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Brain Scientists Learn To Alter And Even Erase Memories

This optogenetic device uses light to activate specific brain cells. (Courtesy McGovern Institute for Brain Research at MIT)

This optogenetic device uses light to activate specific brain cells. (Courtesy McGovern Institute for Brain Research at MIT)

For 32 years, Leslie Ridlon worked in the military. For most of her career she was in army intelligence. Her job was to watch live video of fatal attacks to make sure the missions were successful.

“I had to memorize the details, and I have not got it out of my head, it stays there, the things I saw,” she says. “The beheading — I saw someone who got their head cut off — I can still see that.”

Leslie Ridlon retired from the military eight years ago, but she finds she cannot work because she suffers from severe PTSD. (Courtesy)

Leslie Ridlon retired from the military last year, but she finds she cannot work because she suffers from severe PTSD. (Courtesy)

Ridlon is now 49 and retired from the military last year, but she finds she cannot work because she suffers from severe post traumatic stress disorder. She has tried conventional therapy for PTSD, in which a patient is exposed repeatedly to a traumatic memory in a safe environment. The goal is to modify the disturbing memory. But she says that type of therapy doesn’t work for her.

“They tried to get me to remember things,” she says. “I had a soldier who died, got blown up by a mortar — he was torn into pieces. So they wanted me to bring that back. I needed to stop that. It was destroying me.”

She has concluded that some memories will never leave her. “Everything I could get rid of as far as memory I think I’ve already done it,” she says. “I think the deep ones that you suffer from, I don’t think anyone can take them away. I don’t believe anyone can. I think the ones I have now, they’re going to just stay there. I’m just going to have to manage them.”

But what if these traumatic memories could be altered or even erased permanently? Researchers say they are beginning to be able to do that — not just in animals, but in people as well.

Not long ago, scientists thought of memory as something inflexible, akin to a videotape of an event that could be recalled by hitting rewind and then play. But in recent decades, new technology has helped change the way we understand how memory works — and what we can do with it. Scientists can now manipulate memory in ways they hope will eventually lead to treatments for disorders ranging from depression to post-traumatic stress to Alzheimer’s disease.

“We now understand there are points in time when we can change memory, where we can create windows of opportunity that allows us to alter memories, and even erase specific memories,” says Marijn Kroes, a neuroscientist at New York University.

Kroes is working on doing just that in an NYU lab. On a recent afternoon, he was preparing a 21-year-old female subject for a three-day experiment.

He attached electrodes to the subject’s wrist so he could apply mild electric shocks when certain pictures appeared on the computer. This technique creates a fear memory, which he tests by measuring the subject’s sweat response.

On the second day of the experiment, Kroes shows the subject the same pictures to bring up the fear memory. He then waits 10 minutes — that’s the window, he says, when the memory becomes highly sensitive and vulnerable to change.

NYU neuroscientist Marijn Kroes attaches electrodes to subjects' wrist and applies mild electric shocks when certain pictures appear on a computer. This technique creates a fear memory -- which he tests by measuring the subject’s sweat response. (Courtesy)

NYU neuroscientist Marijn Kroes attaches electrodes to subjects’ wrists and applies mild electric shocks when certain pictures appear on a computer, creating a fear memory. (Courtesy)

“Briefly reactivating the memory weakens or pries the memory loose,” he says. “The connections in the brain for that memory, normally they would re-stabilize again, but if you interfere with that process you cause loss of those connections between brain cells, and as a result you lose the memory.”

After he waits 10 minutes, he again shows the images to the subject without the shocks.

“The trick here is, instead of immediately trying to teach people that a situation is safe, you first remind of their emotional experience,” he says. “And now you wait a little while, and this opens up a window of opportunity in which you can update and alter the memory.”

On the third and final day of the experiment, Kroes tests whether he is successful: Did he get rid of the fear memory?

“In her case, if we truly have been able to override the fear memory, she should not show any fear response to those stimuli,” he says. And indeed, “What we now see is a flat line — that means she doesn’t show fear responses. Thus, we see no evidence that she still has a fear memory.”

While scientists long believed that memories were stored in the brain permanently, they now understand that memory is in fact malleable. Kroes says this knowledge — and the ability to specifically alter memory on a cellular level — could lead to new treatments for people with many conditions.

NYU neuroscientist Marijn Kroes says the ability to alter memories could lead to new treatments for people with many conditions. (Rachel Gotbaum for WBUR)

NYU neuroscientist Marijn Kroes says the ability to alter memories could lead to new treatments for people with many conditions. (Rachel Gotbaum for WBUR)

“By understanding that memory is flexible, we can think of ways we can interfere with that flexibility,” he says. “For example, this allows us to potentially come up with new treatments for psychiatric disorders. But you can also think of ways we can understand how to optimize memories in people with degenerative disorders such as Alzheimer’s and dementia.”

The hope is that these new approaches can also be used to strengthen memories in patients with memory loss; animal studies are already under way. Also under way are human studies with patients who have PTSD and other disorders such as addiction. But Kroes warns that at this point he and other scientists only have a very early grasp of how these new techniques actually work. And they still have much more work to do before these new discoveries can be translated into effective treatments for the millions of patients suffering from memory and anxiety disorders.

Still, he and other researchers see a major shift in the concept of memory.

“I think it forces us not to think of memory as a video tape where we press play at the moment where we experienced an event,” says Elizabeth Kensinger, an associate professor of psychology at Boston College. “But instead think of the process of recalling a past event as a very active process where our brains are constantly trying to fill in pieces.”

And new technology is allowing scientists to manipulate memory directly in animals.

In the lab of Professor Susumu Tonegawa, a Nobel Prize-winning scientist at the MIT Picower Institute for Learning and Memory, researchers are using a powerful new tool called optogenetics to see how memory works in specific cells in real time.

“Moment by moment we our using our memory,” says Tonegawa. “It’s important for us to know how we form a memory, how we record a memory and how it goes bad under certain conditions.”

With optogenetics, scientists use lasers to identify specific memory cells and also to manipulate those cells.

Recently, Tonegawa’s lab used optogenetics to implant false memories into lab mice. Now, his lab is working on altering memories of mice with depression and symptoms of post-traumatic stress. The idea is to modify painful and stressful memories.

People like Ridlon, the veteran with PTSD, are waiting for the progress in labs to reach the point that it can help them.

“If someone took away all the bad memories and I could function every day, that would be great,” she says.

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How Playing Music Affects The Developing Brain

A cellist at the Conservatory Lab Charter School in Boston plays during a recital rehearsal. Research has found music instruction has beneficial effects on young brains. (Jesse Costa/WBUR)

A bassist at the Conservatory Lab Charter School in Boston plays during a recital rehearsal. Research has found music instruction has beneficial effects on young brains. (Jesse Costa/WBUR)

Remember “Mozart Makes You Smarter”?

A 1993 study of college students showed them performing better on spatial reasoning tests after listening to a Mozart sonata. That led to claims that listening to Mozart temporarily increases IQs — and to a raft of products purporting to provide all sorts of benefits to the brain.

In 1998, Zell Miller, then the governor of Georgia, even proposed providing every newborn in his state with a CD of classical music.

But subsequent research has cast doubt on the claims.

Ani Patel, an associate professor of psychology at Tufts University and the author of “Music, Language, and the Brain,” says that while listening to music can be relaxing and contemplative, the idea that simply plugging in your iPod is going to make you more intelligent doesn’t quite hold up to scientific scrutiny.

“On the other hand,” Patel says, “there’s now a growing body of work that suggests that actually learning to play a musical instrument does have impacts on other abilities.” These include speech perception, the ability to understand emotions in the voice and the ability to handle multiple tasks simultaneously.

Patel says this is a relatively new field of scientific study.

“The whole field of music neuroscience really began to take off around 2000,” he says. “These studies where we take people, often children, and give them training in music and then measure how their cognition changes and how their brain changes both in terms of its processing [and] its structure, are very few and still just emerging.”

Patel says that music neuroscience, which draws on cognitive science, music education and neuroscience, can help answer basic questions about the workings of the human brain.
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How Addiction Can Affect Brain Connections

As much of the country grapples with problems resulting from opioid addiction, some Massachusetts scientists say they’re getting a better understanding of the profound role the brain plays in addiction.

Their work is among a growing body of research showing that addiction is a complex brain disease that affects people differently. But the research also raises hopes about potential treatments.

Among the findings of some University of Massachusetts Medical School scientists is that addiction appears to permanently affect the connections between areas of the brain to almost “hard-wire” the brain to support the addiction.

They’re also exploring the neural roots of addiction and seeking novel treatments — including perhaps the age-old practice of meditation.

Meditation As Part Of Addiction Treatment

After spending 40 minutes lying on the floor with his eyes closed, being led through a meditation exercise, one of the students in a recent mindfulness class said something that many of the other students appeared to be thinking.

“I’m irritated,” he said, as several of the 30 other students murmured in agreement. Some giggled.

“I can’t really sit this long with my eyes closed without falling asleep,” he added. “I think this is overall positive. Maybe I just have a long way to go.”

Mindfulness has been touted as a way to boost quality-of-life issues, and the students in the class were there for various reasons: some to learn to relax, others to cope with health issues, and — at least one student — to support her recovery from alcoholism.
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In Search Of ‘Computational Psychiatry:’ Why Is It A Hot New Field?

By Suzanne Jacobs
WBUR Intern

It’s around 10 a.m. on a weekday when I walk into a coffee shop that apparently doubles as the preferred study spot of every student on the Boston University campus. My instinct is to leave immediately and find a quieter place to caffeinate, but I’m not here for the coffee. I’m here for information — information on what I’m hearing is one of the hottest new trends in brain science.

Winding my way through tables of frazzled co-eds, I search every face for that “Are you who I’m looking for?” stare, but no one acknowledges me. So I step back out onto the sidewalk and wait. I’m early anyway.

About five minutes later, a young man who would have otherwise been indistinguishable from the crowd of students locks eyes with me from about 20 feet away. “That’s my guy,” I think to myself.

Lights of Ideas (Andrew Ostrovsky)

(Andrew Ostrovsky)

Minutes later, coffees in hand, we’re seated at a small back table, and I put my digital recorder down on it. “Is it okay if I record this?” I ask. He says that’s fine.

At this point, what I really want to do is grab him by the shoulders and yell, “What are you people doing? Let me into your world!” For weeks, I’ve been looking into this new field of research called computational psychiatry, but for the life of me, I can’t figure out what it is. More frustratingly, I can’t figure out why I can’t figure it out, despite a strong science background and hours of reading what little I could find about the topic on the Internet.

But I hold back, press the little red circle on my digital recorder and let the man speak.

In computational psychiatry, “What you try to do is come up with a toy world…,” he begins.

This all started a few weeks earlier when I was perusing the latest edition of Current Opinion in Neurobiology. Don’t ask me why I was perusing Current Opinion in Neurobiology — I don’t know. To avoid doing something else, probably.

One article caught my eye. It was titled “Computational approaches to psychiatry.” A longtime subscriber to the drugs-and-therapy stereotype of psychiatry, I found the idea of new “computational approaches” intriguing, so I read on. Continue reading

How Childhood Neglect Harms The Brain

Like any new mother, the woman we’ll call Braille was full of hope and excitement the day she welcomed her son into her life seven years ago. “Peter” was 7 years old at the time of his adoption. He’d been living in foster care after being taken from his biological mother.

According to Braille, Peter and his siblings endured years of neglect and abuse living with their biological mother and her violent boyfriend. “It was physical, emotional and continual,” she says.

Peter, now 14, and his adoptive parents are very close now, but the years since the adoption have been challenging. His father recalls Peter’s unpredictable anger, and the times Peter would punch him, out of the blue. His mother says her son could be very sweet and affectionate one minute, but then “he would just fall apart and start banging his head against the wall or start screaming.”

Experts have long known that neglect and abuse in early life increase the risk of psychological problems, such as depression and anxiety, but now neuroscientists are explaining why. They’re showing how early maltreatment wreaks havoc on the developing brain.

Study Of Orphans Finds Smaller Brains

Dr. Charles Nelson, a Boston Children’s Hospital neuroscientist, studies how children’s early experiences shape the developing brain. Abuse and neglect, he says, can cause significant damage to the circuitry of the brain.

“Let’s say there are 1,000 neurons supposed to wire in a certain way, maybe only half wire that way and the other half wire in an incorrect way,” Nelson explains. “By altering the wiring diagram, you are altering behavior and altering psychological states.”

But what prevents the brain from wiring the right way, and how do early experiences get biologically embedded in the brain?
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‘I’m Not Stupid, Just Dyslexic’ — And How Brain Science Can Help

Sixth-grader Josh Thibeau has been struggling to read for as long as he can remember. He has yet to complete a single Harry Potter book, his personal goal.

Growing up with dyslexia: Josh Thibeau, 12, imagines his brain as an ever-changing maze with turns he must learn to navigate. Here he is with his mother, Janet. (George Hicks/WBUR)

Growing up with dyslexia: Josh Thibeau, 12, thinks of his brain as an ever-changing maze with turns he must learn to navigate. Here he is with his mom, Janet. (George Hicks/WBUR)

When he was in first grade, Josh’s parents enrolled him in a research study at Boston Children’s Hospital investigating the genetics of dyslexia. Since then, Josh has completed regular MRI scans of his brain. Initially, it seemed daunting.

“When we first started, I’m like, ‘Oh no, you’re sending me to like some strange, like, science lab where I’m going to be injected with needles and it’s going to hurt,’ I’m like, ‘I’m never going to see my family again,’ ” says Josh, who lives in West Newbury, Mass.

Josh and his three biological siblings all have dyslexia to varying degrees. Pretty much every day he confronts the reality that his brain works differently than his peers’. He’s even shared scans of his brain with classmates to try to show those differences. Some kids still don’t get it.

“There was a student that said, ‘Are you stupid?’ Because my brain was working in a different way,” Josh says. “And I’m just like, ‘No, I am not stupid…I’m just dyslexic.’ ”

The Pre-Reading Brain 

On average, one or two kids in every U.S. classroom has dyslexia, a brain-based learning disability that often runs in families and makes reading difficult, sometimes painfully so.

Compared to other neurodevelopmental disorders like ADHD or autism, research into dyslexia has advanced further, experts say. That’s partly because dyslexia presents itself around a specific behavior: reading — which, as they say, is fundamental.

Now, new research shows it’s possible to pick up some of the signs of dyslexia in the brain even before kids learn to read. And this earlier identification may start to substantially influence how parents, educators and clinicians tackle the disorder.

Until recently (and sometimes even today) kids who struggled to read were thought to lack motivation or smarts. Now it’s clear that’s not true: Dyslexia stems from physiological differences in the brain circuitry. Those differences can make it harder, and less efficient, for children to process the tiny components of language, called phonemes.

And it’s much more complicated than just flipping your “b’s and “d’s.” To read, children need to learn to map the sounds of spoken language — the “KUH”, the “AH”, the “TUH” — to their corresponding letters. And then they must grasp how those letter symbols, the “C” “A” and “T”, create words with meaning. Kids with dyslexia have far more trouble mastering these steps automatically.

For these children, the path toward reading is often marked by struggle, anxiety and feelings of inadequacy. In general, a diagnosis of dyslexia usually means that a child has experienced multiple failures at school.

But collaborations currently underway between neuroscientists at MIT and Children’s Hospital may mark a fundamental shift in addressing dyslexia, and might someday eliminate the anguish of repeated failure. In preliminary findings, researchers report that brain measures taken in kindergartners — even before the kids can read — can “significantly” improve predictions of how well, or poorly, the children can master reading later on.

Implicated in dyslexia: The arcuate fasciculus is an arch-shaped bundle of fibers that connects the frontal language areas of the brain to the areas in the temporal lobe that are important for language (left). Researchers found that kindergarten children with strong pre-reading scores have a bigger, more robust and well-organized arcuate fasciculus (bottom right) while children with very low scores have a small and not particularly well-organized arcuate fasciculus (top right). (Zeynep Saygin/MIT)

Implicated in dyslexia: The arcuate fasciculus is an arch-shaped bundle of fibers that connects the frontal language areas of the brain to the areas in the temporal lobe that are important for language (left). Researchers found that kindergarten children with strong pre-reading scores have a bigger, more robust and well-organized arcuate fasciculus (bottom right) while children with very low scores have a small and not particularly well-organized arcuate fasciculus (top right). (Zeynep Saygin/MIT)

Pinpointing The White Matter Culprit

Using cutting-edge MRI technology, the researchers are able to pinpoint a specific neural pathway, a white matter tract in the brain’s left hemisphere that appears to be related to dyslexia: It’s called the arcuate fasciculus.

“Maybe the most surprising aspect of the research so far is how clear a signal we see in the brains of children who are likely to go on to be poor readers.”
– MIT neuroscientist John Gabrieli

“It’s an arch-shaped bundle of fibers that connects the frontal language areas of the brain to the areas in the temporal lobe that are important for language,” Elizabeth Norton, a neuroscientist at MIT’s McGovern Institute of Brain Research, explains.

In her lab, Norton shows me brain images from the NIH-funded kindergartner study, called READ (for Researching Early Attributes of Dyslexia).

“We see that in children who in kindergarten already have strong pre-reading scores, their arcuate fasciculus is both bigger and more well organized,” she says. On the other hand: “A child with a score of zero has a very small and not particularly organized arcuate fasciculus.”

She says we’re not quite ready to simply take a picture of your child’s brain and say “Aha, this kid is going to have dyslexia,” but we’re getting closer to that point. Continue reading

Unlocking The Brain: Are We Entering A Golden Age Of Neuroscience?

"We still haven’t unlocked the mystery of the three pounds of matter between our ears. That knowledge could be -- will be -- transformative,” President Obama said in announcing the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative on April 2, 2013, at the White House. (Charles Dharapak/AP)

“We still haven’t unlocked the mystery of the three pounds of matter between our ears. That knowledge could be — will be — transformative,” President Obama said in announcing the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative on April 2, 2013, at the White House. (Charles Dharapak/AP)

President John F. Kennedy set the nation’s sights on the moon. Fifty years later, President Obama announced his signature science project: neuroscience, the study of the brain.

“As humans,” he said last April, “we can identify galaxies light years away, we can study particles smaller than an atom, but we still haven’t unlocked the mystery of the three pounds of matter between our ears.”

The president committed an initial $100 million to BRAIN, an acronym for Brain Research through Advancing Neurotechnologies, to fund the development of better tools for studying how the brain works. “That knowledge could be — will be — transformative,” he said.

Over the next two months, WBUR will present a weekly series about brain science advances — many happening in Boston, a major hub for neuroscience research. Today, the overview.

If you click the “Play” arrow above, you’ll hear the hissy, Morse-Code-on-steroids sound of neurons firing, sending signals to each other.

So is this what a thought of yours would sound like, if it were played through an audio monitor like this? No. What you’re hearing is far, far simpler. These neurons belong to a crab; they make up a simple circuit of about 30 neurons that control how it chews and digests food. Their steady, rhythmic cycle is more like what your neurons do to control your breathing.

“Imagine now,” says Brandeis University neuroscientist Eve Marder, “an orchestra with billions of neurons firing in different patterns depending on what you were seeing, what you were hearing, what you were thinking and what you were feeling, so those rhythms would be changing in a tremendous symphony. If you could hear all of the neurons in your brain, it would be very hard to hear patterns, because there would be so many instruments, if you will, playing at the same time. It might sound like a cacophony.”

Making sense of that cacophonous complexity, she says, will be a lot harder than JFK’s moon shot.

“Unlike putting [a] man on the moon, where you knew exactly where the goal was and the problem was largely an engineering problem,” she says, “understanding the brain is a series of engineering problems and a series of intellectually creative, imaginative understandings, and it’s going to require the coordination of creativity across every scientific discipline that we know.”

But even if we give it everything we’ve got, can the human brain ever understand itself?

That’s the monumental gamble of Obama’s BRAIN initiative — and other major neuroscience efforts now getting under way around the world. They’re not trying to solve philosophical questions. They’re responding to the growing realization that brain disorders — from autism to mental illness to dementia — are a worldwide scourge, affecting at least a billion people.

“The global cost from brain disorders is about $2.5 trillion, and will go up more than double over the next two decades,” says Tom Insel, director of the National Institute of Mental Health. “So policymakers look at these numbers and say, ‘Oh my God, we have got to begin investing to make sure we don’t incur those kinds of costs.’ ”

Neuroscientists have been studying the brain for more than a century, and better treatments for brain diseases have been desperately needed for a lot longer than that. What’s different now is that for the first time, researchers say, we’re beginning to get a handle on the workings of the brain’s billions of neurons and trillions of connections. We’re starting to understand how groups of neurons interact, in smaller circuits or bigger networks — and that scale, out of reach even just a few years ago, is what we need if we ever hope to understand how we have a thought, or a memory, or a mental illness.

“This is an exciting time to be a neuroscientist. I’m not sure there’s ever been a more exciting time,” Larry Swanson, president of the Society for Neuroscience, told an audience last fall at the society’s annual conference of about 30,000 scientists. Continue reading

5 Ways The Brain Stymies Scientists And 5 New Tools To Crack It

Dr. Steven Hyman (Maria Nemchuk/Broad Institute)

Dr. Steven Hyman (Maria Nemchuk/Broad Institute)

In past lives, Dr. Steven Hyman has been the director of the National Institute of Mental Health and the provost of Harvard. He’s currently the president-elect of the Society for Neuroscience, and he directs the Stanley Center for Psychiatric Research at the Broad Institute in Cambridge, where we spoke, and where he demonstrated a preternatural professorial ability to speak off-the-cuff in structured outlines. Our conversation, lightly edited and broken down into what seemed to be its natural numbering scheme:

The Obama BRAIN initiative. We’ve had a ‘decade of the brain’ before, in the 1990s —

It accomplished nothing. Because it was a media blitz, it wasn’t based on new science.

So — Why this? Why now? What’s different?

Part of the growing public interest in the brain, and certainly much media attention, is a little bit unfortunate because it focuses on people applying tools, such as brain imaging, in ways that are untutored and underpowered but yield interesting — if not really scientifically valid — ideas about say, why a certain person is liberal or conservative, or why a certain person takes risks or is very self-protective. A subset of those may be scientifically addressable questions, but we’re a long way from understanding them deeply. Nonetheless they’re irresistible to the public and then of course it’s given rise to a new generation of debunkers — fair enough. So maybe we can set aside this false interest, this prurient interest in the brain and focus on the serious matters at hand.

In terms of political will, the question is not why now but why so late?

The bottom line is the brain is well recognized to be the linchpin of being human in the sense that it is the substrate of thought, emotion, control of behavior, and therefore, undergirds our life trajectories, our actions, our morality. And when the brain gets sick in any way we realize that it exacts an extraordinarily severe toll on the sufferer, on families, on society. Just think about Alzheimer’s disease, heroin addiction, major depression, schizophrenia, autism, intellectual disability — these are common conditions in which people can no longer exert reliable, effective agency on their own behalf and therefore society often has to step in for them at great cost and often really great pain.

Tragically, for the longest time there wasn’t so much we could do about it. Using medications that were really discovered by luck, by prepared serendipity; using, in more recent years, the few psychotherapies, especially Cognitive Behavioral Therapies, which have been empirically tested, we have been able to help a lot of people manage their symptoms, in some cases to become better stoics. With imaging technologies we began some decades ago — though at really still very relatively poor resolution — to get spatial maps of what’s happening in the brain. But we were really stymied in terms of getting a deeper understanding, a better picture, for several reasons:

1. The brain is new

The first, which is really important, is that the human brain is evolutionarily very recent in terms of many of its higher functions. What this means is that although we can learn an enormous amount from studying animals the way we do in the rest of biology and medicine, animal models are ultimately limited. Anything that requires language, just to take one example, we can’t model in animals. I think I understand my dog, but I wouldn’t publish it. There are really very many important functions — language, morality, certain kinds of creativity, the arts, humor, not to mention human mental illnesses, that really have not been well modeled in animals.

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