Cerebrum Summer 2021

EMPATHY

FEATURES

14 Ageism: The Brain Strikes Back!

Does the brain improve with age? Our authors, who study successful aging and mental illnesses, address the often debated, complicated question that many of us have long wondered about.

By Tanya T. Nguyen, Ph.D., and Dilip V. Jeste, M.D.

22 Interoception: The Secret Ingredient

Our authors, who co-direct the Interdisciplinary Affective Science Laboratory at Northeastern University, explain how sensations created inside our bodies connect to the mind and brain.

By Lisa Feldman Barrett, Ph.D., and Karen S. Quigley, Ph.D.

30 Narcissism Gets No Respect

Why is narcissistic personality disorder, which has been recognized by the American Psychiatric Association since 1980, under-researched and rarely treated?

By Elise Oberliesen

36 Beauty and the Brain

Since 2014, stunning imagery inspired by brain research has launched an annual art exhibition during Brain Awareness Week at the Icahn School of Medicine in NYC.

By Bill Glovin

“Big

FROM THE EDITOR

Am I Losing It?

BY BILL GLOVIN

Editor-in-Chief

As we get into our forties and beyond, we realize that we can’t run quite as fast or jump as high as we once did. For many of us, reading glasses are required, and physical ailments that once healed quickly take longer to subside. And we can’t help wondering about our mental faculties. Will we start forgetting where we put our keys? Will we have even more trouble remembering names and dates? Will genetic ties to parents or grandparents with dementia affect us?

To find out what happens to our brain as we age, we asked two prominent scientists—Tanya T. Nguyen, Ph.D., and Dilip V. Jeste, M.D., who study aging at the University of California, San Diego—to tell us what the latest research reveals. In our cover story, “Ageism: The Brain Strikes Back,” you may be surprised to learn their thoughts on the findings.

Our issue also contains a smorgasbord of other topics that we think are just as engaging. A hot topic receiving a lot of recent attention in the neuroscience field is interoception—a sense that tells us how our body is feeling on the inside. Have a growling stomach, dry mouth, tense muscles, or racing heart? Lisa Barrett, Ph.D., and Karen Quigley, Ph.D., at Northeastern explain the sense that allows us to experience those kinds of bodily sensations.

We’ve all come in contact with obnoxious narcissists and wonder how they became so self-absorbed and whether anything can be done about it. One of our features examines narcissism as a personality disorder and gets to the bottom of why this disturbing condition is under-researched and difficult to treat. Another feature depicts a feast-for-the-eyes exhibition that includes striking images of the brain from faculty and students who are members of the Friedman Brain Institute at the Icahn School of Medicine in New York City.

Finally, our neuroethics column explores the implications of organoids research while our Clinical Corner is a first-person account from a recent graduate of the Ph.D./M.D. program at Rutgers Medical School. His moving story was first featured on NBC’s Nightly News with Lester Holt, and he agreed to recount his motivations for becoming a doctor and researcher in more detail for our readers.

All in all, an issue that we hope has something for everyone. l

EMERGING IDEAS IN BRAIN SCIENCE

Bill Glovin Editor-in-Chief

Seimi Rurup Assitant Editor

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

Letters to the Editor

Cerebrum Magazine

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

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

CONTRIBUTORS

Agesim: The Brain Strikes Back

> Page 14

TANYA T. NGUYEN, M.D., is an assistant professor of psychiatry at the University of California, San Diego. She is a clinical neuropsychologist with expertise in the assessment and treatment of older adults with neuropsychiatric disorders. Nguyen’s research aims to identify mechanisms of cognitive and biological aging in mental illnesses. Her current work is focused on the relationship between the gut microbiome and brain/behavior. She is the principal investigator of National Institute of Mental Health Career Development Award to investigate the gut microbiota in schizophrenia and how it may contribute to cognitive impairment and accelerated aging in this population. Nguyen received her Ph.D. in clinical psychology from the SDSU/UCSD Joint Doctoral Program in clinical psychology.

DILIP V. JESTE, M.D., is senior associate dean for healthy aging and Distinguished Professor of Psychiatry and Neurosciences at University of California, San Diego, His main areas of research include schizophrenia, neuropsychiatric interventions, and successful aging. He has published 14 books, including Wiser (Sounds True, 2020), an exploration of the neurobiology and psychology of wisdom. He is past president of the American Psychiatric Association and editor-in-chief of International Psychogeriatrics. He served as chief of the Units on Movement Disorders and Dementias at the National Institutes of Health, and later won its Mental Health MERIT Award. A member of the National Academy of Medicine, Jeste obtained psychiatry training in Mumbai, India. In the US, he completed his psychiatry residency at Cornell and his neurology residency at George Washington University.

Interoception: The Secret Ingredient

> Page 22

LISA FELDMAN BARRETT, PH.D., is co-director of the Interdisciplinary Affective Science Laboratory at Northeastern University and Massachusetts General Hospital. She is a University Distinguished Professor of Psychology at Northeastern, with appointments at Harvard Medical School and Mass General. She is also Chief Science Officer for the Center for Law, Brain & Behavior at Harvard University. In addition to the books Seven and a Half Lessons About the Brain and How Emotions are Made, Barrett has published over 250 peerreviewed, scientific papers appearing in Science, Nature Neuroscience, and other top journals in psychology and cognitive neuroscience, as well as six academic volumes published by Guilford Press. She has also given a popular TED talk with over six million views.

KAREN S. QUIGLEY, PH.D., is co-director of the Interdisciplinary Affective Science Laboratory at Northeastern University and Massachusetts General Hospital. She is a Professor of Psychology at Northeastern. Her work focuses on individual differences in emotional and affective experience, how humans utilize information from the body in creating emotional experience, and how emotional experiences impact behavior, cognitions, and health. Quigley received her Ph.D. in psychobiology from The Ohio State University and has published more than 100 scientific papers.

Narcissism Gets No Respect

> Page 30

ELISE OBERLIESEN is a freelance journalist who has written for the Los Angeles Times, the Chicago Tribune, Colorado Daily, AAA HomeandAway Magazine and websites such as AARP.com, nurse.com, and the Colorado Health Foundation. When Oberliesen is not glued to the laptop researching or writing, she spends time lifting weights, skiing, or creating mixed media art. She has two sons and a fur baby called Chester. She earned a B.A. from Michigan State University and now lives in Denver, CO.

ADVANCES

Notable brain-science findings

BY NICKY PENTTILA

A NEW DRUG intended to slow the cognitive decline caused by Alzheimer’s disease was conditionally approved by the US Food and Drug Administration in June. The drug, Aduhelm, reduces the amount of amyloidbeta plaque in the brains of people diagnosed with mild cognitive impairment, but it is less clear that it actually affects their problems with cognition. Under the FDA’s accelerated approval process, used when a potential drug would fill a serious “unmet medical need,” the drug’s maker, Biogen, is required to continue its research in Stage 4 clinical trials in hopes that it will eventually show a clinical benefit that is greater than its sometimes-serious side effects. l

Seeking to stifle the body’s natural rejection of foreign material like electrode arrays and other brain implants, researchers in Canada have invented a more brainlike material for IMPLANTS as well as a gentler way of inserting them. Their implants are formed using flexible silicone, which bends and moves much like brain matter. The new scaffolding holding these micro-implants is made of sugars, which dissolve and are washed away soon after insertion. In rats, the implants appeared to be accepted more readily and for longer than methods using soft polymers or hydrogel coatings. l

A BRAIN-COMPUTER INTERFACE

Mhas helped one man with paralysis to quickly write sentences on a computer screen by picturing himself writing the letters by hand. He had two electrode arrays implanted on the surface of his brain in motor areas; as he imagined writing letters, the electrodes’ signals were fed into a software program that first learned which signal stood for which letter and now can translate it, in close to realtime, to text on a screen. This translation appears to be far faster than current speechto-text systems and comes close to the speed of the average person who “thumb types” on their phone. l

A team of researchers has restored partial VISION to a man who had a form of blindness in which his lightcapturing (photoreceptor) cells had died. They used gene therapy to add light-sensitive (optogenetic) proteins to some of his healthy retinal ganglion cells instead, enabling them to respond to amber light. The man wears goggles that scan their field of view, notice any pixels in which the light changes, and then send a pulse of amber light from that pixel into one of his eyes. After seven months of practice, his brain had learned to convert that signal in a way that helps him see lines on a crosswalk and distinguish when there are two or three glasses on a table. l

ore news that regular physical activity (i.e., EXERCISE and PLAY) may be good for kids comes from an imaging study of nearly 6,000 nine- and ten-year-olds. Those who were active most days for at least an hour at a time showed brain circuitry that was more efficiently organized, flexible, and robust. The study showed that the more physical activity, the bigger the difference when compared with kids who did not move as much. For kids with higher-than-average body mass indexes, which is associated with harmful effects on the same brain circuits, those who were more physically active seemed to be able to offset the effects. These results are correlations based on large data sets, so very suggestive but not direct proof. l

Awearable, lightweight headset that measures brain activity while research volunteers move around, interact, and sit upright is demonstrated by members of the Center for Human Neuroscience Research at Virginia Tech’s Fralin Biomedical Research Institute: Read Montague

professor and director;

assistant;

associate professor. The device, developed in Montague’s lab, uses new optically pumped magnetometry technology and quantum sensor chips to measure the strength and originating location of magnetic fields produced by the human brain. l

(left),

Chris Huck, a research

and Stephen LaConte,

BY THE NUMBERS

1COUNTRY, Chile, will introduce a “neurorights” bill, making it the first nation to pioneer a regulatory framework which protects human rights from the manipulation of brain activity.

1904 is the year the IQ TEST was introduced, which was in response to the French government’s request for a diagnostic test of children’s intellectual abilities.

SIX hours of sleep or more a night is needed for middle-aged people who wish to reduce their chances of developing dementia in their late seventies.

BRAIN IN THE NEWS

Links to brain-related articles we recommend

> New York Times: Earlier Diabetes Onset Could Raise Dementia Risk

> Philadelphia Inquirer: Suicide rate shows decline but maybe not for all groups

> New York Times: The Health Benefits of Coffee

> Washington Post: FDA approves first drug intended to slow cognitive decline caused by Alzheimer’s disease

> New York Times: Many People Have a Vivid ‘Mind’s Eye,’ While Others Have None at All

> Brain & Life: Seth Rogen and Lauren Miller Rogen Use Humor to Educate About Alzheimer’s Disease

> New York Times: How to Think Outside Your Brain

> Scientific American: Electrodes That Stimulate the Brain Reveal the Roots of Conscious Experience

percent of American adults, age 20 to 69, have noise-induced hearing loss

20,000 virus-containing droplets that can stay in the air for up to ten minutes are produced by a single sneeze

6,200,000 Americans have Alzheimer’s, a number projected to more than double by 2050, barring breakthroughs in treatment, according to the Alzheimer’s Association

participants who drank three to five cups of coffee a day, with or without caffeine, were 15 percent less likely to die early from all causes than were people who shunned coffee.  200K

> Discover: Psychologists Explain Why You Can’t Remember the Movie You Just Watched

““We have to really temper expectations and explain to people that this drug is meant for the earliest symptomatic phases. It pains me to say this, but if I have a severe Alzheimer’s patient that can no longer speak or interact much with others and their family member is begging me to give them this drug, I won’t be able to do it.”

— Richard Isaacson, M.D., director of the Alzheimer’s Prevention Clinic at Weill Cornell Medicine and NewYork-Presbyterian, on the Food and Drug Administration’s controversial decision to approve the first new Alzheimer’s disease drug in 20 years.

BOOKSHELF

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

BY BRANDON BARRERA

Hard to Break: Why Our Brains Make Habits Stick by

Russell A. Poldrack (Princeton University Press)

It is not uncommon to have a list of good habits and practices that you intend on implementing but can’t quite get to take hold. For many, establishing good sleeping patterns and ending troublesome behaviors, such as late-night doomscrolling, can be a real challenge. Neuroscientist Russell A. Poldrack, Ph.D., articulates how these habits—actions and thoughts, from the highly valued to the annoyingly undesired—are formed in the brain, explaining to readers why we get “stuck” and how science can optimize behavioral change. Selfadmittedly not an “easy fix” guide, Hard to Break keeps to an evidence-based approach, applying the latest research toward individualized behavioral change. In detail, the book covers dopamine’s complexities and its critical role in modulating plasticity; the different brain systems for habits and planful (goal-directed) behavior; the prefrontal cortex and its relationship to self-control and willpower; and the extreme manifestation of a disease: addiction.

Of Sound Mind: How Our Brain Constructs a Meaningful Sonic World

by Nina Kraus (MIT Press)

Close your eyes for a breath or two and catalog your soundscape. Then, consider how swiftly your brain identified and contextualized those ambient sounds. According to neuroscientist and sound researcher Nina Kraus, Ph.D., the brain’s auditory neurons make calculations at one-thousandth of a second, effectively processing stimuli faster than sight, touch, and our other senses. In her latest book, Of Sound Mind, Kraus reveals how our brains make sense of sound, exploring the deep network of interconnectivity between sensing, moving, thinking, and feeling—a view marking a departure from the classical, one-way hierarchical model of auditory processing. We engage with sounds, Kraus says, and conversely, sounds shape our minds. Both an examination of sound as it exists outside of the brain and the biology of sound, Of Sound Mind is heartfelt and rigorous in its exploration of the power of sound. From music’s capacity for healing, methods to enrich sound processing, the impact of speaking multiple languages, and the destructive

power of noise on the nervous system, Kraus adroitly gives voice to the power and beauty of sound.

A Sense of Self: Memory, the Brain, and

Who We Are by Veronica O’Keane (W. W. Norton & Company)

Having observed and researched mood and psychotic disorders for 37 years, Veronica O’Keane, M.D., professor of psychiatry, developed a fascination with the neural mechanisms that create experience: sensation, cognition, and emotion. Pull on any one of these threads, O’Keane says, and you will see how emotional and feeling states are intrinsically wired to the formation of memory and the act of remembering. In A Sense of Self, O’Keane takes readers on an exploration of memory, consciously refraining from exceedingly intellectual explanations and instead allowing lived experiences—her own and those of her patients—to lead the way. To be sure, there is no dearth of neuroscientific research; it is instead the case that O’Keane’s approach is personal and full of feeling, much in the way memory operates.

REMEMBER: The Science of Memory

and the Art of Forgetting by Lisa Genova (Harmony Books)

We remember what is meaningful to us, says Lisa Genova, Ph.D., neuroscientist and best-selling author of Still Alice Even when we inevitably forget—where you placed your keys, why we walked into a room, maybe the color of your house—our brains are functioning normally and within the parameters of its evolutionary history. Genova’s latest work is an approachable and detailed exploration of memory, explaining how memories are made, how we retrieve them, and why forgetting is a normal part of the human experience. Every memory you hold dear lives as a constellation of disparate neurons throughout your brain, physically existing in your head through neural networks of associations. But why are some things easier to remember than others? REMEMBER will help you better understand how emotions, sleep, stress, and meaning affect memorycreation; how to distinguish between normal forgetfulness and forgetfulness caused by dementia, the nuances of your memory’s reliability (see: fallibility); how deliberate, focused attention is paramount to retaining any new information; and what measures can be taken in those instances where forgetting is the goal. l

The Value of Vulnerability

BY TOM PISANO, M.D., Ph.D.

WHILE ON THE SKI TEAM A FEW WEEKS INTO MY second semester of college, a failed backflip off a jump resulted in me waking up two days later paralyzed from the chest down. I faced my new reality with feelings of terror, depression, confusion, frustration, and anger as a medical team graciously put up with my sullen mood and answered endless questions. Eventually, I channeled my energy into my inpatient rehabilitation, motivated by defying the odds of never walking again.

During a year off, I did a lot of soul-searching, trying to hold off negative thoughts while contemplating the road ahead. Loved ones suggested that I attend a community college close to where I grew up in New Jersey. But I was determined to return to the University of Virginia (UVA), where I had been an engineering major. Further inspiring me were my two younger, teenage brothers who carried me up the stairs to bathe, to the beach to swim, and to hit the ski slopes again. They showed me that I could live a fulfilling life from a wheelchair.

I eventually graduated from UVA with a double degree in cognitive science and biology, then took a year off to work with spinal cord injury patients and on exoskeleton research at the James J. Peters VA Medical Center in the Bronx. Those experiences put me on a path to pursue a career in medicine, not just to help people with spinal cord injuries, but people with other diseases as well.

Fast-forward 14 years as I embark on a neurology residency after having completed an M.D./Ph.D. program at the New Jersey Medical School in May. Although each patient experience is different, I have found that sharing my own story with patients on an almost daily basis and providing a practical, honest assessment (especially to stubborn, adolescent males who have just been told that they have lost use of about half their body) has made me a better doctor—and helped a variety of patients in their own journey to recovery.

Since I use a manual wheelchair, my challenges are obvious to patients, and this can often be used to facilitate empathy and rapport. I met a man in his 40s who was in outpatient rehab several months after having a spinal cord infarction that left him paralyzed from the chest down. Like me, he was forced to also use a manual wheelchair. After his outpatient psychiatry visit, I shared

my story with him. His anxiety about navigating the world in a wheelchair, future relationships, and various other issues came pouring out.

But I have found that sharing my experience and showing vulnerability also helps other kinds of patients. A woman in her 60s who was suffering from partial paralysis a few days after a stroke was angry at the world. She responded to questions with short, curt answers, unwilling to disclose what she was thinking or feeling. I again shared my story, telling her about the myriad of emotions I had felt and how, even though our circumstances were different, there is a life after a hospital bed—a life that can be immensely fulfilling if you’re willing to stay positive. Slowly, over the next few days, she started to open up to her family members and caregivers and begin the road to recovery.

Although not every medical provider has a re-defining story like mine, most have internal motivations for getting into medicine, be it from personal struggles or via family members’ challenges. Common medical wisdom is to maintain professionalism, and in certain cases, distance is needed to sustain oneself from the many heartbreaks and crushing outcomes a physician can experience. But a delicate balance must be struck between complete detachment and over-sympathizing. This balance requires continuous reassessment to make sure the equilibrium is maintained between the two in order to keep humanity in medicine.

I know firsthand that, after a new diagnosis, it takes time for a patient to realign their internal representation with their new external reality. Whether it’s grasping unfamiliar circumstances, expressing feelings, or accepting the isolation that often accompanies an unexpected condition—all factor into the equation. Merely signaling to a patient that you are aware of the difficulties builds a connection and encourages healing. It is human nature to want our experiences validated.

Next time you’re given the chance, consider sharing a story that shows your own vulnerability. Whether or not it’s medically related, you just might find those few minutes to be well worth it. l

TOM PISANO, 33, recently graduated from the Robert Wood Johnson Medical School and New Jersey Medical School with both a medical degree and doctoral degree in neuroscience. He will spend his intern year at Mount Sinai Morningside-West, followed by a residency at the University of Pennsylvania’s Department of Neurology.

Keeping a Close Eye on Organoids

BY PHILIP M. BOFFEY

Iwas astonished to learn while writing a column on the brain-computer interface in 2019 that patients with amyotrophic lateral sclerosis (ALS), whose brain signals were fed into a computer, could control a complex robotic arm, having it pick up a pitcher and pour water into a glass, just by thinking about it.

So you can imagine my surprise when I learned that scientists have achieved comparably difficult tasks—not with signals from a human brain—but simply from a clump of stem calls in a Petri dish.

The achievement is clearly described in Alan Alda’s Clear+Vivid podcast featuring Alysson Muotri, a Brazilian citizen who is director of the stem cell program at University of California, San Diego, where much

or “mini-brains” in a dish, Muotri is more circumspect, describing them as “brain organoids.” The entity, he says, is a miniaturized version of some of the tissue of the brain (containing 2.5 million neurons, the equivalent of a bee brain) that in some aspects behaves like the human brain. As the organoids become more complex, you can see the brain cells oscillate in unison as they start communicating with each other and generate electrical signals that mimic human neural development.

Muotri’s other main focus is to study how the brains of Neanderthals differ from the more complex brains of modern humans, or Homo sapiens. He postulates that if we can understand how this complexity arose, we might understand why our human brain is so susceptible to developmental conditions such as autism.

Evolutionary biologists have identified 61 genes that are different between us, the Neanderthals, and all other species. Muotri and his colleagues have focused on one of those, called NOVA 1, which regulates hundreds of downstream genes, so “if you’ve messed with that one, there are hundreds of other genes that will change as well.” He suggests that species carrying an archaic form of that gene may have earlier gestation or maturation times akin to chimpanzees, whereas humans who have a mutated form of that gene take much longer to mature.

of this pioneering work was performed. The podcast is a useful complement to a more comprehensive report issued on April 8 by the National Academies of Sciences, Engineering, and Medicine.

As Alda’s introduction explains, Muotri uses factors that drive skin cells to revert to stem cells and then become brain tissues that self-organize, forming “brain organoids in a dish. Muotri, who has a personal interest because he has a son with autism, hopes to learn how early brain development can change course in conditions like autism and epilepsy—and how our brains differ from those of our evolutionary? cousins, the Neanderthals.

Although some people call what he has created “brains”

In a feat I found astonishing, Muotri’s team stuck a probe in a Petri dish to generate signals from an organoid that controlled the movements of a tiny robot. Electrical signals generated in the Petri dish were fed into a computer that told the four-legged robot how to move. The robot had infrared detectors that told when it was getting close to a wall. It sent a signal back to the organoid which then sent a second message to the robot to walk back. Eventually, Muotri anticipates that the organoid will do much of this spontaneously in what might be considered learning.

The biggest risk of all these ventures, Muotri says, is that someday an organoid might reach a point of consciousness or

self-awareness. His team has ethicists and philosophers watching how the research develops.

The National Academies report, entitled “The Emerging Field of Human Neural Organoids, Transplants, and Chimeras: Science, Ethics, and Governance” and partially sponsored by the Dana Foundation, found strong moral arguments in favor of research on these laboratory entities, namely the potential for new knowledge to relieve human suffering and mortality caused by brain disorders, provided that certain ethical protections are in place.

The report’s committee also deems it “extremely unlikely that in the foreseeable future” organoids would possess capacities that would be recognized as awareness, consciousness, emotion, or the experience of pain. “Thus, it appears at present that neural organoids have no more moral standing than other in vitro human neural tissues or cultures.” That could change in the future of course, but for now, as one leading researcher told a reporter from Science magazine, the public and funding agencies can be “reassured that nobody is tromping on any ethical boundaries or lines at the moment.”

There is always concern that organizations dedicated to advancing science—as the National Academies surely are—will give short shrift to ethical constraints. But the committee seems to have conscientiously kept ethics front and center. By my count, 5 of the 11 committee members were experts in ethical or legal issues. The committee also heard from a wide range of ethicists, religious scholars, and legal experts.

There is no doubt that the research is potentially valuable. Each year tens of millions of individuals suffer from neurological and psychiatric disorders for which treatments are often completely lacking or only partially effective. These include neurodegenerative diseases such as Alzheimer’s and Parkinson’s and neurodevelopmental disorders such as autism spectrum disorder, depression, and schizophrenia.

The dearth of treatments is due, in large part, to the difficulty of conducting research on an organ containing roughly 86 billion neurons interconnected by trillions of synaptic connections in intricate circuits. Unfortunately, the tools for studying such complex circuits are limited. While research using animal models has advanced understanding, their brains are very different in key respects from the brains of humans, which helps explain why disease treatments that show promise in animals often fail to work in humans.

Direct studies of the human brain are seldom feasible for technical, legal, and ethical reasons, so researchers in recent years have developed new models to study

the human brain. The three models evaluated in the Academies’ report are:

(1) Human neural organoids, which are tiny three-dimensional aggregates of human neural cells, no more than four millimeters in diameter, grown in the laboratory from stem cells. They are useful research tools because they exhibit some developmental, cellular, and molecular features seen in portions of fetal human brains.

(2) Human neural transplants, which insert human stem cells into the brains of nonhuman animals. These transplants enable the study of human neurons, glia, and other brain cells in the context of the behavior of a whole nonhuman animal.

(3) Human neural chimeras, which are a special case of transplants in which stem cells are injected into a nonhuman animal very early in embryonic development. They intermingle with the host cells that form the brain. To date, chimeras that develop to fetal stages have only been generated using rodent stem cells put into rodent hosts. But research is advancing rapidly, and it is possible that viable chimeras could one day be generated from human cells injected into the blastocyst of nonhuman primates. The hope is that these new models may yield insights into brain development and function, disease mechanisms, new therapeutic targets, and better screening of potential new treatments. But as the power of the models advances, so do the ethical concerns they raise. These include the blurring of distinctions between human beings and other animals, the welfare and rights of research animals, and consent from the people whose cells are used for this research, among other issues.

One paramount concern is that an organoid comprised of human cells might somehow achieve consciousness and experience pain or distress. How to prevent that from happening would require a much broader inquiry with lots of public input, the committee said. It believes that current oversight mechanisms, such as institutional review boards, will suffice for the near-term but that additional oversight may be needed in the future. 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.

THE

AGEISM STRIKESBACK

Our authors, who study successful aging and mental illnesses at University of California, , address the much-debated, complicated question that many of us have long wondered about:

Does the brain improve with age?

By Tanya T. Nguyen, Ph.D. and Dilip V. Jeste, M.D.

ILLUSTRATIONS BY DAVID PLUNKERT

N JAMES HILTON’S 1933 NOVEL LOST HORIZON, SHANGRI-LA WAS A MAGICAL utopia where people lived well beyond 100 years. But now, less than a century later, it seems we are well on our way to making Hilton’s vision a reality. The US Census Bureau reported in 2020 that the average life expectancy has increased from 47 in 1900 to over 80 years today, while the number of people over age 60 exceeds children under 15 for the first time ever. By 2060, the average lifespan will approach 90 years. Astonishingly, more than half of the babies born today will live to age 100 and beyond, which will make Hilton’s seemingly far-fetched vision come to pass.

One might think that people living longer would represent an enormous, thrilling milestone. But unfortunately, aging is rarely perceived that way. The increase in older people—metaphorically termed a “silver tsunami” since the 1980s—has economic implications, including unimaginable healthcare costs. Certain segments of western culture sadly equate aging with such “d” words as degeneration, decline, disability, diseases, dementia, depression, and death. Policy makers and economists are outspoken in their fear that spending money on older people’s care will mean less money for children and younger adults, who represent the future.

This attitude—commonly labeled ageism—is analogous to such phenomena as sexism, racism, and bias against certain sexual orientations. Ageism has made many older people feel guilty about living longer and becoming a potential burden. They think—and are encouraged by society to think—that aging is an incurable disease.

Ageism also rears its ugly head in more practical ways. It is often said that the longer people put off retirement and keep working, the fewer opportunities there are for

young people in the workforce. As a result, senior workers are often forced to retire at an arbitrary age, even if they are functioning well. Many are dismissed because they can be replaced by cheaper labor. When they attempt to re-enter the workforce, age, rather than competence, is often the deciding factor.

We are also seeing effects of ageism in medicine and psychiatry. Fewer medical students are pursuing geriatric medicine or geriatric psychiatry careers today compared to 15 years ago, due partly to relatively low reimbursement from health insurance and partly to our society’s focus on youth, health, and beauty. So, while the need for healthcare will continue to increase along with the aging population, fewer experts will be available to meet the demand.

And if further proof is needed, look no further than an entire anti-aging industry built around prevention and cure—an industry now valued at almost $60 billion globally

Ageism Fact and Fiction

But research does not support the perspective that equates aging with gloom and doom. To use a phrase

THINK. REPRESENT.

THAT PEOPLE. LIVING LONGER AN ENORMOUS, THRILLING UNFORTUNATELY, BUT.

ONE MIGHT. RARELY PERCEIVED

popularized by recent politics, it is a question of facts versus “alternative facts.” There is unquestionably some decline in a number of body structures and functions with

PERCEIVED.

LONGER WOULD. ENORMOUS,. THRILLING MILESTONE. UNFORTUNATELY, AGING IS. THAT WAY..

is inaccurate. Both development and degeneration occur throughout life—from childhood almost until death. Loss of formed synapses in adolescence (via pruning) and the formation of new synapses continue to occur throughout life. It is the balance between the two that leads to maturation of the brain—like a Grand Cru wine evolving from bitterness to perfection.

Aging is not simply a physical process—it also entails psychosocial change. And herein lies a paradox: As we grow older, our physical functioning declines, but our mental and social functioning tends to improve. “Successful aging” is not an oxymoron. Sure, with age we slow down physically, and we may have difficulty remembering names and faces, and problems learning new things. Physical capacity and mental speed begin to decline around age 30, and even more noticeably after age 50. But not all mental functions deteriorate. “Crystallized” cognitive skills at age 75 are roughly equivalent to those at age 20. These are the intellectual abilities based on the accumulation of knowledge, facts, skills, and experiences throughout life, such as verbal skills and

While neurocognitive disorders like dementia become increasingly prevalent with aging, the majority of older people do not develop overall prevalence of dementia (of all types) is just one to three percent at age 65, with the prevalence doubling approximately every six years, to 30 percent by age 85. Other mental illnesses, such as major depression and anxiety disorders, are less common in older than in younger adults.

This was part of the findings in our Successful Aging Evaluation

(SAGE) study at the UC San Diego Center for Healthy Aging, where we reported that mental wellbeing improved in an almost linear fashion from age 20 until the 90s. Young adults in their 20s and 30s suffered the most from depressive symptoms, anxiety, and stress. As the years progressed, most people felt they were aging successfully—a sense of well-being that includes attainment of goals, positive attitudes toward oneself and the future, social connectedness, and adaptation—despite worse physical functioning and social stresses. We saw this phenomenon not only in healthy older adults living in communities but also in those with and being treated for serious mental and medical illnesses, including schizophrenia, AIDS, and cancer

In early 2020, as Covid-19 began to spread worldwide, it quickly became apparent that older adults were vastly more likely than younger adults to develop serious physical complications, to require hospitalization, and to die. Many people also worried about a mental health crisis among the older adults whose social life practically disappeared due to social distancing and isolation. The data, however, suggested the opposite: The mental health of older adults was less adversely affected than that of other adult age groups. In other words, older adults were more resilient and less fearful of dying than younger ones.

Of course, when you find that older people are doing better than younger people in anything, an explanation that immediately springs to mind is survivor bias—that is, sicker people die younger, and people who live into old age are a biased sample. While this is certainly true, it is not the only

WE GENERALLY. OF. CHILDHOOD. AS THE. PERIOD THINK.

reason for age-linked improvement in mental health. For example, several long-term studies have shown that mental health improves progressively with aging even in people with serious mental illnesses such as schizophrenia.

Recognizing Wisdom

In eastern cultures, older people are respected for being wiser. But does wisdom really increase with age? Is this why older adults have better mental well-being? More fundamentally, what is wisdom and how is it related to the brain?

The concept of wisdom goes back to the beginning of most religions and philosophies. The word “Homo sapiens” means a wise man (or person). Verses about wisdom are prominent in the Bible and in the Bhagavad Gita of Hinduism. Greek and Eastern philosophers—from Socrates, Aristotle, and Plato to Confucius and Buddha—described

wisdom throughout their texts.

Empirical studies in wisdom started in the 1970s, but the field has grown markedly in the last couple of decades: Since 2010, PubMed has added 2,000 papers on wisdom. Still, many scientists dismiss it as a fuzzy construct. Wisdom cannot be defined or measured, so how can one study it, they argue. However, the same logic was used for decades, if not centuries, to ignore consciousness, emotions, cognition, stress, resilience, and well-being. Today, we accept them as scientifically characterized, biologically based entities.

Wisdom is a personality trait whose principal components are empathy, compassion, emotional regulation, and self-reflection. It includes qualities that are in notably short supply in today’s highly polarized world: acceptance of uncertainty and of diverse perspectives, and socially focused decision-making. Wisdom is associated with superior well-being, quality of life, and life satisfaction. Indeed, it has a greater impact on mental well-being than objective factors such as physical health and socioeconomic status.

The basic conceptualization of wisdom, as described above, has not varied materially across times and cultures, though there are some cultural differences. This suggests that wisdom is largely biologically based and influenced by culture. Since the early 20th century (thanks to the pioneering work of the German neurologist Korbinian Brodmann), we have been able to localize sensory and motor functions, as well as

the production and comprehension of speech, to specific areas of the brain. While it is harder to localize complex behaviors such as compassion and emotional regulation, brain imaging, neuroanatomical, neuropathological, genetic, and other neurobiological studies strongly associate the prefrontal cortex and the limbic striatum with aspects of wisdom.

Neuroplasticity of Aging

Consider Yoda from Star Wars, Gandalf from The Lord of the Rings, and Albus Dumbledore from Harry Potter—popular mythical icons of wisdom who are in the twilight of their long lives. A number of empirical studies show key components of wisdom to be superior in older adults, compared to their younger counterparts: more prosocial behaviors such as empathy and compassion, better theory of mind, and greater emotional regulation. Elders also demonstrate more self-reflection and insight, tolerance of others’ perspectives and awareness of their own limitations, and a superior ability to facilitate compromise and maintain positive relationships. Put simply: As they age, people tend to become wiser. (Of course, this doesn’t apply to everyone. As Oscar Wilde said wryly, “With age comes wisdom, but sometimes age comes alone.”)

More generally, experience—both good and bad—comes with aging and affects people differently, depending on the person and the circumstances. A disaster leads to post-traumatic stress disorder in some, post-traumatic growth in others.

PERIOD. OF. BRAIN. DEVELOPMENT,. AND OLD. AGE OF. BRAIN. DEGENERATION. BUT THIS. IS A. SIMPLIFICATION,. AND IT IS.

Though aging is typically associated with a loss of neurons and cognitive decline, the effect is not homogenous across brain regions and domains. One of the most exciting developments in neuroscience during the past two decades is the discovery that our brain continues to evolve into old age through “plasticity,” i.e., strengthening of existing synapses and formation of new ones, in the context of appropriate physical, cognitive, and psychosocial stimulation. Scientists have shown that in old mice (and various other species), physical activity accompanied by psychosocial stimulation can increase the number of synapses as well as neurons in such subcortical brain areas as the dentate gyrus of the hippocampus, and areas around brain ventricles. This neuroplastic response may

PHOTO: ALAMY

German neurologist Korbinian Brodmann (1868–1918) mapped the cerebral cortex, defining 52 distinct regions known as Brodmann areas, based on their cytoarchitectonic (histological) characteristics.

underlie the brain benefits of an active and stimulated life. People who stay active physically, cognitively, and socially tend to maintain their vocabulary, their ability to recognize events, objects, and people they’ve encountered before, and the motor skills learned during early childhood, such as swimming or bicycling. Their brains are likely to escape the atrophy that occurs in the brains of sedentary, lonely, inactive seniors. Brain imaging and neurophysiology studies have shown that physical exercise as well as mindfulness and meditation increase gray matter volume and white matter brain cells and synaptic connections, respectively, and their activation in the anterior regions that support positive emotions and wisdom.

There is a phenomenon called PASA (Posterior-Anterior Shift in Aging) that may help explain why wisdom improves over the life course. Our brains develop in a back-to-front manner; the prefrontal cortex, the last portion to mature, is not fully formed until one’s early 20s. PASA mirrors that sequence: With age, neural activity shifts from the occipital lobes in the back of the brain, which are centers for processing sensory stimuli, to the prefrontal cortex, which is responsible for executive functions. Therefore, while sensory processing may decrease over the years, the brain may recruit higher-order networks in the prefrontal cortex that are associated with wisdom development.

Another aspect of the aging process, HAROLD (hemispheric asymmetry reduction in older adults), involves reduced lateralization of the

INACCURATE..

brain. This means that in younger people, the brain’s right and left hemispheres specialize in somewhat different tasks. Age reduces this asymmetry: Tasks previously managed by a neural circuit housed in a single hemisphere now call on both sides of the brain. Their ability to recruit neuronal networks from both hemispheres for a given mental activity offsets, to an extent, the loss of synapses and neurons in older people.

Finally, aging changes the way the brain responds to emotions. This might explain the “positivity effect” of aging, a tendency to favor positive emotions and memories. Older people pay attention to and remember pleasurable and gratifying events better than sad, frightening, regrettable ones, whereas younger individuals retain positive and negative information equally well. It is as if young minds are like Velcro® for negative experiences,

Research conducted by the Australian Human Rights Commission revealed that the most common words used to describe older adults in the media are forgetful, slow, frail, vulnerable, burden, grumpy, and sick. The size of each word is directly proportional to the number of mentions of that theme. Responses were based on the question: “Thinking about everything you see and hear in the media (including on TV, online, on the radio, and in newspapers and magazines), how does the media portray older people?”

and older minds like Teflon®. Older adults more easily dispel feelings of disappointment, regret, and remorse, and worry less about events or issues they cannot change.

This may reflect changes in sensitivity of the brain area central to the processing of emotions— the amygdala. In younger people, amygdala activity increases in response to both positive and negative visual images; in their elders, negative images trigger much less activity than positive ones.

One caveat must be kept in mind: No age-linked increase in wisdom can continue indefinitely. It ends when neurodegeneration surpasses the aging brain’s ability to compensate. The age when this happens is not fixed and likely varies subject to a number of factors.

Evolutionary Value of Human Wisdom of Aging

In evolutionary terms, prolonged human longevity would seem to make no sense. Darwin’s theory of evolution is predicated on survival of the fittest, which depends on the ability to procreate. Older people cannot reproduce, so they cannot promote species survival. Among primates, humans are unique in regularly outliving their loss of reproductive capacity by decades. For example, when a person who had menopause or andropause at age 45 lives to age 90, they would have spent the entire second half of their life without fertility.

While human life span is increasing, fertility span is not. The average age at menopause or andropause has remained

unchanged (45-50) over millennia. So, how can we explain exceptional human longevity despite unchanged loss of fertility and physical health in old age?

Homo sapiens is the only species able to produce offspring years before its brain is fully mature. Biologically, we humans are primed to conceive children with the arrival of puberty around age 12 or 13, while our brains continue to undergo considerable refinement, via processes such as synaptic pruning, until the early 20s. How can adolescents with incompletely developed brains (who are not even legally deemed fully responsible adults), care for their own children and make them fit to survive in potentially risky environments?

Here is where data suggests

FIGURE 1: Perceptions of how older people are portrayed in the media

that wisdom of aging may have evolutionary value for humans, both by compensating for loss of fertility (through the Grandmother Hypothesis—i.e., grandmothers helping their adult daughters live longer and be more fertile) and by transmitting the culture’s knowledge and traditions to younger generations.

The Grandmother Hypothesis is based on research in several mammalian species. Orcas, or killer whales, one of the few non-human species in which females have menopause, derive extraordinary bonding and other benefits by having multiple generations within a pod (an extended family unit that travels and hunts together). The death of a post-reproductive female orca in the pod increases the risk of death up to fivefold for female babies, and 14fold for males.

Research suggests similar phenomena among humans. In a remarkable study of complete multigenerational records of about 2,800 Canadian and Finnish women born before 1900, the daughters of older mothers reproduced earlier, more frequently, and more successfully. Maybe “wise” behaviors of these grandmothers helped their own health and longevity and also aided their offspring’s fertility and longevity successes.

Other studies suggest specific ways in which interactions with grandparents, perhaps via sharing of life experiences and the imparting of wisdom, might benefit younger generations. One found that children in households with three generations (i.e., children, parents, and grandparents) had fewer behavioral problems than children in other households. Other studies link the involvement of grandparents

to fewer emotional problems and adjustment difficulties, and more prosocial behaviors in middle school students, especially among those living in single-parent or stepfamily households.

Biologically, old-age-supporting “grandparent genes” may have evolved to enable older adults to retain the physical and mental abilities to help their grandchildren, by protecting elders from neurodegenerative and cardiovascular diseases. Variants of two particular genes, CD33 and APOE, are associated with better brain and cognitive functioning, possibly through less accumulation of beta-amyloid, a peptide involved in Alzheimer’s disease. These variants are expressed at higher levels in humans than in chimpanzees, our closest living relatives.

Enabling older individuals to stay active, have a purpose in life, and transmit wisdom to younger generations will promote healthy lifestyle in everyone, lowering the prevalence of pathology, and reducing societal costs of physical and mental healthcare. Going forward, age-friendly intergenerational communities will hopefully offer generative opportunities for older adults and

WHILE. NEUROCOGNITIVE. DISORDERS. DEMENTIA. BECOME. INCREASINGLY. PREVALENT. WITH AGING,. THE MAJORITY. OF OLDER. PEOPLE DO NOT.

THE SECRET INGREDIENTINTEROCEPTION

By Lisa Feldman Barrett, Ph.D., and Karen S. Quigley, ILLUSTRATION

INTEROCEPTION

INGREDIENT

Quigley, Ph.D.

BY ZOË VAN DIJK

Your brain keeps you alive and well by running a metabolic “budget” for your body. Our authors, who codirect the Interdisciplinary Affective Science Laboratory at Northeastern University and Massachusetts General Hospital, explain how these budgetary activities, and the bodily sensations they create, suggest surprising connections between brain, mind, body, and world.

as you read this text, it may seem like your eyes are simply detecting words out there in the world. But you’re not detecting—you’re constructing. In every moment, outside of your awareness, your brain constructs a model of the outside world, transforming light waves, pressure changes, and chemicals into sights, sounds, touches, smells, and tastes. Your brain continually anticipates what will happen next around you, checks its predictions against sense data streaming in from your eyes, ears, and other sensory surfaces of your body, updates the model as needed, and in doing so creates your experience of the world. This covert construction of your senses is called exteroception

Your brain also models the events occurring inside your body. In much the same way that your brain sees sights, feels things that touch your skin, and hears sounds, it also produces your body’s inner sensations, such as a gurgling stomach, a tightness in your chest, and even the beating of your heart. Your brain also models other sensations from movements that you cannot feel, such as your liver cleaning your blood. The construction of all your inner sensations is called interoception and, like exteroception, it proceeds completely outside your awareness.

For a long time, scientists treated interoception and exteroception as completely separate domains of sensation, bounded by your skin. But recent research has revealed that the two might not be as separate as they seem, and their boundary is fuzzy. Perhaps more importantly, the science of interoception reveals some surprising insights about how your brain works and may be a key to better understanding health and illness.

Your Brain Runs a Budget for Your Body

You live in a complex body. With over 600 muscles in motion and dozens of internal organs, your body pumps 2,000 gallons of blood per day, balances dozens of hormones and other chemicals, regulates the energy of billions of neurons, digests food, excretes waste, and fights illness—all of it nonstop throughout your life. Your brain’s most important job is to coordinate and control the systems of your body as they burn and replenish energy efficiently. Your brain ensures that the right amounts of salt, glucose, water, and other vital resources are available where and when they’re needed, so you can walk, think, learn, innovate, and love. This constant budgeting of your body’s needs is called allostasis

Allostasis is a predictive balancing act. Your brain moves your body through a massively complex world full of other brains-in-bodies, so it must constantly guess which of your cells need what resources… and guess well. If your heart rate is too fast or slow for the physical demands you face, or your lungs don’t process sufficient oxygen, or your cells become insensitive to the glucose that ultimately powers your muscles, you’re not likely to live long. So, your brain is engaged in the constant body-budgeting of allostasis, anticipating your body’s needs at every moment while deciding which efforts are worth the metabolic investment. Right now, for example, your brain is using some glucose and other metabolic resources to read these words. Learning and moving your body are some of your brain’s most costly operations, metabolically speaking.

Efficient energy regulation, therefore, is a major selection pressure for all living things. Animals live longer

and suffer from fewer diseases when their tissues, organs, and systems receive the right nutrients just when they are needed. Such animals are more fit to reproduce. They can explore further for food and better protect themselves from predators, learning all the while and honing their models of the world. The more effectively and efficiently a brain can invest its energy, therefore, the greater the metabolic return.

Sensing the World Around You

Reading this text depends on seeing, which is one form of exteroception. To perform this activity, your brain makes metabolic investments to model the world outside your body. It directs your eye muscles to contract and relax in a pattern that allows your eyes to sweep across a line of text—at each moment predicting what you will see next, based on past experience (see Figure 1). Your brain then directs your eyes to stop and fixate briefly to compare its predictions to the visual data arising from the page. It makes any necessary corrections and then directs the next volley of eye movements.

Vision, like other forms of exteroception, operates in the service of movement. Think about it: How do you know how far away to hold this page, so the article is legible?

your mouth, or pick up a cup with the right amount of force? It’s all about sensation and its intimate ties to allostasis. Your brain sees, hears, feels physical contact, and constructs other sensations not because these activities are intrinsically fun or valuable, but because sensations are the means by which your brain controls your body’s many moving parts. Your movements give your brain the sense data to build its model of the world, and this model guides your actions, ultimately supporting allostasis so you survive, and even thrive, in the world around you.

Exteroception works mostly by prediction. Your brain issues motor commands, say, to move the muscles of your head, eyes, and other body parts (even before you’re aware) and simultaneously predicts the sensations likely to result from those movements. When the actual sense data arrives from the sensory surfaces in your eyes, skin, and other sense organs, your brain integrates the data to confirm or correct the predictions to refine or adjust the motor movements. In constructing your sensations, your brain estimates the state of the world in order to control and coordinate your body’s movements.

Sensing the World Inside You

The muscles attached to your skeleton are not the only moving parts of your body. As you read this article, your brain is conducting a mostly silent symphony of movement inside your body, involving your organs, autonomic nervous system, endocrine system, and immune system. Your lungs continually expand and contract to take in oxygen and expel carbon dioxide as your heart beats to pulse blood throughout your body and brain. If what you’re reading seems interesting or unexpected, your heart rate and respiration may slow.

Many other things that you might not think of as movements are indeed movements of a sort. For example, the flow of your saliva to aid digestion; the surge of chemicals that create inflammation; and the gush of cortisol from your adrenal glands. (Cortisol has been called a stress hormone, but it is more correct to call it a metabolic hormone; it gets glucose into your bloodstream quickly when your brain predicts your body will need it.) Even conversations between the cells of your intestine and

FIGURE 1: This optical illusion demonstrates the power of your brain’s use of past experiences to construct what you read. Sweep your eyes from left to right, and you’ll perceive the central symbol as a “B”; sweep your eyes from top to bottom and it transforms into a “13”.

the bacteria that reside there are considered motor movements; this constant chatting aids digestion, and over time can even adjust the length of your intestine to regulate how quickly you digest!

Interoception, like exteroception, operates in the service of movement predictively. Here’s the gist: Your brain issues motor commands that adjust the insides of your body, and it simultaneously predicts the sensory consequences of those movements. At the same time, the sensory surfaces inside your body, including dozens of cells that monitor pressure changes, temperature, contractions, stretches, nutrients, gases, toxins, and various chemicals, send a steady stream of sensory signals back to your brain via electrical impulses in your spinal cord and swirling chemicals in your blood. Your brain integrates these sensory signals to confirm or correct the predictions and adjust its predicted movements, if necessary, thereby maintaining allostasis efficiently. In this way, your brain anticipates the needs of your body and proactively coordinates the internal movements that deliver glucose, water, salt, oxygen, and other resources to billions of cells just in time.

body position), olfaction (smell), and taste, emerge from signals coming from inside and outside the body. And other signals, like wetness, are entirely computed by the brain. Your skin has no wetness receptors, for example; your brain constructs wetness as a combination of touch and temperature.

For example, think of the last time you were thirsty and drank a glass of water. Within seconds after draining the last drops, you probably felt less thirsty. This event might seem ordinary, but the water actually takes about 20 minutes to reach your bloodstream, so it can’t possibly quench your thirst in a few seconds. What relieved your thirst? Prediction. As your brain plans and executes the actions that allow you to swallow, it simultaneously anticipates the interoceptive consequences of gulping water, causing you to feel less thirsty long before your brain learns from the body about your increased hydration.

New Insights and Deep Implications

There is still much to learn about the mechanisms of interoception and what they mean for health, illness, and basic mental functions. Exteroceptive senses such as vision are relatively better understood—perhaps because scientists are often guided by their experiences, and we don’t experience most interoceptive activity. Nevertheless, creative research by those who do study interoception has brought forth some intriguing insights. New ideas are transforming our most basic understanding of brains and bodies and challenging our most basic assumptions of how they work together to create the mind, control actions, and cause illness. We’ll share three such insights that blur three fundamental boundaries: what is inside versus outside the body, what is mental versus physical illness, and what distinguishes different mental phenomena.

It might sound bizarre, but your brain doesn’t know where your body ends and the world begins. Instead, it approximates a continually shifting boundary. Sometimes the shifts are slow, accomplished by touch, hearing, and watching body parts in action. If you were an ungainly teenager, or you’ve been pregnant with an ever-growing belly that unexpectedly whapped into things around you, then you know what we mean. Other times the shifts are quick. Everyone who has driven around town without hitting other cars or the curb has benefited from just how quickly and effectively a brain can expand the boundaries of a body to include the car’s perimeter. (Exit the car and the boundaries shrink back just as fast.)

There is another way in which internal and external cannot be neatly bisected. Interoception gives you an extra, fuzzy, exteroceptive sense for free: the gut feeling that something has happened around you. Here’s how it works: The light waves that hit your retina and the air pressure changes that reach your cochlea are the outcomes of changes in the world, and your brain guesses, using past experience, what the causes of that sense data might be. Such guesses prompt your brain to prepare for movement internally, such as quickening your breath or secreting cortisol, to support your next actions. These plans for coordinated movement come with predicted sensory consequences.

Evolution did not wire us to feel every interoceptive gurgle, gush, and tug directly, so instead, we often

experience them as simple feelings: pleasure or displeasure, idleness or activation, fatigue or energy. Scientists call these simple feelings affect or mood. Affect does not reveal what in the world has changed, where the change is, or what to do about it. Rather, it is just a quick and dirty sixth sense that something has happened. That particular something may be outside your body and require a rapid and energetically costly response.

But there’s a tricky bit: This arrangement allows and maybe even encourages you to search for the causes of your mood in the outside world—in your relationships with other people, or in your responsibilities at home or at work. Feel on edge? Maybe you’re late for an appointment. Feel unpleasant? Maybe someone has wronged you. Many internal perturbations have purely internal causes, however, such as lack of sleep, dehydration, or eating too much processed fat and sugar. Just because you feel bad doesn’t automatically mean something bad is happening (or is about to happen) to you.

Mental vs. Physical

This brings us to a second insight: Interoception diminishes the boundary between physical and mental. In every moment, your brain transforms something physical—interoceptive predictions (which are neural patterns) and sense data (which are neural or chemical patterns)—into something mental (affect). The same brain circuitry that models the physiological state of your body to create interoceptive sensations also creates the ups and downs you feel every day. Hundreds of studies from laboratories around the world, including

ours, have observed this, but scientists still puzzle over the mechanisms that transform physical signals into mental feelings. They remain one of the great mysteries of consciousness.

A particularly permeable aspect of the mental/physical boundary is between mental and physical disease. Obesity is traditionally viewed as a behavioral disorder, heart disease as a physical disorder, and depression as a mood disorder. But the three are highly comorbid, with any one of them appearing as the so-called “initial” disorder (i.e., depression can precede obesity or vice versa). In addition, the seeds for all three diseases are planted in early life This confluence of findings suggests that some behavioral, physical, and mood disorders share disruptions in efficient energy regulation, implying disruptions in allostasis and interoception.

Scientists are still unraveling the complex entwining of metabolism, the immune system, and other internal systems of the body. For example, problems with energy regulation, if they go on long enough, produce chemicals and activate receptors that kick the immune system into high gear. Immune responses are incredibly energyconsuming, which further burdens your metabolism, and such cascades often end in serious illness. Exploring and understanding such basic mechanisms may open the door to new strategies for prevention, treatment, and cure.

Some say that the body “keeps score” of adversity and trauma from childhood onwards, making you more vulnerable to illness; but in fact your brain keeps score, and your body is the score card.

Mental Phenomena

The more we learn about interoception, the blurrier a third presumed boundary becomes: one between different mental phenomena. For example, you’d never confuse your sense of touch with the act of breathing, right? Well, it turns out that the two are more entwined than you may think. When something is touching your skin, you’re more likely to take in information about it as you inhale than as you exhale. This finding suggests that the sense of touch, which is traditionally considered exteroceptive, may be entwined with interoception at a basic level.

Similarly, you’d never confuse your eyesight with your heartbeat, but the way that your brain receives visual information from the world may be yoked to your heartbeat. People are more likely to take in visual information during the period of each heartbeat when the heart relaxes and blood fills the ventricles, and less likely to take in visual information when the heart contracts and pushes blood out into the arteries. The latter is like a brief,

Two Vital Networks

The brain system that supports allostasis and interoception is composed of two large-scale, intrinsic networks. They are conventionally called the “default mode” network and “salience” network, though scientists use several other names in published research.

Allostatic control signals (“efferent” signals)

MEDIAL SURFACE

dmPFC — dorsomedial prefrontal cortex

vmPFC — ventromedial prefrontal cortex

mOFC — medial orbitofrontal cortex

SMA — supplementary motor area

MC — primary motor cortex

SSC — primary somatosensory cortex

sgACC / pgACC — subgenual and pregenual anterior cingulate cortex

aMCC / pMCC — anterior and posterior mid cingulate cortex

PCC — posterior cingulate cortex

PC — precuneus

RSC — retrosplenial cortex

mTL — medial temporal lobe

Nacc — nucleus accumbens

Thal — thalamus

HPT — hypothalamus and pituitary gland

SC — superior colliculus

PAG — periaqueductal grey

PB — parabrachial nucleus

RVLM rostral ventrolateral medulla

NTS nucleus tractus solitarius

Interoceptive sense data (“afferent” signals”).

LATERAL VIEW

dlPFC — dorsolateral prefrontal cortex

vlPFC — ventrolateral prefrontal cortex

lOFC — lateral orbitofrontal cortex

aI, pI — anterior to posterior insula

PMC — premotor cortex

SMA — supplementary motor area

MC — primary motor cortex

TPJ — temporoparietal junction

mTG — middle temporal gyrus

lOTJ — lateral occipitotemporal junction

Note: all of these are part of the cerebral cortex.

recurring, visual blind spot in time.

Such findings have surprising implications for understanding how your brain and body create your mind. They imply, for example, that neither the conventional “visual system” nor the conventional “somatosensory system” is solely responsible for the ability to see and to feel touch, respectively, but both are components of larger, more distributed neural assemblies that produce these sensations—assemblies that include interoception. Traditional boundaries between the phenomena of everyday life such as vision and touch may not be respected by the brain.

Observations like these may have practical implications with profound societal impact. Imagine your heart is racing at 180 beats per minute, so rapidly that your brain cannot properly sample sense data from the retina. What will you see? Your brain will construct your visual experience mainly from its predictions—your beliefs—and may go uncorrected by actual events in the outside world. Now suppose your heart is racing because you’re a police officer in a high-pressure situation, and you’re armed. It is conceivable that your brain’s predictions could lead you literally to see things that aren’t present

But wait, there’s more. Vision, touch, and the sensations of your lungs and heart are just a few of the many mental faculties that scientists study. What about the boundary between cognition and emotion? How about the boundaries between different types of cognition (thinking, decision-making, attention) or different types of emotion (anger, sadness, fear, happiness)? For over a century, scientists typically have assumed that the human mind is made up of different types of mental faculties, each arising from its own dedicated psychological process or mechanism, implemented in its own dedicated set of physical causes in the body and brain. But are they?

Recent evidence suggests we should replace this type-based approach with a more holistic one to better understand how your whole brain, in constant conversation with the various systems in your body, creates your mind at any given moment. If we consider the brain circuitry that is important for allostasis and examine its connectivity to the rest of the brain, we see two well-known brain networks (see sidebar at left, "Two Vital Networks"). The networks overlap in a set of hubs in the cerebral cortex that serve as the brain’s backbone for neural communication and have extensive projections to subcortical regions that control the autonomic nervous system, immune system, and endocrine systems. These

networks are implicated in various types of sensation and perception, including interoception, and participate in phenomena as diverse as memory, emotion, affect, language, reward, social affiliation, pain, alcohol craving, stress, mental illness, diabetes, and moral judgments of other people. They also converse with groups of cells, deep in the brainstem, that give rise to neurochemicals— dopamine, serotonin, and norepinephrine—that help neurons fire and therefore play important roles in attention, learning, and consciousness. Interoception, it seems, may be at the core of mental phenomena that don’t seem interoceptive at all.

Even when we focus on individual brain structures, we can learn how interoception dissolves traditional psychological boundaries. Consider the hippocampus, a structure deep in the temporal lobe of your brain that is typically thought to be crucial for certain types of memory. Exciting scientific evidence now indicates that the hippocampus is bathed in interoceptive information and plays a key role in estimating the physiological state of the body. A rodent’s hippocampus, for example, receives signals about energy availability in the gut that regulate how much the animal eats in a given meal. But the hippocampus can override these signals, causing animals to eat substantially more food than they otherwise would. Therefore, calling the hippocampus a “memory” structure may be far too limiting.

The impact of interoception reaches far beyond what its conventional definition would suggest. Who would have thought that your heartbeat is linked to what you see and how well you see it? To understand something as fundamental as vision, therefore, we must recognize the importance of interoception. To understand health and illness, and even consciousness and mood, we also must appreciate that metabolism, and therefore interoception, plays a central role. Interoception is a secret ingredient in some of the most important and intimate parts of your life. l

Why is narcissistic personality disorder, which has been recognized by the American Psychiatric Association since 1980, under-researched and rarely treated?

Narcissism

GETS NO RESPECT

BY ELISE OBERLIESEN • ILLUSTRATION BY BORIS SÉMÉNIAKO

nthe relationship fall apart due to narcissistic behaviors, the obvious questions become: Can this person be fixed? What drives narcissists to be narcissists? And finally, is narcissism a mental disorder?

Let’s start with the last question first. Since 1980, a form of narcissism has been recognized in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM) as narcissistic personality disorder (NPD), where it is defined as a personality disorder comprising “a pervasive pattern of grandiosity (in fantasy or behavior), need for admiration, and lack of empathy.”

A NORMAL RELATIONSHIP,

it goes something like this: Two people catch that distinct twinkle in each other’s eyes. Typical behaviors unfold, like flirting, followed by a test of the suitor’s capacity for witty banter. Soon, good morning texts with kissy face emojis start to regularly ping. The pair experiences joy and laughter over espresso and indulgent bites of tiramisu. Weeks stretch into months, and deep emotional connections ignite the honeymoon phase of the relationship. Bliss.

Now, for the not-so-normal relationship: where one person is a narcissist. Kissy face emojis go rogue while good morning texts arrive in scarce supply. Anxiety and confusion set in for the other person. Shared desserts start to taste bland while the narcissist grows obsessed with their phone. Witty conversations are replaced by sentences such as, “I don’t know.” Loneliness and isolation ice over the honeymoon stage, thanks to petty arguments, silent treatments, and explosive bouts of rage.

As you watch someone’s personality slowly unhinge and

Web MD describes personality disorders as mental disorders caused by an unhealthy pattern of thought and behavior, and divides them into categories known as clusters. “People with personality disorders often struggle to interact with the world. Their disorder makes it hard for them to understand social situations and relationships,” says the website, which lists NPD in the Cluster B category, alongside antisocial, borderline, and histrionic personality disorders.

Drawing the distinction between taking a healthy ego to extremes and an NPD diagnosis is an interesting question. In 2009, Emily Yoffe, a contributing editor at The Atlantic, summed it up this way for Slate: “The problem occurs when narcissism becomes the primary principle of someone’s personality. Its most extreme form is NPD, a psychological condition that impairs a person’s ability to form normal relationships and wreaks havoc on those who have close encounters with it.”

The Treatment Factor

The question of fixing someone through treatment is a bit more complicated, however. That’s mainly

because NPD is a less studied condition than most other disorders. One reason for a lack of treatment, say experts, is that narcissists rarely show up in a therapist’s office. Another is that there are no pharmaceutical fixes. A survey study in the American Journal of Psychiatry, in which only ten percent of invited psychiatrists and clinical psychologists responded, found that “clinicians reported feeling anger, resentment, and dread in working with narcissistic personality disorder patients; feeling devalued and criticized by the patient; and finding themselves distracted, avoidant, and wishing to terminate the treatment.”

NPD can run on a continuum from mild to severe, and to develop effective treatment protocols, it’s important to understand its origin and pathogenesis. But because of difficulties encountered in studying this disorder, researchers and clinicians must piece together scientific findings from the few systematic reviews and metaanalyses that exist for NPD.

“We know that NPD is heritable and genetic even when compared to other personality disorders,” says Royce Lee, M.D., psychiatrist and associate professor of psychiatry and behavioral neuroscience at the University of Chicago. “There’s a twin study that seems to suggest among the different personality disorders, its heritability is the highest.”

Adding the nature versus nurture question generates theories suggesting that NPD and other personality disorders originate from childhood trauma that affects emotional development in the brain. The hypothesis holds some plausibility, says Lee, who specializes in trauma and whose research team

has found a link to oxidative stress (an imbalance between free radicals and antioxidants in the body) and personality disorders.

There are three subtypes of NPD: classic, exhibitionist, and high-functioning; the latter has the highest severity of poor psychosocial and interpersonal functioning. Lee says it is also important to consider how personality disorders manifest within different cultures; narcissistic personality disorder will not look the same in western society compared to eastern society, for example. He adds that taking cultural considerations into account could also help clinicians better

diagnose and treat people with such personality disorders that may be tied to obsessive compulsive behavior and paranoia.

Lee says that cultures express things differently and speculates and that “if you view NPD as a stress-related disorder, racism or other factors can increase the rates of the disorder." For example, the drive to accumulate wealth is a mindset often tied to narcissism with deep roots in western culture, Lee believes. In contrast, in nonwestern cultures that put more emphasis on the approval of others and a “de-centered self,” narcissism may likely play out much differently.

That’s why it’s crucial to take cultural consideration and diversity into account during personality disorder assessments.

When Narcissists Go Too Far

On the surface, people with narcissistic traits typically display common, yet harmless, behavioral patterns, including overconfidence, a sense of entitlement, arrogance,

The term "narcissism" comes from the Greek myth of Narcissus, the beautiful boy who was unable to love until he saw his own reflection in the water and died pining away at his image.

or the need for constant praise and admiration. The DSM cites such traits as those of the “grandiose narcissist.” In comparison, the traits of the vulnerable narcissist, run to cognitive challenges like low selfesteem and depression.

Some narcissists share somewhat darker traits—deception, devaluation, gaslighting, manipulation, and control—linked to emotionally and psychologically abusive behavior. Some of these behavioral patterns are documented in the Springer Nature journal Borderline Personality Disorder and Emotion Dysregulation, where a questionnaire study included verbatim reports from family members and current or former romantic partners of narcissists.

One researcher, Brin Grenyer, senior professor at the University of Wollongong Australia and director at Project Air Strategy for Personality Disorders, has found that narcissism is commonly underreported. The study delineates grandiose versus vulnerable narcissistic traits and finds significant overlap between them—with 69 percent of respondents reporting both characteristics. Because narcissists may oscillate between grandiose and vulnerable—the term “pathological narcissism” more broadly describes the disorder.

Lee points out that the true number of people diagnosed with NPD is difficult to calculate—but that it is likely higher than the 0.5 to 5 percent currently reported in the US. “There’s an overdiagnosis of bipolar, when in fact a personality disorder is the better or more accurate diagnosis—and is more predictive of what treatments will be helpful,” Lee says, adding that both NPD and bipolar disorder can coexist, but

One reason for a lack of treatment is that narcissists rarely show up in a therapist’s office.

require different treatment protocols.

Only when a clinician feels that a patient is suffering from bipolar disorder in addition to NPD will medication be prescribed. Otherwise, NPD is generally treated through psychotherapy alone. Lee says more research is needed to make medication a treatment option for NPD. Grenyer agrees, adding, “One of the new frontiers in research is to develop better ways to understand and treat both those with narcissistic traits but also those close to them who themselves can be suffering.”

Processing Deception in the Brain

Some have suggested that narcissists have a greater-thanaverage propensity to lie, perhaps to self-enhance desirable traits. We know that every human lies—from giving false compliments, to making excuses, to taking sick days. Turns out, some people lie more than others. And thanks to neuroimaging, neuroscientists can differentiate between truth-telling and lying and get to those untruths associated with personality disorder.

One study that examined lying in people with NPD suggested

associations between deceptive behavior and both narcissistic traits and self-assessed lying ability. Narcissists are prone to deception, and some actually consider themselves more skilled at lying than the average person. Based on investigations, the researchers discovered positive associations between lying and deceptive communication with narcissism.

In another study about lying, researchers found changes in brain activity that correlate with snowballing lies—known as “dishonesty escalation.” To explore the phenomenon, researchers used brain imaging while subjects carried out behavioral tasks that allowed them to lie repeatedly.

Neil Garrett, Ph.D., lead study author and a cognitive neuroscientist at the University of Oxford, says the behavioral findings indicate that over time, dishonesty increased, and imaging showed that signal reduction in the amygdala is sensitive to dishonest behavior.

Lena Sisco, a former Navy intelligence officer and Marine Corps-certified interrogator who now consults with federal and state law enforcement agencies on criminal cases, says that when the average person lies, a natural stress response causes cognitive abilities to diminish as the limbic brain kicks into high gear. “The limbic brain overrides the thinking brain, and we become more irrational and emotional,” she says. “And because of diminished cognitive ability, we can’t even comprehend simple questions and tasks.”

Powerful liars, not specific to NPD, are described by Sisco as people who appear more skilled in deception, not

because they are, but because they get away with it and have different motivations. “They do not get nervous when they lie and therefore appear calm, cool, and collected,” she says, citing findings from Aldert Vrij, a professor of psychology at the University of Portsmouth in England. Vrij examined examined deception through fMRI imaging and found that different neural activity takes place with deceptive individuals. Sisco adds that powerful liars primarily care about reward and will do whatever it takes at any cost—even when it may hurt others.

Cortisol, a hormone linked to stress, is suppressed so it isn't going into the limbic system of the brain, says Sisco. “Their stress response system has not been triggered; that is why we do not see them looking nervous or showing physiological indicators a polygraph can detect.” She adds that when it comes to detecting lies, fMRI is more reliable than polygraph tests. However, ethical questions surround the use of such an invasive test for all personality disorders.

Neuroimaging Detects Emotions

Another hallmark sign of NPD is emotional dysregulation. A type of fMRI called voxel-based morphometry suggests structural abnormalities in the narcissist’s frontal-paralimbic brain region Specifically, lower-volume gray matter in images of people with NPD is associated with restricted ability for emotional empathy, according to study authors.

fMRI findings suggest that the anterior insula region orchestrates aspects of empathy and compassion—traits that narcissists often lack. This region is also thought

to influence interpersonal decisionmaking—such as an individual’s ability to express traits like fairness and cooperation. Feelings of entitlement and superiority allow narcissists to justify rule-breaking and playing by their own set of rules—even when it’s unlawful.

Seeking Treatment for NPD

Research and data are lacking on the rationale for outcomes for various forms of treatment currently used, and advances will depend upon advancing treatment studies.

In the opinion and experience of Sharie Stines, Psy.D., a therapist and author of Narcissist Survival Guide, narcissists lack the “blueprint” that allows “healthy interpersonal bonding,” perhaps the result of childhood trauma and negative parental involvement that disrupt natural processes.

Stines uses a variety of therapeutic methods designed to help patients change their current thought

We know that NPD is heritable and genetic even when compared to other personality disorders.

process. “In order to heal, they have to create a new blueprint or template out of scratch. I do this using psycho-education, cognitive restructuring, and imagery,” she says. Psychoeducation is a holistic therapy that draws on cognitive-behavioral therapy, learning theory, and group practice to encourage collaboration, coping, and empowerment. Similar approaches are used to treat schizophrenia.

Stines is among therapists who also use Eye Movement Desensitization and Reprocessing (EMDR)—originally designed to alleviate the distress associated with traumatic memories—to help people with NPD resolve unpleasant responses to unpleasant memories. It has also shown positive outcomes in creating a more realistic selfidentity, which can help the narcissist resolve their feelings of superiority.

In their 2009 book, The Narcissism Epidemic, psychologists Jean M. Twenge and W. Keith Campbell write: “Despite the popularity of narcissism as a label, it is difficult to find scientifically verified information on it outside academic journal articles. Many websites on narcissism are based on some combination of conjecture, personal experience, and poorly understood psychoanalytic theories.”

If NPD is truly on the rise, as the data suggests and social scientists believe, society will suffer as work ethic and intellectual interest decline. More aggression, relationship complications, and a lack of empathy are also unavoidable. Write the authors: “Understanding the narcissism epidemic is important because its long-term consequences are destructive to society.” Advancing the research and treatment on NPD and all personality disorders is long overdue. l

rofound and unfathomable imagery is often found in places people never go: millions of miles away in space or thousands of feet beneath the sea, for example. One place where photographer Veronica Szarejko never expected to find immense beauty was through a peek at the brain using a transmission electron microscope. “I felt as if I had been transported back to the darkroom during a time when I was printing my own silver gelatin images for exhibitions,” she recalls. “The depth and beauty of these black and white images were stunning, and I felt an immediate attachment to them.”

Szarejko, who in 2014 was helping to create presentations and posters for scientific conferences for the Nash Family Department of Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City, was inspired to conceive The Art of the Brain, an exhibition of more than 70 photographs, drawings, paintings, videos, and sculptures celebrating the beauty of the brain as seen through the eyes of researchers and medical illustrators at the school’s Friedman Brain Institute

Since the exhibition was launched in 2014 in conjunction with the annual Brain Awareness Week campaign in March, submissions have grown each year. This year—in which Art of the Brain was presented in a 3-D, virtual space due to pandemic concerns—contributions

BEAUTY P the BRAIN &

came from members of ten different departments, including neurosurgery, psychiatry, genetics, and genomic sciences.

Szarejko told the journal The Lancet that the exhibition’s objective is twofold: “to showcase the range of inventive work created and inspired by research undertaken at Mount Sinai; and subsequently to extol the high-tech environment at which avant-garde science research is progressing and developing novel treatments for neurological disorders.” Represented are advanced technologies, such as electron microscopy, laser-based cellular imaging, and confocal microscopy, and techniques including 3-D modeling, immunofluorescent staining, diffusion tractography, and fluorescence microscopy.

All of the artwork was created by institute members, mostly in the workplace. The only criterion is that the piece must relate to the brain or nervous system. Available for purchase, proceeds for the individual pieces go towards the institute’s Diversity in Neuroscience (DiverseBrains) initiative. This year, three modest cash awards were presented; a new honor consisted of one image being selected for the cover of the journal Biological Psychiatry

“Our goal is to not only highlight these amazing images, but for people to learn about the really exciting work being done by institute researchers on advancing our understanding of brain and spinal cord disorders,” says project manager and curator Szarejko. She hopes to add graphic novels as murals and performance art to the mix when the exhibition returns to its gallery space at the institute at the start of Brain Awareness Week next year. l

— Bill Glovin

In “Pop Brain,” infantile features of baby portraits evoke neural activation in the striatum, which is a critical component of the brain's reward system. Collaborating to create the work were An-Li Wang, assistant professor of psychiatry, and physician assistant Chris Kudrich.

Web development coordinator Danny Roldan created “Kodama,” inspired by both the intricacies of neurons and Japanese imagery. neurons depicts the homes of our spirits.

imagery. In Japanese folklore, the term “Kodama” is a word used to name a tree in which spirits live. In Roldan’s piece, a forest of

In “In All Shapes and Sizes,” brain cancer cells that lack access to adequate oxygen (green) move away from and surround dead cells, giving rise to barricading structures of different shapes and sizes. The image was created by postdoctoral fellow Anirudh Sattiraju.

“YAP in the Wild,” created by postdoctural fellow Chrystian Junqueira Alves and medical student Theodore Hannah, shows aggressive brain tumor cells overexpressing the proteins (Plexin-B2 and YAP) that grow abnormally in culture.

Outgrowth of axons from a midbrain organoid in a 2.5D culture format is expressed in “The Spinning Disk of Light,” created by graduate student Lily Sarrafha.

"Embryonic Jewel," a human embryonic stem cell colony stained with cytoskeleton markers, was created by postdoctoral fellow Chrystian Junqueira Alves.

Graduate student Yong Huang, M.D., Ph.D.'s “Reactive Astrocytes Surrounding Amyloid Plaque” depicts star-shaped astrocytes (green color) surrounding amyloid plaque (red color) in the brain of an Alzheimer’s disease mouse model.

Human glioblastoma (brain tumor) cells grown in a mouse brain are expressed in “GBM with YAP Overexpression,” created by medical student Theodore Hannah.

A peripheral neuron cultured in vitro after sciatic nerve injury inspired “DRG sensory neuron,” created by graduate student Yiqun Wang.

“Big Fat Juicy Brain Tumor” was originally a screen capture from a 3-D virtual simulation of Jeannie Gaffigan's choroid plexus papilloma. The rendering helped Jeannie, co-writer of The Jim Gaffigan Show, better understand her diagnosis and neurosurgery. The image was then used in combination with navigation technology in the operating room. Later, the colors were altered by the surgical team, led by Joshua B. Bederson.

ADVISORY BOARD

JOSEPH T. COYLE, M.D.

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

MARTHA J. FARAH, Ph.D.

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

PIERRE MAGISTRETTI, M.D., Ph.D.

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

HELEN S. MAYBERG, M.D.

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

ADVISORY BOARD

RICHARD M. RESTAK, M.D.

Richard Restak is clinical professor of neurology at George Washington Hospital University School of Medicine and Health Sciences, a member of the clinical faculty at St. Elizabeth’s Hospital in Washington, DC, and also maintains a private practice in neurology and neuropsychiatry. A graduate of Georgetown University School of Medicine, Restak has written over 24 books on the human brain and has penned articles for the Washington Post, The New York Times, the Los Angeles Times, and USA Today; and presented commentaries for both Morning Edition and All Things Considered on National Public Radio. He is a past recipient of the Claude Bernard Science Journalism Award, given by the National Society for Medical Research.

HARALD SONTHEIMER, Ph.D.

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

STEPHEN WAXMAN, M.D., Ph.D.

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

CHARLES F. ZORUMSKI, M.D.

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

CAROLYN ASBURY, Ph.D.

In-House advisor

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

CEREBRUM STAFF

Bill Glovin Editor-in-Chief

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

Seimi Rurup Assistant Editor

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

Brandon Barrera Editorial Assistant

Barrera is a New York City journalist, born and raised in Queens and living in Manhattan. A public affairs assistant at the Dana Foundation, he is the host of the Dana Foundation’s Communicating Brain Science podcast and writes about books for the magazine. Before coming to Dana, he helped produce content for Bronx Net, a public access television channel. When not enthralled by all things sci-fi, Barrera is fond of cycling, film, and arguing the finer points of tabletop gaming.

Bruce Hanson Art Director

Hanson is responsible for the design and production of Cerebrum. A graduate of Rutgers University’s journalism program, he has worked in a variety of capacities in publishing and media for more than 30 years. In 1991, he founded EGADS, a studio which specializes in graphic design for education, arts and culture, publishing, and technology. When away from his desk, he'll most likely be playing guitar in a live music venue or plotting with his wife about how to book cheap flights to distant destinations.