Cerebrum Winter 2020

EMERGING IDEAS IN BRAIN SCIENCE

How the Brain CREATES

Brain imaging and behavioral experiments can now examine how creative thinking works in different contexts and domains.

Roger E. Beaty, Ph.D.

The Creative Brain Page 10

Keely A. Muscatell, Ph.D.

Brains, Bodies, and Social Hierarchies

Page 14

Brenda Patoine

Social Media & Teens: No Simple Answers

Page 18

Kayt Sukel

Building a Better Brain Model

Page 21

Roger E. Beaty, Ph D., is an assistant professor of psychology at The Pennsylvania State University, where he directs the Cognitive Neuroscience of Creativity Lab His lab studies the psychology and neuroscience of creativity, using brain imaging and behavioral experiments to examine how creative thinking works in different contexts and domains, from the arts, to the sciences, to everyday life. His research has been supported by grants from the John Templeton Foundation and the National Science Foundation. He received his Ph.D. at the University of North Carolina at Greensboro and completed postdoctoral training at Harvard University.

Keely A. Muscatell, Ph.D., is an assistant professor of psychology and neuroscience at the University of North Carolina at Chapel Hill, where she directs the Social Neuroscience and Health Laboratory. Her research focuses on uncovering the neural, psychological, and physiological mechanisms linking social experiences to physical health and well-being. She completed post-doctoral training at UC Berkeley and UC San Francisco, earned her Ph.D. in psychology from UCLA, and a B.A. in psychology and Spanish from the University of Oregon. When not in the lab, Muscatell can be found reading Dave Eggers, Ben Lerner, and Zadie Smith, watching college football, and/or drinking craft beer while listening to her and her partner’s vinyl collection.

Brenda Patoine is a freelance science writer, reporter, and blogger who has been covering neuroscience research for more than 30 years. Her specialty is translating complex scientific findings into writings for the general public that address the question of “what does this mean to me?” She has interviewed hundreds of leading neuroscientists over three decades, including six Nobel Laureates. She founded ScienceWRITE Medical Communications in 1989 and holds a degree in journalism from St. Michael’s College. Other areas of interest are holistic wellness, science and spirituality, and bhakti yoga. Brenda lives in Burlington, VT with her cat Shakti.

Kayt Sukel‘s work has appeared in the Atlantic Monthly, the New Scientist, USA Today, the Washington Post, Parenting, National Geographic Traveler, and the AARP Bulletin. She is a partner at the award-winning family travel website Travel Savvy Mom, and is also a frequent contributor to the Dana Foundation’s science publications. She has written about out-of-body experiences, fMRI orgasms, computer models of schizophrenia, the stigma of single motherhood, and why one should travel to exotic lands with young children. She is the author of Dirty Minds: How Our Brains Influence Love, Sex and Relationships and The Art of Risk: The New Science of Courage, Caution & Chance

FEATURES

10 The Creative Brain

Brain imaging and behavioral experiments can now examine how creative thinking works in different contexts and domains.

By Roger Beaty, Ph.D.

14 Brains, Bodies, and Social Hierarchies

Does our perception of our social standing impact life expectancy and heart health? Are there interventions available to develop emotion regulation strategies? How does low income impact the way the brain functions?

By Keely Muscatell, Ph.D.

18 Social Media & Teens: No Simple Answers

Our author explores the question on every parent’s mind: Is social media rotting kids’ brains?

By Brenda Patoine

21 Building a Better Brain Model

Advances in technology have led to the development of organoids and chimeric models to study the activity of human neurons—and how they communicate with one another.

By Kayt Sukel

SECTIONS

5 Advances

Notable brain science findings

6 Briefly Noted

By the Numbers;

7 Bookshelf

By Philip M. Boffey

POINTS OF INTEREST

NOTABLE FACTS IN THIS ISSUE

4 Instagram, which is owned by Facebook, is testing a new policy in this country and abroad to hide visible likes on its platform.

The Social Media Conundrum, Page 8

4 A phenomenon known as fixation or impasse—taking a break to let our minds wander may loosen things up and help us find a creative solution.

The Creative Brain, Page 10

4 Hundreds of studies have shown that individuals from lower SES backgrounds have higher blood pressure and greater arterial plaque buildup, and ultimately suffer heart attack and stroke at higher rates, than those of higher status. Brain, Bodies, and Social Hierarchies, Page 14

4 “[Social media use] doesn’t affect all teens the same, and overall, is neither good nor bad for the mental health of teens.”

Social Media & Teens: No Simple Answers, Page 18

4 Researchers are using organoids, or so-called “minibrains,” three-dimensional, self-organizing tissue cultures derived from human iPSCs, to study how brain cells come together as the brain grows.

Building a Better Brain Model, Page 21

Creative minds (and brains) at work

BY BILL GLOVIN Executive Editor, Dana Foundation

At the Dana Foundation, we strive to provide you with the latest in brain science and all that it includes: research, policy, ethics, funding—the list goes on and on. We have done this in a variety of ways: neuroscientist-authored articles followed by podcasts with people such as Thomas Insel, David Van Essen, Helen Mayberg, Steve Hyman, Britt and Edwin Moser—I’m proud to say the list is formidable. We’ve also offered up articles by science writers that explain complex research; a neuroethics column; a print publication that reprinted news articles (Brain in the News), and educational materials.

And while we’re still dedicated to that course, we are consolidating most of these separate parts into a new, quarterly digital publication we are calling Cerebrum magazine. We do this in conjunction with our recent readership survey (in which you told us you very much want us to continue delivering neuroscientist-authored articles), as well as a recent website redesign aimed at helping you find what you’re looking for—a good read, details on a specific disease, something to share with your colleagues or students—more easily.

Our inaugural cover story—“The Creative Brain” by Roger Beaty at Penn State—describes the latest on what we know about the part of the brain that can make the world such an inspiring, wonderful place. Keely Muscatell at University of North Carolina tells us about new research that ties income and other factors to stress and other emotional responses. Other articles (by science writers) cover organoids and the impact of social media on teens.

Philip M. Boffey, former deputy editorial page editor and Pulitzer prize winner at the New York Times, goes in a slightly different direction by examining the effect of social media on society in his column. We are fortunate to feature Phil in an ongoing role as our neuroethics columnist.

Cerebrum is a team effort. Besides the support of our talented staff, our past and future efforts would not be possible without input from my invaluable nine-person advisory board—made of prominent neuroscientists (who weigh in on potential topics and authors, and review articles). Their bios are available in both our web and digital magazine versions.

The Dana Foundation’s mission is “to advance understanding about the brain in health and disease through research grants and public outreach.” We hope our new magazine serves you in advancing your understanding by delivering—at no cost—the kind of content that enhances your own life and the lives of others. l

EMERGING IDEAS IN BRAIN SCIENCE

Bill Glovin Executive Editor

Seimi Rurup Assitant Editor

Megan Messana Editorial Assistant

Podcast

Carl Sherman Copy Editor

Carolyn Asbury, Ph.D. Scientific Consultant

Bruce Hanson Art Director

Jaimie Nally Web Production Coordinator

Cerebrum is published by the Charles A. Dana Foundation, Incorporated. DANA is a federally registered trademark.

© 2020 by The Charles A. Dana Foundation, Incorporated. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher, except in the case of brief quotations embodied in articles.

Letters to the Editor

Cerebrum magazine

505 Fifth Avenue, 6th Floor New York, NY 10017 or cerebrum@dana.org

Letters may be edited for length and clarity. We regret that we cannot answer each one.

ADVANCES

Notable brain science findings

SCREEN TIME has been linked to white matter deficits in preschoolers in a new study led by John S. Hutton, M.D., of Cincinnati Children’s Hospital. The study found that screen time use in 3- to 5-year-olds ranging from 1.5 to 10 hours a day—well beyond the American Academy of Pediatrics recommended limit of one hour per day—were correlated with lower microstructural integrity in the neuronal cables that relay electrical signals across the brain. The cross-sectional design of the study doesn’t prove that screen time caused the deficits, but it points to the need for more research to understand the relationship between digital media use and early brain development. l

CYSTIC FIBROSIS is a rare, progressive, life-threatening disease that results in the formation of thick mucus that builds up in the lungs, digestive tract, and other parts of the body. It leads to severe respiratory and digestive problems as well as other complications such as infections and diabetes. Last fall, the US Food and Drug Administration approved Trikafta (elexacaftor/ivacaftor/ tezacaftor), the first triple combination therapy available to treat patients with the most common cystic fibrosis mutation. Trikafta is approved for patients 12 years and older who have at least one mutation in the gene that regulates cystic fibrosis, which is estimated to represent 90 percent of the cystic fibrosis population. l

AFM, or acute flaccid myelitis, is a mysterious neurological condition that can cause limb weakness and polio-like symptoms, mostly in young children. A new study, published in the New England Journal of Medicine, points to a group of common viruses—known as enteroviruses— that sometimes cause neurological symptoms. The study found antibodies to enteroviruses in the cerebrospinal fluid of nearly 70 percent of the children with AFM, a sign that their bodies had mobilized to defend against enterovirus infection. l

MICROBIOME is a collection of microbes that lives in our intestines and influences our immune system and the way we feel, as well as helps us digest food. An experiment that appeared in Nature Microbiology showed that people’s microbiomes seem to rapidly shift on a diet of raw foods. The study, which had a limited sample size, raises questions about whether starting to eat cooked foods, in the distant past, shaped the evolution of the organisms that live inside us, and whether bacteria from those foods have helped us survive times of scarcity. l

PROBLEM ADAPTATION THERAPY, or PATH, is a novel approach to treat depression. The therapy, developed at Weill Cornell Medicine in New York City and White Plains, N.Y., focuses on solving tangible problems that fuel feelings of sadness and hopelessness. It incorporates tools, such as checklists, calendars, signs, and videos, to make it accessible for people with memory issues. A caregiver is often involved. l

CRISPR, shorthand for “clustered regularly interspaced short palindromic repeats,” allows the cell (or a scientist) to precisely edit DNA or its sister molecule, RNA. A new study, published in Nature Communications, found that CRISPR-associated enzymes have the potential to kill certain bacteria and develop more effective drugs. About 10 million people (up from the current number of 750,000) could die worldwide by 2050 from viruses that are resistant to antibiotics, based on the findings. Viruses have evolved to the point where they disguise themselves from drugs, often by hiding inside host cells (less than 100 antiviral drugs have successfully made it all the way to the clinic since 1963). l

ALZHEIMER’S DISEASE is a disorder where very little progress has been made in finding a cure. But some good news came from a study in Nature Medicine that was featured on the front page of the New York Times on November 5. A woman, whose genetic profile showed she would develop Alzheimer’s by the time she was in her 50s, experienced no cognitive decline until her 70s due to a mutated gene that protected her from dementia. That finding suggests that treatments could be developed to give other people that same protective mechanism. l

OMEGA-3S—found in fish oils and other foods— is a popular supplement for both heart and brain health. But while the jury is still out on heart health, an analysis that included 32 randomized trials testing 41,467 participants found that the supplements are probably ineffective in treating depression and anxiety. Omega-3s are found in seafoods like salmon, swordfish, and mussels. Neither length of treatment nor size of dosage demonstrated effectiveness. The study was published in the British Journal of Psychiatry. l

PHOTO: RICK BERGER

BY THE NUMBERS

1 in 5 adolescents have harmed themselves to sooth emotional pain at least once, according to a review of three dozen surveys in nearly a dozen countries.

10 seconds is the amount of time it takes for nicotine from a cigarette to fill your lungs, surge through your bloodstream, and enter your brain.

20 is the percentage of Americans who suffer anxiety disorders.

25 is the percentage of all adults in Britain who take prescription medication for pain, anxiety, depression, or insomnia, and half of those people had been taking the drugs for a year or more.

200 drug trials have failed in finding a cure for Alzheimer’s disease.

500 mentally ill people in New York City call 911 every day.

IN MEMORIAM

MARGARET LAWRENCE, Pioneering Psychoanalyst

Margaret Lawrence, pediatrician and child psychologist, passed away at the age of 105 on Dec. 4, 2019, in Boston. Lawrence was primarily raised in Vicksburg, M.S., and resolved to become a doctor after learning that her older brother had died in infancy. As an adult, she attended Cornell University in the 1930s as an undergraduate but was denied acceptance into their medical school. After this rejection, Lawrence applied to Columbia University’s College of Physicians and Surgeons, where she was accepted and was the only woman of color in her class of 104 students. Having completed a pediatric residency at Harlem Hospital and then receiving her master’s in public health from Columbia, Lawrence went on to serve as chief of developmental psychiatry services for infants and children at Harlem Hospital for over 20 years and later opened up a private psychiatric practice in Rockland County, New York. l

PETE FRATES, ALS Advocate

27,000 people from around the world attended the annual meeting of the Society for Neuroscience in Chicago in October.

400,000 people around the world have brain implants. Most are for Parkinson’s.

24,000,000 Americans suffer from sleep apnea and don’t know it, and many who do know don’t get treatment.

Peter Frates, the former Boston College baseball player who helped make the ALS Ice Bucket Challenge go viral, died on Dec. 9, 2019, at the age of 34 in his Beverly, M.A., home. The 2014 internet challenge was intended to spread awareness of amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, and to encourage donations to research. It involved a person who was nominated being recorded having a bucket of ice water dumped on his or her head and then posting the video to social media, while also nominating at least three other people to take part. While not the creator of the challenge, Frates’ participation helped make it go viral, which led to the ALS Association receiving over $115 million in donations. Frates, who had ALS himself, also raised awareness about medical costs, revealing that about $70,000 to $95,000 a month was needed for treatment. About $77 million of the money raised by the challenge was used for research that led to the discovery of the NEKI gene, which contributes to the disease and may give scientists guidance in developing treatment drugs. l

BOOKSHELF

A few brain science books that have recently caught our eye

Remembering: What 50 Years of Research with Famous Amnesia Patient H. M. Can Teach Us About Memory and How It Works by

Donald G.MacKay

Widely known only as “Patient H.M.” until recently, Henry Molaison was the victim of brain surgery gone wrong. In 1953, at age 27, he received a bilateral medial temporal lobectomy in an attempt to cure his epilepsy; and while the surgery was successful in controlling the disorder, it also destroyed his hippocampus, leading Molaison to be unable to form new memories. In an attempt to help others, Molaison devoted the rest of his life to helping scientists understand his memory, or lack thereof, and from 1957 to his death in 2008, he was the most studied amnesiac patient in history. One of the doctors who worked with him for 50 years, Donald MacKay, M.D., relays what his studies showed in his book Remembering (Pronetheus Books), along with the importance of memory functions and ways to keep the brain sharp at any age. Most importantly, it keeps the promise made to Molaison that the work done with him would be used to help others. l

The Athletic Brain by Amit

Katwala

There is a theory that in order to become an expert at something, one must devote 10,000 hours to that task. In The Athletic Brain (Simon & Schuster), author Awit Katwala displays just how false that theory might be, particularly when it comes to sports. Through his book, Katwala explains how training changes the brain and, in turn, debunks the 10,000-hour rule. Other issues covered: how athletes handle pressure, ways to train the brain to release an athlete’s full potential, and how technology can

help accelerate training. The concept of neural plasticity, or how the brain is flexible and able to learn from and adapt to new experiences, and how this concept pertains to athletic training is also described. Katwala uses interviews with top athletes and scientists to not only convey the scientific facts regarding athletic training, but to do so in a way that can help anyone who is willing to learn. l

Human Language: From Genes and Brains to Behavior edited by Peter Hagoort

Language is essentially what makes us human. Edited by Peter Hagoort, Human Language (MIT Press) compiles research from various fields to study one of the most complex cognitive functions that we as humans command. This book helps analyze the capacity for language from a plethora of perspectives, and contributors draw on recent developments in fields such as neuroimaging and genetic sequencing, to provide new insights and examine everything from the organization of language skills, to the evolutionary need for communication, to the genome’s role in building a language-capable brain. l

Bedlam: An Intimate Journey Into America’s Health Crisis by Kenneth

Paul Rosenberg

Each year in America, one in five adults experiences mental illness, which translates to around 40 million people. Author Kenneth Rosenberg’s older sister, Merle, was one of them. Her previously diagnosed schizophrenia—which was kept a secret by their parents—erupted into paranoid psychosis when she was 20-years-old. While Rosenberg, M.D., did all that he could to help Merle after their parents passed away, she

continued to refuse help and died at age 55. Rosenberg eventually became a psychiatrist, and Bedlam (Random House/Penguin) chronicles the historical, political, and economic issues surrounding mental illness in America. Drawing on his own experiences, Rosenberg shows what it means to be mentally ill in the United States and how we as a society can and should move forward to help the people who are most in need. l

How to Tame a Fox (and Build a Dog) by Lee

Alan Dugatkin and Lyudmila Trut

Put simply, How to Tame a Fox (University of Chicago Press) is a story about modern-day attempts to domesticate animals, namely silver foxes. More complexly, it is also the story of evolution sped up, hidden research, and Soviet science and history coming to light. In the 1950s, an experiment was devised by geneticist Dmitry Belyaev. He theorized that by selectively breeding only the tamest and gentlest foxes, they could create domesticated ones, essentially recreating the evolution of wolves to dogs in real-time. He recruited Russian geneticist Lyudmila Trut, Ph.D., to join the experiment, and together they began their work while simultaneously attempting to hide it from agrobiologist Trofim Lysenko. (Lysenko rejected Mendelian genetics and, with the help of Joseph Stalin, shut down genetics research in the Soviet Union from the 1930s to the 1950s.) Belyaev died in 1985, but the experiment he coconducted remains ongoing with over 50 generations of foxes bred to date. This book is not only an exploration of those foxes, but about science under siege and how everything—genes, environment, evolution—shapes behavior. l

— Megan Messana

The Social Media Conundrum

BY PHILIP M. BOFFEY

Research on the impact of social media on the mental health of teenagers has yielded a confusing mix of conflicting and inconclusive results. Yet even amidst the uncertainty, the state of play has raised ethical issues for many participants in this arena, including tech companies, parents, clinicians, and researchers.

The confusing landscape of research findings is ably described by Brenda Patoine in “Social Media & Teens’ Mental Health: No Simple Answers,” one of this issue’s articles. She notes the alarms raised by a steeply rising incidence of depression, anxiety, and suicide in young people that has occurred in parallel with the rise of the smart phone and the near-universal use of social media by young people, such as Snapchat and Instagram.

But whether social media use actually causes depression or anxiety, or whether teens who are already depressed or anxious turn to social media more frequently, has yet to be pinned down. Some studies have found negative mental health effects, some have found no effects, and still others have found a positive protective effect. One complication, experts say, is that social media use doesn’t affect all teens the same way; its impact depends on the characteristics of the teens and how they use social media.

In the interests of full disclosure, I am an octogenarian who almost never uses social media but who uses his iPhone 11 for hours at a time—an average of 3.5 hours a day over the past ten days to

...[W]hether social media use actually causes depression or anxiety or whether teens who are already depressed or anxious turn to social media more frequently has yet to be pinned down.

check emails, search the internet, and send text messages. I also watch cable news on television obsessively to keep up with impeachment and election developments which are always described breathlessly as “breaking news” to hook the viewer.

The most fascinating discovery for me, in searching the internet for ethical issues raised by social media, was the anguished hand-wringing by many key players in the tech companies that have produced the social media that so many people are worried about.

Sean Parker, the billionaire first president of Facebook, gave a candid insider’s look in an interview with Axios co-founder and former Politico chief reporter Mike Allen on November 9, 2017. Parker described how social networks purposefully hook and potentially hurt our brains to maximize the time we spend on social media so that the tech companies can charge advertisers as much as possible to reach our eyeballs.

Perhaps the chief insider critic is Tristan Harris, who founded a software company that Google bought out and then hired him as a product manager. Harris has described his concerns most fully in an interview with Anderson Cooper on 60 Minutes on April 9, 2017 and in two TED Talks, the most recent one on July 26 that same year.

Harris says the problem is not that people in the industry are evil or have bad intentions, it’s that they are racing against competitors to gain users’ attentions at all costs. One simple tactic is the use of “likes” and “dislikes” on Facebook and Instagram which keeps people checking in to see how they are doing.

A more devious tactic described by Harris was employed by Snapchat, the chief way that American teenagers communicate. Programmers invented a feature called Snapstreaks, which shows

the number of consecutive days that two people have communicated with each other. That gives two teenagers something neither of them wants to lose. If they communicate 150 consecutive days, they are likely to take extreme measures to keep the streak going.

Programmers on many social media also exploit outrage, an effective measure to get your attention— especially as it relates to politicians. Readers anxiously share their outrage at what someone did or said with friends who in turn pass it on. The danger is that outrage—and outright lies—can spread rapidly on social media, tearing apart the nation’s social fabric and weakening democratic efforts to find common ground.

“I don’t know a more urgent problem than this,” Harris says. “Never before in history have a handful of people at a handful of technology companies shaped how a billion people think and feel every day with the choices they make about these screens.”

Parents, who are primarily responsible to oversee the use of social media by their children, face ethical issues of their own. They have the formidable challenge of monitoring what their children are communicating as well as time spent without snooping and invading their privacy. One idea is to set firm ground rules, perhaps in consultation with their children.

They might note what technology leaders, who know better than anyone the dangers of social media, have done with their own families. In an article in the New York Times on Sept. 10, 2014, entitled “Steve Jobs Was a Low-Tech Parent,” Nick Bilton quotes several technology chief executives and venture capitalists who strictly limit their children’s screen time, often banning all gadgets on school nights and imposing tight time limits on weekends. They worry about exposure to harmful

content like pornography, bullying from other kids, and kids becoming addicted to their devices.

Bill Gates, the founder of Microsoft, revealed in an interview with the Daily Mirror in the United Kingdom on April 21, 2017 that he banned his children from having mobile phones until they were 14, forbade phones at the dinner table, and set a curfew time after which screens could not be used so as to help his youngest get to sleep at a reasonable hour.

Other guidance for parents was posted on December 15, 2017 at an online resource of Harvard’s Graduate School of Education. The crux: avoid blanket condemnations and tailor your approach to the individual child. Stressful factors that your children may feel include seeing people posting about events to which they haven’t been invited, feeling pressure to post positive and attractive comments about themselves, feeling pressure to get comments and likes on their posts, and having someone post things about them that they can’t change or control. Some of the author’s advice was similar to that from tech insiders, such as setting screen-free times before sleep, on car rides to school, and on the occasional weekend or vacation.

Pediatricians must also cope with additional ethical burdens imposed by social media. An editorial in Pediatrics, a journal of the American Academy of Pediatrics, published in May 2018, urged clinicians to expand the kinds of questions they ask young people to include queries about social media use. Such questions might include how much time they spend on social media sites in a typical day (more than 120 minutes would raise concern), whether they think they use social media too much, whether viewing social media increases or decreases their selfconfidence, and whether they have personally experienced cyberbullying,

One proposal would push the industry to change its business model from emphasizing “time spent” on a social media site to ‘time well spent.’

and sexting, or an online user asking to have sexual relations with them. Depending on the answers, the clinician might help craft a family media plan, schedule follow-up appointments, or refer the patient for behavioral health therapy.

The ethical obligations on those who conduct research on social media is a muddle of conflicting opinions. A systematic review of the attitudes of the users of social media and the researchers who want to study their postings was published in the Journal of Medical Internet Research on June 6, 2017. It found no “overarching consensus with regard to social media research ethics.” Respondents disagreed sharply, for example, on whether postings on social media should be considered public, like a letter to the editor, or a private communication, requiring some kind of informed consent. There was much more support for using aggregate statistics than for qualitative research relying on quotes.

The authors, from universities in the United Kingdom, urged that guidelines for ethical conduct be formulated within the research community lest we miss the considerable potential of social media research, which can generate results much more quickly than the traditional published scientific literature.

What can be done to overcome the devious tactics used by tech companies to ensnare teens in compulsively using and returning to social media? The tech companies themselves, responding to rising public concerns, have begun to offer technical fixes to mitigate screen addiction.

Google has recently rolled out some experimental apps that give people help in controlling their usage. Various apps keep track of how many times you unlock your phone in a day in case you want to drive that number down, let you block work-related apps while you’re at home, and leisure-related

apps while you’re at work. These apps let you select and print out the crucial information you’ll need that day, such as schedules, important contacts, map directions, and more, so that you can go through the day without using your phone at all.

Apple has introduced features that inform people how much time they’re spending on screen, how much of that time is devoted to various activities, and how to limit the time they spend on various apps and activities.

Instagram, which is owned by Facebook, is testing a new policy in this country and abroad to hide visible likes on its platform. People will only be able to see the likes awarded their own photos but not how many likes other users have received. The goal is to reduce the anxiety caused by social comparisons.

All these are steps in the right direction but how well these voluntary approaches will work to reduce compulsive use of phones and excessive screen time remains to be seen. If they fail to make a dent in the problem, lawmakers and regulators may need to push the industry to try harder or to change its business model.

The public, which buys and uses the phones and social media apps, has enormous power to change the landscape. We can push the industry to provide even more features to reduce screen time and improve the quality, not quantity, of our communications. We can also declare more and longer holidays from the tyranny of our phones. Those of us who have tried such temporary abstinence say it is liberating. l

Phil Boffey is former deputy editor of the New York Times Editorial Board and editorial page writer, primarily focusing on the impacts of science and health on society. He was also editor of Science Times and a member of two teams that won Pulitzer Prizes.

The

Creative

B R A I N

OBY ROGER E. BEATY, Ph.D.

ILLUSTRATION BY JEAN-FRANCOIS PODEVIN

ur author’s Cognitive Neuroscience of Creativity Lab at Penn State uses brain imaging and behavioral experiments to examine how creative thinking works in different contexts and domains, from the arts to the sciences to everyday life. His article examines the part of the brain that directs creative thought and asks the million-dollar question: Can creativity be enhanced?

When we think about creativity, the arts often come to mind. Most people would agree that writers, painters, and actors are all creative. This is what psychologists who study the subject refer to as Big-C creativity: publicly-recognizable, professional-level performance. But what about creativity on a smaller scale? This is what researchers refer to as little-c creativity, and it is something that we all possess and express in our daily lives, from inventing new recipes to performing a do-it-yourself project to thinking of clever jokes to entertain the kids.

One way psychologists measure creative thinking is by asking people to think of uncommon uses for common objects, such as a cup or a cardboard box. Their responses can be analyzed on different dimensions, such as fluency (the total number of ideas) and originality. Surprisingly, many people struggle with this seemingly simple task, only suggesting uses that closely resemble the typical uses for the object. The same happens in other tests that demand ideas that go beyond what we already know (i.e., “thinking outside the box”). Such innovation tasks assess just one aspect of creativity. Many new tests are being developed that tap into other creative skills, from visuospatial abilities essential for design (like drawing) to scientific abilities important for innovation and discovery.

But where do creative ideas come from, and what makes some people more creative than others? Contrary to romantic notions of a purely spontaneous process, increasing evidence from psychology and neuroscience experiments indicates that creativity requires cognitive effort— in part, to overcome the distraction and “stickiness” of prior knowledge (remember how people think of common uses when asked to devise

Creative thinking is supported in part by our ability to imagine the future—our capacity to envision experiences that have not yet occurred.

creative ones). In light of these findings, we can consider general creative thinking as a dynamic interplay between the brain’s memory and control systems. Without memory, our minds would be a blank slate—not conducive to creativity, which requires knowledge and expertise. But without mental control, we wouldn’t be able to push thinking in new directions and avoid getting stuck on what we already know.

Creativity By Default

Creative thinking is supported in part by our ability to imagine the future— our capacity to envision experiences that have not yet occurred. From planning dinner to envisioning an upcoming vacation, we routinely rely on our imaginations to picture what the future might look like. Interestingly, the same brain region that allows us to imagine a future is also involved in recalling the past: the hippocampus. A seahorse-shaped region embedded in the temporal lobe of the brain, the hippocampus plays an important role in piecing together details of experiences— people, places, objects, actions—both to accurately re-construct past events and to vividly construct possible future events. Early research with amnesiac patients provided clear evidence for the role of the hippocampus in remembering and imagining, finding that patients with damage to this area had trouble not only recalling the past but also imagining the future. Since then, researchers have used functional magnetic resonance imaging (fMRI) to study how the brain remembers and imagines.

Strikingly, some of the same brain regions activate when we recall past experiences and imagine future experiences. Important among them is a large set of cortical regions collectively known as called the default network. This network got its name from early

brain imaging studies that found that the areas it connects—medial prefrontal cortex, posterior cingulate cortex, bilateral inferior parietal lobes, and medial temporal lobes—tend to activate “by default” when people are simply relaxing in a brain scanner without a cognitive task to do When left to our own devices, we tend to engage in all sorts of spontaneous thinking—sometimes referred to as mind-wandering—much of which involves recalling recent experiences and imagining future ones. The engagement of the hippocampus and default network in memory and imagination is consistent with a popular theory of episodic memory known as the constructive episodic simulation hypothesis, which posits that both memory and imagination involve flexible recombination of episodic details, such as people, places, and events that we’ve encountered. On the one hand, remembering a past experience seems to require that we reconstruct that experience: piecing together the relevant people, places, and things that comprised the event—not simply pressing play like a video recorder

Likewise, imagining a future experience apparently requires that we construct that experience based on what has happened in the past. The flexible nature of the episodic system seems to be particularly beneficial for creative thinking, which also requires connecting information in new and meaningful ways.

In a recent study, we explored further whether the same brain regions support memory, imagination, and creative thinking. We presented research participants with a series of object cue words (e.g., cup) and asked them to use the cue words to either 1) remember a personal past experience, 2) imagine a possible future experience, or 3) think of creative uses for the object This design

allowed us to determine which brain regions were common and unique to episodic (remembering and imagining) and creative thinking. We found that memory, imagination, and creative thinking all activated the bilateral hippocampus.

This finding builds on other recent work on memory and creativity using episodic specificity induction, a procedure in which participants are trained to recall episodic memories in a high degree of detail. These studies found that episodic specificity induction (which strongly engages the default network) can improve creative divergent thinking: after the induction (they were instructed to recall in detail a recentlywatched video), participants produced significantly more ideas, and these ideas were significantly more variable in their topics A subsequent fMRI study found that the episodic induction process boosted activity in the left

A controversial question in creativity research concerns the phenomenon of cognitive control: our capacity to regulate the contents of our minds.

anterior hippocampus, linking creative performance to heightened activity in a brain region strongly associated with episodic memory. Together, these findings provide clear evidence that the hippocampus—as part of the medial temporal lobe subsystem of the default network—supports the generation of creative ideas: more proof that the same brain region that supports our ability to remember also supports our ability to imagine and create.

Directing Creative Thought

A controversial question in creativity research concerns the phenomenon of cognitive control: our capacity to regulate the contents of our minds. Does creative thinking happen spontaneously, or can we deliberately direct the process? On the one hand, relaxing the filter on our brains by letting our minds wander—a process governed by the hippocampus and default

network—can allow new ideas to come to mind that might not have otherwise. On the other hand, serendipity and spontaneity alone do not guarantee either novelty or usefulness: we often need to redirect our thought processes away from what we already know and think hard about whether our ideas will actually work This highlights two key elements of the creative thought process: idea generation and idea evaluation.

Cognitive neuroscience has begun to provide insight into these two sides of creativity. For example, one fMRI study asked visual artists to generate and evaluate ideas for a book cover based on short written descriptions. During idea generation, activation of the hippocampus and default network increased, presumably reflecting engagement of the episodic system. During idea evaluation, where artists were asked to critique their drawings, they again activated hippocampal and default regions, and also frontal brain regions associated with cognitive control, including the dorsolateral prefrontal cortex. Most interestingly, the analysis also showed increased communication (i.e , functional connectivity) between these regions during idea evaluation, suggesting cooperation between the spontaneous/generative aspects of the default network and the deliberate/ evaluative aspects of the control network These networks typically work in a complementary fashion: when one activates, the other tends to deactivate When we let our minds wander, for example, we engage the default network, without needing to focus our attention through our control networks; conversely, when we try to focus our attention on a given task, we need our control network to work

efficiently, without distraction from the mind-wandering default network. The study with visual artists, along with subsequent findings with poets and others, suggests that creative thinking involves increased communication between brain networks that usually work separately.

In a recent study, we explored whether this brain connectivity pattern may provide insight into individual differences in creative thinking, i.e., what makes some people more creative than others? One possibility is that creative people can more readily co-activate the default and control networks to solve creative problems. We recruited a large sample of participants, mostly undergraduate and graduate students and asked them to complete the creative uses task during fMRI. We recorded their ideas while they were in the scanner and later scored them for creative quality, allowing us to link each person’s brain patterns to the quality of their ideas. We found that, as expected, people varied widely in their performance on this task. Some consistently came up with common uses for objects, such as saying a brick could be used for building something, while others devised decidedly more innovative responses, e.g. a brick could be ground up and used as a filtering substance To analyze the data, we used a machine learning method called connectome-based predictive modeling (CPM). CPM allows researchers to characterize individual differences in such behavioral traits as personality and intelligence, by identifying functional connections in the brain that reliably predict these traits in new participants who were not used to build the models. In our study, CPM was used to estimate creative thinking ability based on brain connectivity patterns during the creative uses task.

While it remains unclear whether creativity can be improved in the long- term, some strategies may boost short-term creativity.

Our analysis showed stronger functional connections between the default, control, and salience networks (a network involved in switching between the default and control networks) in highly creative people: the brain connectivity pattern reliably predicted the creativity score. Importantly, the association generalized to three other samples of participants: individuals with stronger functional connections between these networks tended to produce more original ideas.

Boosting Creativity

Psychology and neuroscience have made encouraging progress in our understanding of how the creative brain works. As summarized above, we now know that creative thinking involves the interplay of the brain’s default and executive control networks, and that these connections allow us to spontaneously generate ideas and critically evaluate them, respectively. And we are learning about how our memory systems contribute: the same networks that we use to recall the past also allow us to imagine future experiences and think creatively.

Yet several important questions remain. One of the most important concerns whether creativity can be enhanced—and if so, how? Research findings thus far suggest that neuroscience tools can be used to predict the ability to think creatively, based on the strength of their brain network connections. But we do not yet know whether these connections can be strengthened to improve creative thinking. Longitudinal studies are needed. Just as the efficacy of cognitive or brain training programs in improving intelligence has been critically questioned, skepticism should be applied to interventions that claim to boost creativity.

While it remains unclear whether creativity can be improved in the longterm (i.e, trait creativity), some strategies may boost short-term (i.e. state) creativity. Given what we’ve learned about the neuroscience of creativity, it seems possible that harnessing the flexible and generative potential of the default network may provide a shortterm boost. For example, when we are stuck on a problem—a phenomenon known as fixation or impasse—taking a break to let our minds wander may loosen things up and help us find a creative solution Another potentially useful strategy involves priming the episodic system. The episodic induction process mentioned earlier—thinking about a past experience with as much detail as possible—has been shown to temporarily boost the number of ideas people generate on a creative thinking task

Until rigorous science on creativity training has been conducted, there are a few things that may modestly boost creativity in a more sustained way. For one, we can pick up a creative hobby, like painting or learning a musical instrument. One study that trained students how to play music reported gains in their musical creativity over time. But whether such gains transfer to make people generally more creative is not yet known (This is where cognitive “brain training” programs fall short: people tend to get better on specific training tasks, but this improvement doesn’t generalize to other tasks.) Until research has clarified whether cognitive abilities can actually be improved through neurosciencebased intervention, old-fashioned arts education might be our best bet. l

Financial Disclosure: The author has no conflicts of interest to report.

Our author— the director of the Social Neuroscience and Health Laboratory at the University of North Carolina—examines new research that ties income and other factors to stress and emotional responses. Does how we perceive our social standing impact our life expectancy and heart health? Are there interventions available to develop emotion regulation strategies?

Brains, bodies and social hierarchies

BY KEELY A. MUSCATELL, Ph.D. ILLUSTRATION BY WILLIAM HOGAN

Socioeconomic status (SES)— or one’s annual income, years of education completed, and occupation—has long been appreciated as a critical determinant of longevity. Indeed, there are large gaps in life expectancy for those at the top of the socioeconomic ladder compared to those at the bottom, and at many points in between But how can a “macro-level” societal factor, like how much money you make or if you graduated from college or not, “get into the skull and under the skin” to influence an individual’s health and well-being?

Psychologists, sociologists, public health researchers, and, more recently, neuroscientists, are all interested in understanding socioeconomic influences on the brain and body. It perhaps comes as no surprise that living in poverty, without enough money to meet basic needs like food, water, and shelter, or to go to the doctor when you’re sick, can take a toll on health But, interestingly, the data show that the relationship between socioeconomic status and health is present even in countries with universal health care, suggesting that there is more to the psychological experience of being lower in SES beyond just access to health care. Further, some intriguing research shows that our subjective perceptions of our standing in the US are a better predictor of health compared to more objective indicators like income and education. Together, data like these have led some to conclude that, in addition to our objective life circumstances, how we perceive our social standing and how we compare to others in our environments can impact our health

Given the robust associations between socioeconomic status and health, more recent research has focused on understanding the

Psychologists, sociologists, public health researchers, and, more recently, neuroscientists, are all interested in understanding socioeconomic influences on the brain and body.

mechanisms, or pathways, through which SES may impact disease processes and health outcomes. Some of this work has utilized advancements in brain imaging technology to explore how SES impacts the functioning of the brain in ways that could lead to poor health outcomes. Other work has focused on the relationship between socioeconomic factors and physiological processes, such as the functioning of the cardiovascular system and the immune system. What follows is an overview of these areas of recent research, all of which are attempting to fill in pieces of the complex puzzle of the relationship between SES and health

SES Impacts Health-Relevant Brain Functioning

Much past research on the effects of SES on the brain has focused on how socioeconomic factors influence the development of brain regions important for academic achievement among children and adolescents. Together, this work suggests that children whose parents’ make less money or have fewer years of education have different trajectories of development in brain structure (i e , the size and shape of different brain regions) and in brain function (i e , what brain regions are used to perform a task) that may prevent them from performing to their full potential in school and beyond. This research has been critically important in facilitating our understanding of how SES in early life can shape brain development in ways that may perpetuate economic inequality. But given that most SES-based health disparities don’t develop until much later in life, when adults start to develop chronic diseases like heart disease and diabetes, more recent work has begun to shed light on how SES influences

neural activity in brain regions that may contribute to chronic disease development among adults.

One brain region that has received a lot of attention for its potential role in contributing to SES-based health disparities is the amygdala. The amygdala is an “infamous” brain region that is often incorrectly characterized as a “fear center” of the brain. Instead, our current understanding of the primary function of the amygdala is that it plays an important role in helping detect salient information in the environment (which could be feared things, like snakes or spiders or angry faces, or could be positive things, like a smiling baby or winning a raffle). The amygdala is important for health because it has strong connections with other brain regions that can start physiological cascades like the “fight or flight” response, which, if chronically activated, can take a toll on the body and put individuals at risk for chronic disease development.

Given the amygdala’s importance for health, a number of prior studies have investigated the association between socioeconomic factors and amygdala responses to stressful or threatening stimuli, like angry faces or receiving negative performance feedback. This growing area of work shows that individuals from lower SES backgrounds have greater amygdala activity to stressful, threatening stimuli, compared to higher SES individuals. Although speculative, this suggests the possibility that lower SES individuals are more reactive to stressors, which, over time, could increase risk for poor health outcomes.

But of course, it’s not only our initial, “knee jerk” response to a threatening situation that is important for health over time, but also how we cope with the situation. Psychological scientists

often refer to this process as “emotion regulation,” or our ability to turn off our negative emotional responses with different coping strategies. The ability to successfully turn down emotions is facilitated by activity in prefrontal regions of the brain, which, via their connections to other regions like the amygdala, can help down-regulate our initial emotional responses. To date, only two known studies have asked if SES influences neural responses during emotion regulation. Both of these studies found that people from lower SES backgrounds showed lower levels of activity in the prefrontal cortex when they attempted to regulate their emotional responses to negative images, like a picture of a gruesome car crash. Interestingly, one of these studies found that higher levels of chronic stress among people from lower SES backgrounds was a major contributor to this association between SES and lower prefrontal cortex activity, once again pointing to stress as a critical pathway through which SES may influence the brain and, ultimately, health.

It’s important to pause here and point out that studying associations between SES and brain function raises challenging physiological questions. For example, do people from lower SES environments have brains that are “wired differently” based on something inherent in them (like genetics), or are factors related to the socioeconomic climate the drivers of observed differences in brain functioning between the rich and the poor? In other words, if there are differences in brain functioning between people who have less and those who have more, is that due to “nature” or “nurture”?

Interestingly, research suggests that people with less money or fewer years of education are not inherently

Nowhere is the influence of SES on the body clearer than in the cardiovascular system.

less capable than those with more, but rather that the psychological toll of being low income can impact the way the brain functions. For example, research by Sendhil Mullainathan and Eldar Shafir, discussed in their book, Scarcity: Why Having Too Little Means So Much, has shown that cognitive performance varies with current financial resources, even within the same person. In a fascinating study on farmers in India, researchers found that immediately following harvest time, when the farmers were comparatively rich, they performed well on challenging tasks designed to test their executive functioning, specifically their ability to plan, maintain, and manipulate information (analogous to “thinking on your feet”). Before the harvest, when the farmers had fewer financial resources, they performed worse These findings suggest that cognitive ability is not simply a trait that operates at the same level regardless of circumstances, but rather that our financial situation at any given time can influence how well we perform. In other words, it’s unlikely that people with fewer years of education or who make less money are inherently less capable than those with more, but rather, that the stress of not having enough financial resources and needing to constantly juggle what little money we have can take a toll on our cognitive performance.

It’s not difficult to imagine the implications this has for work productivity and school performance; for people living paycheck to paycheck or reliant on student loans, their work or academic performance may suffer during times of the month or year in which they have less money, because the lack of resources is preventing them from functioning at their peak

Taking Social Class to (the) Heart

It is now clear from the past decade of neuroimaging research that one’s socioeconomic status influences how the brain is functioning, particularly activity in the amygdala and the prefrontal cortex, both of which are critical for how we react to and recover from stress. But how does that brain activity translate into physiological changes that can influence health?

Nowhere is the influence of SES on the body clearer than in the cardiovascular system. Hundreds of studies have shown that individuals from lower SES backgrounds have higher blood pressure and greater arterial plaque buildup, and ultimately suffer heart attack and stroke at higher rates, than those of higher status.

Unhealthy behaviors undoubtedly contribute to this link: tobacco companies are more likely to advertise in and offer discounts at shops in low SES neighborhoods, contributing to greater cigarette smoking; many lower SES communities are “food deserts,” with an abundance of fast food restaurants and convenience stores and a lack of healthy, affordable food options (like grocery stores and farmers markets); and lower SES neighborhoods are less likely to have parks and other green spaces where people can safely exercise and spend time outdoors. Over time, these limited opportunities for healthy eating, physical activity, and smoke-free living can take a toll on the heart and arteries, increasing risk for heart disease and major cardiovascular events like stroke and heart attack.

Beyond these behavioral pathways linking SES and cardiovascular risk, research suggests that cardiovascular responses to stress represent another way in which social hierarchies can impact the heart. So many studies have investigated this question that a

meta-analysis, or “study of studies,” was recently conducted to determine the strength of the relationship between SES and stress reactivity across the whole body of research in this area

This seminal paper reported a somewhat surprising pattern of findings. There were no differences in blood pressure or heart rate responses during stressful experiences as a function of SES There were, however, differences in how the heart was functioning once the stressor was over, with heart rate and blood pressure remaining elevated for longer in lower SES individuals. This suggests that everyone, regardless of SES background, has an initial cardiovascular response to a stressor, but that lower SES individuals recover more slowly. In other words, stress may “live on” in the bodies of people with lower social status, producing greater wear and tear on the heart and arteries that leads to greater health risks over time This may be due in part to the lower levels of prefrontal cortex activity in the brain during emotion regulation mentioned above, though no known research has tested this directly.

If you’re like me, it’s distressing to think that something as uncontrollable as the social class you’re born into determines your lifespan.

Promoting Health Equity Moving Forward

If you’re like me, it’s distressing to think that something as uncontrollable as the social class you’re born into determines your lifespan. So what can we do to mitigate the deleterious impacts of socioeconomic status on the brain and body? Some ongoing research is testing whether simply giving money to people living in poverty can change their cognitive and emotional functioning, while work by Natalie Brito at New York University examines if paid parental leave policies could lessen the financial burden of parenthood, which would benefit everyone, especially those with lower SES

Such institutional changes at the level of societal structure may prove useful for promoting health but would require significant policy change that not all Americans favor This awareness has led some psychologists to ask if there are other strategies we can arm lower SES families with to promote better health outcomes even in the absence of sweeping policy change

One interesting intervention—called Parents and Children Making Connections- Focusing on Attention worked with parents of young children to provide them with strategies for dealing with regulating emotional responses to stressors in the family, and for training their children’s’ attention After eight weeks of attending two-hour small group classes, children whose parents were in the intervention showed significant improvements in cognitive function and in brain activity critical for attention, compared to those in a control condition whose parents did not receive the intervention. This suggests that working with parents to help develop emotion regulation strategies and strengthening childrens’ abilities to sustain their attention on a task could facilitate better outcomes. Of course, there are challenges with interventions

like this, given the time commitment involved (i.e., eight weeks of two-hour classes) and the fact that lower SES parents may not have the time available or mental bandwidth to dedicate to such training programs due to working multiple jobs, etc.

Further, the research showing that it’s not just objective economic circumstances that matter for health, but also our perception of our standing in a social hierarchy, suggest that we may also want to implement interventions to improve health for people who feel low on the social ladder So, what else can be done? To the extent that individuals who perceive themselves to be lower on the social ladder feel that they are not valued and don’t belong in certain places, it becomes much harder to shut down the stress response.

Groundbreaking research by Gregory Walton and Geoffrey Cohen at Stanford University suggests that this is indeed the case When lower SES minority students at Stanford were given a brief social belonging intervention emphasizing that they, and people like them, did belong and could thrive at such a prestigious university, their grades, and their health, improved drastically, even when measured four years later. So, while we should strive to ensure that everyone’s material needs are met, we should also be keenly aware that social belongingness is another life-sustaining need that all must have to live happy, healthy lives. To achieve true health equity then we need to promote both monetary and psychological fulfillment so all Americans can thrive, regardless of their social class background l

Financial Disclosure: The author has no conflicts of interest to report.

ILLUSTRATION: SHUTTERSTOCK

BY BRENDA PATOINE ILLUSTRATION BY LIA KANTROWITZ

Social Media & Teens: No Simple Answers

Is social media

rotting kids’ brains?

Parents, educators, and clinicians alike are increasingly concerned that contemporary youth’s seeming obsession with social media sites like Snapchat and Instagram may be fundamentally changing how their brains develop and heightening their risk for mental health disorders. Alarm bells are ringing in part because of the steeply rising incidence of depression and anxiety in young people and the striking increase in teen suicide, now at its highest rate in 20 years. These trends parallel the rise of the smartphone culture and near-universal use of social media by young people.

But is social media the smoking gun behind the apparently deteriorating mental health of adolescence, or just a coincidental phenomenon?

Sorting out those questions turns out to be no simple task, with decidedly mixed results. While many studies have found social media use to have significant negative mental health effects, some have found no effects, and still others have shown a protective effect. The only thing that seems clear at this point is that the relationship of social media to mental health is not at all clear.

Which Came First?

A big question is causality, the chicken-or-egg issue of which came first. Cross-sectional studies, which comprise the bulk of current research, capture a moment in time and can show only an association between two or more things, in this case time spent on social media and psychological symptoms. But just because social media use appears at the same time as depression or anxiety doesn’t mean that social media is the cause of depression or anxiety. It may be that teens who are already depressed or anxious turn to social media more frequently. Proving causality requires long-term tracking, and results from these kinds of studies are just beginning to appear.

One of the first studies to examine the social media-mental health interaction over time found a heightened risk of depression in adolescents who spent three or more hours a day on social media. Kira Riehm and colleagues at Johns Hopkins University examined data from a nationally representative cohort of 6,595 US adolescents, tracking selfreported mental health symptoms and social media across a three-year period (mental health as baseline in year 1; social media use in year 2, and mental health again in year 3). Even a half hour

Young people at the highest risk for depression, who tend to have poorer social support networks and fewer friends on and off line, tend to use social media more passively.

of social media use, compared to none, was correlated with greater depression symptoms one year later, particularly so-called “internalizing” behaviors such as withdrawal, avoidance, and loneliness. In an interview, RIehm emphasized that while her team’s study doesn’t prove causality, it does provide clues about the temporal course of depressive symptoms as they relate to time on social media.

Patricia Conrod, Ph.D., and colleagues at the University of Montreal found that depression symptoms increased with every hour of increased time on social media, and corresponding drops in self-esteem seemed to explain the changes. The report is based on data collected over four years from 3,826 adolescents (mean age of 12.7) enrolled in a preventative clinical trial in metro Montreal schools. A follow-up report from the same group found that anxiety also increased in concert with increased time on social networking sites. Data on substance use in relation to social media is forthcoming.

In contrast to these findings, psychologist Sarah Coyne, Ph.D., and colleagues at Brigham Young University found no association between time spent on social media and depression or anxiety at an individual level among 500 adolescents followed for 8 years, from age 13 to 20.

It’s Complicated

Each new study “adds to our general understanding that it’s complicated,” Paul Weigle, M.D., a child and adolescent psychiatrist who co-chairs the American Academy of Child and Adolescent Psychiatry’s media committee, said in an interview. “[Social media use] doesn’t affect all teens the same, and overall, is neither good nor bad for the mental health of teens.”

That doesn’t mean, Weigle was quick to add, that using social media doesn’t have significant effects on mental health. Rather, he said, “the effects

on young people depend both on the characteristics of the teen and the characteristics of how they use social media.” Young people who have strong social support networks and are at low risk for depression (based on recognized risk factors) tend to use social networks more actively, engaging with others and posting frequently. For them, social media may boost self-esteem and have a protective effect against mental illness, Weigle said.

In contrast, he continued, young people at the highest risk for depression, who tend to have poorer social support networks and fewer friends on and off line, tend to use social media more passively, scrolling and “lurking” rather than contributing in an engaged manner. When they do post, they are more likely to get negative feedback, probably due to the types of things they post. They are also more likely to engage in risky online behaviors like cyberbullying (both as perpetrators and victims) and “sexting,” sharing sexually explicit photos or posts. For these already high-risk kids, social media use appears to increase the risk of depression still further.

All Screen Time is Not Equal

These observations, borne out by recent research, that it’s not just how much social media is used, but rather how it is used, are in line with emerging insights about the much broader category of “screen time,” which also includes video gaming, watching television or movies, video chatting, and scrolling the Web for any use, educational or otherwise.

“All media is not created equally,” says Pamela Hurst-Della Pietra, M.D., president and founder of Children and Screens, a nonprofit foundation focused on digital media and child development. “An hour Skyping with grandma is not the same as playing a violent video game or multi-tasking online or

scrolling social media.” She stressed the importance of understanding which platforms young people are using, how they are engaging, and what kind of characteristics define the groups they are interacting with, such as chat rooms for gaming enthusiasts. These are factors that most studies of social media’s effects on youth have not looked at in detail. “They all play a part in how kids are growing up today, in shaping their identities and how they feel about themselves,” Della Pietra said.

Reinforcing Spirals

A leading theory of how social media influences mental health, positively or negatively, is the idea of “reinforcing spirals.” People who are well connected with others tend to receive more positive reinforcement on social sites, which may make them feel better about themselves, whereas people with fewer connections and poorer networks may receive negative reinforcement, which can exacerbate pre-existing vulnerabilities to depression or anxiety The Montreal study’s finding that self-esteem mediated social media’s effects on depression supports this mechanism. Moreover, the negative effects of social media were slightly greater in adolescents with high levels

Across the full spectrum of digital media, results were mixed in terms of both psychopathology and cognitive performance.

of depression to begin with, consistent with a downward spiral. The algorithms that drive social media likely exacerbate this spiral, Conrod said in an interview. “How information is presented makes [social media] particularly effective in promoting depression,” she said.

Her group found no evidence to support “displacement,” the idea that time on social media displaces face-toface social interaction, physical exercise, or other health-promoting activities, as a mechanistic explanation for the increase in depression, though other studies have suggested this.

Conrad noted another important characteristic of social media. “[It] is a powerful way of promoting unrealistic social norms,” she said. “Young people are being exposed to this warped, distorted reality at a time when they are constructing their own schema of the world and themselves. Their brains are developing in interaction with the messages from social media, and we have no idea what the implications of that are.”

What’s It Doing to the Brain?

Scientists are just beginning to investigate how social media and other digital media may physically impact the developing brain. The largest ongoing investigation is the federally funded Adolescent Brain Cognitive Development (ABCD) study, a prospective longitudinal study that will eventually enroll 11,500 9- and 10-year-olds at 21 sites and follow them for 10 years. Participants undergo once-yearly brain scans to track how their brains develop, which can then be related to a host of behavioral and environmental factors, including social media use and other “screen media activity.” The first cross-sectional data published from the ABCD study was directed at screen time, with the goal

of establishing baselines for time spent on digital media and how that relates to brain structure and neuropsychological measures.

The results underscore the complexity of the questions around digital media use. Among all forms of digital media, time spent on social media was the least associated with structural brain changes linked to vulnerability to psychiatric disease. Social media time was, however, associated with lower scores in tests of both fluid intelligence, the ability to think and reason regardless of prior experience, and crystallized intelligence, which relates to experience and accumulation of knowledge. Across the full spectrum of digital media, results were mixed in terms of both psychopathology and cognitive performance.

“The diversity of findings provides an important public health message: screen media activity is not simply ‘bad for the brain’ or ‘bad for brainrelated functioning,’ the authors wrote. Like others, they called for further investigations to examine how various digital media platforms influence the brain and cognition, and how these effects change over the course of development.

Until such investigations provide clearer answers, there seems to be a tenuous consensus for caution when it comes to adolescents and screen time. Guidelines from the American Academy of Pediatrics (AAP) urge families to create screen media plans that set aside “screen-free” times and areas of the home, including bedtime and bedrooms to encourage good sleep. The AAP guidelines emphasize parental supervision, modeling healthy screentime behavior, and teaching digital media literacy—wise and mindful use of screen time—beginning at a young age. l

ILLUSTRATION: SHUTTERSTOCK

Bui B g

By Kayt Sukel

ILLUSTRATION BY WILLIAM HOGAN

S

“We’ve now cured Alzheimer’s disease a dozen times over in mice, but we haven’t cured it in human patients,” said Matthew Blurton-James, Ph.D., a neurobiologist at the University of California, Irvine. “There’s clearly a big species difference in how this disease develops, which means our current animal models can’t get us the answers we’re searching for.”

In the past few years, however, advances in technology have led to the development of innovative models to study the activity of human neurons— and how they communicate with one another. Such models, which include ex vivo tissue harvested from living human donors, organoids, and chimeric models (animal tissue modified with human genes or cells), are enabling scientists to investigate processes in ways that were previously unthinkable.

“These new technologies, including those that use induced pluripotent stem cells (iPSCs), are really quite striking,” said Walter Koroshetz, M.D., director of the National Institute of Neurological Disorders and Stroke. “And the real advantage of these is that they offer us a new way to study human brain cells, particularly when it comes to developmental processes, that is incredibly valuable.”

Despite that value, there are numerous concerns, both practical and ethical, surrounding the use of such models—concerns that experts say should be addressed now before the technologies that support the development of models dramatically outpace scientific policy and oversight regarding their use.

Understanding the Models

What do you imagine when you hear the term, “brain in a dish?” Or “human brain experimental model”? It may conjure an image straight out

These models offer us a way to study things we have never had access to before.

of a science fiction movie—a full-size, pulsating brain in a jar of fluid that can think and feel, even without a body. At first glance, said Jonathan Ting, Ph.D., a researcher at the Allen Institute, most people wouldn’t even realize that most of these new experimental models are made of human brain tissue. His own laboratory is using sugar cubesized samples of ex vivo tissue—actual brain tissue harvested from consenting patients undergoing brain surgery—to better catalogue the variety of cell types found in the human cortex. “We now have the ability to collect tissue from the operating room and then transport it to our lab by ambulance and keep it alive with oxygen for a few days,” he explained. “That allows us to gain a deep understanding of the composition of the brain in different regions, including how many different cell types reside there, and what their defining molecular, morphological, and anatomical properties are. It gives us a strong foundation to understand the component parts of the brain –and use that as a jumping off point to understand what may go wrong in disease.”

Yet Ting’s tissue models, taken from adults, can tell us little about the developing brain. Hence researchers like Paola Arlotta, Ph.D., chair of the Department of Stem Cell and Regenerative Biology at Harvard University, are using organoids, or socalled “mini-brains,” three-dimensional, self-organizing tissue cultures derived from human iPSCs, to study how brain cells come together as the brain grows. Arlotta said most people have no idea what organoids look like—instead of life-sized, fully functioning brains, they are actually 4-to-5-millimeter pieces of tissue that resemble potato gnocchi rather than any bodily organ.

But despite their small stature, Arlotta

said, these assemblages of cells allow scientists like her to investigate both brain development and the genetic aspects of disease in a very precise manner.

“You don’t have to be a neuroscientist to know that an animal model is different than a human,” she said. “While animal models have been essential, there’s only so much we can learn. And as we have no access to actual human brain development and how different genes contribute to that, since so much occurs in utero, we have not been able to experimentally study it. Organoids, as primitive as they are, offer us the opportunity to ask new questions and do some of those experiments.”

ILLUSTRATION: SHUTTERSTOCK

Finally, researchers like BlurtonJames are utilizing chimeric models of the brain, or experimental models where an animal’s brain has been “humanized” with the addition of human genes or cell types. His own work is looking at how microglia, a special type of neural support cell, are affected in Alzheimer’s disease.

“We study microglia and how they contribute to different brain disorders,” Blurton-James explained. “Before, we would isolate microglia in a dish and study them. Yet, when we cultured these cells, we saw that their gene expression changes. In fact, the longer they culture, the [greater the change]. So we put two and two together and realized that we needed to put these stem cells in a brain—in our case, a mouse brain—and what we found is gene expression very similar to what we see in cells we’ve just taken out of the human brain. By using this type of model, we’ve dramatically reduced the differences we saw in microglia in a dish.”

The Scientific Limitations – and Ethical Concerns

Over the last few years, scientists have used these different models to make discoveries about how different genes contribute to both brain development and disease—discoveries they would have been unable to make without them. Researchers working with these approaches said they are not meant to replace animal models in full, but rather to offer new insights they would be unable to investigate otherwise. As organoid models appear to mimic the rich diversity of cell types found in the human cortex, Arlotta said, it gives scientists a rare opportunity to access some aspects of human development.

“It’s exciting, even as primitive and

As organoid models appear to mimic the rich diversity of cell types found in the human cortex, it gives scientists a rare opportunity to access some aspects of human development.

reductionist as these models are, to look at what is happening in the brain during this time,” she said. “We can answer questions about how different genes are affecting brain development –and with that, we have hope that we can one day understand what may start different brain disorders.”

Yet these models do have their limitations. First and foremost, they are limited by size and development. Organoids, to date, max out at the 4-5-millimeter size, even after months of development. And without vital vasculature and other bodily support, the brain cells contained within those models cannot reproduce normal developmental patterns of cell organization and architecture. Arnold Kriegstein, M.D., Ph.D., a researcher at the University of California, San Francisco, agreed with Arlotta that organoids can produce a variety of different cell types, but single cell RNAsequencing comparisons of organoid cells show that they lack the “cellular and structural complexity” of cells found in a normally developing brain.

“Our genetic analysis is showing that the organoid cells lack specificity. It’s almost as if their identity is a bit confused,” said Kriegstein. “Compared to normally developing cells, the organoids are relatively impoverished in terms of diversity...and they don’t mature according to the development programs that you see in normally developing brain tissue. Both cell identity and maturation are important in the study of human disease and these are not faithfully reproduced in current organoid models.”

Several laboratories are hard at work to create new paradigms to improve each of these models—techniques that can extend the amount of time ex vivo tissue donations can survive outside the body as well as technologies to improve

the ability of organoid and chimeric models to better mimic normal development. As they do, neuroethicists say it is vital that scientists discuss the potential consequences of such advances. Could scientists inadvertently create a super-mouse, à la The Secrets of NIMH? Could more sophisticated organoids start to learn or perhaps feel pain? While Joshua Gordon, M.D., Ph.D., director of the National Institute of Mental Health, stated that these models remain quite basic today, he agrees that scientists, scientific agencies, policy makers, and other science stakeholders should be talking about the future now.

“We don’t take for granted that these models will stay this simple,” he said. “That’s why we’ve had several workshops specifically looking at the question of what we need to think about as organoid preparations and other models get more complex.”

He said a few themes have emerged from those discussions, including the need for scientists to appropriately educate and patients who donate tissue and gain their consent about how that tissue will be used, as well as the need to monitor these models to check for more advanced brain activity. Arlotta agreed—but cautioned that it’s important to make sure these discussions are grounded in facts.

“We have to constantly consider these issues within the context of the science,” she said. “It doesn’t do us much good to discuss things without relating them to the actual biology of the systems we’re studying. These models offer us a way to study things we have never had access to before. Today, they are so reductionist that I think there is little ethical concern. But as we make advances, it is absolutely necessary that every conversation is strongly rooted in the science or it does us little good in the end.” l

ADVISORY BOARD

BRUCE McEWEN, PH.D. (1938-2020)

We are deeply saddened by the loss of esteemed neuroscientist and neuroendocrinologist Bruce McEwen, Ph.D., who made groundbreaking contributions to research on the effects of stress and sex hormones on the brain. Bruce was an invaluable member of the Cerebrum advisory board for many years, always incredibly generous with his time and knowledge, and an inspiration to all who knew him. He was a founding member of the Dana Alliance for Brain Initiatives, a former president of the Society for Neuroscience, and the co-author of The End of Stress as We Know It (Joseph Henry Press, Dana Press, 2002) and The Hostage Brain (The Rockefeller University Press, 1994). We will miss him.

JOSEPH T. COYLE, M.D.

Joseph T. Coyle is the Eben S. Draper Chair of Psychiatry and Neuroscience at Harvard Medical School. A graduate of the Johns Hopkins School of Medicine in 1969, he was a research fellow at the National Institute of Mental Health with Nobel Laureate, Julius Axelrod. After psychiatric residency at Hopkins, he joined the faculty in 1975. In 1982, he became the director of the Division of Child and Adolescent Psychiatry. From 1991 to 2001, he was chairman of the Department of Psychiatry at Harvard Medical School. His research interests concern the causes of neuropsychiatric disorders. He is the past-president of the Society for Neuroscience (1991), a member of the National Academy of Medicine (1990), a fellow of the American Academy of Arts and Sciences (1993), a fellow of the American Association for the Advancement of Science (2005), and the former editor of JAMA Psychiatry

MARTHA J. FARAH, PH.D.

Martha J. Farah is the Walter H. Annenberg Professor of Natural Sciences at the Center for Neuroscience & Society, University of Pennsylvania. She is a cognitive neuroscientist who works on problems at the interface of neuroscience and society. Her recent research has focused on socioeconomic status and brain development. Farah grew up in New York City, was educated at MIT and Harvard, and taught at Carnegie-Mellon University before joining the University of Pennsylvania. She is a fellow of the American Academy of Arts and Sciences, a former Guggenheim Fellow and recipient of honors including the National Academy of Science’s Troland Research Award and the Association for Psychological Science’s lifetime achievement award. She is a founding and current board member of the International Society for Neuroethics.

PIERRE MAGISTRETTI, M.D., PH.D.

Pierre Magistretti is the dean of the Division of Biological and Environmental Science and Engineering at King Abdullah University of Science and Technology and professor emeritus in the Brain Mind Institute, EPFL and Center for Psychiatric Neuroscience, Department of Psychiatry–CHUV/UNIL, Switzerland. Magistretti received his M.D. from the University of Geneva and his Ph.D. from the University of California at San Diego. Magistretti’s research team has made significant contributions in the field of brain energy metabolism. His group has discovered some of the cellular and molecular mechanisms that underlie the coupling between neuronal activity and energy consumption by the brain. This work has considerable ramifications for the understanding of the origin of the signals detected with the current functional brain imaging techniques used in neurologic and psychiatric research.

HELEN S. MAYBERG, M.D.

Helen S. Mayberg is a neurologist renowned for her study of brain circuits in depression and for her pioneering deep brain stimulation research, which has been heralded as one of the first hypothesis-driven treatment strategies for a major mental illness. She is the founding director of Mount Sinai Health System’s The Nash Family Center for Advanced Circuit Therapeutics Mayberg received an M.D. from the University of Southern California, trained at the Neurological Institute of New York at Columbia University, and was a post-doctoral fellow in nuclear medicine at Johns Hopkins Medicine. Immediately prior to joining Mount Sinai, Mayberg was Professor of Psychiatry, Neurology, and Radiology and held the inaugural Dorothy C. Fuqua Chair in Psychiatric Neuroimaging and Therapeutics at Emory University School of Medicine. She is a member of the National Academy of Medicine, The American Academy of Arts and Sciences, and the National Academy of Inventors. She is on the board of the International Society for Neuroethics and won the society’s Steven E. Hyman for Distinguished Service to Neuroethics (2018).

ADVISORY BOARD

JOHN H. MORRISON, PH.D.

John H. Morrison is UC Davis Distinguished Professor, director of the California National Primate Research Center (CNPRC), Professor of Neurology in the School of Medicine, and professor in the Center for Neuroscience at UC Davis. Morrison earned his bachelor’s degree and Ph.D from Johns Hopkins University and completed postdoctoral studies in the laboratory of Dr. Floyd E. Bloom at the Salk Institute for Biological Studies. Morrison’s research program focuses primarily on the neurobiology of aging and neurodegenerative disorders. His laboratory is particularly interested in age-related synaptic alterations that compromise synaptic health, lead to cognitive decline, and potentially leave the brain vulnerable to Alzheimer’s Disease. Morrison is a member of the National Academy of Medicine.

HARALD SONTHEIMER, PH.D

Harald Sontheimer is I. D Wilson Chair and professor and founder and executive director of the Virginia Tech School of Neuroscience. He is also Commonwealth Eminent Scholar in cancer research and director of the Center for Glial Biology in Health, Disease & Cancer and the Fralin Biomedical Research Institute A native of Germany, Sontheimer obtained a master’s degree in evolutionary comparative neuroscience, where he worked on the development of occulomotor reflexes. In 1989, he obtained a doctorate in Biophysics and Cellular & Molecular Neuroscience form the University of Heidelberg. He moved to Yale University for post-doctoral studies and later founded Transmolecular Inc., which was acquired by Morphotec Pharmaceuticals. He is the author of Diseases of the Nervous System (Elsevier, 2015).

STEPHEN WAXMAN, M.D., PH.D.

Stephen Waxman is the Bridget Flaherty Professor of Neurology, Neurobiology, and Pharmacology at Yale University, and served as chairman of neurology at Yale from 1986 until 2009 His research uses tools from the “molecular revolution” to find new therapies that will promote recovery of function after injury to the brain, spinal cord, and peripheral nerves A member of the National Academy of Medicine, Waxman has been honored in Great Britain with the Physiological Society’s annual prize, an accolade that he shares with Nobel Prize laureates Andrew Huxley, John Eccles, and Alan Hodgkin. In 2018, Waxman received the Julius Axelrod Prize from the Society for Neuroscience.

CHARLES F. ZORUMSKI, M.D

Charles Zorumski is the Samuel B. Guze Professor and head of the Department of Psychiatry and Professor of Neuroscience at Washington University School of Medicine in St. Louis. Zorumski is also Psychiatrist-in-Chief at Barnes-Jewish Hospital and founding director of the Taylor Family Institute for Innovative Psychiatric Research. Zorumski’s laboratory studies synaptic transmission in the hippocampus. Since 1997, he has served on the steering committees of the McDonnell Center for Cellular and Molecular Neurobiology and the McDonnell Center for Systems Neuroscience and was director of the Center for Cellular and Molecular Neurobiology from 2002 to 2013. Zorumski has also served on the editorial boards of JAMA Psychiatry, Neurobiology of Disease, and served on the board of Scientific Counselors for the NIMH Intramural Research Program from 2009 to 2013. Since 2011, he has also served on the scientific advisory board of Sage Therapeutics, a publicly-traded company developing neurosteroids and oxysterols as treatments for neuropsychiatric illnesses.

CAROLYN ASBURY, PH.D.

In-House advisor

Carolyn Asbury has worked in health philanthropy for more than two decades, directing neuroscience-related health programs at the Robert Wood Johnson Foundation and directing the Pew Charitable Trusts’ Health and Human Services Program prior to consulting with the Dana Foundation. Her own research, through the University of Pennsylvania’s Leonard Davis Institute, concerns policies to facilitate development and market availability of drugs and biologics for “orphan” (rare) diseases. She undertook pro bono research and helped to design the Orphan Drug Act; authored “Orphan Drugs: Medical vs Market Value,” and has authored several journal articles and book chapters on these topics. She has served on the boards of several nonprofit health-related organizations, including the National Organization for Rare Disorders, U.S. Pharmacopeia, College of Physicians of Philadelphia, and Treatment Research Institute.

Bill Glovin Executive Editor

Glovin has been a working journalist for more than 30 years. He is executive editor of the Dana Foundation and hosts a regular podcast on brain science. He has served as editor of Cerebrum since 2012. Previously, he was senior editor at Rutgers Magazine, managing editor of New Jersey Success, editor for New Jersey Business and a staff writer for The Bergen Record. Glovin graduated from George Washington University with a degree in journalism. He sometimes escapes from in front of the monitor to enjoy basketball, biking, and guitar.

Seimi Rurup Assistant Editor

Rurup oversees the production of all digital and print content at the Dana Foundation. She previously served as editor of Brain in the News, which was the Foundation’s longest running print publication, and utilizes her background in fine arts to contribute to current publications and social media. She also contributes to the Foundation’s Neuro News section. Rurup graduated from Sarah Lawrence College with a degree in writing. When she is not in the office, she can be found in one of NYC’s many museums, Brooklyn cafés, or at home cooking with friends.

Megan Messana Editorial Assistant

Messana is a journalist based in Brooklyn, N.Y. An alumna of Columbia’s Graduate School of Journalism, she has previously worked as an editor for Broken Records Magazine, had her own science column for Brooklyn College’s Excelsior, and has contributed to theink.nyc. She is currently an editorial assistant at The Dana Foundation and contributes to the organization’s Neuro News section. When not working, she can be found either at home with her three cats and ever-growing book collection or in one of Brooklyn’s various karaoke bars.

their work has the potential to make a difference in people’s lives.