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Neuroscience, NIH, Research, Stanford News

Federal BRAIN Initiative funds go to create better sensors for recording the brain’s activity

Optical voltage sensorYesterday the National Institutes of Health handed out the first $46 million in funding for the BRAIN Initiative, announced in 2013. Stanford got one of those awards, worth almost $1 million to develop improved ways of recording activity in the brain.

The award went to applied physicist Mark Schnitzer, PhD, and bioengineer Michael Lin, MD, PhD, to expand on work they published last year. The pair had each developed tiny sensors that could detect voltage changes within a neuron. These provided the first real-time view of a nerve’s activity. When I wrote about their initial work earlier this year I described how these probes could be used:

With these tools scientists can study how we learn, remember, navigate or any other activity that requires networks of nerves working together. The tools can also help scientists understand what happens when those processes don’t work properly, as in Alzheimer’s or Parkinson’s diseases, or other disorders of the brain.

The proteins could also be inserted in neurons in a lab dish. Scientists developing drugs, for example, could expose human nerves in a dish to a drug and watch in real time to see if the drug changes the way the nerve fires. If those neurons in the dish represent a disease, like Parkinson’s disease, a scientist could look for drugs that cause those cells to fire more normally.

The BRAIN initiative award will help the team develop better sensors, and also improve the technology for recording the signals. In a conversation, Lin told me that the brain fires at a rate of about 4 milliseconds. Any camera for recording that activity needs to record about 1,000 frames per second, and current cameras operate at about one tenth of that speed. Schnitzer has expertise in developing tiny cameras for recording biological activity and will be working to create a faster camera to pair with Lin’s improved sensors.

Previously: Thoughts light up with new Stanford-designed tool for studying the brainBold and game-changing” federal report calls for $4.5 billion in brain-research fundingNIH announces focus of funding for BRAIN initiative and New tool for reading brain activity of mice could advance study of neurodegenerative diseases
Image courtesy of Michael Lin

CDC, In the News, Infectious Disease, Neuroscience, Pediatrics

Stanford experts offer more information about enterovirus-D68

Stanford experts offer more information about enterovirus-D68

Below is an updated version of an entry that was originally posted on Sept. 26.

SONY DSCLast week, the California Department of Public Health confirmed that the season’s first four cases of enterovirus-D68 respiratory illness had been found in the state, three in San Diego County and one in Ventura County, with more expected to surface. As of Sept. 29, this makes California one of 40 states across the nation to be affected by EV-D68.

Health officials in Colorado are now investigating a handful of cases of paralysis in children there; the paralysis began a few weeks after respiratory illness and appears to be connected to EV-D68. Since the same virus was tentatively linked to paralysis cases in California children earlier this year, California officials are monitoring the situation closely.

Below, Yvonne Maldonado, MD, service chief of pediatric infectious disease at Lucile Packard Children’s Hospital Stanford, answers additional questions about the respiratory symptoms caused by this virus. Keith Van Haren, MD, a pediatric neurologist who has been assisting closely with the California Department of Public Health’s investigation, also comments on neurologic symptoms that might be associated with the virus.

Enteroviruses are not unusual. Why is there so much focus from health officials on this one, EV-D68?

Maldonado: The good news is that this virus comes from a very common family of viruses that cause most fever-producing illnesses in childhood. But it’s been more severe than other enteroviruses. Some hospitals in other parts of the country have had hundreds of children coming to their emergency departments with really bad respiratory symptoms. The fact that it’s been so highly symptomatic and that there has been a large volume of cases is why it has gotten so much attention.

Van Haren: It’s important to remember that most children and adults who are exposed to enteroviruses don’t get sick at all. A smaller percentage come down with fever and/or respiratory symptoms, as Dr. Maldonado has described. And as far as we can tell, it’s only a very, very small number of children, if any, who get paralysis, typically affecting one arm or leg. The Centers for Disease Control and the California Department of Public Health are still investigating to try to determine conclusively whether EV-D68 is causing neurologic symptoms, such as paralysis.

What do we know about the course of possible neurologic symptoms of EV-D68 and their potential treatments?

Van Haren: We’re still learning about the possible neurologic symptoms and how we might treat them. To start, we have a growing suspicion that EV-D68 may be associated with paralysis. In the patients we’ve seen with paralysis, progression of weakness appears to stop on its own, and recovery of strength is very slow and usually incomplete.

Which groups are most at risk?

Maldonado: Children with a history of asthma have been reported to have especially bad respiratory symptoms with this virus. It can affect kids of all ages, from infants to teens. So far, only one case has been reported in an adult, which makes sense because adults are more likely to have immunity to enteroviruses. We do worry more about young infants than older children, just because they probably haven’t seen the virus before and can get worse respiratory symptoms with these viral infections.

Van Haren: We don’t yet know who is most at risk for paralysis or other neurologic symptoms, but we are studying this carefully to find out why some children get sick and some do not. So far, it seems that the children who have been affected by paralysis were generally healthy prior to their illness.

What is the treatment for EV-D68?

Maldonado: There is no treatment that is specific to the virus. At home, parents can manage children’s fevers with over-the-counter medications, make sure they drink lots of fluids to avoid dehydration, and help them get plenty of rest. For children who are very ill, doctors will check for secondary illnesses such as bacterial pneumonia, which would be treated with antibiotics, and may hospitalize children who need oxygen or IV hydration to help them recover.

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Events, Neuroscience, Stanford News

Open Office Hours: Stanford neurobiologist taking your questions on brain research

Open Office Hours: Stanford neurobiologist taking your questions on brain research

Newsome

Last year Stanford launched the new Stanford Neurosciences Institute, led by visionary neurobiologist William Newsome, PhD. Part of his job over the past year has been to inspire faculty to think beyond their own labs and to dream about what they could accomplish if they work together. He called this the Big Ideas in Neuroscience.

This week, Newsome will be taking questions about your Big Ideas (or Big Questions) in brain research as part of a Stanford Open Office Hours event on Facebook. Are you curious how we learn and remember? What technologies might allow us to peer into the brain and even manipulate its function? How a deeper understanding of the brain could influence public policy, education and the law? Go to the Facebook page for the event and submit your questions by tomorrow (Oct 1).

Previously: “Bold and game-changing” federal report calls for $4.5 billion in brain-research fundingDinners spark neuroscience conversation, collaborationBrain’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 from Stanford News Service

Aging, In the News, Neuroscience, Stanford News

Exercise and your brain: Stanford research highlighted on NIH Director’s blog

Exercise and your brain: Stanford research highlighted on NIH Director’s blog

B0007367 Thigh muscle fibrilsThomas Rando, MD, PhD, who studies stem cells in muscle and longevity, and Tony Wyss-Coray, PhD, who studies the immune system’s impact on the brain, were awarded an NIH Director’s Transformative Research Award to study the slew of molecules that muscles release and how they help muscle cells communicate with other cells. (Rando and Wyss-Coray call this cellular communication network “the communicome.”) The onset of both depression and Alzheimer’s disease have been shown to be delayed with exercise, and Rando and Wyss-Coray theorize that molecules released by muscles during exercise may be the key to understanding how exercise can affect brain function so profoundly and so beneficially.

Today on the NIH Director’s blog, Francis Collins, MD, highlighted the Stanford duo’s research:

To study the communicome, Wyss-Coray and Rando will use a technique called parabiosis to couple the circulatory systems of physically active mice with mice that are less active. If the “couch potato” mice benefit from the blood of the active mice, then the team will analyze the blood to find the responsible factor(s).

This is definitely high-risk high-reward research. It won’t be easy, but finding molecules that mimic exercise’s brain-boosting effects may open the door to new ways of preventing or treating age-related cognitive declines and a wide range of other neurological conditions. This is especially important for people for whom it is difficult or even hazardous to exercise because of conditions such as arthritis, osteoporosis, and Alzheimer’s disease and other forms of dementia.

Earlier this year, Wyss-Coray published a study showing that older mice that received transfusions of younger mice’s blood improved their brain function. That study was based in part on Rando’s previous research showing that young mouse blood could activate old stem cells and rejuvenate older tissue. Their new collaboration may shed more light on the molecular mechanisms behind such observations.

Previously: Young mouse to old mouse: “It’s all in the blood, baby”, The rechargeable brain: Blood plasma from young mice improves old mice’s memory and learning, “Alert” stem cells speed damage response, say Stanford researchers and Red light, green light: Simultaneous stop and go signals on stem cells’ genes may enable fast activation, provide “aging clock”
Photo, of thigh muscle fibrils, by David Gregory & Debbie Marshall, via Wellcome Images

Neuroscience, Research, Stanford News, Stem Cells

Cellular padding could help stem cells repair injuries

Cellular padding could help stem cells repair injuries

The idea of using stem cells to heal injuries seems so obvious. If you have a spinal cord injury, why not inject some new cells that can replace the ones that are lost?

Unfortunately, the very act of injecting those cells is rife with trouble. The scraping as they move through the needle damages the cells and can even kill them. Then, once in the site of the injury, the cells can easily ooze away into other tissue, or die from the onslaught of chemicals in the injury.

Material scientists Sarah Heilshorn, PhD, is trying to help these cells with a type of gel that can protect and support them, allowing them to live long enough to possibly repair the injury. A grant from Stanford Bio-X, the pioneering interdisciplinary life sciences institute, is now helping Heilshorn and her colleagues, neurosurgeon Giles Plant, PhD, and chemical engineer Andrew Spakowitz, PhD, get the project off the ground.

In a story I wrote about the work, Heilshorn equates the gel to ketchup:

It’s pretty thick, but when you bang on the bottle the sauce flows smoothly through the neck, then firms back up on the plate – a process she calls self-healing. “We want our polymers to self-heal better than ketchup,” she said. “It flows a bit across the plate.”

Her goal is to develop a polymer that supports the cells when they are loaded in a syringe, but then flows freely through the needle, padding and protecting the cells, then firming up quickly when it reaches the site of injury. “We don’t want the cells to flow away,” she says.

These Seed grants from Bio-X have been credited as part of what has made the institute so successful in bringing together people from diverse disciplines to solve biomedical problems. “The seed grants are the special Bio-X glue that brings teams of faculty from all over the university to tackle complex problems in human health using new approaches,” said Carla Shatz, PhD, who directs Bio-X.

We’ll be writing about a few of the most exciting projects being funded with the recently announced 2014 Bio-X Seed grants over the next few weeks.

Previously: They said “Yes”: The attitude that defines Stanford Bio-X

Neuroscience, Research, Stanford News

The life of a brain, captured by Stanford scientists

The life of a brain, captured by Stanford scientists

4_brains_fibertracts

At last, Stanford psychologists have come up with an explanation for our 20s. Or at least my 20s. That period of time when I was in so many ways an adult and yet some higher processing – inpulse control, for example – did not yet seem fully formed.

A group led by psychologist Brian Wandell, PhD, measured the brain composition of 102 people spanning ages 7 to 85 in 24 regions of the brain. The were specifically measuring what’s known as white matter – the fatty protective covering on our nerves that helps them fire more efficiently and, as the name implies, makes up the white part of our brains. People have long known that the white matter increases as the brain matures and white matter abnormalities have been associated with schizophrenia and other conditions. As I wrote in a Stanford News piece:

What [the researchers] found is that the normal curve for brain composition is rainbow-shaped. It starts and ends with roughly the same amount of white matter and peaks between ages 30 and 50. But each of the 24 regions changes a different amount. Some parts of the brain, like those that control movement, are long, flat arcs, staying relatively stable throughout life.

Others, like the areas involved in thinking and learning, are steep arches, maturing dramatically and then falling off quickly. (The group did point out that their samples started at age 7 and a lot of brain development had already occurred.)

That’s right. Thinking, learning, emotional control – none of those are firing at full capacity until around age 40. Beyond providing an excuse for a few bad decisions, the work could also become useful for doctors. In this study, the group examined the brains of people with multiple sclerosis, and they were able to detect more subtle decreases in white matter than doctors can when monitoring the disease. The researchers also say the work could help monitor effects of drugs, or diagnose kids who appear to have learning delays.

Previously: Learning how we learn to read and Teaching an old dog new tricks: New faster and more accurate MRI technique quantifies brain matter

Behavioral Science, Evolution, Imaging, Neuroscience, Research, Stanford News, Surgery

In a human brain, knowing a face and naming it are separate worries

In a human brain, knowing a face and naming it are separate worries

Alfred E. Neuman (small)Viewed from the outside, the brain’s two hemispheres look like mirror images of one another. But they’re not. For example, two bilateral brain structures called Wernicke’s area and Broca’s area are essential to language processing in the human brain – but only the ones  in the left hemisphere (at least in the great majority of right-handers’ brains; with lefties it’s a toss-up), although both sides of the brain house those structures.

Now it looks as though that right-left division of labor in our brains applies to face perception, too.

A couple of years ago I wrote and blogged about a startling study by Stanford neuroscientists Josef Parvizi, MD, PhD, and Kalanit Grill-Spector, PhD. The researchers recorded brain activity in epileptic patients who, because their seizures were unresponsive to drug therapy, had undergone a procedure in which a small section of the skulls was removed and plastic packets containing electrodes placed at the surface of the exposed brain. This was done so that, when seizures inevitably occurred, their exact point of origination could be identified. While  patients waited for this to happen, they gave the scientists consent to perform  an experiment.

In that experiment, selective electrical stimulation of another structure in the human brain, the fusiform gyrus, instantly caused a distortion in an experimental subjects’ perception of Parvizi’s face. So much so, in fact, that the subject exclaimed, “You just turned into somebody else. Your face metamorphosed!”

Like Wernicke’s and Broca’s area, the fusiform gyrus is found on each side of the brain. In animal species with brains fairly similar to our own, such as monkeys, stimulation of either the left or right fusiform gyrus appears to induce distorted face perception.

Yet, in a new study of ten such patients, conducted by Parvizi and colleagues and published in the Journal of Neuroscience,  face distortion occurred only when the right fusiform gyrus was stimulated. Other behavioral studies and clinical reports on patients suffering brain damage have shown a relative right-brain advantage in face recognition as well as a predominance of right-side brain lesions in patients with prosopagnosia, or face blindness.

Apparently, the left fusiform gyrus’s job description has changed in the course of our species’ evolution. Humans’ acquisition of language over evolutionary time, the Stanford investigators note, required the redirection of some brain regions’ roles toward speech processing. It seems one piece of that co-opted real estate was the left fusiform gyrus. The scientists suggest (and other studies hint) that along with the lateralization of language processing to the brain’s left hemisphere, face-recognition sites in that hemisphere may have been reassigned to new, language-related functions that nonetheless carry a face-processing connection: for example, retrieving the name of a person whose face you’re looking at, leaving the visual perception of that face to the right hemisphere.

My own right fusiform gyrus has been doing a bang-up job all my life and continues to do so. I wish I could say the same for my left side.

Previously: Metamorphosis: At the push of a button, a familiar face becomes a strange one, 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 in brain where numeral recognition takes place revealed and Why memory and  math don’t mix: They require opposing states of the same brain circuitry
Photo by AlienGraffiti

Neuroscience, Research, Stanford News

Brain’s wiring more dynamic than originally thought

Brain's wiring more dynamic than originally thought

brain branches

I write a lot about news developments in which scientists learn new things about the body – how diseases develop or can be treated, how genes and proteins in our bodies make us who we are, how different areas of the brain work together to help us learn, remember and interact with our environment.

Yesterday I wrote a story in which the scientists learned that they have more work to do.

It all started when Joanna Mattis was looking for a PhD project. She had been working  in the lab of bioengineer Karl Deisseroth, MD, PhD, helping to develop optogenetics. At the time, that was an entirely new tool that scientists could use to turn parts of the brain on and off to see what happens. Mattis wanted to use optogenetics to map the wiring of two regions of the brain that were known to work together to help develop a spatial map of the environment. Those two regions are known as the hippocampus and the septum.

Some of the expertise needed to do this project didn’t exist in the Deisseroth lab. Mattis got a fellowship through Stanford Bio-X that specifically allows students to work with multiple mentors  – Mattis added neuroscientist John Huguenard, PhD, – bringing interdisciplinary expertise together to solve problems. In this case, those combined expertise didn’t so much solve a problem as create a new one.

What they found is that nerves in the hippocampus create one reaction in the septum if they fire slowly and a completely different reaction of they fire quickly. It was like learning that the wiring diagram of the brain shifts depending on how the brain sends signals.

Mattis told me, “There’s a lot of excitement about being able to make a map of the brain with the idea that if we could figure out how it is all connected we could understand how it works. It turns out it’s so much more dynamic than that.”

She said that next steps will include learning how widespread this type of wiring is throughout the brain, and understanding how it ties back to learning and memory.

Previously: Optogenetics: Offering new insights into brain disorders
Photo by nednapa/Shutterstock

Behavioral Science, Chronic Disease, Mental Health, Neuroscience, Research, Stanford News

Can Alzheimer’s damage to the brain be repaired?

Can Alzheimer's damage to the brain be repaired?

repair jobIn my recent Stanford Medicine article about Alzheimer’s research, called “Rethinking Alzheimer’s,” I chronicled a variety of new approaches by Stanford scientists to nipping Alzheimer’s in the bud by discovering what’s gone wrong at the molecular level long before more obvious symptoms of the disorder emerge.

But Stanford neuroscientist Frank Longo, MD, PhD, a practicing clinician as well as a researcher, has another concern. In my article, I quoted him as saying:

Even if we could stop new Alzheimer’s cases in their tracks, there will always be patients walking in who already have severe symptoms. And I don’t think they should be forgotten.

A study by Longo and his colleagues, which just went into print in the Journal of Alzheimer’s Disease, addresses this concern. Longo has pioneered the development of small-molecule drugs that might be able to restore nerve cells frayed by conditions such as Alzheimer’s.

Nerve cells in distress can often be saved from going down the tubes if they get the right medicine. Fortunately, the brain (like many other organs in the body) makes a number of its own medicines, including ones called growth factors. Unfortunately, these growth factors are so huge that they won’t easily cross the blood-brain barrier. So, the medical/scientific establishment can’t simply synthesize them, stick them into an artery in a patient’s arm and let them migrate to the site of brain injury or degeneration and repair the damage. Plus, growth factors can affect damaged nerve cells in multiple ways, and not always benign ones.

The Longo group’s study showed that – in mice, at least -  a growth-factor-mimicking small-molecule drug (at the moment, alluded to merely by the unromantic alphanumeric LM11A-31) could counteract a number of key Alzheimer degenerative mechanisms, notably the loss of all-important contacts (called synapses) via which nerve cells transmit signals to one another.

Synapses are the soldier joints that wire together the brain’s nerve circuitry. In response to our experience, synapses are constantly springing forth, enlarging and strengthening, diminishing and weakening, and disappearing.They are crucial to memory, thought, learning and daydreaming, not to mention emotion and, for that matter, motion. So their massive loss — which in the case of Alzheimer’s disease is a defining feature – is devastating.

In addition to repairing nerve-cells, the compound also appeared to exert a calming effect on angry astrocytes and  microglia, two additional kinds of cells in the brain that, when angered, can produce inflammation and tissue damage in that organ. Perhaps most promising of all, LM11A-31 appeared to help the mice remember where things are and what nasty things to avoid.

Previously: Stanford’s brightest lights reveal new insights into early underpinnings of Alzheimer’s, Stanford neuroscientist discusses the coming dementia epidemic and Drug found effective in two mouse models of Huntington’s disease
Photo by Bruce Turner

Aging, Complementary Medicine, Health and Fitness, Mental Health, Neuroscience, Research

Mindfulness training may ease depression and improve sleep for both caregivers and patients

Mindfulness training may ease depression and improve sleep for both caregivers and patients

meditatingDepression and poor sleep often affect both dementia patients and their caregivers. Now new research shows that caregivers and patients who undergo mindfulness training together experience an improvement in mood, sleep and overall quality of life.

While past studies have shown that yoga and simple meditations can relieve caregivers’ stress, researchers at Northwestern University wanted to determine if patients and caregivers could be trained together.

In the small study (subscription required), pairs of patients and caregiver participated in an eight-week mindfulness program. Patients were diagnosed with dementia due to Alzheimer’s disease or mild cognitive impairment, often a precursor to dementia. Caregivers included spouses, adult children or other relatives. The training was designed specifically to meet the needs of  individuals with memory loss due to terminal neurodegenerative illness and their caregivers. Researchers evaluated participants within two weeks of starting the program and two weeks of completing it.  Lead author Ken Paller, PhD, explained the results in a release:

We saw lower depression scores and improved ratings on sleep quality and quality of life for both groups… After eight sessions of this training we observed a positive difference in their lives.

Mindfulness involves attentive awareness with acceptance for events in the present moment… You don’t have to be drawn into wishing things were different. Mindfulness training in this way takes advantage of people’s abilities rather than focusing on their difficulties

Since caregivers often have limited personal time, mindfulness programs that accommodate them as well as patients could be an effective approach to helping both groups regularly attend sessions, said researchers.

The findings were published Monday in the American Journal of Alzheimer’s Disease and Other Dementias.

Previously: Regularly practicing hatha yoga may improve brain function for older adults, Study suggests yoga may help caregivers of dementia patients manage stress and How mindfulness-based therapies can improve attention and health
Photo by Alex

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