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Aging, Neuroscience, Stanford News, Stroke, Videos

Examining the potential of creating new synapses in old or damaged brains

Examining the potential of creating new synapses in old or damaged brains

Synapses are the structures in the brain where neurons connect and communicate with each other. Between early childhood and the beginning of puberty, many of these connections are eliminated through a process called “synaptic pruning.” Stroke, Alzheimer’s disease, and traumatic brain injury can also cause the loss of synapses. But what if new synapses could be created to repair aging or damaged brains?

Stanford neurobiologist Carla Shatz, PhD, addresses this question in the above Seattle+Connect video. In the lecture, she discusses the possibility of engaging the molecular and cellular mechanisms that regular critical developmental periods to regrow synapses in old brains. Watch the video to learn how advances at the neural level around a novel receptor, called PirB, have implications for improving brain plasticity, learning, memory and neurological disorders.

Previously: Drug helps old brains learn new tricks, and heal, Cellular padding could help stem cells repair injuries and Science is like an ongoing mystery novel, says Stanford neurobiologist Carla Shatz and “Pruning synapses” and other strides in Alzheimer’s research

Imaging, In the News, Neuroscience, Research, Stanford News

Studies on ME/chronic fatigue syndrome continue to grab headlines, spur conversation

Studies on ME/chronic fatigue syndrome continue to grab headlines, spur conversation

neural-pathways-221719_640The proof’s in the pudding, the old saying — which seems slightly seasonal — goes. So when a Stanford team compared images of brains affected by chronic fatigue syndrome, with those healthy brains, they found noticeable differences, including misshaped white matter, the cells that coordinate communication between brain regions. The news garnered immediate attention and has now been featured in a New York Times  piece:

The relationship between the symptoms experienced by patients and the findings is unclear. The two parts of the brain connected by the abnormally shaped white matter are believed to be important for language use, said Michael Zeineh, MD, a radiologist at Stanford and the lead author…

“This opens the door to more detailed investigations because now we have targets for future research,” he said.

The Times also refers to another study, published in March, that found cerebral inflammation in patients who suffer from chronic fatigue syndrome, or, as it is also called, myalgic encephalomyelitis/ C.F.S. This is big news for a condition that’s often misdiagnosed — patients are sometimes forced to visit numerous doctors and battle insurance companies — all while fighting the debilitating symptoms — before securing a diagnosis.

The Times touches on the tricky politics of the disease as well:

Next month, a panel convened by the National Institutes of Health will hold a two-day workshop  charged with “advancing the research” on the illness of the disorder. The Institute of Medicine is conducting a separate, government-sponsored initiative to assess and evaluate the many sets of diagnostic criteria for M.E./C.F.S., with the results expected next year.

Advocacy groups have questioned the rationale for two separate efforts. They have also criticized the initiatives because in both cases many people with little or no expertise in M.E./C.F.S. will be voting on recommendations that could have a significant impact on the government’s future efforts.

Previously: Patients’ reaction to ME/CFS coverage in Stanford Medicine magazine, Some headway on chronic fatigue syndrome: Brain abnormalities pinpointed and Unbroken: A chronic fatigue syndrome patient’s long road to recovery
Image by geralt

Neuroscience, Podcasts, Science, Stanford News

Stanford neurobiologist Bill Newsome: Seeking gains for the brain

Stanford neurobiologist Bill Newsome: Seeking gains for the brain

14601014695_30cfe1972d_zBill Newsome, PhD, knows the brain perhaps as well as the back of his hand. The Stanford neurobiologist was vice chair of the federal BRAIN Initiative launched by President Obama, and he directs the Stanford Neurosciences Institute. From that spot, he’s just funded a first round of interdisciplinary grants to Stanford faculty that he calls “risk taking.”  The need, he told me in this just-published 1:2:1 podcast, is critical:

When biomedical research money gets tight, as it now is, the funding agencies tend to get conservative. Right now we have these talented faculty at Stanford, many of them young faculty. They’re at the most creative parts of their career.  They’re at a place where they’re thinking big and dreaming big. We wanted to create this mechanism to allow them to do that.

I asked Newsome about the greatest challenges for neuroscience in the next few years. He had one word: technology. “If we were to improve the technology… If we could read out signals from the human brain and read in signals, actually do the circuit-tuning in the human brain non-invasively, at a spatial scale on the order of a millimeter or less and with fairly rapid time, it would revolutionize neuroscience,” he said.

So paint the picture, I asked, and  look ten years out. What would you like to see as far as progress? He told me:

I would like to see fundamental, substantive change on at least one devastating neurological or psychiatric disease. I don’t really care which one. Give me Alzheimer’s. Give me autism. Give me depression. Give me Parkinson’s disease. At the end of 10 years, if we can really have a breakthrough in the understanding of what causes one of those diseases mechanistically and have a therapy that dramatically improves people’s lives… I would say, ‘It’s worth it. We’ve done our job.’

Any worries or words of caution? He laments the current state of federal funding for science and worries that fiscal constraints will squeeze out young star scientists. “How do you keep convincing talented people to come into the field?” he said. “We’re deprioritizing science… How do we convince our brightest, our best, that this is a field with a really bright future?”

Previously: Deciphering “three pounds of goo” with Stanford neurobiologist Bill Newsome, Neuroscientists dream big, come up with ideas for prosthetics, mental health, stroke and more, BRAIN Initiative and the Human Brain Project: Aiming to understand how the brain works, Brain’s gain: Stanford neuroscientist discusses two major new initiatives and Co-leader of Obama’s BRAIN Initiative to direct Stanford’s interdisciplinary neuroscience institute
Photo by Allan Ajifo

Neuroscience, Research, Stanford News

Building a bridge between education and neuroscience

Building a bridge between education and neuroscience

3537327425_d0c519ed1e_zIt wasn’t long ago that my kids could barely identify all the letters in the alphabet and now I have to yell at them to put down books and eat dinner. That transition, from identifying symbols to learning how to interpret them in math and reading, is something that involves creating new pathways in the brain.

Neuroscientists have long known that those changes must be taking place in the brain, but only recently has brain imaging been good enough to reveal where and how those changes are taking place. With that advance, neuroscientists and faculty in the School of Education are now starting to work together to better understand the changes and also come up with ways of using what’s learned in neuroscience to develop ways of helping kids who fall behind.

I recently wrote about a new education professor, Bruce McCandliss, PhD, who is pulling together the interdisciplinary team of faculty from across Stanford to build the educational neuroscience program here. From my story:

In one set of experiments, McCandliss used a type of brain imaging that reveals connections or tracts of neurons to look at the brains of kids who were good readers and others who showed signs of dyslexia. He found that the kids who were better readers had stronger brain connections in that region.

“There is a profound relationship between the way a person’s brain is organized and how well that person masters abstract intellectual skills, such as reading or mathematics,” he said.

In a follow-up study, he and a team that included Allan Reiss, the Howard C. Robbins Professor of Psychiatry and Behavioral Sciences and professor of radiology, found that kids with dyslexia who activate a particular brain region when trying to read went on to make much greater improvements in their reading ability. Kids who did not activate that region made very little reading gain after the age of 14.

“The hope is that by understanding the nature of these differences we might be able to tailor interventions for those individuals,” McCandliss said.

The people I talked with for my story all said that we have many years to go before discoveries made in the lab start showing up as personalized learning in the classroom. Still, it’s nice to think that some of the kids who are struggling with reading or math might one day be able to get help that’s based on what’s actually known about learning in the brain.

Previously: Learning how we learn to read, Study shows brain scans could help identify dyslexia in children before they start to read and Stanford study furthers understanding of reading disorders
Photo by John Morgan

History, Neuroscience, Research, Science, Stanford News

Illustration from 1881 resolves century-old brain controversy

Illustration from 1881 resolves century-old brain controversy

Figure2_WernickeThese days, a person can get through graduate school in the sciences practically without touching a physical publication. Most journals are available online going back decades. So it was a bit unusual when graduate student Jason Yeatman and postdoctoral scholar Kevin Weiner found themselves in the basement of Lane Medical Library trying to get to the bottom of a medical mystery.

It all started when Yeatman found a nerve pathway in brain images he’d taken as part of his work studying brain changes as kids learn to read.  This pathway didn’t appear anywhere in the available literature. He and Weiner became curious how this pathway – which clearly showed up in their work – could have escaped the notice of previous neuroscientists.

Their curiosity eventually led them back to an 1881 publication, still available in the basement of Lane Medical Library, where Carl Wernicke, MD, described identifying this brain pathway. Weier said, “That was a really cool experience that most people don’t have anymore, when you have to check your belongings at the door because the book you are about to look at is worth thousands of dollars per page. You are literally smelling 100 year-old ink as you find the images you have been searching for.”

Wernicke’s discovery contradicted theories by the eminent neuroanatomist at the time, Theodor Meynert, MD. I describe the controversy that led to this pathway expulsion from the literature in this Stanford News story:

Meynert strongly believed that all of the brain’s association pathways run from front to back – horizontal. This pathway, which Wernicke had called the vertical occipital fasciculus, or VOF, ran vertically. Although Yeatman and Weiner found references to the VOF under a variety of different names in texts published for about 30 years after Wernicke’s original discovery, Meynert never accepted the VOF and references to it became contentious before eventually disappearing entirely from the literature.

The group, whose work was published this week in the Proceedings of the National Academy of Sciences, says this was all more than just an exercise in curiosity. Psychologist Brian Wandell, PhD, in whose lab Yeatman was working, says it also shows the value of modern publishing methods, where making data available means scientists worldwide can try to reproduce results. He says it’s now less likely that a dispute could lead to a discovery being lost to history.

Image courtesy of PNAS

Anesthesiology, Neuroscience, Research, Stanford News, Surgery

Stanford anesthesiologist explores consciousness – and unconsciousness

Stanford anesthesiologist explores consciousness - and unconsciousness

face-275015_1280Anesthesiologist Divya Chander, MD, PhD, is one of a leading group of neuroscientists and anesthesiologists who are using high-tech monitoring equipment in the operating room to explore the nature of consciousness – which isn’t quite as simple as on or off, asleep or awake.

Stanford Medicine magazine profiled Chander’s work last summer, but I came across it when the title of one of Chander’s recently published papers grabbed my eye: “Electroencephalographic Variation During End Maintenance and Emergence from Surgical Anesthesia.” Okay, that might not pique your curiosity, but when I spotted the words, “for the first time” in the abstract I was hooked. I read on to learn that Chander and her team attach electrodes to the foreheads of patients during surgery, measuring the brain’s electrical signals.

After a bit of scrambling you might expect when trying to get in touch with someone who spends her days in the operating room, I managed to reach Chander on the phone. Our conversation strayed far from the bounds of her paper:

In this work, what did you do for the first time?

It’s not that no one has ever used an EEG during anesthesia. During the middle of the 20th century, several anesthesiologists attempted to record brain activity under increasing levels of anesthesia, just as many neuroscientists were using the EEG to characterize the stages of sleep. The process of recording EEG was really cumbersome back then, unlike today when you can stick a frontal set of leads on a patient’s forehead in the OR in a matter of seconds. Certain general stages of anesthesia were identified, but a formalized staging nomenclature, based on the relative contribution of dominant slow-wave oscillations in the EEG, had never been defined. Non-REM (slow-wave) and REM (rapid eye movement sleep) were staged in this way by sleep neurobiologists, but not anesthesiologists. In our study, we built upon the sleep stage classification system, to define maintenance patterns of general anesthesia. The formalized nomenclature helps us examine the stages of unconsciousness under anesthesia and communicate with other anesthesiologists.

What did you find?

We recorded the frontal EEGs (from the forehead) of 100 patients undergoing routine orthopedic surgeries. We discovered four primary electrical patterns that patients exhibit when they’re unconscious, and also as they’re waking up from anesthesia. The unconscious patterns show variety – not all patients’ brains look the same under anesthesia, despite similar drug exposure, meaning there are ‘neural phenotypes,’ or patterns of neuronal activity. The emergence patterns from anesthesia (pathways people’s brains take to reestablish conscious awareness after the anesthetic is turned off) bear some similarity to those pathways traversed when people are awakening from sleep.

When wakening from anesthesia, some people spend a relatively long time in non slow-wave anesthesia, which is similar to REM, the stage of sleep where dreams occur that usually precedes awakening. Others go straight from deep anesthesia, what we call slow-wave anesthesia (because of its dominant EEG patterns) to awakening. Interestingly, these patients were more likely to experience post-surgical pain, a situation akin to awakening from a deep sleep and experiencing confusion or discomfort; some childhood parasomnias like sleep terrors are characterized by moving abruptly from slow wave sleep to waking.

We began to see some tantalizing suggestions certain patterns of wake-ups from anesthesia might be more preferable. Could paying attention to these emergence trajectories prevent some problematic complications, like post-operative cognitive dysfunction? Could we ‘engineer’ or optimize anesthetic delivery to favor certain types of maintenance and emergence patterns? Can we monitor these patterns in a way that makes delivering anesthesia safer? Recognizing the variety of maintenance and emergence patterns under anesthesia also opens an entirely new possibility in the field of personalized medicine – imagine tailoring anesthetics to a person’s genome? I am trying to develop an initiative that addresses this in collaboration with Stanford’s new GenePool Biobank program.

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Chronic Disease, Imaging, Immunology, Neuroscience, Research, Stanford News

Patients’ reaction to ME/CFS coverage in Stanford Medicine magazine

Patients' reaction to ME/CFS coverage in Stanford Medicine magazine

me-cfs-brain-zeineh

In the last few weeks, Stanford published two articles on chronic fatigue syndrome, a.k.a. myalgic encephalomyelitis, and the outpouring of positive feedback from ME/CFS patients has been tremendous. In my long-form Stanford Medicine story and video, I describe a young woman’s seven-year battle with the disease and the groundbreaking research being done by her physician, José Montoya, MD, and immunologist Mark Davis, PhD, to identify the biomarkers and root causes of ME/CFS. My colleague Bruce Goldman followed up with an elegantly written article describing the distinct differences between the brains of ME/CFS patients with those of healthy people, in a newly released study from this same research team.

While our primary job as medical science writers is to explain new research accurately, it’s a bonus to know that we captured the patient experience in a compassionate way, and that we have in some way eased their suffering with hope.

Here is a sampling of a few of these letters from around the world:

From British Columbia, Canada:
Thank you for an article that is very well done. I will be printing it for my MD and forwarding it to family and a few close friends because it captures this devastating illness so well. I will keep a copy for myself to remind me (on those dark days) that Dr. Montoya is in my corner.

From Sweden:
I would like to thank you for your very informative and interesting article! This kind of information of what research is going on at Stanford, etc., is very important for us patients with ME all over the world! There is a lot of disinformation coming out about this disease and I therefore very much appreciate your article and especially Dr. Montoya’s passionate engagement with this disease.

From Cali, Colombia:
Here in Cali, Colombia, the city of birth of Dr. Montoya, I feel very happy reading your excellent article, and learning the marvelous and difficult investigation performed by these brilliant scientists. I was moved to tears. Thank you.

From the San Francisco Bay Area:
I want to thank you very much for the powerful piece you wrote about ME/CFS. You tell the story in a very engaging way, which is so compelling. It’s not the usual doom/gloom/dark room story which my daughter and I have encountered frequently in what people write about ME/CFS. Family and friends with whom I have shared the article are appreciative of your writing so descriptively and articulately about all aspects of ME/CFS: the science, the inequity of research funding, the personal experience of a patient, the work of Drs. Montoya/Mark Davis/Holden Maecker.

From India:
Today I have gone through your article about Erin’s story. How she recovered from CFS had given me a ray of hope as I am also suffering from such an ailment for the last 6-8 years.

From Atlanta, Georgia:
I just read your beautifully written article on Immune System Disruption. First soccer caught my eye, then “swimming in the primordial soup of creative disruption” locked me in. I read every word … and I am going to spend the rest of the night in Atlanta copying [my internal medicine doctor] on the article.

From Australia:
Just wanted to thank you for your excellent article. It could really make a difference in raising awareness and I appreciate the quality of your writing. I have suffered from CFS/ME for many years in Australia and find the research project and your understanding very encouraging.

From the blogosphere:
I just wanted to thank you for taking the time to write such an in-depth, accurate article on our oft-ignored illness. Dr. Montoya is a hero within the ME/CFS community, but I didn’t know about the others at Stanford also working on ME/CFS — that gives me some hope for a better future! I plan to share your article on my ME/CFS blog and in several Facebook groups for ME/CFS that I belong to.

Previously: Some headway on chronic fatigue syndrome: Brain abnormalities pinpointedUnbroken: A chronic-fatigue patient’s long road to recovery, Deciphering the puzzle of chronic-fatigue syndrome and Stanford Medicine magazine traverses the immune system
Image, showing white matter differences between a ME/CFS patient sample an a healthy control, by Michael Zeineh/Stanford

Aging, Neuroscience, Research

Being bilingual “provides the brain built-in exercise”

Being bilingual "provides the brain built-in exercise"

Spanish_booksWith less than two months left in 2014, many of us will soon begin the annual ritual of selecting our New Year’s resolutions. Those who are looking to boost their brain power may want to consider learning a second language in 2015: Research published today in the journal Brain and Language shows that being bilingual makes the brain more efficient at processing information.

In the study, researchers used functional magnetic resonance imaging (fMRI) technology to examine participants’ brains as they performed language comprehension tests. For example, researchers would say the word “cloud” to individuals while showing them four pictures, including one of a cloud and others of similar-sounding objects, like a clown. To complete the exercise, participants had to recognize the correct photo and ignore the irrelevant images. According to a release, study results showed:

The bilingual speakers were better at filtering out the competing words because their brains are used to controlling two languages and inhibiting the irrelevant words, the researchers found.

The fMRI scans showed that “monolinguals had more activation in the inhibitory control regions than bilinguals; they had to work much harder to perform the task,” [said lead author Viorica Marian, PhD.]

“Inhibitory control is a hallmark of cognition,” said Marian. “Whether we’re driving or performing surgery, it’s important to focus on what really matters and ignore what doesn’t.”

The fact that bilinguals are constantly practicing inhibitory control could also help explain why bilingualism appears to offer a protective advantage against Alzheimer’s and dementia, said Marian.

“That’s the exciting part,” she said. “Using another language provides the brain built-in exercise. You don’t have to go out of your way to do a puzzle because the brain is already constantly juggling two languages.”

The findings add to the growing body of scientific evidence showing that being bilingual can have profound impacts on your brain.

Previously: Study shows bilingualism may enhance attention and working memory and ¿Habla Español? How bilingualism may delay the onset of Alzheimer’s symptoms
Photo by Megan Morris

Aging, Health and Fitness, Neuroscience, Public Health, Research

Neighborhood’s “walkability” helps older adults maintain physical and cognitive health

Neighborhood’s “walkability” helps older adults maintain physical and cognitive health

3275748024_c4914d4ae0_zLiving in a walkable neighborhood could be an important factor in helping older adults maintain their physical and cognitive health, according to new research from the University of Kansas.

In the small study, researchers monitored a group of adults diagnosed with mild Alzheimer’s disease and compared them to those without any cognitive impairment. Over a two-year period, individuals completed cognitive tests designed to measure attention, verbal memory and mental status. The ”walkability” of participants’ neighborhoods was determined using geographic information systems (GIS). Medical News Today reports:

Results from the study suggest that communities that are easier to walk in are linked to better physical health outcomes – such as lower body mass and blood pressure – and cognition – including better memory.

[Researchers] believe their findings could benefit older adults, health care professionals, caregivers and even architects and urban planners.

Finding also showed that environments with more complex layouts appeared to aid residents in staying mentally sharp, rather than confusing them. Researchers presented their findings over the weekend at the Gerontological Society of America’s annual meeting in Washington, DC.

Previously: Walking and aging: A historical perspective, Even old brains can stay healthy, says Stanford neurologist,  Exercise and your brain: Stanford research highlighted on NIH Director’s blog , Moderate exercise program for older adults reduces mobility disability, study shows and Creating safer neighborhoods for healthier lifestyles
Photo by Ed Yourdon

Neuroscience, Research, Sleep, Stanford News, Technology

Cheating jet lag: Stanford researchers develop method to treat sleep disturbances

Cheating jet lag: Stanford researchers develop method to treat sleep disturbances

jets landing in sunset - 560

Last month, I went to a conference back East. It was a short trip, four days, and I was jet lagged the whole time. I spent my mornings gulping down hot coffee to help shake off the sleepy haze; in the evenings, when I should have been making up the lost sleep, I was wired, tossing and turning in bed. I could have tried adjusting to East Coast time in the days before I left by getting to bed a few hours earlier and getting up around 4 AM, but that would have required a level of coordination and planning that I’m unlikely to muster in the days before an out-of-town trip.

So I was curious when I learned that a team of Stanford researchers, led by neurobiologist Jamie Zeitzer, PhD, were working on a technique that helps people shift their sleep cycles by flashing light briefly at their eyes while they sleep. They recently published their findings in the Journal of Biological Rhythms.

Beyond the obvious job of vision, our eyes and brain are constantly processing information about the light around us. Light affects our moods and the daily ebb and flow of our biological clocks. It influences when we are sleepiest and most alert. Our brains do a lot of this work behind the scenes and because it happens unconsciously, we are rarely aware of these circadian rhythms – unless something disturbs them, like flying across several time zones.

Zeitzer and his team recruited volunteers and had them get on a routine sleep-wake cycle, going to bed and waking up at the same time every day for about two weeks. The researchers then had the volunteers come sleep in the lab, where the experimental group was given a series brief flashes of light about two millisconds long – about as long as a camera flash – aimed at their eyes. A control group slept in complete darkness, and the volunteers didn’t know which group they were assigned to. The team then measured whether the subjects’ sleep cycle had been affected by measuring the amount of melatonin in their blood. The brain floods the body with melatonin a couple of hours before bedtime and continues releasing the hormone until about an hour after wake time.

The researchers found that the volunteers who got the light flashes were able to shift the sleep phase of their circadian systems. What was surprising was that the intervention did not noticeably disturb the subjects’ sleep. The volunteers in the experimental group didn’t report any less restful sleep than the controls. “This kind of treatment can help people adjust even before they leave for a trip,” says Zeitzer. “Leaving for Australia, the night before you leave, you can adjust a couple of hours. On the plane, you can adjust a couple more. By the time you arrive, you’re already half-way adjusted.”

Besides jet-lagged travelers, this technique could also help teenagers who have a hard time getting up at the right time (a clinical condition for many that goes beyond adolescent laziness) and shift workers. Current treatments for sleep disturbances include sitting in front of bright lights for sometimes hours at a time, which often means it’s only used in extreme cases.

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