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“It’s Not Fair!”

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Americans cherish their ideals of fairness. And American children can be especially strident advocates for equality. Anyone who has ever painstakingly cut and distributed a child’s birthday cake knows how closely those little eyes watch for injustice. And when they see it, especially in their ever-so-slightly-smaller slice, they protest with the anguished cry: “No fair!”

How does this sense of fairness emerge in children? Is it innate or learned? And does it vary across cultures, or do American values represent the norm? Peter Blake, a College of Arts & Sciences assistant professor of psychological and brain sciences and director of BU’s Child Development Labs, has spent a decade studying these questions. His latest research, a collaboration with psychology researcher Katherine McAuliffe, tested an unprecedented 866 pairs of children across seven diverse societies to examine how ideas of fairness emerge, finding surprising similarities among children in Canada, the United States, and Uganda. The research, funded by the Templeton Foundation, was published in the November 18, 2015, issue of Nature.

Human norms of fairness, cooperation, and altruism have puzzled scientists since Darwin’s day and remain vital to our understanding of human evolution. “If you really want to understand humans, you need to understand cooperation,” says Felix Warneken, a Harvard associate professor of psychology and coauthor on the Nature paper. “We can’t survive on our individual abilities; so much of what we do depends on cooperation.”

In their earlier research, Blake and McAuliffe, who will join the faculty of Boston College in January 2016, tried to establish when children acquire concepts of fairness. “It wasn’t obvious that we’re just born with a sense of fairness, but everyone seems to have one,” says Blake. “How do these different senses of fairness emerge? And do they have a common foundation or origin?”

To examine these questions, the scientists built a toy they call the “inequity apparatus,” or—less forbiddingly—the Skittle-ator. It’s a two-foot-long wooden plank with two small, raised trays near the center. Two children sit on either side, facing each other, as the scientists place Skittles on the trays. In front of one child are two handles, one red and one green. If the child pulls the green handle, the trays tip toward each child and dump Skittles into bowls where they can keep them. But if the kid pulls the red handle, the Skittles slide into a bowl in the center, where neither child can keep them.

In general, when the scientists offer a young child, about age four or five, a “good deal”—she gets four Skittles and the other child gets one—she pulls the green handle and happily takes the four Skittles. But when the scientists offer a “bad deal”—she gets one and the other kid gets four—most kids pull the red handle and walk away empty-handed. It seems like pure spite—if you get more, I don’t want any—and the scientists say that’s part of it. But there may be more going on: giving up one Skittle is a sacrifice, but it prevents another kid (“the competition”) from gaining a relative advantage. By pulling the red handle, a child also signals that she won’t be cheated or exploited, even for a tasty sugar hit. “Kids are willing to pay the price to prevent the bad deal,” says Blake. “And it just becomes stronger with age.”

But a funny thing happens around age eight—kids begin rejecting the “good deal,” too, refusing to take four Skittles when the other child gets only one. “At age eight, we saw this sudden shift,” says Blake. “And when we asked the children why, they would say, ‘It’s not fair.’” Not fair, that is, to the other kid.

Peter Blake's inequity apparatus—also known as the Skittle-ator

The inequity apparatus—also known as the Skittle-ator—tests kids’ sense of fairness. Green handle: both kids get Skittles; red handle: no deal. Photo by Cydney Scott

To double-check these results, the scientists offered children equal allocations of Skittles—I get one, you get one—in what might be called “a good deal for everybody.” Children accepted this offer at all ages.

“It’s a really good test of a child’s sense of fairness,” says Warneken of the Skittle-ator. “The game tests not just what people say, but what they actually do.”

The study design built on McAuliffe’s previous work with cotton-top tamarins. “Tests from animal studies are very intuitive—you can’t use language or written instructions with monkeys—so the tests also work well with children,” says McAuliffe. The tamarins, it turns out, gobbled Froot Loops at any opportunity, whether the handouts were fair or not. Human children were far more discerning.

These early studies got the scientists thinking. If this trait—refusing a deal that’s unfair to others—appears only around age eight, only in humans, and goes against economic models of rationality, something bigger than biology must be at work. “This seems like a behavior that is shaped by culture,” says Blake.

But the scientists had only tested children in the United States—actually, only in public parks in and around Boston. Would the results hold across cultures? It’s a question that many researchers are asking more often, especially after an influential 2010 paper in Behavioral and Brain Sciences noted that behavioral scientists conduct most of their research on subjects from Western, educated, industrialized, rich, and democratic (WEIRD) societies.

“Most of what we know about psychology comes from studying university undergrads in Western countries,” says McAuliffe. “But is the developmental trajectory in the United States the same across cultures? What is the true sense of human fairness?”

To test that question, the scientists teamed up with researchers who had ongoing projects in other countries, trained them on the inequity apparatus, and asked them to include the experiment in their repertoire. Over four years, the collaborators tested a total of 866 pairs of children in Canada, India, Mexico, Peru, Senegal, Uganda, and the United States. (While some scientists used different local candies or cookies in the test, others stuck with Skittles if they could find them in local stores. “Skittles have surprising penetration into the global market,” notes Blake.)

The scientists suspected that children from all cultures would reject the bad deal (I-get-one-you-get-four), and that turned out to be the case. However, children tested in Mexico rejected the bad deal at a much later age, around 10 instead of 4. Blake isn’t sure why this happened, but the Mexican children were from small villages and most knew each other, so he suspects that this personal dynamic might have reduced competition.

The big surprise came with the good deal. The scientists had speculated that children in Canada, like those in the United States, would reject the good deal around age eight, because of common cultural norms. But they weren’t sure how children in non-Western societies would react. “Will older kids reject that good deal everywhere? We predicted that no, that probably is not going to happen,” says Blake. “We found that it showed up in the United States and Canada, but it also showed up in Uganda, which kind of threw us.”

Among all the countries tested, only Canada, the United Sates, and Uganda showed this common trend. The scientists have a few possible explanations for the surprising find. The area of Uganda tested is rural and agrarian—very different from urban United States and Canada—but many schools in the area show a heavy Western influence. Perhaps Western-trained teachers transmitted cultural norms of fairness to their students. Or, says Blake, children in other countries might see this type of fairness as a valuable trait, but one that applies only to adults. “Or it’s possible that there’s a completely different reason,” says Blake. “Maybe kids in the United States will reject the good deal for one reason, and in Uganda they do it for another. We don’t know.”

The study is “really just a first pass,” says McAuliffe, which opens up many questions and avenues for further research. The scientists want to go both broader, studying more societies, and deeper, learning more about each group’s culture. “Right now, we have a good measurement of behavior, but no in-depth understanding of cultural patterns, socialization, or anthropology,” says Warneken. The scientists also note that they tested children only up to age 15 and want to test adults at various stages of life—probably with a prize other than Skittles.

The work contributes to a larger area of research examining both the short- and long-term effects of scarcity and inequity on things from IQ scores to self-confidence.

“We put kids in a situation where they’re either receiving less than a peer or more. That’s kind of what children are born into, right? They’re born into a circumstance where they have less or more than others,” says Blake. “There are bigger questions there, about when kids really become aware of this and whether it affects the rest of their lives.”

Barbara Moran can be reached at bmoran@bu.edu.

A version of this article was originally published in BU Research.

 


The Cocktail Party Problem

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Alan Wong first noticed the problem a few years ago. In a crowded bar or restaurant, he could barely understand his companion’s conversation. The 35-year-old Wong blames the problem on a well-spent youth: “I went to a lot of loud concerts in my 20s, and now my hearing sucks,” says Wong (COM’02), executive producer at BU Productions. “It’s a bummer, especially when I have a hard time hearing the lady friends.”

Scientists call it the “cocktail party problem,” and it’s familiar to many people, even those who pass standard hearing tests with flying colors: they can easily hear one-on-one conversation in a quiet room, but a crowded restaurant becomes an overwhelming auditory jungle. For people with even slight hearing problems, the situation can be stressful and frustrating. For those with significant hearing loss, hearing aids, or cochlear implants, cocktail parties become an unnavigable sea of babble.

“It can really affect communication,” says Gerald Kidd, a Sargent College professor of speech, language, and hearing sciences. “It causes people to avoid those kinds of places, either because they don’t want to work that hard or it’s just unpleasant to be in a situation where they’re not following things. So it’s a big problem.”

Kidd and colleague Jayaganesh Swaminathan, a SAR research assistant professor of speech, language, and hearing sciences, study the cocktail party problem, trying to understand exactly why this particular situation is difficult for so many people. Their research, funded by the National Institutes of Health and the Air Force Office of Scientific Research, and published in Scientific Reports in June 2015, asked an intriguing question: can musicians—trained to listen selectively to instruments in an ensemble and shift their attention from one instrument to another—better understand speech in a crowded social setting?

“Music places huge demands on certain mechanisms in the brain, and at some levels, these overlap with language mechanisms” says paper coauthor Aniruddh Patel, a Tufts University professor of psychology, who studies the cognitive neuroscience of music and language. “The question is: would a high level of musical training advance speech and language as well?” In other words, can musical training help fix the cocktail party problem?

At first, the answer seems obvious: of course musicians, either through training or talent, would be more skilled at focusing on one specific human voice amid competing voices. How could they not be? But it’s a difficult skill to test. A 2009 Northwestern University study found that trained musicians were slightly better at identifying speech amid “masker” signals such as white noise. But the results had limitations. After all, white noise is just loud and boring; but competing voices may sound similar to your companion, and may even be saying something more interesting.

“Everybody realizes that the coffee grinder in a coffee shop creates all this noise and racket that you want to avoid,” says Kidd. But the cocktail party problem is more subtle and complicated. “When you communicate in a room full of people,” he says, “the noise is not just loud, it’s also interesting, and competes with the information that you’re trying to process.”

The scientists hypothesized that a musician, trained to listen selectively to one particular source, in competition with other interesting and informative sources, ought to be able to translate that training into a multiple-talker cocktail-party situation. Swaminathan designed an experiment to test it.

He found 12 musicians (the criteria: at least 10 years of musical training, and actively practicing three to five times a week) and 12 nonmusicians. Each subject sat in front of a computer wearing headphones, listened to multiple masking voices coming from different directions, and had to pick out the “target voice” coming from straight ahead. “It was like walking into a crowded room, with people all around you,” says Swaminathan. As expected, the musicians performed better than nonmusicians, able to pick out the target voice from the maskers even when the target signal was five to six decibels softer.

But then Swaminathan tried something different: playing the masking voices backward so they were unintelligible. “It sounded like a foreign language,” he says. “A rough analog I use is an American walking into an American bar, versus a bar in Germany.” In this case, musicians and nonmusicians performed about the same. “It was a really beautiful manipulation,” says Patel. To the scientists, this finding was key, indicating that the musicians’ enhanced ability lay not in the signal their ears picked up, but rather in how their brains process that signal. It isn’t that musicians have better hearing, Patel says, “but they have the ability to laser-beam focus on one stream of sound among others.”

The scientists don’t know if musicians are born with this enhanced ability or gain it through training. “That’s the million-dollar question,” says Kidd. “The whole issue of causality and correlation—is it innate or is it learned?—is an open question.” There’s also the question of whether the cognitive gains musicians experience may be outweighed by the hearing loss many of them suffer. All these bear further research, the scientists say, because what we learn from musicians may benefit society as a whole.

“What is the particular mix of cognitive and sensory abilities that make musicians so much better at this?” asks Patel. “Hopefully, understanding this will help us design training or devices than can directly help people with hearing loss.”

A version of this article originally appeared on BU Research.

What Rapid Eye Movement Reveals

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Michele Rucci wants to look deep into your eyes. And when he does, he sees something amazing in those windows to your soul: they’re jittering around like popcorn kernels in a hot air popper. A disconcerting image? Perhaps. But Rucci, a College of Arts & Science professor of psychology and director of BU’s Active Perception Laboratory, has found that these coordinated microscopic jitters allow us to see fine spatial detail like letters on a page.

Rucci’s research, published in a recent edition of  Current Biology, reveals that problems with visual acuity may actually stem from inaccurate motor control of your eyes, head, and neck—not damage to the eye. His research may eventually lead to a clearer understanding of vision disorders.

BU Today spoke to Rucci about his vision of vision and why movements so tiny may have impacts so large.

BU Today: What questions does your lab want to answer about vision and why are they  not known yet?

Rucci: The main question is: how is it that some light gets in our retina, activates retinal receptors, and gets transformed into what we see? We recognize a face; we recognize objects. But all we have to start are neural responses signaling light characteristics at individual points in the scene. How do we put them together? It’s the basic mechanics of vision, but it’s a really hard question.

Photoreceptors in the retina fire neurons and the signals go to the brain?

Right—we are such visual creatures that we don’t even realize that there is a question there. It seems so effortless. You open your eyes and you see. So you wonder, what is the question? But how does our brain transform individual pixels into an image of, say, a dog? How do you know that these points go together into the same object and these others belong to another object? How are we able to interpret this?

That’s a big question. How did people first start thinking that head movements, eye movements, and micromovements of the eye fit into the picture?

First the question was: Why is it so hard to replicate human capabilities in machines? What are we missing? And it’s been really a struggle. One aspect that is clearly missing is the behavior of the observer: our eyes are constantly active, always moving. And that movement actually helps us extract the information.

I’ll give you an example. Let’s just consider the scene in front of me. If I look at one point and I move a little bit, that gives me information of three-dimensionality, what we call parallax. So already behavior is introducing new cues, new pieces of information. We have this idea that we don’t need motion to see. But if in the laboratory we remove every kind of motion, a procedure known as retinal stabilization, the image will literally fade away.

That’s weird.

We’re not aware of it, but that’s how it is. We reconstruct a scene by moving our eyes around.

We unconsciously focus on different points to construct an image?

Exactly. Your eyes jump from one point to the next. You make these very rapid eye movements, called saccades, which separate brief periods of fixation in which you grasp information. But the term fixation is inaccurate: small eye movements incessantly occur, even during these periods.

What does saccade mean?

I think it comes from the way horses move their heads. It’s the French word for “jerk.”

And how rapid are saccades?

They’re very, very fast. We stop at each point for like 200 to 300 milliseconds, and then we very rapidly jump to another point. So, three times a second, we move our eyes. It’s jumping, jumping, jumping, jumping. And the eyes continually jitter even in the periods in between saccades. We can’t stop our eyes: incessant eye movements occur even when we attempt to maintain a steady gaze on a single point. We call the movements microscopic because they’re very difficult to record, but they’re actually very large compared to the size of individual receptors on the retina.

Is it just your eyeball moving or your whole head or both?

Well, it’s the eyes, but as you’re trying to keep your head fixed, you’re actually also making very small head movements. So the two things combine together to create a lot of retinal motion.

It would seem like it would ruin your vision, all this movement.

Exactly. So the first question is: why don’t you see the world blurred? It actually gets more interesting.

What do the micromovements do, these little jitters?

The standard idea is that they help refresh the image by preventing neural adaptation. To me, it always seemed a sort of superficial level of explanation. The interesting question is: how do they actually help you see? And they’re revealing a lot. In 2007, we discovered that this jitter contributes to vision of fine spatial detail, and in 2010, that some of these movements, known as microsaccades, are very precisely controlled. It’s amazing, the level of control that we have on these eye movements. They are reshaping the stimulus on the retina in a very interesting way.

So it was a surprising discovery that we had that level of control over it?

Yes. So microsaccades are controlled, and now in this latest paper, we are finding out that drift is also controlled—that’s the jittery motion that is there all the time.

Do the head and eyes move the same way or move differently, but in conjunction somehow?

What we have found in this last study is that the head and the eyes move together even at this microscopic scale. So you’re not aware of making very small head movements, but the eye will partially but not completely compensate for the movement of the head. It’s as if the amount of motion on the retina is designed to be at a fixed level.

And coordinating everything like that allows you to see a coherent image?

Well, it allows you to start extracting information. One important point is: how do you know where edges of objects are? How do you start extracting this information? The processing of edges is believed to occur up in the cortex. It’s a complicated operation. It requires a few steps. But everything we know is based on assumptions that are very static, which are implicit to the way vision is traditionally studied in the laboratory.

What is starting to emerge is that these small eye movements reformat the input to the retina; they transform it into something that is spatial-temporal. This transformation turns out to be tuned to the characteristics of the natural world and starts a very important function, which is the function of extracting useful information—including edges.

Are there specific visual disorders or diseases that mess this up?

Usually these very small movements are not considered, because they are so difficult to record. They are known to exist, they are known to be important, but in most vision science they are thrown under the carpet, because how do we deal with them? In fact, they’re even regarded as a nuisance because you can’t control them. So most of what we know about vision comes from experiments in which we take an image, we flash it; most neurophysiological data come from experiments with paralyzed animals. So we know practically nothing about how these small movements vary in different pathological conditions. It’s a completely unknown world out there.

What this research is leading to is the possibility that visual acuity is not just a visual phenomenon; it’s really a visual-motor achievement. If you don’t make microsaccades that are precise, if you don’t control your eye jitter, or drift, you’re not going to be able to thread a needle well. So you need to have that level of control. Now, if you cannot thread the needle, is that because your visual acuity went bad or because you’re now controlling your eye movements less accurately? The second part is not even considered so far.

Is that what you’re thinking about for your next line of research?

Yes, exactly. That’s how we are evolving.

A version of this article was originally published in BU Research.

CTE Investigators Launch $16 Million Study

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Tim Fox, the 62-year-old former New England Patriots safety, was describing to a room full of brain scientists at the Boston University School of Medicine (MED) the ferocious style of play that he’d been trained in from an early age, one that had led to countless head injuries during his 20-year college and pro career. “We were taught to use your head to tackle,” he said. “It was to be used as a weapon.”

Fox, who also played for the Los Angeles Rams and the San Diego Chargers, recalled two occasions as a Patriot when he was knocked unconscious, revived, and sent back on the field, where he was knocked unconscious again. “The doctor would come over and ask you, ‘What’s your birthday, what’s your phone number,’” he said. “Your buddy would be sitting next to you, he’d whisper in your ear, give you the answer, you give the answer to the doctor, and you’re back in the game.”

Some 50 scientists—from MED and School of Public Health (SPH), the Cleveland Clinic, the Banner Alzheimer’s Institute, the Mayo Clinic, Brigham and Women’s Hospital, and other major institutions around the country—gathered on the medical campus Wednesday to launch their landmark, seven-year, $16 million National Institutes of Health (NIH) and National Institute of Neurological Disorders and Stroke (NINDS)–funded study aimed at diagnosing CTE, a degenerative brain disease, during life. CTE, which is associated with repetitive brain trauma and characterized by changes in behavior, mood, and cognition—including the development of dementia—can currently be diagnosed only by postmortem examination of the brain. It has been found in professional football players, boxers, and other athletes with a history of repetitive brain injuries.

Robert Stern, the clinical core director of BU’s Alzheimer’s Disease & Chronic Traumatic Encephalopathy (CTE) Center, who is leading the study, introduced Fox at the meeting.

“I’d like to do anything in my power to help you folks get to the bottom of this,” Fox told the scientists. He said he has significant cognitive impairments—memory problems, difficulty with organizational tasks, severe mood changes—that he believes are clear symptoms of CTE. He said that he’d gotten lost driving to the meeting on the Medical Campus—“and I’ve lived here for 25 years.” As for his mood, he said, “my irritability factor has gone through the roof.”

The symptoms Fox described have been identified in people who were found, after death, to have had CTE. Does Fox have CTE? “We don’t know,” Stern said. And that, he said, is the point of the study: To develop ways of diagnosing CTE during life as well as to examine risk factors—repetitive hits to the head and genetics, among other things.

“We have to figure out why some people get this disease and some don’t,” Stern said.

He and his colleagues will study 240 people: 120 former NFL players (with and without CTE symptoms), 60 former college football players (with and without CTE symptoms), and 60 control subjects who have never played contact sports or experienced any type of brain trauma. Researchers will examine the participants at MED and three other centers: the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, the Mayo Clinic in Scottsdale, Ariz., and the New York University Langone Medical Center in New York City. In addition to extensive clinical examinations, participants will undergo positron emission tomography (PET) imaging, MRI scans, blood work, and other tests with the potential to detect changes in the brain associated with CTE. Data will be shared with researchers worldwide.

Eric Reiman, executive director, Banner Alzheimer’s Institute; Martha Shenton, director, Psychiatry Neuroimaging Laboratory and senior scientist, Brigham and Women’s Hospital; Robert Stern, clinical core director of BU’s Alzheimer’s Disease and Chronic Traumatic Encephalopathy (CTE) Center; and Jeffrey Cummings, director, Cleveland Clinic Lou Ruvo Center for Brain Health

Robert Stern, a MED professor and clinical core director of BU’s Alzheimer’s Disease Center and CTE Center, second from right, with his three co-principal investigators on the study, left to right: Eric Reiman, executive director, Banner Alzheimer’s Institute; Martha Shenton, director, Psychiatry Neuroimaging Laboratory and senior scientist, Brigham and Women’s Hospital; and Jeffrey Cummings, director, Cleveland Clinic Lou Ruvo Center for Brain Health.

Stern is one of four principal investigators on the study. The others, whom he introduced yesterday, are Martha Shenton, director of the Psychiatry Neuroimaging Laboratory and senior scientist at Brigham and Women’s Hospital; Jeffrey Cummings, director of the Cleveland Clinic Lou Ruvo Center for Brain Health; and Eric Reiman, executive director of the Banner Alzheimer’s Institute. Stern and others at the meeting emphasized the sweeping, multidisciplinary, multi-institution, collaborative nature of the research they are about to embark upon together. “We hear about this often as ‘the Stern study,’” Stern told his colleagues. “I can’t stand that, and I’ve been trying to do everything possible to undo that.”

Cummings, who is a physician, talked about the importance of early diagnosis. “How can we inform athletes, soldiers, other people involved in repetitive brain injury, about their future?” he said. However, he added: “This is not just about diagnosis. Eventually, this has to be about prevention and treatment.”

Cummings also sounded a cautionary note. “This is a very newsworthy study,” he said. “As representatives of the study, we all need to make sure we accurately represent what the study is and what it isn’t. This is not epidemiology. This is a convenient sample of people we’re able to recruit for the study. We cannot extrapolate from what we see to the entire population. The scientific process is key. This is about open, transparent interrogation. It’s about asking questions, finding answers, trying to set all our pre-inclinations aside.”

“This is funded by the public in order to help the public,” he added. “We want to protect athletes’ brain health and I believe everyone involved in athletics wants that. There is no advantage in having an athlete who is beaten up and can’t sustain a high level of performance. We want to protect against the effects of head injury wherever it occurs. We’re concerned about soldiers, traffic accidents, domestic abuse. This is a set of lessons that will have wide implications in society.”

Ann McKee, Boston University professor of neurology and pathology during the Annual Investigator Meeting

Ann McKee, a MED professor of neurology and pathology, is director of BU’s CTE Center and has been studying the brains of people found to have CTE for more than eight years.

Stern noted that the new study will build on the groundbreaking work of MED professor of neurology and pathology Ann McKee, director of the CTE Center and associate director of BU’s Alzheimer’s Disease Center (ADC), who first identified the telltale mark of CTE—tiny tangles of a protein called tau, clustered around blood vessels—in the dissected brain of a boxer who had been diagnosed with Alzheimer’s disease.

McKee, who oversees the ADC Neuropathology Core’s Brain Bank and has studied the brains of more than 200 people found to have CTE, gave the group an overview of her eight years of research into CTE. “We know this is a very biased sample,” she said. “You can’t take anything from these numbers in an absolute sense. But if this were a rare disease, there’s no way we could be this successful at brain collection. I couldn’t just go out and say, ‘I’m going to look at some strange, unusual disease and collect 200 cases in seven years.’ What this says is that this disease is much more common than we thought. Your study is going to show that.”

She showed a montage of the faces of dozens of athletes who have been found to have CTE over the years. “This is a study about people,” she said. “We do this because we are speaking for those people who can’t speak for themselves any longer. We tell their stories because people need to know.”

A Congressional investigation found last week that top NFL health officials had improperly pressured the NIH to remove Stern, who has been critical of the NFL, from the study. When the NIH refused, the NFL backed out of a signed agreement to pay for the study, according to the investigation by the House Committee on Energy and Commerce. Stern has declined to comment, saying he prefers to focus on the important science.

Sara Rimer can be reached at srimer@bu.edu.

Genetic Risk for Stroke

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Each year, stroke kills nearly 129,000 Americans, according to the American Stroke Association. It is the fifth leading cause of death in the United States and the top neurological cause of death and disability.

Scientists have associated a number of genes with a higher risk of stroke, especially—and predictably—genes involved with atherosclerosis and blood clotting. But they know little about the genes’ biological mechanisms—how they actually work in the body and lead to stroke.

A study published in April 2016 in Lancet Neurology takes the link between genes and stroke one step further. The study not only identifies a gene called FOXF2 that is associated with stroke, but it also offers preliminary evidence on how the gene may cause stroke: by affecting pericytes, a type of cell on the walls of small arteries and capillaries. This insight is important, because pericyte damage is suspected to play a major role in Alzheimer’s disease as well.

“It’s exciting because this finding is important for both stroke and dementia, the two major neurological scourges of mankind,” says senior author Sudha Seshadri, a School of Medicine professor of neurology, whose work is funded by the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Aging, and the National Heart, Lung, and Blood Institute. “These results have given us a lot of interesting stuff to look at.”

“Stroke is really a major public health issue,” says study corresponding author Stéphanie Debette, a MED adjunct associate professor of neurology and also a University of Bordeaux professor of epidemiology and neurology. “The known risk factors only explain a limited portion of the disease. It’s important to unravel novel risk factors and mechanisms.”

Three School of Public Health scientists were coauthors on the paper: Alexa Beiser (GRS’85) and Anita DeStefano, both SPH professors of biostatistics, and Seung-Hoan Choi (GRS’16).

Seshadri says that scientists have discovered relatively few genes associated with stroke, as compared to other common diseases, and most have been the obvious contenders, affecting things like cardiac function and fat deposits. Hoping to find some novel biology, Seshadri says, she and colleagues at the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, where she leads the neurology working group, combined data from 18 previously published studies on stroke. They then analyzed the nearly 90,000 pooled cases—including about 4,300 stroke victims—using a technique called genome-wide association, which compares the genomes of stroke victims against those of healthy people and looks for significant genetic differences.

A spider-shaped pericyte, seen here in light blue, encircles a capillary, helping maintain the blood-brain barrier

A spider-shaped pericyte, seen here in light blue, encircles a capillary, helping maintain the blood-brain barrier. The gene FOXF2 seems to affect pericytes, leading to small vessel disease. Image courtesy of XVIVO Scientific Animation

The analysis pointed to several interesting genes, including one called FOXF2. Seshadri, Debette, and colleagues also looked for—and found—evidence of FOXF2 malfunction in another large patient database through collaboration with the NINDS-funded Stroke Genetics Network, which contains more than 70,000 people, including 19,000 stroke victims.

“This was a surprising find,” says Debette. “This was not a gene we had thought of; it was not known as a risk factor for people with stroke.” FOXF2 has several functions. During fetal development, it helps build the blood-brain barrier, which separates circulating blood from cerebrospinal fluid, protecting the brain from neurotoxins. In adults, FOXF2 is also present in pericytes enveloping the small blood vessels that feed the brain. Scientists don’t fully understand the pericytes’ role, but know that they help maintain the blood-brain barrier.

The team decided to follow the trail further. Coincidentally, Seshadri and Debette had begun to collaborate with other scientists studying FOXF2 equivalents in mice and zebrafish bred to have no copy, or a nonfunctioning copy, of the gene. Talking to these other scientists, they learned that both mice and fish developed small vessel disease, a condition in which the lining of small arteries and capillaries is damaged and the vessels become more porous. This discovery also matched up with reports of rare cases of small vessel disease in children, related to malfunctioning FOXF2. Although small vessel disease is an important cause of stroke, responsible for 20 to 30 percent of cases, scientists had not known about any genetic risk factors for common forms of the disease, and there is currently no treatment. “We know a lot about preventing and treating heart disease and atherosclerosis,” says Seshadri, “but not much about preventing or treating small vessel disease.”

Also, Debette adds, small vessel disease had been implicated in the tiny, silent strokes that contribute to a gradual decline in balance, memory, and cognition in many older people. The next research steps, she says, are detailed genetic sequencing to discern which variations of FOXF2 lead to the disease and more animal studies to refine these results.

“If we can better understand the biology of small vessel disease, maybe we’ll find drug targets that could ultimately lead to treatments,” says Debette. “If we could find a way to prevent the disease, it could have a major public health impact.”

A version of this article was originally published in BU Research.

The Right Memory at the Right Time

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You’ve got a plan to pick up groceries for dinner on the way home. Right now, though, you’re in your office, coffee in hand. A co-worker drops by asking what materials are needed for an upcoming meeting.

Your answer, most likely, isn’t “carrots.” That’s because the human brain contains circuitry that retrieves memories appropriate for the current situation.

New work from the lab of Howard Eichenbaum, Boston University William Fairfield Warren Distinguished Professor and director of BU’s Center for Memory & Brain, suggests that this circuitry spans long distances in the brain and supports a complex dialog between two brain structures. The work, published online in June in Nature Neuroscience, is among the first to describe the operations of a large brain circuit that controls complex behavior. By revealing the details of the communications between brain regions to access appropriate memories, the findings may give clinical researchers clues about which communication channels may be impaired in brain disorders that disrupt memory.

“Understanding this system has implications for almost any disorder that affects memory, from schizophrenia, depression, and epilepsy to traumatic brain injury and post-traumatic stress disorder,” says Charan Ranganath, a neuroscientist at the University of California, Davis, who studies human memory but was not involved in this research. “We’re really interested in understanding the ability to use knowledge to make decisions.”

Foraging for Froot Loops

To study a complex human behavior, such as remembering appropriate information at the right time, Eichenbaum had to train rats to memorize an important piece of information and then find a way for them to use it. So his team trained rats to find Froot Loops in flowerpots. “Rats are absolutely nuts about Froot Loops,” he says.

For example, the rats learned that in room A the cereal is hidden in a pot filled with purple plastic beads that smell sweet. But in room B, the goods are in the pot filled with black paper shreds that smell spicy. “Rats are great with odors and textures, so we’re using textural and olfactory cues to direct them to express their memory,” says Eichenbaum.

As the rats navigate from room to room, Eichenbaum’s team records their brain activity using electrodes inserted into the brain. They monitor both the hippocampus, known to be the seat of memory in the brain, and the prefrontal cortex, thought to be a coordinator.

diagram showing flow of memory information in a rat brain

The circuitry that guides the selection of memories based on the current context spans the rat brain. Information flows from the ventral hippocampus (vHPC), in the lower part of the brain, to the prefrontal cortex (mPFC), and then back to the dorsal hippocampus (dHPC), near the top of the brain. Breakdowns in the circuitry can cause different types of memory problems, including loss of memory and also the inability to determine which memories are appropriate for the current situation. Diagram courtesy of Howard Eichenbaum

In previous studies, the team had already learned that neurons in the prefrontal cortex fire in relation to cues that signal rewards, such as a particular pot that contains a stash of Froot Loops. They had also identified neurons in a region called the ventral hippocampus that recognize the room the rat is in. Neurons in the dorsal hippocampus fire when the rat recognizes a flowerpot it has seen before. In this most recent experiment, they learned how the brain puts these pieces of information together to guide a decision, like which pot to dig in.

For instance, when the rat enters room A, the ventral hippocampus transmits to the prefrontal cortex, setting the context to room A. The dorsal hippocampus begins firing as it recognizes flowerpots. The prefrontal cortex, which knows that the reward in room A is in the pot with purple beads, sends this information to the dorsal hippocampus, telling it which memory to act on. “The two regions operate together as a system, kind of like handshaking,” says Eichenbaum. “We’re seeing at the level of neurons what happens in cognitive life.”

Memory with Purpose

This handshaking is important because many things can go wrong to interrupt it. When Eichenbaum’s team temporarily disabled the prefrontal cortex, the rats foraged in every pot, not because they don’t recognize the pots but because they don’t know which pot contains a reward based on the room they are in. “The prefrontal cortex has a very specific role,” says Eichenbaum. “It doesn’t activate the right memories, but rather it prevents the wrong memories from intruding.”

This finding may be relevant to human diseases like schizophrenia. People with this disorder don’t have trouble remembering things but often have trouble filtering out irrelevant or inappropriate information. “If the hippocampus remembers something, it’s the sound of one hand clapping,” says Ranganath. “It doesn’t help you unless it reaches areas that can use the information to make a decision or action.”

There is no direct anatomical connection in the brain between the prefrontal cortex and dorsal hippocampus, so it isn’t clear how messages are passed between them. But Eichenbaum’s studies suggest that there may be an indirect, bidirectional route that involves slow, pulsing brain rhythms called theta rhythms. These rhythms originate in deep structures in the middle of the brain, synchronize between the hippocampus and the prefrontal cortex, and allow information to flow between them.

To explore this possibility, Eichenbaum is using optogenetics, a powerful tool that allows researchers to configure specific neurons in the brains of rats so that they can be turned on or off using laser light. “We hope to trace the whole pathway of the circuit that is crucial to this dialog,” says Eichenbaum.

Theta rhythms are an important clue for researchers like Ranganath, too. “We’ve got to study theta activity in the human brain now that we think it’s related to your ability to remember the things you need to remember when you need to remember them,” he says.

A version of this article originally appeared on BU Research.

Alzheimer’s Start-up Gets $1.49 Million from NIH

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Carmela Abraham came home one day three years ago from her BU lab, where she has been researching Alzheimer’s disease for nearly three decades, and told her husband, a retired entrepreneur, that she wanted to start a company.

“I said to Menachem, ‘I believe we have the scientific seed for something that can be developed into a drug for Alzheimer’s,’” she says. “It was becoming increasingly challenging to get federal academic research grants, and I told him maybe it would be easier to fund this project as part of a start-up.”

Menachem, who has cofounded and helped build three successful technology companies in Boston since the mid-1980s, volunteered to handle the business part of the project. “Immediately, he got very excited,” says Carmela, a School of Medicine professor of biochemistry and of pharmacology and experimental therapeutics. “He loves start-ups.”

So, in 2015, the Abrahams founded Klogene Therapeutics, Inc., with Carmela’s medicinal chemistry collaborator Kevin Hodgetts, director of the Harvard Medical School–affiliated Laboratory for Drug Discovery in Neurodegeneration (LDDN) at Brigham and Women’s Hospital. Klogene, which will develop novel therapeutics for Alzheimer’s disease, grew out of Carmela’s work on Klotho, a large, multifunctional protein produced in the kidneys and brain that circulates in the blood and cerebral spinal fluid and may protect against Alzheimer’s and other neurodegenerative diseases. In a collaboration that spanned years, Abraham, Hodgetts, and their team, MED senior research scientist Ella Zeldich, CiDi Chen, a MED research assistant professor of biochemistry, and LDDN instructor Xiao Wang, have developed novel small molecule compounds that boost Klotho levels in the brain. This intellectual property is being licensed from BU by Klogene and is the initial basis for its drug development program.

In May 2016, the company won a $1.49 million Small Business Innovation Research grant from the National Institute on Aging of the National Institutes of Health (NIH). “I dedicated the last 36 years of my career to Alzheimer’s disease research, and I do not intend to stop until we have a treatment or a cure,” Carmela says. “I am more optimistic than ever that we will succeed.”

Carmela Abraham with lab assistants in her lab at Boston University School of Medicine

Abraham (center), with the team in her MED lab, has been researching Alzheimer’s disease for 36 years and has pledged that she will not stop until there is a treatment or cure. Photo by Cydney Scott

Abraham and Hodgetts act as consultants to Klogene, while Menachem is working full-time as the company’s unpaid CEO. Their new partnership is the latest chapter in the Abrahams’ 47-year marriage, one that brings together her distinguished career as a scientist and passion for research with his business acumen in pursuit of a way to treat, or prevent, Alzheimer’s disease.

They met half a century ago, in high school in Israel, after their families both emigrated from Romania. Their parents belonged to the wave of Eastern European Jews who survived the Holocaust and resettled in Israel and were investing all their hopes in their children and their futures as college-educated professionals.

Carmela and Menachem were classmates in a rigorous four-year program, affiliated with Tel Aviv University, that combined the last two years of high school with two additional years of demanding college-level training in chemical or electrical engineering. The aim was to produce 20-year-old graduates with the technical and scientific know-how to help build a still-developing Israel into a powerhouse.

“As immigrants,” recalls Menachem, “your idea is to get a profession so you don’t depend on your parents, who are struggling.”

“It was a very exciting time,” says Carmela, who fell in love with chemistry (and toward the end of the program, with Menachem), graduating with an associate’s degree in chemical engineering. “I’m a very molecular person,” she says. “I try to understand everything at that level.” Menachem earned an associate’s degree in electrical engineering.

After she and Menachem were married in 1969, she earned a bachelor’s degree in biology at Tel Aviv University and gave birth to their son and daughter, all while taking care of her elderly father, whose heart was failing (her mother, who had been ill for years, died when she was 18). Menachem, meanwhile, served a four-year term in the Israeli Army and was then deployed in a tank brigade to Egypt and the Sinai Peninsula during the 1973 Yom Kippur War.

After the war, she became a research assistant in immunology and physiology labs at the Technion-Israel Institute of Technology while he pursued bachelor’s and master’s degrees in electrical engineering there.

In 1980, the young couple and their two children made their first trip to the United States, a monthlong cross-country vacation. During the trip, Menachem was offered a job in Boston with the fast-growing Digital Equipment Corporation. Later that year, Carmela landed a position as a research assistant in the lab of Dennis Selkoe, a Harvard Medical School professor of neurologic diseases and a pioneer in the study of a disease she had never heard of—Alzheimer’s. In 1982, Selkoe and his colleagues broke new ground when they developed a method to isolate and describe the abnormal plaques and tangles from the brains of Alzheimer’s patients.

Carmela eventually went to graduate school, earning a PhD in neuroscience at Harvard Medical School in 1989. BU recruited her as an assistant professor, with her own lab, and she began her own work on Alzheimer’s and other neurodegenerative diseases. “In 1980, I can say almost nothing was known about Alzheimer’s,” says Carmela, whose research has been supported by the NIH and the Alzheimer’s Drug Discovery Foundation. “Over the years I saw everything unfolding in front of my own eyes—all the discoveries. I kind of grew with it.”

Her team at BU was the first to publish research, in the journal Glia in 2008, showing that Klotho levels are lower in the aged brain. Several years later, in a Biochemistry Journal study, Carmela suggested that small molecules that cross the blood-brain barrier and enhance Klotho protein have the potential to become novel therapeutics for age-related and other neurodegenerative diseases by protecting neurons against damage caused by abnormal protein aggregates, such as the clumps of amyloid protein in Alzheimer’s disease. In subsequent Cell Reports and Journal of Neuroscience studies, she and her collaborators showed that increased levels of Klotho are associated with improved cognition in humans and mice.

A few years ago, Menachem raised the possibility of his wife’s retirement. Perhaps they could go back to Israel, where their daughter, son-in-law, and three grandchildren moved six years ago. But Carmela didn’t want to retire. With all the advances in Alzheimer’s research, and the rapidly increasing numbers of people with the disease, her work felt even more compelling and urgent.

“Drug development takes a long time,” she says. “If everything goes perfectly with our project at Klogene, we may be able to start clinical trials three years from now.”

“I realized she had no intention to retire—ever,” says Menachem. “She told me she couldn’t imagine not going to the lab every day. She loves what she does. I’m okay with it. I’m busy helping her now, and I am having a blast. All these years, I’ve been following her work very closely, and I wanted to learn. It’s a lot more challenging than computers and electronics, and at this point, it’s more important that we make a difference.”

A version of this article originally appeared on BU Research.

NSF Funds State-of-the-art MRI Scanner

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Boston University researchers are getting a fundamental tool for studying the brain. The National Science Foundation (NSF) has awarded BU $1.6 million for a state-of-the-art Siemens 3 Tesla Magnetic Resonance Imaging (MRI) scanner, which will be the centerpiece of the new Center for Cognitive Neuroimaging at BU.

Chantal Stern, a College of Arts & Sciences professor of psychological and brain sciences, the principal investigator on the NSF grant, will be the director of the imaging center, which will be housed in BU’s Center for Integrated Life Sciences & Engineering (CILSE), scheduled to open in spring 2017. CILSE is intended to foster multidisciplinary, collaborative work among researchers from neuroscience, engineering, biological design, computational and computer science, and other fields across the University’s schools and colleges.

“This award signals recognition by our peers and the NSF not only of the quality of our faculty and the work they are doing,” says Gloria Waters, vice president and associate provost for research, “but also that our vision of bringing together interdisciplinary teams—with the Center for Integrated Life Sciences & Engineering as the hub—will allow us to address the grand challenge of understanding the brain in unique ways.”

The scanner will be used to advance research in BU laboratories focusing on the mechanisms and networks that support memory, attention, visual and auditory perception, navigation, and decision-making in the human brain. It will also be used by faculty who are pursuing basic research in human auditory neuroscience, speech production, and communications.

Until the new center opens, BU researchers will continue to use neuroimaging machines at other institutions around the city, says Stern, currently director of BU’s Cognitive Neuroimaging Laboratory. “This award and the development of an imaging center will bring state-of-the-art imaging equipment to the Charles River Campus,” she says, “and that’s going to have a major impact on our ability to build collaborative teams that not only include these neuroimaging investigators who have been doing their scanning at other institutions, but allow them to interact more collaboratively with engineering and computational and computer science faculty. It will also allow us to more effectively train students here.” Stern, who also directs BU’s Graduate Program in Brain, Behavior, and Cognition and is a member of BU’s Graduate Program for Neuroscience, says she and her colleagues in cognitive and systems neuroscience are committed to training the next generation of scientists, especially those from underrepresented groups in STEM fields, and that the new scanner will help them broaden their efforts in this area.

The Siemens 3 Tesla Magnetic Resonance Imaging scanner

The Siemens 3 Tesla Magnetic Resonance Imaging scanner will be housed within the new Center for Integrated Life Sciences & Engineering building, on BU’s Charles River Campus. Photo courtesy of Siemens Healthineers

In addition to housing the new Center for Cognitive Neuroimaging, CILSE will be home to the Center for Systems Neuroscience, the Center for Memory & Brain, the Biological Design Center, and the Center for Sensory Communication & Neuroengineering Technology. In awarding the grant for the MRI scanner, the NSF noted BU’s strong commitment to strengthening basic cognitive and systems-level neuroscience research as well as the close ties among its life sciences and engineering faculty. The University has made significant investments in neuroscience by recruiting new junior faculty, including a number of faculty who primarily use neuroimaging research methods. These junior faculty include Jason Bohland (GRS’07), a Sargent College of Health & Rehabilitation Sciences assistant professor of health sciences and of speech, language, and hearing sciences; Tyler Perrachione, a SAR assistant professor of speech, language, and hearing sciences; Sam Ling and Joseph McGuire, both CAS assistant professors of psychological and brain sciences; and Karin Schon (GRS’05), a School of Medicine assistant professor of anatomy and neurobiology.

One of the shared goals of the Center for Systems Neuroscience and the Center for Cognitive Neuroimaging is to better understand how different regions and networks of the brain interact and communicate with one another and how these brain systems relate to cognition and behavior. Reaching this goal will require multidisciplinary collaboration among scientists using cutting-edge experimental research methodologies, Stern says, including advanced neuroimaging technology and other computational tools. BU neuroimaging faculty, she adds, have developed strong collaborations that bridge the gap between animal, computational, and human research. In her proposal to the NSF, Stern noted that the new MRI scanner and its placement within CILSE “will foster neuroscience research that does not adhere to the traditional human-animal divide, allowing the development of models that link the understanding of neural circuits to cognition and behavior.”


BU-Led Neuroscientists Get $7.5 Million from US Navy

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Learning new rules is a part of life. The rules may be simple, like stopping at a red light. Or they might be a bit more complex. Sometimes, for instance, you can turn right at a red light, unless there’s a sign saying you can’t, but only in certain states, and not when a pedestrian is crossing the street. Most human brains learn complex rules like these, and their myriad exceptions, with seeming ease. But how they do this has puzzled neuroscientists for decades.

“So much of human behavior is guided by rules,” says Michael Hasselmo, a College of Arts & Sciences professor of psychological and brain sciences and director of BU’s Center for Systems Neuroscience. “But how do brain circuits mediate learning rules of different types? To me, this is a central question of brain research.”

Hasselmo is the principal investigator on a five-year, $7.5 million Office of Naval Research (ONR) grant to investigate, broadly, the question of exactly how human brains learn rules, and how this might be translated into computer programs, especially for autonomous systems. “If we understand this, it could massively enhance the capability of computers,” he says.

The grant was awarded as part of the ONR’s Multidisciplinary University Research Initiative program, or MURI, which supports team research involving more than one traditional scientific discipline, according to the Department of Defense. Most of the program’s efforts involve researchers from multiple academic institutions and academic departments. Hasselmo will oversee a team that includes Marc Howard and Chantal Stern, both CAS professors of psychological and brain sciences, as well as researchers from Brown University and the Massachusetts Institute of Technology. The award provides $4.5 million over the first three years, with the option to renew for an additional two years.

“One of the most exciting things about the MURI awards is the opportunity to work with exceptionally talented researchers across different universities,” according to Stern. “For the current MURI, I am excited to be collaborating with MIT researcher Earl Miller and Brown University researcher David Badre.”

The research will focus on two areas of the brain associated with learning: the prefontal cortex, known to be critical for working memory and for gating (the process by which the channel in a cell membrane opens or closes) memories in and out of the rest of the cerebral cortex, and the basal ganglia, which most people associate with movement and motor function. The scientists will investigate how the basal ganglia perform the mental action of loading working memories into the correct part of the brain, Hasselmo says.

He will oversee the development of computational models of neural circuits used in learning, while Badre and Stern will use functional magnetic resonance imaging (fMRI) to study the brain in humans as they learn. Badre will examine how the brain learns tasks using rules involving matching of letters and symbols; Stern will study how people learn new rules and changes in rules by trial and error. Stern will use BU’s newly acquired MRI scanner, the centerpiece of a new Center for Cognitive Neuroimaging, to be housed in BU’s Center for Integrated Life Sciences & Engineering (CILSE). The center is scheduled to open in spring 2017.

Stern notes that the National Science Foundation award for the MRI system arrived the same week as the MURI award notice, “which was a great start to the academic year,” she says.

For Hasselmo, the MURI award, coupled with the new neuroimaging facilities, will help open new windows onto the deepest mysteries of the brain. “To me, it’s just fascinating to try to figure this out,” he says. “Neurons are single cells with no individual cognitive ability, yet their interactions underlie every single action we take, every single belief we have. It’s fascinating to investigate how it comes together.”

The Dyslexia Paradox

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It’s there, at the start of every conversation: the moment it takes your brain to adjust to an unfamiliar voice. It lasts for only a second or two, but in that brief time, your brain is thumbing its radio dial, tuning in to the unique pitch, rhythm, accent, and vowel sounds of a new voice. Once it is dialed in, the conversation can take off.

This process is called rapid neural adaptation, and it happens constantly. New voices, sounds, sights, feelings, tastes, and smells all trigger this brain response. It is so effortless that we are rarely even aware it’s happening. But, according to new work from Tyler Perrachione, a Sargent College of Health & Rehabilitation Sciences assistant professor of speech, language, and hearing sciences, and colleagues at the Massachusetts Institute of Technology and Massachusetts General Hospital, problems with neural adaptation may be at the root of dyslexia, a reading impairment that affects millions of Americans, including an estimated one in 5 to one in 20 schoolchildren. Their experiments, published December 21, 2016, in the journal Neuron, are the first to use brain imaging to compare neural adaptation in the brains of people with dyslexia and those who read normally. The research was supported by the Lawrence Ellison Foundation, the National Institutes of Health, and the National Science Foundation.

In the team’s first experiment, volunteers without dyslexia were asked to pair spoken words with images on a screen while the researchers used functional magnetic resonance imaging (fMRI) to track their brain activity. The subjects tried the test two different ways. In one version, they listened to words spoken by a variety of different voices. In the second version, they heard the words all spoken by the same voice. As the researchers expected, the fMRI revealed an initial spike of activity in the brain’s language network at the start of both tests. But during the first test, the brain continued revving with each new word and voice. When the voice stayed the same in the second test, the brain did not have to work as hard. It adapted.

But when subjects with dyslexia took the same tests, their brain activity never eased off. Like a radio that can’t hold a frequency, the brain did not adapt to the consistent voice and had to process it fresh every time, as if it were new. The difference was even clearer in dyslexic children between ages six and nine, who were just learning to read; in a similar experiment, their brains didn’t adapt at all to repeated words.

fMRI images show how people with dyslexia (right) and people without (left) adapt differently to a speaker’s voice

These fMRI images show how people with dyslexia (right) and people without (left) adapt differently to a speaker’s voice. The colored regions show adaptation, or the change in brain activation upon hearing a voice for the first time, and hearing it repeatedly. The average of nondyslexic brains shows stronger adaptation than the average of dyslexic brains. Courtesy of Tyler Perrachione

Perrachione and his colleagues wondered if the adaptation glitch was unique to spoken words, or if people with dyslexia would have trouble adapting to other kinds of stimuli, too. So they tried a second set of experiments, showing subjects a repeating series of words, pictures, or faces, again using fMRI to look for the decline in brain activity that signals neural adaptation. Again, they found that the brains of people with dyslexia did not adapt—or did not adapt as well—as those without. “We found the signature everywhere we looked,” says Perrachione.

The results suggest that dyslexic brains have to work harder than “typical” brains to process incoming sights and sounds, requiring additional mental overhead for even the simplest tasks. “What was surprising for me was the magnitude of the difference. These are not subtle differences,” says Perrachione. This finding dovetails with his other work on the dyslexic brain, which has found that individuals with dyslexia also struggle with phonological working memory. The extra brainwork might not be noticeable most of the time, but it seems to have a singularly prominent impact on reading.

The results could solve a paradox that has stumped dyslexia researchers for decades. “People with dyslexia have a specific problem with reading, yet there is no ‘reading part’ of our brain,” says Neuron article coauthor John Gabrieli, an MIT professor of brain and cognitive sciences, who was Perrachione’s PhD advisor when he conducted much of the research reported in the paper. Injuries to specific parts of the brain can cause people to lose particular skills, like the ability to speak, that sit in those brain regions. But because the brain doesn’t have a discrete reading center, it’s hard to understand how a disorder could handicap reading and only reading.

This new work partially solves the paradox because rapid neural adaptation is a “low-level” function of the brain, which acts as a building block for “higher-level,” abstract functions. Yet that opens up another mystery, says Gabrieli. “Why are there other domains that are so well done by people with reading difficulty?”

Image of black dots of a dalmation

This optical illusion shows rapid neural adaptation in action. At first, the image looks like random black spots. But look a little longer and you will see a Dalmatian. (The dog’s nose is in the center of the image and his body extends to the right.) After seeing the Dalmatian once, most people see it every time they view the picture, even if they don’t explicitly remember where to look. Neural adaptation has primed the brain to read the spots in a new way. Photo by Ronald C. James

The answer has to do with the way we learn to read, the researchers think: “There’s almost nothing we learn that’s as complicated as reading.” That’s because learning to read is mentally cumbersome. The human brain did not evolve to read—literacy has been commonplace only in the last two centuries—so the brain must repurpose regions that evolved for very different ends. And the evolutionary newness of reading may leave the brain without a backup plan. “Reading is so demanding that there’s not a successful alternative pathway that works as well,” says Gabrieli. It’s like using a stapler to pound a nail—the stapler can get the job done, but it takes a lot of extra effort.

The fMRI results show which parts of the brain are straining but don’t tell researchers exactly why people with dyslexia have a different adaptation response. In the future, Perrachione and his colleagues hope to examine how neurons and neurotransmitters change during adaptation. “Finding a basic thing that’s true in the whole brain gives us a better opportunity to start looking for connections between biological models and psychological models,” says Perrachione. Those connections may one day lead to better ways to identify and treat children with dyslexia.

Links Found among Concussion, Genes, and Alzheimer’s

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A concussion today could increase the risk of developing Alzheimer’s disease later in life, but only if your genes already tip the odds toward dementia, according to a study published in the journal Brain on January 11, 2017.

Researchers have known for more than a decade that people who experience a severe or moderate traumatic brain injury are at greater risk of getting Alzheimer’s disease later on, but far less is known about how mild traumatic brain injuries, or concussions, affect brain health over time, even though they make up more than 70 percent of all head injuries.

“People tend to ignore concussion and just shake it off, and don’t follow up with care,” which makes it difficult to study the lifelong impact of such injuries, says study lead author Jasmeet Hayes, a School of Medicine assistant professor of psychiatry. The study was supported by grants from the US Department of Veterans Affairs (VA) and the National Institute of Mental Health.

As a psychologist and faculty member at the National Center for PTSD and the Neuroimaging Research for Veterans Center, Hayes works with veterans of the conflicts in Iraq and Afghanistan, many of whom have suffered head injuries from improvised explosive devices (IEDs). One patient, J.G., a retired marine who had been near more than 50 significant explosions in his 14 years with the US Marine Corps Explosive Ordnance Disposal Service, prompted Hayes to look more closely at the lifelong impact of concussions.

Despite his work with powerful explosives, J.G. had never lost consciousness on the job, so his head injuries were all classified as mild. But when he came to see Hayes at the age of 55, he was struggling. He couldn’t figure out how to use his computer, although he had previously had no trouble; he was stuttering and having trouble articulating words; he had been picking up the same book for two and a half years but could never seem to remember what he’d read at the last sitting. She coauthored a case study on J.G., which was published in Neurocase in 2012.

“My personal opinion was that he was headed for neurodegenerative disease at an early age,” says Hayes. “He was one of the driving factors for me to continue this line of research.”

Graphic images of the human brain highlighting seven key brain areas affected by thinner grey matter in people's with Alzheimer's disease

Researchers have found that Alzheimer’s is linked with thinner gray matter in seven key brain areas, highlighted here. Image courtesy of Jasmeet Hayes

Drawing on data from the Translational Research Center for TBI and Stress Disorders (TRACTS) study, which is led by coauthors Regina McGlinchey and William Milberg, both of the VA and Harvard Medical School, Hayes identified 160 Iraq and Afghanistan conflict veterans who had experienced either no brain injury or a mild brain injury during or before their deployment. Then she and her colleagues looked for brain changes, using MRI scans to measure the thickness of the gray matter folds at seven key brain areas that typically thin out in Alzheimer’s. For comparison, they also looked at the thickness of seven other parts of the cerebral cortex that aren’t linked with Alzheimer’s.

Averaged across the full sample, veterans who had experienced concussions were not significantly more likely to have thinning in the seven brain areas tied to Alzheimer’s. But when the researchers added genetic risk to the mix, they got a key insight: veterans with both a genetic predisposition to Alzheimer’s and a previous concussion did have marked thinning in the important memory-related areas.

To gauge each participant’s genetic risk, Hayes worked with coauthors Mark Logue, a MED research assistant professor at the VA, and Mark Miller, a MED associate professor at the VA, to run a genome-wide genetic association, which calculates a polygenetic risk score using the entire genome rather than just a single gene or gene cluster. Scientists have used this approach to study a wide variety of complex diseases, including schizophrenia and bipolar disorder, and it has proved a more powerful predictor of Alzheimer’s than any single gene. “The future of genetics is really looking at the polygenetic approach and letting every gene contribute to the total risk,” Hayes says.

To see if they could find early signs of memory loss along with the brain changes, the researchers also looked at veterans’ scores on a word-recall test. They found that the test results paralleled the results of the brain scans: those who had trouble remembering a list of words that they’d seen 20 minutes earlier were also the likeliest to have thinning in the Alzheimer’s regions, and to have the deleterious combination of genetic risk and mild brain injury.

Hayes hopes that a better understanding of the factors that contribute to Alzheimer’s will allow individuals at high risk to intervene early, whether that means making smart choices about injury prevention or trying out experimental drug therapies that may start fighting Alzheimer’s before symptoms become disabling. “If we can identify who’s going to be at risk, then maybe they can have positions in the military that would not lead them to getting a concussion,” she says. “That’s the hope in the future—to try to figure out who’s at risk, who’s not, whose brain might be more resilient.”

Because the current study includes only brain scans made at one point in time, Hayes points out, it does not tell the full story of how a concussion progresses into brain changes. “Because we can only look at this one time point, it doesn’t allow us to track changes over time,” she says. “We don’t know, if someone had an injury 5 years ago, did their injury develop 30 days later, or did it take all 5 years?” She plans to continue to follow her subjects via the TRACTS study so that she can see the process as it unfolds.

The new study is likely to raise fresh concerns about injuries that were once shrugged off. However, says Hayes, not every person who has had a concussion—and almost everyone probably has had one, she says—will go on to develop Alzheimer’s. Still, we shouldn’t take the brain for granted, she says. “We only have one brain in this lifetime, so we should protect it as much as possible.”

BU Names Kilachand Honors College Associate Directors

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BU has named two associate directors of the Arvind and Chandan Nandlal Kilachand Honors College, one with a background in the sciences and the other in creative interdisciplinary approaches to education, as well as in science. Their knowledge and expertise will help broaden students’ undergraduate experience both in the classroom and beyond, says the college’s director, Carrie Preston, Arvind and Chandan Nandlal Kilachand Professor and a College of Arts & Sciences professor of English.

Linda Doerrer is a CAS associate professor of chemistry and a College of Engineering Materials Science & Engineering division associate professor. Paul Lipton (GRS’01) is a CAS research associate professor and director of the interdepartmental undergraduate program in neuroscience as well as the outgoing director of the Undergraduate Research Opportunities Program (UROP). The two were chosen by a six-member search committee chaired by Preston. She says that they will bring “their experience building visionary programs” to their new roles.

Established in 2011 with a $25 million gift from University trustee Rajen Kilachand (Questrom’74), the Kilachand Honors College is a general education program with a current student population of 353, all housed within the neoclassical contours of Kilachand Hall (formerly Shelton Hall), at 91 Bay State Road.

The Kilachand curriculum, according to its mission statement, has several keynotes: “First, it attempts to integrate the arts, sciences, and professions and attempts to lower the barriers between pure and applied knowledge while avoiding an instrumental, utilitarian approach. Second, the curriculum explores the commonalities and differences of various disciplines’ ways of knowing by looking at specific problems in a wide range of fields. Third, the curriculum tries to connect teaching with research and creative activity by introducing students to their professors’ work and gradually preparing them to do research and partake in creative activity on their own. Finally, the curriculum pays close attention to ethical, aesthetic, and social issues in order to foster self-development and citizenship.”

“I’ve been attracted to the honors college since I taught here a couple of years ago,” says Lipton. “I love the experience and the perspective of its students, and how the honors college provides an opportunity to be part of a vibrant, active, and multidimensional community that for some may be hard to find at BU because it is such a big place.” Lipton’s primary research interests are in cognitive neurobiology and science education. He joined the undergraduate program in neuroscience when he came to BU in 2007 and became director in 2013, overseeing its growth from approximately 30 students to close to 400 today. He will continue as director, along with his Kilachand appointment. (A successor has not yet been named to direct UROP.)

Lipton says he has found great satisfaction in helping to build an academic and intellectual environment where students and faculty come together to learn about and explore the brain and mind. Already familiar with an interdisciplinary approach (neuroscience at BU embodies eight departments across four colleges), he is interested in creating courses reflecting the reach of neuroscience in unexpected directions. The relatively new field of neuroeconomics, for example, probes the neurobiological mechanisms involved in decision-making behavior. The fledgling field of neuroaesthetics looks at questions of neurological hardwiring of artistic preferences (why is blue a favorite color worldwide?), and, he notes, BU already offers a new joint major in philosophy and neuroscience.

In a letter last month introducing the new associate directors to Kilachand students, faculty, and staff, Preston said that “Doerrer’s lab is investigating the use of highly fluorinated aryloxide and alkoxide ligands for C-H and O-H bond oxidations” and that a second research area of the lab is exploring “the behavior of quasi one-dimensional nanowires as templates for developing structure-property relationships in electronic conduction and single-chain magnetic behavior.”

Doerrer offers a more user-friendly description: “I make new molecules that can help solve problems.” She describes herself as “a person passionate about clear communication, oral and written,” with a love of history that informs her teaching. “In 1900 some of what my group and I do might have been called metallurgy,” she says. “In 1200 it would be alchemy.” A vigorous advocate for women in science and engineering, she speaks eloquently of the honors college’s devotion to liberal arts and what she calls “the life of the mind. There is a constant reframing of human knowledge into different disciplines, and that has been going on for very long time, even when Aristotle tutored Alexander the Great.”

Preston says the naming of associate directors in the sciences will help the college expand its multitextured approach. “I’m a humanist interested in everything that makes us human,” says Preston, whose new book Learning to Kneel: Noh, Modernism, and Journeys in Teaching (Columbia University Press, 2016), chronicles her long-term practice of the highly specialized and nuanced Japanese dance form. “I needed associate directors in the sciences to supplement my knowledge,” she says.

With its new triumvirate guiding it, Kilachand Honors College should be better equipped to give students what Preston refers to as “the critical skills and flexibility of mind to think about global challenges in all their complexity and from multiple perspectives.” After she was appointed director last September, she expressed her commitment to preparing Kilachand students “to consider the ethical dimensions and human impact of any action or decision, from technological advances to policy changes, scientific discoveries to business platforms.” In the coming years, she says, the Kilachand curriculum “will be enhanced to embrace challenges such as climate change and global health, and incorporate service learning as well as fieldwork, both locally and abroad.”

Tuning In

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On a cool May evening, the sounds of a tuning orchestra fill a performance hall in Concord, Massachusetts, spilling out into the otherwise quiet streets of bistros with carved wooden signboards and quaint shops selling antiques, fine wine, and artisanal cheese.

Before the entire orchestra has assembled on the stage—in a historic, converted barn with klieg lights fixed to its rafters—it is still possible for an untrained ear to pluck specific instruments from the musical jumble. But as the official start of rehearsal nears, the growing ranks of musicians produce a louder and less decipherable cacophony. Finally, the conductor steps to his post and holds up a hand to signal “Quiet, please!”

Among the musicians waiting in the sudden silence that follows is Barbara Shinn-Cunningham, a professor of biomedical engineering in Boston University’s College of Engineering (ENG). By her side rest an oboe and an English horn (imagine an overgrown oboe), both of which she will play during the Concord Orchestra’s “Pops” rehearsal tonight.

Music isn’t a hobby for Shinn-Cunningham. Long before she was a scientist, she was a musician. She switched from piano to the oboe and then added the English horn in junior high. For a brief period in high school, she considered pursuing music as a professional, but she enjoyed science and math too much to follow through. When she chose a research focus in graduate school, her deep love of music led her to study the neuroscience of hearing.

For nearly three decades, Shinn-Cunningham has studied how our brains make sense of sound. Her lab’s investigations stretch from the precise algorithms of auditory signal processing to the black boxes of cognition and how shifting attention changes the way our brains sort through the daily mix of sounds we encounter.

Read the full story about hidden hearing loss research

Mind Reader

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Celeste Hamre and her sister Britta, 23, are fraternal twins. They have the same blue eyes and amber-blonde hair, the same love of Brie and running. But it was clear early on that there was something different, too. When Britta began learning to read and write, Celeste lagged behind. When Celeste tried to speak new words, a mixed-up jumble spilled out. Sounding out words in front of her class was so embarrassing that Celeste would try to memorize the stories Britta read aloud so she could parrot them back to her teachers and classmates. She coveted the thick New York Times readers her classmates got, but her teacher passed her a skinny abridged version instead.

Tyler Perrachione, Director of Boston University Sargent College Communication Neuroscience Research Laboratory, holds a card showing a word used in the nonword repetition tests studying phonological working memory in his dyslexic brain research

The girls’ parents signed Celeste up for specialized testing, which revealed that she has a reading disorder called dyslexia. They enrolled her in intensive one-on-one tutoring, and it worked: by the time she was 11, she recalls, she was snagging books from her siblings and sneaking them into bed. Less than a decade later, Celeste (CAS’16)—who graduated high school as valedictorian and joined the Boston University Class of 2016 with a full merit scholarship—entered the laboratory of Tyler Perrachione, an assistant professor at BU’s College of Health & Rehabilitation Sciences: Sargent College. Perrachione studies how language and reading skills develop—and how they sometimes go awry—and he was looking for volunteers with dyslexia, just like Celeste.

Researchers estimate that between 5 and 17 percent of schoolchildren have dyslexia, which is defined as any difficulty reading single words. Contrary to common belief, people with dyslexia don’t read words backward, says Perrachione, and the disorder doesn’t have anything to do with overall intelligence.

Read more about Tyler Perrachione’s dyslexia research

Is Soda Bad for Your Brain? (And Is Diet Soda Worse?)

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Americans love sugar. Together we consumed nearly 11 million metric tons of it in 2016, according to the US Department of Agriculture, much of it in the form of sugar-sweetened beverages like sports drinks and soda.

Now, new research suggests that excess sugar—especially the fructose in sugary drinks—might damage your brain. Researchers using data from the Framingham Heart Study (FHS) found that people who drink sugary beverages frequently are more likely to have poorer memory, smaller overall brain volume, and a significantly smaller hippocampus—an area of the brain important for learning and memory. The FHS is the nation’s longest running epidemiological study, begun in 1948, supported by the National Heart, Lung, and Blood Institute, and run by BU since 1971.

But before you chuck your sweet tea and reach for a diet soda, there’s more: a follow-up study found that people who drank diet soda daily were almost three times as likely to develop stroke and dementia when compared to those who did not.

Researchers are quick to point out that these findings, which appear separately in the journals Alzheimer’s & Dementia and Stroke, demonstrate correlation but not cause and effect. While researchers caution against overconsuming either diet soda or sugary drinks, more research is needed to determine how—or if—these drinks actually damage the brain, and how much damage may be caused by underlying vascular disease or diabetes.

“These studies are not the be-all and end-all, but it’s strong data and a very strong suggestion,” says Sudha Seshadri, a School of Medicine professor of neurology and a faculty member at BU’s Alzheimer’s Disease Center, senior author on both papers. “It looks like there is not very much of an upside to having sugary drinks, and substituting the sugar with artificial sweeteners doesn’t seem to help.”

Matthew Pase, Framingham Heart Study investigator

Matthew Pase is lead author on two studies that link higher consumption of both sugary and artificially sweetened drinks to adverse brain effects. Photo by Cydney Scott

“Maybe good old-fashioned water is something we need to get used to,” she adds.

Matthew Pase, a fellow in the MED neurology department and an FHS investigator, who is lead author on both papers, says that excess sugar has long been associated with cardiovascular and metabolic diseases like obesity, heart disease, and type 2 diabetes, but little is known about its long-term effects on the human brain. He chose to study sugary drinks as a way of examining overall sugar consumption. “It’s difficult to measure overall sugar intake in the diet,” he says, “so we used sugary beverages as a proxy.”

For the first study, published in Alzheimer’s & Dementia on March 5, 2017, researchers examined data, including magnetic resonance imaging (MRI) scans and cognitive testing results, from about 4,000 people enrolled in the FHS Offspring and Third-Generation cohorts. (These are the children and grandchildren of the original volunteers enrolled in 1948.) The researchers looked at people who consumed more than two sugary drinks a day of any type—soda, fruit juice, and other soft drinks—or more than three per week of soda alone. Among that high-intake group, they found multiple signs of accelerated brain aging, including smaller overall brain volume, poorer episodic memory, and a shrunken hippocampus, all risk factors for early-stage Alzheimer’s disease. Researchers also found that higher intake of diet soda—at least one per day—was associated with smaller brain volume.

In the second study, published in Stroke on April 20, 2017, the researchers, using data only from the older Offspring cohort, looked specifically at whether participants had suffered a stroke or been diagnosed with dementia because of Alzheimer’s disease. After measuring volunteers’ beverage intake at three points over 7 years, the researchers then monitored the volunteers for 10 years, looking for evidence of stroke in 2,888 people over age 45, and dementia in 1,484 participants over age 60. They found, surprisingly, no correlation between sugary beverage intake and stroke or dementia. However, they found that people who drank at least one diet soda per day were almost three times as likely to develop stroke and dementia.

Although the researchers took age, smoking, diet quality, and other factors into account, they could not completely control for preexisting conditions like diabetes, which may have developed over the course of the study and is a known risk factor for dementia. Diabetics, as a group, drink more diet soda on average, as a way to limit their sugar consumption, and some of the correlation between diet soda intake and dementia may be due to diabetes, as well as other vascular risk factors. However, such preexisting conditions cannot wholly explain the new findings.

“It was somewhat surprising that diet soda consumption led to these outcomes,” says Pase, noting that while prior studies have linked diet soda intake to stroke risk, the link with dementia was not previously known. He adds that the studies did not differentiate between types of artificial sweeteners and did not account for other possible sources of artificial sweeteners. He says that scientists have put forth various hypotheses about how artificial sweeteners may cause harm, from transforming gut bacteria to altering the brain’s perception of sweet, but “we need more work to figure out the underlying mechanisms.”


Science Coalition: Federal Funding Sparks Innovation

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One company has created an artificial pancreas that automatically regulates blood sugar levels in people with type 1 diabetes. Another is developing novel therapeutics to treat Alzheimer’s disease. A third was an early provider of big data solutions, pioneering state-of-the-art network traffic analysis that detects the spread of computer viruses and other malicious activity.

The start-ups, born in BU labs, are 3 of 102 young companies featured in a report on the benefits of federally funded research that was released yesterday by the nonprofit, nonpartisan Science Coalition. The report, American-Made Innovation Sparking Economic Growth, documents the ways that these companies and others are bringing to market transformational innovations in areas ranging from health care to defense and are contributing to US job creation and economic growth. The report’s release coincides with Congressional consideration of funding for America’s science agencies, which is threatened by cuts proposed by the Trump administration, including a reduction of 18.3 percent, or about $5.8 billion, of the National Institutes of Health (NIH) budget.

The Science Coalition is an organization of more than 50 of the country’s public and private research universities, including BU.

Not long after his infant son was diagnosed with type 1 diabetes, 17 years ago, Ed Damiano, a College of Engineering professor of biomedical engineering, began working on a technology that could automatically manage his son’s glucose levels. In 2015, with strong support from BU, Damiano started the public benefit corporation Beta Bionics, Inc., to bring to market his team’s artificial, or bionic, pancreas, called the iLet, a pocket-sized, wearable medical device. The core technology of the iLet was developed by Damiano’s research team at BU and has demonstrated in clinical trials dramatic improvements in blood sugar levels of people with type 1 diabetes.

Damiano’s work on the bionic pancreas has been supported by about $22 million in NIH funding. He says that is about two thirds of the total his research team at BU has raised to build and test the bionic pancreas. “This support from the NIH has added tremendous value by allowing us to test, refine, and test again our technology in real-world, investigator-initiated clinical trials,” he says. “The bionic pancreas simply would not be where it is today had it not been for our NIH-funded clinical research.”

Carmela Abraham, a MED professor, and her husband, Menachem, started Klogene Therapeutics, Inc., to develop novel therapeutics for Alzheimer’s disease. Photo by Jackie Ricciardi

According to the Science Coalition, each of the companies in its report—including Beta Bionics–exists today because academic researchers had access to competitively awarded grants from many of the federal agencies imperiled by budget cuts. The coalition works to sustain strong federal funding of basic scientific research as a way to stimulate the economy, spur innovation, and drive America’s global competitiveness. Its reports are frequently cited by members of Congress and other federal policymakers.

“Lawmakers love to see how their support for federally funded research leads to the creation of new companies and therapies that change the world around us,” says Jennifer Grodsky, the University’s vice president for federal relations. “We are thrilled to share these impressive BU success stories with members of Congress.”

The total investment in the foundational research behind the 102 companies cited in the report was just over $265 million, spread over several decades, according to the Science Coalition report. The companies employ 8,900 workers in communities across the country. Many of the companies—like Beta Bionics—are addressing America’s most chronic and costly health challenges, such as Alzheimer’s, diabetes, cardiovascular disease, and cancer.

“Each one of these companies is an American innovation success story and illustrates the powerful ripple effect that the partnership between the federal government and our nation’s research institutions has on society and our economy,” says Glynda Becker, president of the Science Coalition. “If Washington, D.C., is serious about creating good jobs, producing American goods, and keeping the United States ahead of our international competitors, then, as this report shows, continued strong and steady funding for basic scientific research is a wise investment.”

Gloria S. Waters, a BU vice president and associate provost for research, says investment in academic research is a critical driver of innovation, future economic growth, and job creation. “Not only will a failure to invest in education and research have an effect on scientific discovery,” she says, “but it will also have a profound effect on the economy and job creation in both the city and the state.”

Mark Crovella, a CAS professor, helped Anukool Lakhina, one of his doctoral candidates, develop new, more effective methods for analyzing traffic in data networks than previous technology.

Mark Crovella, a CAS professor, helped Anukool Lakhina (CAS’01, GRS’01,’07), one of his doctoral candidates, develop new, more effective methods for analyzing traffic in data networks than previous technology. Lakhina drew on that to found Guavus, Inc. Photo by Jackie Ricciardi

In 2015, Carmela Abraham, a School of Medicine professor of biochemistry and of pharmacology and experimental therapeutics, cofounded Klogene Therapeutics, Inc., which develops novel treatments for Alzheimer’s disease by focusing on small molecule compounds to boost levels of the large protein Klotho in the brain. The company grew out of Abraham’s work on Klotho, which circulates in the blood and cerebral spinal fluid and may protect against Alzheimer’s and other neurodegenerative diseases. She says that more than $2.8 million in funding from the NIH National Institute on Aging (NIA) enabled her group to conduct the research that led to the discovery of the protein.

“This was the very first program project grant from the NIA, and the BU School of Medicine had it for over 36 years,” she says. “I was lucky to be a project leader of this grant for over 20 years.” In 2016, Klogene won a $1.49 million NIA Small Business Innovation Research grant.

The third BU company cited in the Science Coalition report is Guavus, Inc., which was founded by Anukool Lakhina (CAS’01, GRS’01,’07) and grew out of his work as a BU doctoral student under Mark Crovella, a College of Arts & Sciences professor of computer science. That research—and additional work by BU researchers that led to the founding of Guavas—was supported by about $6 million in funding from the Office of Naval Research and the National Science Foundation. Lakhina, winner of a Computer Science Distinguished Alumni Award in 2015, is the CEO of Guavus, based in San Mateo, Calif. The company develops data analysis platforms and applications that enable companies to process high-volume streaming data for business analytics and engineering; it has more than 400 employees.

“Guavus pioneered big-data analytics before the emergence of data science,” says Crovella, a member of the company’s technical advisory board. “Anukool Lakhina’s PhD thesis benefited from cross-disciplinary collaboration between BU’s departments of computer science and statistics, and the power of the resulting methods he developed led directly to the founding of Guavus. Its success has been a testament to the way that federally funded basic research attacks problems before they become mainstream, and thereby drives innovation. BU provided the ideal scientific environment to nurture the innovative contributions in Anukool’s research.”

According to the Science Coalition report, the initial federal research investment in the companies cited is relatively small, with 80 percent of them reporting that they received less than $5 million in federal funding for their foundational work. For 40 percent of companies, that figure was less than $1 million.

“Basic scientific research is the smallest slice of the nation’s R&D pie, yet it is the spark that ignites discovery and innovation in the United States,” says Anna Quider, coalition vice president. “The budget cuts for many of America’s preeminent science agencies would risk an entire generation of discovery and innovation and all of the benefits that flow from it.”

Neurophotonics Center: Advancing Understanding of the Brain

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The understanding of the human brain has leaped forward in recent years, with the help of the emerging field of neurophotonics, a noninvasive, light-based technology that allows scientists to study the brain’s functioning in real time. Boston University has been a leader in the field and is now capitalizing on its expertise in neuroscience and photonics to create the Neurophotonics Center, led by one of the field’s preeminent researchers.

David Boas is joining the College of Engineering faculty as the new center’s founding director and a professor of biomedical engineering. He comes from Massachusetts General Hospital, where he has pioneered new technologies to see deep into the brain to improve understanding of its healthy functioning and offer new pathways to understand how strokes, migraines, Alzheimer’s disease, and other neurologic maladies affect it. Boas is recruiting faculty from throughout ENG and across the University to pool expertise and further accelerate neurophotonics technologies.

“There are tremendous advantages to biomedical and photonics engineers working with neuroscientists,” says Boas. “Neuroscientists have questions and problems that engineers want to solve. Those solutions advance the field and lead to new questions and new solutions. Boston University has a wealth of expertise in photonics, biomedical engineering, and neuroscience that is excellent fuel for this virtuous cycle.”

Many of the center’s efforts will use multiphoton microscopy, a method that even 25 years after it began still has an increasing impact on neuroscience. In addition, the center will be developing and applying novel approaches to measuring human brain function with light.

Human functional brain imaging has been done for several years using fMRI (functional magnetic resonance imaging) scans, which produce sharp images of brain blood oxygenation and flow, key to seeing which areas of the organ are being stimulated at a given time. But fMRI scans require the subject to lie perfectly still in a confining machine for an extended period, obviously not a natural state and a difficult procedure to use with infants, small children, and many others. They are also expensive.

Instead, Boas uses functional near-infrared spectroscopy (fNIR), which penetrates through the scalp and skull as much as a centimeter into the brain, where it detects blood oxygenation, ultimately enabling the imaging of brain function. The images aren’t as crisp as fMRI scans, but the wearable device allows wearers to move around naturally, engage socially, and go about their activities while researchers observe blood flow and oxygenation changes in the brain in real time at a far lower cost. Furthering this research is expected to be one of the Neurophotonics Center’s initial projects.

Faculty from the College of Arts & Sciences, Sargent College of Health & Rehabilitation Sciences, and the School of Medicine will join ENG faculty in the center, among them Thomas Bifano, an ENG mechanical engineering professor and director of the Photonics Center, Barbara Shinn-Cunningham, an ENG biomedical engineering professor, and Howard Eichenbaum and Chantal Stern, both CAS psychological and brain sciences professors. The Neurophotonics Center will draw on the work of doctoral students through the new $2.9 million Research Traineeship grant for neurophotonics from the National Science Foundation, which will award its first fellowships in 2017.

CTE Found in 99 Percent of Former NFL Players Studied

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A new study suggests that chronic traumatic encephalopathy (CTE), a progressive, degenerative brain disease found in people with a history of repeated head trauma, may be more common among football players than previously thought. The study, published Tuesday in the Journal of the American Medical Association (JAMA), found CTE in 99 percent of brains obtained from National Football League (NFL) players, as well at 91 percent of college football players and 21 percent of high school football players.

Jesse Mez

Jesse Mez, MED assistant professor of neurology and lead author on the new study, says: “The data suggest that there is very likely a relationship between exposure to football and risk of developing [CTE].” Photo by Cydney Scott

“The data suggest that there is very likely a relationship between exposure to football and risk of developing the disease,” says Jesse Mez, a Boston University School of Medicine (MED) assistant professor of neurology and lead author on the study.

The study has several important limitations, most notably the lack of a control group, and selection bias in the brain collection itself—families of players with symptoms of CTE are far more likely to donate brains to research than those without signs of the disease. Despite these limitations, researchers note that the study—the largest and most methodologically rigorous CTE case series ever published—offers important information and direction for further research.

“The fact that we were able to gather so many instances of a disease that was previously considered quite rare, in eight years, speaks volumes,” says corresponding author Ann McKee, a MED professor of neurology and pathology and director of BU’s CTE Center. “There’s just no way that would be possible if this disease were truly rare.”

“I think the data are very surprising,” she adds. “We’ve sort of become accustomed to it, but it is very shocking.”

McKee, who is also chief of the Neuropathology Service at the VA Boston Healthcare System, first encountered CTE in 2003, identifying its telltale mark—tiny tangles of tau protein clustered around blood vessels—in the dissected brain of a boxer. In 2014, grants from the National Institute of Neurological Disorders and Stroke and the National Institute of Biomedical Imaging and Bioengineering—both part of the National Institutes of Health—allowed McKee to begin a study called UNITE (Understanding Neurologic Injury and Traumatic Encephalopathy), a retrospective analysis of brains donated to the VA-BU-CLF Brain Bank, the results of which comprise much of the current JAMA article.

A sample of normal brain tissue (left), alongside samples showing mild and severe CTE. The brown stain indicates tangles of tau protein. Defective tau is associated with CTE, as well as Alzheimer’s disease and Parkinson’s disease. The bottom row shows microscopic images of tau, stained red, embedded in brain tissue. Photo by Ann McKee

For the study, the researchers began with the donated brains of 202 football players. Pathologists, knowing nothing of a patient’s history or symptoms, examined each brain for evidence of CTE. At the same time, clinicians—blinded to each brain’s pathology—used medical records and interviews with family members to collect detailed information about each patient’s medical history and symptoms. The group met for regular consensus meetings, where the pathologists and the clinicians presented their findings. They limited the study to football players, providing a somewhat homogeneous sample.

Of the 202 brains studied, the group diagnosed 177 with CTE, including 110 of 111 from the NFL players (99 percent); 7 of 8 from the Canadian Football League (88 percent); 9 of 14 semi-professional players (64 percent); 48 of 53 college players (91 percent), and 3 of 14 high school players (21 percent). (The group also studied the brains of two pre-high-school players, neither of whom was diagnosed with CTE.) The brains of former high school players showed only mild pathology, while the majority of college, semi-professional, and professional players showed severe pathology.

Dave Duerson, a former safety for the Chicago Bears, committed suicide in 2011 at age 50. His suicide note read, “Please, see that my brain is given to the NFL’s brain bank.” McKee analyzed his brain and diagnosed moderately severe CTE. Duerson’s brain is among the 202 included in a study published Tuesday in JAMA. Photo by Owen C. Shaw/Getty Images

Mez notes some puzzling findings from the study. Most striking, the researchers observed clinical symptoms such as depression, anxiety, disinhibition, memory loss, and other mood and behavior impairments even in patients with fairly mild CTE pathology. “Why do you still see symptoms even without that much CTE pathology?” asks Mez. “It suggests that there might be even more going on than just the tau pathology; there might be other things that we need to look at, like inflammation or axonal injury, or there might be regions of the brain that we’re not looking at sufficiently.”

The findings also suggest that there may be other environmental factors at play, like substance abuse, other head traumas, or a genetic component. Mez says that clues may come from outliers in the study, like the one NFL brain that did not show evidence of CTE or the brains from high-school players that did.

“Those people are probably genetically protected from this disease or they’re genetically predisposed to it, depending on which extreme you’re looking at,” says Mez. “I think you can certainly learn a lot from them. And as we move forward and we collect more of those extremes, they will be really informative.”

The researchers emphasize that the data represent a new tool for scientists. “This is an enormous advance in a resource, because we have developed this brain bank of frozen and fixed tissue on these individuals who have been affected by this disease,” says McKee. “Our goal is to try to understand the disease from its earliest beginnings in the brain, what molecular pathways are involved, how it spreads, which regions it affects most severely—all to give us ideas how to diagnose this disease during life, and also to give us information about how to treat it.”

MED Neuroscience Program Gives Undergrads Experience and Insight

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From their looks of cheerful expectation, you might think the eight undergraduates gathered around a U-shaped table in the BU School of Medicine anatomy lab are waiting to see a movie or a band. Except the next thing they do is don lab aprons, gloves, and safety glasses.

Then neuroanatomy instructor Joseph Goodliffe, a MED postdoctoral researcher, brings out the brains.

“Try to identify some of those structures we were discussing in class earlier,” says Goodliffe (MED’16) as he lifts several white plastic buckets onto the table.

Inside, floating in a preservative solution, are cadaver brains that have been donated to the anatomy lab, most of them already cut in half along the median, providing a nice clear cross section for the students searching out structures such as the corpus callosum, hypothalamus, and caudate. The students speak with a mix of awe and seriousness, but no one seems intimidated. It’s not their first time, after all.

“That one still has the spinal cord attached,” one says, nodding toward a nearby bucket. “That’s pretty intense.”

Welcome to the new Summer Program in Neuroscience (SPIN), which gives high-achieving undergraduates from colleges and universities around the country a head start in the subject, offering experiences that they wouldn’t normally get until grad school.

“They’re a joy to work with. They’re really, really interested in learning,” says James Holsapple, a MED associate professor and chair of neurosurgery and an associate professor of pediatrics, who began the program last year.

Holsapple, who is also Boston Medical Center neurosurgery department chair and neurological surgery program director, aimed SPIN at undergrads who are studying neuroscience or who are on a premed track, and at biology and computer science students. “There’s a lot of crossover between neuroscience and computer science now,” he says, from computational neuroscience to artificial intelligence.

SPIN, the Summer Program in Neuroscience, is an eight-week course for undergraduates to integrate neuroscience research, hands-on teaching of human neuroanatomy, and clinical neurosurgery. It allows them experiences they otherwise wouldn’t have until graduate school.

The program has three components:

  • Lab: The students are assigned to a neuroscience lab, where they assist in ongoing research, from benchwork to behavioral experiments to numerical simulations.
  • Didactic: Students attend rounds and participate in subsequent sessions where the whole neurosurgery department meets to review cases, hear lectures from staff, and ask questions. They also have their own neuroanatomy class with Goodliffe, “so they get a taste of what medical school looks like,” Holsapple says.
  • Clinical: Students see patients with Holsapple in clinical settings, and they observe neurosurgery right in the operating room. “They’re wearing scrubs, roaming the hospital with us, and watching surgery being done,” he says. Seeing a living human’s brain for the first time, “that’s pretty exciting.”

The students certainly agree about the “exciting” part.

Boston native Joy Yang is a rising junior at Emory University, studying neuroscience and behavioral biology. She plans to attend medical school, and says she never worried about her ability to handle the operating room. “I was open-mouthed the whole time. It’s such a surreal experience. You’re watching someone be cut open and helped and saved. I liked the blood. It was pretty cool. I watch a lot of gruesome TV shows. I was ready.”

“This has been the first real clinical experience I’ve had,” says Rachel Feltman, from Long Island, a University of Michigan rising senior studying for a BS in biopsychology, cognition, and neuroscience. “I’ve worked in a doctor’s office, but it was just at the front desk.”

Feltman says her first experience following Boston Medical Center residents as they were caring for a postsurgical patient with a serious head trauma was “very overwhelming.” As she prepared to attend a surgery the next morning, she called her mother, acknowledging that she didn’t know if she could handle it. To her relief, the surgery was canceled. However, she says now, the experience of waiting in the operating room for an hour before the cancellation gave her a level of confidence that helped her get through the next surgery.

“Your brain controls everything you do,” she says. “I’ve learned about it in lectures and in books and we’ve been working with the cadaver brains, but just seeing it pulsating and knowing blood was flowing through it was just incredible.”

Feltman, who dropped a study-abroad trip to Copenhagen to take the summer course, says SPIN has confirmed her commitment to a career in neurology or psychiatry. She will apply to medical school after a gap year.

Undergraduates from across the country and instructor Joseph Goodliffe (MED’16) (center, in blue coat) study the anatomy of the brain in a MED lab.

Goodliffe has taught medical students and grad students, but this is his first time teaching undergraduates. That meant adjusting some of the content, which he says he doesn’t mind. “They’re just so enthusiastic and so excited to be here,” he says. “It’s a great energy level that they bring, and they’re learning neuroanatomy at the same level and pace we teach the med students.”

Holsapple ran a pilot program last year with two students from Drake University, his undergraduate alma mater. This year there were more than 100 applications for 8 slots, the small number constrained by the need to find a lab mentor for each student and to fit them all into clinical and operating rooms. He hopes to find ways to modestly expand the program next year.

He says SPIN benefits MED as well as the students. “As far as we know, this is the only program of its type,” he says. “It brings attention to BU as being innovative in the educational space, and it brings great students from all over the country to work in BU labs. It’s a good recruitment tool.”

Some SPIN students have already expressed interest in returning to BU for graduate studies or for medical school. And the program’s informal lunch speakers have included faculty offering advice about the medical school application process.

As Holsapple sees it, the neuroscience program could be just a beginning. “The SPIN framework could be adapted to other clinical specialties. You could do the summer program in nephrology, the summer program in psychiatry, the summer program in internal medicine.”

At the beginning of the eight weeks, he gave each student a blank lab notebook and told them they should write down anything they see or hear that they don’t understand. During the Tuesday morning didactic sessions with staff, time is always set aside for them to ask questions about those things.

“That inculcates a culture of inquiry and openness about questions,” Holsapple says, “of not being embarrassed to admit you don’t know something, which is the first step to knowing something.”

Four Generations of Philanthropy behind BU’s Largest Gift

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University leaders, researchers, and donor Rajen Kilachand talk about the importance of philanthropy and the promise of the interdisciplinary research that will be conducted at the Rajen Kilachand Center for Integrated Life Sciences & Engineering. Video by Alan Wong. Photo by Conor Doherty

When Rajen Kilachand came to Boston University in September 1971, he was impressed by the quality of US higher education. He was equally impressed, he recalls, by how much that quality appeared to depend on gifts from wealthy donors. “Whether it was the Mellons, the Carnegies, or the Rockefellers, it was giving for education,” says Kilachand (Questrom’74, Hon.’14). “That’s why today the United States is one of the great centers of higher learning. It is second to none in the world.”

Four-and-a-half decades later, with his latest gift to Boston University, a $115 million commitment to research at the intersection of the life sciences and engineering, Kilachand approaches the ranks of those historic architects of higher education. His contribution, the largest in the history of Boston University, directs $15 million to support construction of the new Rajen Kilachand Center for Integrated Life Sciences & Engineering and $100 million to establish an endowment known as the Rajen Kilachand Fund for Integrated Life Sciences and Engineering. That fund will serve as a foundation for BU’s continuing investment in interdisciplinary research that joins the life sciences and engineering, and will support research projects aligned with the grand challenges of life sciences and human health research and its impact on our global society.

This gift from Kilachand, a BU trustee, is not the first incidence of his generosity to the University. In 2011, he pledged $25 million to establish the Arvind and Chandan Nandlal Kilachand Honors College, which has a current student population of 407. One year later, he increased that commitment by $10 million for a face-lift of Kilachand Hall, the 91 Bay State Road student residence formerly known as Shelton Hall. Those gifts, plus his latest, collectively constitute one of the 50 largest gifts to higher education ever in the United States.

“This magnificent new gift from Rajen Kilachand is the capstone of our efforts to generate philanthropic support for the University,” says BU President Robert A. Brown. “A center like the Kilachand Center and the resources from the fund will have enormous impact, because they fund the very best people, who have the very best ideas and create the very best outcomes. That is what has built the greatness of a lot of the private research universities in the United States. It’s a very strong differentiator. This is the largest gift in our history, and the important thing is that it’s the largest gift to scientific research in our history, by far.”

“A center like the Kilachand Center and the resources from the fund will have enormous impact, because they fund the very best people, who have the very best ideas and create the very best outcomes.” —Robert A. Brown

Brown says the Rajen Kilachand Fund has the potential to help the University garner additional funding from the federal government and from industry. “It is my hope that this fund will help us continually generate leadership in important research areas,” he says.

Robert A. Knox (CAS’74, Questrom’75, Hon.’17), a BU trustee for 20 years and chair of the Board of Trustees for 8, describes Kilachand as a force of nature. “We first met him, I think, in 2010,” says Knox, “and since then his engagement and support of the University has been remarkable. So to have Rajen step forward and become by far the largest donor to Boston University is truly an amazing endorsement of the University, and it’s an amazing gift from a person who is exuberant, smart, thoughtful, and really loves—loves—BU.”

It was at BU that Kilachand first understood the influence of philanthropy on higher education. That understanding, he says, combined with his family’s deep, four-generation tradition of giving, has guided a lifelong personal mission of good works.

At the heart of that mission, he says, lies a conviction of the karmic obligation of a human soul to participate morally and ethically on the path of duty that brings wellness to humanity. In fact, Kilachand senses a karmic connection between his family’s past and his present. His great-grandfather Kilachand Devchand, who became wealthy trading in oil seeds and cotton in Bombay in the 1880s, dealt extensively with the Lawrence family, prominent New England industrialists who built the textile mills of Lawrence, Mass., and—coincidentally—the Gothic Revival Brookline mansion now known as Sloane House, which is the home of the BU president.

It was that same great-grandfather who began the family’s philanthropy, building a clean water system in his childhood village. That system, in turn, was improved upon by his eldest son, Chottalal Kilachand, who also brought electricity to the village and built its first hospital and then a second hospital—for the camels, dogs, donkeys, and other animals that were commonly used for transport.

“He was one of the great philanthropists of his time,” says Kilachand. “He gave practically his entire fortune to the village from which his ancestors came. This was an example handed down generation to generation of what philanthropy was about—it was our duty in life to support those less fortunate than ourselves. And that tradition has continued. I would like to think that it’s almost part of our genes now.”

night photo of the rajen kilachand center for integrated life sciences and engineering interdisciplinary science building at boston university

Rajen Kilachand’s gift, the largest in the history of Boston University, directs $15 million to support construction of the new Rajen Kilachand Center for Integrated Life Sciences & Engineering and $100 million to establish an endowment known as the Rajen Kilachand Fund for Integrated Life Sciences and Engineering. Photo by Janice Checchio

“Unless you dream about it, it’s not going to happen”

Kilachand says his commitment to improving education and health care was galvanized by business travel to the interior of India, Malaysia, Indonesia, and Africa, where access to schools and health care was largely nonexistent.

He became head of his family’s development company, the Dodsal Group, in 1982—and methodically expanded the company into a global player in mining, construction, manufacturing, and trading. When he moved the company to Dubai in 2004, he says, he decided it was time “to do philanthropy on a much larger scale.”

And he has done that. In addition to his record gifts to BU, Kilachand has given more than $35 million to health, education, and cultural causes in the United Arab Emirates, Africa, and India. He is the largest contributor to the first medical research institute in the UAE, the Al Jalila Foundation, and a regular contributor to the Sheikh Rashid Centre for the Disabled. He supports a Dubai Police Force program that encourages youth to participate in sports, and he is the sponsor of the Kilachand Theatre at Ductac, which anyone in the UAE can rent at minimum cost for events related to arts and culture. Kilachand has built clinics, hospitals, and facilities for the handicapped in India, and several primary schools in Africa. He is also a major supporter of the New Orleans Jazz and Heritage Festival, and his love of the arts (his were the winning bids for guitars owned by Carlos Santana and Mark Knopfler) has led to generous sponsorship of community theaters and arts and cultural festivals, including Gujarat’s annual kite festival, which he hosts in honor of his family’s love of the sport and also participates in.

Kilachand says his support for BU, which began six years ago with his $25 million gift, was inspired by a meeting with Brown, and, more fundamentally, by the influence of his mother, who instilled in him an appreciation for the humanities, particularly art and history.

“I give to BU and to education in the United States because I am a firm believer that there is not a country like the United States for higher education and research,” he says. “No place does it with such integrity and honesty. I really believe that in the coming century, leaders at all levels of society and leaders in every field must have a very strong sense of the importance of ensuring that some seven billion people have an opportunity to have a good education and quality health care. Maybe I’m asking for utopia, but unless you at least dream about it, it’s not going to happen. It’s not even going to get close.”

A gift like this “allows research to grow and perpetuate Boston University as one of the great research universities, not just in the United States, but also in the world.” —Kenneth J. Feld

Knox, who is also a generous benefactor of BU, shares the conviction. In his view, philanthropy like Kilachand’s is more important today than it has ever been. “For the past several years, there have been cuts in the research grants that come from the National Institutes of Health,” he says. “So it’s critical, it’s absolutely critical, that universities have support from private philanthropy to take up that slack that’s been created by government cutbacks. This tremendous commitment to the University by Rajen Kilachand will help us to make sure we are staying in the forefront of research.”

Kenneth J. Feld (Questrom’70), current chair of the BU Board of Trustees and also chair of the $1.5 billion Campaign for Boston University, says Kilachand’s recent gift is an “astounding gesture.”

“It means so much to the campaign and to Boston University,” says Feld, another of the University’s leading donors. “The most important results of the campaign are what it does for research, what it does for student aid, and what it does to bring professorships. It allows us to get the best people in the world to teach all those young people. It allows research to grow and perpetuate Boston University as one of the great research universities, not just in the United States, but also in the world.”

“The reputation of a great research university comes from the output of our faculty and students in research and scholarship,” says Brown. “Great universities are about the people, and the people are about the infrastructure you can supply and the environment you can give them to succeed. The Kilachand Center, in this area of life sciences and engineering, gives us the resources to attract those people and give them the resources to make an impact on the world.”

Kilachand says he is doing what his family has done for generations, but now with more urgency than ever. “Historically, the leaders of mankind went out and conquered for territory or for riches or for power or for ego,” he says. “The leaders of tomorrow have to go out and conquer for the environment and for health care and for education for seven billion people. And even if they do do it for ego, that’s OK.”

Read more about the Kilachand Center

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