Cerebrum Spring 2022

EMERGING IDEAS IN BRAIN SCIENCE • SPRING 2022

and the Developing Brain

SPRING 2022 | VOLUME 3, ISSUE 2

FEATURES 12 Poverty and the Developing Brain

From a team that studies this issue at Washington University School of Medicine, our authors explain the challenges and necessary steps to build a healthier, more productive society. By Joan L. Luby, M.D., Deanna M. Barch, Ph.D., and John N. Constantino, M.D. 18 Managing Pain: Ancient Ideas and New Frontiers A cognitive psychologist and head of Dartmouth College’s Cognitive and Affective Neuroscience Lab, our author examines what pain looks like in the brain, and how new research findings are leading to new treatments for pain. By Tor Wager, Ph.D. 26 The Miracle of Light A Q&A with Karl Deisseroth, a winner of the 2021 Lasker Prize in Basic Medical Research for his pivotal work in optogenetics and author of the widely praised book, Projections: A Story of Human Emotions . By Carl Sherman 32 Sleep’s Dark and Silent Gate Neuroscientists across the globe have new tools to study the integral role that sleeps plays in memory. But they agree that there are still many questions to be answered. By Kayt Sukel 38 Poetry of the Brain This year’s winning entries on the 20th anniversary of the annual Neuroscience for Kids Poetry Contest, which is designed to educate kids about the brain through creative writing. By Bill Glovin

SECTIONS 6

Advances • Notable brain science findings

7 Briefly Noted • By the Numbers, Brain in the News 8 Clinical Corner • Mental Health for Refugees, By Anne Glowinski, M.D., M.P.E. 10 Neuroethics • The Debate Over Safe Injection Sites, By Philip M. Boffey

4 From the Editor | 5 Contributors | 40 Advisory Board | 42 Cerebrum Staff

COVER ILLUSTRATION: LUISA JUNG

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FROM THE EDITOR

A Final Good-Bye

BY BILL GLOVIN Editor-in-Chief T o our many faithful subscribers and other readers who have been with us since the early 1990s—through many iterations and, for the past three years, as an expanded e-magazine and regular podcast—I’m sorry to report that Cerebrum is ending after this last issue. The Dana Foundation is shifting its focus away from publications to increased grant-giving on how brain science impacts society. These future grants will aim to strengthen neuroscience’s positive role in the world through interdisciplinary programs and public engagement. Putting the magazine together has been a true team effort. First and foremost, I’d like to give an enormous shoutout to Bruce Hanson , our freelance art director who helped bring the text to life and worked closely with the many talented illustrators whose work has graced our pages. If you have enjoyed our presentation, I have Bruce mainly to thank. Associate Editor Seimi Rurup was always instrumental in suggesting visual concepts and contributing to our editorial content. Our Copy Editor, Carl Sherman , also authored features and worked tirelessly behind the scenes to make sure that our science was delivered clearly. Nicky Penttila and Brandon Barrera always did great work on our Advances and Books columns, respectively, and our regular contributors Kayt Sukel and Brenda Patoine wrote extraordinary long-form journalism from the beginning. Finally, a huge note of thanks to my scientific advisory board, who suggested topics and authors, vetted articles, and brought their wisdom and experience in neuroscience to the table. I’ll surely miss our Zoom calls. Our recently retired in-house scientific adviser/ advisory board member Carolyn Asbury was a major sounding board through thick and thin, and recently retired Executive Vice President Barbara Gill , former Acting President Burt Mirsky, and the Dana Board helped me realize my vision and allowed for the expansion to a quarterly magazine. I’m eternally grateful to them. Corny as it may sound, editing Cerebrum has been an awesome learning experience—and even fun sometimes. To get to work with all these gifted individuals and all our neuroscientist authors has truly been an absolute privilege. Best of luck to new President Caroline Montojo and all my other wonderful colleagues at Dana as they transition to their new and important direction. Enjoy this final effort, and thanks for your time and attention. l

EMERGING IDEAS IN BRAIN SCIENCE

Bill Glovin Editor-in-Chief Bruce Hanson Art Director Seimi Rurup Associate Editor Brandon Barrera Staff Writer

Carl Sherman Copy Editor

Khara M. Ramos, Ph.D. Scientific Consultant

Cerebrum is published by the Charles A. Dana Foundation, Incorpo- rated. DANA is a federally registered trademark owned by the Foundation. © 2022 by The Charles A. Dana Foundation, Incorporated. All rights reserved. No part of this publica- tion may be reproduced, stored in a retrieval system, or transmitted in any form by any means, electronic, mechanical, photocopying, record- ing, 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 10 Rockefeller Plaza, 16 Floor New York, NY 10020 or cerebrum@dana.org Letters may be edited for length and clarity. We regret that we cannot answer each one.

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CONTRIBUTORS

Poverty and the Developing Brain > Page 14

JOAN L. LUBY , M.D., is the Samuel and Mae S. Ludwig Professor of Psychiatry (Child) at the Washington University School of Medicine, where she had founded and leads the Early Emotional Development Program. Luby specializes in infant/ preschool psychiatry and her clinical and research program has focused on early childhood psychopathology and emotional development, specifically in application to the risk trajectory for early onset depressive disorders. Her clinical expertise is on early childhood psychopathology in the mood and affective domain and how this relates to alterations in emotion development. DEANNA M. BARCH , Ph.D., is Couch Professor of Psychiatry and a professor of radiology and chair of the Department of Psychological & Brain Sciences at Washington University School of Medicine. Her research focuses on understanding the mechanisms that give rise to the challenges in behavior and cognition found in illnesses such as schizophrenia and depression, and utilizing psychological, neuroimaging and computational approaches. She is deputy editor at Biological Psychiatry , editor-in-chief of Biological Psychiatry : Global Open Science , and president of the Psychology Section of the American Association for the Advancement of Science. JOHN N. CONSTANTINO , M.D., is the Blanche F. Ittleson Professor of Psychiatry and Pediatrics and Director of the Division of Child and Adolescent Psychiatry at the Washington University School of Medicine in St. Louis. He previously served as chair of the Mental Health Commission of the State of Missouri and is currently psychiatrist-In-chief of St. Louis Children’s Hospital. Constantino’s work focuses on understanding genetic and environmental influences on disorders of social development in childhood, for the purpose of reducing risk for lifelong impairment. He and his team have worked to understand and offset the influence of early adverse environmental experience on social development in children, particularly in relation to the prevention of child maltreatment. TOR WAGER , Ph.D., is the Diana L. Taylor Distinguished Professor in Neuroscience at Dartmouth College and the director of Dartmouth’s Cognitive and Affective Neuroscience laboratory, the Dartmouth Brain Imaging Center, and the Dartmouth Center for Cognitive Neuroscience. He received his Ph.D. from the University of Michigan in cognitive psychology and served as an assistant and associate professor at Columbia University, and as associate and full professor at the University of Colorado, Boulder. Since 2004, he has directed the Dartmouth lab devoted to research on the neurophysiology of affective processes—pain, emotion, stress, and empathy—and how they are shaped by cognitive and social influences. Wager also teaches courses and workshops on fMRI analysis and has co-authored Principles of fMRI . CARL SHERMAN has written about neuroscience for the Dana Foundation for ten years. His articles on science, medicine, health, and mental health have appeared in national magazines including Psychology Today , Self , Playboy , and Us . He has been a columnist for GQ and Clinical Psychiatry News , and is the author of four books. He holds a doctorate in English literature and has taught at various universities. When not writing about the mind, the brain, and the interesting things people do with them, he enjoys travel, listening to music, looking at art, and copyediting. He lives and works in New York City. 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 .

Managing Pain: Ancient Ideas and New Frontiers > Page 18

The Miracle of Light > Page 26

Sleep's Dark and Silent Gate > Page 32

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ADVANCES Notable brain-science findings

I n a study led by Cedars-Sinai Medical Center and part of a multi-institutional BRAIN Initiative consortium funded by the National Institutes of Health, researchers discovered two types of BRAIN CELLS that play a key role in dividing continuous human experience into distinct segments that can be recalled later. The discovery—published in the peer-reviewed journal Nature Neuroscience —provides new promise as a path toward developing novel treatments for memory disorders such as dementia and Alzheimer’s disease. l

EVERY YEAR IN THE US, about 100,000 young people will experience a first episode of PSYCHOSIS , which can include hallucinations,

paranoia, delusions, disordered speech and behavior, and significant impairment at home and school. In a study and clinical trial led by Kelly Allott from the University of Melbourne, the youth who got placebos and those who got antipsychotics had similar levels of improvement in their social and occupational functioning. The findings support the need for careful consideration of the risks and benefits of various antipsychotics and the importance of accounting for their cognitive effects in longitudinal research. l FOLLOWING A CORONAVIRUS INFECTION, even mild cases of Covid-19 are associated with subtle tissue damage and accelerated losses in brain regions tied to sense of smell, as well as a small loss in the brain’s overall volume, a new British study finds. The paper, published in Nature and led by University of Oxford investigators, is the first study of the disease’s potential impact on the brain that is based on brain scans taken both before and after participants contracted the coronavirus. l BY EMPLOYING ARTIFICIAL INTELLIGENCE (AI) and robotics to formulate therapeutic proteins, a team led by Rutgers researchers has successfully stabilized an enzyme able to degrade scar tissue resulting from spinal cord injuries and promote tissue regeneration. The study , recently published in Advanced Healthcare Materials , details the team’s groundbreaking stabilization of the enzyme Chondroitinase ABC (ChABC), offering new hope for patients coping with spinal cord injuries. l

California Governor Gavin Newsom has proposed to

address the overlapping MENTAL HEALTH AND HOMELESSNESS CRISIS facing Los Angeles and other cities. The proposal, which would need approval by the Legislature—is called Community Assistance

N OSTALGIA decreases activity in pain-related brain areas and decreases subjective ratings of thermal pain, according to research recently published in Journal of Neuroscience . Researchers from the Chinese Academy of Sciences measured the brain activity of adults with fMRI while the participants rated the nostalgia levels of images and rated the pain of thermal stimuli. Viewing nostalgic images reduced pain ratings compared to viewing control images, with the strongest effect on low-intensity pain. It also reduced activity in the left lingual gyrus and parahippocampal gyrus, two brain regions implicated in pain perception. l Recovery and Empowerment, or “ CARE Court .” It would enable people with severe untreated mental illness or substance use disorders to be placed under court-ordered psychiatric care at the request of family members, clinicians, and others who work closely with them. l

ILLUSTRATIONS: SHUTTERSTOCK

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BRIEFLY NOTED

B Y T H E N U M B E R S

BRAIN IN THE NEWS Links to brain-related articles we recommend

1% percent of people in indigenous groups in the Bolivian Amazon suffer from dementia , in contrast to 11 percent of people over 65 in the US.

> The Economist: Video game makers must address worries about addictiveness > New York Times: How Exercise May Tame Our Anxiety > CNN Health News: Dogs can recognize different languages and nonsense words, study says > NBC News: Even mild Covid is linked to brain damage, brain scans show > New York Times: Wildlife Personalities Play a Role in Nature > Brain + Life: Smart Ways to Make Playing Video Games Healthier > New York Times: We Will Forget Much of the Pandemic. That’s a Good Thing > Washington Post: This is why it’s hard to find mental health counseling right now > Star-Ledger: ‘We must act’ on kids’ mental health crisis, experts say > American Scholar: Footage from a war and the effects on your brain > New York Times: Is Geometry a Language Only Humans Know? > Psyche: Bias in mental health diagnosis gets in the way of treatment

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of these natural

FIVE neuromyths , including the “silent cortex” theory that a person uses only 10 percent of his or her brain, have been

types of

foods have been shown

debunked by researchers.

to combat anxiety and depression.

credits are the maximum number (down from 23) engineering majors can now take each semester at Cornell University. The new threshold is an effort to improve student mental health.

140 MILLION people around the world now play Minecraft , a video game that a neuroscientist in Scotland uses to explain neuroscience and biological principles.

The strategy the White House has laid out in its mental health landscape.” — Schroeder Stribling , president and CEO of Mental Health America “ fact sheet is a necessary beginning—and it will save lives. Their approach will meet people where they are and will reduce disparities and promote equity across the

is the investment President Biden has proposed for programs that provide clinicians with the tools to treat mental health and substance use treatment in rural and underserved communities.

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CLINICAL CORNER

Mental Health for Refugees

express what my experience was like on my very first day in Bangladesh: ——— After two days and three flights through Dubai and Dhaka, Dr. Ali Anwar (one of my chief child and adolescent psychiatry fellows at Washington University) and I arrive at the Friends in Village Development Bangladesh (FIVDB) headquarters in Sylhet, a northeastern Bangladesh city. We started our 1 to 5 p.m. workshop almost an hour late. We were jetlagged and nervous but exhilarated. “It is clear that all refugees fleeing armed conflict and danger share the same almost unbearable human anguish, thirst for justice, and for the fraternity of others more fortunate.” Tomorrow, we will conduct a more intimate in-training session for their refugee camps’ staff in Cox’s Bazaar, where we will be heading later today. The rest of our time we will visit remote Rohingya refugee camps near the Myanmar border. FIVDB has helped to organize help for many refugees through the educational programs that they are famous for, such as community theater (e.g., to inform the Rohingya about the risks of child marriage). At yesterday’s workshop, during obligatory computer issues, Ali and I learn from our audience—mainly

the leaders and main coordinators from FIVDB—that the NGO’s vision is “A vibrant society based on justice, equity, democracy, and environmentally sound principles.” Like almost everywhere around the world, education does not necessarily translate to mental health literacy. That is why we have been invited.: Mental health problems are plaguing the refugees. So, Ali and I start, daunted and yet reassured by the outstanding reputation of FIVDB. They understand adult learning; it is not just about content. It is about inspiring by tapping into pre-existing relevance for the adults, who, unlike children, do not always integrate novelty with abundant enthusiasm. Our presentation stresses concepts such as depression or the impact of trauma on the mind and body, and we find it especially impactful to have the audience participate and role play. We quickly attain a high level of trust, candor, and (according to participants’ feedback) a true consolidation or awakening that mental health, an area of taboo in Bangladesh and many other parts of the world, must be heeded and integrated into healthcare. Ali and I cannot offer many specialized resources, so we demonstrate basic skills, especially those recommended by the World Health Organization and others for psychological first aid by lay people. We focus particularly on active listening, a skill that can also facilitate self-care and community support for a work force at enormous risk for burnout. This is especially true for the refugee camp workers we will meet tomorrow. We are also listening actively and learn that access to remote camps built on slopes requires daily back and forth walking for several kilometers in heat and humidity. Also, the monsoon

BY ANNE GLOWINSKI, M.D., M.P.E. L AST MONTH, AGAINST THE backdrop of tens of thousands of refugees fleeing Ukraine, the US formally accused Myanmar of committing genocide against its minority Rohingya population. This genocide was evident during two trips I and younger colleagues made in 2018 to Bangladesh to provide mental health training and support to relief workers on the frontlines of the refugee camps. Depression, anxiety, distrust, post-traumatic stress disorder, and substance abuse were among the problems. Invited by a Non-Governmental Organization (NGO), our first visit took place about a few months after hundreds of thousands of Rohingya refugees—many of them children—had perilously crossed the Myanmar border into south-eastern Bangladesh. In my role as a professor of child and adolescent psychiatry, I engaged in myriad activities, which included visiting NGO headquarters and refugee camps. We observed living conditions, spoke to Rohingya people of all ages, and listened to the stories of villagers—several of which had been at the epicenter of massacres by Myanmar’s military-led government. One particularly vivid memory is having long conversations with three wonderful brothers ages 8, 14, and 21, who were the sole survivors among a sibship that included initially 15 brothers. I kept a journal throughout the visit, and here is some of what I wrote to

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Anne Glowinski observes a group of kids at a child safe place within a refugee camp as they learn rudimentary new Bangla vocabulary through song.

T raveling forward to 2022, present day: Despite heroic efforts by NGOs and their workers and their many innovative programs, the situation in Rohingya refugee camps continues to be harrowing. This is not a complete surprise: Refugees are the fastest growing population in the world, and the average time spent in a camp by a refugee is 10 to 20 years. Justice, even symbolical, is slow: evidence is the five years it has taken for the US to recognize the Rohingya as victims of genocide. Much is being said about the sentimental discrepancy between our average emotional reactions to the plight of Ukrainians (many now refugees), and our less intense average reactions to the plight of other refugees, such as the Rohingya and many others. It is clear that all refugees fleeing armed conflict and danger share the same, almost unbearable human anguish, thirst

season is near, with its flooding and cyclones; half of the refugees, or almost 400,000 people, will need to be relocated. However, no firm plans have been proposed yet, creating a toxic level of anxiety among the relief workers. We hear about the challenges of working with refugees who have partially unfamiliar customs in this new country and have been acutely traumatized recently, but also chronically for decades before that. We hear about leadership challenges and that the refugee crisis is leading to an unprecedented level of scrutiny by NGOs from all over the world. So, FIVDB is getting a lot of well-meaning expert advice—some contradictory. Afterwards, we are exhausted yet rich with new connections and grateful for what our learners have taught us, too. We fall asleep underestimating mosquitoes and a few other things that we will encounter in the week ahead. ———

for justice, and for the fraternity of others more fortunate. In a conversation I had with Rohingya elders in 2018 when we gathered to discuss their cultural identity before making any substantial mental health recommendations, one of the men told me: “If you have a cow that is brown, you call it brown cow. If you have one with spots, you call it a spotted cow. We are like a cow without a name. To the world we don’t have a name.” l ANNE GLOWINSKI, M.D., M.P.E. , is the Robert Porter Professor of Child and Adolescent Psychiatry and Division Director for Child and Adolescent Psychiatry at the UCSF Child, Teen, and Family Center in San Francisco. Glowinski previously worked as Professor and Associate Chief of Child and Adolescent Psychiatry at Washington University in St. Louis.

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PHOTO COURTESY OF ANNE GLOWINSKI

NEUROETHICS

The Debate Over Safe Injection Sites BY PHILIP M. BOFFEY I N THE FINAL WEEKS OF HIS administration, Bill de Blasio, then mayor of New York, opened the nation’s first two overdose prevention centers to save the lives of people with substance use disorders who inject dangerous narcotics. Such sites are almost certainly illegal under an outdated federal law designed to close places where drug use is prevalent. But is it also unethical or immoral to operate the new sites? Or would it be even more unethical to close them down and leave people struggling with addiction to the mercy of the streets? The section of federal law that seemingly prohibits such sites makes it a felony to own, rent, or operate a location for the purpose of facilitating illegal drug use. Violators can be punished by up to 20 years in prison and served hefty fines. Simply raising that threat was enough to deter Philadelphia from opening a planned site. There were more than 95,000 drug overdose deaths in the year ending in February 2021, an all-time record, according to the Centers for Disease Control and Prevention. The chief culprits were opioids, including fentanyl, heroin, and prescription opioids, among others. The federal statute—dating back to the Anti-Drug Abuse Act of 1986— was designed to close buildings where people would shoot up and often die in shadowy corners in scenes worthy of a Dickens novel.

But the clean, modern facilities that federal authorities are targeting seem a much better option. The new facilities are sometimes called “safe injection sites” or “overdose prevention sites’” to underscore their important public health mission. Shortly after New York City’s first two sites opened in November 2021, reporters for the New York Times described the scene inside. People brought their own drugs to the sites, were provided with clean needles to use, and if they overdosed, were quickly given naloxone to reverse the overdose and save their lives. They were also told about options to receive treatment for their addiction, often crucial information for people struggling with substance use disorders. The sites have been supported by four of the city’s five district attorneys and by Eric Adams, the new mayor, who has a strong police background. The local law enforcement authorities can draw on their experience to understand what cities desperately need to combat rising addiction rates. The arguments against such sites were laid out by Rod Rosenstein, then deputy attorney general for the Trump administration, in an

opinion piece in the New York Time s on August 27, 2018. He called the sites “very dangerous” and said they “would only make the opioid crisis worse.” He claimed drug dealers would flock to the area, destroying the surrounding community. People “do not need a tax-payer sponsored haven to shoot up,” he said. “Injection sites normalize drug use and facilitate drug addiction by sending a powerful message to teenagers that the government thinks illegal drugs can be used safely.” Some opponents of injection sites also raise moral arguments—saying that injection drug use is

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intrinsically evil because it is non- therapeutic and causes serious harm to the user. They believe injection sites entice some users to continue by providing them a site to shoot up. Interestingly, Rod Rosenstein did not make a moral or ethical argument but rather predicted dire consequences if sites are opened. Regardless, observers on both sides of the discussion need to choose appropriate language to reduce stigma and avoid undermining the likelihood that people will seek help. A paper published in Neuropsychopharmacology

indicates that “stigma—negative attitudes toward people based on distinguishing characteristics— contributes in multiple ways to poorer health outcomes; consequently, it has been identified as a critical focus for research and interventions.” On the opposite side of this debate, William F. Haning III, a physician in Hawaii, made a strong case for supporting injection sites in a September 29, 2021, opinion piece

the spread of blood-borne infectious diseases. The trend nationwide is running toward greater use of injection sites. Rhode Island last year became the first state to enact a law to open sites with local approval under a

two-year pilot program. San Francisco is poised to open a site later this year, and other cities are expected to join the parade. The Boston Globe editorial board called for their own mayor to follow quickly on the heels of New York. Whether the Biden administration will be more receptive than the Trump administration to safe injection sites and other harm reduction approaches is not yet clear. The president may be too preoccupied with a host of domestic and foreign crises and political battles to pay much attention to this issue. His staff and cabinet appointees would be wise to recognize that the most ethical course of action would be to open more of these sites and pledge not to arrest their staff or clientele working to combat addiction and save lives. 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 views and opinions expressed are those of the author and do not imply endorsement by the Dana Foundation.

for STAT news. Writing as president of the American Society of Addiction Medicine, he cited great value in opening sites where people can consume previously obtained drugs in a hygienic monitored environment without fear of arrest. The American Medical Association has also endorsed such sites. Haning cited research in other nations which showed that injection sites did not increase drug use, trafficking, or crime. Instead of destroying the surrounding community, the sites reduced the volume of public injecting as well as the number of syringes discarded on streets and sidewalks. On the plus side, the sites achieved important health goals by reducing harm among drug users and connecting some to health and social services. The sites are no panacea, of course, and can’t solve all the societal factors that contribute to drug use. But they can at least reduce deaths and provide clean needles to prevent

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Evidence continues to mount that the brains of children living

in poverty show tangible alterations. Our authors, all part of a team that studies the issue at Washington University School

of Medicine, explain the challenges and the necessary steps

needed to build a healthier and more productive society.

and the Developing Brain By Joan L. Luby, M.D., N umerous studies of children in the US across decades have shown striking correlations between poverty and less-than- John N. Constantino, M.D., & Deanna M. Barch, Ph.D. Illustration by Luisa Jung

optimal physical and mental health and developmental outcomes. Trauma, poor health care, inadequate nutrition, and increased exposures to psychosocial stress and environmental toxins—all of which have significant negative developmental impact—are likely to be involved.

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The effects of elevated stress on child-caregiver relationships appear to be particularly detrimental, unsurprising in that nurturing and supportive caregiver relationships are foundational for healthy development in early childhood. For adults whose job options are unconducive to their role as parents (such as working multiple jobs or night shift hours), or for whom family support is unavailable, or for those do not have the material resources they need, the resulting stress may result in sleep disruption, depression, and anxiety—all of which translate to poor developmental trajectories for their children. Other health and developmental risks often associated with poverty include lead and other pollutants in air and water, poor nutrition (often related to living in “food desert” areas where healthy foods such as fresh fruits and vegetables are scarce), neighborhood violence, and trauma. “Toxic stress” that exceeds a child’s ability

A growing body of evidence demonstrates quantifiable re

to adapt can occur when the burden of stressful life experience overwhelms the brain’s regulatory capacity, or when the compensatory abilities of brain and body are compromised. A lack of cognitive stimulation (due to such factors as the absence of books and educational materials in the home, poor immersion in language, and a lack of after school or other enrichment activities) or disruption of sleep and circadian rhythms (by neighborhood noise or parents’ irregular work schedules) is likely to impact brain development and emotional and behavioral regulation when these systems are rapidly developing. How the Environment Shapes the Developing Brain Building on a robust body of literature in the behavioral sciences, developmental neuroscientists have begun to investigate whether tangible effects of poverty and adversity can be detected in the structure and function of the developing brain. A growing body of evidence demonstrates quantifiable relationships between adverse environmental exposures and alterations in neurodevelopment visible in brain scans. Work in animal models has shown that environmental exposures influence the sculpting of neural circuits, particularly during early developmental “sensitive” periods when the brain is uniquely malleable. This sculpting occurs through processes such as neurogenesis (the sprouting of new brain cells), synaptogenesis (the growing of new connections between brain cells), and synaptic pruning (the elimination of less-used connections between brain cells to enhance efficiency of communication among neurons and in brain circuits). The environmental influence

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be involved. For example, work in both humans and animals has shown that early exposure to enriched versus depleted environments, as well as variations in maternal care, can change the expression of key genes (i.e., turning on and off the production of proteins encoded by each gene) that are involved in brain development and function. Such epigenetic mechanisms represent an interface at which nature and nurture interact. For example: A healthy response to stress requires activation of a brain system called the hypothalamic pituitary adrenal axis (HPA axis); it regulates the release of the brain hormone cortisol, which helps prepare the body for adaptive coping. Excessive or prolonged HPA activation (such as the chronic stress that commonly accompanies poverty), generates too much cortisol, and can change gene expression in a way that causes lasting disruptions in hippocampal structure and function.

on this shaping process is thought to prepare the organism for adaptation to experiences and challenges it is likely to encounter in the future. In human studies during childhood, developmental neuroscientists have used tools such as electro- encephalography (EEG) and both structural and functional magnetic resonance neuroimaging (sMRI/fMRI) to show an association between early exposure to poverty and changes in brain structures critical for emotion regulation and cognitive function. For example, research has linked early poverty to a reduction in the size of the hippocampus, a brain region critical for healthy stress response and memory function. Further, studies using both EEG and fMRI have shown different patterns of brain activation in response to stimuli that evoke emotion or the need for emotional regulation. Children growing up in poverty showed greater amygdala

elationships between adverse environmental exposures and alterations in neurodevelopment visible in brain scans.

A similar process has been described in immune system reactivity, where chronic exposure to poverty and related stresses results in a “pro-inflammatory” state where the immune system remains activated, even without microbial threats. This chronic low level of elevated inflammation poses long-term health risks. In addition, living in poverty is associated with disruptions in the sleep-wake cycle; noise and light and patterns of household function that accompany challenging work hours (e.g., late shift work) can reduce the amount of sleep for children as well as adults. These disruptions have their own impact on brain circuits, interfering with neural restorative processes that accompany regular sleep and are critical for learning and emotion. As noted above, poverty is frequently associated with exposure to environmental toxins known to harm brain development, such as lead, polycyclic aromatic hydrocarbons (produced when oil, gas, and tobacco are burned), and nitrogen dioxide (present in air pollution). All too frequently, poverty also means reduced access to adequate nutrition, green space, and health care, all of which can directly and indirectly impact brain and overall development. Understanding the mechanisms of risk is complicated by the fact that poverty typically brings many risks at once, making it difficult to determine which risk factor drives which specific negative outcome (e.g., emotion dysregulation, failure to achieve potential), or whether multiple exposures have synergistic effects. And while causality may be suggested by association, it can be

activity in response to threatening stimuli. Researchers have also found an association between early poverty and alterations in brain circuits that are important for experiencing emotions, generating adaptive behavior patterns, and learning. These changes include reduction in the connections between the hippocampus and other brain regions, such as the prefrontal cortex and the anterior cingulate, that support cognition. As environmental shaping helps prepare an organism for its expected future, such stress-related differences in brain structure and function might be adopted to help a child manage uncertainty or respond to difficult circumstances later on. Over time or in response to chronic exposure to stress, however, adversity may also contribute to enduring disruptions in physical and mental health or in cognitive and emotional function. There is evidence suggesting that the link between early poverty and later psychopathology is mediated through some of the alterations in brain structure and function described above. Findings of this nature have re-ignited public health attention to the problem of child poverty; their insights into the mechanistic pathways of poverty’s deleterious effects on the brain pave the way to more directed targets for prevention and early intervention. Studies of Mechanisms As with brain development, while the association between exposure to poverty and negative developmental child outcomes have been apparent for many decades, the underlying cellular-level and psychosocial processes are more elusive. Numerous mechanisms appear to

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clearly established only with experimental designs that measure key outcomes before and after exposure to risk factors. Such studies are very rare but have been possible in the face of an environmental change (e.g., income increases brought out by an economic boon to a community, a pandemic, or policy change, or natural or man-made disasters that bring about social adversity in a previously well-resourced community). Knowledge gaps notwithstanding, the robust evidence for a connection between poverty and poor physical and developmental outcomes, and the high proportion of US children born into poverty, argue an ethical imperative to determine whether ensuring economic equity would bring benefits comparable to avoidance of toxic exposures and iron deficiency, which is now the standard of care and practice. Further enhancing income may also be a first step towards ameliorating other negative social forces

and psychosocial support of parents during their children’s first years of life (Early Head Start and Healthy Families America); and educational support of preschoolers (Head Start). Each program has overwhelmingly demonstrated incremental improvements in the average outcomes of the children such as overall achievement and lower rates of psychopathology. But they have not been nearly enough to close the developmental and mental health gap between children who grow up in underprivileged environments and those who do not. Interventions designed to enhance the parent-child relationship and reduce the likelihood of severe adverse experiences, such as child abuse and neglect, have proven a feasible and effective next-line-of-defense in the roster of federal programs for children in poverty. Ranging from home-visiting programs to live coaching during parent-child interactions, they aim to enhance emotional

Despite the growing knowledge base, there has been surprisingly little sustained public interest or investment in supporting

such as environmental and racial injustices associated with low SES. Studies that provide income transfers to young families living in poverty have provided some promising initial results, but most have not followed children long enough to show the enduring neural and mental health benefits. Understanding the pathways and mechanisms of poverty’s negative effects on the developing child is essential if we are to understand the importance of alleviation of risks associated with poverty and develop more cost-effective and targeted preventions and early interventions . That the direct consequences of economic insufficiency on brain development are entirely avoidable in the US, given its wealth as a nation, underscores the importance of these scientific endeavors. Interventions to Protect Developing Children Despite the growing knowledge base, there has been surprisingly little sustained public interest or investment in supporting robust programs to interrupt poverty’s deleterious impact on children. A notable exception is the “War on Poverty” with its federal programs for children living below the poverty line, initiated by President Lyndon Johnson in 1964 and still operational in all 50 states. Temporary Assistance for Needy Families (TANF) and the annual Child Tax Credit, contemporary mechanisms for direct cash transfers to impoverished families, evolved from the War on Poverty. Other federal programs have focused on consequences of poverty that damage the development of children, including nutritional support (the Women, Infants, and Children program WIC); educational

connection and warmth between parent and child and teach caregivers how to set nurturing but firm limits. These strategies have shown strong efficacy in buffering the negative emotional impact of poverty. Such interventions may be delivered in clinical settings or in the home or, more recently, by video conferencing. Extending them through community settings such as school or primary care sites will facilitate access to high-risk populations. There are now a number of empirically tested (and proven effective) models of this type of preventive intervention whose low cost makes them feasible for broad delivery with minimal social investment (through taxpayer dollars into social programs) and a high return on that investment. The question becomes: How to emphasize the importance of these interventions and their effectiveness to administrators responsible for child health and well-being? Science Policy Gap In regard to the above question, the gap between scientific advances and changes in social policy and healthcare practices is well-known. The field of implementation science was developed to address it by identifying barriers to the uptake of advances in medicine, social science, and psychology by practitioners and healthcare systems. This gap can be even more daunting in the area of public policy, where political perspectives and agendas can obstruct the integration of scientific findings. In the area of poverty and child development, the science-policy gap is strongly influenced by political philosophies and belief systems about the merits and liabilities of social safety nets. Even tangible economic

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benefits —compelling data that early interventions for children living in poverty result in a high return on investment and significant savings in tax-payer dollars over the long-term when they are used to fund these social programs—often fail to influence policy in a logical manner. Changing Social Attitudes More generally, stereotypes about poverty continue to thwart progress in this area. The idea that people live in poverty because they are unmotivated to work, or fail to take responsibility for themselves, or are genetically destined to fail, often drives social investment or lack thereof, even when it affects the well-being of young children. The commonly held misconception that people living in poverty are predominantly racial/ethnic minorities in cities may fuel beliefs based on implicit or explicit bias. In fact, the majority of people in poverty in the

g robust programs to interrupt poverty’s impact on children.

US are white and live in rural areas. This is because even though the percentage of racial and ethnic minorities living in poverty is higher than the percentage of white individuals, there are a larger number of white individuals in the US. For example, in 2020, 15.6 percent of white non-Hispanic households were living on $24,999 or less a year, with 29.7 percent of household identifying as black were living at or below the same income levels. However, in terms of numbers of households, this reflects 13.3 million households identifying as white non-Hispanic and 5.2 million households identifying as Black. This is not to suggest that we should only care about poverty if it happens to majority culture individuals, but simply to point out that poverty affects people of all racial and ethnic identities in our society. We need to develop interventions that support people facing poverty across all racial, ethnic, geographic, and other identity lines. Greater attention to the forces that drive individuals into poverty, such as a lack of inter- generational transmission of wealth, systemic racism and discrimination, social rejection, drug and alcohol abuse, and limitations in opportunity, is of paramount importance when addressing this problem on a larger scale. Otherwise, the unacceptably high proportion of young children—the next generation of adults— growing up in poverty represents our future. An understanding of how powerfully early life experiences shape the development of their minds and brains provides compelling evidence of what can and needs to be protected, and points to a great opportunity for building a healthier and more productive society. The public needs to know. l

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More than suffer from pain. Our psycholog College’s C Neuroscie relationsh feelings, a the actual what pain and how n leading to

P AIN IS AN INCONVENIENT REALITY. It is the most common reason people seek medical attention, affecting more people than diabetes, heart disease, and cancer combined. It exacts enormous costs in quality of life, not just for the pain sufferer, but for their families, caregivers, and communities. It is a symptom in hundreds of disorders, cutting across virtually every specialty in medicine. It is also intimately related to the ongoing opioid epidemic in America and beyond. Managin

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n 20 percent of US adults m some form of chronic author, a cognitive gist and head of Dartmouth Cognitive and Affective ence Lab, examines the hip among our thoughts, and beliefs about pain and l physical pain that we feel, n looks like in the brain, new research findings are o effective new treatments.

ng

By Tor D. Wager, Ph.D.

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to deal with chronic pain. Pain barely appears in the Diagnostic and Statistical Manual of Mental Disorders and is absent from the Research Domain Criterion framework, although in real life it co-occurs substantially with depression and anxiety. In fact, there is evidence that links between pain and mental illness spot when it comes to pain. Pain researchers are uncommon in academic psychology departments and neuroscience programs. And though many forms of chronic are causal and bidirectional . Psychology also has a blind pain are treatable with behavioral methods , clinical training programs equip newly minted psychologists to treat anxiety, depression, obsessive- compulsive disorder, panic disorder, personality disorders and more— but not pain. There is no National Institute of Pain. Pain is a central part of being human: Many of our oldest philosophical and spiritual traditions address ways to manage, avoid, and sometimes accept it. The Bhagavad Gita , for instance, instructs us to be at peace “in cold and heat, in pleasure and pain, in honor and dishonor.” The Roman stoic Marcus Aurelius wrote in the book Meditations , “Pain is neither intolerable nor everlasting, if thou bearest in mind that it has its limits, and if thou addest nothing to it in imagination…” These traditions teach us how to think about suffering and how to tap into our brains’ innate capacity to self-regulate. Although our ancestors knew nothing of the brain pathways that create pain, the central principles they taught and lived by have been rediscovered and adapted by modern approaches to pain treatment.

Patients are routinely prescribed opioids for acute pain after injury or surgery, and a substantial fraction of them will go on to become chronic opioid users. For some of these, the effects are devastating: In 2021, America saw over 100,000 drug overdose-related deaths, 75 percent of them caused by opioids, and the numbers have been climbing each year. For those who survive, opioid use takes a toll as well, causing changes in the brain that make it more difficult to work and to find enjoyment in daily life. Pain and pleasure are two fundamental forces that motivate us. Our history with pain goes back to our most ancient ancestors: Protozoa, sponges, insects, crustaceans, and more possess the same families of ion channels that enable pain in humans. These channels sense harm- related signals in the environment, like noxious chemicals, and turn them into electrical signals in the nervous system, providing the basis for escape, avoidance, and learning. The dual teachers of pain and reward are at the core of our brain’s ability to rewire itself to avoid threats and pursue opportunities in changing environments. Pain Falls Between the Cracks In spite of its fundamental importance, pain has fallen between the cracks in our scientific disciplines and healthcare systems. Most medical schools provide only a handful of hours of pain education , distributed across four years. If a peripheral cause cannot be determined and eliminated, chronic pain patients are shuttled across departments, their pain “managed” but with little hope for a cure. They are often referred to psychiatrists, but few psychiatrists are equipped

The Oldest Cure in the Book Morphine–derived from the opium poppy–is the oldest drug in modern medicine’s pharmacopeia. Its medicinal use dates to ancient Egypt. It also has long been known that morphine and other opioids are addictive. One of the earliest synthetic drug formulations— developed by Bayer in the 1890s— was designed to make morphine less addictive and marketed as a “soothing syrup” to help children sleep. That drug is heroin, which is illegal in the US because of its high risk for abuse. The evidence from randomized clinical trials of opioid treatment shows that its benefits are surprisingly modest. In the most recent meta-analysis , pain control was less than one point on a ten-point scale, and its efficacy declined with prolonged treatment. Meanwhile, basic research indicates that opioids can sensitize nociceptive neurons in the spinal cord, increase neuroinflammation, and increase pain in the long-term. The dose required to maintain the same degree of pain

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ILLUSTRATIONS: BRUCE HANSON AND SHUTTERSTOCK

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