda Time to stop targeting teens with By the Editors

11 Forum

Congress must protect scientific and stop abuses of power. By Clock

12 Advances Abandoned buildings' dangerous mo

engineered to produce psychedelic d

while asleep. New chemical maps of e

22 Meter Poetry returns to the pages of Scientif

By Diane Ackerman

23 The Science of Health Our gut microbes activate some medici others and provoke side effects. By Cla

24 Ventures

Technology will make elections secure-but By Wade Roush

63 Recommended

Birds of a feather must stick together. Love of the future. SETI, phone home. Math can be of life and death. By Andrea Gawrylewski

64 Observatory Why we shouldn't fact-check scientific judgme

By Naomi Oreskes

66 Anti Gravity

Rats learned to drive tiny cars as a model for a new skills. By Steve Mirsky

67 50, 100 & 150 Years Ago

70 Graphic Science The colorful past 175 years of Scientific American By Jen Christiansen and Nicholas Rougeur ScAnenan (5N 6-7 Value 121 Number Uanuary 2005, publiced monly by the Hadion of Nature America, Inc., 1 New York Plaza, Suite 4600, New York, NY 100045 patage pato Now York, and at additional maling offices Canada Postal Canadian Drabution Sales Agreement No. 40012504. Canadian BN No. 127387652RT TVO Publication Mail A40250m undeverte wall to Soube Anacan, Ba Sh Main Marc

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external reality but are not that reality it self. Furthermore, most of our conscious thoughts build on our understanding of external reality and affect it through our actions Mathematics is only as fictional as law, love, economics and government. CLYDE OAKLEY Centennial, Colo.

Why are mathematical constructs singled out when the question of existence is ap plicable to every word, symbol and con cept? To suggest the number one or the verb "run" are real rather than models of real things is to espouse a dualism similar to Plato's worlds of being and becoming. The instantiations of mathematics and ev ery field of study are discovered; the mod els are invented. Otherwise the current theory of physics is foundationally flawed. CHARLES H. JONES Eugene, Ore.

WEAPONIZED INFORMATION

In "A New World Disorder," Claire Wardle refers to Russians hacking into e-mails from the Hillary Clinton campaign as an example of "genuine information that is shared with an intent to cause harm."

I don't understand the fuss about Rus sians' efforts to discredit Clinton. If they didn't falsify anything, I would have con sidered it a public service. Aren't voters entitled to get as much information about the character of a candidate as possible? FRED BUSHNELL Pfalzgrafenweiler, Germany

WARDLE REPLIES: There are a number of reasons certain information should be leaked or shared, which is why we have protections for whistle-blowers. But ille gally hacking into an e-mail service to "re veal" information that should have been secured is not a characteristic of a func tioning society. We have freedom-of-infor nation laws in many countries to allow he investigation of communications and ctions by people in authority. I wrote the rticle partly to get people to think about e complexities of this space. Sometimes Es in our interest to have access to genu information, but that's why we have es and ethical guidelines around secret ordings, hacking and whistle-blowing: same techniques that can be used for public good can be used by bad actors are trying to publicize information does not benefit the public interest.

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Time's Up for "Anti-Gay Therapy"

Most states still allow this damaging practice targeting young teens

Last summer a South Carolina man named McKrae Game, who founded a network to promote "conversion therapy" for gay peo ple, disavowed his own work. The Hope for Wholeness group Game established tries to help individuals follow his entreaty to attain "freedom from homosexuality through Jesus Christ." But Game, who revealed that he was gay last year, pleaded on Facebook: "I WAS WRONG! Please forgive me!"

It might be assumed from this refutation that any attempts to forcibly change a young person's sexual orientation are about to go the way of bloodletting frontal lobotomy and trepanation. But that supposition would be wrong: if past trends hold, 16,000 LGBTQ-lesbian, gay, bisexual, transgender and queer-teenagers in the US will go through conversion therapy before they turn 18, according to the Williams Institute at the U.C.L.A. School of Law, and only 18 states have banned this harmful practice for minors,

Some conservative religious organizations still back "anti-gay therapy" and on occasion end up in court to defend it. Their chances of prevailing have been bolstered by an increasingly right-leaning judiciary fostered by the nation's red/blue divide. The reason no minor should be subjected to this practice has nothing to do with partisan politics or religious beliefs. The putative therapy should be discarded because it is rooted in bad science. Its origins are tied to both rejected concepts about sex-

uality and therapies based on those discredited notions.

Homosexuality-once explained erroneously as the result of an overbearing mother-was classified as a form of mental illness in psychiatry's first diagnostic manual, published in 1952. In the past, treatments to "cure" it included electroshock, chemical ther apies such as the forced hormone treatments infamously inflict ed on British mathematician Alan M. Turing, and the hiring of prostitutes for "behavioral" interventions. But milder versions penist today in the form of aggressive counseling and, at times, the administration of measures that induce nausea or vomiting. Trying to alter an individual's sexual identity should be banned simply because of the irreparable harm it causes. In a 2019 survey of almost 35,000 young people, the Trevor Project, which provides crisis intervention for LGBTQ youths, found that 42 percent of a

subgroup who had received conversion therapy attempted suicide. The medical establishment, thankfully, has become a solid critic of anti-gay conversion. The American Medical Association, the American Psychological Association and other organizations

10 Scientific American, January 2020

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characterize it as useless and injurious. The public is also op posed: a 2019 Reuters/Ipsos national poll found that 56 percent of U.S. adults think conversion therapy should be illegal. Although medical and psychological associations have asked

explicitly that Congress and state governments ban anti-gay.co version, there has been a backlash from groups such as the lib erty Counsel, which promotes "evangelical values." Listed by the Southern Poverty Law Center (SPLC) as an anti-LGBTQ hate group, the Liberty Counsel noted in a press release that it is fighting several existing bans on conversion therapy. Luckily verdicts can go both ways: in a 2015 case brought by the SPLC, New Jersey state court ruled that Jews Offering New Alternatives for Healing-tellingly abbreviated as JONAH-had engaged in consumer fraud by offering conversion therapy because home sexuality is not a mental illness.

The best way to stop this practice is through a federal resolo tion or through additional bans by the other 32 states-or even by local jurisdictions. Bills have been introduced to put a ban in place at the federal level, but these are still languishing in the House of Representatives.

Time may be running out. New York City had a ban but voted to undo it in September 2019: the City Council feared that a law suit to quash the ban, filed by another Christian advocacy group, might make its way up to an ever more conservative Supreme Court that could rule against the injunction. Whether this detest. able practice continues may depend on the 2020 presidential and congressional elections-which, depending on the outcome, might provide an opening for legislation to finally put an end to a pseudoscientific technique masquerading as therapy.

JOIN THE CONVERSATION ONLINE Visit Scientific American on Facebook and Twitter or send a letter to the editor: editors@sciam.com

Illustration by Thomas Fuchs

EVOLUTION

WHY YOUR BRAIN NEEDS EXERCISE

Key transitions in the evolutionary history of humans may have linked body and mind in ways that we can exploit to slow brain aging

By David A. Raichlen and Gene E. Alexander

Illustration by Bryan Christie Design

January 2020, Scientific American.com 27

WE

biological sciences and director of the evolutionary biology of exercise laboratory at the University of Southern California. His research focuses on the biomechanics and physiology of exercise from an evolutionary perspective.

David A. Raichlen is

a professor of

Gene E. Alexander is a professor of psychology and psychiatry and director of the brain imaging, behavior and aging laboratory at the University of Arizona. He studies the aging brain in both healthy adults and those suffering from neurodegenerative disease.

N THE 1990S RESEARCHERS ANNOUNCED A SERIES OF DISCOVERIES THAT WOULD UPEND a bedrock tenet of neuroscience. For decades the mature brain was under stood 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, sci entists 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 neurodegenera tive conditions. But the research raised a key question: Why does exercise affect the brain at all?

IN BRIEF

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 build- ing 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?

It is by now well established that exercise has positive effects on the brain, especially as we age. Less clear has been why physical activi ty affects the brain in the first place. Key events in the evolutionary history of humans may have forged the link be tween exercise and brain function. Cognitively chal lenging exercise may benefit the brain more than physical activity that makes fewer cogni tive demands.

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 under stand why and how exercise engages the brain, per- haps we can leverage the relevant physiological path- ways to design novel exercise routines that will boost people's cognition as they age-work that we have begun to undertake.

28 Scientific American, January 2020

FLEXING THE BRAIN

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 research ers 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 oth ers went on to demonstrate that exercise-induced neurogenesis is associated with improved perfor mance on memory-related tasks in rodents. The re sults of these studies were striking because atrophy of the hippocampus is widely linked to memory difficul ties 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

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aut in humans, just like in rodents, acrobic exercise leads to production of BDNF and augments the structure-that is, e sire and connectivity-of key areas of the brain, including he hippocampus. In a randomized trial conducted at the Uni wity of Illinois at Urbana-Champaign by Kirk Erickson and Arthur Kramer, 12 months of aerobic exercise led to an increase BDNF levels, an increase in the size of the hippocampus and provements in memory in older adults. Other investigators have found associations between exer

ce 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 UK., published in 2019 in Brain Imaging and havior, 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 cogni tive functions.

Researchers have also documented clear links between aero be 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, the 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.

UPRIGHT AND ACTIVE

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 examin ing 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, chim panzees and bonobos, between six million and seven million years ago. In that time, hominins evolved a number of anatomi cal and behavioral adaptations that distinguish us from other primates. We think two of these evolutionary changes in partic ular 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 adjust ments 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.

New Neurons in Aging Brains

Exercise leads to beneficial changes in the adult brain, including the birth of new neurons and increased connections among existing neurons. One of the ways in which physical activity seems to induce this neuroplasticity is by increasing production of a protein called brain-derived neurotrophic factor (BDNF), which promotes neuron growth and survival. Recent research suggests that cognitively engaging the brain during physical activity enhances this process.

Cognitively engaged exercise may aug ment neuroplasticity by exploiting

physiological pathways between the body and the brain that were

forged in our hunter gatherer forebears, who had to multitask to find food.

Spatial memory and navigation

Motor system and control

BDNF

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Hippocampus

Stem cell

Stem cells. give rise to cells destined to become new neurons

Nascent neuron

New cell migrates and develops into an immature new neuron

New neuron is active and wired into a learning network

Executive function (decisions and planning)

January 2020, Scientific American.com 29

Bipedalism

By around six million to seven million years ago human ancestors had abandoned walking on all fours for striding upright on their hind limbs like The shift from quadrupedal to bipedal locomotion introduced balance challenges that may have placet new demands on the brain.

Hunting and Gathering Some two million years ago our ancestors

began to forage in a new way, hunting animals and gathering plant foods. This strategy involves far more aerobic activity than is seen in other apes, which subsist mainly on plants And it requires that the brain carry out an array of cognitive tasks while on the move.

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In the six million to seven million years since the human lineage diverged from that of the chimpanzees and bonobos, our kind has evolved a host of character istics that set us apart from other apes. The beneficial effects of cognitively engaged exercise on the brain may stem from two evolutionary changes in particular that made humans more physically active than our ape cousins and supercharged our ability to multitask: the shift to upright walking and the adop tion of hunting and gathering as a subsistence strategy.

Orangutans

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Chimpanzees

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 proba- bly 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 subsis- tence 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 to ward 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 de-

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ed by the hippocampus and the prefrontal cortex, among oth regions. Hunter-gatherers also often forage in groups, in whic case they may have conversations while their brains are ma taining their balance and keeping them spatially located their environment. All of this multitasking is controlled, in p by the prefrontal cortex, which also tends to diminish with a

Although any foraging animal must navigate and figure of where to find food, hunter-gatherers have to perform the functions during fast-paced treks that can extend over ment than 20 kilometers. At high speeds, multitasking becomes eve more difficult and requires faster information processing. Pr an evolutionary perspective, it would make sense to have brain ready to respond to an array of challenges during and ter foraging to maximize the chances of success in finding food But the physiological resources required to build and mainta the vival of new neurons-cost the body energy, meaning that i we do not regularly make use of this system, we are likely to lo these benefits.

This evolutionary neuroscience perspective on exercise and the brain, which we detailed in an article published in 2017 Trends in Neurosciences, has profound implications for humans today. In our modern society, we do not need to engage in aere bie physical activity to find food for survival. The brain atrop cisions and plan their routes-cognitive tasks that are support-aging may be partly related to our sedentary habits. and attendant cognitive declines that commonly occur during

30 Scientific American, January 2020