Tag: brain

Deep brain stimulation may help children with Rett syndrome

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The dentate gyrus of a mouse that received deep brain stimulation, with cell nuclei in blue and expression of the gene c-Fos in red.

By Shawna Williams

Even as patients with Parkinson’s disease, obsessive-compulsive disorder, and other conditions turn to deep brain stimulation (DBS) to keep their symptoms in check, it’s been unclear to scientists why the therapy works. Now, researchers in Texas report that in mice, the treatment dials the activity of hundreds of genes up or down in brain cells. Their results, published in eLife March 23, hint that DBS’s use could be expanded to include improving learning and memory in people with intellectual disabilities.

“The paper is very well done. . . . It’s really a rigorous study,” says Zhaolan “Joe” Zhou, a neuroscientist at the University of Pennsylvania’s Perelman School of Medicine who reviewed the paper for eLife. Now that the genes and pathways DBS affects are known, researchers can home in on ways to improve the treatment, or perhaps combine the therapy with pharmacological approaches to boost its effect, he says.

In DBS, two electrodes are surgically implanted in a patient’s brain (the area depends on the disorder being treated), and connected to generators that are placed in the chest. Gentle pulses of electricity are then passed continuously through the electrodes. The treatment reduces motor symptoms in many people with Parkinson’s, and allows some patients to reduce their use of medications, but it does not eliminate symptoms or slow the disease’s progression.

In addition to its use in movement disorders, DBS is being explored as a potential therapy for a range of other brain-related disorders. For instance, as a way to boost learning and memory in people with Alzheimer’s disease, researchers are looking into stimulating the fimbria-fornix, a brain region thought to regulate the activity of the memory-storing hippocampus.

Such studies made Huda Zoghbi, a neurogeneticist at Baylor College of Medicine, wonder what effect DBS might have on learning- and memory-related disorders that strike earlier in life. “We rationalized that maybe in Alzheimer’s, many of the neurons are already gone, but perhaps in a healthier brain, like that of a Rett syndrome model, we can test the idea if stimulation of the fornix can improve learning and memory,” she explains. Rett syndrome, a genetic disease that almost exclusively strikes girls, includes intellectual disability, autism-like deficits in social interactions, and a loss of motor function. Several years ago, Zoghbi and colleagues tried zapping the fimbria-fornix, a C-shape bundle of nerves adjacent to the hippocampus in the brain, in mouse models of Rett syndrome. Published in 2015, their results showed that after two weeks of daily, one-hour DBS sessions, the mice with an intellectual disability performed like their peers without the disorder on a range of hippocampus-dependent tasks.

“We were struck that everything became indistinguishable after deep brain stimulation from a baseline normal,” Zoghbi says. This prompted her team to ask, “How does it work at a molecular level?” The answer, she thought, could determine whether DBS of the fimbria-fornix has the potential to serve as a multipurpose tool, treating not just Rett syndrome but other childhood-onset intellectual disabilities with a variety of causes. “It’s going to be really tough, perhaps, to solve these diseases one gene at a time, so that learning can be corrected,” she says. “You could eventually consider an intervention that can be broadly applicable, irrespective of the molecular cause of the defect.”

For the latest study, the research team analyzed baseline differences in gene activity between mice with and without the Rett syndrome–like condition in a part of the hippocampus called the dentate gyrus. They also treated the mice with the intellectual disability once with 45 minutes of DBS. Of the many genes with marked differences in initial activity between the two groups of mice, one-quarter (39 genes) became normal in the Rett mice after treatment, they report.

Zoghbi’s group also tested the effects of DBS in normal mice; in addition to changing the activity levels of thousands of genes, the researchers found, the treatment prompted alternative splicing of the RNA copies of other genes, which would result in differences in the resulting proteins. Many of the genes affected by the alternative splicing are known to be involved in the growth of new neurons or in maintaining the synapses through which brain cells communicate. In the 2015 study, the group had found that DBS enhances some hippocampus-related abilities in wildtype mice, such as spatial learning.

For hints as to whether DBS might have the potential to treat intellectual disabilities other than Rett syndrome, the researchers compared their list of genes whose activity levels changed after DBS in normal mice with existing data on genes known to have abnormal expression levels in mouse models of several such disorders. As with Rett syndrome, DBS in wildtype mice altered the activity levels of about one-quarter of the genes involved in each of the disorders.

The fact that a short period of stimulation had such profound effects on gene expression is interesting, says Svjetlana Miocinovic, a movement-disorders neurologist at Emory University who was not involved in the study. Most research on the mechanism of DBS has focused on changes it induces in the electrical or physical properties of the brain, she tells The Scientist. “I think this kind of study, where they actually look at the molecular environment in these neurons that are exposed to stimulation . . . is really the way to figure out what exactly is going on and how is that neural plasticity accomplished.”

Now that they have a way to measure such molecular effects, Zoghbi and her collaborators plan to optimize DBS for models of intellectual disabilities—figuring out how long the current needs to be on, for example, and how often. Another question they’d like to address is whether stimulating other brain areas in addition to the fimbria-fornix could add to the benefits seen in the mice.

Zoghbi emphasizes that even if DBS turns out to be safe and effective for children with Rett syndrome, it won’t be a silver bullet, because patients will have missed out on some important developmental milestones. “To really get the full benefit,” she says, “we’re going to have to combine any intervention with intensive physical and behavioral therapy.”

A. Pohodish et al., “Forniceal deep brain stimulation induces gene expression and splicing changes that promote neurogenesis and plasticity,” eLife, doi:10.7554/eLife.34031, 2018.

https://www.the-scientist.com/?articles.view/articleNo/54581/title/Deep-Brain-Stimulation-Affects-the-Activity-of-Hundreds-of-Genes/&utm_campaign=TS_DAILY%20NEWSLETTER_2018&utm_source=hs_email&utm_medium=email&utm_content=62919749&_hsenc=p2ANqtz-_Wc4T-kVW-WjClgnxcSv-OaWmpr8r7DtQJQRRztFWWATkUzGmgHVi5RLo74kNAO-J2872OymH-_uX0WKTVquRF4v7QAw&_hsmi=62919749

University of Calgary scientists discover a new way to battle multiple sclerosis that challenges conventional thinking about its root cause

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The Dr. Peter Stys lab within the Hotchkiss Brain Institute at the Cumming School of Medicine, University of Calgary, is equipped with highly specialized microscopes used for researching multiple sclerosis, Alzheimer’s and other neurodegenerative disease. In this customized lab, the researchers can’t wear white lab coats, they have to wear dark clothing. Photons could reflect off light clothing and interfere with the experiments. From left: Megan Morgan, research assistant, and Craig Brideau, engineering scientist. Photo by Pauline Zulueta, Cumming School of Medicine

By Kelly Johnston, Cumming School of Medicine

Ridiculous. That’s how Andrew Caprariello says his colleagues described his theory about multiple sclerosis (MS) back when he was doing his PhD in Ohio.

Caprariello’s passion to explore controversial new theories about MS propelled him to seek out a postdoctoral fellowship with a like-minded thinker, whom he found in University of Calgary’s Dr. Peter Stys, a member of the Hotchkiss Brain Institute at the Cumming School of Medicine (CSM).

The collaboration paid off. Caprariello, Stys and their colleagues have scientific proof published in the Proceedings of the National Academy of Sciences (PNAS) that their somewhat radical theory has merit. “I’ve always wondered ‘what if’ MS starts in the brain and the immune attacks are a consequence of the brain damage,” says Caprariello, PhD, and lead author on the study.

Currently, MS is considered to be a progressive autoimmune disease. Brain inflammation happens when the body’s immune system attacks a protective material around nerve fibers in the brain called myelin. Conventional thinking is that rogue immune cells initially enter the brain and cause myelin damage that starts MS.

“In the field, the controversy about what starts MS has been brewing for more than a decade. In medical school, I was taught years ago that the immune attack initiates the disease. End of story,” says Stys, a neurologist and professor in the Department of Clinical Neurosciences at the CSM. “However, our findings show there may be something happening deeper and earlier that damages the myelin and then later triggers the immune attacks.”

To test the theory, the research team designed a mouse model of MS that begins with a mild myelin injury. In this way, researchers could mirror what they believe to be the earliest stages of the disease.

“Our experiments show, at least in this animal model, that a subtle early biochemical injury to myelin secondarily triggers an immune response that leads to additional damage due to inflammation. It looks very much like an MS plaque on MRI and tissue examination,” says Stys. “This does not prove that human MS advances in the same way, but provides compelling evidence that MS could also begin this way.”

With that result, the researchers started to investigate treatments to stop the degeneration of the myelin to see if that could reduce, or stop, the secondary autoimmune response.

“We collaborated with researchers at the University of Toronto and found that by targeting a treatment that would protect the myelin to stop the deterioration, the immune attack stopped and the inflammation in the brain never occurred,” says Stys. “This research opens a whole new line of thinking about this disease. Most of the science and treatment for MS has been targeted at the immune system, and while anti-inflammatory medications can be very effective, they have very limited benefit in the later progressive stages of the disease when most disability happens.”

It can be very hard to find funding to investigate an unconventional theory. The research team was funded by the Brain and Mental Health Strategic Research Fund, established by the Office of the Vice-President (Research) at UCalgary to support innovative, interdisciplinary studies within the Brain and Mental Health research strategy.

“We chose high-risk, novel projects for these funds to support discoveries by teams who did not have the chance to work together through conventional funding sources,” said Ed McCauley, PhD, vice-president (research). “The MS study shows the potential of brain and mental health scholars to expand capacity by tapping into new approaches for conducting research. Their work also exemplifies the type of interdisciplinary research that is propelling the University of Calgary as an international leader in brain and mental health research.”

http://www.ucalgary.ca/utoday/issue/2018-05-04/ucalgary-scientists-discover-new-way-battle-multiple-sclerosis

New peptide treatment for obese patients suffering from insatiable hunger

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In a new study researchers from the Institute for Experimental Pediatric Endocrinology of the Charité – Universitätsmedizin Berlin have successfully treat patients whose obesity is caused by a genetic defect. Aside from its beneficial effects on the patients, the researchers also provided insights into the fundamental signaling pathways regulating satiety of the new drug. The results of this research have been published in Nature Medicine*.

A mutation in the gene encoding the leptin receptor (LEPR) can cause extreme hunger starting with the first months of life. As a result, affected individuals develop extreme obesity during childhood. Increased exercise and reduced caloric intake are usually insufficient to stabilize body-weight. In many cases, obesity surgery fails to deliver any benefits, meaning that a drug-based treatment approach becomes increasingly important.

Two years ago, Dr. Peter Kühnen and the working group successfully demonstrated that treatment with a peptide, which activates the melanocortin 4 receptor (MC4R) could play a central role in the body’s energy metabolism and body weight regulation. Leptin, which is also known as the satiety (or starvation) hormone, normally binds to the LEPR, triggering a series of steps that leads to the production of melanocyte-stimulating hormone (MSH). The act of MSH by binding to its receptor, the melanocortin 4 receptor (MC4R) which transduce the satiety signal to the body. However, if the LEPR is defective, the signaling cascade is interrupted. The patient’s hunger remains unabated, placing them at greater risk of becoming obese. As part of this current study, researchers used a peptide that binds to the MC4R in the brain, and this activation trigger the normal satiety signal. Working in cooperation with the Clinical Research Unit at the Berlin Institute of Health (BIH), the researchers were able to record significant weight loss in patients with genetic defects affecting the LEPR.

“We also wanted to determine why the used peptide was so effective and why, in contrast to other preparations with a similar mode of action, it did not produce any severe side effects,” explains Dr. Kühnen. “We were able to demonstrate that this treatment leads to the activation of a specific and important signaling pathway, whose significance had previously been underestimated.” Dr. Kühnen’s team is planning to conduct further research to determine whether other patients might benefit from this drug: “It is possible that other groups of patients with dysfunctions affecting the same signaling pathway might be suitable candidates for this treatment.”

*Clément K, et al., MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency, Nature Medicine (2018), doi:10.1038/s41591-018-0015-9.

https://www.charite.de/en/service/press_reports/artikel/detail/den_unstillbaren_hunger_abschalten/

Scientists at Indiana University discover the first evidence that non-human animals can replay episodic memory in their heads, which could help find new treatments for patients with Alzheimer’s disease or normal memory loss with aging

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Neuroscientists at Indiana University have reported the first evidence that non-human animals can mentally replay past events from memory. The discovery could help advance the development of new drugs to treat Alzheimer’s disease.

The study, led by IU professor Jonathon Crystal, appears today in the journal Current Biology.

“The reason we’re interested in animal memory isn’t only to understand animals, but rather to develop new models of memory that match up with the types of memory impaired in human diseases such as Alzheimer’s disease,” said Crystal, a professor in the IU Bloomington College of Arts and Sciences’ Department of Psychological and Brain Sciences and director of the IU Bloomington Program in Neuroscience.

Under the current paradigm, Crystal said most preclinical studies on potential new Alzheimer’s drugs examine how these compounds affect spatial memory, one of the easiest types of memory to assess in animals. But spatial memory is not the type of memory whose loss causes the most debilitating effects of Alzheimer’s disease.

“If your grandmother is suffering from Alzheimer’s, one of the most heartbreaking aspects of the disease is that she can’t remember what you told her about what’s happening in your life the last time you saw her,” said Danielle Panoz-Brown, an IU Ph.D. student who is the first author on the study. “We’re interested in episodic memory — and episodic memory replay — because it declines in Alzheimer’s disease, and in aging in general.”

Episodic memory is the ability to remember specific events. For example, if a person loses their car keys, they might try to recall every single step — or “episode” — in their trip from the car to their current location. The ability to replay these events in order is known as “episodic memory replay.” People wouldn’t be able to make sense of most scenarios if they couldn’t remember the order in which they occurred, Crystal said.

To assess animals’ ability to replay past events from memory, Crystal’s lab spent nearly a year working with 13 rats, which they trained to memorize a list of up to 12 different odors. The rats were placed inside an “arena” with different odors and rewarded when they identified the second-to-last odor or fourth-to-last odor in the list.

The team changed the number of odors in the list before each test to confirm the odors were identified based upon their position in the list, not by scent alone, proving the animals were relying on their ability to recall the whole list in order. Arenas with different patterns were used to communicate to the rats which of the two options was sought.

After their training, Crystal said, the animals successfully completed their task about 87 percent of the time across all trials. The results are strong evidence the animals were employing episodic memory replay.

Additional experiments confirmed the rats’ memories were long-lasting and resistant to “interference” from other memories, both hallmarks of episodic memory. They also ran tests that temporarily suppressed activity in the hippocampus — the site of episodic memory — to confirm the rats were using this part of their brain to perform their tasks.

Crystal said the need to find reliable ways to test episodic memory replay in rats is urgent since new genetic tools are enabling scientists to create rats with neurological conditions similar to Alzheimer’s disease. Until recently, only mice were available with the genetic modifications needed to study the effect of new drugs on these symptoms.

“We’re really trying push the boundaries of animal models of memory to something that’s increasingly similar to how these memories work in people,” he said. “If we want to eliminate Alzheimer’s disease, we really need to make sure we’re trying to protect the right type of memory.”

https://news.iu.edu/stories/2018/05/iub/releases/10-scientists-find-first-evidence-animals-can-mentally-replay-past-events.html

When artificial intelligence was allowed to learn how to move through a virtual environment, it spontaneously generated patterns of activity found in grid neurons of the human brain.

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Futuristic cityscape maze.

By Diana Kwon

A computer program can learn to navigate through space and spontaneously mimics the electrical activity of grid cells, neurons that help animals navigate their environments, according to a study published May 9 in Nature.

“This paper came out of the blue, like a shot, and it’s very exciting,” Edvard Moser, a neuroscientist at the Kavli Institute for Systems Neuroscience in Norway who was not involved in the work, tells Nature in an accompanying news story. “It is striking that the computer model, coming from a totally different perspective, ended up with the grid pattern we know from biology.” Moser shared a Nobel Prize for the discovery of grid cells with neuroscientists May-Britt Moser and John O’Keefe in 2014.

When scientists trained an artificial neural network to navigate in the form of virtual rats through a simulated environment, they found that the algorithm produced patterns of activity similar to that found in the grid cells of the human brain. “We wanted to see whether we could set up an artificial network with an appropriate task so that it would actually develop grid cells,” study coauthor Caswell Barry of University College London, tells Quanta. “What was surprising was how well it worked.”

The team then tested the program in a more-complex, maze-like environment, and found that not only did the virtual rats make their way to the end, they were also able to outperform a human expert at the task.

“It is doing the kinds of things that animals do and that is to take direct routes wherever possible and shortcuts when they are available,” coauthor Dharshan Kumaran, a senior researcher at Google’s AI company DeepMind, tells The Guardian.

DeepMind researchers hope to use these types of artificial neural networks to study other parts of the brain, such as those involved in understanding sound and controlling limbs, according to Wired. “This has proven to be extremely hard with traditional neuroscience so, in the future, if we could improve these artificial models, we could potentially use them to understand other brain functionalities,” study coauthor Andrea Banino, a research scientist at DeepMind, tells Wired. “This would be a giant step toward the future of brain understanding.”

https://www.the-scientist.com/?articles.view/articleNo/54534/title/Artificial-Intelligence-Mimics-Navigation-Cells-in-the-Brain/&utm_campaign=TS_DAILY%20NEWSLETTER_2018&utm_source=hs_email&utm_medium=email&utm_content=62845247&_hsenc=p2ANqtz-_1eI9gR1hZiJ5AMHakKnqqytoBx4h3r-AG5kHqEt0f3qMz5KQh5XeBQGeWxvqyvET-l70AGfikSD0n3SiVYETaAbpvtA&_hsmi=62845247

What is synesthesia and what’s it like to have it?

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Synesthetes can taste sounds, smell colors or see scents, and research proves these people experience reality differently.

By Laura Moss

I know that the number four is yellow, but I have a friend who insists four is red.

She also says four has a motherly personality, but my four has no personality — none of my numbers do. But all of my numbers have colors, and so do my letters, days and months.

My friend and I both have synesthesia, a perceptual condition in which the stimulation of one sense triggers an automatic, involuntary experience in another sense.

Synesthesia can occur between just about any combination of senses or cognitive pathways.

Synesthetes — or people who have synesthesia — may see sounds, taste words or feel a sensation on their skin when they smell certain scents. They may also see abstract concepts like time projected in the space around them, like the image on the right.

Many synesthetes experience more than one form of the condition. For example, my friend and I both have grapheme-color synesthesia — numbers and letters trigger a color experience, even though my experience differs from hers.

Because her numbers have personalities, she also has a form of synesthesia known as ordinal-linguistic personification.

Scientists used to think synesthesia was quite rare, but they now think up to 4 percent of the population has some form of the condition.

What’s it like?

David Eagleman, a neuroscientist and director of the Laboratory for Perception and Action at the Baylor College of Medicine, isn’t a synesthete, but he often uses this analogy to explain the phenomenon.

When you see this photo, you likely think “President Barack Obama” even though those words aren’t written anywhere on the picture. Your brain automatically and involuntarily makes that connection, much like my brain makes a connection between the number four and the color yellow.

“It’s not the same as a hallucination,” Eagleman explains in the documentary “Red Mondays and Gemstone Jalapenos.” “It’s not actually interfering with their ability to see, so in that same way, you could picture a giant orange pumpkin sitting in front of you, but that doesn’t prevent you from seeing through that and past that.”

Synesthesia is a sensory phenomenon that’s unrelated to memory, so if you’re not a synesthete, you could teach yourself to associate a color with a certain number for example, but your brain wouldn’t respond the same way a synesthete’s would.

For instance, someone without grapheme-color synesthesia would have a more difficult time picking out the black twos from the black fives in the image on the left.

However, if your numbers have colors, you’ll see the triangle of twos almost instantly.

But this task may be even easier for some grapheme-color synesthetes.

Daniel Smilek, a psychology professor at the University of Waterloo, has identified two groups of synesthetes among those who associate colors with letters and numbers. There are projectors, those whose colors fill the printed letter in front of them, and associators who see the colors in their mind’s eye, like I do.

What about people who can hear silent videos?

Synesthesia doesn’t just apply to people who associate certain colors with images. Some people have the ability to hear sounds in videos when there is actually no sound being played.

Psychologist Chris Fassnidge calls this phenomenon “visually evoked auditory response” (vEAR). While it’s technically not synesthesia, Fassnidge believes it’s a new form that warrants further study. “Some people describe it as a buzzing sound in their head,” Fassnidge told Vox. “For other people, it’s kind of like a white noise. And then other people say it varies depending on what it is they are looking at.”

A 2008 study suggests that vEAR is fairly common — affecting 20 to 30 percent of people — and many people may not realize they are associating faint sounds with imagery.

“A lot of people don’t realize they have this thing until you start testing for it in the laboratory,” Fassnidge said. “Maybe because they co-occur so frequently you either aren’t aware of the mental sound until you strip away everything else.”

What causes it?

About 40 percent of synesthetes have a first-degree relative with synesthesia, and many synesthetes recall having synesthesia as long as they can remember.

“I was definitely playing with it when I was 5 or 6 years old because I remember raiding my parents’ record cabinet, searching for records that I liked to listen to for colors,” said Sean Day, a synesthete who associates colors with both sounds and tastes.

A 2018 study conducted by scientists from the Max Planck Institute for Psycholinguistics and the University of Cambridge analyzed DNA samples from several families who have multiple generations of synesthetes. They concluded that while the families differed in DNA variations, there was one commonality. There was an enhancement of genes involved in cell migration and axonogenesis – a process that enables brain cells to wire up to their correct partners.

“This research is revealing how genetic variation can modify our sensory experiences, potentially via altered connectivity in the brain,” Professor Simon Baron-Cohen stated in the study. “Synesthesia is a clear example of neurodiversity which we should respect and celebrate.”

Other experts believe that everyone may be born with the ability to experience synesthesia.

Daphne Maurer, a psychologist at McMaster University, has speculated that all of us may be born with the neural connections that allow synesthesia, but that most of us lose those connections as we grow.

Eagleman acknowledges there may be synesthetic correspondences in the brains of non-synesthetes, but that people are unaware of them until they’re teased out.

He points to something called the bouba/kiki effect as an example. When asked to choose which of two shapes on the right is named “bouba” and which is “kiki,” most people choose kiki for the angular shape and bouba for the rounded one.

Research also shows that people are likely to say that louder tones are brighter than soft ones and that darker liquids smell stronger than lighter ones.

In his book, “Wednesday Is Indigo Blue,” Eagleman says these examples prove that these analogies are actually “pre-existing relationships.”

“In this way, synesthetic associations our ancestors established long ago grew into the more abstract expressions we know today — and this is why metaphors make sense,” he writes.

However, synesthesia differs from these examples in that the sensory experience triggered is automatic and unlearned, making it different from metaphorical thinking.

“It’s a genuine phenomenon, and people who have it are actually experiencing the world differently,” Eagleman said.

How is it tested?

Consistency is one of the best ways to test for synesthesia.

“If you tell me that your letter ‘J’ is a very particular shade of powder blue … I can test you on that and have you identify exactly the shade that best matches,” Eagleman said. “If you’re just being poetic or metaphorical or making something up, then you can’t capture those colors again. But if you’re really synesthetic, then you’ll be able to pick exactly those colors out years later.”

Researchers also look at synesthetes’ brains. Using positron-emission tomography and functional magnetic resonance imaging, they’ve found that people who report seeing colors in music, for example, have increased activation in the visual areas of the brain in response to sound.

Pictured right are the regions of the brain that are thought to be cross-activated in grapheme-color synesthesia.

The pros and cons

Some synesthetes say their condition can be uncomfortable at times. For example, seeing words printed in the wrong color can be strange, or certain names may taste bad to a synesthete. Others report suffering sensory overload or feeling embarrassed at a young age when they describe experiences they didn’t know were atypical.

However, most synesthetes think of their abilities as a gift and wouldn’t want to lose them.

“You’ve experienced extremely unpleasant odors,” Day points out. “Do you want to permanently lose your sense of smell?”

There may also be some benefits to being a synesthete, such as an ability to discern similar colors and easily memorize information. For example, I might not remember a digit in a phone number, but I’ll have an impression of green and therefore know the mystery number is six. (Some of my numbers are pictured above, as depicted by the Synesthesia Battery.)

In 2005, Daniel Tammet set the European record for pi memorization by memorizing 22,514 digits in five hours. He attributed the feat to his ability to see numbers with color, texture and sound.

There’s also evidence that synesthesia may enhance creativity. A 2004 study at the University of California had a group of students take the Torrance Tests of Creative Thinking. The synesthetes who took the test scored more than twice as high in every category.

In some instances, the neurological condition has even led to unique job opportunities. Some car manufacturers, for example, are hiring synesthetes to help designers create cars that are more pleasing to potential drivers.

And synesthetes keep good company. The list of known synesthetes is long and includes Vladimir Nabokov, Vincent Van Gogh, Marilyn Monroe, Billy Joel and Mary J. Blige.

Musician Pharrell Williams associates music with colors and says he can’t imagine life without this “gift.”

“If it was taken from me suddenly I’m not sure that I could make music,” he told Psychology Today. “I wouldn’t be able to keep up with it. I wouldn’t have a measure to understand.”

If you think you may be a synesthete, you can take the Synesthesia Battery created by David Eagleman’s lab: https://www.synesthete.org/pretest_start.php?action=register&remail=&semail=&ch=

Learn more about synesthesia and Eagleman’s research in the video below.

https://www.mnn.com/health/fitness-well-being/stories/what-is-synesthesia-and-whats-it-like-to-have-it

Risk of later developing dementia is doubled after a concussion

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High school football player in for the touchdown.; Shutterstock ID 408266332; Purchase Order: –

Researchers reported on Monday in the journal JAMA Neurology that dementia was a possible complication following concussion even if the patient did not lose consciousness.

Scientists from the University of California, San Francisco (UCSF) tracked more than one-third of a million American veterans, and found that the likelihood of dementia more than doubled following concussion.

After adjusting for age, sex, race, education and other health conditions, they found that concussion without loss of consciousness led to 2.36 times the risk for dementia.

According to the study, these risks were slightly elevated for those in the loss-of-consciousness bracket (2.51 times) and were nearly four times higher (3.77 times) for those with the more serious moderate-to-severe traumatic brain injury.

In the total of 357,558 participants, whose average age was 49, half had been diagnosed with traumatic brain injury, of which 54 percent had concussion. The study followed participants for an average of 4.2 years, and 91 percent were male and 72 percent were white.

“There are several mechanisms that may explain the association between traumatic brain injury and dementia,” said the study’s senior author Kristine Yaffe, professor with the UCSF departments of neurology, psychiatry, and epidemiology and biostatistics.

“There’s something about trauma that may hasten the development of neurodegenerative conditions. One theory is that brain injury induces or accelerates the accumulation of abnormal proteins that lead to neuronal death associated with conditions like Alzheimer’s disease,” said Yaffe.

“It’s also possible that trauma leaves the brain more vulnerable to other injuries or aging processes,” said Yaffe, “but we need more work in this area.”

http://www.xinhuanet.com/english/2018-05/08/c_137162226.htm

Targeting astrocytes, the brain cells that support neurons, in the brain might help alleviate symptoms of Alzheiemer’s disease

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A study by scientists of the German Center for Neurodegenerative Diseases (DZNE) points to a novel potential approach against Alzheimer’s disease. In studies in mice, the researchers were able to show that blocking a particular receptor located on astrocytes normalized brain function and improved memory performance. Astrocytes are star-shaped, non-neuronal cells involved in the regulation of brain activity and blood flow. The findings are published in the Journal of Experimental Medicine (JEM).

Alzheimer’s disease is a common and currently incurable brain disorder leading to dementia, whose mechanisms remain incompletely understood. The disease appears to be sustained by a combination of factors that include pathological changes in blood flow, neuroinflammation and detrimental changes in brain cell activity.

“The brain contains different types of cells including neurons and astrocytes”, explains Dr. Nicole Reichenbach, a postdoc researcher at the DZNE and first author of the paper published in JEM. “Astrocytes support brain function and shape the communication between neurons, called synaptic transmission, by releasing a variety of messenger proteins. They also provide metabolic and structural support and contribute to the regulation of blood flow in the brain.”

Glitches in network activity

Similar to neurons, astrocytes are organized into functional networks that may involve thousands of cells. “For normal brain function, it is crucial that networks of brain cells coordinate their firing rates. It’s like in a symphony orchestra where the instruments have to be correctly tuned and the musicians have to stay in synchrony in order to play the right melody”, says Professor Gabor Petzold, a research group leader at the DZNE and supervisor of the current study. “Interestingly, one of the main jobs of astrocytes is very similar to this: to keep neurons healthy and to help maintain neuronal network function. However, in Alzheimer’s disease, there is aberrant activity of these networks. Many cells are hyperactive, including neurons and astrocytes. Hence, understanding the role of astrocytes, and targeting such network dysfunctions, holds a strong potential for treating Alzheimer’s.”

Astrocyte-targeted treatment alleviated memory impairment

Petzold and colleagues tested this approach in an experimental study involving mice. Due to a genetic disposition, these rodents exhibited certain symptoms of Alzheimer’s similar to those that manifest in humans with the disease. In the brain, this included pathological deposits of proteins known as “Amyloid-beta plaques” and aberrant network activity. In addition, the mice showed impaired learning ability and memory.

In their study, the DZNE scientists targeted a cell membrane receptor called P2Y1R, which is predominately expressed by astrocytes. Previous experiments by Petzold and colleagues had revealed that activation of this receptor triggers cellular hyperactivity in mouse models of Alzheimer’s. Therefore, the researchers treated groups of mice with different P2Y1R antagonists. These chemical compounds can bind to the receptor, thus switching it off. The treatment lasted for several weeks.

“We found that long-term treatment with these drugs normalized the brain’s network activity. Furthermore, the mice’s learning ability and memory greatly improved”, Petzold says. On the other hand, in a control group of wild type mice this treatment had no significant effect on astrocyte activity. “This indicates that P2Y1R inhibition acts quite specifically. It does not dampen network activity when pathological hyperactivity is absent.”

New approaches for research and therapies?

Petzold summarizes: “This is an experimental study that is currently not directly applicable to human patients. However, our results suggest that astrocytes, as important safeguards of neuronal health and normal network function, may hold the potential for novel treatment options in Alzheimer’s disease.” In future studies, the scientists intend to identify additional novel pathways in astrocytes and other cells as potential drug targets.

Reference:
Reichenbach, N., Delekate, A., Breithausen, B., Keppler, K., Poll, S., Schulte, T., . . . Petzold, G. C. (2018). P2Y1 receptor blockade normalizes network dysfunction and cognition in an Alzheimer’s disease model. The Journal of Experimental Medicine. doi:10.1084/jem.20171487

https://www.dzne.de/en/news/public-relations/press-releases/press/detail/the-brains-rising-stars-new-options-against-alzheimers/

Stanford scientists find fear, courage switches in brain

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Pinpoint stimulation of a cluster of nerve cells in the brains of mice encouraged timid responses to a perceived threat, whereas stimulation of an adjacent cluster induced boldness and courage.

Researchers at the Stanford University School of Medicine have identified two adjacent clusters of nerve cells in the brains of mice whose activity level upon sighting a visual threat spells the difference between a timid response and a bold or even fierce one.

Located smack-dab in the middle of the brain, these clusters, or nuclei, each send signals to a different area of the brain, igniting opposite behaviors in the face of a visual threat. By selectively altering the activation levels of the two nuclei, the investigators could dispose the mice to freeze or duck into a hiding space, or to aggressively stand their ground, when approached by a simulated predator.

People’s brains probably possess equivalent circuitry, said Andrew Huberman, PhD, associate professor of neurobiology and of ophthalmology. So, finding ways to noninvasively shift the balance between the signaling strengths of the two nuclei in advance of, or in the midst of, situations that people perceive as threatening may help people with excessive anxiety, phobias or post-traumatic stress disorder lead more normal lives.

“This opens the door to future work on how to shift us from paralysis and fear to being able to confront challenges in ways that make our lives better,” said Huberman, the senior author of a paper describing the experimental results. It was published online May 2 in Nature. Graduate student Lindsey Salay is the lead author.

Perilous life of a mouse
There are plenty of real threats in a mouse’s world, and the rodents have evolved to deal with those threats as best they can. For example, they’re innately afraid of aerial predators, such as a hawk or owl swooping down on them. When a mouse in an open field perceives a raptor overhead, it must make a split-second decision to either freeze, making it harder for the predator to detect; duck into a shelter, if one is available; or to run for its life.

To learn how brain activity changes in the face of such a visual threat, Salay simulated a looming predator’s approach using a scenario devised some years ago by neurobiologist Melis Yilmaz Balban, PhD, now a postdoctoral scholar in Huberman’s lab. It involves a chamber about the size of a 20-gallon fish tank, with a video screen covering most of its ceiling. This overhead screen can display an expanding black disc simulating a bird-of-prey’s aerial approach.

Looking for brain regions that were more active in mice exposed to this “looming predator” than in unexposed mice, Salay pinpointed a structure called the ventral midline thalamus, or vMT.

Salay mapped the inputs and outputs of the vMT and found that it receives sensory signals and inputs from regions of the brain that register internal brain states, such as arousal levels. But in contrast to the broad inputs the vMT receives, its output destination points were remarkably selective. The scientists traced these outputs to two main destinations: the basolateral amygdala and the medial prefrontal cortex. Previous work has tied the amygdala to the processing of threat detection and fear, and the medial prefrontal cortex is associated with high-level executive functions and anxiety.

Further inquiry revealed that the nerve tract leading to the basolateral amygdala emanates from a nerve-cell cluster in the vMT called the xiphoid nucleus. The tract that leads to the medial prefrontal cortex, the investigators learned, comes from a cluster called the nucleus reuniens, which snugly envelopes the xiphoid nucleus.

Next, the investigators selectively modified specific sets of nerve cells in mice’s brains so they could stimulate or inhibit signaling in these two nerve tracts. Exclusively stimulating xiphoid activity markedly increased mice’s propensity to freeze in place in the presence of a perceived aerial predator. Exclusively boosting activity in the tract running from the nucleus reuniens to the medial prefrontal cortex in mice exposed to the looming-predator stimulus radically increased a response seldom seen under similar conditions in the wild or in previous open-field experiments: The mice stood their ground, right out in the open, and rattled their tails, an action ordinarily associated with aggression in the species.

Thumping tails

This “courageous” behavior was unmistakable, and loud, Huberman said. “You could hear their tails thumping against the side of the chamber. It’s the mouse equivalent of slapping and beating your chest and saying, ‘OK, let’s fight!’” The mice in which the nucleus reuniens was stimulated also ran around more in the chamber’s open area, as opposed to simply running toward hiding places. But it wasn’t because nucleus reuniens stimulation put ants in their pants; in the absence of a simulated looming predator, the same mice just chilled out.

In another experiment, the researchers showed that stimulating mice’s nucleus reuniens for 30 seconds before displaying the “looming predator” induced the same increase in tail rattling and running around in the unprotected part of the chamber as did vMT stimulation executed concurrently with the display. This suggests, Huberman said, that stimulating nerve cells leading from the nucleus reunions to the prefrontal cortex induces a shift in the brain’s internal state, predisposing mice to act more boldly.

Another experiment pinpointed the likely nature of that internal-state shift: arousal of the autonomic nervous system, which kick-starts the fight, flight or freeze response. Stimulating either the vMT as a whole or just the nucleus reuniens increased the mice’s pupil diameter — a good proxy of autonomic arousal.

On repeated exposures to the looming-predator mockup, the mice became habituated. Their spontaneous vMT firing diminished, as did their behavioral responses. This correlates with lowered autonomic arousal levels.

Human brains harbor a structure equivalent to the vMT, Huberman said. He speculated that in people with phobias, constant anxiety or PTSD, malfunctioning circuitry or traumatic episodes may prevent vMT signaling from dropping off with repeated exposure to a stress-inducing situation. In other experiments, his group is now exploring the efficacy of techniques, such as deep breathing and relaxation of visual fixation, in adjusting the arousal states of people suffering from these problems. The thinking is that reducing vMT signaling in such individuals, or altering the balance of signaling strength from their human equivalents of the xiphoid nucleus and nucleus reuniens may increase their flexibility in coping with stress.

Reference:
Salay, L. D., Ishiko, N., & Huberman, A. D. (2018). A midline thalamic circuit determines reactions to visual threat. Nature. doi:10.1038/s41586-018-0078-2

http://med.stanford.edu/news/all-news/2018/05/scientists-find-fear-courage-switches-in-brain.html

“Noisy” Neurons May Repeatedly Disrupt Your Sleep

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You don’t remember it, but you woke up at least 100 times last night. These spontaneous arousals, lasting less than 15 seconds each, occur roughly every five minutes and don’t seem to affect how well-rested you feel. They are unrelated to waking up from a bad dream or your partner tossing and turning. Instead, they seem to be linked to some internal biological mechanism.

Frequently waking up throughout the night may have protected early humans from predators by increasing their awareness of their surroundings during sleep. “The likelihood someone would notice an animal is higher [if they] wake up more often,” says Ronny Bartsch, a senior lecturer in the Department of Physics at Bar-Ilan University in Israel. “When you wake up, you’re more prone to hear things. In deep sleep, you’re completely isolated.”

Sleep scientists, however, have been stumped as to what triggers these nocturnal disruptions. In a new Science Advances paper Bartsch proposes an innovative hypothesis that spontaneous arousals are due to random electrical activity in a specific set of neurons in the brain—aptly named the wake-promoting neurons.

Even when you are asleep your brain cells continuously buzz with a low level of electrical activity akin to white noise on the radio. Occasionally, this electrical clamor reaches a threshold that triggers the firing of neurons. The new paper suggests that when random firing occurs in the wake-promoting neurons, a person briefly jerks awake. But this is countered by a suite of sleep-promoting neurons that helps one quickly fall back to sleep.

Low-level electrical activity in neurons increases in colder temperatures whereas warmer temperatures flatten it. As a result, there should be fewer spontaneous arousals in hot weather. To test this theory, the researchers created computer models that mapped how neuronal noise should act at different temperatures and how the varying electrical activity could affect spontaneous arousals. They also measured sleep in zebra fish, which have similar day/night cycles to humans but are ectothermic, meaning their body temperature is controlled by the environment rather than by internal processes.

The researchers compared the fish’s sleep rates at four different water temperatures: 77, 82 (ideal for zebra fish), 84 and 93 degrees Fahrenheit. Across the board, the colder the water the more often the zebra fish woke up and the longer they stayed awake. The data from the zebra fish and the models of temperature, neuronal noise and arousal matched perfectly. “I think their theory is a perfectly good one and may even be correct,” says Clifford Saper, a neuroscientist at Harvard Medical School’s Division of Sleep Medicine and head of Neurology at Beth Israel Deaconess Medical Center who was not involved with the study. “But the experiment they did doesn’t test that hypothesis.”

The zebra fish experiment shows the fish wake up more frequently and stay awake for longer in colder temperatures but reveals nothing about these animals’ neuronal noise—or humans’, for that matter. Bartsch says that, so far, no studies have figured out how to measure neuronal noise in a sleeping animal.

The idea that warm temperatures cause fewer nocturnal disruptions also seemingly flies in the face of conventional wisdom that a colder bedroom leads to better sleep. But waking up because you are hot and uncomfortable is different from these brief spontaneous arousals. In fact, our bodies are pretty good at regulating their core brain and body temperatures, so the difference of a few degrees outside would not alter neuronal activity. In contrast, zebra fish’s temperature varies quite a bit. Saper says because of this zebra fish “are probably the last animal that I would use to try to make this point.”

Bartsch emphasizes the study is not trying to make a claim about thermoregulation in adults but he says it may have implications for newborn babies. “Because very young infants are more ectothermic than endothermic, their arousability could scale similarly to fish for different ambient temperatures.”

Infants are not as good at regulating their own temperature and so are more vulnerable to changes in the environment. (This is why premature babies have to be kept in incubators.) Consequently, the researchers think newborns may be more susceptible to heat-related fluctuations in neuronal noise.

The theory may have important implications for infant sleep. Although they may be disruptive to parents, spontaneous arousals could help save a baby’s life. Sudden infant death syndrome (SIDS) has been a leading cause of mortality in children between one month and one year of age and yet largely remains a mystery. One idea is that SIDS is caused by a stoppage in breathing, often through accidental suffocation. Waking up during the night can prompt babies to shift or cry out, helping to ensure that they do not have anything obstructing their airways and are still breathing. “We came up again with a theory that the babies with SIDS have low neuronal noise and therefore they have lower arousals,” says Hila Dvir, a physicist at Bar-Ilan. “Because they have low arousals, they are less protected from any hypoxic event—a shortage of oxygen.”

Not everyone is convinced, though. “Over the years, people have come up with ideas to explain SIDS, like a single explanation for it, and they just keep hitting dead ends with it because it’s probably a complex, heterogeneous situation,” says Rafael Pelayo, a clinical professor at the Stanford Center for Sleep Sciences and Medicine “It is a cool idea that this neuronal noise is explaining the arousals. I just think they jumped a little bit when they got into SIDS. It has to be more complicated than that.”

https://www.scientificamerican.com/article/sound-awake-noisy-neurons-may-repeatedly-disrupt-your-sleep1/