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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.
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Inspired By Family Illness, Philanthropist Gives $650 Million For Psychiatric Research

The Broad Institute of Harvard and MIT  summer student Lydia Emerson and aesearch associate Aldo Amaya. (Courtesy/Kelly Davidson Photography)

Researchers at the Broad Institute plan to use Ted Stanley’s money to catalog all the genetic variations that contribute to severe psychiatric disorders. (Courtesy/Kelly Davidson Photography)

In the largest-ever donation to psychiatric research, Connecticut businessman Ted Stanley is giving $650 million to the Eli and Edythe Broad Institute of MIT and Harvard. The goal — to find and treat the genetic underpinnings of mental illnesses — was inspired by a family experience.

Ted Stanley made his fortune in the collectibles business. He founded The Danbury Mint, a company (later MBI, Inc.) whose first product was a series of medals commemorating the biggest scientific achievement of its time: the moon landing in 1969. While his business grew, his son Jonathan Stanley grew up as a normal Connecticut kid. Until, at age 19, Jonathan came down with bipolar disorder with psychosis, which got worse over the next three years.

“We’ll call it the epiphany from my dad’s standpoint at least,” Jonathan Stanley remembered of the turning point in his illness. “I went three days straight running through the streets of New York, no food, no water, no money, running from secret agents. And not surprisingly, after I stripped naked in a deli, ended up in a psychiatric facility.”

Jonathan was a college junior at the time.

“My dad came to visit, and he got to see his beloved son in a straitjacket,” Jonathan Stanley said.

The Stanleys were lucky. Jonathan responded well to the lithium, then a newly-approved drug. He went on to graduate from college and law school, too. Yet along the way, his father had met other fathers whose sons did not respond to treatment. He met other families who had to keep living with uncontrolled mental illness.

Ted Stanley said that gave him a focus for his philanthropy.

There was something out there that our son could take, and it made the problem go away,” he said. “And I’d like to see that happen for a lot of other people. And that’s why I’m doing what I’m doing.”

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Medical Marijuana 101: What’s In Your Drug?

Jack Boyle reaches across the marble island in his kitchen for a small blue glass bottle with a black rubber cap. He holds it to the light, shaking the liquid, a marijuana concentrate.

“The person who made this didn’t make it properly,” Boyle says.

Boyle’s wife Susan Lucas uses the marijuana concentrate, or tincture, to prevent epileptic seizures. The first batch helped, so Boyle went back for more.

But then, “Sue started seeing her symptoms coming back,” he says. “We immediately took [the new batch] to the lab, had it tested. It didn’t have the CBD in it.”

The second batch, it seems, wasn’t heated enough to activate CBD, one of the compounds in marijuana that supporters say helps with muscle spasms and seizures.

Now Boyle is learning how to make a perfect concentrate on his own, in his kitchen in Stow. He bought a Crock-pot and found a recipe for marijuana tinctures online.

“I’ll make a batch and have Michael Kahn test it again, and if [it] matches up to at least as strong as the first batch then we’re good to go for six months to a year,” Boyle says. “It’s my wife, I just want to do the best I can.”

Michael Kahn is an analytical chemist and president of Massachusetts Cannabis Research, or MCR Labs, in Framingham. It’s the first marijuana testing lab to open in Massachusetts.

“We provide quality control,” Kahn says.

With all the attention to dispensaries that will grow and sell marijuana for medical use, the question of who will test the drug has been largely overlooked. The state Department of Public Health (DPH) is expected to issue testing protocols soon, but they may be a work in progress — at least for the first few years — as this industry takes shape across the country.
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New Concerns About Coakley-Partners Deal

There are new concerns about an agreement Attorney General Martha Coakley negotiated to try and control the prices and market power of Partners HealthCare. The implication, from a commission created to help reduce health spending, is that the deal does not go far enough.

“Without lasting change to the market structures,” the Health Policy Commission (HPC) writes in comments to be filed in court, “price caps may not be effective in keeping costs down.”

Price caps?

The commission dug in on a portion of the deal Coakley reached with Partners — the part that says network prices could not rise faster than inflation for six and a half years.

“Prices themselves, they are important,” said commission chairman Stuart Altman, “but they’re not the end of the game.”

To explain why, picture a colleague, neighbor, maybe your grandmother — someone who’s had hip replacement surgery. Now picture two hospitals.

“In one place,” said Altman, “a hip costs $10,000 to replace. In another, it’s $15,000.”

Under Coakley’s deal, prices at each of these Partners hospitals would rise slowly. But there’s nothing to keep Partners from sending more patients to the $15,000 facility. If more patients have hips replaced at the higher-cost hospital, then total health care costs would go up, even if prices don’t.

“Total medical expenditures, when we finally figure it out, is going to up by a lot, but yet the price increases were fine,” Altman said.

Coakley would have someone monitoring Partners, who could, in theory, intervene if a significant number of patients shift from lower- to higher-cost hospitals. But that monitor would only have access to spending for patients covered by a global budget, which Partners says is about 25 percent of its business.
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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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For Rwandan Man In Boston, New Arms Replace Those A Father Destroyed

Greig Martino fits a new prosthetic on Patrick Mbarushimana at the United Prosthetics workshop in Dorchester. (Jesse Costa/WBUR)

Greig Martino fits a new prosthetic on Patrick Mbarushimana at the United Prosthetics workshop in Dorchester. (Jesse Costa/WBUR)

In the mid-1990s, following the Rwandan genocide, clashes between government forces and mostly Hutu rebels continued along the country’s border with then Zaire. One day, soldiers came to a mud brick home in a small village and questioned a father while his young son listened.

The father denied helping rebels, but the boy, then 6 years old, said yes, some men had slept in the house the night before. The soldiers took the father away.

When the father returned a day later, “he said that he’s going to do something that I won’t forget,” recalled Patrick Mbarushimana, now 22.

(Jesse Costa/WBUR)

(Jesse Costa/WBUR)

The details of Patrick’s punishment are murky. In one story that circulated through his village, the father tied Patrick by the arms to a tree. Gangrene set in before he was released. In Patrick’s memory, his father started a fire and sat on him, with his bound arms facing the blaze until rope burned through to the bone.

Patrick says his father left him to die, but he ran away to the soldiers and told them what happened. The father was arrested.
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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

To Beat Heroin Addiction, A Turn To Coaches

Two young men sit in a car outside a church or union hall where they just attended a Narcotics Anonymous meeting. Both men are addicted to heroin. But they haven’t used the drug since they finished a residential treatment program a week or so earlier.

“This happens a lot, there’s the two of us sitting together,” says Jeremy Wurzburg, a thin, pale 21-year-old who became addicted to heroin two years ago.

Gosnold recovery coach Kristoph Pydynkowski, right, takes Jeremy Wurzburg kayaking, building a life of healthy, positive activities in early recovery. (Courtesy Pydynkowski)

Gosnold recovery coach Kristoph Pydynkowski, right, takes Jeremy Wurzburg kayaking, building a life of healthy, positive activities in early recovery. (Courtesy)

“We both,” Wurzburg pauses, “we’re not sure whether we’re going to use or not and someone makes like a half joke: ‘We could just go out and drink right now’ or something and the other one’s like, ‘Yeah, let’s do that, sounds good.’ And then it’s off.”

That moment, for Wurzburg, could lead right back to his drug of choice, heroin. Most recovery programs, he says, don’t — and maybe can’t — prepare patients in early recovery to fight that urge alone.

“Once I got out of treatment into the real world, it was a big shock,” Wurzburg says. “It’s easy not to use while you’re in rehab. It’s not put in front of you or anything. But then once I got out into the real world, it’s like, I had the knowledge of what to do, but I didn’t have the, those skills yet, or the tools to say ‘no.’”

Of patients addicted to heroin who stop, 40 to 60 percent relapse within the first year. For many it happens soon after finishing a recovery program.

‘Custom-Tailored’ Recovery Help

The next time Wurzburg walked out of a treatment facility, he stepped into a new young adult recovery program. It’s a one-year pilot project at Gosnold, which runs a network of addiction treatment services on Cape Cod.

Wurzburg agreed to live in a sober house, attend daily 12-step group meetings and get individual counseling. Participants can download a smartphone app that has a panic button, a list of addiction services and GPS tracking if patients want their coaches to know when they are near common heroin sale and use sites. There are group trips to ski, hike and listen to the symphony. Perhaps most importantly, Wurzburg has help daily, sometimes hourly, from a recovery coach.
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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