NYUTHE MAGAZINE OF NEW YORk UNIVERSITYPh SCHOOL OF MEDICINEysiciaspring - 2010n volume 61 • No. ConneCTIONS 3 Surprising Insights into Diseases of the Brain

plus Auditory Brainstem Implants Images of Addiction The Peak Experience Help Us Make Dreams Come True

Ev ery aspiring physician dreams of the day someone will Make a Gift Online call him or her “Doctor” for the first time. But getting there Please visit www.nyu.edu/alumni. takes a lot more than hard work and dedication—it takes resources. By contributing to the NYU School of Medicine Alumni Campaign, you help To discuss special ensure that our next generation of physicians will have access to the best giving opportunities, teaching and research, along with a competitive financial assistance package. call Anthony J. Grieco, MD, Associate Dean for Alumni Relations, When you make a gift, you help us guarantee that all of our students will at 212.263.5390. have the means to complete our rigorous education. One day, you may even have the privilege of addressing them yourself as “Doctor.”

Thank you for your generosity. THE MAGAZINE OF NEW YORk UNIVERSITY SCHOOL OF MEDICINE spring 2010 volume 61 no. NYUPhysician 3 New York University Cover Stories Martin Lipton, Esq. connecting to memory Chairman, Board of Trustees Surprising insights into diseases of the brain. John Sexton President memories of fear Robert Berne 10 Exective Vice President Can we erase the bad memories for Health associated with phobias, panic attacks, • and anxiety? Neuroscientist Joseph NYU Langone LeDoux, PhD, thinks it may be possible, Medical Center and his transforming research is Kenneth G. Langone attracting wide attention. Chairman, Board of Trustees 14 memory and the senses Robert I. Grossman, MD New findings by pioneering Dean and Chief Executive Officer researcher Donald Wilson, PhD, are revealing that our olfactory system serves Deborah Loeb Bohren Vice President, as a window into how our brains first Communications and begin to malfunction when diseases such Public Affairs as Alzheimer’s and schizophrenia strike. • NYU Physician 18 connecting to sound Steven B. Abramson, MD For those left profoundly deaf, Anthony J. Grieco, MD (’63) a new type of high-tech implant that Editors, Science bypasses the auditory nerve helps restore and Medicine some hearing. Frank W. Lopez Managing Editor 22 improving mri Marjorie Shaffer 10 Diffusion tensor imaging (DTI) Senior Editor and diffusion kurtosis imaging (DKI), are proving helpful in mapping the brain’s Royce Flippin Contributing Editor “Humans have two major problems microstructures. with memory. Sometimes we can’t Rob Hewitt Art Director remember, and sometimes we can’t Sherry Zucker forget.” Joseph LeDoux, PhD Print Production Coordinator Mel Minter Copy Editor Departments

On the Cover:• 02 F rom the Dean 04 News from Medicine 26 Patient Stories Illustration by •Sensational Research •Storming the Gates Ancient Drug for Terminally Jeffrey Decoster •Pulitzer Prize for Bellevue •Herpes: The Reawakening ILL. Can psilocybin, once known as the Literary Press •Taming Runaway “psychedelic” mushroom, ease extreme 03 A round Campus Inflammation emotional distress at the end of life? Plans Advance for •Sounding an Early Alarm Integrating New Kimmel on Alzheimer’s 28 Alumni Profile Pavilion and Renovated •The Long and New Image of Addiction. Tisch Hospital (Un)Winding Road of DNA Q&A with Dr. Nora Volkow, who has •The Brain’s Balancing Act pioneered the use of brain imaging to 30 F aculty News study effects of drug addiction. photograph: sasha nialla photograph: 31 A lumni News

NYU Physician spring 2010 1 Message from the Dean & CEO

Literary Sensational Efforts Spawn a Research Pulitzer That loud yell you heard in April Less than one year ago, an extraordinary was the sound of Martin Blaser, MD, $100 million gift from the Druckenmiller chairman of the Department of Foundation was announced to establish a Medicine, from his office atB ellevue Hospital. He was expressing his delight state-of-the-art neuroscience institute at NYU at learning that a volume produced Langone Medical Center. Building on our long- by fledglingB ellevue Literary Press, standing expertise in both basic and clinical younger cousin of the Bellevue Literary neuroscience, this gift leaves the Medical Review, had just been awarded the Center well positioned to play a leading role Pulitzer Prize for Fiction. That’s right. The Pulitzer Prize for in a field expected to grow enormously in the Fiction. coming decades. The book is Tinkers, by Paul Harding, So it seems only fitting that we devoted most a meditation of sorts about an elderly of this issue of NYU Physician to research in this manifold, fascinating clock repairman dying of cancer who, field. A range of basic and clinical research is offered in these pages, in hallucinations, reconnects with his deceased father—“a powerful from captivating studies focusing on the neurological underpinnings celebration of life,” according to the of fear and on the loss of smell as a biomarker for early signs of brain Pulitzer citation. It was the literary find disease to the latest innovations in neurosurgery and brain imaging of Erika Goldman, the press’s editorial that are advancing patient care. Our researchers are also illuminating director, The manuscript had been how antidepressants physically prevent the influx of chemicals passed along to Goldman, a veteran editor who has worked at Scribner and into neurons, how experience shapes the architecture of our nerve Simon & Schuster, by a colleague at cells, and how the reemergence of a type of herpes virus can wreak another small press. “It sang out to me,” neurological havoc. Goldman recalls. Although we cannot hope to cover in any one issue the full extent The five-year-old press has its office of the significantL work in neuroscience at our Medical Center, I hope in the Department of Medicine on the sixth floor of OldB ellevue. Its mission is you will agree that these stories reflect the vibrancy of this field and “to bring together medicine, science, indeed demonstrate that “the brain is one of the last great frontiers and humanism through literature.” of medicine,” as Fiona Druckenmiller, a Medical Center trustee since From the press’s inception, NYU 2006 and a former portfolio manager at the Dreyfus Corporation, Langone Medical Center has provided has said. She and her husband, Stanley Druckenmiller, founder of it with space, services, and in-kind support, and recently, both the School Duquesne Capital Management, have endowed our neuroscience of Medicine and New York University institute, and through their generosity, our Medical Center is poised have made generous contributions. to make great strides. Its operations, however, are primarily Please stay tuned for further advances in this remarkable field of financed by foundation grants, private endeavor. donors to the Medical Center, and • revenues from book sales. “The prize will make a big difference for us,” says Jerome Lowenstein, MD, professor of medicine and the press’s Dean & Ceo robert i. grossman, md founder and publisher. He now expects more of everything—submissions, number of titles published, and financial support.B eyond that, adds Goldman, “I hope it means that when we publish a book, people will take a closer look.” •

NYU Physician 2 spring 2010 Around Campus

Artist’s rendering add 800,000 of the new square feet to the Kimmel Pavilion facility’s patient- from East River, centered clinical (left), and from care resources, First Avenue including inpatient (below). beds, procedure rooms with clinical support, and public amenities—more than doubling the amount of space currently devoted to Plans Advance for Integrating these activities. The keystone of the plan, explains Match Suna, is that both Kimmel New Kimmel Pavilion and and Tisch will eventually contain only private rooms. While the Medical Center’s Renovated Tisch Hospital total bed count will remain relatively constant, its overall capacity will increase The Boards of Trustees of NYU Langone Medical Center significantly because of gains in efficiency. and New York University recently approved a sweeping plan Private rooms will not only afford patients that will turn the north end of the Medical Center campus into an and their families more privacy and expanded and fully integrated clinical facility dedicated to acute care. eliminate gender-related issues, but also Bounded by First Avenue, 34th Street, and the FDR Drive, the site will make it easier to manage infection control. be anchored by the new Kimmel Pavilion at the north end and Tisch The facility will be designed with a Hospital, the Medical Center’s flagship clinical facility, at the south end. flexible and easily adaptable model to accommodate emerging medicine and As part of the plan, Tisch Hospital will her late husband, Martin, also a Medical technology. Reflecting the growing trend undergo an extensive makeover, thanks to Center trustee. Construction of the toward outpatient care, so-called “non- the Tisch family’s $110 million gift, made Kimmel Pavilion is targeted to begin in inpatient beds” will accommodate stays in 2008, that will enable the renovation 2013, with completion scheduled for the up to 30 hours long. Patient rooms—like program, the first phase of which is end of 2017. the new building’s procedure rooms already under way. The renovations and “The goal,” says Vicki Match Suna, and ORs—will all be standardized, yet new facilities include a new Critical Care AIA, senior vice president and vice dean adaptable for use as acute care, intensive Unit, private rooms, expanded lobby, for real estate development and facilities, care, or step-down units. and clinical pharmacy and labs. A key “is to provide one standard of care and A variety of features will make the feature of the renovation will be large one patient experience in a consistent and Kimmel Pavilion and Tisch Hospital truly Tnew elevators that will be designated for uniform environment across the Medical integrated. A lobby-level concourse will different groups—patients, visitors, staff, Center.” create a seamless connection between the and service—to enhance privacy and Overall, the Kimmel Pavilion will Tisch and Kimmel buildings. Through facilitate flow. signage and design, navigation will be The Kimmel Pavilion, which will be made simple and intuitive, with separate connected to Tisch on several floors, is pathways for patients and their families, made possible by a $150 million lead staff, and materials. donation from Helen Kimmel. A Medical The project team includes the Polshek Center trustee since 1984 and a life trustee Partnership/NBBJ as the architects and of the University, Helen Kimmel made Turner Construction as the construction the gift in 2008 on behalf of herself and managers. •

NYU Physician spring 2010 3

News from Medicine

Storming the Gates Researchers get a new view of how antidepressants work da-neng wang

Imagine trying to find the right key for a gate you can’t see. maarten Reith For years, that dilemma has confronted researchers struggling to understand how drugs such as antidepressants prevent the reuptake of chemical messengers by nerve cells. Experiments had indirectly The first few years of their resulting suggested that some drugs work by closing off gatelike transporter collaboration required both patience proteins that direct these chemical messengers, or neurotransmitters, and determination as they tried to coax back into neurons so they can be recycled. But discerning the structures the temperamental bacterial protein to of the cell-membrane–spanning gates has been notoriously difficult, form crystals. Proteins that span cell due in large part to their instability in the laboratory. membranes account for about 70% of all drug targets but less than 1% of protein Now a structural biologist and a psychiatry and pharmacology, arrived structures solved to date. “Our lab is doing pharmacologist at NYU Langone Medical at NYU Langone in 2003 with a deep crystallography, so we are used to failures,” Center have joined forces to overcome interest in how this block happens Dr. Wang says, laughing, “but I wasn’t sure this roadblock and, in the process, have in neurons. By then, Da-Neng Wang, if Maarten and his lab would stay with us.” obtained an unprecedented view of how PhD, professor of cell biology, had been They did, and the collaborators antidepressants may physically prevent trying for about three years to use persevered. In two high-profile papers the influx of neurotransmitters such as crystallography—growing tiny crystals published in 2007 and 2009 (in Science serotonin and norepinephrine into neurons. of proteins to reveal their complex and Nature Structural & Molecular Biology, Antidepressants such as Prozac and structures—to resolve the architecture respectively), they demonstrated how Zoloft are called serotonin reuptake of a bacterial relative of human a bacterial leucine transporter—a inhibitors because they stop the movement neurotransmitter transporters. “I was stand-in for human neurotransmitter of serotonin back into neurons. With the desperate to find someone who could transporters—binds the amino acid leucine block in place, serotonin’s concentration work on the human proteins,” he says. within a pocket inside its gated structure. increases in the brain, exerting a strong “By reading a book that Maarten edited, Crucially, the researchers also showed how influence on mood. Cocaine acts in a I saw his address: NYU. So I just called different kinds of antidepressant drugs similar way on dopamine. him up and said, ‘We may have similar can physically “lock the gate” from the Maarten Reith, PhD, professor of interests. Can I come over and talk?’ ” outside and prevent more leucine from getting into the cell. By using that structural This picture shows the complex three-dimensional structure of a bacterial information to tinker with the equivalent transporter protein membrane that spans the cell membrane. sites in the related human neurotransmitter transporter proteins, the researchers demonstrated that the same mechanism is likely at work in our neurons. “For me, it has been an eye-opener of what these techniques can accomplish, in terms of detail,” says Dr. Reith. The ultimate prize would be a precise view of how our own neurotransmitter transporters interact with antidepressants and other drugs. “It may take some years,” says Dr. Wang, “but we are determined to do it.” • —bryn nelson image: nathan k. karpowich k. nathan image:

NYU Physician illustrations by 4 spring 2010 peter oumanski

pamela roehm

Nerve cells grown in Petri dishes.

Herpes: The Reawakening How an unwanted viral sequel may spur neurological syndromes Pamela Roehm, MD, PhD, never thought a common herpes virus a neurotrophin known as nerve growth would become the focal point of her neurological research. As a factor may be a culprit. “But nobody has neurotologist at NYU Langone Medical Center, the assistant professor ever understood how that works,” says Dr. of otolaryngology specializes in treating disorders of the inner ear. But Chao, who has devoted much of his career the possibility that the herpes simplex virus type 1, or HSV-1, plays to research on neurotrophins, which an unexpected role in neurological syndromes that affect the ear has neurons require for proper support. led her to collaborate with Moses Chao, PhD, professor of cell biology, The collaborators decided to find out by physiology and neuroscience, and psychiatry. growing rat vestibular ganglion neurons in the laboratory. These neurons are Together with Ian Mohr, PhD, and Angus elsewhere can be more harmful. so small that 200 could fit on the head Wilson, PhD, Department of Microbiology, “There are all of these odd syndromes of a pin, though their branchlike nerve the researchers are examining how a that we see clinically that have been endings reach much farther in making dormant version of the virus normally circumstantially linked to herpes simplex connections to neighboring cells. By associated with cold sores may suddenly virus,” says Dr. Roehm. Vestibular growing and deliberately infecting these reawaken within various nerve cells and neuritis, for example, is characterized by neurons with HSV-1 within small lab lead to far more serious consequences. A vertigo, nausea, and vomiting that can dishes, Dr. Roehm is hoping for a better principal aim is to figure out how proteins last for days. It is thought to be caused view of what might be happening within that aid neuron growth and survival, by HSV-1 reactivating in the vestibular our own nerve cells. She also is developing known as neurotrophins, may be sending ganglion neurons of the inner ear. Bell’s a test that can detect reactivation of signals to keep the virus quiet. That palsy, characterized by muscle weakness the virus after removing individual information, in turn, could offer improved on one side of the face, affects the facial neurotrophins from the mix. strategies for blocking any reemergence. nerve. Weaker evidence suggests viral Tracing the biological steps leading The effects of viral reactivation, Dr. reactivation may be linked to sudden to viral reactivation could explain the Roehm says, seem to depend upon location. hearing loss. difference between a lifetime free of cold If the herpes virus has holed up within a How can this virus reactivate after a sores or more serious complications, and a branch of the trigeminal nerve, the main prolonged period of quiet, or latency? host-viral collaboration that keeps the virus nerve for facial sensation, the reawakened Stress and ultraviolet light are commonly coming back for more. “We’d love to be able virus can migrate to epithelial cells and cited triggers, and experiments some 25 to connect the dots,” says Dr. Chao. • image: vladimir camarena image: cause cold sores. Reactivation of the virus years ago suggested that the absence of —bryn nelson

NYU Physician spring 2010 5

News from Medicine

Taming Runaway Inflammation New findings suggest a way to rein in overactive immune cells Armed with new information about how the immune system’s molecular detective work and powerful checks and balances go haywire when autoimmune diseases strike, microscopy, the new study’s collaborators researchers are discovering effective ways of fighting back. found that an enzyme known as protein In the March 25, 2010, online issue of Science, NYU Langone Medical kinase C theta can interfere with that Center researchers revealed how an investigational drug warded off communication but is largely constrained within active regulatory T cells. “In fact, the inflammation accompanying infection-fighting T cells to go overboard, most of the interfering enzyme is physically rheumatoid arthritis by holding a specific thereby holding inflammation in check. In kept far away from the area important for enzyme at bay. “This is an unusual rheumatoid arthritis, either an abnormal cell-to-cell communication,” Dr. Dustin says. mechanism that could provide a potential surge by infection-fighting T cells or a dip “It’s a very unique distribution.” therapeutic approach for the treatment in the activity of inflammatory-fighting The research showed that a molecule of autoimmune diseases like rheumatoid T cells—or perhaps both—could cause called Compound 20, in development arthritis or inflammatory diseases like the immune system to attack our own by pharmaceutical company Boehringer Crohn’s disease,” says Michael Dustin, joints instead. Ingelheim, dramatically boosted the PhD, the Muriel G. and George W. Singer “Therefore, if you have an abnormal normal activity of regulatory T cells Professor of Molecular Immunology, and and suppressed regulatory T cell by improving their ability to keep this professor of pathology. function, you have enhanced potential for enzyme out of the way. Within the past few years, researchers autoimmunity,” says Steven Abramson, The collaborators also found that at NYU Langone and other institutions MD, professor of medicine and pathology. among 25 patients with rheumatoid have learned that immune system These regulatory T cells exert their arthritis, those who were sicker had less- components known as regulatory T influence by communicating with other active regulatory T cells. The enzyme- cells counterbalance the tendency of parts of the immune system. Through inhibiting Compound 20, however, dramatically revived the defective In this magnified image, an interfering protein (red dot) is kept far away from the regulatory cells in tissue cultures. “We action of immune cells, thereby helping to ward off inflammation. could get them back to almost a normal level of activity, like what you’d see in a healthy individual,” says Dr. Dustin. In a mouse version of the intestinal autoimmune disorder known as Crohn’s disease, the investigational drug likewise protected the mice from inflammation. The study, supported through the National Institutes of Health Nanomedicine Development Center Program and the Cancer Research Institute, was spearheaded by Alexandra Zanin-Zhorov, PhD, a postdoctoral fellow in Dr. Dustin’s lab, in collaboration with Juan Lafaille, PhD, associate professor of pathology and medicine, and Dr. Abramson. Drs. Dustin and Zanin-Zhorov have applied for several patents based on their success. Dr. Abramson is especially excited about the potential for targeting the newly discovered pathway in rheumatoid arthritis. “The theory is that if you could restore normal regulatory T cell function,” he says, “then you could restore their ability to suppress the inflammation process, and prevent this abnormal destruction of your joints.” • —bryn nelson sudha kumari image:

NYU Physician illustrations by 6 Spring 2010 peter oumanski

lisa mosconi

lidia glodzik

Top: Two views of Bottom: Similar a composite brain composite image reveal that images show the among healthy varying patterns adults with an of higher-than- Alzheimer’s- normal deposits afflicted mother, among volunteers some regions had with a mother two-fold (red) or (red) or a father four-fold (yellow) (blue) afflicted by more amyloid- Alzheimer’s. beta deposits than Sounding an Early normal. Alarm on Alzheimer’s During the “silent phase” of Alzheimer’s disease, early damage to brain tissue often goes undetected for years. Two recent international collaborations led by researchers at NYU Langone Medical Center, maintain proper cell structure and however, have uncovered independent risk markers in otherwise shape, and it is essential for transporting healthy adults, pointing the way toward diagnostic tools that may help substances along the neuron. When warn of impending danger. damaged, however, the same protein forms tangled clumps that can accumulate Advanced age and a family history years ahead of memory problems in and lead to the demise of neurons. of Alzheimer’s are the biggest known Alzheimer’s disease, the goal is now Published in an online edition of risk factors for the incurable memory- to shift therapeutic approaches for the the journal Neurobiology of Aging in robbing disease, which affects more than disease toward earlier detection, and February, the study found that among 5 million Americans. One study, led by ultimately prevention.” healthy volunteers, higher levels of the Lisa Mosconi, PhD, research assistant The new study combines positron defective protein were associated both professor of psychiatry, has now identified emission tomography (PET), which with declining memory and atrophy the likely basis for heightened familial measures the brain’s metabolism, with within a portion of the brain known as risk—especially from the maternal side. a fluorescent dye called Pittsburgh the medial temporal lobe. Researchers Aided by a new version of a brain Compound B. The dye attaches to plaques have identified this region as one of the scanning technique, Dr. Mosconi and her and acts like a temporary beacon to first sites of tissue damage in Alzheimer’s colleagues discovered significantly more highlight their presence during a PET disease. The new findings suggest that Alzheimer’s-associated protein clumps scan. The presence of plaques doesn’t p-tau231 could be an early marker capable among healthy adult children of parents necessarily mean an individual will of identifying preclinical stages of the with the disease than among counterparts develop Alzheimer’s. Dr. Mosconi also disease, though Dr. Glodzik cautions that with no family history of dementia. The cautions that the technique, published more long-term observations are needed. average increase in these clumps, called in the March 15, 2010, online edition Mony J. de Leon, EdD, professor of amyloid-beta plaques, was particularly of Proceedings of the National Academy of psychiatry, director of the Center for striking among study volunteers whose Sciences, must be validated before it can be Brain Health at NYU Langone, and a co- mothers had been diagnosed with the considered for diagnostic use in the clinic. author of both studies, says they provide disease. Another study, led by Lidia Glodzik, “perhaps the ideal combination,” a specific “Overall, people with mothers who have MD, PhD, assistant research professor of signpost of the plaques and protein Alzheimer’s appear to be at higher risk psychiatry, concludes that elevated levels tangles so characteristic of Alzheimer’s for the disease than those whose fathers of a defective protein known as p-tau231 disease. That powerful pairing, he says, have it, and our new study supports this in the cerebrospinal fluid may be another “would appear to offer the best chance of a association,” Dr. Mosconi says. “Given important early indicator of Alzheimer’s correct pre-symptomatic diagnosis.” • that brain pathology begins to accumulate risk. Normally, the tau protein helps —bryn nelson

NYU Physician Spring 2010 7

8 microscope. with an electron chromatin obtained is an image of Inside the nucleus Road of T transferring information fromDNA toRNA todirectprotein synthesis. molecules are needed to unwind it and start transcription, the process of fiber. If that couldbe accomplished, theynext wanted tofigureout what one at atime, into atest tube, hopingtorecreate acompact DNA-protein dozens ofproteinsfromcells.Then, theyloaded themback together, PhD, professorofbiochemistry, have painstakingly purifiedDNA and powerful new methodwillallow scientists regulate gene expression.The team’s what actually happens inside cellsto significant step closer tounderstanding says histeam’s latest work brings usa transcription formorethantwo decades, has tobeadded.” has tobepurifiedandtheexact amount multiprotein system, where each protein incredible inhisability todeal witha fellow inthelab, Guohong Li,PhD, “was Institute Investigator. But apostdoctoral who isalsoaHoward Hughes Medical researcher can do, says Dr. Reinberg, A better understanding of gene expression News from Medicine For thelast seven years, Dr. Reinberg, who hasbeenstudying It’s notthekindofwork that just any he Long and ( DNA researchers inthelab ofDanny Reinberg, U Spring 2010 NYU Phy turned off, compared towhen thegene is together more tightly when the gene is and thecellcontrols thefit. The fibers pack to form compact fibers called chromatin, and wrapped around proteincomplexes Inside thecell,however, DNA istwisted which is a long double-stranded helix. they were working with naked DNA, transcription in a test tube, but at the time, just a few proteins could lead to gene and other investigators learned how cancer andotherdiseases. examine how theprocessgoes wrongin toturnonindividualnecessary genes and worldwide toinvestigate thediscretesteps In the1980s and1990s, Dr. Reinberg n) Winding sician

or moleculeswe want totarget,” hesaid. can start devising assays totest forsteps and analyze how things happen. Then, we idea now istoread each ofthosechapters we have abookwithlotofchapters. The chromatin totranscription.Right now, out therethat goes fromhighly compact a nicestorythat Ibelieve is theonlystory Dr. Reinberg thinks so. “In theend,we got which iscontrolledPEPCK, by RAR. transcription started from their test gene, DNA continued to stretch out, until finally, in more and more protein factors, the just as critical as RAR. As the team added make room for other transcription factors called nucleosomes, were moved aside to to unwind and large protein complexes, Snf complex. Then, the chromatin began acetyltransferase p300andtheS in chromatin remodeling, thehistone key proteins previously implicated hormone that stimulates RAR and two researchers added to the system the most tightly wound state. DNA even when the chromatin was in its (RAR) could access its binding site on the protein called the retinoic acid receptor colleagues found that a DNA regulatory and start transcription. Dr. Reinberg and and add particular proteinstounwind it team shows how it can recreate a fiber 2010, issue ofMolecular Cell, Dr. Reinberg’s in atest tube. no one could recreate a 30-nanometer fiber tool to study the phenomenon in vitro since diameter. Moreover, they had lacked a key compact one, which is 11 nanometers in of smoke from cooking oil), to the less across (about the size of the tiniest particle compact fiber, which is30nanometers cell controls theshift fromthemost highly states for years, they didn’t know how the scientists have known about these different turned on and being transcribed. Though So was allthetimeandeffortworth it? The chromatin loosened when the Now, in a study published in the April 9,

—rabiya tuma peter oumanski illustrations by wi/ • •

Photographers credit:

image: guohong li

image: wen-biao gan

Photographers credit: the brain’s andeliminating neuralcircuitry oldones.” neuroscience. “It does thisintwo ways: by adding new connectionsto says Wen-Biao Gan, PhD, associate professorofphysiology and “We’ve known foralongtimethat thebrainremodels after learning,” a new taskonaspinning (running different places alongthecage) orlearning new stimulus (a string ofbeads hung at and after theanimalsexperienceda changes inthe brainsofmicebefore Nature, Dr. Gan andhisassociates tracked gained, andotherslost. of nerve cells.With learning, spines are alongthebranchingprotrusions ends to thedendritic spines, theknobby Dr. Gan, prompts alterations specifically novel situation. New knowledge, explains learning anew task orbeingexposedtoa nerve cellscommunicate, in thewake of place at synapses, thejunctionswhere to view theprecisechanges that take Medicine have beenable forthe first time the Skirball Institute ofBiomolecular he devised, Dr. Gan andcolleagues at a mystery—until now. Using atechnique tolearning, allamatterWhen itcomes t’s ofgiveandtake Learning by adding and subtracting synaptic connections The Brain’s Balancing In astudy published inthejournal But exactly how itdoes thishasbeen time asthesenew andlasting spines were researchers alsonotedthat at thesame new spines continued generating. The became improved at spinning thewheel, the wheel. They saw, too, that asthemice beads’ placement on or learning torun spines emerging inresponse tothe across themonths, theyobserved new adulthood. a month oldandfollowed themthrough photographing themicewhen they were newly positionedbeads. The teambegan they ranonthewheel orencountered the snapped photosofthedendrites after special microscopeand camera,they up thenerve dendrites. Then, usinga mice withafluorescent dye that lights key roleinmemory. They injected the animal’s cortex,thesectionthat plays a the teamshaved away theskull over each wheel). To openawindow tothebrain, When theteamcompared thephotos Act NYU Phy Spring 2010 sician . Dr. Gan. “It hasaway tobalance.” brain isadynamic andstable organ,” says without losingexisting memories.“The experiencing andlearningnew things, one neuron,tolive each day, constantly have hundreds ofthousandsspines on as tohow itispossibleforhumans, who on each nerve cell.The study gives aclue hundred spines were eithergainedorlost Alzheimer’s Association, onlyafew study, which received fundingfromthe on itsdendrites. Over themonths ofthe 10,000mouse neuroncancarry spines remained overwhelmingly secure. A spines, theanimals’brain circuitry experiment began,disappeared. in theanimals’development beforethe spines, which had beenformedearly created, acorresponding number ofolder Despite the rise and fall ofdendriticDespite theriseandfall ends of nerve cells. along the branching knobby protrusions appear like glowing Dendritic spines

— amanda schupak • 9

Memories of

An NYU researcher probes the nature of memories associated with severe stress and how they can be undone. by Eric Goldscheider

Illustration by Jeffrey Decoster

NYU Physician Spring 2010 11 humans experience two major problems with memory, neuroscientist Joseph LeDoux, PhD, likes to tell his audiences: “Sometimes we can’t remember, and sometimes we can’t forget.” Brushes with danger have a way of creating some of our most intractable memories, he adds, because fear is closely linked to survival. “Evolution places a high value on not having to relearn about danger,” says Dr. LeDoux, University Professor and the Henry and Lucy Moses Professor of Science in the Center for Neural Science, and director of the Emotional Brain Institute at the Nathan S. Kline Institute for Psychiatric Research. More to the point, when these indelible fear memories are triggered, they take over our brains and, through the fight-or-flight mechanism, our entire bodies. a snapshot While fear may be an essential survival tool, however, Dr. LeDoux believes that after a memory of fear it can also undermine some people’s ability to is activated, there is a period of time during which in any given function, wreaking havoc with their lives. But what it is reconsolidated as a new long-term memory. year...* if therapies could be developed that relieve their During that period, it is vulnerable to drugs that suffering by erasing specific fear memories? This can chemically block the reconsolidation process, Anxiety Disorders is the tantalizing promise of Dr. LeDoux’s research. effectively eliminating the memory and the fear It’s also why, over the past decade, his work has response it triggers. Approximately attracted attention from clinicians who treat an Daniela Schiller, PhD, a postdoctoral student 40 million American adults age 18 and array of fear-related maladies, including phobias, who collaborates with Dr. LeDoux, draws an older, or about 18.1% panic attacks, social anxiety, and post-traumatic analogy to a word-processing file: when you open it of people in this age stress disorder (PTSD). up and then hit “save,” the previous form of the file group, have an Dr. LeDoux’s research focuses on the is gone, replaced by something new. anxiety disorder. neurological underpinnings of fear in rats— To understand the neurological basis for especially the role that a small almond-shaped the consolidation and reconsolidation of Panic Disorder structure called the amygdala, buried deep within fear memories, Dr. LeDoux created a simple the brain, plays in storing fear memories and experiment. It starts with fear conditioning, in Approximately 6 million activating fear responses. His groundbreaking which a rat is exposed to a 30-second tone followed American adults age 18 work to understand the neural pathways that by a half-second shock to the feet. The animal is and older, or about 2.7% stimuli (such as sounds or sights) activate in videotaped, and its fear response is measured by of people in this age group, have rats’ brains and how these nerve impulses are a set of uniform criteria. The next day, the tone by panic disorder. consolidated in the brain as long-term memories itself elicits the fear response. has changed the way scientists think about Through a long series of experiments that memory itself. included disabling specific brain regions before O bsessive- The common perception is that a memory is observing the rats’ behavior, inserting probes into Compulsive more or less fixed, and that each time we bring the brains to measure electrical activity in specific ( ) Disorder OCD it to the fore we are retrieving the same original regions, and dissecting the brains of dead fear- Approximately 2.2 memory. Based on his work with animal models, conditioned rats to examine their neural pathways million American adults age 18 and older, or about 1.0 % of people in this age group, have OCD.

Post-Traumatic Stress Disorder (PTSD) Approximately 7.7 million American adults age 18 and older, or about 3.5 % of people in this age group, have PTSD.

Joseph LeDoux, PhD, in his office at NYU’s Center for Neural Science.

NYU Physician photograph by 12 spring 2010 sasha nialla under an electron microscope, Dr. LeDoux was “We have two goals, which are not mutually able to show that there is a high-speed connection exclusive,” said Dr. Schiller, whose interest in fear to the amygdala that bypasses the cerebral cortex. was motivated in part by her own experiences Certain regions of the amygdala store emotional with skydiving. “We want to understand how memories such as fear, he found. When these areas memory works in the normal brain with regard to are triggered, they begin to send alarm signals how emotions are represented, and we want to see to the rest of the body before the slightly slower if we can make use of this knowledge to improve pathways of the cerebral cortex—the part of the treatment.” brain associated with thought, decision making, The standard approach to treating certain fear and language—can catch up. disorders is extinction therapy, which involves To illustrate this, Dr. LeDoux points to an repeatedly pairing anxiety-provoking situations amateur video made in the vicinity of the bombing with benign or even positive outcomes until over at the 1996 Summer Olympics in Atlanta. First time, the impact of those stimuli is diminished. everyone freezes (an involuntary response) before New understandings of the plasticity of memories the thinking about which way to run kicks in. If and the fact that they can actually be altered or memories associated with basic emotions such even erased could lead to much more effective as fear can trigger responses independently of use of extinction therapy. If indeed there is a very AND... the cerebral cortex, he notes, one consequence specific time window during which memory for humans is that “you can have an emotional reconsolidation occurs, then much more precise Generalized response that you don’t understand. You could and effective therapies could potentially be Anxiety Disorder go to therapy for 95 years and never figure it out developed that use the principles of extinction (GAD) because you can’t verbalize it.” therapy to target debilitating memories. This could Approximately 6.8 After instilling a fear response in a rat, Dr. be done through talk therapy or with drugs that million American adults LeDoux then eliminated it. He and his colleagues inhibit reconsolidation of a memory that has been age 18 and over, or discovered that when a fear response is activated, deliberately activated in a therapeutic setting. about 3.1 % of people there is a window of up to six hours during which The idea of using drugs to erase memories in this age group, the memory is reconsolidated. By strategically draws criticism from some ethicists, who say that have GAD. administering drugs that interfere with the our memories are at the core of who we are. Dr. synthesis of proteins used by the brain to establish Schiller counters this concern by pointing out that Social Phobia long-term memories, he was able to disrupt the while pain plays a vital role in survival, nobody reconsolidation process and, in a relatively short wants to do away with painkillers. “At a certain Approximately 15 million time, transform rats that freeze at the sound of the point, pain loses its function—it’s not effective American adults age tone to rats that don’t, essentially unfreezing fear. anymore, and you just suffer.” She believes the 18 and over, or about same is true of maladaptive memories. “You have 6.8 % of people in this age group, have dr. ledoux, who a natural process that allows you to overcome fear social phobia. grew up the son of a and to continue functioning normally despite the butcher in a small Louisiana bad memory,” said Schiller, “but if the memories town, began his academic career are so bad that they affect your everyday Agoraphobia with two degrees in marketing. functioning, this is where you need treatment.” Approximately 1.8 Along the way he discovered a Aside from their scientific collaborations, Drs. million American adults passion for psychology that led to graduate studies LeDoux and Schiller conspire to make rock and age 18 and over, or in neuroscience. When his advisor told him that roll music together as part of an all-scientist band about 0.8 % of people nobody in the field was grappling with emotions, that Dr. LeDoux started several years ago with in this age group, have he was off and running. Today, his work on fear is NYU biology professor Tyler Volk, PhD. The agoraphobia without a generating intense interest, which isn’t surprising, Amygdaloids perform original songs with themes history of panic disorder. given that 40 million Americans suffer from that originate in the lab, and have played venues anxiety disorders, at an annual cost of $50 billion ranging from the 92nd Street Y and the Kennedy SpecificP hobia in terms of treatment and lost productivity. Then, Center in Washington, D.C., to Kenny’s Castaways Approximately 19.2 of course, there is the human anguish. “As bad as on Bleecker Street. The refrain from “Memory Pill,” million American adults anxiety is for those of us who are quote unquote one of the songs on their first album,Heavy Mental, age 18 and over, or normal, it’s really bad for people who have anxiety goes, “Just give me a pill, oh yes oh please. Just give about 8.7 % of people disorders,” he says. me a pill, wash away my memories.” Their new CD, in this age group, Dr. Schiller is part of a lab that is taking Dr. which will be out in June, features Rosanne Cash on have some type of LeDoux’s findings on involuntary fear responses in two songs. specific phobia. rats and seeing if they apply to humans. Her work The author of two popular books (The Emotional *National Institute on emotional learning in her native Israel led her to Brain, Simon & Schuster, 1996, and Synaptic Self, of Mental Health NYU, she said, because Dr. LeDoux and Elizabeth Viking, 2002) and dozens of scientific articles, Phelps, PhD, his former postdoctoral fellow, who Dr. LeDoux addresses the propriety of altering is now a professor of psychology and runs her own or erasing memories head on. “We’re changing lab, are at the cutting edge of their field. Dr. Schiller’s memories every time a person meets someone subjects are usually NYU students who have agreed or goes to therapy or reads a book,” he says, so to let themselves be shocked with a mild electrical why not try to eliminate memories that interfere current. The stimulus is paired with the display of with our ability to function? Looking ahead to the a yellow square, and the students’ responses are future of his field, Dr. LeDoux says, “My fondest recorded through highly calibrated measurements hope would be that we get to the point where the of perspiration. Like the auditory stimulus in the ethicists are really worried—in other words, where rats, the visual stimulus of the yellow square soon we really can alter these debilitating memories.” elicits a fear response without the shock. •

NYU Physician spring 2010 13

Memory and the Senses Research suggests that Smell may be an early marker for Alzheimer’s, Schizophrenia, and other Brain Diseases.

by SHARON KAY Illustration by JILLIAN TAMAKI

NYU Physician Spring 2010 15 IN THE NOSE, NIKOLAI GOGOL’S FAMOUS 1836 SATIRE, A NOSE IS MYSTERIOUSLY separated from the face of a low-level orange. But our understanding of exactly of these areas directly,” he notes. “Other civil servant and becomes a person in how we smell coffee, citrus, dirty socks, sensory systems enter very low in the its own right—a high-ranking official no or that indescribable but familiar scent of brain, through the thalamus and even the less. Sleeper, Woody Allen’s futuristic 1973 our grandmother’s kitchen is a relatively spinal cord. This means that information film, features a similar story line about an recent discovery. from your eyes or ears has to go through assassinated dictator’s nose that continues When you first inhale the scent of many connections to reach the frontal to rule over his followers, who hope to coffee, for example, over 600 different cortex. But the olfactory system is just two clone the nose and recreate their leader. kinds of airborne coffee-related connections away.” As science is discovering, these molecules are absorbed into the olfactory The result is an immediate pathway allegories about the controlling nature receptor cells that line the mucous from the environment through our nose to of our noses aren’t as far-fetched as they membranes at the back of your nostrils. our memory. “You can inhale a chemical,” might seem. Researchers have shown There are some 350 varieties of these adds Dr. Wilson, “and boom—you’re back that our olfactory system—the complex receptor cells, each specialized to detect in grandma’s kitchen.” network that links our sense of smell to the certain odor molecules and convert parts of our brain responsible for emotion, this information into nerve impulses. memory, and cognition—has a powerful These impulses are transmitted to the Alzheimer’s: When Scent influence over our social interactions. brain’s two olfactory bulbs (one for Memories Fail Us New research at NYU Langone Medical each nostril), which sit just behind your Dr. Wilson, the co-author of the textbook Center now reveals that this system is also nose. The olfactory bulbs translate the Learning to Smell: Olfactory Perception from a window into how our brains first begin impulses into information your brain Neurobiology to Behavior, has been fascinated to malfunction when diseases such as can understand. This information is then by the olfactory system’s connection to Alzheimer’s and schizophrenia strike. sent to the olfactory cortex, where the memory for more than 20 years. “Memory “Our sense of smell tends to be a combination of molecules is remembered is the thread that gives you continuity background sense that sets a mood or and identified as “coffee.” in life. Each smell would be unfamiliar makes you hungry,” says Donald Wilson, Finally, the olfactory cortex passes without it,” he says. Because memory PhD, research professor of child and “coffee” on to your brain’s limbic system— and smell are so intimately linked, when adolescent psychiatry, and senior research including your amygdala, hypothalamus, a message from the olfactory bulbs to scientist at the Emotional Brain Institute and hippocampus—where memories the limbic system becomes scrambled, at the Nathan S. Kline Institute for associated with this smell pattern are a strawberry might be mistaken for Psychiatric Research, who is a pioneering accessed. The limbic system interacts peppermint, or both smells may become researcher on the neurobiology of smell. with your prefrontal cortex to determine indistinguishable, even if the memory of “It’s easy to ignore, even when it starts to what, if anything, you need to do about this each smell remains intact in the brain. In deteriorate, but this deterioration is an particular odor: “Don’t drink the coffee— either case, says Dr. Wilson, “it’s an early important signal telling us that something it’s hazelnut, and you’re allergic to it.” sign of trouble that may give us time to is wrong.” Working in combination, our olfactory prevent further damage to the brain.” Recent findings by Dr. Wilson and receptors can identify many thousands Olfactory dysfunction in mouse his colleagues indicate that smell tests of different smells, each of which is models first led Dr. Wilson to question may serve as a significant biomarker for stored as a template in our memory. The why diseases like Alzheimer’s strike early detection of Alzheimer’s disease. scientists who discovered this receptor the olfactory region first, and how They hope such tests may also provide a system in the 1990s, Richard Axel and this knowledge might lead to early noninvasive tool to evaluate the progress Linda Buck, were awarded the 2004 interventions. In a study published in the of the disease. Disruptions in our sense of Nobel Prize in Physiology for their work. January 13, 2010, issue of The Journal of smell also appear to offer an early warning Now, researchers are taking their findings Neuroscience, he and his fellow researchers of other diseases, including schizophrenia, a step further by probing how various Daniel Wesson, PhD, Efrat Levy, PhD, Parkinson’s, and autism. The reason, say brain diseases cause breakdowns in this and Ralph Nixon, MD, PhD, set out researchers, has to do with the unique way identification process. to investigate how the progression of our olfactory system connects our brains to Smell is unique among our senses, Alzheimer’s correlated with diminished the world around us. explains Dr. Wilson, because it has olfactory function. One of Alzheimer’s direct connections to brain regions like hallmarks is an abundance of amyloid- the amygdala, which controls emotions beta, which forms damaging plaques The Anatomy of an Odor and physiology, and also to higher-order outside the brain’s neurons. The olfactory Most of us of us take it for granted when regions like the prefrontal cortex, which is bulbs are one of the first places where we wake up to the scent of fresh-brewed involved in cognition and planning. “The the protein accumulates, thwarting coffee or the fragrance of a newly sliced olfactory system talks and listens to all communication between what we smell

NYU Physician 16 spring 2010 found that adolescents with schizophrenia- related psychosis had difficulty identifying odors, while a similarly aged cohort with psychosis from bipolar disorder had no impairment in their sense of smell. Dr. Malaspina believes that treatments to sharpen schizophrenic patients’ sense of smell might one day be used to improve their social functioning. Because the olfactory region of the brain is one of the few places where new brain cells continue to generate, she is also hopeful that the nose may someday provide a powerful means of restoring brain function. “It’s not inconceivable that future treatments may be directed to making new brain cells and that olfactory tests will be used to track Donald Wilson, their success,” she notes. PhD, with the organ that has animated his Applying the Smell Test research. If it’s true that dysfunction in our sense of smell is our brain’s earliest warning system that something’s going wrong, then the use of smell tests, combined with other biomarkers, may prove the key to the early diagnosis of Alzheimer’s, schizophrenia, and how we remember smells. symptoms of schizophrenia that frequently and other brain diseases. “I’ve always been In their study, Dr. Wilson and his emerge during adolescence—are linked to fascinated by the hunt for biomarkers that group tested genetically engineered mice the same brain region that identifies how don’t require imaging the brain or drawing for their capacity to remember smells we feel about smells. “I don’t think it’s a spinal fluid,” says Dr. Nixon, professor of as Alzheimer’s progressed. They found coincidence that an odor conjures so much psychiatry and cell biology, and director of that mice just three to four months old, emotion and context for us,” says Dolores the Center of Excellence on Brain Aging. In with excess amyloid-beta but little or no Malaspina, MPH, MD, MScPH, the Anita addition to their possible diagnostic value, plaque in the brain, already exhibited Steckler and Joseph Steckler Professor Dr. Nixon is optimistic that smell tests will some loss in short-term smell memory. By of Psychiatry. “In fact, our nose might be provide an efficient and reliable means to six to nine months, with plaque buildup the most exciting frontier right now in assess the efficacy of experimental drug similar to that of a person with early understanding the brain.” therapies. stage Alzheimer’s, the mice had a more significant loss of short-term memory and trouble distinguishing between smells. “ M emo r y is t h e t h r e a d t h at By the final stage of 21 to 29 months gives you continuity in life. (equivalent to advanced Alzheimer’s in humans), olfactory behaviors were Eac h sm e l l wo u l d b e completely abnormal, and the mice seemed disoriented when presented with odors. unfamiliar without it.” Autopsies across the age groups revealed progressive amounts of plaque throughout Dr. Malaspina is currently studying how Having shown that odor memory and the olfactory system of the brain. smell tests may serve as an important new perception are impaired even before biomarker for developing treatments for symptoms of Alzheimer’s disease schizophrenia, as well as how abnormal become apparent, Drs. Wilson and Schizophrenia: When Smell odor processing may be related to impaired Nixon want to understand what makes Never Fully Develops emotional and social functioning. Her the olfactory system begin to fall apart Unlike Alzheimer’s disease, in which research group found that patients with so early in the course of the disease. patients progressively lose their ability schizophrenia did significantly worse than “The earlier a marker can indicate the to smell, schizophrenia often inhibits the healthy subjects when asked to identify 40 presence of a brain disease, the earlier normal development of odor processing, common odors, and those patients with the we can act to stop the disease process in starting at a young age. Interestingly, loss most severe social dysfunction did worst humans,” says Dr. Wilson. “Olfaction of drive and emotion—both debilitating of all. Another study, published in 2005, may be that marker.” • photograph by NYU Physician lynn saville spring 2010 17 c o n n e c t i n g to sound

by GARY GOLDENBERG Illustration by EMILY COOPER F o r t h o s e left profoundly deaf, a n auditory b r a i n s t e m i m p l a n t restores some hearing.

NYU Physician 18 spring 2010

For Jackie Murphy, t h e w o r l d e n d e d o n January 22, 1997— or at least it seemed that way. About a decade earlier, while in college, FDA-sponsored clinical trials at a handful she lost her hearing on her left side when of sites around the country, including a schwannoma (a benign, slow-growing NYU Langone Medical Center. Dr. Roland, tumor) engulfed her auditory nerve. Now, who was one of the investigators leading a similar growth was threatening her the trial at NYU Langone, implanted right side, inching precariously toward Jackie’s ABI in 1998. her brainstem. With her life in danger, she Initially, Jackie was “very had little choice but to undergo surgery, disappointed.” She couldn’t tell a car’s although it would probably leave her horn from a dog’s bark. Speech sounded profoundly deaf. garbled, strangely monotonal, and When she awoke from anesthesia mechanical. “Eventually, I began to that January day, all was silent. “I was notice differences in rhythm, duration, devastated,” says Murphy, who retreated and pitch that helped me distinguish to her Brooklyn apartment for months on between sounds,” she says. “I could hear end. “I didn’t want to socialize. I felt ill at my own voice and tell whether someone ease when I was outdoors, particularly was laughing or crying.” The device also when I was alone.” What’s more, she was greatly improved her lip-reading skills, beset with facial paralysis, double vision, easing communication with friends, Jackie Murphy with audiologist muscle weakness, and other problems— family, and co-workers. William Shapiro, AuD. all related to tumors caused by her With newfound confidence, Jackie underlying condition, neurofibromatosis returned to school, switching majors type 2 (NF2), a genetic disease that strikes from education to computer science. about one in 25,000 people. She now works in the clinical data- Slowly, depression and anger turned entry department at NYU Langone’s to acceptance and hope as Jackie sought Tisch Hospital. “Jackie, all she has ever a route back to the hearing world. First, wanted to do was get back to work,” says Remarkably, Jackie’s ABI experience she tried a cochlear implant, to no avail. Dr. Roland. “She is incredible. All these is the rule, not the exception, says Dr. While a cochlear implant (which converts patients are just so courageous about how Roland, who has implanted about 40 of sound waves into electrical signals) they go on with their lives.” these devices over the years, a caseload can substitute for a damaged cochlea— another consequence of her illness—it requires a certain degree of auditory nerve function. Evidently, the damage to her nerve was too severe. stimulate the auditory nerve. Types of Hearing Loss Hearing aids offer some At this point, she had one last hope: an There are two types of relief to people with mild- auditory brainstem implant (ABI), which hearing loss: Conductive hearing loss to-moderate hearing loss of can restore “sound awareness,” if not quite and Sensorineural hearing loss. Some people this type. However, for those hearing, to people with auditory nerve have a combination of the two. with severe-to-profound damage, reports J. Thomas Roland, Jr., impairment, the only MD, chairman of otolaryngology, and the Conductive conventional hearing aids, remedy may be a cochlear Mendik Foundation Associate Professor hearing loss is which amplify sound. implant—in essence, an of Otolaryngology. He recently established characterized Less common, and harder artificial cochlea. a center dedicated to NF2 patients, the by damage to to treat, is sensorineural Some sensorineural the structures that transmit hearing loss. This usually deafness is caused by only one in the New York metropolitan sound waves from the stems from damage to damage to the auditory area. An ABI bypasses the entire auditory outer ear to the inner ear. the snail-shaped cochlea, nerves, which relay signals system (the outer, middle, and inner ear; Sounds become fainter, as particularly its tiny “hair” from the cochleas to the the cochlea; and the auditory nerve), if the ear’s volume control cells, which convert sound brainstem. Most often, this establishing a direct sonic connection to has been lowered. This waves into electrical nerve happens as a complication the brainstem. Sounds are captured by form of hearing loss can impulses, which, in turn, of surgery to remove benign an external microphone, converted into stem from genetic bony tumors of the auditory electrical impulses by a speech processor, diseases, trauma to the ear, nerves, leading to profound and then transmitted across the scalp to a infections, and chronic ear hearing loss. Birth defects diseases; less commonly, it decoding chip embedded in the skull, just and traumatic head injuries is a consequence of aging. can also impair the auditory behind the ear. The chip then relays the Depending on the cause, nerves. For this form of impulses along a wire that is connected conductive hearing loss hearing loss, an auditory to an electrode paddle attached to the can be treated medically brainstem implant (ABI) is brainstem. or surgically or with the only remedy. At the time, ABIs were undergoing

NYU Physician photographs by 20 spring 2010 RENÉ PEREZ nonauditory side effects, like dizziness,” Dr. Shapiro explains. (A pair of electrodes is necessary to generate an electrical current.) Early ABI models, like Jackie’s, had only eight electrodes. Today’s have 21, increasing the odds of finding usable pairs. In subsequent programming sessions, the audiologist adjusts the rate, intensity, and duration of the signals in an attempt to make the ABI-generated sounds as lifelike as possible. “The ABI user does not get nearly the amount of hearing that a cochlear implant user does,” says Dr. Roland. The difference lies in the cochlea, which is arranged tono-topographically, that is, with low-frequency-detecting cells at one end and high–frequency cells at the other. Cochlear implants are designed to match this layout. The brainstem’s cochlear nucleus, on the other hand, has little frequency organization, so ABI hearing is comparatively primitive. “We did have one ABI patient who could understand speech with no lipreading,” says Dr. Golfinos. “The tumor was small, the anatomy was perfect, and J. Thomas Roland, Jr,. MD, (left) and we got to him just after he lost his hearing, John Golfinos, MD, with their operating microscope. so his hearing-related brain pathways hadn’t degenerated.” Fortunately, once these pathways are lost, they can be reorganized, which explains why ABI recipients typically experience hearing improvement for years and years. “Ultimately, most of our patients second only to doctors at the House cells—all best left undisturbed. The are happy with the results,” reports Ear Institute in Los Angeles, where ultimate target is the cochlear nucleus, Dr. Golfinos. “If their expectations are the devices were developed. ABIs have a bundle of neurons that relay auditory realistic going in—and all our patients get steadily improved over the years and signals to the brain’s higher regions. counseling beforehand—they won’t be remain the only hearing-restoration “The placement of the electrode is disappointed. In general, they’re thrilled therapy for people deafened by NF2. critical,” says Dr. Golfinos. “If the tumors that they can be in a room reading and Dr. Roland and his team perform an ABI were small and the underlying anatomy is hear a door open and know somebody is implant every few months, just often enough good, we can usually get it right first time. coming in the room, or that they walk in for this difficult surgery to become routine— With big tumors, the normal anatomical traffic and hear a car horn.” and routinely successful. In people with landmarks can be obscured.” Jackie would agree. “I set my NF2, the implant is done at the same time the At this point, audiologist William expectations unrealistically high, so I was tumors are removed, sparing patients the Shapiro, AuD, clinical associate professor frustrated and angry,” she says. “I blamed trauma and risk of a second operation. of otolaryngology, steps in, sending test the ABI for my inability to hear well, and To begin, Dr. Roland drills a dime-size signals to the electrode paddle. If the paddle I refused to wear the device. After a while, hole into the mastoid bone, behind the is well positioned, the signals will generate I realized I could live in total silence or ear, allowing access to the auditory nerve particular waveforms over the surface work with the ABI. Little by little, my and brainstem. In addition, he carves a of the brain, as measured by an auditory hearing improved.” small depression into the skull, making brainstem response test—basically, a “My ABI helped me emerge from my room for the internal decoding chip. hearing-specific EEG. The test can also self-imposed seclusion and gave me back Then, using an operating microscope and reveal whether the paddle is situated too a part of my life that I had lost when I was miniaturized surgical instruments, he close to nearby nerves that control facial deafened,” she adds. “I can interact more removes the tumors. Since this can take movement, swallowing, and other functions. easily with hearing people, and I do not hours, he typically works on the tumors in Finally, the paddle is fixed in place with feel apprehensive about being outdoors. tandem with John Golfinos, MD, chairman small globules of the patient’s own fat, I am able to hear environmental sounds, of neurosurgery. which acts like a natural, long-lasting glue including sirens, car horns, and motors.” Once the tumors are cleared, the ABI and is commonly used in neurosurgery. That ability probably saved her life a electrode paddle is implanted, an exacting The surgery ends here, but months, if not few years ago while crossing the street. “A task that falls to Dr. Golfinos. Here, the years, of rehabilitation remain, beginning car had turned the corner as I was about challenge is to snake the match-head–size with implant programming. Each electrode to cross,” she says. “I didn’t see it because paddle through a natural opening called paddle has a number of electrodes on it. another car was obstructing my view, but the fourth ventricle until it reaches the “In the first programming sessions, we’re I heard the motor.” Jackie rushed back to auditory area of the brainstem, a journey basically searching for electrode pairs that the sidewalk, spraining her ankle—but of several inches and a billion nerve produce auditory sensations, with minimal she lived to tell the tale. • NYU Physician spring 2010 21 patterns of diffusion help build a better picture of the brain’s complexity by gina shaw

NYU Physician Spring 2010 23 it’s hard to imagine see that some of the water appears to any worse news for a move randomly in no particular direction whereas some of the water appears to parent than hearing, move in only one direction,” says Dr. Helpern. “Diffusion MRI scans work in essentially the same way. The movement “ y o u r c h i l d of the water molecules is affected by the microstructure of the tissue,” he explains. “With diffusion MRI, the brighter the has a brain image, the slower the water is moving, probably due to the presence of complex tissue microstructure. The darker the tumor.” image, the faster it’s moving, probably due But in fact, many brain tumors that to reduced microstructure.” d . develop in children are low-grade and Many MRI scanners at NYU have benign, and can be successfully removed if already been retrofitted with the the surgeon can get to them safely. Surgery technology needed to do DTI and a for tumors appearing on the surface of the related tool called diffusional kurtosis brain results in a 90% cure rate. When imaging (DKI), which was developed they arise deep in the brain, near the here at NYU. More effective surgical basal ganglia and thalamus, however, it’s techniques for pediatric brain tumors a different story. “Neurosurgeons have are just the beginning of what these traditionally had great trepidation about scans, which add only a few minutes DTI/DKI s c ans : mariana l a z ar , p h attacking these tumors surgically,” says to standard MRIs, can help to achieve. Jeffrey Wisoff, MD, associate professor of With these new, finely detailed images of neurosurgery and pediatrics, “for fear of the brain and its function, scientists are damaging vital structures, like those that gaining unprecedented insights into how control motor function.” conditions ranging from Alzheimer’s and Now, an advanced form of magnetic schizophrenia to brain tumors and stroke resonance imaging (MRI) called diffusion affect the human brain and other organs. tensor imaging, or DTI, is making it possible to excise these formerly scanning the brain and inoperable tumors by giving pediatric beyond in one intriguing f

neurosurgeons a way to fine-tune their application, radiologists at NYU, o

map of the motor pathways inside the including Matilde Inglese, MD, PhD, tion

brain and, using stereotactic surgical associate professor of radiology and c rese

navigation, plan a surgical route that neurology, and Robert Grossman, MD, in avoids these key regions. “When you dean and CEO of NYU Langone Medical superimpose DTI on top of stereotactic Center, are using DTI to study the earliest imaging, you get almost real-time phases of multiple sclerosis. “When imaging feedback,” explains Dr. Wisoff. you try to explain the accumulation of So far, his team has used this new disabling symptoms in a patient based tensor imaging technique to treat six children, Standard DTI (top) and a more detailed only on the volume of MRI-visible all successfully. Next, he plans to use DKI scan (bottom), shown against an lesions, the correlation is very poor,” sion artificial background. ffu DTI to help map surgical routes around says Dr. Inglese. In other words, a patient di f o

other important pathways, including with a lot of lesions on a standard MRI t r ics 4:495-505, 2009. u sed wit h permission e sensory and visual processing centers. Standard MRI cannot provide detailed scan might still have good neurological l ro l:

Ultimately, Dr. Wisoff hopes to apply DTI images of some of the smaller and most function, while another patient might a

to surgeries for malignant pediatric brain critical microstructures of the brain, such have only a few visible lesions yet be et l y,

tumors, such as gliomas. as neurons and their axons. For that, you totally disabled. With DTI, she explains, e “In adults, gliomas are almost need another key parameter: diffusion, a “we can detect and quantify microscopic h mos universally fatal,” he says. “But in term that refers to patterns of molecular injury in white and gray matter that in

children, you get about a 25% disease-free movement over time. Through a complex otherwise appear normal. It also lets us ed h

survival rate if you can achieve a near- mathematical formula, MRI scans can grade the severity of individual lesions on is ubl

total resection of the malignant glioma. be adapted to measure these diffusion the brain. Standard MRI imaging simply p ly Until now, though, we’ve been concerned patterns in a way that makes it possible to shows if there’s a lesion. With diffusion- s u io

about doing more harm than good getting map networks of microscopic structures weighted imaging, we can see that one v

there. DTI may allow us to attack these in human tissue. lesion might be repairing itself, while pre tumors more aggressively.” To understand how diffusion imaging another might have demyelination and is able to map these networks, says axonal loss.” mri: an image writ in water Joseph Helpern, PhD, professor of DTI’s uses extend beyond the brain, brain surgery is just one of the radiology, psychiatry, and physiology as well. Eric Sigmund, PhD, assistant ways that diffusion technology is helping and neuroscience, imagine you’re looking professor of radiology, and Dr. Helpern physicians to map and treat illness. It can in a swimming pool using special goggles are using diffusion imaging to paint a also be used to evaluate neural networks that let you see the movement of the “head to toe” picture of the function of for early signs of disease and to illuminate water molecules. multiple organs in the body. For example, other complex body structures. RY: pedi a t h a l ami c juv eni e pi o cy ti astro toma . JOURNAL OF n uro sURG E RY: “Looking through those goggles, you’d DTI contrast images can help provide IMAGES ON PAGES 22 AND 23 WERE

NYU Physician 24 spring 2010 and axons invariably form. For multiple sclerosis, that capability allows researchers to better assess damage to gray matter (an area once thought not to be involved in the disease), which may eventually help them identify early indicators of injury. Today, most D. treatments address only the inflammation caused by the disease, but there are treatments in the pipeline that could be neuroprotective—that is, stop the d . breakdown of neurons and axons in the gray matter—which would make such an early warning system invaluable. “We need a valid, sensitive marker to monitor a patient’s response to these treatments,” says Dr. Inglese, “and I believe DKI has the potential to provide this marker.” DKI may also advance the understanding and early diagnosis of 7-TES L A TRA C TOGRAP HY IMAGE: ERI SIGM U ND, P h DTI/DKI s c ans : mariana l a z ar , p h dementias. Dr. Helpern and Dr. Jensen Using NYU’s powerful 7-Tesla MRI scanner, a diffusion-based technique called are currently conducting an NIH-funded fiber tractography reveals the brain’s connectivity. study of 80 patients with mild cognitive impairment, a precursor to dementia, and a more complete understanding of the physiology and neuroscience, devised 80 age-matched controls. “We’ve been changes in the spinal cord that occur after DKI, which enables scientists to more getting better information about diffusion a traumatic injury, or during the course of fully characterize the complexity and properties with DKI,” says Dr. Jensen. spondylosis, degenerative arthritis of the functionality of the tortuous networks “Now, we’re trying to see if our data is joints between the spinal vertebrae. that microstructures such as neurons sensitive to things like changes in myelin “Surgeons who work on the spinal cord and axonal integrity. Our research is still need much more quantitative information Images of six test tubes containing sugar early, but results are encouraging.” f

o to help them make decisions such as DKI can also be applied to areas where

water. One test tube (F) also contains whether or not to decompress the spine,” puréed asparagus. Standard DTI (top) two microstructures cross, allowing tion c says Dr. Sigmund. “In a pilot study, can’t distinguish the test tube containing researchers to map the connectivity of

rese the asparagus, but DKI (bottom) clearly

we’re assessing whether or not diffusion the brain’s nerve fibers. This unique in information can help to predict the indicates the correct test tube. ability may help scientists studying success of surgery.” schizophrenia. “We plan to look closely Another diffusion imaging project at fiber tracts in areas of the brain that we imaging is focused on the motion and diffusion think involve executive function, which of water inside the blood vessels of is impaired in schizophrenia,” says tensor cancerous tumors. “We have tools to treat Mariana Lazar, PhD, assistant professor sion tumors, but those treatments don’t arrive of radiology. “Since these particular ffu di at the target because the tissue pressure fibers intersect with other major fiber f o t r ics 4:495-505, 2009. u sed wit h permission is so high or the vascularity so sluggish tracts, DTI can’t resolve them, but we e l inside the tumor that the drugs aren’t believe DKI and fiber tractography can.” ro l:

a delivered,” says Dr. Sigmund. “If we can Such connections, adds Dr. Lazar, may

et use a drug to address that problem first, also be important in the study of autism. l y, e then we could send in high-impact drugs “For autism, a large body of information h to kill the tumor.” suggests that brain connectivity is mos impaired. Using DKI, we hope to in

ed when fibers intersect reconstruct certain brain networks and h is as useful as it is, however, DTI see how connectivity is affected.” ubl p has its limitations. Its technology assumes For researchers involved in diffusion ly s that water diffuses in tissue according imaging, the future is exciting. “It’s no u io

v to a Gaussian process—basically, along longer just about anatomy, but about

pre a bell curve—as it does over a relatively anatomy, connectivity, and function,” straight axon segment, for example. But explains Daniel Sodickson, MD, PhD, there are many areas where the water associate professor of radiology, and diffusion doesn’t follow a Gaussian curve, physiology and neuroscience; vice chair for particularly where neurons or other research, Department of Radiology; and structures intersect, fork, or abruptly director, Center for Biomedical Imaging. change direction, as they frequently “Both kurtosis and diffusion tensor do. To measure both types of diffusion, imaging can contribute to an active Dr. Helpern and Jens Jensen, PhD, connectivity map and help to build a DTI/DKI TEST T UB E IMAGES: J ENS ENSEN, PhD AND OSEP H L PERN, PhD. RY: pedi a t h a l ami c juv eni e pi o cy ti astro toma . JOURNAL OF n uro sURG E RY: IMAGES ON PAGES 22 AND 23 WERE associate professor of radiology, and holistic picture of the human brain.” • NYU Physician spring 2010 25 Patient Story For the Terminally Ill, an Ancient Drug Offers a New Path to Spiritual Healing When Matt Meza learned that he had terminal cancer, the Grob, the trial’s principal investigator, devastating news brought to the surface some difficult personal inquiring about the study. Although Dr. issues—particularly his inability to accept help from those closest Grob’s study had no openings, he put Matt to him. “I’ve always been an independent person who’s drawn in touch with Stephen Ross, MD, assistant strength from overcoming adversity,” he says. “But those traits professor of psychiatry and oral medicine. don’t necessarily work when you have a terminal illness.” An expert on addiction, Dr. Ross is also the principal investigator in a similar clinical Matt found himself suffering from “and it mentioned a study at UCLA in trial being conducted at NYU School severe anxiety and was even considering which terminally ill cancer patients were of Medicine in collaboration with NYU assisted suicide when a solution came given psilocybin to help them to come to College of Dentistry. Knowing he had a from an unexpected direction. “I was spiritual terms with their illness.” watching a television documentary Matt, who is 49 and lives in Los Angeles, Stephen Ross, MD, in the room used for Wabout the war on drugs,” he recalls, placed a cross-town call to Dr. Charles psilocybin study.

NYU Physician photograph by 26 spring 2010 sasha nialla good friend in Manhattan with whom he that started meeting once a week. Once we needed, but other than checking vital could stay, Matt agreed to participate. heard about the other studies under way, signs frequently and assuring safety, our The clinical trial he found himself part we decided to attempt one ourselves.” goal isn’t to engage them. They’re doing of is unconventional, but also rooted in In relatively short order, the group more important work than anything we history. Psilocybin is a psychedelic drug secured funding from the Heffter Research might offer at that time.” found in hundreds of species of wild Institute and got approval from the FDA For Matt, the psilocybin session proved mushrooms around the world, which and NYU’s Institutional Review Board. In to be profound. “I knew very quickly that for centuries have been used as part of a nod to the project’s controversial nature, I’d received the real drug the first time,” he religious ceremonies and healing rituals the study is a model of caution. Each patient says. “I was being driven by the music and in Mexico, South America, and elsewhere. is supervised by a male-female therapist started seeing deities and spiritual shamans. In the 1950s, scientists began exploring team who themselves undergo additional A couple of hours into it, some Turkish the therapeutic potential of psilocybin and training, including a half-dozen intensive music was playing, and I literally saw other hallucinogens to treat the terminally sessions aimed at building trust and whirling dervishes. The faster they spun, ill, as well as those suffering from exploring their attitudes toward death and the deeper I fell into a trancelike state.” alcoholism and other addictive disorders. dying. “It’s essential the therapists present At a certain point, Matt’s defenses The results were encouraging, but the rising a unified presence,” explains Dr. Guss, who crumbled. He sobbed and asked to be use of recreational drugs during the 1960s directs the study’s training program. held by his therapists. “At that moment, spurred a political backlash that effectively Patients are carefully screened to rule he experienced a sense of transformation ended research for decades. “As therapies, out anyone with cardiovascular, liver, in his ability to feel supported and these drugs were basically erased from our and kidney disease or a personal or loved,” says Dr. Guss, who supervised collective memory,” says Dr. Ross. family history of schizophrenia or bipolar Matt’s sessions along with Julie Feuer, a It wasn’t until the early 1990s that the disorder. Anyone taking antidepressants is licensed clinical social worker. “That peak federal government began permitting excluded, as well. of intensity only lasted 10 minutes, but clinical studies involving the use of The experience with the study medicine the experience stood out vividly in the hallucinogens in human subjects. The itself actually consists of two sessions, integration sessions.” methodology of current scientific studies— seven weeks apart. In one, the patient is “It wasn’t like I was cured by the double-blind and placebo controlled—is given a synthetic version of psilocybin end of the session,” adds Matt. “The more rigorous than the prevailing manufactured in a government-approved real breakthroughs came during the standards of four decades ago, but the goals laboratory; in the other, a placebo. integration sessions, when I brought what remain essentially the same. “Psilocybin (Neither patient nor therapists are told happened that day into the real world. I’d has the potential to bring about what is which is which, although in practice, been burdened by a lot of sadness, and called a mystical, or peak, experience,” says the psilocybin session usually becomes while that’s not completely gone, I’m in Anthony Bossis, PhD, clinical assistant evident as the session unfolds.) A series a better place now. This has helped me professor of psychiatry and anesthesiology of psychotherapy sessions in the months resolve past issues about my parents and and the NYU study’s co-principal following the psilocybin experience siblings. Now, I can die unburdened by investigator. This deeply spiritual state are then used to integrate the insights the angst of my childhood.” has been found to inspire a sense of peace, triggered by the drug session. “It’s easy To date, Matt and two other subjects, fulfillment, and connection to others that to focus just on the psilocybin,” notes both women in their 70s, have completed can dramatically counter the fear and Dr. Ross, “but what we’re really doing is the study. The ultimate goal is to enlist 32 desolation felt by those nearing death. psilocybin-assisted psychotherapy.” subjects, which Dr. Ross acknowledges Such benefits were clearly observed in The dosing session lasts a full day and could take five years or more. the recently completed UCLA study, in takes place in a room where everything Matt continues to talk to his therapy which 12 terminally ill patients were given is designed to facilitate a mystical team by telephone on a weekly basis. As a psilocybin. In addition to establishing experience: A couch is made up with result of his therapy, he has agreed to move feasibility and safety, that study found sheets, quilt, and pillows, and bouquets in with a close friend and let his friend care significant reductions in cancer-related of flowers and bowls of fruit are placed for him. “Matt is saying his good-byes, but anxiety and depression. around the room. Patients are also paradoxically, he’s more attached than he’s It was this UCLA study and a similar encouraged to bring in family photos ever been,” says Dr. Guss. study at Johns Hopkins, the only other and other objects of importance. The “This has been a gift to me,” says Matt. psilocybin trials currently approved by psilocybin or placebo is administered “I feel honored and humbled to know the the Food and Drug Administration (FDA) 40 minutes into the session, and the group at NYU. I know they’re doing this and the Drug Enforcement Agency, that patient is then encouraged to lie down out of a true feeling that they can help inspired Dr. Ross, Dr. Bossis, Jeffrey and put on eyeshades and headphones, many more people in the future. They’re Guss, MD, clinical assistant professor which, like the room’s speakers, play wonderful people, and I love them all.” • of psychiatry, and their colleagues to a six-hour tape of instrumental music, —royce flippin undertake their own investigation. painstakingly assembled with the help of “Back in 2006, Dr. Bossis, Dr. Guss, and ethnomusicologists. Note: Matt Meza passed away on March I realized we all had a common interest “As therapists, we sit very close to the 27, 2010, as this article was being written. in the potential value of hallucinogenic patient,” says Dr. Bossis, a psychologist For more information and details regarding this study, drugs as therapeutic agents,” says Dr. who specializes in palliative care. “We’re please call Krystallia Kalliontzi, MSc, clinical research Ross. “So we formed an educational group there to offer support and guidance as coordinator, at 212-998-9252.

NYU Physician spring 2010 27 Alumni Profile Creating a New Image of Addiction It’s not often that a scientist opens an entirely new Among other things, this would make avenue of investigation, but Nora Volkow, MD, (Res ’84,) has psychotherapy more effective for addicts done just that in the field of addiction research. As a psychiatric in the early stages of recovery. resident at NYU School of Medicine—where she arrived in 1981 after graduating first in her medical school class at the National How can you integrate this new knowledge with University of Mexico—Dr. Volkow was drawn to the emerging brain imaging? technology of positron emission tomography (PET), which lets Using functional MRI [fMRI] scans researchers image the brain’s metabolic processes. She went on to [which measure changes in the brain’s pioneer the use of brain imaging as a tool for studying the effects blood flow], we’ve also found that of drug addiction, and she is the author maladaptive learning is central to addiction. of more than 380 peer-reviewed articles actions, and controlling emotion-driven This conditioning effect is what drives on the subject. In recognition of her actions—including drug cravings. There’s people to desire one specific drug and accomplishments, Time magazine named currently great interest in interventions to not another. A key challenge now is to her one of the world’s 100 most influential improve prefrontal cortex function, either integrate our knowledge of addiction’s people in 2007. through medication or cognitive therapy. biochemistry, gained through PET From 1987 through 2003, Dr. Volkow worked at the Brookhaven National Nora Volkow, MD Laboratories, conducting research and also serving as associate director for life sciences, director of nuclear medicine, and director of the Regional Neuroimaging Center, funded by the National Institute on Drug Abuse (NIDA) and the U.S. Department of Energy. In 2003, Dr. IVolkow (who is the great-granddaughter of Russian revolutionary Leon Trotsky) was named director of NIDA. There, she oversees an annual budget of over $1 billion, including some $600 million in research grants, while continuing to pursue her own work. NYU Physician spoke with Dr. Volkow recently about addiction research.

As you and others build on the research you’ve pioneered, it’s becoming clear that addiction affects the brain in complex ways. How is this realization influencing the search for treatments? The first areas to suffer functional disruption from addiction lie deep inside the brain, in an area of the limbic system [structures associated with memory and emotion] called the striatum. That’s where drugs of abuse trigger exaggerated levels of dopamine that are related to the euphoria sought by users. With time, however, these repeated bursts of abnormally high dopamine levels trigger a cascade of dysfunction elsewhere in the brain. One of these secondary areas lies in the prefrontal cortex, which is critical for strategic planning, pondering the consequences of our

28 “An addicted person’s brain is less able to inhibit the desire for drugs—but the brain can be retrained.” scans, with information from fMRI. By treatments will soon be available? hope to fund in-depth analyses of these understanding how the brain’s learning Yes, I am. Brain research is already genes, as well. On a related topic, there are circuits are involved in addiction, we opening new treatment opportunities that also multiple clinical trials under way of may be able to harness the same learning were unimaginable just a few years ago. a cocaine vaccine, which should produce processes to weaken, erase, or write over Advances in understanding the different results in two to three years. those deleterious conditioned associations. brain circuits involved in addiction will This would probably involve behavioral help us expand our medication targets Your work has helped redefine drug addiction as retraining or therapy, potentially and improve our behavioral treatments a disease rather than a moral failing. Is there any augmented by pharmacological or other by devising approaches that correct room for free will in drug addiction? modalities. For example, D-cycloserine very specific aspects of disrupted brain Ultimately, as with any disease, it’s the [an antibiotic developed originally to function. These include neurofeedback, responsibility of the person who has treat tuberculosis] has shown promise which holds great promise for retraining the disorder to seek help. But many in promoting the extinction of specific the brain, behavioral therapy, and factors in addiction lie outside free will, phobias. Similar strategies might help cybertherapy [the use of virtual including our genes and our childhood override conditioned cue effects that environments] to counter detrimental environments. Approximately 50% of trigger cravings in drug users. conditioning effects and strengthen brain vulnerability to addiction is genetically circuits involved in new learning and determined. Another major risk factor is Are researchers using other types of imaging behavioral inhibition. stress early in life, particularly exposure technology in addition to PET and fMRI scans? to drugs—including nicotine—during fetal Yes. Near infrared spectroscopy, for How is epidemiological research contributing to development. Epidemiological studies also example, is an optical technique that this effort? show that if a person experiences five or measures brain oxygenation by shining One exciting development involves the more childhood adverse events—defined infrared light through the skull. combination of massive genetic and as physical or sexual abuse, neglect, or Magnetoencephalography [MEG] is imaging databases, which will produce living in a household with an absent another extremely sensitive imaging detailed and multidimensional maps parent or a parent who is mentally ill or technique that measures the magnetic of individual variability. A new field incarcerated—that person has 10 times the fields produced by the brain’s electrical of research is also sprouting around addiction risk of someone without those activity. MEG can also be used as a our ability to measure the function and experiences. complement to the emerging field of activity of the brain at rest, when it’s not neurofeedback, in which subjects learn engaged in a specific task. This research is So how does someone at risk for addiction to modulate activity in specific regions providing a population baseline against combat these odds? of their brains by getting pictorial which we can investigate the functional We’re all faced daily with the pull representations of the fMRI activity impact of a host of mental disorders, between desiring something and deciding in those areas fed back to them in real including addiction. cognitively whether or not to go after it. time. Though not yet demonstrated for An addicted person’s brain is less able addiction, this technique has shown At NIDA, you’ve made nicotine addiction a to inhibit the desire for drugs, so in that promising results for altering the top priority. Are there new treatments on the respect, addiction really robs us of free perception of pain in some healthy adults horizon for smokers? will. But as I’ve noted, the brain can be and chronic pain patients. It doesn’t work We just awarded a $10 million grant for a retrained. Our lab recently published equally well for everyone, but for some Phase III trial of a nicotine vaccine that’s a paper showing that if recovering people, the training lets them voluntarily shown promising results. These kinds cocaine addicts are told they are going dial brain activity up or down, in concert of vaccines are designed to stimulate to be exposed to drug stimuli and then with a targeted behavior or perception, production of antibodies that bind to the instructed to try and control their such as pain. drug while it’s still in the bloodstream, reaction, they can actually inhibit the In addition, ongoing new developments blocking its entry into the brain and addiction-related brain circuits from in MRI technology are letting us preventing any psychoactive effect. If firing. I was surprised—I didn’t think look in unprecedented detail at the successful, this strategy would be an they’d be able to do it. This gives us insight microstructure of gray or white matter invaluable addition to a comprehensive into how an addicted person might be and the functional connectivity between treatment approach, by reducing the prepared to deal with an environment that different brain regions. All of these chances of relapse. We’ve also identified triggers their craving. Although we can technologies are providing new insights a number of genes that encode for inform addicted people during treatment into how addiction affects the brain. nicotine receptors, three of which appear about the importance of changing their particularly linked to nicotine addiction, environment, many will end up in their Given these many promising research areas, so we’ve asked for proposals to develop original surroundings. In reality, where are you optimistic that effective addiction medications targeting these receptors. We else can they go? • —royce flippin photograph by NYU Physician aaron clamage spring 2010 29 Faculty News

5. 3. 4. 2. 1.

International on may 3, in stockholm, sweden, Robert Faculty and I. Grossman, MD, Dean and CEO, received Alumni Inducted Recognition the gold medal of the International Society for Magnetic Resonance in Medicine “for into Alpha for Our Dean major research contributions to the field of Omega Alpha Magnetic Resonance,” the highest honor in joining the ranks of nyu school and Ceo its field. The society is a scientific association of Medicine legends Jonas Salk, with a membership of over 6,000 clinicians, Albert Sabin, and Frank Netter, as physicists, engineers, biochemists, and technologists. well as Nobel Prize-winners Severo Ochoa Dr. Grossman is well known for his work as a neuroradiologist in developing imaging and Otto Loewi, five alumni and faculty techniques that have led to important new insights into multiple sclerosis (for which members were admitted the Delta Chapter he received the prestigious Javits Neuroscience Investigator Award by the National of Alpha Omega Alpha in ceremonies this Institutes of Health) and other diseases of the brain. Prior to becoming Dean and CEO past March. 1 the Druckenmiller of NYU Langone Medical Center in 2007, he had served as chairman of the Department Neal Lewin , MD, Clinical Professor of Emergency Medicine, of Radiology here since 2001. A widely published researcher, au- received the AOA Outstanding Clinical thor, and mentor to over 100 fellows, he continues to be an active Faculty Award for exceptional contribu- investigator of NIH-funded studies. tions to the clinical training and education The University of Pennsylvania School of Medicine will honor of medical students. Dr. Lewin is director of Dean Grossman with its Distinguished Graduate Award, given didactic education, Emergency Medicine to “highly accomplished alumni for their outstanding service to Residency Program, at NYU Langone and society and to the profession of medicine.” The award, the highest Bellevue Hospital Center. honor given by the school to its alumni, will be presented to Dean Iman Osman2, MD, and Harvey Pass3, m d, Grossman May 14. Prior to joining NYU Langone, Dr. Grossman were honored as faculty inductees into AOA. Dr. Osman, associate professor of had been a member of the faculty at the Hospital of the University dermatology and urology, was elected of Pennsylvania, where he had been professor of radiology, neu- to AOA for her leadership in translational rosurgery, and neurology; chief of neuroradiology; and associate research. She joined the School’s faculty in chairman of Radiology. 2000 as director of the Interdisciplinary Mela- On June 4, the University of Bordeaux in France, is scheduled to award Dean Gross- noma Cooperative Group and translational man an honorary doctorate. The University of Bordeaux, founded under King Henry VI research leader of the melanoma program. of England in 1441, is renowned for its excellence in science and technology. Dr. Pass, professor of cardiothoracic • surgery and surgery, chief of the Division of Thoracic Surgery, and director of thoracic oncology at NYU Cancer Institute, joined the School in 2005. He is currently vice chairman for research in the Department of Cardio- thoracic Surgery and director of surgical NYU Confers Distinguished research in the Department of Surgery. He Teaching Award was elected to membership in AOA for his research in lung cancer and mesothelioma, on Dr. david zagzag and for his many peer-reviewed articles. Alumni inductees into the Delta Chapter twice named Teacher of the Year by the School of Medicine in 2006 and 2008, David of AOA were Burton Rose4, MD (’67), and Zagzag, MD, associate professor of pathology and neurosurgery, was recently Fritz Francois5, MD, MS (’97). Dr. Rose, named a recipient of New York University’s Distinguished Teaching Award. clinical professor of medicine at Harvard The prestigious honor is given annually to faculty members who have demonstrated their Medical School, was recognized for his work excellence as educators over a sustained period of time and who have contributed sig- as an educator and author of textbooks on nificantly to the intellectual life of the University through their teaching. A special University renal physiology and physiopathology. In committee made up of faculty, students, alumni, and administrators selects the winners. 1989 he founded and became editor-in- Dr. Zagzag came to NYU Langone in 1988 as an anatomic pathology resident and chief of the Web-based clinical research completed a fellowship in neuropathology. Today tool UpToDate, one of the most respected he is considered a “triple threat”—an NIH-funded clinical information resources for physicians, investigator, a nationally and internationally recog- students and patients. nized clinician, and an award-winning educator. Dr. Francois, assistant professor of Describing his teaching approach, Dr. Zagzag medicine and assistant dean for academic stresses that a pathologist must consider the patient affairs and diversity at the School of as a whole, not just as information on a histologi- Medicine, was chosen for induction be- cal slide. “This kind of emphasis encourages the cause of his stature as a superior teacher, medical students to think like doctors,” he said. He physician, investigator and administrator. considers teaching a major focus of his professional Most recently, he led the team of NYULMC career and thinks that developing students’ minds to HEART physicians and nurses who joined in analyze, process, and apply information is the true the relief efforts following the earthquake measure of a successful teacher. • in Haiti. • Photogra p h of dr. zagzag by john abbott 30 Alumni News

Solomon A. Berson Medical Achievement Awards for 2010 At Medical Alumni Reunion Day, April 10, 2010, five physician alumni were recognized for achievement in their fields, and a distinguished trustee who is Congressional Gold Medal presented by one of the most generous and farseeing benefactors of President Ronald Reagan to Elie Wiesel. our institution was named an honorary alumna. Julia Zelmanovich Young Alumni Award Award in Basic Science Award in Health Science lisa j. kalik, md (’04), is a Peter Lipsky, md (’69), has E. Albert Reece, MD (’78), general internist in NYU Internal Medicine served as director of the intramural PhD, is vice president for medical Associates faculty group practice and research program at the National Institute affairs, the John Z. and Akiko K. Bowers a clinical instructor in medicine at the of Arthritis and Musculoskeletal and Distinguished Professor, and dean of School of Medicine. An Alpha Omega Skin Diseases and founder and chief of the school of medicine at the University Alpha graduate, Dr. Kalik’s commitment the Autoimmunity Branch at the National of Maryland in Baltimore. He also to provide medical care worldwide is Institutes of Health. His major research concurrently holds professorships extraordinary. She has served with Doctors interests are related to the immune basis of in the Departments of Obstetrics and without Borders in Africa and worked autoimmune and inflammatory diseases, Gynecology, Medicine, and Biochemistry with the Flagstaff International Relief and he is recognized internationally for his and Molecular Biology. In addition to Effort in Ulaan Bataar, Mongolia, among work on T cell–macrophage interactions, his administrative responsibilities, Dr. many other activities. Dr. Kalik also has the mechanisms of immune cell activation, Reece is actively involved in research participated in the primary care clinic of and the role of T cell and B cell subsets in and education; his research focuses on Odyssey House, an enhanced therapeutic autoimmune disease, as well as for his role diabetes in pregnancy, birth defects, and community serving individuals with in the development of novel therapeutics prenatal diagnosis. The author of 11 books, substance abuse. In addition, she has for rheumatoid arthritis. An author of 5 monographs, and over 450 articles, provided outpatient care to students, at more than 600 peer-reviewed articles, chapters, and abstracts, Dr. Reece is a NYU’s Student Health Service. Dr. Lipsky has trained more than 140 member of the Institute of Medicine of postdoctoral fellows and students, many of the National Academy of Sciences, and he Honorary Alumna whom have gone on to serve in leadership serves on many governmental and civic in the Class of 2010 roles in rheumatology and immunology. organizations and committees. helen l. kimmel has served as a trustee for more than 25 years and Award in Clinical Science Medicine in the is a life trustee of New York University. Steven Shak, md (’77), is director Humanities Award Through their great generosity, she and of the Genomic Health Laboratory for mark h. podwal, md (’7o), her late husband, Martin S. Kimmel, New York State, and co-founder and chief is clinical associate professor of have given wings to many of our most medical officer of Genomic Health, Inc. dermatology at NYU and also serves gifted scientists, making possible the He also serves on the board of directors of as adjunct professor at NYU’s College Center for Biology and Medicine and the the Cystic Fibrosis Foundation. Among of Arts and Science, where he teaches a Center for Stem Cell Biology, as well as his many accomplishments, Dr. Shak freshman seminar in art history. He may professorships of molecular immunology, has directed worldwide clinical trials be best known for his distinctive drawings pathology, microbiology, and just recently, demonstrating the efficacy of the anti- published by the The New York Times on advanced cardiovascular therapeutics. HER2 antibody in breast cancer; cloned its op-ed page over the past four decades. Last year, a transformational gift from the human DNase I gene, the basis for a An author and illustrator of numerous Mrs. Kimmel and her late husband made treatment for cystic fibrosis; and initiated books, including Doctored Drawings, Freud’s possible the new Helen L. and Martin S. clinical development of the angiogenesis da Vinci, and Jerusalem Sky, he won a Silver Kimmel Pavilion at NYU Langone Medical inhibitor Avastin. A member of Phi Beta Medal from the Society of Illustrators for Center, which is scheduled for completion Kappa and Alpha Omega Alpha, Dr. Shak King Solomon and His Magic Ring, written in 2017. Her passionate engagement has has received many honors and awards, in collaboration with Elie Wiesel, and a helped shape organizations as diverse including the Howard Waters Doughty National Jewish Book Award for Ever You as the American Friends of the Israel Prize in Chemistry, the Valentine Mott Know, with Francine Prose. Dr. Podwal’s Museum, the Metropolitan Opera, and Award in Anatomy and Cell Biology, the artistry has been employed in an array the Washington Square campus of NYU, Prix Gallien from Portugal for discovery of projects, including the design of and she has an unswerving commitment of Pulmozyme, and NYU’s Biotechnology decorative plates for the Metropolitan to learning, discovery, and bettering the Award. Museum of Art and an engraving on a human condition. •

NYU Physician spring 2010 31 Obituaries

michael l. freedman, md, founding director of the Division of Geriatrics at Dr. Michael NYU Langone Medical Center and pioneer in the field of geriatrics, died at his Freedman home in Scarsdale, N.Y., on February 16. He was 73 years old. An Alpha Omega Alpha graduate of Tufts University School of Medicine, Dr. Freedman served as a faculty member, scientist and clinician at NYU since 1963. Originally trained as a hematologist, Dr. Freedman was instrumental in spearheading the creation of the Division of Geriatrics at NYU in 1979. He was named the Diane and Arthur Belfer Professor of Medicine in 1988 and served as director of the Diane and Arthur Belfer Geriatric Center until his retirement in 2008. A devoted educator, Dr. Freedman was chief of the Linda Laubenstein Firm for teaching third-year medical students at NYU School of Medicine. To honor his lasting achievements in the field of geriatrics, NYU Langone launched a campaign to raise $7.5 million for the creation of the Michael L. Freedman Center for Geriatric Research and the establishment of an eponymous endowed professorship in geriatric research, under the leadership of Christina Seix Dow and Robert Dow. Based on his illustrious career, the Michael L. Freedman Professorship in Geriatric Medicine has been established and endowed, and the Michael Freedman Center for Geriatric Research has been initiated in his honor, said Martin Blaser, MD, chairman of the Department of Medicine. “One of his biggest contributions was as an educator,” said Dr. Blaser. “Many of the practitioners and leaders in the field of geriatrics came through the program under Dr. Freedman. He was universally respected and admired as a teacher, as a clinician, and as a person.” Dr. Freedman is survived by his wife, Cora; his son, Lawrence Freedman; his daughter, Deborah, and son-in-law, Steven Schapiro, and his granddaughters, Allison, Sophie, and Talia. •

department’s educational activities. broadly referenced to this day in the dr. joseph Attending Grand Rounds lectures and medical literature. dancis morbidity and mortality conferences, Dr. Dancis is survived by his daughter, he continued to impart his special Dale Dancis, of New York City; his son, Joseph Dancis, MD, chairman brand of knowledge, which reflected Dr. Andrew Dancis, of Philadelphia; and of the Department of Pediatrics an unwavering dedication to excellent three grandchildren. at NYU School of Medicine from patient care and relevant, meaningful • 1974 to 1989, died Tuesday, March 30. He resident and fellow education. In his was 94. honor, the department’s annual Dancis Dr. Dancis received a bachelor’s degree Day is dedicated to presentation of from Columbia College in 1934 and gradu- resident, fellow and young faculty ated from St. Louis University School research. Dr. Dancis’ generous support of of Medicine in 1938. He completed his the Department of Pediatrics will long be residency training at Bellevue Hospital remembered. and subsequently pursued research train- Dr. Dancis’ influence extended far ing in protein and nucleic acid chemistry beyond the School of Medicine. He wrote at NYU and Sloane-Kettering. Dr. Dancis scores of peer-reviewed papers and was joined the NYU faculty in 1947 and, in an expert on inherited metabolic diseases 1962, was promoted to professor. and the physiology of the placenta. As chair, Dr. Dancis was known for In 1983, he was elected president of his commitment to academic excellence. the American Pediatric Society and He emphasized that progress in basic subsequently, in 1986, received its highest investigation had important implications honor, the Howland Award, recognizing for the department’s daily clinical and a career of accomplishment in academic educational activities. After retiring pediatrics. His prodigious works in the as chairman, he remained active in the field of inborn errors of metabolism are

NYU Physician 32 spring 2010

You, too, can make a difference at NYU Langone. To learn more, about how to create your own legacy and become a member of The John Revere Society, please contact Marilyn Van Houten at 212.404.3653 or email her directly at [email protected]. The Gift of a Lifetime

elping others is life’s driving force for HEugene Kalnitsky, MD,’54, a retired physician and air force officer, and his wife, Linda, a former teacher and coordinator of volunteers for local Florida charities. Eugene completed his medical degree and residency in internal medicine at NYU School of Medicine. He was especially affected by his classes with Samuel Standard, MD, who opened Eugene’s eyes to the value of patient- centered care.

Linda Kalnitsky and Eugene Kalnitsky, MD, `54

With the compassion they have shown throughout their lives, and in gratitude for Eugene’s medical education, Eugene and Linda made the gift of a lifetime through a charitable annuity. Legacies like theirs help transform the future of medicine.

You, too, can make a difference at NYU Langone. To learn more about how to create your own legacy, please contact Marilyn Van Houten at 212.404.3656 or email her at [email protected]. 1RQSURÀW2UJ 863RVWDJH 3$,' Office of Communications and Public Affairs 3HUPLW1R 550 First Avenue, New York, NY 10016 1HZ