Cerebrum Winter 2022

The winter issue of Cerebrum magazine takes a deeper look at health disparities in telemedicine, the accidental discovery of the brain's default network, substance abuse brought on by the pandemic, five finalists of the first Int'l Brain Bee and where they are now, and winning photographs from a grant that increases understanding of Alzheimer's and dementia.


Covid + Addiction

Cheryl St. Onge’s mom, Carole, cared for horses while living with vascular dementia. For more images and the full story, turn to page 20.



FEATURES 14 A Perfect Storm

Our authors, who direct the Addiction Institute for the Mount Sinai Health System, address the substance-abuse avalanche brought on by the Covid-19 pandemic. By Yasmin Hurd, Ph.D., and Timothy Brennan, M.D. 20 In Her Own Words Her photographs won the annual Bob and Diane Fund award—a grant that increases the understanding of Alzheimer’s and dementia. By Cheryle St. Onge, M.F.A. 28 Imaging’s Groundbreaking Discovery: 30 Years Later Randy L. Buckner, who was ranked among the top ten most influential brain scientists by Science magazine in 2016, answers questions about his role in the discovery of a brain network that is triggered by thinking when the brain is at rest or imagining possibilities. By Bill Glovin 34 The Great Telemedicine Experiment Covid precautions have led to a massive increase in treatment from screens and phones. Is it worsening health disparities—and changing medicine permanently? By Brenda Patoine 40 Brain Bee Alumni: Where Are They Now? Since the first Brain Bee in 1998, the competition has inspired many of its top finishers to pursue careers in neuroscience and related fields. By Kayt Sukel


Advances • Notable brain science findings

8 Briefly Noted • By the Numbers, Brain in the News 9 Bookshelf • A few brain science books that have recently caught our eye 10 Clinical Corner • Unlocking the Mystery of Brain Injury, By Michael L. Lipton, M.D., Ph.D. 12 Neuroethics • The Fast-Moving Neuroprosthetics Frontier, By Philip M. Boffey

4 From the Editor | 5 Contributors | 48 Advisory Board | 50 Cerebrum Staff





Thank You, Carolyn

BY BILL GLOVIN Editor-in-Chief O ur content looked like it might finally be gradually drifting away from pandemic-related articles through the fall when, suddenly, Covid-19 came roaring back with the Omicron variant. Many of us have been infected or live in fear—who doesn’t know someone who has died or come down with one variant or another? And then there’s the endless controversies surrounding mandates, protocols, booster shots, virtual vs. in-person instruction, traveling—you name it. And while Covid has certainly had a huge impact on brain research, its implications are even more impactful in the area of neuro-related disorders and mental health treatment. That’s mainly why we decided to feature two related topics in this issue. Yasmin Hurd and Timothy O’Brien—both on the frontlines of addiction research and treatment at Mount Sinai’s Addiction Institute— address the reasons for an alarming rise in alcohol and drug abuse in our cover story, “A Perfect Storm.” Their article tells us how the brain reacts to stress and increased isolation, and the ways public policy and addiction treatment has shifted. And you’ll be glad to read that it’s not all “doom and gloom.” The rise in telemedicine, and some of the disparities that have come along with it, are the focus of freelance writer Brenda Patoine’s “The Great Telemedicine Experiment.” Telehealth comprised a third of all visits to behavioral health specialists in 2020, a massive increase over 2019. And new datasets not yet available will tell us it has continued to rise in 2021. Turn to page 34 to find out what it all means. There’s also a lot of non-pandemic content that we hope is of interest. Randy L. Buckner, professor of psychology and neuroscience and principal investigator of the Cognitive Neuroscience Laboratory at Harvard University, tells us about the accidental discovery of the default network and what we know about it 30 years later. Freelance writer Kayt Sukel looks back at the impact that the International Brain Bee has had on the lives of five finalists. Finally, photographer Cheryl St. Onge—winner of this year’s Bob and Diane Fund grant—writes about the images she took of her mom and the impact Alzheimer’s disease had on their relationship. Lastly, with this issue, we bid a fond retirement to Carolyn Asbury, our in-house scientific adviser and a leading voice on the Cerebrum advisory board since I first joined the Foundation in 2011. Her wisdom, guidance, considerable patience, and sense of humor always kept complex, scientific principles clear and accurate, and on track. We wish her the


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

Carl Sherman Copy Editor

Carolyn Asbury, Ph.D. Scientific Consultant

Cerebrum is published by the Charles A. Dana Foundation, Incorpo- rated. DANA is a federally registered trademark owned by the Foundation. © 2022 by The Charles A. Dana Foundation, Incorporated. All rights reserved. No part of this publica- tion may be reproduced, stored in a retrieval system, or transmitted in any form by any means, electronic, mechanical, photocopying, record- ing, or otherwise, without the prior written permission of the publisher, except in the case of brief quotations embodied in articles. Letters to the Editor Cerebrum Magazine 10 Rockefeller Plaza, 16 Floor New York, NY 10020 or cerebrum@dana.org Letters may be edited for length and clarity. We regret that we cannot answer each one.

very best as she begins this next chapter of her life. Happy new year to all, and stay safe out there! l



Covid and Addiction: A Perfect Storm > Page 14

YASMIN HURD , Ph.D., is a professor of psychiatry, neuroscience, and pharmacological sciences at the Icahn School of Medicine at Mount Sinai in New York City; director of the Addiction Institute at the Mount Sinai Behavioral Health System; Ward-Coleman Chair of Translational Neuroscience at Mount Sinai; and a member of the Dana Alliance for Brain Initiatives. She has conducted pioneering research on the neurobiology of opioid abuse, the neurodevelopmental (and cross- generational) effects of cannabis, and potential treatments for opioid addiction. A member of the National Academy of Medicine, Hurd and her research have been featured on NPR, ABC, and CNN, and in the New York Times , Time , and Discover . TIMOTHY K. BRENNAN , M.D., is the chief of clinical services for the Addiction Institute of Mount Sinai in New York City and oversees addiction services across all campuses of the Mount Sinai Health System. He is also the director of the Fellowship in Addiction Medicine Program at the Icahn School of Medicine. Brennan completed his Fellowship in Addiction Medicine at The Addiction Institute, a Fellowship in Medical Ethics at Harvard Medical School, a residency in pediatrics at New York Presbyterian Hospital/Weill Cornell Medical College, and internship in Internal Medicine at Georgetown University Hospital. CHERYLE ST. ONGE ’s work has been featured in the New Yorker , the New York Times , Time magazine, Photograph Magazine , and been exhibited at London’s National Portrait Gallery, the Guggenheim, Princeton University, etc. The mother of three children, she divides her time between Durham, N.H. and coastal Maine. Her featured work, "Calling the Birds Home," was this year’s winner of the Bob and Diane Fund, an annual photographic award dedicated to photography that increases the RANDY L. BUCKNER, Ph.D., is Sosland Family Professor of Psychology and Neuroscience and principal investigator of the Cognitive Neuroscience Laboratory at Harvard University and member of the Center for Brain Science, where he is affiliated with the Center for Biomedical Imaging at the Massachusetts General Hospital and Harvard Medical School. Buckner earned his Ph.D. from Washington University in 1995, trained as a postdoctoral fellow at Massachusetts General Hospital, and returned to Washington University in 1997 as a faculty member. He moved to Harvard as a full professor in 2005 and, from 2005-2012, was an Investigator for the Howard Hughes Medical Institute. Buckner’s research applies neuroimaging techniques to explore brain areas involved in human memory. understanding of Alzheimer’s and dementia. BRENDA PATOINE is a freelance science writer, reporter, and blogger who has been covering neuroscience research for more than 30 years. Her specialty is translating complex scientific findings into writings for the general public that address the question of “what does this mean to me?” She has interviewed hundreds of leading neuroscientists over three decades, including six Nobel Laureates. She founded ScienceWRITE Medical Communications in 1989 and holds a degree in journalism from St. Michael’s College. Other areas of interest are holistic wellness, science and spirituality, and bhakti yoga. Brenda lives in Burlington, V.T., with her cat Shakti. KAYT SUKEL ‘s work has appeared in the Atlantic Monthly , the New Scientist , USA Today , the Washington Post , Parenting , National Geographic Traveler , and the AARP Bulletin . She is a partner at the award-winning family travel website Travel Savvy Mom, and is also a frequent contributor to the Dana Foundation’s science publications. She has written about out-of-body experiences, fMRI orgasms, computer models of schizophrenia, the stigma of single motherhood, and why one should travel to exotic lands with young children. She is the author of Dirty Minds : How Our Brains Influence Love, Sex and Relationships and The Art of Risk : The New Science of Courage, Caution & Chance .

In Her Own Words > Page 20

Imaging’s Groundbreaking Discovery: 30 Years Later > Page 28

The Great Telemedicine Experiment > Page 34

Brain Bee Alumni: Where Are They Now? > Page 40



ADVANCES Notable brain-science findings


I n 2020, researchers found great success in treating nearly two dozen people who had INTRACTABLE DEPRESSION by using a five-day, intensive course of transcranial magnetic stimulation (TMS) called Stanford Neuromodulation Therapy (SNT). That study was “open label,” which means doctors and patients knew they were getting the experimental treatment. Now the researchers have repeated the procedure as a randomized, controlled test, with some patients receiving the treatment and some receiving something that looked just like it (holding a figure-8 shaped handset close to their heads) but did not send the signal; neither they nor their doctors knew who was getting what. Patients received ten treatment sessions per day for five days. Many patients reported their mood lifting within days, and within a month of treatment, 79 percent of the patients no longer scored as clinically depressed. Current TMS methods use lower magnetic intensity, are given once daily, and go on for six weeks; they show far less success than the new method but also do not require that patients stay in a hospital or treatment center for the course of their treatment. If this method continues to shine in clinical studies, it will be especially useful for emergency care. l

People with serious mental illness represent a quarter of all police shootings and account for more than two million jail bookings a year. Margaret E. Balfour, M.D., Ph.D., and colleagues recently published a paper that addresses the composition of response teams, the need for collaboration across systems, and offers an alternative to the current 911 number. The alternative, 988, would offer a new number to call in the event of mental health emergencies. The approach would dispatch a team of using some combination of nurses, social workers, EMTs, and behavioral health technicians, rather than armed police officers in a patrol car. l

Researchers have found evidence that there may be a “critical window” for recovering motor skills after a person has had a STROKE . In a randomized, controlled study of 72 older people (83

percent African American, 50 percent women), those who added 20 hours a week of specific motor-skills training to the usual therapies at 2-3 months after their stroke showed a significant increase in motor function compared with controls (who were doing just the usual therapies). Those who did the additional training in the first month after stroke and then stopped also showed significant improvement over controls, but not as much as the 2-3-month group. Those who started the additional training at 6 months or more post-stroke looked like the control group. This matches what other researchers have learned from animal studies and suggests that the increased neural plasticity seen in post-injury brains behaves in some ways like the plasticity in childhood, which also has sensitive periods. l

Nolan Williams demonstrating their SNT treatment on an unnamed patient.


People who go through MENOPAUSE experience a range of symptoms, including a decline in the volume of the brain’s gray matter in regions that are also affected by Alzheimer’s disease. A new observational study at Weill Cornell suggests that the more estrogen a person has been exposed to during their life, the more likely it is these volumes will return to pre-menopause levels, which could mean less danger of developing dementias. Some ways to increase estrogen exposure are environmental—bearing more children, taking oral contraceptives, or being on hormone replacement therapy—and some are genetic—having a longer timespan between menarche and menopause and not having an APOE-4 gene variant. Past studies have suggested that hormone replacement therapy was not helpful post- menopause; more research is needed. l and whether there were differences between musicians and non-musicians, researchers scanned the brains of six musicians and eight non-musicians as they listened to music they’d chosen themselves, and to music they’d heard for the first time, one hour before the scanning. In all the listeners, the “long-known” music fired up areas involved in autobiographical memory, which can fade with dementia, but also subcortical, emotion-regulating regions, which do not so quickly fade. They did find subtle but distinct structural differences in response between the musicians and non-musicians but need a larger sample A dose of familiar, beloved MUSIC can help people with mild cognitive impairment and early dementia score better on tests of cognition. To see how, to verify those differences. “Music is an access key to your memory, your prefrontal cortex,” says lead researcher Michael Thaut at University of Toronto. “Keep listening to the music that you’ve loved all your life.” l Scientists from Purdue University and Jinan University have developed a way to use GENE EDITING to transform glia—cells in the brain that usually support neurons— into neurons themselves. In studies using mice, the researchers damaged neurons in the visual system and then used their editing technique to convert some nearby glia into functional neurons. These new neurons remade

Most BRAIN-COMPUTER INTERFACES (BCIs) depend on a few sensors implanted on the cortex, reading—and sometimes transmitting— signals among a few hundred nearby neurons. Researchers at Brown University have developed a network using independent, wireless microscopic neural sensors, which they call “ neurograins ,” that can be distributed all around the cortex, recording and transmitting information from far more neurons. They have successfully tested it with a rat, placing 48 grains on the animal’s cerebral cortex, the maximum they thought a rat brain could handle. Theoretically, they say, the system could support up to 770 grains in a human. Now, they are trying to make the grains even smaller and trying to find ways to avoid problems with the body rejecting foreign material and the surgical scar tissue that causes implants to fail after a few years. l

connections in a way that seems to mimic regular circuit development, and three weeks later, the mice started to see again. Should this technique prove stable, another possible use would be restoring connections in motor system areas. l





B Y T H E N U M B E R S Percentage of people developing eye or ear symptoms after Covid. 1 % studies are the result of

BRAIN IN THE NEWS Links to brain-related articles we recommend > Washington Post: Is there really such a thing as ‘mommy brain’? > Molly Wright: How every kid can thrive by five/TED > The New Yorker: The Science of Mind Reading > The New York Times: Cognitive Rehab: One Patient’s Painstaking Path Through Long Covid Therapy > NBC News: Surgeon general issues rare public health advisory over youth mental health crisis > The New York Times: Nation’s First Supervised Drug Intervention Centers Open in New York > Scientific American Mind: How Brains Seamlessly Switch between Languages > MindSite News: Multilingual learning good for the brain > The New York Times: Why 1,320 Therapists Are Worried About Mental Health in America Right Now > Fast Company: Neuroscientists are using virtual reality to unlock a whole new world of brain research > Washington Post: Is artificial intelligence about to transform the mammogram?


five years of work by a huge consortium of researchers to identify the myriad of different cell types in the primary motor cortex.

One Half of all mental health disorders show first signs before a person turns 14 years old, and three quarters of mental health disorders begin before age 24.

54 clinical sites were used in a Phase 3 clinical trial to

test lumateperone, a promising new

antipsychotic drug to treat bipolar disorder. THREE HUNDRED FIFTEEN

brains of National Football League players have been diagnosed, posthumously, with chronic traumatic encephalopathy, or C.T.E., a progressive disease in which symptoms can arise long after hits to the head have ceased.

“Neuroethicists need to provide a stronger

voice about what is neuroethics. Most of the populace in many countries are not very clear


3 0 , 0 0 0 post-9/11 vets and service members have died by suicide, 4 times the

in America will have an eating disorder at

about neuroethics—are not even aware that something like this exists.” — Nandini Chatterjee Singh , a cognitive

some point in their lives.

number that have died in combat.

neuroscientist and senior project officer at UNESCO at the Gandhi Institute of Education for Peace and Sustainable Development in New Delhi, India



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

Feeling & Knowing: Making Minds Conscious by Antonio Damasio, M.D., Ph.D. (Pantheon) Antonio Damasio, David Dornsife

From Survive to Thrive: Living Your


Best Life with Mental Illness by Margaret S. Chisolm, M.D., with John Hanc (Johns

Projections: A Story of Human Emotions by Karl Deisseroth, M.D., Ph.D. (Random House) In a chapter from his memoir Projections , psychiatrist and

Hopkins University Press) Distilling years of experience and evidence-based research into this practical guidebook, professor of psychiatry and behavioral sciences Margaret S. Chisolm believes that a healthy and fulfilling life is achievable for everyone. It is in this spirit that From Survive to Thrive markets itself as a resource to anyone finding themselves (or their loved ones) juggling personal problems and anxieties, those currently on antidepressants, and, of course, those who have been diagnosed with psychiatric illness. Chisolm admits the guide is not a panacea— each one of us has variables such that the road to well-being will be singular to our conditions. That is why the guidebook emphasizes the perspectives/pathway approach— four perspectives through which mental distress should be professionally assessed and four pathways of action (family, work, education, community) to well- being—as the analytical and practical toolset that will ultimately enable one to flourish. Will it take time? Yes, says Chisolm. The model she outlines is one shown to have borne positive results for not only many of her patients, but also herself. She hopes it will enable readers to live their best lives, too.

Professor of Neuroscience, Psychology, and Philosophy at the University of Southern California, returns with another addition to his formidable catalog of works exploring consciousness. Feelings, Damasio says, are integral to the subjective experience, and in Feeling & Knowing , he explores the converging biological processes—in both brain and body—that produce consciousness. Encouraged by his editor to create a concise and focused volume, Damasio distills his ideas and theories on what constitutes the “mental experience” in a compact 180-plus pages, using recent findings across biology, psychology, philosophy, and physics as supporting evidence. His efforts make for an approachable text spanning the difference between feelings and emotion, the distinction between sensing and being conscious, the pivotal role homeostasis plays in creating our subjective experience, and why investigations of consciousness should probe beyond the brain and include the body. For Damasio, consciousness is a difficult, awe- inspiring problem, but it’s a problem with a solution, nonetheless. l

researcher Karl Deisseroth tells the story of a former patient, Winnie. Trained as both a lawyer and engineer, Winnie was admitted into emergency psychiatric care one day after accosting her law firm’s senior partner in his office and accusing him of conspiring against her. Under Deisseroth’s care, Winnie would develop a keen interest in the biological utility of schizophrenia, the brain disorder altering her thinking and sense of reality. Projections weaves together a trio of threads— Deisseroth’s journey as a psychiatrist, his patients’ stories, and the leaps in neuroscientific knowledge made possible by technological breakthroughs (e.g., optogenetics)— to explore what mental illness can teach us about human emotions. The recipe, as it turns out, is compelling. Within the case studies of patients living with eating disorders, autism, dementia, and other psychiatric diseases, Deisseroth illuminates the neural mechanisms of behavior and emotions while lacing the threads into a vibrant, tapestry, buzzing with humanity.




Unlocking the Mystery of Brain Injury

concussion during the crash, would “recover over time,” and should follow up with his personal physician “if needed.” Charles checked in with his doctor the next week, who ordered a magnetic resonance imaging (MRI) scan, “to confirm that there was no injury to the brain that would have been missed by the CT scan.” Although neither the MRI nor the doctor’s examination revealed any abnormality, Charles was not at all back to himself. His symptoms had worsened following the crash and now interfered greatly with his day- to-day functioning. Charles was on a leave of absence from graduate school when I confirmed signs of his traumatic brain injury (TBI) by employing advanced MRI techniques that detected pathology to which prior testing was essentially blind. Charles would not complete his graduate degree. He ultimately came to understand his post-TBI “new normal” and, with much support and guidance, forged a new path that leveraged his strengths and minimized disruptions caused by his new limitations. “TBI” conjures images of bloody and bruised brain tissue. This is the significant injury the ED physician ruled out in Charles. Concussion, on the other hand, is defined by the absence of visible signs of

concussion each year. Also termed mild TBI (mTBI), concussion is diagnosed based on symptoms of altered brain function following an impact or a jarring force to the head, in the absence of visible injury on CT. The good news is that the vast majority of concussions produce only transient symptoms, followed by full recovery of function. But, in a miserable minority of concussion patients, perhaps 15-25 percent, symptoms persist for longer periods and may never fully remit. “Mild” in the case of mTBI/concussion refers to the relative severity and duration of acute symptoms, such as unconsciousness and confusion, and absence of CT signs of brain injury. mTBI does not preclude lasting difficulties due to the injury. However, persistent disabling brain dysfunction after concussion, as in Charles’s case, does present a major conundrum for patients and caregivers. They know something is wrong, but testing repeatedly shows their brains to appear normal. As a medical student, I learned

BY MICHAEL L. LIPTON, M.D., Ph . D . C harles was age 23 when he walked into my clinic looking for answers. It was a year after a terrible car accident on an icy winter night during his final year in graduate school. His vehicle had slid off the road, hit a tree, and left him trapped and alone. Charles was awake but confused when firefighters extracted him from the vehicle, and he was still somewhat disoriented in the small rural hospital emergency department (ED). Immediately following the accident, a computerized tomography (CT) scan of his head “ruled out significant injury.” Charles, who was observed until morning, complained of a headache, fatigue, and blurry vision but was alert and oriented. The ED physician told Charles he had sustained a

concussion was a functional disturbance and did not arise from a physical brain injury. Moreover, concussion always

brain injury on CT. Millions of Americans experience



Trauma incites a cellular and molecular cascade, which, proceeding unchecked, will lead to permanent injury to the axons that form the network infrastructure of the brain.

implicates factors such as genes and biological sex in the divergence of outcomes among individuals who experience similar head injuries. A decade ago, at a medical conference, a Veteran’s Affairs physician stood up after I had presented research findings on the detection of brain injury and, with passion, recounted the desperate “need to know” of countless combat veterans who repeatedly heard that their brain appeared normal on MRI scans. Yet, they and their families knew they had been changed by their injury. My laboratory has focused for nearly two decades on the disconnect between symptomatic brain dysfunction and the failure of diagnostic testing to detect the underlying brain injury. Our work has advanced MRI methods that detect microscopic injury in the living human brain and provide insight into mechanisms of persistent brain dysfunction. We are hopeful these insights will seed novel approaches

resolved completely and in short order. We now understand that concussion symptoms do arise from a physical injury, though it occurs at the level of brain cells to which tests such as CT and MRI are essentially blind due to their limited resolution. We now understand to brain injury as a process, not an event—like a fracture, which occurs at an instant—in time. Trauma incites a cellular and molecular cascade, which, proceeding unchecked, will lead to permanent injury to the axons that form the network infrastructure of the brain. On the other hand, injury might be minimized, and function thereby normalized, with early termination of the injury cascade. The difference between two individuals who experience a similar head injury but sustain divergent outcomes—transient concussion in one and enduring, life-altering brain injury in the other—seems to lie in the persistence of the injury cascade. Emerging evidence

to directly treat the evolving injury cascade and improve outcomes for patients like Charles. l MICHAEL L. LIPTON, M.D., Ph.D. , is a neuroradiologist and neuroscientist at Albert Einstein College of Medicine and Montefiore Medical Center in New York. His research program focuses on detecting and characterizing the effects of mild brain injury and the cumulative effects of repetitive subconcussive head injury in sports.




The Fast-Moving Neuroprosthetics Frontier BY PHILIP M. BOFFEY T he science and technology embodied in neuroprosthetics are progressing far faster than the law can keep up. It’s not even clear whether existing law can, with suitable adjustments, handle the problems or whether we need a whole new legal approach, possibly including a bill of rights for neuroprosthetics. That was the overriding message I took away from Jennifer Chandler, a professor of law at the University of Ottawa in Canada, who delivered the David Kopf Neuroethics lecture on November 9, at the annual meeting of the Society for Neuroscience— conducted virtually this year in deference to the ongoing Covid pandemic. Her topic: How the law is evolving to deal with neuroprosthetics, a fast- moving frontier in the long-standing practice to use artificial devices to replace or enhance body parts and functions. The idea that science and technology are progressing faster than existing law is a recurring theme in many issues I have written about, including the ethics of conducting research on brain organoids in a dish and of linking brain signals to computers, the so-called brain- computer interface. Professor Chandler elaborated on her views in a lengthy book chapter that she made available

is one deranged malefactor bent on evil deeds. Or such harm might conceivably be caused by a technical malfunction or glitch or inadvertent human error. Another ethical issue emerged when the initial spread of Covid-19 overwhelmed many hospitals and forced some to consider allocating the use of scarce ventilators for the sickest patients or those most likely to recover. In those cases, the ventilators were considered objects that could be transferred from one patient to another. But that understandably raised alarm among chronically ill patients who relied on ventilators to breathe. As one patient explained it, “My vent is part of my body—I cannot be without it for more than an hour at the most due to my neuromuscular disability. For clinicians to take my vent away from me would be an assault on my personhood and lead to my death.” Even before the pandemic, one bioethicist argued that a ventilator used for chronic illness was part and parcel of the person, not subject to being commandeered in a crisis. Neuroprostheses, like ventilators, can also be critical for the physical or psychological survival of a patient. A spinal cord stimulator to ease chronic pain may be lifesaving by preventing some patients from death by suicide. And, given that memories are crucial to knowing who we are, prosthetics being explored to improve memory formation in Alzheimer’s patients would seem literally indispensable for the survival of the person. There is no doubt that tinkering with the brain can be therapeutically valuable. Deep brain stimulation with implanted electrodes is being used to alleviate conditions such as Parkinson’s disease and to treat

and in emails exchanged with this columnist. Before definitively answering questions about a host of evolving legal issues, she wanted to first identify the central human interests at stake with the adoption of complex neuroprosthetics and the potential threats to those interests. Although humans have a long history with prostheses of many primarily because they stimulate the brain directly, thereby influencing its mental contents, and can be read outside the brain, allowing access to a person’s thoughts. I had long considered this a privacy issue, which it clearly is. But types, neuroprostheses raise perplexing new issues. This is Professor Chandler warned that such thoughts could also provide a potentially dangerous pathway to harm an individual. For example, she wrote, Medtronic’s new deep brain stimulation device, known as Percept, simultaneously captures brain signals (using an implanted lead) that can be recorded, while delivering therapeutic stimulation— both inside and outside the clinic. Since many devices and prostheses are networked, they not only transmit information about the person but present a portal through which harm could be done. In August 2017, for example, the Food and Drug Administration warned patients that a particular implanted pacemaker had a security vulnerability that might allow an intruder to harm them through hacking. Worse yet, with wide scale networking, the intruder could dole out harm en masse. It is not far-fetched to think that a neuroprosthetic device could be similarly hacked and used to harm an individual, or many people, at once. All it would take



vigorous things to escape the fire. Police obtained a search warrant for the electronic data stored on his pacemaker and a cardiologist found it “highly improbable” that he could have done all the things he claimed. Sooner or later the same issue will arise with a neuroprosthetic device. Stay tuned to see whether the law and bioethics can find a way to resolve such perplexing issues as the field of neuroscience races ahead. l

depression, OCD, eating disorders, aggression, and addiction. A July 15 article in the New England Journal of Medicine describes how doctors were able to help a patient who had lost his ability to articulate words and sentences after a brain-stem stroke. They implanted a multi-electrode array over the part of the cortex that controls speech, recorded cortical activity while the participant attempted to say words—and eventually sentences—and were able to decode what he was trying to say without him actually saying it. That raises the question of whether such imagined speech or thoughts should be made available to outsiders who might use it against a person. The possibility was raised in a case in Ohio in which a man was found guilty of arson and insurance fraud after a fire in his home. He claimed to have done all sorts of

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.



Our authors, who direct the Addiction Institute for the Mount Sinai Health System in NewYork City, address the substance-abuse avalanche brought on by the Covid-19 pandemic. ByYasmin L. Hurd, Ph.D., and Timothy Brennan, M.D. Illustration by Jarred Briggs

A S AMERICAN ADDICTION they were likely feeling pretty optimistic. Overdose death rates involving heroin, while still high, had dropped for the third year in a row. Indeed, it seemed like the opioid crisis had not only plateaued but was slowly starting to improve. Access to medication- assisted treatment had increased around the country; and for the first time in history, a variety of health tech startups were looking to leverage their expertise in innovative ways to bring treatment to economically disadvantaged areas. RESEARCHERS AND TREATMENT PROFESSIONALS WENT TO SLEEP ON NEWYEAR’S EVE 2019,




oft-repeated mantra of “90 meetings in 90 days” exists for good, practical reasons: Active addiction takes up an extraordinary amount of time in people’s lives; the relentless pursuit of acquiring, using, and recovering from the effects of a substance can crowd out almost all of their other responsibilities. People in early recovery suddenly have a lot of time on their hands , and self-help and group therapy settings provide a safe place to spend it. But as America entered the Covid lockdown in March of 2020, formal and informal addiction treatment settings were quickly forced to close down. A warm and welcoming AA meeting full of tears, laughter, and hugs, which previously might have felt like one of the safest places in the world, suddenly became one of the most unsafe. For people who had already established a network of recovery supports, the migration to online-only meetings was an annoyance, but not insurmountable. But for those who had not yet established themselves in recovery, an important lifeline now required a high-speed internet connection and involved the awkwardness of “meeting” people online when you have never met them in person. Storm Clouds Form Not surprisingly, the massive rise in unemployment, disruptions in work/life balance, and general stress and anxiety induced by the pandemic led to increased reliance on both healthy and unhealthy coping mechanisms. Just as sales of exercise bikes and yoga mats soared, so too did alcohol consumption . Prior to the pandemic, it was both socially unacceptable and unprofessional to consume alcohol while working. But as people became accustomed to the “work from home” lifestyle, the social boundaries of office culture started to melt away. Who would know if a bottle of wine that would have been uncorked at 6 p.m., was now poured at 4 p.m.? Not only did alcohol sales increase dramatically during the pandemic, but so too did illicit drug consumption: Americans reported using substances like alcohol and cannabis more than ever to cope with anxiety and stress. There were also reports that the illicit drug supply chain became disrupted, which may have increased drug adulteration. What had previously been a steady flow of pure heroin became an unsteady supply of heroin adulterated with highly potent synthetic opioids like fentanyl and its analogues, which are more than 50 times more potent than heroin, and 100 times more potent than morphine.

None of us knew that we would soon be facing an unprecedented storm. Indeed, it would be a perfect storm, particularly for vulnerable groups such as those suffering from substance-use disorders. On February 11, 2020, Covid-19 became the official name given by the World Health Organization for the highly infectious disease caused by infection with the SARS-CoV-2 coronavirus— and of a pandemic that would transform the world, creating a new norm of social distancing, isolation, and loneliness that exacerbated substance-use disorders. The bedrock of modern addiction treatment is the fellowship gained by participating in group therapy, either in formal settings such as addiction treatment programs, or informal settings such as Alcoholics Anonymous (AA). When people first seek help for their addiction, they often feel impossibly alone and adrift. They can’t conceive that anyone else in all of human history has ever felt the way that they feel. They are lonely, ashamed, and terrified. But when they start meeting other people with the same condition, something magical happens; they realize that not only are they not alone but there is a way through their suffering, a light at the end of the tunnel. The group setting, which at the outset may have felt absolutely terrifying, will frequently become their refuge—a place where they can be fully present, fully accountable, and fully accepting of their disease. The


and those already suffering from it are particularly sensitive to stress —a reflection of the intricate links between the brain’s stress and reward systems. Addiction neurobiology is an extremely complex system that involves numerous neurochemicals and interconnected circuits, all of which are influenced by both internal and external stressors. Each phase of addiction—intoxication, habitual compulsive drug-seeking, withdrawal, abstinence—can result in changes to our neurobiology. One of the most important chemicals in our brain’s “reward pathway” is the neurotransmitter dopamine. Most drugs of abuse will directly or indirectly increase dopamine in this pathway. Stress, especially acute or intense stress, boosts dopamine in these same brain areas, via the release of such compounds as corticotrophin-releasing hormone and cortisol. Consequently, stress can heighten reward sensitivity, potentiating the reinforcing effects of drugs. Conversely, drug use can sensitize the brain to stress. In its attempt to protect the brain against the effects of acute stress, the body recruits neurobiological processes that feedback to increase neurochemicals that reduce dopamine levels and normalize other neurobiological systems (e.g., production of stress hormones). With repeated drug use or chronic stress, however, the biological picture changes: the brain is highly plastic and attempts to return neurobiological systems to “normal,” can lead to adverse pathological states. For example, chronic use of drugs can result in reduced baseline dopamine release, decreasing the drug’s rewarding effects and increasing negative emotions. This phenomenon, “tolerance,” can have two effects: the user requires more and more of the drug to achieve the high experienced initially; and now he or she also needs the drug to provide relief of the negative mood state. The result: transition to uncontrolled compulsive drug use. By reducing dopamine levels, chronic stress also increases neurochemicals that promote stress, such as the neuropeptide called dynorphin, in brain areas such as the amygdala, which is involved in emotional regulation and drug-seeking behavior. Negative emotional states induced by these changes also drive compulsive drug-seeking behavior.

Now, fentanyl contamination was being regularly detected in various drugs, including counterfeit pain pills and sedatives, such psychostimulants as methamphetamine and cocaine, and even cannabis. As overdose data started to trickle in during 2020, it soon became clear that all of the gains that had been made from 2017 to 2019 had been lost. Shockingly, overdose death rates in the US skyrocketed higher than they have ever been at any time during the opioid crisis—with synthetic opioids accounting for more than 60 percent. This historic rise in overdose deaths was, of course, multifactorial—besides the turn to addictive substances to cope with Covid-related stress, the disruption in access to drug treatment, and adulteration with toxic synthetic opioids, more people were using drugs in isolation. This meant limited opportunity for others to provide lifesaving help by administering naloxone (an opioid antagonist also known as Narcan) when overdose occurred. As more data became available regarding Covid-19 risks, disparity, and outcomes, it was evident that substance- use disorders were a significant underlying medical condition associated with high risk for severe Covid-19 illness. Not only were individuals with substance use disorders (SUD) at increased risk of Covid-19, but they also experienced significantly worse outcomes than those without SUD. Knowing that they were at increased risk of bad outcomes from Covid-19 further heightened the already elevated anxiety of the addicted, causing more reactive substance use and more death. Overall, a perfect storm. Stress: A Neurobiological Force Though Covid-related stressors increased psycho- pathological states of fear, depression, and anxiety in most people, these were more elevated in individuals with SUD. Numerous factors associated with Covid—from social distancing and lockdown isolation to economic downturn—converge in the state of mental or emotional strain or pressure we call “stress.” Biologically , stress refers to the body’s response to change. Clearly, the pandemic involved profound changes and demands in all aspects of life. This development was not unexpected: It is well documented that individuals at risk for addiction



A vicious cycle is likely to occur. In trying to cope with stress, people begin to use drugs, thinking this will alleviate their negative mood. But during extended stressful periods, occasional self-medication readily escalates to regular use. This boosts output of stress- related hormones and neurotransmitters, contributing to heightened stress responsivity and negative emotional states, which in turn increase the motivation for continued drug use. Even individuals maintaining drug abstinence prior to Covid were at great risk for relapse during the pandemic, since withdrawal is dominated by negative affect and activation of the stress and anxiety systems that contribute to drug-craving. The Vulnerable Brain A particularly challenging dynamic of the pandemic has been the lack of in-person socialization for children and adolescents. The human brain has evolved to maximize social interaction and connectivity, which are dependent on the precise orchestration of complex neurodevelopmental processes. Forced isolation, lack of peer support, and minimal teacher oversight created a perfect storm for heightened stress and risky decision- making. Although restrictions have eased considerably with new variants, the support of peers and schools that is a central part of children’s daily lives, could disappear again. Friendships, cliques, sports, and extra-curricular activities may again be fundamentally altered. An entire social structure might once more be disrupted. For many children, school is the only predictably safe and nurturing place in their lives. In the 2020 academic year, they were uprooted from this stabilizing force and required to attend school virtually. We know from developmental neurobiology that the adolescent brain is uniquely vulnerable to addiction due to a genetically programmed increase in risk-taking and anxiety-related behaviors driven by the amygdala, coupled with a relatively immature “executive” cognitive control center in the brain (the prefrontal cortex), which does not reach full maturity until the third decade of life. Differences in the development of executive versus emotional networks in the adolescent brain make adolescents more sensitive to rewarding and stressful stimuli than adults . So, as challenging as Covid lockdown was for most adults, it was more difficult and neurobiologically perilous for most teens. Significant neurodevelopment continues well into adolescence, as is evident in various brain structures. Particularly relevant to stress, social connectivity, and

addiction is the profound functional and structural maturing of the amygdala, prefrontal cortex, and ventral striatum. For instance, activation of the ventral striatum in response to reward (including social reward) is stronger in adolescents than in adults and children, which parallels the adolescent maturation of the dopamine system. Adolescence is also a period of enhanced activity in the hypothalamic-pituitary-adrenal (HPA) axis—the neuroendocrine regulator of stress—and hormone levels following puberty enhance the stress response and increase the motivation and value of reward. Another critical maturation process during adolescence is in amygdala- prefrontal cortex connectivity , a key neural circuit for the generation of negative affect and its regulation. The peak in social drive that occurs during adolescence coincides with this period of prefrontal cortex-amygdala maturation. Adolescence is a sensitive period of enhanced amygdala reactivity when emotional stimuli, stress, and social interactions are extremely important. It should be emphasized that this period is also characterized by a relatively immature prefrontal cortex that is responsible for cognitive function. Indeed, cognitive control via inputs from the prefrontal cortex to the amygdala does not fully mature until early adulthood, leaving the ability of the prefrontal cortex to inhibit amygdala activity significantly low during adolescence. Stress further weakens this moderating process. Altogether, the neural signatures of adolescence parallel heightened reward sensitivity, stress sensitivity, and risk-taking as compared to other age groups. It’s not


What remains to be seen is how long regulatory relief measures will stay in place. Will they become permanent, or will we backslide? As Americans return to the office and its associated etiquette, will alcohol consumption return to pre-pandemic levels, or has a new—and elevated—normal been created? With new and perhaps future variants delaying any hope of an abrupt end to the pandemic, it remains critical that we leverage the insights that have been gained about disparities and vulnerable groups into new preventative and proactive measures. This is particularly true in regard to teenagers. Given the heightened stress reactivity of adolescence, and the possibility of long-lasting neural changes linked to Covid experiences, we must focus attention and support not only to help affected teens today, but to mitigate the development of addiction-linked psychopathologies in the future. Stay tuned. l

surprising then that social environment or high-stress exposure at this time produces heightened vulnerability to anxiety-related disorders, a factor that is linked with a rise in alcohol and drug use associated with increased likelihood of addiction later in life. Out of the Storm While the emergence of new variants and uncertainty prolongs our fragile state, the pandemic has not been all doom and gloom. The Covid storm, like any crisis, has also provided opportunities—including a chance to develop new strategies to help individuals suffering from substance use disorders. Perhaps one of the most unexpected outcomes of the pandemic has been the profound relaxation in regulatory laws that govern addiction treatment, particularly for the use of buprenorphine , a medication for opioid-use disorder. Buprenorphine, like heroin or oxycodone, is an opioid, but it is nowhere near as euphorogenic or intoxicating. Substituting a very safe medication like buprenorphine for a very unsafe drug like heroin dramatically lowers the risk of overdose. Before the pandemic, it was very difficult to enroll someone onto buprenorphine over the phone or internet due to regulatory laws requiring in-person assessment for treatment. During the pandemic, virtual therapy became commonplace. Hard-to-reach areas that required a long drive for personal contact could now be accessed via an internet connection. Another silver lining of the regulatory relief that occurred during the pandemic was the relaxation of laws regarding methadone maintenance treatment. Prior to Covid, many patients enrolled in methadone programs had to come to the clinic six days a week to pick up their dose. During Covid, they were able to stay safe in their homes and visit the clinic on a weekly or bi-weekly basis in order to pick up several doses at one time. While it is still too early to judge the epidemiological impact of these liberalized policies, they have been very well-received by patients. In addition, accessing self-help groups like AA was easier during the pandemic for some people, as connecting through the phone or computer provided a protective layer of anonymity that overcame concerns about attending in person. Networks expanded, and new connections were made as people in New York City could suddenly join groups in Los Angeles or London. There is quite literally an AA meeting happening online every hour of every day —great news for those in recovery.



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