TAG: "brain"

UC receives nearly a quarter of NIH brain research grants


14 projects are led by researchers from six UC campuses.

The National Institutes of Health awarded UC researchers nearly a quarter of the $46 million in grants announced today (Sept. 30) in support of President Barack Obama’s BRAIN Initiative.

UC scientists have long been at the frontline of efforts to understand the brain’s inner workings — a pre-eminence reflected by the grants: Of the 58 NIH awards, 14 are projects led by researchers from UC Berkeley, UC Davis, UC Irvine, UCLA, UC San Diego and UC San Francisco.

Collectively, UC researchers will receive more than $10 million of the $46 million that the NIH is awarding for 2014.

“The human brain is the most complicated biological structure in the known universe. We’ve only just scratched the surface in understanding how it works — or, unfortunately, doesn’t quite work when disorders and disease occur,” said NIH Director Dr. Francis S. Collins in a statement. “There’s a big gap between what we want to do in brain research and the technologies available to make exploration possible.”

The BRAIN Initiative was launched last year by Obama as a large-scale federal effort to help scientists develop new tools and technologies to gain a deeper understanding of how the brain functions and to accelerate the creation of new treatments for neurological disorders.

“These initial awards are part of a 12-year scientific plan focused on developing the tools and technologies needed to make the next leap in understanding the brain,” Collins said. “This is just the beginning of an ambitious journey and we’re excited about the possibilities.”

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Seeding innovations in brain research


UC Berkeley, UCSF, Berkeley Lab join forces on BRAINseed collaboration.

Michel Maharbiz of electrical engineering and computer science describes a project to probe more deeply into the cerebral cortex. (Photo by Roy Kaltschmidt, Berkeley Lab)

Two state-of-the-art research areas – nanotech and optogenetics – were the dominant theme last Thursday, Sept. 18, as six researchers from UC Berkeley, UC San Francisco and Lawrence Berkeley National Laboratory sketched out their teams’ bold plans to jump-start new brain research.

The rapid-fire talks kicked off a one-of-a-kind collaboration among the three institutions in which each put up $1.5 million over three years to seed innovative but risky research. Called BRAINseed, the partnership could yield discoveries that accelerate President Barack Obama’s national BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative and California’s own Cal-BRAIN Initiative.

“It’s clear to everybody that any attempt to understand how the brain works, or ultimately what we might mean by cognition, is so daunting and so large that no one institution could hope to be a stand-alone leader in such an effort,” said Graham Fleming, UC Berkeley vice chancellor for research. “The synergies between UCSF, Lawrence Berkeley National Lab and UC Berkeley are very strong, and we complement one another in very effective ways.”

“This tri-partnership is unprecedented in the history of our institutions,” noted Horst Simon, deputy director of Berkeley Lab. “We are putting money down to fund a real collaboration that makes people sit down together and address some of the most challenging questions today.”

“BRAINseed underscores the tremendous power embodied in the institutions in the Bay Area, and the potential for amazing things to happen if we can overcome the geographical separations,” said Keith Yamamoto, UCSF vice chancellor for research.

When Obama announced the federal BRAIN Initiative in April 2013, he allocated $110 million for fiscal year 2014. This funding is already supporting several projects at UC Berkeley. Obama has proposed even more funding in future years “to revolutionize our understanding of the human mind and uncover new ways to treat, prevent, and cure brain disorders like Alzheimer’s, schizophrenia, autism, epilepsy and traumatic brain injury.”

Similarly, Cal-BRAIN — short for California Blueprint for Research to Advance Innovations in Neuroscience — aims to “accelerate the development of brain mapping techniques, including the development of new technologies.” The initial appropriation in this year’s state budget was $2 million.

Both Cal-BRAIN and the national initiative are expected to spur new startups in the area of neurotechnology based on the tools and inventions created in research labs. The innovations developed through these initiatives could have broad applications in disease monitoring beyond the brain and even outside the health care field.

“What we want to do is build a climate of collaboration so that we are stronger competitors in the national brain program and Cal-BRAIN,” Fleming said. “We see BRAINseed as a model for future collaborations (among the three institutions).”

Probing deeper into the brain

The six winning projects of 17 proposals originally submitted focus on new methods of mapping the brain and studying neurons deeper in the brain than ever before.

Fiberless deep brain imaging: Using novel nanocrystals developed by Bruce Cohen at Lawrence Berkeley National Laboratory, and biosensing and bioactuating molecules synthesized by Chris Chang and Ehud Isacoff at UC Berkeley, researchers hope to probe cell-to-cell communication deeper in the brain than ever before. The technique takes advantage of the fact that near infrared (NIR) light with its shorter wavelengths penetrates deeper into the brain than does visible light. The nanocrystals from Cohen’s lab absorb the NIR light and convert it into visible light. The visible light can then trigger optogenetic photoswitches that turn neuron receptors on and off, as well as activate biosensors that record the release of neurotransmitters at the synapse. Coupled with techniques developed by Charly Craik and Robert Edwards at UCSF for targeting probes to specific cells, the researchers on this project hope to be able to study cell signaling in the many layers of the cortex.

Integrated nanosystems: Our senses of touch and hearing, as well as our ability to feel pain and detect the position of our body in space, are all made possible by a special class of proteins known as mechanoreceptors. Scientists studying this system in cell culture have traditionally used micropipettes to apply pressure to mechanoreceptors, while microelectrodes record the resulting neural activity. But small as they are, these devices are much too bulky to precisely stimulate single receptors or make accurate neural recordings. A team led by UCSF’s Young-wook Jun is devising a system to overcome these limitations. In the new setup, magnetic nanoparticles controlled by micromagnetic “tweezers” will have the capacity to stimulate individual mechanoreceptors, and high-resolution optical signals emitted by “quantum dots,” developed in the lab of Paul Alivisatos of UC Berkeley and Berkeley Lab, will offer a truer picture of neural activity in sensory neurons. They will collaborate with UCSF’s Yuh Nung Jan.

In vivo optogenetic mechanisms: We think of the action of neurotransmitters as rapid and localized, but the effects of acetylcholine (ACh) in the brain are actually quite diffuse and unfold slowly. The hormone-like characteristics of ACh make it difficult to understand through conventional neurophysiology experiments. As a result, ACh transmission, which plays a role in Alzheimer’s and Parkinson’s diseases and in addiction, is poorly understood despite decades of study. UC Berkeley’s Richard Kramer has devised a system that enables researchers to use light to switch ACh receptors on and off in animals. Using this system, Kramer and UCSF’s Michael P. Stryker will be able to study how ACh modulates behavior in a wholly new way.

Acousto-optic virtual waveguides: Optogenetics approaches to probe the brain’s grey matter, or cortex, work only as deep as the light can penetrate, typically only a fraction of a millimeter below the surface. UC Berkeley engineers have developed a novel way to channel light deeper – more than a millimeter deep – to probe cell-to-cell signaling. Engineer Michel Maharbiz proposes to use ultrasound to create ‘waveguides’ that can steer light below the surface of the cortex, stimulating photoswitches that enable the study of neurotransmitters. With light-sensitive probes developed at Berkeley Lab and cell-imaging techniques from UCSF, the technology would open new avenues for non-invasive in-vivo imaging and stimulation of local brain areas. Maharbiz’s collaborators are Jim Schuck of Berkeley Lab, Reza Alam of UC Berkeley and Vikaas Singh Sohal of UCSF.

Optical integrators of neuronal activity: One of the greatest challenges in understanding the brain is connecting what happens over large volumes and hundreds of thousands of neurons to the signals transmitted at the individual synapse, the connection between nerve cells where communication takes place. Because calcium is key to neuronal signaling, a team led by Evan Miller, UC Berkeley assistant professor of molecular and cell biology and of chemistry, plans to use probes developed in his lab that ‘remember’ calcium concentration. Along with co-collaborators Pam den Besten and Terumi Kohwi-Shigematsu at UCSF and Berkeley Lab, respectively, Miller plans to investigate neuronal activity in models of disease. They can then correlate this with what happens over a larger volume of the brain. The technique combines “click chemistry” pioneered at UC Berkeley with probes generated in the Department of Chemistry to integrate images over different scales. This technique is a vital first step in developing tools that remember neuronal activity and enable 3D reconstruction of activity across entire brain regions with cellular resolution.

Development of instrumentation and computational methods: Though great progress has been made in mapping the function of the human brain, researchers have been stymied by limitations in both recording devices and the ability to analyze and understand brain signals. UCSF’s Edward F. Chang, M.D., is leading a team that aims to achieve up to a thousandfold increase in the density and electronic sophistication of recording arrays. The vast amount of data collected by these arrays will be stored and analyzed by some of the world’s most powerful computers at the National Energy Research Scientific Computing Center (NERSC), enabling a new level of understanding of the brain in both health and disease. Chang’s collaborators are Peter Denes and Kristofer Bouchard of Berkeley Lab and Fritz Sommer of UC Berkeley.

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Brain Innovation Group funded for brain tumor tool


National Cancer Institute grant boosts development of optical wand technology.

Laura Marcu, UC Davis

The UC Davis Comprehensive Cancer Center’s Brain Innovation Group has received a grant from the National Cancer Institute (NCI) to improve brain cancer surgery and treatment using UC Davis-developed biophotonic technology.

The $400,000 grant is the first for the cancer center’s eight cancer research innovation groups, which link scientists, oncologists, surgeons, engineers and other experts in discussions about patient care needs and potential innovations.

“The groups were started to fulfill a big part of our mission as a comprehensive cancer center by enhancing clinical and translational cancer research,” said cancer center director Ralph de Vere White. “This grant is a clear example of the success of this endeavor.”

UC Davis researchers will use the funding to adapt state-of-the-art optical biopsy technology, the Multispectral Scanning-Time Resolved Fluorescence Spectroscopy, to help neurosurgeons distinguish between radiation necrosis and cancer recurrence during brain cancer surgery. The technology was developed by Laura Marcu, professor of biomedical engineering and neurological surgery and principal investigator on the project.

The collaborative Brain Innovation Group includes specialists from adult and pediatric oncology, neurology, neurosurgery, neuroradiology, radiation oncology, biomedical engineering and biophotonics, hematology and biochemistry. They meet once a month in an open forum to present their projects and look for ways to combine and translate their work into high-impact clinical trials.

“This NCI grant demonstrates the benefit of having experts with different backgrounds work together to find new ways to better diagnose and treat cancer,” said Marcu, adding that the idea to apply the novel photonic technology in distinguishing between brain tumor recurrence and radiation necrosis was sparked during an innovation meeting.

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‘Dimmer switch’ discovered for mood disorders


UC San Diego study’s findings have implications for how to treat depression.

Basal ganglia neurons (green) feed into the brain and release glutamate (red) and GABA (blue) and sometimes a mix of both neurotransmitters (white).

Researchers at the UC San Diego School of Medicine have identified a control mechanism for an area of the brain that processes sensory and emotive information that humans experience as “disappointment.”

The discovery of what may effectively be a neurochemical antidote for feeling let-down is reported today (Sept. 18) in the online edition of Science.

“The idea that some people see the world as a glass half empty has a chemical basis in the brain,” said senior author Roberto Malinow, M.D., Ph.D., professor in the Department of Neurosciences and neurobiology section of the Division of Biological Sciences. “What we have found is a process that may dampen the brain’s sensitivity to negative life events.”

Because people struggling with depression are believed to register negative experiences more strongly than others, the study’s findings have implications for understanding not just why some people have a brain chemistry that predisposes them to depression but also how to treat it.

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Brain scans used to forecast early reading difficulties


White matter predictive of reading acquisition beyond effects of genetic predisposition.

Fumiko Hoeft, UC San Francisco

UC San Francisco researchers have used brain scans to predict how young children learn to read, giving clinicians a possible tool to spot children with dyslexia and other reading difficulties before they experience reading challenges.

In the United States, children usually learn to read for the first time in kindergarten and become proficient readers by third grade, according to the authors. In the study, researchers examined brain scans of 38 kindergarteners as they were learning to read formally at school and tracked their white matter development until third grade. The brain’s white matter is essential for perceiving, thinking and learning.

The researchers found that the developmental course of the children’s white matter volume predicted the kindergarteners’ abilities to read.

“We show that white matter development during a critical period in a child’s life, when they start school and learn to read for the very first time, predicts how well the child ends up reading,” said Fumiko Hoeft, M.D., Ph.D., senior author and an associate professor of child and adolescent psychiatry at UCSF, and member of the UCSF Dyslexia Center.

The research is published online in Psychological Science.

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Neural compensation found in people with Alzheimer’s-related protein


Study provides evidence of plasticity in aging brain that appears to be beneficial.

Shown are scans that represent all subjects with beta-amyloid deposits in their brain. The yellow and orange colors show areas where greater brain activation was associated with the formation of more detailed memories. (Image courtesy of Jagust Lab)

The human brain is capable of a neural workaround that compensates for the buildup of beta-amyloid, a destructive protein associated with Alzheimer’s disease, according to a new study led by UC Berkeley researchers.

The findings, published today (Sept. 14) in the journal Nature Neuroscience, could help explain how some older adults with beta-amyloid deposits in their brain retain normal cognitive function while others develop dementia.

“This study provides evidence that there is plasticity or compensation ability in the aging brain that appears to be beneficial, even in the face of beta-amyloid accumulation,” said study principal investigator Dr. William Jagust, a professor with joint appointments at UC Berkeley’s Helen Wills Neuroscience Institute, the School of Public Health and Lawrence Berkeley National Laboratory.

Previous studies have shown a link between increased brain activity and beta-amyloid deposits, but it was unclear whether the activity was tied to better mental performance.

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Study shows evidence that sleep apnea hurts brain


UCLA researchers find that people suffering from sleep apnea have weaker brain blood flow.

This brain scan shows that the brain blood flow in a subject with obstructive sleep apnea (left) is markedly lower compared to a subject without the sleep disorder.

Employing a measure rarely used in sleep apnea studies, researchers at the UCLA School of Nursing have uncovered evidence of what may be damaging the brain in people with the sleep disorder — weaker brain blood flow.

In the study, published Aug. 28 in the peer-reviewed journal PLOS ONE, researchers measured blood flow in the brain using a non-invasive MRI procedure: the global blood volume and oxygen dependent (BOLD) signal. This method is usually used to observe brain activity.  Because previous research showed that poor regulation of blood in the brain might be a problem for people with sleep apnea, the researchers used the whole-brain BOLD signal to look at blood flow in individuals with and without obstructive sleep apnea (OSA).

“We know there is injury to the brain from sleep apnea, and we also know that the heart has problems pumping blood to the body, and potentially also to the brain,” said Paul Macey, associate dean for Information Technology and Innovations at the UCLA School of Nursing and lead researcher for the study. “By using this method, we were able to show changes in the amount of oxygenated blood across the whole brain, which could be one cause of the damage we see in people with sleep apnea.”

Obstructive sleep apnea is a serious disorder that occurs when a person’s breathing is repeatedly interrupted during sleep, hundreds of times a night. Each time breathing stops, the oxygen level in the blood drops, which damages many cells in the body. If left untreated, it can lead to high blood pressure, stroke, heart failure, diabetes, depression and other serious health problems. Approximately 10 percent of adults struggle with obstructive sleep apnea, which is accompanied by symptoms of brain dysfunction, including extreme daytime sleepiness, depression and anxiety, and memory problems.

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Brain inflammation disrupts memory retrieval networks


UC Irvine research sheds light on cognitive losses seen with chemotherapy.

In their study, UCI neurobiologists Jennifer Czerniawski and John Guzowski show for the first time a link among immune system activation, altered neural circuit function and impaired discrimination memory.

Brain inflammation can rapidly disrupt our ability to retrieve complex memories of similar but distinct experiences, according to UC Irvine neuroscientists Jennifer Czerniawski and John Guzowski.

Their study – which appears today in The Journal of Neuroscience – specifically identifies how immune system signaling molecules, called cytokines, impair communication among neurons in the hippocampus, an area of the brain critical for discrimination memory. The findings offer insight into why cognitive deficits occurs in people undergoing chemotherapy and those with autoimmune or neurodegenerative diseases.

Moreover, since cytokines are elevated in the brain in each of these conditions, the work suggests potential therapeutic targets to alleviate memory problems in these patients.

“Our research provides the first link among immune system activation, altered neural circuit function and impaired discrimination memory,” said Guzowski, the James L. McGaugh Chair in the Neurobiology of Learning & Memory. “The implications may be beneficial for those who have chronic diseases, such as multiple sclerosis, in which memory loss occurs and even for cancer patients.”

What he found interesting is that increased cytokine levels in the hippocampus only affected complex discrimination memory, the type that lets us differentiate among generally similar experiences – what we did at work or ate at dinner, for example. A simpler form of memory processed by the hippocampus – which would be akin to remembering where you work – was not altered by brain inflammation.

In the study, Czerniawski, a UCI postdoctoral scholar, exposed rats to two similar but discernable environments over several days. They received a mild foot shock daily in one, making them apprehensive about entering that specific site. Once the rodents showed that they had learned the difference between the two environments, some were given a low dose of a bacterial agent to induce a neuroinflammatory response, leading to cytokine release in the brain. Those animals were then no longer able to distinguish between the two environments.

Afterward, the researchers explored the activity patterns of neurons – the primary cell type for information processing – in the rats’ hippocampi using a gene-based cellular imaging method developed in the Guzowski lab. In the rodents that received the bacterial agent (and exhibited memory deterioration), the networks of neurons activated in the two environments were very similar, unlike those in the animals not given the agent (whose memories remained strong). This finding suggests that cytokines impaired recall by disrupting the function of these specific neuron circuits in the hippocampus.

“The cytokines caused the neural network to react as if no learning had taken place,” said Guzowski, associate professor of neurobiology & behavior. “The neural circuit activity was back to the pattern seen before learning.”

The work may also shed light on a chemotherapy-related mental phenomenon known as “chemo brain,” in which cancer patients find it difficult to efficiently process information. UCI neuro-oncologists have found that chemotherapeutic agents destroy stem cells in the brain that would have become neurons for creating and storing memories.

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Study ties honesty to prefrontal region of brain


Results indicate that willpower is necessary for honesty when it is advantageous to lie.

Are humans programmed to tell the truth? Not when lying is advantageous, says a new study led by assistant professor Ming Hsu at UC Berkeley’s Haas School of Business. The report ties honesty to a region of the brain that exerts control over automatic impulses.

Hsu, who heads the Neuroeconomics Laboratory at the Haas School of Business and holds a joint appointment with the Helen Wills Neuroscience Institute, said the results, just published in the journal Nature Neuroscience, indicate that willpower is necessary for honesty when it is personally advantageous to lie.

It is well-established that the brain’s dorsolateral prefrontal cortex is important for exerting control over impulses, but the role of this region in honesty and deception has been a matter of debate.

“So far, studies investigating the role of the dorsolateral prefrontal cortex in honesty have primarily used correlational methods, like neuroimaging,” said study co-author Adrianna Jenkins of the Neuroeconomics Laboratory. “So it hasn’t been clear whether this region is involved in curbing honesty or enabling it.”

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Colds may temporarily increase stroke risk in kids


Study shows colds, flu can create short-lived increased stroke risk in vulnerable children.

A new study suggests that colds and other minor infections may temporarily increase stroke risk in children. The study found that the risk of stroke was increased only within a three-day period between a child’s visit to the doctor for signs of infection and having the stroke.

The study was led by researchers at UCSF Benioff Children’s Hospital San Francisco in collaboration with the Kaiser Permanente Division of Research.

“These findings suggest that infection has a powerful but short-lived effect on stroke risk,” said senior author Heather Fullerton, M.D., a pediatric vascular neurologist and medical director of the Pediatric Brain Center at UCSF Benioff Children’s Hospital San Francisco.

“We’ve seen this increase in stroke risk from infection in adults, but until now, an association has not been studied in children.”

Strokes are extremely rare in children, affecting just 5 out of 100,000 kids per year. “The infections are acting as a trigger in children who are likely predisposed to stroke,” said Fullerton. “Infection prevention is key for kids who are at risk for stroke, and we should make sure those kids are getting vaccinated against whatever infections – such as flu – that they can.”

The study appears in today’s (Aug. 20) online issue of Neurology.

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UC scientists awarded 8 grants in support of BRAIN Initiative


Projects seek to gain understanding of the brain.

Eight University of California scientists are among 36 recipients nationwide who have been awarded early concept grants for brain research from the National Science Foundation, the agency announced today (Aug. 18).

The awards were made to fund research projects that the federal science agency determined could produce “potentially transformative insights into understanding the brain.” The funding comes from the agency’s allocation for President Obama’s BRAIN Initiative, a multi-agency research effort that seeks to accelerate the development of new neurotechnologies that promise to help researchers answer fundamental questions about how the brain works.

The NSF’s 36 early concept grant awards, which total $10.8 million, are intended to “enable new technologies to better understand how complex behaviors emerge from the activity of brain circuits,” the agency said.

Each of these Early Concept Grants for Exploratory Research, or EAGER, awards will receive $300,000 over a two-year period to “develop a range of conceptual and physical tools, from real-time whole brain imaging, to new theories of neural networks, to next-generation optogenetics,” the NSF said.

UC scientists played a major role in the creation of Obama’s BRAIN initiative in April 2013 and also led a similar state initiative that, two months ago, was awarded $2 million in the budget signed into law by Gov. Jerry Brown. The state’s research grant effort, known as Cal-BRAIN – short for California Blueprint for Research to Advance Innovations in Neuroscience – aims to “accelerate the development of brain mapping techniques, including the development of new technologies.”

“These awards are yet another manifestation of the excellence of our neuroscience faculty and our long tradition in neuroscience research, which were key factors in building the number one ranked neuroscience graduate program in the nation and establishing our Kavli Institute for Brain and Mind,” said UC San Diego Chancellor Pradeep K. Khosla.

UC early concept grant awardees include:

UC Berkeley
Ehud Isacoff

UC Davis
Martin Usrey
Karen Zito

UC San Diego
Brenda Bloodgood
Andrea Chiba
David Kleinfeld
Charles Stevens

UC San Francisco
Steven Finkbeiner

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Mapping the infant brain


Findings may be key in identifying, treating earliest signs of neurodevelopmental disorders.

A recent study conducted by researchers at the UC San Diego School of Medicine and the University of Hawaii demonstrates a new approach to measuring early brain development of infants, resulting in more accurate whole brain growth charts and providing the first estimates for growth trajectories of subcortical areas during the first three months after birth. Assessing the size, asymmetry and rate of growth of different brain regions could be key in detecting and treating the earliest signs of neurodevelopmental disorders, such as autism or perinatal brain injury.

The study will be published in JAMA Neurology today (Aug. 11).

For the first time, researchers used magnetic resonance imaging (MRI) of the newborn brain to calculate the volume of multiple brain regions and to map out regional growth trajectories during the infant’s first 90 days of life. The study followed the brain growth of full term and premature babies with no neurological or major health issues.

“A better understanding of when and how neurodevelopmental disorders arise in the postnatal period may help assist in therapeutic development, while being able to quantify related changes in structure size would likely facilitate monitoring response to therapeutic intervention. Early intervention during a period of high neuroplasticity could mitigate the severity of the disorders in later years,” said Dominic Holland, Ph.D., first author of the study and researcher in the Department of Neurosciences at UC San Diego School of Medicine.

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