Cerebrum Fall 2020

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E M E R G I N G I D E A S I N B R A I N S C I E N C E

Neuroscience Expansion Putting treatment and technology into place across the globe using cultural and ethical guidelines

CONTRIBUTORS

Ilina Singh, Ph.D. Neuroscience for Global Mental Health Page 12

Ilina Singh, Ph.D., is Professor of Neuroscience & Society at the University of Oxford and co-director of the Welcome Trust Center for Ethics and Humanities. Her core research examines the psychosocial and ethical implications of advances in biomedicine and neuroscience for young people and families. She received a Wellcome Trust Senior Investigator Award in 2015 on the ethics of early intervention in child psychiatry . Since 2016, Singh has led a global collaborative project on the science and ethics of psychiatric genomics in Africa. She is the academic lead for Patient and Public Involvement and Engagement in the Oxford Health Biomedical Research Center and sits on the UK Research and Innovation Covid-19 Rapid Response Taskforce. Singh is also treasurer of the International Neuroethics Society . She received her doctorate in human development and psychology from Harvard University. Frank R. Lin, M.D., Ph.D., is professor and director of the Cochlear Center for Hearing and Public Health at Johns Hopkins University. As an otologic surgeon and epidemiologist, he has translated his experiences caring for older adults with hearing loss into foundational public health research and federal policy. His research established the association of hearing loss with cognitive decline and dementia, and he now leads two ongoing, National Institutes of Health-funded randomized trials that are evaluating the efficacy of hearing interventions. In parallel, Lin has collaborated with the National Academies, the White House, and Congress to develop policies to ensure hearing loss can be effectively and sustainably addressed in society. 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 . 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, V.T., with her cat Shakti.

Frank R. Lin, M.D., Ph.D. Hear and Now Page 20

Kayt Sukel Adapting to the (Not So) New Age of Computer Learning Page 26

Brenda Patoine Pandemic Brain: Parsing the Mental Health Toll : Page 32

COVER ILLUSTRATION: JF PODEVIN

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FALL 2020 | VOLUME 1, ISSUE 4

FEATURES 12 Neuroscience for Global Mental Health Our author—Professor of Neuroscience & Society at the University of Oxford and co- director of the Wellcome Trust Center for Ethics and Humanities—reflects on efforts to grow recognition of neuroscience in low- and middle-income countries. By Ilina Singh, Ph.D. 20 Hear and Now As a practicing otologic surgeon with a Ph.D. in epidemiology, our author tells us what we’ve learned and what we still need to know about the relationship between hearing loss and cognitive decline in older adults.on education and personal development. By Frank R. Lin, M.D., Ph.D. 26 Adapting to the (Not So) New Age of Computer Learning Schools have had no choice but to embrace virtual learning. But the question remains: How does it work when compared to traditional, face-to-face instruction? By Kayt Sukel 32 Pandemic Brain: Parsing the Mental Health Toll Many experts have sounded the alarm for an approaching tsunami of psychological maladies that could sink an already overburdened mental healthcare system. By Brenda Patoine 38 Art on the Spectrum Showcasing the works and stories of talented, under-the-radar artists with developmental disabilities. By Seimi Rurup SECTIONS 5 Briefly Noted • By the Numbers, Brain on the Web, Reading Is Fundamental 6 Advances • Notable brain science findings 7 Bookshelf • A few brain science books that have recently caught our eye 8 Neuroethics: Neuroscience Confronts Racism • By Philip M. Boffey 9 In Memoriam • Leslie Iversen, Masakazu Konishi, Frederick Goodwin, Stephen Lieber 10 Clinical Corner: The Normally Abnormal • By Michael P.H. Stanley, M.D. 11 Talking Neuroscience • A Sampler of Cerebrum Podcast Episodes

POINTS OF INTEREST NOTABLE FACTS IN THIS ISSUE 4 The overwhelming majority of what we know about the human brain is derived from research on people of Anglo-European descent living in Western countries. Neuroscience for Global Mental Health , Page 12 4 For those who obtained effective treatment for their hearing loss with hearing aids or a cochlear implant, the effects were often equally dramatic. Hear and Now , Page 20 4 “We’ve learned the average attention span of a high schooler lasts for about a six-minute video. You get even less time for the little ones. So, you need to create the kind of structure and routine for kids so they can stay engaged and motivated.” Adapting to the (Not So) New Age of Computer Learning , Page 26 4 While the Covid-19 pandemic rages on worldwide, the immediate mental health impact of this collective trauma is coming into focus even as the outlook for long-term psychological effects remains considerably fuzzier. Pandemic Brain: Parsing the Mental Health Toll , Page 32 4 The Arc Westchester provides support for more than 2,000 individuals with intellectual and developmental disabilities, and its gallery provides opportunities for artists to develop their talents alongside a community where artistic expression is cultivated and supported. Art on the Spectrum , Page 38

2 Contributors | 4 From the Editor | 42 Advisory Board | 44 Editorial Staff

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FROMTHE EDITOR

One Year In

BY BILL GLOVIN Executive Editor, Dana Foundation W hile Cerebrum has published individual articles and book reviews since 1998, this issue signifies our first year of publishing Cerebrum as a magazine. We’ve enjoyed bringing it to you and hope you’ve found it useful. The objective is to provide a visually appealing mix: first and foremost, articles by neuroscientists who tell us why their area of research has the potential to help people, as well as the topic’s funding and public- policy implications. We also offer articles by science journalists on subjects we think are of interest. Since reliable information on Covid-19’s relationship to the brain and mental health continues to slowly unravel, we examine two related topics in this issue: live instruction versus computer learning and collective trauma’s impact on mental health. Front and center in recent months has also been the Black Lives Matter movement, and inclusion and diversity in the neuroscience field are the focus of both our cover story and neuroethics column. We’ve asked Ilina Singh, Ph.D., Professor of Neuroscience & Society and co-director of the Wellcome Centre for Ethics and Humanities at the University of Oxford, to tell us why neuroscience is mostly invisible in some parts of the world and the strategies by leadership to expand outreach. Our neuroethics columnist, Phil Boffey, confronts diversity with his column titled, “Neuroscience Confronts Racism.” We are also offering a feature on a topic that has been under the radar for far too long: hearing loss and its link to dementia and cognitive function. Frank Lin, M.D., Ph.D., professor and director of the Cochlear Center for Hearing Loss and Public Health at Johns Hopkins University, tells us what we’ve learned and what we still need to know about an issue that effects millions of people and their families. Additionally, assistant editor Seimi Rurup helps us showcase the art of talented, under-the-radar artists with developmental disabilities. With this issue, we also introduce a new regular column, “Clinical Corner,” a first-person account from someone on the frontlines of neurodegenerative or mental health treatment. The idea is to help humanize some of the complex research that is often at the heart of some of our stories. In this first column, “The Normally Abnormal,” neurologist Michael P.H. Stanley, M.D., addresses the challenges of treating a patient with multiple neuropsychiatric symptoms. We hope you find this new column informative. Meanwhile, our new Cerebrum magazine welcomes your feedback ; whether it be on our content, what we should consider covering, or how you feel about anything at all.. l

EMERGING IDEAS IN BRAIN SCIENCE

Bill Glovin Executive Editor

Seimi Rurup Assitant Editor

Podcast

Brandon Barrera Editorial Assistant

Carl Sherman Copy Editor

Carolyn Asbury, Ph.D. Scientific Consultant

Bruce Hanson Art Director

Cerebrum is published by the Charles A. Dana Foundation, Incorporated. DANA is a federally registered trademark owned by the Foundation. © 2020 by The Charles A. Dana Founda- tion, Incorporated. All rights reserved. No part of this publication may be repro- duced, 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 publish- er, 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.

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BRIEFLY NOTED

BY THE NUMBERS

BRAIN ON THE WEB A few brain-related articles we recommend: > CNN Health: Americans over 30 have been drinking more during the coronavirus pandemic, research shows

$3 million was awarded by the Breakthrough Prize Foundation earlier this year to Virginia M.Y. Lee, Ph.D., at Pennsylvania State University, for discovering protein aggregates in frontotemporal dementia and amyotrophic lateral sclerosis. 02.20.2020 was the date for the first shipping of Buzz , a wearable wristband that allows people to sense sound through their skin. The technology was conceived in neuroscientist David Eagleman’s lab at Stanford University and is sold through his company, Neosensory. 23% of preschool children ages two to five with family dogs were less likely to have social interaction problems than children whose households do not have a dog. The “mere presence of a family dog was associated with many positive behaviors and emotions,” said one of the researchers. 25 of October 2020 is the deadline for submissions to an annual visual storyteller photography competition that documents Alzheimer’s disease and dementia. Sponsored by the Bob and Diane Fund , the competition awards a $5,000 grant in mid-November during National Caregivers Month. 55% of coronavirus patients still have neurological problems three months later, according to a study published in Lancet . 80% of kids who stutter grow up to have normal speech patterns, while the other 20 percent continue to stutter into adulthood. 1,000 is the number of older adults in their 70s and 80s recruited for the Aging and Cognitive Health Evaluation in Elders ( ACHIEVE ) trial. 8,557 is the number of subscribers to the Neuroscience for Kids newsletter, which has been published by neuroscientist Eric Chudler, Ph.D. and colleagues at the University of Washington since 1997.

> Washington Post: Creators call digital game pre- scription for ADHD the future of medicine. Critics call it a marketing ploy. > CNN: Scientists find intact brain cells in skull of man killed in Vesuvius eruption nearly 2,000 years ago > New Scientist: Cyborg grasshoppers have been engineered to sniff out explosives > The Guardian: Researchers find a western-style diet can impair brain function > Brain Facts/SfN: How Microdosing Psychedelic Drugs Affects Mental Health > New York Times: The Brain Implants That Could Change Humanity > Smithsonian Magazine: What Neuroscientists Are Discovering About Stuttering > New York Times: How the Coronavirus Attacks the Brain > AARP’s The Daily: 3 Reasons the Pandemic Is Ruining Your Sleep—And What to Do About It Reading is fundamental [Print reading] is kind of like meditation—focusing our attention on something still. And it’s a whole different kind of immersion than responding to [digital] stimuli. I think it’s healthy for us as human beings to sit down with something that doesn’t move, ping, or call on our attention.” — Anne Mangen , a literacy professor at the University of Stavanger in Norway “

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ADVANCES Notable brain science findings

BY NICKY PENTTILA

The effects of high blood pressure and diabetes can already be seen among middle-aged people, who appear otherwise healthy, as reduced scores on tests of COGNITIVE FUNCTION and in altered

bereavement therapy, CBT, and others, they showed significant improvement in measures of immune system function. Beneficial immune system functions showed an increase for at least six months after the intervention, while harmful immune system functions showed a decrease. l The Food and Drug Administration (FDA) has approved another use of the anesthetic and party drug KETAMINE : as a nasal spray for suicidal patients with major depression. The drug, Spravato , which contains esketamine, a chemical cousin of ketamine, was approved last year for people with Research supported in part by donations from the Ice Bucket Challenge , the social media sensation that raised more than $200 million worldwide, has led to an experimental medication that may slow the progression of amyotrophic lateral sclerosis, or ALS , according to a study at Massachusetts General Hospital’s Sean M. Healey & AMG Center for ALS. The drug is not a cure, but it may help slow the inexorable disability caused by ALS, which rapidly destroys the nerve cells that control the muscles that allow us to move, speak, eat, and even breathe. l The drug’s advantage over other depression treatments is its speed: People report relief from some symptoms within 24 hours, compared with weeks for other drugs. l Another reminder for researchers to take care to describe their analysis: REPRODUCIBILITY . A study led by researcher Russel Poldrack asked 70 teams of scientists to analyze the same set of fMRI data. Using different software, steps, and setting different thresholds for results, the groups came to different conclusions more than half the time. “There was something about going from the intermediate steps of analysis workflow, to determining the right threshold, to denoting a final yes/no answer that changed things,” Poldrack told a reporter. “It was really striking.” He suggests researchers describe their methods precisely and consider running multiple analyses before they submit results for publication. l major depression who had not responded to other treatments. Now, the FDA has extended its approved use to people who are having suicidal thoughts or have recently attempted self-harm.

brain structure, according to a review of health data from 22,000 people in the UK Biobank project. Researchers found the effect was strongest in people ages 44-69 and increased in proportion to how far above 140mm a person’s systolic blood pressure (BP) was. Earlier studies have shown that mid- life troubles with blood pressure and diabetes increase the risk of dementia in older age; this study suggests that people with “mildly” high BP try to keep their number below 140. l

PARKINSON’S DISEASE (PD) may originate in two separate ways: A “brain-first” (top-down) type that starts in the brain and spreads into motor and other systems, or a “body-first” (bottom-up) type

that starts in the autonomic nervous system in the gut and spreads to the brain. Using PET brain imaging and CT colon imaging from 37 volunteer patients with Parkinson’s and 22 volunteers who had one symptom (Isolated REM sleep behavior disorder) but not PD, the researchers could trace the two pathways. The sleep symptom is an early signal for the body-first subtype, they reported in the journal Brain . l

Studying living brains is tough: They are dense and well-protected by skull and other materials. To investigate at the molecular level, magnetic resonance imaging (MRI) uses contrast agents,

which often contain metals that are foreign to the body. Now, researchers have described a method that uses something already in our bodies: AIR . Our cells contain gas vesicles, tiny genetically encodable protein structures filled with air, which read on scans differently than water and can be tracked as they move through the brain. Best of all, turning them from “on” to “off” can be safely done via ultrasound; a calibrated soundwave will burst the vesicle, and the air drains out, changing the image and showing that the effect a researcher is studying is real, not just a mistake in the scan. l

Psychosocial interventions—especially COGNITIVE BEHAVIORAL THERAPY (CBT)—may also result in improvements in how the human immune system works. A meta-analysis of 56 randomized

controlled studies found that after people underwent one of eight interventions, including psychotherapy, psychoeducation,

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BOOKSHELF A few brain science books that have recently caught our eye

Livewired: The Inside Story of the Ever- Changing Brain by David Eagleman (Penguin Random House) The brain is a dynamic structure, changing in response to both internal and external factors. Neuroscience refers to this as neuroplasticity—in essence, experience sculpts our “plastic” neural landscape, and

BY BRANDON BARRERA

Mind, Consciousness, and Well-Being Edited by Daniel J. Siegel and Marion F. Solomon (W. W. Norton)

our brains retain these changes in a continuous process with no end. It is because of this ever-present flux that David Eagleman, Ph.D., professor of neuroscience at Stanford University and host of the acclaimed television series The Brain , shies away from relying on the term "plastic" and its association with a final, landfill-bound end product. Instead, Eagleman introduces a new concept: livewired. This framework, Eagleman writes, recognizes the brain as the extraordinary self-configuring organ it is. Remove a limb and the corresponding cortical region in the brain will cede ground to its neighbors, essentially reorganizing the brain map to reflect the new, current form of the body. Introduce a new data stream, one captured and converted into electrical signals by novel sensors, and the brain will figure out how to use the data. Eagleman’s book lays out these livewiring principles, illustrating why he considers the concept to be “quite possibly the most gorgeous phenomenon in biology.”

Discovering and implementing strategies to cultivate your personal and professional well-being is invaluable, especially during tumultuous times. This latest volume in the Norton Series on Interpersonal Neurobiology invites readers to join scientists, clinicians, and mindfulness instructors in conversation—the transcribed format of the book is meant to preserve the flow of engagement, exercises, and human moments found in the live sessions. Across 15 presentations, experts with backgrounds in psychology, neuroscience, neurobiology, law, and physics share their perspectives on the science of self-compassion; the value of positive emotions and social connections in nurturing a naturally antidepressant brain; social justice and interconnectedness; bridging science and spirituality with physics and yoga; what Alzheimer’s can teach us about the mind and who we are; and many other thought-provoking reflections. Anyone interested in wellness, mental training, and consciousness will find this compilation to be a valuable resource.

Mind to Matter: The Astonishing Science of How Your Brain Creates Material Reality by Dawson Church (Hay House) When scientific principles brush against the metaphysical, it is possible to become disoriented—where once you stood on solid ground, you may find yourself wading out into the ethereal. It is this space, where

fMRI by Peter A. Bandettini (MIT Press) With close to three decades of fMRI (functional magnetic resonance imaging) research shaping his perspective, Peter A. Bandettini, Ph.D., leans on his experience to discuss the history and fundamental concepts of fMRI—the non-invasive and high-sensitivity technique for measuring brain

science probes the limits of knowledge, at times blurring into the fantastical, that author Dawson Church, Ph.D., chooses to explore. A self-described mystic and scientific researcher, Church’s interests lie in the power of thought and discovering the limits of “intention.” Church’s book addresses the research into the mind’s influences on the objective, external world. Neuroplasticity, emotional regulation, and what is known about the different frequencies of brainwaves are presented in ways that empower readers to benefit from potential health and therapeutic qualities associated with each. To be sure, the book concerns itself with much of the metaphysical and spiritual realms as well. While all are presented with references, many claims merit further investigation, such as the ability to alter a radioactive substance’s rate of decay through intent alone. Nevertheless, the curious will find much to consider and may find a new appreciation of the power of their mind. l

activity that has helped reshape brain science over the last two decades. Bandettini, chief of the section on functional imaging and director of the Functional MRI Facility at the National Institute of Mental Health, infuses fMRI with insights that are unique to pioneers of the field like himself. The book includes a brief primer of the brain imaging landscape and mostly concerns itself with fMRI methods: hardware and acquisition, brain activation experiments, and the crucial processing of data. One chapter is dedicated to fMRI controversies and challenges, chronologically cataloging more than 20 scientific debates that consider the various views and issues which inevitably surface. fMRI is a worthy companion for, as Bandettini puts it, the “curious layperson” and the “sophisticated developer and user.”

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NEUROETHICS

Neuroscience Confronts Racism

Neuroscience Degree Awards by Degree Level and Race/Ethnicity in 2018

Bachelor's degrees Total: 6,191

Advanced degrees Total: 865

BY PHILIP M. BOFFEY T he Black Lives Matter protests have triggered an intense bout of soul-searching and frantic efforts to erase all vestiges of racism from institutions around the nation. With all this ferment, it is not surprising that the tides of re-evaluation have lapped into the field of neuroscience. Webinars sponsored by the Society for Neuroscience (SfN) in July and September laid bare the appalling lack of diversity in neuroscience and called for reforms to do something about it. Just as there was a moral obligation to end slavery in the 19th century and there is a moral obligation today to end police brutality against Black people, so too is there a moral and ethical obligation to increase the representation of minorities in neuroscience as part of a national effort to rectify the injustices still permeating many aspects of American life. There would even be a scientific advantage to doing so. But there is clearly a long way to go. Joanne Berger-Sweeney, Ph.D., the president of Trinity College, who moderated the SfN webinar, cited a startling and depressing statistic. She said that over the past 60 years, the percentage of Black, tenured professors in all fields (not just in neuroscience or other technical fields) increased by only two percent, suggesting that there is “clearly a problem in the system.” The percentage for neuroscience was almost certainly even worse than the two percent overall average, which would have been buoyed by faculty hired to teach social science and political science courses focused on race-related issues. A commentary in the July 23 issue of the journal Cell by an African American neuroscientist at Duke University asserted that “Even now, only one to two percent of scientists awarded major grants by the National Institutes of Health are Black.” He complained that the review systems used to select winners of these grants are biased against Black people. The National Science Foundation published the number of neuroscience degrees awarded to various racial minorities and white people each year from 2008 through 2018. At all levels, Black students showed minimal gains over that recent decade. Meanwhile, a report from the Association of American Medical Colleges on “Diversity in Medicine” said that in 2018, only 3.6 percent of the full-time faculty positions in medical schools were held by Black people, who comprised 14.7 percent of the population in 2019. The Black share was well below the 63.9 percent held by white faculty and the 19.2 percent held by Asian faculty, the two largest contingents.

SOURCE: National Center for Science and Engineering Statistics, National Science Foundation, Integrated Data System.

The most distressing findings were analyses showing that years-long efforts to promote greater diversity by recruiting more "minority" applicants and using “holistic” measures, not just test scores, to evaluate them had made only a marginal difference in advancing diversity in medical education, with the number of Black faculty members noticeably lagging. Once on the job, practicing physicians from non-white backgrounds often confront racism and bias not only from peers and superiors but also from patients. Such implicit and explicit bias can only be countered by an all-out effort to develop an inclusive, equity-minded environment. A timely place to start would be to include many more Black subjects and physicians in the ongoing clinical trails for a vaccine to combat Covid-19. Four Black medical leaders have persuasively argued that participation by the groups most severely infected by the pandemic could build trust in the results and detect side effects not seen in white participants. The editors of Cell pledged to do their part to highlight Black authors and perspectives in an editorial entitled, “Science Has a Racism Problem.” They acknowledged that Black scientists were underrepresented among their authors, reviewers, and on the advisory board, and they pointed to the “extreme disparity” in the genetic and clinical databases that scientists have built. The overwhelming majority of data comes from white Americans of European descent, resulting in a dearth of understanding of health and disease in Black individuals. Meanwhile, the editor-in-chief of the Journal of the American Heart Association retracted a viewpoint article that had argued against affirmative action on the grounds that Black and Latino trainees in medicine were supposedly inferior to white and Asian trainees. He said that he and the

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IN MEMORIAM

Leslie Iversen , Ph.D., a neuropharma- cologist at the University of Oxford and a member of the Dana Alliance for Brain Initiatives (DABI) — Iversen, along with DABI members Ed Kravitz and Zach Hall, were the first to

association “condemn discrimination and racism in all forms” and that much more needs to be done to increase diversity in medicine and cardiology, including the publication of viewpoints recommending alternate approaches. An apology for even more appalling past racism has been issued by the American Academy of Pediatrics, which repeatedly rejected Black physicians applying for membership starting in 1939 because, a member of the all-white executive board explained, “if they became members they would want to come eat with you at the table. You cannot hold them down.” To atone for past sins, the Academy’s board published a resolution apologizing for contributing to the racism that Black pediatricians had endured and stressed that Academy membership does not discriminate on the basis of race or multiple other categories. A key federal agency published its strategies for enhancing the diversity of neuroscience researchers. The agency will search for talent at every level, from high school on up, and will provide resources and guidance to help them succeed until they reach faculty positions. One key element is meaningful mentorship all along the way. A collateral benefit is that diversity would help scientists solve many of the tough questions within neuroscience, the article said. It pointed to research showing that teams from diverse backgrounds outperform homogeneous teams in addressing complex scientific problems because they bring different perspectives and more innovative ideas to bear on the problem. A positive development is that many universities and health care systems are launching efforts to diversify, including a particularly ambitious program established at Trinity College by Berger-Sweeney. Among multiple “action steps,” Trinity will (1) require all campus members and trustees to complete anti-racist and unconscious bias educational training this fall and (2) create six “special opportunity hires” (preferably at senior tenured positions) each year for the next three years to increase faculty diversity. The college also established a task force that will provide “key metrics” to monitor its progress toward its goals. That could show whether a vigorous campus-wide effort to eradicate racism and promote diversity can succeed when so many previous efforts have fallen short. Other institutions need to follow Trinity’s example. 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.

demonstrate that GABA was released from inhibitory nerve terminals. During his career, he headed the United Kingdom drug discovery unit for Merck and was a member of UK’s Advisory Council on the Misuse of Drugs Committee. He was awarded the Lifetime Achievement Award of the British Association for Psychopharmacology in 2005. Masakazu Konishi , Ph.D., a

neuroethologist at Caltech and member of DABI, was a leader in the field of avian neuroethology— the neurobiological study of natural behavior — Konishi became

the Bing Professor of Behavioral Biology in 1980. Konishi’s autobiography, written for the Society for Neuroscience’s The History of Neuroscience , Volume 6, can be found here . Frederick Goodwin , M.D., world- DABI — The second edition of his 1990 seminal text, Manic Depressive Illness , was awarded the 2008 Best Medical Book Award from the American Medical Writers Association. He also headed the Alcohol Drug Abuse & Mental Health Administration and hosted the popular Infinite Mind weekly radio show on National Public Radio. Stephen Lieber , chairman of the Brain renowned psychiatrist, former director of the National Institutes of Mental Health, and a founding member of

and Behavior Research Foundation (BBRF) and an advocate for mental health research — Lieber helped grow a modest philanthropic group known as the National Alliance for Research

on Schizophrenia & Depression (NARSAD) into today’s BBRF—the largest private supporter of psychiatric research grants in the country. His philanthropy helped create the Lieber Recovery and Rehabilitation Clinic for Psychotic Disorders and the Lieber Schizophrenia Clinic at Columbia University, as well as the Lieber Institute for Brain Development (affiliated with Johns Hopkins University) in Baltimore.

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CLINICAL CORNER

Every day, hospitalized patients ask when they can go home, and Jane was no different. Inherent in home is the past life before illness and back to the familiar.

The Normally Abnormal

neurology are more porous than our system is prepared to address. She started on prednisone, a steroid to quell the inflammation, and as the confusion abated, Jane couldn’t tell if hours or months had gone missing. She kept reintroducing herself to doctors who had seen her daily for two weeks. Once she rallied to pun off one of the doctor’s dry statements, an attempt to show herself and her doctors that— despite the hospital gown—she still retained a sense of humor. When no one laughed, self-doubt crept back in. “Am I sicker than they thought?” she wondered. She was making progress against the inflammation, but when the brain

and address all three if we are aiming for wellness. Every day, hospitalized patients ask when they can go home, and Jane was no different. Inherent in home is the past life before illness and back to the familiar. Jane explained that after the near constant reevaluation of attentive physicians and nurses abruptly stopped, “I’m home. I go to work. I’m suddenly supposed to feel well. My friends have stopped calling because I look like myself, but I’m not quite myself. I don’t want to be a burden, to admit that I could still use that support. I don’t know what to expect because no one knows what to expect with what I’ve got, and I don’t want to bother my doctors over what might be nothing.” For those with concomitant psychiatric illness, such as OCD, it is doubly difficult—at first for the initial diagnosis, but now in preventing relapse. OCD can reinforce the anxieties surrounding the neuropsychiatric manifestations of an encephalitis like Jane’s, leaving doctor and patient bewildered as to which disease is flaring up. For many with dual diagnoses, the possibility of being considered a “problematic patient” to a doctor is paralyzing. No one wants to be dreaded, and patients with psychiatric disease are all too familiar with the dread of being dreaded. Hearts beat. Lungs breathe. Brains who and what and why. When people like Jane suffer brain injuries, their sense of Self can change. Some of that is an organ’s defect, but the rest is our response to it—that “our” exists where the brain meets the mind and especially where psychiatric illness is concerned, organic or otherwise. Recovery is not just repairing the cerebrum but renovating someone’s sense of self as we make our way towards a new “normally abnormal.” l Michael P.H. Stanley, M.D., is a neurology resident of the Massachusetts General Hospital and the Brigham & Women’s Hospital.

BY MICHAEL P.H. STANLEY, M.D.

I feel old,” said Jane. “I see the pillbox every morning and think it’s my parents’ pillbox, not mine!” To her students, she still looks like the same warm, engaged young teacher, but in between the jokes she cracks and the details of her upcoming lessons, there is still a catch in her voice. Jane is recovering from an unnamed inflammation of the brain. Peculiar symptoms of falling out of bed and mistaking names progressed into odd trembling at the whiteboard and clumsiness in sports, before finally culminating into such profound incoordination and incoherence that, by the third or fourth emergency room visit, physicians could no longer attribute it to a woman with an “extensive psych history.” As Jane kept reaching out for care, her ER visits provided further fodder to reluctant doctors to anchor upon an expedient psychiatric excuse. But to Jane, these symptoms could not be explained by her personal experience with anxiety or obsessive-compulsive disorder (OCD). “I know what my normally abnormal feels like, but the way I was feeling was abnormally abnormal for me.” It was not until subtle, objective signs coalesced around these enigmatic, traditionally “psychogenic” phenomena of inconsistent tremor and distractible weakness that a neurologist suspected her problem wasn’t “just in her head,” but precisely in her head. Jane's presentation suggested an encephalitis. The shift from a complaint of the mind to a condition of the brain illustrates that the provinces of psychiatry and

is inflamed, the intact networks are like frustrated hostages witnessing the networks still perturbed. And when that observation is focused through a lifelong lens of anxiety and compulsion, doctors need to reframe what (and whom) they’re caring for. Jane’s case illustrates the wisdom of that Hippocratic axiom, “cure sometimes, treat often, comfort always.” Drugs like prednisone affect the course of diseases, but healing is an ongoing negotiation between a patient and their body, with doctors as guides. Patients suffer and recover from the experience of illness —a complex feature of identity formulated in equal parts biology, psychology, and culture—and physicians must remember to assess

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ILLUSTRATION: SHUTTERSTOCK

TALKING NEUROSCIENCE

A Sampler of Cerebrum Podcast Episodes A selection of some of Bill Glovin’s engaging and memorable interviews with top neuroscientists who discuss their Cerebrum articles, their personal stories, and how their work has the potential to make a difference in people’s lives. Subscribe to Cerebrum here or on your favorite platform.

FROM THIS ISSUE

Ilina Singh , Ph.D., Professor of Neuroscience & Society and co-director of the Wellcome Center for Ethics and Humanities at the University of Oxford, and author of this issue’s cover story on global neuroscience expansion.

Frank R. Lin , M.D., Ph.D., director of the Cochlear Center for Hearing and Public Health at Johns Hopkins University and author of this issue’s feature on the link between hearing loss and dementia.

PREVIOUS EPISODES

Gregory Bern , M.D., Ph.D., director of the Center for Neuropolicy and Facility for Education & Research in Neuroscience at Emory University, on his Spring 2020 cover story, “Decoding the Canine Mind.” Jerold Chun , M.D., Ph.D., senior VP of Neuroscience Drug Discovery at Sanford Burnham Prebys, on his January 2019 article, “The Gene Conundrum in Alzheimer’s Disease.” Thomas R. Insel , M.D., former director of NIMH and co-founder and president of Mindstrong Health, on his November 2018 article, “Building the Thermometer for Mental Health.” Howard Hurtig , M.D., co-founder of the Parkinson's Disease and Movement Disorders Center at the University of Pennsylvania, on his August 2019 article, “The Many Faces of Parkinson’s Disease.”

Lee Alan Dugatkin , Ph.D., a biologist at the University of Louisville and coauthor of How to Tame a Fox (and Build a Dog) , on his Spring 2020 article, “Jump-Starting Evolution.” Maheen Mausoof Adamson , Ph.D., senior scientific research director for Defense and Veterans Brain Injury Center in Palo Alto, CA, on her November 2019 article, “Rewiring the Brain: Zapping with Precision.” Michael L. Lipton , M.D., Ph.D., associate director of the Gruss Magnetic Resonance Research Center at Einstein College of Medicine, on his September 2019 article, “Rethinking Youth Sports.” Karen Moxon , Ph.D., director of the Neurorobotics Laboratory at UC-Davis, on her June 2019 article, “Mind Over Matter: Cognitive Engineering.”

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Our author— Ethics

Neuro

12 DANA FOUNDATION CEREBRUM | Fall 2020

oscience Global Mental —Professor of Neuroscience & Society at the University of Oxford and co-director of the Wellcome Trust Center for and Humanities—reflects on efforts to grow recognition of neuroscience in low- and middle-income countries. for Health

By Ilina Singh, Ph.D. Illustration by JF Podevin

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E ARLY IN 2016, I WAS INVITED TO JOIN THE LANCET COMMISSION on Global Mental Health and Sustainable Development to work on a report that followed up the seminal 2007 series of articles in the journal Lancet that launched the field of global mental health. I was excited and honored. The Lancet reports are

processing deficits in schizophrenia ; or regulation of affective and cognitive pathways in depression . Drawing on the Evidence One thing that we did was to fundamentally change the trajectory of the Commission: we drew on emerging evidence from neuroscience and genomics to describe brain development as a function of convergent, multi-level factors: environmental, psychosocial, and biological. We relied heavily on research on the correlations between socio- economic status and its associated variables (such as malnutrition, lack of stimulation, and chronic stress), and early brain development . We also drew on brain plasticity research that depicted current knowledge about sensitive periods during childhood and adolescence. We wanted to stimulate further research in this area and help support arguments to health policymakers to develop early intervention and prevention strategies. One overall message was, instead of supporting categorical claims about ultimate causes of mental disorder, or about the presence or absence of mental illness, genomic neuroscience research could be used to help illuminate the highly complex and dynamic pathways to mental health and in illness across the life course. Another important point was to emphasize some of the similarities between “Global

a biomedical model of mental disorder is reductive and essentialist, and potentially harmful to interests of dignity and justice. I have argued for many years that such a hard-line critique of “the biomedical model” is not a useful or necessarily accurate account of scientific thinking. However, suspicions about biological approaches linger, particularly in the form of concerns about “medicalization” of mental health and overuse of biological treatments. Such concerns are especially resonant in low- and middle- income country (LMIC) contexts, where medicalization of mental health has been associated with studied indifference to culture and context. Promotion of dehumanizing, essentialist ideas about non-Western brains and minds and persons is part of a painful history of colonialism and oppression . So if the discoveries of biological psychiatry were to inform the Commission’s report, it would be important and right to acknowledge these critiques, while also evidencing the value of biological approaches to the high-level aims of the report: improving mental health at the population level and reducing the contribution of mental illness to the global burden of disease. My working group included some of the world’s leading biological psychiatrists and neuroscientists, and we ultimately convinced fellow commission members to give biological dimensions of mental health more airtime in the final report. The value of biological research was clearest when we could demonstrate identifying targets for effective interventions. Digital mental health, for example, is often positioned as a technology that could revolutionize global mental health— there are currently about 10,000 mental health “wellness” apps available for a broad range of conditions. But most of these apps do not leverage mechanistic understanding of underlying behaviors and cognitions, as, for example, reward

multi-authored and rigorously evidence- based; they also frequently contribute to shaping global health policy. At last, I thought, my discipline, neuroethics, would contribute analysis of substantive ethical challenges that arise when addressing mental health needs in a global context, such as the dignity and care of persons with mental and neurological disorders; equitable access to treatments; and the problem of stigma. As it turned out, while the Commission wanted to address and tackle these concerns, my role would not just be to contribute ethical thinking. Rather, I was to represent the potential for neuroscience, and, more broadly, biological psychiatry, to help position mental health as a development priority in efforts to reduce the global burden of disease. The World Health Organization (WHO) had explicitly acknowledged mental health as a global development issue in a summit hosted jointly with the World Bank in 2016; in the WHO Comprehensive Mental Health Action Plan; and in the inclusion of mental health in the WHO High Level Commission on Non-Communicable Diseases. The desire to integrate biological approaches to mental health and illness in the Commission represented an important progression from the original 2007 Lancet series. In working with Commission colleagues, I began to understand that a core challenge that lay before us could be construed as ethical: to confront the contention that

I

n working w that a core c to confront essentialist justice in glo

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Ilina Singh, Ph.D., Professor of Neuroscience & Society at the University of Oxford and co-director of the Wellcome Trust Center for Ethics and Humanities

with Commission colleagues, I began to understand challenge that lay before us could be construed as ethical: the contention that biological psychiatry is reductive, t, and potentially harmful to the interests of dignity and obal mental health.

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M y working group included some of the world’s leading biological psychiatrists and neuroscientists, and we ultimately convinced fellow commission members to give

North” and the “Global South” in relation to the political economy of mental health. These descriptive terms are used by the United Nations and World Bank to point to political and economic differences in LMIC countries (Global South) as compared to other countries (Global North). However, all countries are vulnerable, to some extent, to economic, political, and environmental conditions that contribute to health inequalities, such as conflict and displacement, urbanization, income inequalities, and climate change. Better understanding of the contributions of these “social determinants” in the pathophysiology of mental illness, and proportionate action to improve health inequalities, is therefore crucial to progress in all countries. As part of the Lancet Commission, we explored the question: Should neuroscience find its way into LMIC settings, in the context of global mental health? Our conclusion was “yes”; but in order to meet the ethical challenges of relevance and utility, neuroscience research needed to more clearly speak to challenges arising in LMIC contexts. I hope that in the future we will do better at demonstrating that relevance and utility. The Next Steps: Ethical Considerations Since the Commission, my own work with LMIC partners has expanded considerably, which has convinced me of the need to keep asking that should question to illuminate ethical concerns and ensure benefits. Increasingly we have also focused on a secondary question: If biological research is to inform our understanding of human brain development and functioning in LMIC contexts, how should this happen? The overwhelming majority of what we know about the human brain is derived from research on people of Anglo-European descent living in Western countries. If we agree that

biological dimensions of mental health more airtime in the final report.

human brain development is a dynamic “eco-bio-developmental” process, as a highly cited recent model suggests, then this limited evidence base means that we likely have limited epidemiological understanding of patterns of risk and resilience in brain development. Moreover, most of the brain research that has been done in LMICs was conducted by Western researchers. This reality raises a range of ethical considerations, including the relevance and accessibility of neuroscience knowledge and interventions in LMICs, and the need to build capacity among local researchers to participate in and to lead LMIC-based research projects. Compounding these challenges is the fact that human biological research by Western researchers in LMICs has a long history of unethical behavior. For example, biological materials, such as saliva, blood, and tissue, derived from research on the African continent, have for centuries been transported to the West. Despite the transformations in Western research ethics following the 1979 UK Belmont Report , the flow of such research materials still involves significant risk of ethical violations, such as lack of valid consent, biological material transfer agreements, and benefit sharing. As recently as last year, the UK Wellcome Sanger Center was accused of “bio-piracy” for allegedly planning to commercialize a gene chip

that used DNA from indigenous African tribes. Groups like H3Africa ( Human Heredity and Health in Africa ) are a robust response to historic injustices, focused on African leadership and facilitation of sustainable research infrastructure and ethical guidelines. This history and such LMIC responses as H3Africa have guided us in developing NeuroGenE , a global initiative in psychiatric ethics. The endeavor grew out of a partnership with the Stanley Center at the Broad Institute of Harvard University and MIT in a project called “Neuropsychiatric Genetics in African Populations” (NeuroGAP). Although all human beings are genetically very similar, African populations have the greatest genetic diversity in the world but are, for historical, practical, and cultural reasons, severely under- represented in genetic studies. The genetic architecture of psychiatric illnesses is highly complex and still not well understood; large-scale collections from African and other under- represented populations in genetic studies of neuropsychiatric disorders may accelerate genetic discovery and drive development of targeted therapeutics . Led by principal investigator Karestan Koenen and a team of African co-researchers, NeuroGAP encompasses scientific

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