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Biomed Bites, Imaging, Neuroscience, Research, Science, Videos

Vrrrooom, vrrrooom vesicles: A Stanford researcher’s work on neurotransmission

Vrrrooom, vrrrooom vesicles: A Stanford researcher's work on neurotransmission

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers.

When one neuron wants to communicate with another neuron, it doesn’t talk, make gestures, or perform an interpretive dance. Instead, it ejects a vesicle filled with chemical information. That vesicle travels like an interstellar ship to the next neuron, which sucks it up, receiving the message.

And this isn’t a slow, hmm, maybe-I-should-send-this-out-sometime-today kind of message.

“The process of effusion of synaptic vesicles is very fast,” says Axel Brunger, PhD, in the video above. “It occurs on the order of a millisecond. It’s one of the fastest known biological processes, so we’re trying to understand this process at a molecular level and how it actually works is a big mystery at the moment.”

Brunger, the chair of the Department of Molecular and Cellular Physiology, and his team use a variety of optical imaging methods and high-resolution structural methods to examine the transmission of synaptic vesicles:

We’re now using our [in vitro] system to study the effect of a number of factors, including factors involved in a number of diseases.

What we are hoping from these studies is to obtain a better understanding of how these factors and then secondly and importantly, to develop new strategies or therapeutics to combat these diseases.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: New insights into how the brain stays bright, Revealed: The likely role of Parkinson’s protein in the healthy brain and Examining the potential of creating new synapses in old or damaged brains 

Neuroscience, Research, Stanford News, Technology

Stanford’s Karl Deisseroth awarded prestigious Albany Prize

Stanford's Karl Deisseroth awarded prestigious Albany Prize

Karl D with light - 560

Prizes abound for the most skillful of scientists, but a few stand out as particularly significant ones. The Albany Medical Center Prize in Medicine and Biomedical Research, which honors top biomedical researchers, is one of those prizes.

And today, before the sun rose over Stanford University, Karl Deisseroth, MD, PhD, was awarded the 2015 Albany Prize for his pioneering work in optogenetics. He will share the $500,000 cash award with Sunney Xie, PhD, a professor of chemistry and chemical biology at Harvard.

Deisseroth commented in our release:

It’s a great honor to receive this prize. The recognition of optogenetics is not only a testament to the creativity and vigor of everyone in the lab and our collaborators over the last decade or more, but also a signal to the world beyond the scientific community regarding the importance of basic science research to understanding the biology of health and disease.”

Optogenetics is a technique that enables researchers to control neurons in living animals.

The Albany Prize was founded in 2000 with a $50 million gift from New York philanthropist Marty Silverman. It is the United States’ highest value prize in medicine and biomedical research.

Previously: New York Times profiles Stanford’s Karl Deisseroth and his work in optogenetics, An in-depth look at the career of Stanford’s Karl Deisseroth, “a major name in science” and Optogenetics: Offering new insights into brain disorders
Photo by Lee Abel

In the News, Neuroscience, Research, Sleep, Stanford News

Stanford researcher’s work, which clarifies role of brain activity during sleep, featured on NPR

Stanford researcher's work, which clarifies role of brain activity during sleep, featured on NPR

ParviziMuch to my delight, I heard the voice of Josef Parvizi, MD, PhD, on NPR yesterday afternoon. He was discussing the results of his latest study, which showed that the brain’s activity during sleep is far from random.

“There is something that’s going on in a very structured manner during rest and during sleep,” Parvizi told NPR. “And that will, of course, require energy consumption.”

A Shots blog entry accompanying the segment describes the findings:

The team saw activity in two widely separated brain areas known to be involved in episodic memories. And the activity was highly coordinated — suggesting the different brain regions were working together to answer the questions…

“What we found,” he says, “was that the same nerve cells that were activated to retrieve memories… have a very coordinated pattern of noise.”

This explains, in part, why the brain consumes 20 percent of the body’s energy, although it constitutes only 2 percent of its weight. There are more details on the study in our press release.

Previously: New findings on exactly why our “idle” brains burn so much fuel, The brain whisperer: Stanford neurologist talks about his work, shares tips with aspiring doctors and How epilepsy patients are teaching Stanford scientists more about the brain

Mental Health, Neuroscience, Rural Health

Seven ways laughter can improve your well-being

Seven ways laughter can improve your well-being

3336353424_df38db0c8a_zEveryone enjoys a good laugh, but who actually makes time for it in their lives? Sure, we like hearing a funny joke, talking to people with a good sense of humor and watching comedies. But few of us take our laughs seriously (no pun intended!) nor do we make a concerted effort to laugh more. But we should! The science of laughter – though still preliminary – suggests that it has tremendous benefits for our health and psychological well-being.

Laughter can improve your relationships. According to a recent study led by research assistant Alan Gray of University College London, the act of laughing can make you more open to new people and can help you build relationships.

Laughter may also boost memory and lower stress. A study by researchers at Loma Linda University found that laughter can sharpen your ability to remember things while also reducing the stress hormone, cortisol, especially in older people.

Laughter may make you more resilient. Ever had nervous laughter in an awkward or difficult situation? That’s because laughter may help you regulate your emotions in the face of challenge, according to a study led by Yale psychologist Erica J. Boothby, PhD.

Laughter can improve your health. A study of diabetic patients by Lee S. Berk, PhD, and Stanley A. Tan, MD, of Loma Linda University found that laughing can lower stress and inflammation and increase good cholesterol. Ever found yourself laughing while telling a joke or funny story? Maybe you were anticipating the ending and laughed your way through the end of the joke? Another study by Berk and Tan suggests that just anticipating a funny event boosted immune function while decreasing stress-related hormones.

Laughter can make you a better learner. When we are trying to learn something new, we usually are pretty serious, but research by Mark Shatz, PhD, and Frank LoSchiavo, PhD, of Ohio University show that a good laugh while learning new material will help you engage with it more!

Laughter can make you more attractive.  Another recent study by Shatz and LoSchiavo shows that humor and playfulness are highly valued traits in potential romantic partners.

Laughter can help you make the world a better place. Why? It’s contagious. At least on the level of the brain, according to research by Sophie Scott, PhD, of University College London.

Emma Seppala, PhD, is associate director of Stanford’s Center for Compassion and Altruism Research and Education and a research psychologist at the School of Medicine. She is also a certified yoga, pilates, breath work and meditation instructor. A version of this piece originally appeared on Psychology Today.
Photo by Arnet Gill

Biomed Bites, Imaging, Neuroscience, Research, Technology, Videos

Peering under the hood – of the brain

Peering under the hood - of the brain

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers.

Fixing a broken brain is much like fixing a malfunctioning car, misbehaving computer or most anything else that isn’t working as it should.

“Whenever we’re trying to fix something that’s broken, it can be very helpful indeed to understand how that thing works,” says Stephen Smith, PhD, in the video above. “I believe the brain does not pose an exception to this rule.”

That’s why Smith, a professor of molecular and cellular biology, emeritus, has spent his career developing better ways to understand — and see — the brain.

Currently, he’s most excited about a technique called array tomography that allows researchers to observe the brain’s wiring, the linkages between neurons, and gain a better understanding of how it functions.

That technique, as well as others, offers real hope for fixing brains broken by autism, Alzheimer’s disease or other brain disorders. Here’s Smith:

I think the progress we’re making today in understanding basic brain mechanisms is likely to help us greatly as we develop new drugs that can help lessen or reverse the wide array of neurodegenerative or neurodevelopmental or injury-related disorders of the brain.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Visualizing the brain as a Universe of synapses, Examining the potential of creating new synapses in old or damaged brains and Fantastic voyage: Stanford researcher offers a virtual flight through the brain

Big data, Imaging, Neuroscience, Research, Science, Stanford News, Technology, Videos

All data – big and small – informs large-scale neuroscience project

All data - big and small - informs large-scale neuroscience project

The thought of gaining access to data from thousands of brains would make most neuroscientists salivate. But now, a team of Stanford and Oxford researchers is able to do just that. Led by Jennifer McNab, PhD, assistant professor of radiology, the group compares magnetic resonance images from as many as 100,000 people with in-depth 3-D scans developed using CLARITY, a technique developed at Stanford that visualizes intact tissue.

“This is a tremendous resource in terms of scientists being able to look and see who develops a particular disease and who does not and why that may be,” McNab said in the video above.

Her team — which includes Karl Deisseroth, MD, PhD; Michael Zeineh, MD, PhD and Michael Greicius, MD, MpH — is tapping the U.K. Biobank, which has about 500,000 participants. It also uses data from the NIH Human Connectome Project, which could include up to 1,200 MRI images. The project received a 2014 Big Data for Human Health Seed Grant and is part of Stanford Medicine’s Biomedical Data Science Initiative (BDSI), which strives to make powerful transformations in human health and scientific discovery by fostering innovative collaborations among medical researchers, computer scientists, statisticians and physicians.

The project uses two distinct types of “big data.” The large databases with hundreds of entries clearly falls under this umbrella, but even one dataset from CLARITY, which produces extremely high-resolution images, produces big data, she said.

The project may make it possible to glean more diagnostic information from MRIs, McNab said. “Then we can hopefully develop early biomarkers of disease that will ultimately help to guide treatment plans and preventative measures,” she said.

This project offers just a glimpse at the potential of data science. For more on important work being done in this area, mark your calendars for Stanford’s Big Data in Biomedicine conference May 20-22. More information is available here.

Previously: Registration for the Big Data in Biomedicine Conference now open, How CLARITY offers an unprecedented 3-D view of the brain’s neural structure and Euan Ashley discusses harnessing big data to drive innovation for a healthier world

Neuroscience, Research, Sleep, Stanford News

New findings on exactly why our “idle” brains burn so much fuel

New findings on exactly why our "idle" brains burn so much fuel

1959 Cadillac

“The human brain is a greedy organ,” I wrote in my release describing a new Stanford study before elaborating:

Accounting for only 2 percent of the body’s weight, it consumes 20 percent of the body’s energy. Yet the rate at which the brain gobbles glucose (the fuel our brain cells run on) barely budges when we cease performing a physical or mental activity. Even at rest, the brain seems engaged in a blizzard of electrical activity, which neuroscientists have historically viewed as useless “noise.”

The study, which appears today in in Neuron, sheds light on why the brain paradoxically appears to exhaust so much energy in what at first glance seems akin to the idling of a car’s engine. Although you wouldn’t know it from just staring at it, the human brain is a complicated orchestra of electrical circuits constantly humming along with one another over the comparatively long distances that separate one part of the organ from another.

Over the past decade, neuroscientists using brain-imaging methods have identified dozens of distributed, collaborative clusters of brain regions working in concert and dedicated to various mental activities from solving math problems to recalling what one ate for breakfast.

Now a team led by Stanford neuroscientist Josef Parvizi, MD, PhD, has tracked the electrical activity within and between these simultaneously pulsing clusters (or, in Neurospeak, “networks”) with more precision than has previously been possible, and shown that these closely coordinated firing patterns persist even during sleep. This, in turn, may go a long way to explaining why when it comes to how fast the brain guzzles energy, the most intense thoughts, emotions or actions on our part barely budge the needle.

In their study, Parvizi and his colleagues were able to dig deeper than brain-imaging studies can usually go, because they could directly record electrical activity in selected areas in living human subjects’ brains.

The areas in question are distinct parts of a well-studied brain network called the default mode network, which is perhaps the most energetic of the dozens that have so far been discovered. That’s because the default mode network is most active when a person is at rest — lying still with eyes closed or just staring off into space  — or is retrieving an autobiographical memory (“What did I eat for breakfast?”).

Parvizi and his associates showed that the same pattern of coordinated electrical activity observed in the default mode network regions when experimental subjects were performing an autobiographical-memory task persisted even when those individuals were sound asleep.

It adds up to this, Parvizi told me: “The vast amount of energy consumption by our brain is due to its spontaneous activity at all times when we are not consciously involved in a specific task.”

It may be that, all through the night, the brain’s circuits are talking to each other, taking each other’s measure, and staying tuned for optimal function when day breaks. An idling engine puts you just one gas-pedal pump away from a fast take-off.

Previously: In a human brain, knowing a human face and naming it are separate worries, Mind-reading in real life: Study shows it can be done (but they’ll have to catch you first), We’ve got your number: Exact spot inbrainwhere numeral recognition takes place revealed, Metamorphosis: At the push of a button, a familiar face becomes a strange one and Why memory and math don’t mix: They require opposing states of the same brain circuitry
Photo by Don O’Brien

Biomed Bites, Neuroscience, Research, Stroke, Videos

Taking the “molecular brakes” off learning

Taking the "molecular brakes" off learning

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers. 

When Carla Shatz, PhD, was a child, her grandmother suffered a stroke.

“At the time, people really couldn’t do anything for her and they didn’t understand how to give her rehab,” Shatz, a professor of biology and neurbiology, said in the video above. Shatz was sad and frustrated, but also curious: How does the brain change and recover, allowing for learning and growth?

“This research is something I’ve been working on for my entire career,” she said.

But now she and her team are starting to glean some insights into how the brain operates that could prove helpful for stroke treatments. Children learn effortlessly, but in adulthood, “molecular brakes” stymie the brain’s ability to create new connections, Shatz explained.

“If we could only take those brakes on learning off, we could restore learning to the amazing childlike state,” Shatz said. She and her collaborators have several ideas, ones that have shown promise in helping mice recover from stroke:

The last few years we’ve actually been able to come back to this question of stroke and address it with the knowledge of molecular mechanisms and the concept that enhancing brain plasticity and understanding how it works could actually allow for better recovery from stroke.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Science is like an ongoing mystery novel, says Stanford neurobiologist Carla Shatz, Examining the potential of creating new synapses in old or damaged brains  and Drug helps old brains learn new tricks 

Aging, Chronic Disease, Events, Health Policy, Neuroscience, Public Health, Women's Health

Alzheimer’s forum with Rep. Jackie Speier spurs conversation, activism

Alzheimer's forum with Rep. Jackie Speier spurs conversation, activism

10776927963_3dd8d244da_zWhat happens when you bring together a woman with Alzheimer’s, a congresswoman, a policy expert and two doctors? No, this isn’t a joke – but an intro to an informative and wide-ranging discussion on Alzheimer’s disease and its effects on women.

“I was pretty ignorant until fairly recently,” said Rep. Jackie Speier (D-CA), who organized the forum Alzheimer’s: A women’s health issue held in San Mateo, Calif. yesterday. She also penned an opinion piece published recently in the San Francisco Chronicle. “I had no idea that two out of three people diagnosed with Alzheimer’s are women.”

Although it’s the fifth leading cause of death in California, Alzheimer’s receives much less federal money than many other major diseases, she said.

To spur conversation and provide information, Speier invited Cynthia Ortiz Guzman, a former nurse who suffers from Alzheimer’s; Ruth Gay, director of public policy and advocacy for the Alzheimer’s Association; Elizabeth Landsverk, MD, medical director of ElderConsult, and Stanford’s Michael Greicius, MD, MPH, an associate professor of neurology and neurology and medical director of the Stanford Center for Memory Disorders. Greicius has done research on women’s risk of the disease.

Nearly all of the 150-plus people who attended the forum had a loved one who suffered from Alzheimer’s. “We still have a good life, but there is so much that needs to be done,” Guzman told them.

Greicius and Landsverk fielded questions about how to diagnose and treat Alzheimer’s as well as promising directions of research.

At Stanford, Greicius said a person with memory impairment would meet with a neurologist, take a several hour neuropsychological exam, have bloods tests and a brain scan, and meet with social workers and nurses. He emphasized that this is far above the level of care available in more community medical centers. Sometimes physicians are able to find biomarkers that signal Alzheimer’s presence more than a decade before symptoms appear he said.

Greicius urged attendees to find out if they’re eligible for a neurological research trial at Stanford and to consider donating their brains and the brains of their loved ones to use for research. He also thanked Speier for focusing attention on Alzheimer’s.

“We’ve got to get the attention of policymakers to address this issue,” Speier said, adding that she might try to secure federal funds as part of the defense budget.

Gay, who recently traveled to Washington, D.C. to advocate for the disease, agreed. “We know that today we need a game changer – we need people to step forward and speak out about this disease,” she said.

Previously: Science Friday explores women’s heightened risk for Alzheimer’s, The state of Alzheimer’s research: A conversation with Stanford neurologist Michael Greicius and The toll of Alzheimer’s on caretakers 
Photo by Marjan Lazarevski

Complementary Medicine, In the News, Mental Health, Neuroscience, Research

An oasis of peace in “the 500 channel universe”: Research on mindfulness and depression

An oasis of peace in "the 500 channel universe": Research on mindfulness and depression

1135112859_45dc222725_zEarlier this month, the American Psychological Association issued a feature on mindfulness and depression, highlighting research that suggests mindfulness is an effective way to ameliorate and treat mood disorders, particularly recurrent depression. Some of the featured research suggests a strong neurological basis for the association.

Zindel Segal, PhD, a psychologist at the University of Toronto who is quoted in the article and who was on the three-person team that created Mindfulness-Based Cognitive Therapy (MBCT), wonders if all the attention mindfulness is now receiving is part of a backlash against “the 500 channel universe” of distractions in modern society. It’s not a pill that can be taken and done with, though – it’s a restructuring of mental attitude that requires maintenance. Through MBCT, people learn to pay attention to sensations and feelings rather than evaluative thoughts.

The studies in the review suggest that MBCT works at least as well as medication to prevent recurrence, that it is effective for peri-natal depression, and that it may work especially well for people with histories of relapse or depression stemming from childhood. A brief prepared for the Department of Veterans Affairs found that mindfulness approaches were most effective against depression compared to other health conditions.

I found the neuroscience particularly interesting: Part of the reason for MBCT’s effectiveness may be that practicing mindfulness increases connectivity and tissue density in certain areas of the brain. This is a classic example of neuroplasticity – the idea that neurological pathways can adapt and change throughout one’s life.

Norman Farb, PhD, a neuroscientist at the University of Toronto, distinguishes two forms of self-reference that activate different areas of the brain: extended/narrative self-reference, which links experiences across time, and momentary/experiential self-reference, which is centered on the present. Mindfulness exercises emphasize the present, in contrast with destructive narrative patterns of thought common in those suffering from stress, anxiety, and depression. In Farb’s study, fMRI results show that regular mindfulness practice strengthens areas of the brain that focus on the moment. It suggests that although we habitually integrate these two forms of self-reference, they can be neurally dissociated through attentional training.

Neural differences may have effects even when someone is not actively engaging in mindfulness: A study led by Veronique Taylor at the University of Montreal showed that the experienced meditators has less activity in narrative self-referential areas than novice meditators even in a resting state. Another study led by Harvard University neuroscientist Sara Lazar, PhD, showed that over the course of an 8-week mindfulness stress reduction program, the gray matter in participants’ amygdala shrank in density, while density increased in areas related to sustained attention and emotion regulation. The amygdala is implicated in anxiety as well as depression, which correlates with the finding that the participants’ stress levels decreased.

According to the feature, Segal has been impressed with the dramatic rise in popularity of meditation over the past 20 years, which “resonates with people’s desires to find a way of slowing down and returning to an inner psychological reality that is not as easily perturbed,” he says. Perhaps most encouragingly, mindfulness practice has no adverse side-effects or contraindications, so I would expect to see more research into its efficacy, which could be good for all of us in our “500 channel universe.”

Previously: Mindfulness training may ease depression and improve sleep for both caregivers and patients, Using mindfulness-based programs to reduce stress and promote health, Using mindfulness therapies to treat veterans’ PTSD, How mindfulness-based therapies can improve attention and health and Study shows mindfulness may reduce cancer patients’ anxiety and depression.
Photo by ronsho

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