brain research


Researchers Say They Can Lift Depression In Mice By Activating Happy Memories



You know when you’re feeling really down, or worse, in the throes of depression, and there’s always that chirpy person who earnestly says: “Just try to focus on happy thoughts; think positive!” Well, it turns out, that unshakeable optimist may have a point.

MIT scientists report that they are able to “cure” the symptoms of depression — in mice — by artificially activating happy memories that were formed before the depression took hold.

The findings, published in the journal Nature, hint at a future in which depression might be treated by manipulating brain cells where memories are stored.

MIT graduate student Steve Ramirez, the lead author on the paper, explains that while the work is tantalizing, it’s a long way from any real-world application in people:

“We’re doing basic science that aims to figure out how the brain works and how it can produce memory,” Ramirez said in an email. “The more we know about how the brain works, the better equipped we are to figure out what happens when brain pieces break down to give rise to broken thoughts. In my opinion, we’re a technological revolution away from being able to do this in humans; everything that exists currently is too invasive and not targeted enough. That said, the underlying proof-of-principles are there, as we can do these kinds of manipulations in animals. The question is how we can do this in humans in an ethically responsible and clinically-relevant manner.”

Still, he says, researchers did not expect such clear results:

“The finding that stimulating positive memories over and over actually forces the brain to make new brain cells was surprising,” he wrote. “We did not expect to have such a clean result demonstrating that artificially activated positive memories correlates with an increase in the number of new brain cells that are made.” Continue reading

The Complex Interplay Of Genetics And The Placebo Response

Why do some people respond to placebos while others don’t?

One possible answer: genetics.

A provocative new paper introducing the concept of a “placebome” — that is, the complex interplay between genetics and an individual’s response to placebos — raises questions that might ultimately lead to changes in how clinical studies of drugs are evaluated.

Indeed, researchers from Harvard Medical School suggest that genes, and genetic variation, might play a far bigger role in the placebo response than previously thought.

That the placebo effect is an actual physiological response is well established. But the new report, a research review, looks specifically at the placebo response in the context of drug studies, where some participants get the active medication while others get a placebo, or non-active version of the drug.

The new findings, “call into question whether or not the outcomes in a drug treatment arm of a clinical trial are limited to the effect of the drug on the condition,” says Kathryn Hall, an integrative medicine fellow in the Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center, and one of the study authors.

Instant Vantage/flickr

Instant Vantage/flickr

Several neurotransmitters, such as dopamine, appear to be involved in the placebo response, Hall said, and variation in the genes in these pathways appears to change our response to placebo. So different people with different genotypes respond differently to placebos.

But Hall takes it one step further. “When you are in a trial you don’t know if you are getting the drug or the placebo, so not just the people in the placebo arm can have placebo responses. We are curious about the drugs’ effect on the placebo response.”

It’s all a bit tough to wrap your brain around, so I asked Hall to give me an example. Here’s what she said:

In the literature we see several studies in which in the placebo arm one group of people with a certain genotype have a strong placebo response and the other group has a weak placebo response. And when we look at the drug treatment arm, we see the outcomes are reversed, the people who had the strong response in the placebo arm now have a low response and the people who didn’t have a response in the placebo arm now have a strong response. The historical interpretation of these results has been that only one group of people responds to the drug and we’re pointing out that it’s more complicated than that. It’s that one group responded to the placebo and that response is eliminated in the drug treatment arm.

What all this means in the real world is still hard to know. But in their paper published this week in the journal, Trends in Molecular Medicine, the researchers offer these three key takeaways in the abstract:

•The predisposition to respond to placebo treatment may be in part a stable heritable trait.

•Candidate placebo response pathways may interact with drugs to modify outcomes in the drug treatment arms of clinical trials.

•Genomic analysis of randomized placebo and no-treatment controlled trials are needed to fully realize the potential of the placebome.

Continue reading

A Podcast For Your Brain: The Checkup, Episode 8

It’s the only organ in the human body that tries to understand itself (though not always successfully).

Still, the brain is on our brains in the latest episode of The Checkup, our recently relaunched health news podcast, a joint venture between WBUR and Slate.

Can you enhance your brain through music? Detect dyslexia even before kids learn to read? Alleviate the symptoms of deep depression with a brain implant?

Carey and I explore these and other questions as we delve into some of the latest advances in brain research.

And in case you missed our last episode, “Scary Food Stories,” where we tell the tale of a recovering sugar addict and offer sobering news to kale devotees, you can listen now, or download it anytime.

Make sure to tune in next week, when we present: “Grossology,” an episode on how the dirty corners of your life might benefit your health.

Each week, The Checkup features a different topic — previous episodes focused on college mental health, sex problems, the Insanity workout and vaccine issues.

Sugar On The Brain Circuit: Mice Seeking Sweets May Hold Key To Compulsive Overeating

You know the feeling: you’re tired, cranky, low or just have a serious, relentless desire for something sweet. Part of your brain cries out, “No, don’t do it, this will end badly.” But another (louder) part wants what it wants and won’t let up until that pint of Cherry Garcia, or red velvet cupcake or Caramel Macchiato is in plain sight. It’s an itch that must be scratched.

Now, brain scientists at MIT say they’ve identified a specific neural circuit in mice that can increase that compulsive overeating of sweets, but doesn’t interfere with normal eating patterns necessary for survival. More specifically, turning on this set of neurons drove mice to seek the reward of a sugary drink even in the face of punishment (a shock to the foot); and compelled them to eat voraciously even when full.  When the researchers shut down this pathway, however, the compulsive sucrose-seeking decreased.

Why does this matter? The new research, published in the journal Cell, may ultimately provide a target for the treatment of compulsive overeating and sugar addiction in humans, without undermining the clearly critical drive of eating to live, the scientists say.

“Imagine if I told you that in the future, we could change the way our neural circuits communicate in a way that I did not want to binge on sweets, but still allowed me to eat healthy foods when I’m hungry?” says Kay Tye, the study’s senior author and an assistant professor in the Department of Brain & Cognitive Sciences at MIT. “Obviously there is a ton of work that needs to be done to make this vision a reality, but our study suggests that it is possible.”

A Binge-Free Future?

As obesity rates have spiked in recent decades, experts say that overeating in general and consuming too much sugar in particular are major threats to human health.

But Tye says “the real underlying problems are the cravings that lead to compulsive eating, and the behavior of compulsive overeating itself.”

To tease out what might be driving that compulsion, Tye looked to a particular set of neurons in the mouse brain.

She and her colleagues showed that when mice perform reward-seeking actions enough that they become habits, that activates neurons connecting two key areas: a brain region called the lateral hypothalamus (an area important for hunger, feeding and homeostasis) and the ventral tegmental area (a brain region important for motivation and reward).

“If we want to understand how the brain gives rise to these feelings, thoughts and actions, we need to know more than what they are saying, we need to know who they are talking to,” Tye said. The team used so-called “optogenetic projection-defined phototagging” [essentially using laser light to activate or silence neurons] to see “which neurons…were saying what…and who they were talking to…”

These neural communications are quite distinct, Tye said; for instance, it’s important to distinguish between two types of reward-seeking behavior: binge-eating and drug addiction: “You don’t need cocaine to survive, you need food to survive,” she said.

The “Wanting” Neurons

Tye says that one of the biggest challenges with treating the obesity that comes from compulsive overeating disorders is that “most treatments are just a band-aid — treating the symptoms instead of the core problems.  Gastric bypass for example, is something that just makes it harder to eat, it doesn’t always change a person’s habits and eventually many people relapse and regain the weight.” Again, she theorizes that it’s the craving embedded in the brain that drives the compulsive behavior. She says there may be a distinctive set of  “wanting neurons” as opposed to “liking neurons.” Continue reading

Making Peace With My Abnormal Brain

(Andrew Ostrovsky)

(Andrew Ostrovsky)

By Dr. Annie Brewster
Guest Contributor

What you never want to hear from the radiologist: “I wouldn’t mistake it for a normal brain.”

Yet this is what I recently heard from my radiologist friend who kindly took a look at an MRI of my brain. Let me repeat: it was my abnormal brain under discussion here, and I’ll tell you, his assessment was tough to hear.

The state of my brain isn’t exactly news to me. I have had Multiple Sclerosis since 2001, and I have frequent MRIs. Moreover, as a physician at the hospital where I get my treatment, I have the dubious privilege of having complete and immediate access to my medical chart. As such, I often see the MRI images and read the reports before my neurologist does, and fortunately or unfortunately, I understand “medicalese.” (And I have radiologist friends.)

Every time I get an MRI, I devour these reports as soon as they become available on the computer, scanning optimistically for words like “stable.” I even hold onto the absurdly magical hope that old lesions will have disappeared, and that this whole diagnosis of MS has been a big mistake. Instead, I find mention of new “hyperintense foci of white matter signal abnormality” and “enhancing” lesions, “consistent with actively demyelinating MS plaques.” I fixate on words like “volume loss” and “atrophy” and in one preliminary report generated by a resident, I think I saw the word “diminutive.” Did I imagine this?

Despite the sting of these words, I am able to remain somewhat detached. As a doctor, I spend my days looking at radiology images and reading such reports.

Often — due to the formal and impersonal language that is used — it’s hard to remember that the body part being referred to is actually part of a human being. It is even harder to remember that it is part of me!

“I wouldn’t mistake it for a normal brain” penetrates deeper. I understand. My brain is under attack, and is irreparably damaged.

My first response is to mount a defense. I feel the need to tell you that my brain is still a good brain. It just has a few small blemishes. It still works! I recently passed the required ten year recertification medical boards (apparently I will never escape bubble tests), and I feel smarter than ever. I am the mother of four and the primary logistical organizer in my
household, and my (short term) memory is at least ten times better than my husband’s (no offense, honey). Furthermore, research has clearly shown that MRI findings do not necessarily correlate with clinical symptoms in Multiple Sclerosis. So there is no cause for alarm.

Also, the research is promising. Exhibit A is this massive MS conference currently underway in Boston with many great minds focusing their attention on new approaches, such as potential remyelinating therapies, to tackle the disease. (MS damages the myelin, the sheath around nerve cells, and remyelination would restore it.)

My neurologist, Eric Klawiter, at Massachusetts General Hospital, writes me this:

As a research community, we have gained a great deal of knowledge on the mechanism of remyelination and how that process can go awry in MS. There are several candidate compounds demonstrated to promote the body’s ability to differentiate precursor cells into cells that lay down new myelin (oligodendrocytes). It is yet to be established whether these candidate therapies will work best to promote immediate recovery from relapses or whether they will also be effective in the setting of remote demyelination.

Of course, any potential new therapies are years or more away and don’t do much for me right now.

So, underneath my bravado, there is vulnerability. Continue reading

Cheap, Low-Tech Devices Help Paralyzed Patients ‘Speak Their Minds’


Cathy Hutchinson, who had a brainstem stroke, is using a head mouse to type on a prototype keyboard, and has typed that she likes it. (Courtesy SpeakYourMind Foundation.)

By Suzanne Jacobs
Guest contributor

When the man started quoting Shakespeare with his eyebrow, Dan Bacher knew he was on to something.

All it took was an off-the-shelf webcam, a green sticker and an app, and the stroke victim had regained his ability to communicate.

“Before that, what he would do is, someone would stand next to him and literally read through the alphabet, and then he would raise his eyebrow to pick a letter,” Bacher says. “He was fully dependent on someone else, and he couldn’t initiate conversation. Someone had to say, ‘Do you want to say something?’”

So Bacher, an engineer, and his colleagues put a green sticker the size of a pencil eraser on the man’s eyebrow and turned a webcam into a tracking system that could follow the green sticker and register a raised eyebrow as a mouse click. With a custom-made app, the man could then scroll through the alphabet and type on his own.

And then Shakespeare — part of a line from “Henry IV” that goes, “A good wit will make use of anything; I will turn diseases to commodity.”

“It was just like one of those wow moments, where we realized, ‘Wow, what we’re doing here really is making a difference,’” Bacher recalls. The device was just a prototype, but Bacher said he hopes to have something permanent for the patient in the coming months.

Bacher is the founder and CEO of the SpeakYourMind Foundation, a nonprofit organization based in Providence, Rhode Island, that’s developing low-cost and easy-to-use communication devices for people with neurological disorders who are “locked in,” virtually unable to move.

So far, the organization has only worked with about 12 clients and is still experimenting with prototype devices, but ultimately, Bacher says, he wants to have products that are widely available. Already, he says, people have been contacting him from around the country asking for help.

SpeakYourMind is far from the cutting edge of research on “brain-computer interfaces,” but that’s the point. Having worked in Brown University’s BrainGate Lab, one of the leading research centers for advanced brain-computer interface technology, Bacher knows all about the cutting edge, and that’s why he decided to start SpeakYourMind — to give people a simpler option, at least for now. Continue reading

Pop Awake At Night? Researchers Blame ‘Sleep Switch’ In Your Aging Brain

(eflon via Compflight)

(eflon via Compflight)

If you’re on the older side and find yourself popping hideously awake in the middle of the night or far-too-early morn, here’s your line for the next time it happens: “Oh, that darned ventrolateral preoptic nucleus of mine! How I miss my old galanin!”

Researchers have just reported in the journal Brain that they’ve found a group of neurons — in the aforementioned nucleus — that function as a kind of “sleep switch,” and whose degeneration over the years is looking very much like the cause of age-related sleep loss. It’s also looking pivotal in the insomnia that often causes nocturnal wandering in people with Alzheimer’s disease.

“This is the first time that anyone has ever been able to show in humans that there is a distinct group of nerve cells in the brain that’s critical for allowing you to sleep,” said the paper’s senior author, Dr. Clifford Saper, chair of neurology at Beth Israel Deaconess Medical Center and professor of neurology at Harvard Medical School.

You may well be wondering exhaustedly how soon this insight — based on the post-mortem analysis of 45 human brains — will lead to better sleeping pills for older folks. I asked Dr. Saper that, too. No promises with timeframes at this point, but he does see the prospect for better-targeted sleeping pills for seniors, with fewer side effects like Ambien’s balance-related problems.

Our conversation, lightly edited:

Can this group of neurons actually explain the lion’s share of sleep problems that older people and people with Alzheimer’s disease have?

It really can. Let me give you a little background. We discovered this cell group in the brains of rats in 1996. We found that there’s a group of of nerve cells in a part of the brain called the hypothalamus that fire when animals are asleep. And we later found that if you eliminate those nerve cells, that animals lose up to 50 percent of all their sleep time, and the remaining sleep is fragmented. They can’t sleep for long bouts at a time; they keep waking up all the time.

At that time, we weren’t sure whether this would be the same in other species. So we looked at the brains of half a dozen other species — of mice and cats and monkeys — and we found that all of them have this cell group and that the cells were active during sleep in all of them. In every species we looked at, this same cell group had a particular neurotransmitter in it, called galanin.

I’ve never heard of that neurotransmitter before… Continue reading

‘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

Tracking Dyslexia In The Preschool Brain

By Karen Weintraub
Guest Contributor

Roughly one child in 10 will struggle to learn to read, but no one can tell which one until he or she starts to fall seriously behind.

At that point – often in 3rd grade – they’ve already taken a hit to their self-esteem and they’re too old for early intervention that can make the biggest difference.

This conundrum has troubled MIT professor John Gabrieli for years.

The area highlighted in yellow, called the arcuate fasciculus, is less robust in children at high risk for dyslexia, according to a new study.

The area highlighted in yellow, called the arcuate fasciculus, is less robust in children at high risk for dyslexia, according to a new study.

Today, the neuroscientist and colleagues published a study that begins to address the problem. They showed on brain scans that kindergartners at risk for dyslexia also had less robust connections between two key language areas on the left side of the brain.

Previously, researchers weren’t sure whether the differences they saw in the brains of people with dyslexia were causes of the condition, or effects of their struggle to read. Because Gabrieli’s group saw the distinction in children too young to read, their brain differences must predate reading problems.

His ultimate hope, of course, is to use these differences to identify children before they begin to struggle, and get them into early intervention programs. Continue reading

Why To Exercise Today: Better Grades

Granted, this is a study about kids, but don’t we all want better grades in life, too?

Reuters reports here today:

“Children who get more exercise also tend to do better in school, whether the exercise comes as recess, physical education classes or getting exercise on the way to school, according to an international study. The findings, published in the Archives of Pediatrics & Adolescent Medicine, come as U.S. schools in general cut physical activity time in favor of more academic test preparation.”

Dr. John Ratey, a Cambridge-based psychiatrist and author of the excellent book “Spark,” is all over the topic of how exercise helps children learn, and I see on his Website that it even hosts a documentary called “Brain Gains” about the effects of pilot exercise programs in schools.

Reuters reports:

Three of the four studies involving an exercise intervention found that students given more exercise time scored higher on measures of academic performance. Continue reading