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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

Health and Fitness, Neuroscience, Research

Regularly practicing hatha yoga may improve brain function for older adults

77878_webPast studies have suggested that practicing yoga can help those suffering from insomnia rest easier and boost the immune system. Now new research shows that regularly participating in hatha yoga, which emphasizes physical postures and breath control, may improve older adults’ cognitive function.

In a study (subscription required) involving more than 100 adults ages 55 to 79, researchers assigned roughly half of the individuals to attend hatha yoga classes three times a week for eight weeks while the others participated in sessions in which they engaged in stretching and toning exercises. The Huffington Post reports:

At the end of eight weeks, the group that did yoga three times a week performed better on cognitive tests than it had before the start of yoga classes.

The group that did stretching and toning displayed no significant change in cognitive performance over time. In addition, researchers say the differences seen between the groups were not the result of age, gender, social status or other similar factors.



Edward McAuley
, PhD, who co-led the study, noted that participants in the yoga group displayed significant improvements in working memory capacity. “They were also able to perform the task at hand quickly and accurately, without getting distracted,” he said in a press release. “These mental functions are relevant to our everyday functioning, as we multitask and plan our day-to-day activities.”

Previously: Stanford researchers use yoga to help underserved youth manage stress and gain focus, Third down and ommm: How an NFL team uses yoga and other tools to enhance players’ well-being, Yoga classes may boost high-school students’ mental well-being and Study shows yoga may improve mood, reduce anxiety
Photo by Neha Gothe

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Bioengineering, Cardiovascular Medicine, Neuroscience, Research, Stanford News, Stroke

Targeted stimulation of specific brain cells boosts stroke recovery in mice

big blue brainThere are 525,949 minutes in a year. And every year, there are about 800,000 strokes in the United States – so, one stroke every 40 seconds. Aside from the infusion, within three or four hours of the stroke, of a costly biological substance called tissue plasminogen activator (whose benefit is less-than-perfectly established), no drugs have been shown to be effective in treating America’s largest single cause of neurologic disability and the world’s second-leading cause of death. (Even the workhorse post-stroke treatment, physical therapy, is far from a panacea.)

But a new study, led by Stanford neurosurgery pioneer Gary Steinberg and published in Proceedings of the National Academy of Sciences, may presage a better way to boost stroke recovery. In the study, Steinberg and his colleagues used a cutting-edge technology to directly stimulate movement-associated areas of the brains of mice that had suffered strokes.

Known as optogenetics – whose champion, Stanford psychiatrist and bioengineer Karl Deisseroth, co-authored the study – the light-driven method lets investigators pinpoint a specific set of nerve cells and stimulate only those cells. In contrast, the electrode-based brain stimulation devices now increasingly used for relieving symptoms of Parkinson’s disease, epilepsy and chronic pain also stimulate the cells’ near neighbors.

“We wanted to find out whether activating these nerve cells alone can contribute to recovery,” Steinberg told me.

As I wrote in a news release  about the study:

By several behavioral … and biochemical measures, the answer two weeks later was a strong yes. On one test of motor coordination, balance and muscular strength, the mice had to walk the length of a horizontal beam rotating on its axis, like a rotisserie spit. Stroke-impaired mice [in which the relevant brain region] was optogenetically stimulated did significantly better in how far they could walk along the beam without falling off and in the speed of their transit, compared with their unstimulated counterparts. The same treatment, applied to mice that had not suffered a stroke but whose brains had been … stimulated just as stroke-affected mice’s brains were, had no effect on either the distance they travelled along the rotating beam before falling off or how fast they walked. This suggests it was stimulation-induced repair of stroke damage, not the stimulation itself, yielding the improved motor ability.

Moreover, levels of some important natural substances called growth factors increased in a number of brain areas in  optogenetically stimulated but not unstimulated post-stroke mice. These factors are key to a number of nerve-cell repair processes. Interestingly, some of the increases occurred not only where stimulation took place but in equivalent areas on the opposite side of the brain, consistent with the idea that when we lose function on one side of the brain, the unaffected hemisphere can step in to help restore some of that lost function.

Translating these findings into human trials will mean not just brain surgery, but also gene therapy in order to introduce a critical light-sensitive protein into the targeted brain cells. Steinberg notes, though, that trials of gene therapy for other neurological disorders have already been conducted.

Previously: Brain sponge: Stroke treatment may extend time to prevent brain damage, BE FAST: Learn to recognize the signs of stroke and Light-switch seizure control? In a bright new study, researchers show how
Photo by Shutterstock.com

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Neuroscience, Pediatrics, Research, Stanford News

Kids’ brains reorganize as they learn new things, study shows

Kids' brains reorganize as they learn new things, study shows

arithmeticWhy do some children pick up on arithmetic much more easily than others? New Stanford findings from the first longitudinal brain-scanning study of kids solving math problems are shedding light on this question. The work gives interesting insight into how a child’s brain builds itself while also absorbing, storing and using new information. It turns out that the hippocampus, already known as a memory center, plays a key role in this construction project.

Published this week in Nature Neuroscience, the research focuses on what’s happening in the brain as children shift from counting on their fingers to the more efficient strategy of pulling math facts directly from memory. To conduct the study, the research team collected two sets of magnetic resonance imaging scans, about a year apart, on a group of grade-schoolers. From our press release:

“We wanted to understand how children acquire new knowledge, and determine why some children learn to retrieve facts from memory better than others,” said Vinod Menon, PhD, the Rachel L. and Walter F. Nichols, MD, professor of psychiatry and behavioral sciences at Stanford and the senior author of the study. “This work provides insight into the dynamic changes that occur over the course of cognitive development in each child.”

The study also adds to prior research into the differences between how children’s and adults’ brains solve math problems. Children use certain brain regions, including the hippocampus and the prefrontal cortex, very differently from adults when the two groups are solving the same types of math problems, the study showed.

“It was surprising to us that the hippocampal and prefrontal contributions to memory-based problem-solving during childhood don’t look anything like what we would have expected for the adult brain,” said postdoctoral scholar Shaozheng Qin, PhD, who is the paper’s lead author.

The study found that as children aged from an average of 8.2 to 9.4 years, they counted less and pulled facts from memory more when solving math problems. Over the same period, the hippocampus became more active and forged new connections with other parts of the brain, particularly several regions of the neocortex. But comparison groups of adolescents and adults were found on brain scans not to be making much use of the hippocampus when solving math problems. In other words, Menon told me, “The hippocampus is providing a scaffold for learning and consolidating facts into long-term memory in children.” And the stronger the scaffold of connections in an individual child, the more readily he or she pulled math facts from memory.

Now that the scientists have a baseline understanding of how this brain-building process normally works, they hope to run similar brain-scanning tests on children with math learning disabilities, with the aim of understanding what goes awry in the brains of children who really struggle with math.

Previously: Unusual brain organization found in autistic kids who best peers at math, Peering into the brain to predict kids’ responses to math tutoring and New research tracks “math anxiety” in the brain
Photo by Yannis

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Behavioral Science, Neuroscience, Research

Why memories of mistakes may speed up learning

Why memories of mistakes may speed up learning

mistake_learningRemember when you burnt the crab cakes on one side while testing a new recipe for a dinner party and had to compensate by generously dressing them with a creamy sauce? What about the time you were introduced to a friend’s new girlfriend, whose name was somewhat similar to the last one, and you called her the wrong name? Or that accidental trip down a one-way street while in an unfamiliar city? Chances are you didn’t make these mistakes twice.

Now findings (subscription required) published today in Science Express may explain how memories of past errors speed learning of subsequent similar tasks. As explained in a release, scientists have known that when performing a task, the brain records small differences between expectation and reality and uses this information to improve next time. For example, if you’re learning how to drive a car the first time you may press down on the accelerator harder than necessary when shifting from the break pedal. Your brain notes this and next time you press down with a lighter touch. The scientific term for this is “prediction errors,” and the process of learning is largely unconscious. What’s surprising about this latest study is “that not only do such errors train the brain to better perform a specific task, but they also teach it how to learn faster from errors, even when those errors are encountered in a completely different task. In this way, the brain can generalize from one task to another by keeping a memory of the errors.”

To arrive at this conclusion, researchers used a  simple set of experiments where volunteers were placed in front of joystick that was hidden under a screen. More from the release:

Volunteers couldn’t see the joystick, but it was represented on the screen as a blue dot. A target was represented by a red dot, and as volunteers moved the joystick toward it, the blue dot could be programmed to move slightly off-kilter from where they pointed it, creating an error. Participants then adjusted their movement to compensate for the off-kilter movement and, after a few more trials, smoothly guided the joystick to its target. In the study, the movement of the blue dot was rotated to the left or the right by larger or smaller amounts until it was a full 30 degrees off from the joystick’s movement. The research team found that volunteers responded more quickly to smaller errors that pushed them consistently in one direction and less to larger errors and those that went in the opposite direction of other feedback.

Daofen Chen, PhD, a program director at the National Institute of Neurological Disorders and Stroke, commented on the significance of the findings saying, “This study represents a significant step toward understanding how we learn a motor skill … The results may improve movement rehabilitation strategies for the many who have suffered strokes and other neuromotor injuries.”

Previously: Depression, lifestyle choices shown to adversely affect memory across age groups, Newly identified protein helps explain how exercise boosts brain health and Exercise may protect aging brain from memory loss following infection
Photo by Grace

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Neuroscience, Parenting, Pediatrics

Can musical training help close the achievement gap between high and low-income children?

Can musical training help close the achievement gap between high and low-income children?

scope Music and kids

Drawing data from hundreds of students from low-income urban communities, a recent study offers new insights into understanding the academic gap between children from varying socioeconomic backgrounds and demonstrates the impact of musical training in helping low-income youth improve their language and reading comprehension skills.

The research (.pdf) was presented at the American Psychological Association’s annual convention and involved elementary and high school-aged students who participated in two separate projects measuring neural responses along with language and cognitive evaluations over a two-year period. Younger participants were part of Los Angeles-based nonprofit Harmony Project and older subjects attended three public high schools in Chicago. As explained in a press release:

[Researchers] studied children beginning when they were in first and second grade. Half participated in musical training and the other half were randomly selected from the program’s lengthy waiting list and received no musical training during the first year of the study. Children who had no musical training had diminished reading scores while Harmony Project participants’ reading scores remained unchanged over the same time span.

Over two years, half of the [Chicago] students participated in either band or choir during each school day while the other half were enrolled in Junior Reserve Officer’s Training Corps classes, which teaches character education, achievement, wellness, leadership and diversity. All participants had comparable reading ability and IQs at the start of the study. The researchers recorded the children’s brain waves as they listened to a repeated syllable against soft background sound, which made it harder for the brain to process. The researchers repeated measures after one year and again at the two-year mark. They found music students’ neural responses had strengthened while the JROTC students’ responses had remained the same. Interestingly, the differences in the music students’ brain waves in response to sounds as described above occurred after two years but not at one year, which showed that these programs cannot be used as quick fixes, [Northwestern neurobiologist Nina Kraus, PhD] said. This is the strongest evidence to date that public school music education in lower-income students can lead to better sound processing in the brain when compared to other types of enrichment education, she added.

“Research has shown that there are differences in the brains of children raised in impoverished environments that affect their ability to learn,” Kraus further explained in the release. “While more affluent students do better in school than children from lower income backgrounds, we are finding that musical training can alter the nervous system to create a better learner and help offset this academic gap.”

Jen Baxter is a freelance writer and photographer. After spending eight years working for Kaiser Permanente Health plan she took a self-imposed sabbatical to travel around South East Asia and become a blogger. She enjoys writing about nutrition, meditation, and mental health, and finding personal stories that inspire people to take responsibility for their own well-being. Her website and blog can be found at www.jenbaxter.com.

Previously: Pump up the bass, not the volume, to feel more powerful, Denver rappers’ music motivates kids (of all ages) to eat better and Brains of different people listening to the same piece of music actually respond in the same way.
Photo By: CherryPoint

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Anesthesiology, Medicine and Literature, Neuroscience

Exploring the conscious (and unconscious) brain in every day life

Exploring the conscious (and unconscious) brain in every day life

line of peopleThe first time I fainted, I was seven. I passed out while racing my fellow second-graders across the playground. One minute, I was leading the pack in the race; the next thing I knew, I was lying in the nurse’s office with adult faces hovering all around me. My parents explained to me that I’d lost consciousness – it was like falling asleep for a minute, they told me.

It frustrated me to no end- even as a seven year old – that I didn’t know where that time had gone. Why couldn’t I remember those moments where I collapsed onto the grass and got scooped up by a petrified teacher? I ended up fainting a handful of times over the next few years (luckily doctors chalked it up to nothing more than dehydration and a genetic propensity to faint), and each time I was reminded of that frustration of not being able to grasp what was going on in my brain during those lost minutes.

As a seven-year-old, I didn’t have the chance to call up scientists and ask them to explain the brain to me, so when I started working on a feature article on consciousness for the latest issue of Stanford Medicine magazine, I was thrilled that maybe I’d get that chance to finally answer those questions that had been lingering in my head for decades. What makes the brain go from awake and aware to such a blank state, and then back again?

But it’s not that simple, I learned: There’s no single switch that flips the brain from conscious to unconscious. In fact, consciousness isn’t an on-off switch at all; it’s a whole spectrum of states. Anesthesiologist Bruce MacIver, PhD, pointed me toward this handy chart that shows different levels of consciousness. Each state of consciousness has its own unique place on two scales: physical arousal and mental awareness. As I looked at it, I realized that my experience with altered consciousness wasn’t just limited to my childhood fainting episodes – we all go in and out of multiple states of consciousness on a daily basis, and not only when we fall asleep and wake up.

“If you’re an elite athlete and you get in that so-called ‘zone,’ that’s an altered state of consciousness,” anesthesiologist Divya Chander, MD, PhD, explained to me. I’m no elite athlete, but after talking to Chander, I suddenly started paying attention to those not infrequent times when I “zone out” while driving or exercising. And when I woke up to a noise in my house on a recent night, I immediately noticed my heightened senses – that alertness is an altered state of consciousness too.

“What I’m always hoping is that hearing about this kind of work makes people ask more questions about what it means when they themselves enter different states,” Chander said to me when we talked. Her message was not lost on me; I’ve become an active observer of my shifts in attention and awareness.

My Stanford Medicine story delves much deeper than these observations of daily life, to look at how and why anesthesiologists are probing what it means to be conscious – and how their research could lead to better anesthetic drugs. But I hope that in addition to conveying the science, it also helps readers realize that subtle changes in consciousness happen in your brain all the time.

As for the questions I had as a seven-year-old, they’re not fully answered, but I’ve only gotten more intrigued to know how the brain mediates consciousness, and more excited to follow where this research goes in the future.

Sarah C.P. Williams is an award-winning science writer based in Hawaii, covering biology, chemistry, translational research, medicine, ecology, technology and anything else that catches her eye.

Previously: Stanford Medicine magazine opens up the world of surgery, Your secret mind: A Stanford psychiatrist discusses tapping the motivational unconscious and Researchers gain new insights into state of anesthesia
lllustration by Jon Han

Neuroscience, Research, Stanford News

Non-invasive technique uses lasers and carbon nanotubes to provide view of blood flow in the brain

Non-invasive technique uses lasers and carbon nanotubes to provide view of blood flow in the brain

When researchers want to explore the brain of living animals, they have two options: surgically remove part of the skull, a procedure that can alter its function or trigger an immune response, or use CT or MRI scans, which isn’t effective for visualizing activity of individual vessels or groups of neurons. But a new approach developed by Stanford chemists holds the promise of offering a third option that is non-invasive and captures “an unprecedented look at blood flowing through a living brain.”

The technique involves injecting water-soluble carbon nanotubes into the subject’s bloodstream, in this case mice, and using near-infrared light to illuminate the brain vasculature and track cerebral blood flow. The work, which was published in Nature Photonics, could be useful in advancing the study of stroke and migraines, as well as Alzheimer’s and Parkinson’s diseases. According to a recent Stanford Report story:

Amazingly, the technique allows scientists to view about three millimeters underneath the scalp and is fine enough to visualize blood coursing through single capillaries only a few microns across, said senior author Hongjie Dai, a professor of chemistry at Stanford. Furthermore, it does not appear to have any adverse affect on innate brain functions.

….

The technique could eventually be used in human clinical trials, Hong said, but will need to be tweaked. First, the light penetration depth needs to be increased to pass deep into the human brain. Second, injecting carbon nanotubes needs approval for clinical application; the scientists are currently investigating alternative fluorescent agents.

Previously: Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, Peering into the brains of freestyle rappers to better understand creativity and Brain imaging, and the “image management” cells that make it possible

Stanford Medicine Resources: