TAG: "Neuroscience"

Neurobiologists restore youthful vigor to adult brains

Reactivated plasticity points to new treatments for developmental disorders.

UC Irvine neurobiologist Sunil Gandhi led the study that, in a sense, coaxed old brain processes to become young again. (Photo by Steve Zylius, UC Irvine)

By Tom Vasich, UC Irvine

They say you can’t teach an old dog new tricks. The same can be said of the adult brain. Its connections are hard to change, while in children, novel experiences rapidly mold new connections during critical periods of brain development.

UC Irvine neurobiologist Sunil Gandhi and colleagues wanted to know whether the flexibility of the juvenile brain could be restored to the adult brain. Apparently, it can: They’ve successfully re-created a critical juvenile period in the brains of adult mice. In other words, the researchers have reactivated brain plasticity – the rapid and robust changes in neural pathways and synapses as a result of learning and experience.

And in doing so, they’ve cleared a trail for further study that may lead to new treatments for developmental brain disorders such as autism and schizophrenia. Results of their study appear online in Neuron.

The scientists achieved this by transplanting a certain type of embryonic neuron into the brains of adult mice. The transplanted neurons express GABA, a chief inhibitory neurotransmitter that aids in motor control, vision and many other cortical functions.

Much like older muscles lose their youthful flexibility, older brains lose plasticity. But in the Gandhi study, the transplanted GABA neurons created a new period of heightened plasticity that allowed for vigorous rewiring of the adult brain. In a sense, old brain processes became young again.

In early life, normal visual experience is crucial to properly wire connections in the visual system. Impaired vision during this time leads to a long-lasting visual deficit called amblyopia. In an attempt to restore normal sight, the researchers transplanted GABA neurons into the visual cortex of adult amblyopic mice.

“Several weeks after transplantation, when the donor animal’s visual system would be going through its critical period, the amblyopic mice started to see with normal visual acuity,” said Melissa Davis, a postdoctoral fellow and lead author of the study.

These results raise hopes that GABA neuron transplantation might have future clinical applications. This line of research is also likely to shed light on the basic brain mechanisms that create critical periods.

“These experiments make clear that developmental mechanisms located within these GABA cells control the timing of the critical period,” said Gandhi, an assistant professor of neurobiology & behavior.

He added that the findings point to the use of GABA cell transplantation to enhance retraining of the adult brain after injury. Furthermore, this work sparks new questions as to how these transplanted GABA neurons reactivate plasticity, the answers to which might lead to therapies for currently incurable brain disorders.

Dario Figueroa Velez, Roblen Guevarra, Michael Yang, Mariyam Habeeb and Mathew Carathedathu of UCI contributed to the study, which was supported by a National Institutes of Health Director’s New Innovator Award (DP2 EY024504-01), a Searle Scholars award, a Klingenstein Fellowship and a postdoctoral training grant from the California Institute for Regenerative Medicine (TG2-01152).

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Even when we’re resting, our brains are preparing us to be social

UCLA research helps resolve a nearly 20-year-old mystery.

Researchers asked people to to judge whether photo captions — some focusing on a mental state, others on a physical description — accurately described the images. (Image courtesy of Robert Spunt)

By Stuart Wolpert, UCLA

A new study by UCLA neuroscientists sheds light on why Facebook is such a popular diversion for people who feel like taking a break. Their research shows that even during quiet moments, our brains are preparing us to be socially connected to other people.

“The brain has a major system that seems predisposed to get us ready to be social in our spare moments,” said Matthew Lieberman, a UCLA professor of psychology and of psychiatry and biobehavioral sciences. “The social nature of our brains is biologically based.”

The research helps resolve a nearly 20-year-old mystery. Neuroscientists have known since the 1990s that the brain includes a network of regions that seems to be most active during periods of rest — this became apparent when they examined brain scans of people who were attempting to answer challenging questions during scientific experiments and noticed that certain areas of the brain became unusually active during the periods in between the problem-solving. But until now, scientists knew very little about what purpose is served by the brain’s activity during those interludes.

The UCLA research, published in the June print edition of the Journal of Cognitive Neuroscience, shows that during quiet moments, the brain is preparing to focus on the minds of other people — or to “see the world through a social lens,” said Lieberman, the study’s senior author.

In experiments at UCLA’s Ahmanson–Lovelace Brain Mapping Center, the researchers showed photos with captions to 21 people, and tracked their brain activity using functional magnetic resonance imaging, or fMRI. Most of the photos showed people performing actions in a social setting and expressing a certain emotion. In one set of 40 photographs, images were paired with captions that reflected the person’s mental state — “He is feeling bored” or “She is expressing self-doubt,” for example. The second set of photos had identical images, but with captions that merely described what the person was doing — “He is resting his head” or “She is looking to her side.” And a third set of images depicted a number accompanied by a simple mathematical equation — for example, “10: 18-8.”

Participants were asked to judge whether the captions accurately expressed what the images showed. Among the findings:

  • The same regions of the brain that were active during the brief times that subjects were not looking at photos also were active when the participants were considering the photos with captions about people’s emotions. But those areas of the brain were not active when the participants were viewing the cards with captions about the person’s physical activity and those with the math equations.
  • Sometimes, a part of the brain called the dorsomedial prefrontal cortex was more active during the rest period immediately before participants were asked to look at photos. In those cases, the participants made significantly faster judgments if the next photo they saw presented a statement about the person’s mental state.
  • There was no relation between activity in the dorsomedial prefrontal cortex during rest and the speed of people’s decision-making on the questions involving math equations or the photographs with physical descriptions.
  • Study participants who were found to have traits characteristic of autism spectrum disorders — the researchers identified them using questionnaires administered prior to the brain scans — had less brain activity in the dorsomedial prefrontal cortex during periods of rest and were slower to judge the mental state of people in the photographs. Those with the least amount of dorsomedial prefrontal cortex activity were 10 percent slower than those with the most.

The difference in decision-making speed that the researchers observed could have a significant effect in people’s everyday lives, Lieberman said. “It might not seem like a huge advantage, but being 10 percent faster, time after time, in each conversation will allow a person to be much better prepared and in control of their social lives.”

Lieberman, author of the best-selling book “Social: Why Our Brains Are Wired to Connect,” describes the dorsomedial prefrontal cortex as the “CEO of the social brain.” It’s part of a network in the brain that turns on when we dream and during periods of rest, in addition to when we explicitly think about other people, he said.

► Watch: Lieberman’s September 2013 TEDx talk on the social brain

Based on activity in that region of the brain when the study participants were resting, researchers could accurately predict how quickly the participants would perform the next task. When the dorsomedial prefrontal cortex was highly active before participants saw a photo with a description of a mental state, they were faster in making their judgment; when the region was only slightly active, their decision-making was slower. The phenomenon applied equally among men and women.

“It’s the same photograph; the only thing that differs is whether the caption is mind-focused or body-focused,” said lead author Robert Spunt, who conducted the research when he was a UCLA doctoral student in psychology and is now a postdoctoral scholar at Caltech. “It’s remarkable.”

Lieberman said that people who struggle to read social cues in other people’s facial expressions might be able to improve this skill with practice, and he is conducting additional research to examine whether certain kinds of practice at social thinking can help improve people’s social abilities more broadly.

The findings suggest that the dorsomedial prefrontal cortex might turn on during dreams and rest in order to process our recent social experiences and update our assumptions and understanding of the social world, Lieberman said.

“It is getting us ready to see the world socially in terms of other people’s thoughts, feelings and goals,” he said. “That indicates it is important; the brain doesn’t just turn systems on. We walk around with our brain trying to reset itself to start thinking about other minds.”

So although Facebook might not have been designed with the dorsomedial prefrontal cortex in mind, the social network is very much in sync with how our brains are wired.

“When I want to take a break from work, the brain network that comes on is the same network we use when we’re looking through our Facebook timeline and seeing what our friends are up to,” said Lieberman, one of the founders of the field of study known as social cognitive neuroscience. “That’s what our brain wants to do, especially when we take a break from work that requires other brain networks.”

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Measuring ‘brainstorms’

Researchers pioneer technique permitting peek inside neurons at activity of ion channels.

A team led by Peter Burke, UC Irvine professor of electrical engineering & computer science, developed a detector that offers a window into the inner workings of the brain and a brand-new tool for future research. (Photo by Steve Zylius, UC Irvine)

By Pat Brennan, UC Irvine

Like a gathering storm, tiny electrical pulses in a brain cell coalesce into a kind of explosion: the firing of a single neuron.

And the firing of billions of neurons provides each of us with the inner experiences that define our lives – seeing, hearing, thinking, even noting the passage of time between heartbeats.

In a feat of engineering that could extend the reach of both nanotechnology and neurobiology, UC Irvine researchers have found a way to peer inside a neuron and watch as the storm gathers.

Using carbon nanowires only a few atoms thick, the team – led by electrical engineering & computer science professor Peter Burke – managed to eavesdrop on the opening and closing of ion channels at the scale of a single brain cell.

Ions are charged particles that transmit electrical signals. The collective activity of thousands or millions of channels through which they flow is what causes a neuron to fire.

“When it rains, you get a weather report that tells how many inches of rain fell in a given period,” says Burke, whose work was published last month in Scientific Reports. “The weatherman doesn’t measure each drop.”

But the technique his team developed, he says, is the equivalent of “measuring each individual drop of rain.”

That’s a first. “No one has ever measured a single ion channel with a single nanowire before,” Burke says.

The method offers a window into the inner workings of the brain and a brand-new tool for future research.

And it could significantly advance the goals of President Barack Obama’s BRAIN Initiative, announced in 2013, which seeks to map brain functions and attack neurological disorders such as Alzheimer’s, epilepsy and autism.

The team began by creating an artificial cell. Its wall, like that of a real cell, is pockmarked with pores that open and close, allowing ions to flow in and out.

Next, the scientists installed nanowires just outside the artificial cell’s wall. The wires are capable of registering minuscule fluxes of energy and picked up the pelting of “raindrops” – in this case, the size of atoms – signaling the opening and closing of ion channels.

For now, the nanowire detector is confined to its carefully constructed laboratory setting. Asked to speculate, however, Burke sees a number of potentially revolutionary applications in the years and decades ahead.

A nanowire detector, for example, could be implanted in a living human brain, perhaps providing therapy for brain disorders or simply monitoring the organ itself and learning the submicroscopic details of information traffic among brain cells.

No one has yet developed a way to implant such a device, Burke notes, and doing so might be difficult. One possible avenue: attach the detector to a free-floating “nano radio” that could broadcast data about the state of ion channels.

“So many processes in life, in biology, are using electricity,” Burke says. “The cell, in a sense, is converting some physical phenomenon into an electrical signal. It all involves these ion channels.”

All our senses, from vision to smell, rely on these channels, he says, adding that in the future “you could have an artificial nose, an artificial eye.”

Electricity is critical to coordinate the beating of our hearts and other life-or-death bodily functions, such as the release of insulin in response to sugar in the blood. So the new detectors could, for instance, lead to a better understanding of diabetes.

And the ability to spy on ion channel activity could prove invaluable for cancer researchers. “You could use this technique to measure how chemotherapy affects cell death or to figure out why cancer cells don’t die,” Burke says.

Another important potential use is in drug screening. Fifteen percent of all pharmaceuticals act on ion channels; knowing how they do it could greatly improve the reliability of testing to ensure a drug’s safety and effectiveness.

“This wire, a few atoms across, is sensitive enough to measure with unprecedented resolution the way neurons work,” Burke says.

The study’s lead author is Weiwei Zhou, and co-authors are Yung Yu Wang, Tae-Sun Lim, Ted Pham and Dheeraj Jain.

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UC teams receive $3.5M for neuroscience research

UCLA, UCSF teams among Allen Distinguished Investigator recipients.

Six groups of researchers from leading academic institutions, including three from the University of California, have been awarded funding from the Paul G. Allen Family Foundation in the field of neuroscience.

The Allen Distinguished Investigator (ADI) grants fund a total of $7.5 million over three years to solve one of the most challenging roadblocks in neuroscience: growing mature human brain cells in the laboratory.

The recipients include two teams from UCLA and one from UC San Francisco.

UCLA honorees William Lowry and Kathrin Plath will receive $1.3 million, while the other UCLA team, Daniel Geschwind and Steve Horvath, will receive $1.2 million.

UCSF honorees Erik Ullian and David Rowitch will receive $1 million in funding.

“I was happily surprised by the announcement,” Ullian said. “The great thing about this funding is that it will allow us to try to move our research forward in a new and high risk/high reward direction.”

The six projects chosen to receive ADI grants in the field of neuronal maturation all tackle one or more of these challenges in bold new ways, including using innovative technologies and novel points of view.

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Seeing through Alzheimer’s disease

UC Berkeley’s William Jagust uses imaging to help find insights into Alzheimer’s.

William Jagust’s Alzheimer’s research has found evidence of neuron networks breaking down. (Photo by Peg Skorpinski, UC Berkeley)

By Wallace Ravven

A jury would have to acquit. Two tough guys are caught at the scene of a brutal beating, but no one witnessed the crime. No video cameras or cell phone captured the assault. Maybe both men arrived after the attack. Or one might have acted alone. They’re suspicious, but not guilty beyond a reasonable doubt.

The same might be said about our current understanding of how Alzheimer’s disease develops. Two proteins — called beta-amyloid and tau — definitely muck up neurons in Alzheimer’s victims.  Amyloid clumps into plaques that interfere with cell-to-cell communication. Tau proteins contort into tangled fibers inside the cells.

But until recently, neuroscientists have not been able to track the course of Alzheimer’s in the brain. Amyloid and tau might not destroy neurons directly, or perhaps amyloid works alone, wrecking the delicate integrity of neural networks and degrading memory.

Researchers have been limited to a single snapshot of the brain — one view of the battlefield provided by an autopsy. The course and chronology of the damage that steals memory are still up for grabs.

“We’ve been scratching our heads about how these two proteins are related to each other and to the cause of Alzheimer’s for literally 100 years,” says Berkeley neuroscientist William Jagust. “We don’t know the difference between ‘normal’ memory loss and the likely pathology associated with tau. We don’t know whether amyloid or tau is most important in Alzheimers, or if amyloid plaques between neurons affect the tau tangles inside cells.”

But there’s a sense of anticipation in the air, buoyed by researchers’ increasing ability to peer into the brains of people struggling with Alzheimer’s as well as  seniors free of its grip. In the past decade, PET scans and other powerful new imaging tools have begun to fill in the story of how healthy and damaged brains change throughout life.

“We still have many questions and few answers,” Jagust says. “But brain PET scanning in both diseased and healthy people is sort of blowing that wide open. We now have the tools to study the progression of plaque formation from its earliest stages and to determine how amyloid and tau affect cognitive decline over time.

Before PET scanning, Jagust says, researchers already knew from autopsies that about a third of older people with amyloid plaques had no symptoms of cognitive decline.

“This created the argument: ‘If they have no symptoms, how can it be that amyloid causes Alzheimer’s?’ You can’t answer that with an autopsy.” But if periodic PET scans show increasing plaque deposition over time as cognitive loss becomes severe, then the plaque argument becomes much stronger.

Research in his lab supports the hypotheses that plaques interfere with the formation or maintenance of synaptic connections. Using the metabolic imaging technique of functional MRI, he focused on plaque-ridden brains of healthy older people, and found indirect, but strong evidence that connections within networks of neurons were breaking down.

“Parts of the brain that should be connected strongly are becoming weakly connected, and parts that are normally not strongly connected become so. It’s almost like the brain is becoming rewired.”

But the rewiring evidence cuts both ways. In another study, Jagust found that some people with amyloid plaques performed as well on memory tests as those who were plaque-free. In some of them, novel connections appeared between neurons in their brains, suggesting new networks were in play.

“There is evidence of ‘rewiring’ that appears to be detrimental, but also evidence of ‘rewiring’ that may serve a compensatory role  — providing a cognitive reserve,” he says. “The balance between these in individuals may explain why some decline and others do not.” The research was published in 2013 in the Journal of Neuroscience and in 2014 in Nature Neuroscience.

Several large clinical trials have shown that experimental immunotherapeutic drugs can at least moderately slow Alzheimer’s amyloid plaque deposition. So far, the decline in plaque buildup has not slowed memory loss. But Jagust is confident that the tremendous boost in brain imaging will lead to effective therapies.

One ambitious study, just launched at Harvard and UC San Diego neuroscientists, combines refined imaging and drug trial, focusing on 1,000 people in their 70s and 80s. Study participants do not have Alzheimer’s, though some have amyloid plaques. Researchers hope that by intervening early enough with drugs to slow plaque accumulation, they can prevent or at least delay severe cognitive loss. If early intervention is key, then so is the ability to detect even the slightest sign of neurological damage. The Jagust Lab is using statistical and computational approaches to refine PET scan sensitivity.

In images of people’s brains with significant amyloid deposits, the protein shows up clearly as fiery orange bands across the cerebral cortex, or gray matter areas of the brain. Jagust suspects that improved scanning will allow researchers to spot mere traces that hint at possible trouble to come. The lab is also beginning studies that will image accumulations of tau, allowing the researchers to understand the relationships between tau and amyloid, and provide another target for drug development.

“If the images can tease apart the different roles of beta-amyloid and tau, and if we can detect damage in its very earliest stages, we would have strong reason to hope that new drugs can spare or significantly slow cognitive damage. I don’t think this is being overly optimistic.”

In recognition of his research on brain aging and dementia, Jagust received the 2013 Potamkin Prize for Research in Pick’s, Alzheimer’s and Related Diseases by the American Academy of Neurology and the American Brain Foundation.

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Spinal cord axon injury location determines neuron’s regenerative fate

Imaging advances revealing insights into body’s ability to respond to spinal cord injuries.

Injury to a spinal cord axon after a major branch point.

By Heather Buschman, UC San Diego

Researchers at the UC San Diego School of Medicine report a previously unappreciated phenomenon in which the location of injury to a neuron’s communication wire in the spinal cord — the axon — determines whether the neuron simply stabilizes or attempts to regenerate. The study, published today (April 30) by Neuron, demonstrates how advances in live-imaging techniques are revealing new insights into the body’s ability to respond to spinal cord injuries.

While the body of a neuron is small, its axon can extend far up or down the spinal cord, which is about one and half feet long in humans. Along that distance, the axon branches out to make hundreds of connections with other cells, sending out signals that allow us to sense and respond to the world around us. Unless something happens to disrupt the axon’s reach, that is. Adult human axons in the brain and spinal cord are very limited in their ability to regenerate after injury — a hurdle that many researchers are trying to overcome in the treatment of spinal cord injuries and neurodegenerative diseases of the brain.

In this study, senior author Binhai Zheng, Ph.D., associate professor of neurosciences, first author Ariana O. Lorenzana, Ph.D., and colleagues used a sophisticated optical imaging technique that allows them to directly visualize the spinal cord in living mouse models. With this approach, the researchers were able to systematically examine the effects of axon injury location on degeneration and regeneration of the injured branch. The injury locations they compared were just before an axon’s major branch point (where a single axon branches into two) and just after it. The injuries just after the branch point cut off one branch, leaving the other intact, or cut both branches.

The researchers found that injury to the main axon, before a branch point, resulted in regeneration in 89 percent of the cases. Axons with both branches cut after a branch point regenerated in 67 percent of cases. Regeneration occurred in the form of axon elongation, branching or both for at least five days after injury. In contrast, regeneration occurred only 12 percent of cases following cuts to just one of two axon branches after a major branch point. In this case, the injured branch trims itself all the way back to the base, preserving the function of the other, uninjured branch.

“What we think is happening is that if an axon is injured in such a way that it still has some kind of connection, is still transmitting signals, the neuron can justify stabilization, but not the energy it would take to either regenerate axon length or just kill the whole thing off,” Zheng said. “On the other hand, once both branches of an axon are cut and there’s no longer any connection or output, the neuron can justify the energy and resources to regenerate, even though that effort is largely futile in the central nervous system of an adult mammal.”

This is a new, yet very fundamental, understanding of neuron behavior — one that will be important to keep in mind as new therapeutic approaches are proposed for spinal cord injuries, the researchers say.

Co-authors of this study include Jae K. Lee, Matthew Mui, and Amy Chang, all of UC San Diego.

This research was funded, in part, by the National Institutes of Health (grants R01NS054734, R21NS088536, F31NS074867 and F32NS056697), Dana Foundation and Roman Reed Foundation.

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Graduate student uses math to study deadly diseases

Research could have implications for Alzheimer’s, Parkinson’s and Huntington’s diseases.

Jason Davis uses computer modeling and applied mathematics to study prion diseases.

By James Leonard, UC Merced

Graduate student Jason Davis doesn’t use a traditional lab to study prion diseases. Instead, he relies on computer modeling and applied mathematics.

Working with Suzanne Sindi, a professor of applied mathematics at UC Merced, Davis is trying to unlock the mysteries of prions and the destructive diseases they create. It’s a growing form of interdisciplinary research that uses math to examine biological functions.

“Working in applied math is a great opportunity to see the ‘big ideas’ from across various scientific disciplines,” said Davis, a Ph.D. candidate in applied mathematics. “Few areas of study have such broad application and it is very rewarding to apply my mathematical knowledge to real problems, particularly in health.”

Prion diseases result from proteins that become misshapen or misfolded — often in the brain. These destructive proteins clump together as masses or chains and multiply by converting other healthy proteins into a corrupted form.

Mad cow disease is perhaps the most well-known prion disease. While prion diseases always are fatal in mammals, researchers have found that a protein in yeast can actually reform misfolded proteins and head off infection.

Through his research, Davis is trying to understand why and how that occurs in yeast, and to look for a similar healing thread in humans. To do so, he creates mathematical models of prion diseases and uses a computer to simulate the infection. Such computer modeling is faster and less expensive than traditional lab work, and no animals or organisms are used in the experiments.

Davis’ research could have implications for neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s. These crippling and ultimately fatal diseases are all caused by protein misfolding disorders.

Uncommon path to Merced

Davis took an uncommon route to UC Merced. He grew up in Bridgewater, Maine, a tiny town near the Canadian border where schoolchildren once took a “harvest break” to work on family potato farms. He had an affinity for math and spent most of his high school years at the magnet Maine School of Science and Mathematics in Limestone, Maine.

“That school got me started on my academic trajectory,” said Davis, a first-generation college student. “It made me realize that I could handle academia.”

The demanding curriculum gave Davis a head start at Brown University, where he earned the equivalent of bachelor’s degrees in both mathematics and education studies. Davis then took a job with the Air Force Office of Scientific Research in Arlington, Virginia, where he helped manage research funds in the areas of applied mathematics and computer science. While there, he also earned a master’s in mathematics and statistics from Georgetown University.

Davis might never have headed west without an invitation from Sindi, whom he met and worked with while she was doing postdoctoral work at Brown. Sindi asked him to join her research team at UC Merced, where she had just accepted a job in 2012.

Davis hopes to finish his doctorate in a few years and then work in a national lab or manage research projects. He said he appreciates his time at UC Merced, where the campus’s small size and interdisciplinary approach to research allow him to directly engage with faculty members and find collaborative opportunities.

He’s also happy to have traded the big-city lifestyle for a relaxed pace — although it’s still a step up from his hometown. “Merced is a booming metropolis compared to where I grew up,” he said.

Sindi praised Davis as a hard-working and thoughtful student. In addition to his research work, Davis also has helped mentor other students and aided in recruitment efforts.

“He’s a very energetic, positive guy,” she said. “He has contributed a lot to the program.”

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The art of mantaining cognitive health as our brains age

Most people can take steps to improve their health, UCSF professor says.

By Laura Kurtzman, UC San Francisco

Brains age, just like the rest of the body, even for those don’t get neurological disease, according to an Institute of Medicine report released on April 14.

“Some of the changes that one observes doesn’t mean that it’s all over, gloom and doom,” the committee’s vice chair, Kristine Yaffe, M.D., told the Washington Post.

While aging does more damage to some than others, most people can take steps to improve their health, according to Yaffe, the Roy and Marie Scola Endowed Chair and professor of psychiatry, neurology and epidemiology at UCSF and chief of geriatric psychiatry and director of the Memory Disorders Clinic at the San Francisco VA Medical Center.

The committee proposed three actions to help maintain cognitive function with age: staying physically active; managing blood pressure and diabetes; and stopping smoking. Aging adults should also pay careful attention to health conditions and medications that could influence their cognitive health.

Having an active social and intellectual life can also promote cognitive health, as can getting good sleep. Aging individuals should treat any sleep disorders that develop and be aware of the delirium that can be caused by medications and hospitalization.

The committee advised caution when evaluating claims that brain training and nutritional supplements can improve cognition.

The scientific literature has shown that older adults can get better at trained abilities, although often more slowly than younger adults, and that they can maintain these skills. But it’s less clear whether these benefits transfer to real-world activities like driving or remembering an appointment.

As for nutritional supplements, the report says the medical literature does not offer convincing support that any of them can prevent cognitive decline.

The committee urged more protections for older adults, who lose an estimated $2.9 billion a year, directly and indirectly, because of financial fraud. The report said government and the financial services industry should take steps to protect older adults from exploitation and help preserve their independence.

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Washington Post: Everything ages, even your brain. Don’t worry so much. It’s probably not Alzheimer’s.

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Brain development suffers from lack of fish oil fatty acids

UC Irvine researchers point to dietary link for proper pre- and postnatal neural growth.

By Tom Vasich, UC Irvine

While recent reports question whether fish oil supplements support heart health, UC Irvine scientists have found that the fatty acids they contain are vitally important to the developing brain.

In a study appearing today (April 15) in The Journal of Neuroscience, UCI neurobiologists report that dietary deficiencies in the type of fatty acids found in fish and other foods can limit brain growth during fetal development and early in life. The findings suggest that women maintain a balanced diet rich in these fatty acids for themselves during pregnancy and for their babies after birth.

Susana Cohen-Cory, professor of neurobiology & behavior, and colleagues identified for the first time how deficits in what are known as n-3 polyunsaturated fatty acids cause molecular changes in the developing brain that result in constrained growth of neurons and the synapses that connect them.

These fatty acids are precursors of docosahexaenoic acid, or DHA, which plays a key role in the healthy creation of the central nervous system. In their study, which used female frogs and tadpoles, the UCI researchers were able to see how DHA-deficient brain tissue fostered poorly developed neurons and limited numbers of synapses, the vital conduits that allow neurons to communicate with each other.

“Additionally, when we changed the diets of DHA-deficient mothers to include a proper level of this dietary fatty acid, neuronal and synaptic growth flourished and returned to normal in the following generation of tadpoles,” Cohen-Cory said.

DHA is essential for the development of a fetus’s eyes and brain, especially during the last three months of pregnancy. It makes up 10 to 15 percent of the total lipid amount of the cerebral cortex. DHA is also concentrated in the light-sensitive cells at the back of the eyes, where it accounts for as much as 50 percent of the total lipid amount of each retina.

Dietary DHA is mainly found in animal products: fish, eggs and meat. Oily fish – mackerel, herring, salmon, trout and sardines – are the richest dietary source, containing 10 to 100 times more DHA than nonmarine foods such as nuts, seeds, whole grains and dark green, leafy vegetables.

DHA is also found naturally in breast milk. Possibly because of this, the fatty acid is used as a supplement for premature babies and as an ingredient in baby formula during the first four months of life to promote better mental development.

The UCI team utilized Xenopus laevis (the African clawed frog) as a model for this study because it allowed them to follow the progression and impact of the maternal dietary deficit in the offspring. Because frog embryos develop outside the mother and are translucent, the researchers could see dynamic changes in neurons and their synaptic connections in the intact, live embryos, where development can be easily studied from the time of fertilization to well after functional neural circuits form.

They focused on the visual system because it’s an accessible and well-established system known to depend on fatty acids for proper growth and utility.

Miki Igarashi and Rommel Santos of UC Irvine contributed to the study, which was supported by the National Eye Institute (grant EY-011912).

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Exploring the ADHD-autism link

UC Irvine research is revealing similarities between the two disorders.

“This is an emerging field with great promise,” says Jean Gehricke, an associate professor of pediatrics at UC Irvine and a licensed clinical psychologist with the Center for Autism & Neurodevelopmental Disorders. “We know a bit about the underlying causes of ADHD, and through this, we may be able to improve how we treat autism.” (Photo by Jocelyn Lee, UC Irvine)

By Tom Vasich, UC Irvine

For the better part of the last decade, a growing body of research has been revealing more and more similarities between attention-deficit/hyperactivity disorder and autism.

Jean Gehricke, an associate professor of pediatrics at UC Irvine and a licensed clinical psychologist with the Center for Autism & Neurodevelopmental Disorders, is focusing on this link to better understand why people with ADHD and autism may be more prone to substance abuse and, in the process, to develop more effective behavioral therapies.

“This is an emerging field with great promise,” Gehricke says. “We know a bit about the underlying causes of ADHD, and through this, we may be able to improve how we treat autism.”

The Center for Autism & Neurodevelopmental Disorders – which provides assessment, diagnosis, treatment, care coordination, family support and education for children, teens and young adults with autism and other developmental disorders – is one of only a few in the region to deliver a continuum of services until age 22 and to conduct research aimed at transforming the approach to autism.

Gehricke, who teaches 25 students in his lab, has expertise in the assessment and treatment of autism, ADHD and co-occurring problems such as depression, anxiety and drug abuse.

He joined the center in 2013. Before that, he worked at the UCLA Neuropsychiatric Institute & Hospital, the UCI Transdisciplinary Tobacco Use Research Center and the UCI Child Development Center, where he also provided comprehensive clinical assessments and cognitive behavioral therapy.

Gehricke is well-known for his scientific work on the underlying mechanisms of ADHD and drug abuse, having published a number of breakthrough articles showing why individuals with ADHD are more prone to smoke cigarettes or get hooked on other nicotine and tobacco products.

He’s taking this knowledge and applying it to autism. While people with ADHD and high-functioning autism share certain characteristics, such as difficulty interacting with others and problems with emotional control, Gehricke is especially interested in whether these issues have similar neurobiological underpinnings.

In a December 2014 study, he and his colleagues identified a genetic trait shared by those with ADHD and those with autism that sheds light on some of the more troubling behaviors associated with the disorders.

Gehricke explains that aggression and health-risk actions are driven by distorted dopamine signaling in the brain and that the DRD4 gene is critical in regulating this function. The researchers found that one form of the gene – called the 7R allele and linked to altered dopamine regulation – is overrepresented in both individuals with ADHD and those with autism. It’s the genetic fingerprint of these types of conduct, Gehricke says.

“This study provides a conceptual model for risky behaviors, which we often see in our patients, and explores the possibility of tailoring information to reduce them,” he says. “More specifically, it points to the need to use strong visual images to induce behavioral changes.”

Gehricke is especially focused on nicotine addiction – which, he points out, is another shared ADHD-autism inclination. He believes that early behavioral intervention with autistic children could be a particularly effective deterrent to smoking – the No. 1 preventable health threat in the world – and “vaping.”

Gehricke says that the intervention should include warning labels (such as those used with nicotine and tobacco) depicting the negative consequences of health-risk behaviors and presenting distinctive imagery visually stimulating enough to alter the activities of teenagers and young adults with ADHD and autism. Testing the effectiveness of this deterrent is the next step Gehricke plans to take with his 7R allele group.

“Research – such as the projects conducted by Jean – is one of the core pillars of our mission at the Center for Autism & Neurodevelopmental Disorders,” says Catherine Brock, executive director. “Through his efforts and the families that participate, we are better able to understand the underlying mechanisms of autism spectrum disorders and ADHD.”

The Santa Ana-based center is a collaboration of the UC Irvine School of Medicine, CHOC Children’s Hospital, Chapman University’s College of Educational Studies, the Children & Families Commission of Orange County, and the William & Nancy Thompson Family Foundation.

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How deep-brain simulation reshapes neural circuits in Parkinson’s

UCSF study reveals mode of action of highly effective but poorly understood therapy.

In the new research, during surgery to implant a permanent DBS device (green with yellow tip) deep in the brains of Parkinson's disease patients, six recording electrodes (red) were temporarily placed on the surface of the brain. (Photo by Coralie de Hemptinne, UC San Francisco)

By Pete Farley, UC San Francisco

UC San Francisco scientists have discovered a possible mechanism for how deep-brain stimulation (DBS), a widely used treatment for movement disorders, exerts its therapeutic effects.

Few medical treatments show results as rapid and dramatic as those seen with DBS, in which surgically implanted devices deliver electrical pulses to inner brain structures involved in movement. In most Parkinson’s disease (PD) patients who receive the treatment, symptoms of slow movement, tremor and rigidity sharply diminish soon after the stimulation device is activated, and quickly return if the device is turned off.

But surprisingly, there has been very little understanding of precisely why and how DBS works so well — a lack of knowledge that has held back efforts to further improve the therapy. Despite the great success of DBS, some significant problems remain. Customizing the stimulation delivered by DBS devices for each patient to maximally reduce symptoms is challenging and time-consuming. And a minority of patients never obtains the full benefit their physicians expect. With a better understanding of how DBS acts on brain circuits, researchers hope to address these shortcomings and make DBS an even more effective treatment.

The new research, published online today (April 13) in Nature Neuroscience, reveals that DBS keeps PD symptoms in check by reducing excessive synchronization of brain activity in the motor cortex, a region on the outer surface of the brain that governs movements of the body.

“This therapy is becoming widespread for many brain disorders aside from movement disorders, including psychiatric conditions such as depression, but no one knows how it works,” said UCSF’s Philip Starr, M.D., Ph.D., the Dolores Cakebread Chair in Neurological Surgery and senior author of the new study. “This is a significant step in answering this question on the level of brain networks, not just addressing where you’re actually applying the stimulation in the brain.”

Previous research led by Coralie de Hemptinne, Ph.D., a postdoctoral fellow in Starr’s laboratory, laid the groundwork for the new study. In 2013, de Hemptinne, Starr, and colleagues reported in the Proceedings of the National Academy of Sciences that a measure of synchronized rhythmic activity in the brain, which normally varies with movement or other behaviors, is excessively high in in the cortex in PD.

In that paper, the team hypothesized that this lockstep synchronization of brain circuits in PD thwarts the flexibility the brain requires to plan and execute movements, and that DBS might work by decoupling activity patterns in the motor cortex.

In the new work, “since we had found this excessive synchrony in PD patients, we decided to see if there’s a relationship between that synchrony and symptoms, and whether synchrony is lessened when symptoms are improved by DBS,” said de Hemptinne, first author of the Nature Neuroscience paper. “We measured synchrony in the motor area of the brain before, during, and after DBS, and while the patient was resting or engaged in a movement task in which they had to reach and touch a computer screen.”

During surgery on 23 patients with Parkinson’s disease in whom permanent DBS electrodes were being surgically implanted, the UCSF team slid a temporary strip of six recording electrodes under the skull and placed it over the motor cortex. As in the prior research, recordings of neural activity showed excessive synchronization of activity rhythms in the patients.

As the name of the therapy implies, the end of the stimulating lead of DBS devices is placed in a structure deep in the brain known as the subthalamic nucleus (STN), which is part of a “loop” of neural circuitry that includes the motor cortex on the brain’s surface. When the DBS device was activated and began stimulating the STN, the effect of the stimulation reached the motor cortex, where over-synchronization rapidly diminished. If the device was turned off, excessive synchrony re-emerged, more gradually in some patients than others.

DBS surgery generally takes about six hours, and during the middle of the  procedure patients are awakened for testing of the device and to ensure that the stimulating lead is properly placed in the STN. During this period the researchers asked 12 of the patients to perform a reaching task in which they had to touch a blue dot appearing on a computer screen. Importantly, said Starr, recordings revealed that DBS eliminated excessive synchrony of motor cortex activity and facilitated movement without altering normal changes in brain activity that accompany movements.

“Our 2013 paper showed how Parkinson’s disease affects the motor cortex, and this paper shows how DBS affects the motor cortex,” said Starr. “With these two pieces of information in hand, we can begin to think of news ways for stimulators to be automatically controlled by brain activity, which is the next innovation in the treatment of movement disorders.”

Because in these experiments the recording strip had to be removed before the end of surgery, recording data was collected over a relatively short time. To broaden opportunities for research, Starr and his team have collaborated with medical device company Medtronic on a new generation of permanently implantable DBS devices that can record activity in the motor cortex while delivering stimulation to the STN.

Five UCSF patients have been implanted with these new devices, and all data they collect can be uploaded for research during follow-up visits, de Hemptinne said, which will bring an even deeper understanding of how DBS reshapes brain activity.

“Now we can try to find even better correlations between DBS and symptoms, and we can even look at the effects of medications,” said de Hemptinne. “This new ability to collect data over a longer time course will be very powerful in driving new research.”

Other UCSF researchers taking part in the work were postdoctoral fellow Nicole Swann, Ph.D.; Jill L. Ostrem, M.D., professor of neurology; Elena Ryapolova-Webb, now a graduate student at UC Berkeley; Marta San Luciano, M.D., professor of neurology; and Nicholas Galifianakas, M.D., M.P.H., assistant professor of neurology.

The research was funded by the Michael J. Fox Foundation for Parkinson’s Research and by the National Institutes of Health.

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UC Davis neuroscientist recognized for color vision, aging contributions

John Werner to receive Verriest Medal from International Colour Vision Society.

John Werner, UC Davis

By Carole Gan, UC Davis

John S. Werner, a UC Davis neuroscientist and international authority on visual perception, has been selected to receive the 2015 Verriest Medal from the International Colour Vision Society for his contributions to understanding the structural and functional basis of color vision, how and why vision changes across the life span, and factors that contribute to loss of vision associated with disease. He will receive the award at the society’s biennial symposium in Sendai, Japan, in July.

Understanding, monitoring visual mechanisms

A distinguished professor at the UC Davis Eye Center and director of the Vision Science and Advanced Retinal Imaging Laboratory, Werner uses several different approaches to investigate both normal aging and age-
related diseases leading to blindness. These include psychophysical methods to show how perception of color adapts to changes in the degree of illumination throughout the day; electrophysiological methods to detect and quantify the response of cells at the back of the eye when stimulated by light; and custom instruments unique to his laboratory for ultra-high resolution. Imaging of the human retina at the cellular level, revolutionizing the field of vision science and the noninvasive diagnosis and monitoring of eye diseases.

One class of instrument uses adaptive optics to correct temporally varying, higher-order aberrations of the eye. Another class of instrument uses interferometry to detect faint reflections from cells that would otherwise make them invisible in the living eye.

Phase-variance optical coherence tomography, for example, is a noninvasive imaging technique that generates 3-D volumetric images of the retina, its microvasculature and other retinal layers without the need for fluorescent dyes. This discovery, recently published in the Proceedings of the National Academy of Sciences, has the potential to evaluate therapies and understand the underlying mechanisms of diseases of the retina and optic nerve, such as age-related macular degeneration progression, the latter of which is a leading cause of vision loss among people age 50 and older in the U.S. for which there is no cure. This movie shows the region of the retina, called the optic nerve, where fibers leave the eye and send their signals to different regions of the brain.

Innovating to advance vision science

Werner has made important contributions to understanding the development and aging of color mechanisms, as well as the processes of aging in perception, particularly as they relate to plasticity and potential clinical applications. He has demonstrated the function of the different classes of color receptor and their connections to the first visual area of the brain in infants as young as four weeks of age. Reductions in the response of these receptor types changes slowly from early adulthood and continues throughout life. His work showed that when the lens of the eye is removed in cataract surgery, the light reaching the back of the eye changes dramatically, leading to color vision changes that are slowly compensated in the brain to restore normal perception.

Throughout his career, Werner has maintained an active interest in opponent color mechanisms, color in art and color illusions. Some examples have appeared in popular venues such as Scientific American and a series of lectures held at the Crocker Art Museum in Sacramento, the Duke Institute for Brain Sciences and Duke University’s Nasher Museum of Art.

Career history

Werner received his doctoral degree in psychology from Brown University and conducted postdoctoral research at the Institute for Perception TNO in Soesterberg, The Netherlands. He was a member of the psychology faculty at the University of Colorado, Boulder, before joining UC Davis in 2000, where he holds appointments in the Center for Neuroscience, College of Biological Sciences and School of Medicine. He has co-edited several books that bring together discoveries from anatomy, physiology and psychophysics to illuminate fundamental mechanisms underlying human perception. These include “Visual Perception: The Neurophysiological Foundations,” “Color Vision: Perspectives from Different Disciplines,” “The Visual Neurosciences”  and “The New Visual Neurosciences.”

For his many contributions to the field of visual perception Werner has received many honors and awards. He is a fellow of the American Association for the Advancement of Science, American Psychological Association, American Psychological Society, Association for Research in Vision and Ophthalmology, the Gerontological Society of America and the Optical Society of America. He received the Pisart Vision Award from Lighthouse International and he presented the University of Colorado, Boulder, distinguished research lecture and the Optical Society of America Robert M. Boynton lecture. He has received a research prize from the Alexander von Humboldt Foundation in Bonn and was an elected scholar at Caius College, University of Cambridge.

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