TAG: "Neuroscience"

UCSF receives $100M gift to advance health sciences mission


Landmark gift cements Chuck Feeney’s role as UC system’s top philanthropist.

Chuck Feeney

By Jennifer O’Brien, UC San Francisco

UC San Francisco has received a $100 million gift from visionary philanthropist Charles F. “Chuck” Feeney to support its new Mission Bay hospitals, world-class faculty and students, and research programs focused on the neurosciences and aging.

This donation brings the longtime supporter’s total UCSF giving to more than $394 million, making Feeney the single largest contributor to the University of California system.

“I get my gratification from knowing that my investments in medical research, education, and the delivery of health care at UCSF will provide lifelong benefits to millions of people not only in the Bay Area but also around the world,” said Feeney, who, despite his global presence as a successful entrepreneur and discerning philanthropist, prefers remaining out of the limelight. “I can’t imagine a more effective way to distribute my undeserved wealth.”

Reflecting on Feeney’s contributions, UCSF Chancellor Sam Hawgood, M.B.B.S., said, “As we celebrate UCSF’s 150th anniversary this year, it is only fitting that we acknowledge the unique role Chuck has played in our history. While his impact has been felt most profoundly during this past decade, his generosity will carry on forever at our university, in the San Francisco community, throughout the Bay Area and globally, as our faculty and students advance knowledge and provide the finest clinical care. We are honored that he has decided to invest again in UCSF.”

Feeney’s gifts to UCSF are most visible at the university’s Mission Bay campus, where he has provided indispensable support to create advanced facilities and foster the environment for the biomedical research and patient care that goes on within them.

Before the latest funding, Feeney’s most recent gift to the campus was to UCSF Global Health Sciences, enabling the October 2014 opening of Mission Hall, which houses global health researchers, scientists and students under the same roof for the first time. Feeney, who coined the term “giving while living,” also generously supported the building of the Smith Cardiovascular Research Building and the Helen Diller Family Cancer Research Building.

“Chuck Feeney has been our partner at Mission Bay for more than 10 years,” added Hawgood. “He immediately embraced the Mission Bay concept, and he has enthusiastically helped us shape a larger vision for the campus and finance its development because he knew that our research and clinical programs could not flourish without state-of-the-art buildings.”

Gift to support four primary areas

The Campaign for the UCSF Medical Center at Mission Bay
Funds will support the $600 million philanthropy goal of the $1.5 billion hospitals project. The latest donation builds upon the transformative $125 million matching gift Feeney made to support the hospitals complex and its programs in 2009, the largest gift received toward the campaign.

The opening of the 289-bed hospital complex – which includes UCSF Benioff Children’s Hospital San Francisco, UCSF Betty Irene Moore Women’s Hospital, UCSF Bakar Cancer Hospital, and the UCSF Ron Conway Family Gateway Medical Building – was the culmination of more than 10 years of planning and construction. Strategically located adjacent to UCSF’s renowned Mission Bay biomedical research campus, the new medical center places UCSF physicians in close proximity to UCSF researchers and nearby bioscience companies who are working to understand and treat a range of diseases, from cancer to neurological disorders.

“It’s been thrilling to see the reactions of our patients and their families as they encounter the amazing care offered at our new UCSF Mission Bay hospitals,” said Mark Laret, CEO of UCSF Medical Center and UCSF Benioff Children’s Hospitals. “This world-class experience would never have been possible without the support of Chuck Feeney who, as the largest contributor to the project, helped us create the hospitals of our dreams. Every patient cured, every breakthrough discovered at Mission Bay, will be thanks in part to Chuck. His legacy is unparalleled.”

Neuroscience and aging
The gift also supports UCSF’s pre-eminent neuroscience enterprise, including its Sandler Neurosciences Center and neurology programs at Mission Bay.

The center, a five-story, 237,000-square-foot building that opened in 2012, brings under one roof several of the world’s leading clinical and basic research programs in a collaborative environment. UCSF’s neurology and aging efforts are focused on finding new diagnostics, treatments, and cures for a number of intractable disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stroke, migraine, epilepsy and autism. The programs also seek to integrate neuroscience and clinical disciplines with public health initiatives in order to disseminate and implement novel findings from research centers of excellence, as well as conduct community outreach to raise awareness about the diseases of aging.

“Chuck Feeney has taken a keen interest in the challenges of aging,” said Hawgood. “In turn, he has recognized UCSF’s extraordinary talent in the neurosciences, among both basic researchers and those who translate research into clinical care and public policy. This gift will build on UCSF’s strengths while encouraging strong partnerships at other research institutions around the world where Chuck also has made important investments.”

Student scholarships and housing
Even with its extraordinary academic firepower, UCSF has extremely limited funds to support scholarships for professional students in its schools of dentistry, medicine, nursing and pharmacy. Part of the gift will provide scholarship support, bolstering UCSF’s ability to recruit the best and brightest students, regardless of their financial circumstances.

Recent decreases in state funding led to tuition increases and higher demand for scholarships. This, in turn, increased student debt. Combined with Bay Area housing prices that are among the highest in the nation – from 2011 to 2013, the median rent increased by 24 percent – the prospect of overwhelming debt can deter economically vulnerable students as well as those from middle-class backgrounds from attending UCSF. By minimizing debt upon graduation, the scholarships will help ensure that a UCSF education remains in reach for students from underserved populations, as well as for those students who choose to become health care leaders in underserved communities.

“Scholarships give our students the gift of freedom: to make career choices based on purpose and passion, rather than the price of education; to use time to study, explore science, and volunteer to help others, rather than working to make ends meet; and to succeed because someone who never met them saw enough potential to invest in their dreams,” said Catherine Lucey, M.D., vice dean for education at UCSF’s School of Medicine. “These scholarships catalyze our schools’ ability to find, recruit, educate and nurture the workforce our country needs: talented professionals whose life experiences enable them to provide compassionate care to today’s diverse communities and advance science to improve the health of future communities.”

Faculty recruitment
The donation also will help UCSF recruit the next generation of promising faculty in an increasingly competitive marketplace.

New funding will attract junior faculty – who frequently find it more challenging to secure research funding – and provide initial startup funds as they launch their research careers and clinical practices. With decreasing federal support for young investigators, this gift will underwrite a new generation of brilliant upcoming faculty.

“While Chuck’s unprecedented generosity has been focused primarily on Mission Bay, he understands the power of the entire UCSF enterprise, from our cutting-edge stem cell research at Parnassus to our innovative cancer programs at Mount Zion,” Hawgood said. “We’re thrilled that Chuck has inspired other philanthropists to join him in creating one of the most vibrant life science communities in the world, where progress will ripple far beyond Mission Bay and the campus for generations to come.”

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UCSF researchers redefine role of brain’s ‘hunger circuit’


Unexpected findings have implications for anti-obesity therapies.

By Pete Farley, UC San Francisco

Using techniques developed only over the past few years, UC San Francisco researchers have completed experiments that overturn the scientific consensus on how the brain’s “hunger circuit” governs eating.

Because of this circuit’s potential role in obesity, it has been extensively studied by neuroscientists and has attracted intense interest among pharmaceutical companies. According to the UCSF scientists, their unexpected new findings could reshape basic research on feeding behavior as well as strategies for the development of new anti-obesity drugs.

Scientists have generally believed that the hunger circuit, made up of two groups of cells known as AgRP and POMC neurons, senses long-term changes in the body’s hormone and nutrient levels, and that the activation of AgRP neurons directly drives eating. But the new work shows that the AgRP-POMC circuit responds within seconds to the mere presence of food, and that AgRP neurons motivate animals to seek and obtain food, rather than directly prompting them to consume it.

“No one would have predicted this. It’s one of the most surprising results in the field in a long time,” said Zachary Knight, Ph.D., assistant professor of physiology at UCSF. “These findings really change our view of what this region of the brain is doing.”

It has been known for 75 years that a region at the base of the brain called the hypothalamus exerts profound control over eating behavior. As neuroscientists refined this observation over the ensuing decades, they zeroed in first on a small area of the hypothalamus known as the arcuate nucleus, and more recently on AgRP and POMC neurons, two small populations of cells within that nucleus.

These two groups of cells, which collectively occupy an area smaller than a millimeter in the mouse brain, are functionally organized in a seesaw-like fashion: when AgRP neurons are active, POMC neurons are not, and vice versa.

Hundreds of experiments in which scientists added hormones or nutrients to brain slices while recording the activity of AgRP and POMC neurons have laid the foundation of the dominant model of how the hunger circuit works. As we grow hungry, this view holds, gradual changes in hormone levels send signals that begin to trigger AgRP neurons, the activity of which eventually drives us to eat. As we become sated, circulating nutrients such as glucose activate POMC neurons, which suppresses the desire to eat more food.

Yiming Chen, a graduate student in Knight’s lab, was expecting to build on the prevailing model of the hunger circuit when he began experiments using newly developed fiber optic devices that allowed him to record AgRP-POMC activity in real time as mice were given food after a period of fasting. “No one had actually recorded the activity of these neurons in a behaving mouse, because the cells in this region are incredibly heterogeneous and located deep within the brain,” said Chen. “The technology to do this experiment has only existed for a few years.”

But as reported in the Feb. 19 online issue of Cell, just seconds after food was given to the mice, and before they had begun to eat, Chen saw AgRP activity begin to plummet, and POMC activity correspondingly begin to rise.

“Our prediction was that if we gave a hungry mouse some food, then slowly, over many minutes, it would become satiated and we would see these neurons slowly change their activity,” Knight said. “What we found instead was very surprising. If you simply give food to the mouse, almost immediately the neurons reversed their activation state. This happens when the mouse first sees and smells the food, before they even take a bite.”

The researchers found that the AgRP-POMC circuit could be quickly “reset,” with POMC cell activity dampened and AgRP neurons again beginning to fire, if the food were taken away. The magnitude of the transition from AgRP to POMC activity was also directly correlated with the palatability of the food offered: peanut butter and chocolate, both of which are much preferred by mice over standard lab chow, caused a stronger and more rapid reversal of AgRP-POMC activity. The AgRP-POMC responses also depended on the accessibility of the food. A slower and weaker transition was seen if the mice were able to detect the presence of peanut butter through smell, but couldn’t see the food.

These results show that, while slow, hunger-induced changes in hormones and nutrients activate AgRP neurons over the long term, these neurons are rapidly inactivated by the sight and smell of food alone. A major implication of this discovery, Knight and Chen said, is that the function of AgRP neurons is to motivate hungry animals to seek and find food, not to directly control eating behavior itself.

The fact that more accessible and more palatable, energy-rich foods engage POMC neurons and shut down AgRP activity more strongly suggests that the circuit also has “anticipatory” aspects, by which these neurons predict the nutritional value of a forthcoming meal and adjust their activity accordingly.

Both of these roles of the AgRP-POMC circuit make sense, said the researchers: if an animal has successfully obtained food, the most adaptive brain mechanism would suppress the motivation to continue searching; likewise, since energy-dense foods alleviate hunger for longer periods, discovery of these foods should more strongly tamp down the hunger circuit and the desire to seek additional nutrition.

“Evolution has made these neurons a key control point in the hunger circuit, but it’s primarily to control the discovery of food,” said Knight. “It’s controlling the motivation to go out and find food, not the intake of food itself.”

So far, clinical trials of drugs that target AgRP-related pathways have been disappointing, Knight said, and he believes the new research may provide a new perspective on these efforts. “What probably drives obesity is the rewarding aspect of food. When you want dessert after you’ve finished dinner, it’s because it tastes good, and that doesn’t require hunger at all,” Knight said. “Finding that this circuitry primarily controls food discovery rather than eating changes our view of what we might be manipulating with drugs targeting AgRP pathways. We might be manipulating the decision to go to the grocery store, not necessarily the decision to take the next bite of food.”

Other members of the Knight laboratory participating in the research were Yen-Chu Lin, research specialist, and graduate student Tzu-Wei Kuo. The research was supported by the New York Stem Cell Foundation, the Rita Allen Foundation, the McKnight Foundation, the Alfred P. Sloan Foundation, a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation, the Esther A. and Joseph Klingenstein Foundation, the Program for Breakthrough Biomedical Research, the UCSF Diabetes Center Obesity Pilot Program, and the National Institutes of Health.

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Brain’s iconic seat of speech goes silent when we actually talk


UC Berkeley discovery has implications for diagnoses, treatments of stroke, epilepsy.

New findings will better help map out the brain’s speech regions (Photo courtesy of Adeen Flinker)

By Yasmin Anwar, UC Berkeley

For 150 years, the iconic Broca’s area of the brain has been recognized as the command center for human speech, including vocalization. Now, scientists at UC Berkeley and Johns Hopkins University in Maryland are challenging this long-held assumption with new evidence that Broca’s area actually switches off when we talk out loud.

The findings, reported today (Feb. 16) in the Proceedings of the National Academy of Sciences journal, provide a more complex picture than previously thought of the frontal brain regions involved in speech production. The discovery has major implications for the diagnoses and treatments of stroke, epilepsy and brain injuries that result in language impairments.

“Every year millions of people suffer from stroke, some of which can lead to severe impairments in perceiving and producing language when critical brain areas are damaged,” said study lead author Adeen Flinker, a postdoctoral researcher at New York University who conducted the study as a UC Berkeley Ph.D. student. “Our results could help us advance language mapping during neurosurgery as well as the assessment of language impairments.”

Flinker said that neuroscientists traditionally organized the brain’s language center into two main regions: one for perceiving speech and one for producing speech.

“That belief drives how we map out language during neurosurgery and classify language impairments,” he said. “This new finding helps us move towards a less dichotomous view where Broca’s area is not a center for speech production, but rather a critical area for integrating and coordinating information across other brain regions.”

In the 1860s, French physician Pierre Paul Broca pinpointed this prefrontal brain region as the seat of speech. Broca’s area has since ranked among the brain’s most closely examined language regions in cognitive psychology. People with Broca’s aphasia are characterized as having suffered damage to the brain’s frontal lobe and tend to speak in short, stilted phrases that often omit short connecting words such as “the” and “and.”

Specifically, Flinker and fellow researchers have found that Broca’s area — which is located in the frontal cortex above and behind the left eye — engages with the brain’s temporal cortex, which organizes sensory input, and later the motor cortex, as we process language and plan which sounds and movements of the mouth to use, and in what order. However, the study found, it disengages when we actually start to utter word sequences.

“Broca’s area shuts down during the actual delivery of speech, but it may remain active during conversation as part of planning future words and full sentences,” Flinker said.

The study tracked electrical signals emitted from the brains of seven hospitalized epilepsy patients as they repeated spoken and written words aloud. Researchers followed that brain activity – using event-related causality technology – from the auditory cortex, where the patients processed the words they heard, to Broca’s area, where they prepared to articulate the words to repeat, to the motor cortex, where they finally spoke the words out loud.

In addition to Flinker, other co-authors and researchers on the study are Robert Knight and Avgusta Shestyuk at the Helen Wills Neuroscience Institute at UC Berkeley, Nina Dronkers at the Center for Aphasia and Related Disorders at the Veterans Affairs Northern California Health Care System, and Anna Korzeniewska, Piotr Franaszczuk and Nathan Crone at Johns Hopkins School of Medicine.

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UC experts urge Congress to fund brain research


UCSF’s Bruce Miller, UC Davis’ Cameron Carter, UCLA’s Christopher Giza speak at briefing.

(From left) UC Davis' Cameron Carter, UCLA's Christopher Giza and UCSF's Bruce Miller spoke at a Jan. 29 Capitol Hill briefing discussing the current state of brain research. (Photo by Bara Vaida)

By Bara Vaida

The funding support provided by the National Institutes of Health remains crucial to finding treatments for neurodegenerative diseases, UC San Francisco’s Bruce Miller, M.D., told U.S. congressional staff last week on Capitol Hill.

The NIH’s research grants to the Department of Neurology at the UCSF School of Medicine have resulted in tremendous strides in understanding how neurodegenerative diseases, like Alzheimer’s, Parkinson’s and frontotemporal dementias develop, according to Miller, director of the UCSF Memory and Aging Center. With that understanding is the potential for treating and preventing those diseases, he added.

“The work you do here is unbelievably important to our mission,” Miller said during the Jan. 29 congressional briefing, attended by about three dozen people who work for members of Congress. The staff were invited by the University of California to learn about the latest on brain research.

NIH funding had helped foster understanding and treatment of schizophrenia, said Cameron Carter, M.D., director of UC Davis’s Center for Neuroscience and the Imaging Research Center. Christopher Giza, M.D., director of UCLA’s Steve Tisch BrainSPORT program, also spoke at the briefing. He underscored how federal research money was used to better understand and treat brain injuries.

All three physicians emphasized the need for more public money to be invested in brain disease research.

“While other diseases are declining, like heart disease, cancer and stroke, Alzheimer’s is not. We think its going to double in prevalence,” Miller told congressional staff. “The NIH is spending about $500 million a year on Alzheimer’s research. Our mantra is, this year, spend $1 billion.”

A growing risk of brain disease

Alzheimer’s is one of the most costly diseases in the U.S. – $109 billion to $240 billion a year in medical and caregiver costs, according to Rand Corp. It is also the sixth leading cause of death. About 5 million people currently live with Alzheimer’s and 500,000 of them live in California.

Miller went on to describe how NIH funding had helped scientists understand which proteins caused different types of dementias, and how those proteins aggregate and destroy brain cells. With NIH money, scientists developed molecular imaging technology that now enable researchers to see proteins accumulating in the brain before symptoms develop, offering an opportunity to potentially prevent dementia from developing.

“I am proud to say, that with NIH funding, we are starting to treat pre-symptomatic” dementia, Miller said. “Those imaging costs are huge – $3,000 to $5,000 per patient– so there are very few places in the U.S. that can do that.”

Earlier in the day, all three physicians held private discussions with staff members working for California lawmakers, including Democratic House Minority Leader Nancy Pelosi and Reps. Doris Matsui and Ted Lieu.

“I was really struck by how helpful our legislators are,” Miller said. “We reach out to them, and they reach back out to us.”

Miller provided the briefing to staff as Congress begins considering the budget for 2016, which begins on Oct. 1, 2015. The NIH’s annual budget was about $30 billion in 2015. President Barack Obama proposed increasing the NIH budget to $31.3 billion in 2016.

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Tackling brain injuries head on


UC Davis scientists developing system to better assess on-field concussions.

For much of this fall, as in falls past, a Friday night crowd comes out for the weekly football game and likely witnesses the star running back getting rattled by a hard tackle.

The coach faces a decision: keep the player in the game and risk serious head injury or pull him and face the wrath of the player, the team and the crowd. What the coach needs is a way to accurately assess the player’s status – right now.

This scenario is being played out at sports fields around the world. How do we make objective decisions about a player’s health in the heat of competition?

The problem intrigues UC Davis physician Khizer Khaderi. A neuro-ophthalmologist, Khaderi is applying his expertise in the eye-brain connection to investigate traumatic brain injury (TBI). Whether the result of a car accident, explosion, skiing or a tackle, TBI can affect vision, memory and even mental health.

Imperfect solutions

Khaderi and colleagues are developing a system that will take the guesswork out of assessing an on-field concussion, an early form of TBI.

It would replace a system of neurocognitive tests that many teams use now. In these tests, a player is asked a number of questions, of which answers are compared to baseline results recorded earlier. However, with players’ strong incentive to stay in the game, some have learned to circumvent the system.

“One of the problems with the neurocognitive approach is that it’s very subjective,” says Khaderi, an assistant professor of clinical ophthalmology and head of the Sports Vision Lab. “Players will intentionally do poorly on the baseline test, so if they do get injured, it won’t look as severe.”

Khaderi’s solution focuses on the eyes. A third of the brain is devoted to the visual system, making the eyes an ideal window on brain health. Several biometric tests exist but Khaderi’s team has found that relying on three established biometric tests greatly increases the chances of accurately assessing TBI risk on the field in real time.

UC Davis neuro-ophthalmologist Khizer Khaderi tests a system he and his team developed to facilitate a quick assessment of an on-field concussion, an early form of traumatic brain injury. Helping with the test is medical resident Rachel Simpson.

Eyes, pupils and brain waves

Using eye movements to assess TBI has advantages. For example, researchers have measured how long the eye takes to move from a central to peripheral focus. This would be the motion a driver would make when shifting attention from the road to a child crossing it. This motion takes less than seven-tenths of a second for a healthy person, but much longer for those who’ve experienced a brain injury.

The opposite motion is also informative. In the same scenario, the driver could make the decision to look away from the child stepping into the road.

“The natural reaction is to look at the child,” says Khaderi, “but instead you look away. This involves cognition, so it’s a good measure of executive function.”

Pupil function can also measure an injury’s severity. A coach could use a flashlight to assess dilation, but background light can skew results. To combat this, Khaderi has adopted a psychological method called the International Affective Picture System, which uses pictures to make the pupil respond.

The third metric measures brain waves. When they’re awake, people generally have a higher ratio of fast alpha waves to slow theta waves. However, that ratio is reversed after a brain injury. High theta waves indicate a dreamy state of mind.

Moving forward

Khaderi plans to bring these tools to playing fields everywhere. Fortunately, much of this technology is being used for other purposes and can be repurposed for TBI detection.

“Our goal is to create a platform that integrates commercially available eye tracking hardware and EEG (brain wave) systems,” says Khaderi.

The group has found a development partner and is working with the UC Davis athletic department to set up clinical trials. The ultimate goal is to create a system that could be accessed through a tablet computer or other device.

“These injuries don’t just strike kids who are playing sports, but anyone who leads an active life,” says Khaderi. “Our brains are precious and we need to do all we can to protect them.”

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Why protein mutations lead to familial form of Parkinson’s


UC San Diego study focuses on alpha-synuclein.

By Jan Zverina, UC San Diego

Researchers at the San Diego Supercomputer Center (SDSC) at the University of California, San Diego, have shown for the first time why protein mutations lead to the familial form of Parkinson’s disease.

The study, available online in prepublication in ACS Chemical Neuroscience and partially funded by the National Institutes of Health, focuses specifically on alpha-synuclein (αsyn), a protein whose function in healthy tissue is unknown but which represents the major structural component of Lewy bodies – protein clumps found in the brains of individuals with Parkinson’s disease and other neurological disorders.

Parkinson’s disease is characterized by impairment or deterioration of neurons in an area of the brain known as the substantia nigra. In the familial form of the disorder, a set of mutations in αsyn had been identified but what was unknown was the molecular mechanism by which these mutations caused disease.

“As an unstructured protein, αsyn is sometimes called ‘chameleon’ because it has no stable configuration and constantly changes its shape,” said lead author Igor F. Tsigelny, a research scientist with SDSC as well as the UC San Diego Moores Cancer Center and the Department of Neurosciences. “Nevertheless when these changes seem to be random on first glance, they have specific intrinsic rules that control the evolution of the αsyn shape.”

Using SDSC’s data-intensive Gordon supercomputer to find hidden rules of the conformational changes of αsyn, researchers conducted extensive calculations of the possible evolution of the protein structure.

Through computer modeling, researchers showed that αsyn mostly can bind the membrane with four main sites, or zones. While binding was shown to be superficial by three of the sites, one site – Zone 2 – had a particular affinity for the membrane. Researchers found that αsyn contacting the neuron membrane in that site immediately and deeply penetrated it, which led to the creation of ring oligomers in the membrane, and eventually opened pores that allowed an uncontrolled influx of ions that ultimately killed the cell. Most of the mutations changed the shape of the protein in a way that increased binding of αsyn to the membrane by this zone.

These theoretical predications were confirmed by a set of experimental methods conducted in the laboratory of Eliezer Masliah, a professor in UC San Diego’s Department of Neurosciences. “Previous to this study, researchers could not say why these mutations caused Parkinson’s disease,” said Tsigelny. “The discovery of Zone 2 as the distinguishing feature of the membrane-penetrating configurations of αsyn paves the road to possible prevention of such a binding. Now we can affect this region with rational drug design, for example by creating compounds that would change its electrostatic profile.”

In addition to Tsigelny and Masliah, researchers involved in the study include Yuriy Sharikov, Valentina L. Kouznetsova, and Jerry P. Greenberg from SDSC; Wolf Wrasidlo from the Moores Cancer Center; and Cassia Overk, Tania Gonzalez, Margarita Trejo, Brian Spencer, and Kori Kosberg, from the Department of Neurosciences at UC San Diego.

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Multiple, short learning sessions strengthen memory formation in fragile X


UC Irvine study suggests the method could aid children with the autism-related condition.

Christine Gall and Gary Lynch found that fragile X model mice trained in three short, repetitious episodes spaced one hour apart performed as well on memory tests as normal mice. (Photo by Chris Nugent, UC Irvine)

By Tom Vasich, UC Irvine

A learning technique that maximizes the brain’s ability to make and store memories may help overcome cognitive issues seen in fragile X syndrome, a leading form of intellectual disability, according to UC Irvine neurobiologists.

Christine Gall, Gary Lynch and colleagues found that fragile X model mice trained in three short, repetitious episodes spaced one hour apart performed as well on memory tests as normal mice. These same fragile X rodents performed poorly on memory tests when trained in a single, prolonged session – which is a standard K-12 educational practice in the U.S.

“These results are dramatic and never seen before. Fragile X model mice trained using this method had memory scores equal to those of control animals,” said Gall, professor of anatomy & neurobiology and neurobiology & behavior. “Our findings suggest an easily implemented, noninvasive strategy for treating an important component of the cognitive problems found in patients with fragile X syndrome.”

Fragile X syndrome is an inherited genetic condition that causes intellectual and developmental disabilities and is commonly associated with autism. Symptoms include difficulty learning new skills or information.

It’s been known since classic 19th century educational psychology studies that people learn better when using multiple, short training episodes rather than one extended session.

Two years ago, the Lynch and Gall labs found out why. They discovered a biological mechanism that contributes to the enhancing effect of spaced training: Brain synapses – which are the connection points among neurons that transfer signals – encode memories in the hippocampus much better when activated briefly at one-hour intervals.

The researchers found that synapses have either low or high thresholds for learning-related modifications and that the high-threshold group requires hourlong delays between activation in order to store new information.

“This explains why prolonged ‘cramming’ is inefficient – only one set of synapses is being engaged,” said Lynch, professor of psychiatry & human behavior and anatomy & neurobiology. “Repeated short training sessions, spaced in time, engage multiple sets of synapses. It’s as if your brain is working at full power.”

The finding was significant, Gall added, because it demonstrated that a ubiquitous and fundamental feature of psychology can, at least in part, be explained by neurobiology.

It also gave the researchers time-sequencing rules for optimizing forms of learning dependent upon the hippocampus – utilized in the current study. Results appear in the Nov. 25 issue of Proceedings of the National Academy of Sciences.

The UCI scientists stress that the new brain-based training protocols, if applied during childhood, have the potential to offset many aspects of fragile X-related autism. “We believe that synaptic memory mechanisms are used during postnatal development to build functional brain circuits for dealing with confusing environments and social interactions,” Lynch said. “Implementing the brain-based rules during childhood training could result in lifelong benefits for patients.”

He and Gall look forward to collaborating with UCI’s Center for Autism Research & Translation to further evaluate the effect of multiple, short training episodes on learning in fragile X children.

Ronald Seese led the study as part of his work toward a Ph.D. and was assisted by Kathleen Wang and Yue Qin Yao. The research was funded by the National Science Foundation (grant 1146708), the National Institutes of Health (grants MH082042 and NS04260), and the William & Nancy Thompson Family Foundation, via UCI’s Center for Autism Research & Translation.

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Scientists detect brain network that gives humans superior reasoning skills


Findings suggest subtle shifts in frontal, parietal lobes of brain linked to superior cognition.

By Yasmin Anwar, UC Berkeley

When it comes to getting out of a tricky situation, we humans have an evolutionary edge over other primates. Take, as a dramatic example, the Apollo 13 voyage in which engineers, against all odds, improvised a chemical filter on a lunar module to prevent carbon dioxide buildup from killing the crew.

UC Berkeley scientists have found mounting brain evidence that helps explain how humans have excelled at “relational reasoning,” a cognitive skill in which we discern patterns and relationships to make sense of seemingly unrelated information, such as solving problems in unfamiliar circumstances.

Their findings, reported in today’s (Dec. 3) issue of the journal Neuron, suggest that subtle shifts in the frontal and parietal lobes of the brain are linked to superior cognition. Among other things, the frontoparietal network plays a key role in analysis, memory retrieval, abstract thinking and problem-solving, and has the fluidity to adapt according to the task at hand.

“This research has led us to take seriously the possibility that tweaks to this network over an evolutionary timescale could help to explain differences in the way that humans and other primates solve problems,” said UC Berkeley neuroscientist Silvia Bunge, the study’s principal investigator.

“It’s not just that we humans have language at our disposal. We also have the capacity to compare and integrate several pieces of information in a way that other primates don’t,” she added.

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Memory expert receives Grawemeyer Award for Psychology


UC Irvine founding faculty member James McGaugh honored for learning, memory research.

UC Irvine neuroscientist and founding faculty member James McGaugh stands in front of the campus building that is named after him. (Photo by Steve Zylius, UC Irvine)

UC Irvine neurobiologist James McGaugh, whose research has vastly contributed to our knowledge of the brain’s learning and memory abilities, has won the 2015 University of Louisville Grawemeyer Award for Psychology.

A research professor in neurobiology & behavior and a founding UCI faculty member, McGaugh is receiving the prize for discovering that stress hormones such as epinephrine and cortisol are key to why we remember some things more vividly than others.

The hormones activate the brain’s emotional center, the amygdala, which in turn regulates other brain areas that process and consolidate memories – a sequence that explains why emotional experiences are easier to recall, he found.

“His work has transformed the field,” said award director Woody Petry. “It has profound implications for helping us understand and treat memory disorders such as post-traumatic stress disorder.”

McGaugh began studying the link between emotion and memory in the 1960s, when he discovered that giving stimulants to animals immediately after training fostered retention of the new skills. Later, he learned that naturally occurring stress hormones had a similar memory-enhancing effect.

Recently, McGaugh has been studying people with highly superior autobiographical memory to see if differences in brain structure may account for the trait.

“The list of previous Grawemeyer Award for Psychology recipients is remarkable,” he said. “It’s an honor to be included.”

Five Grawemeyer Award winners are being named this week. The University of Louisville presents the prizes annually for excellence in music composition, ideas improving world order, psychology and education; it confers a religion prize jointly with Louisville Presbyterian Theological Seminary. This year’s awards are $100,000 each.

UCI’s Elizabeth Loftus, Distinguished Professor of social ecology and professor of law, received the Grawemeyer Award for Psychology in 2005.

About James McGaugh

James McGaugh’s seminal work on emotion and memory has been featured on popular television programs such as CBS’s “60 Minutes,” described in dozens of textbooks, and cited about 31,000 times in more than 15,000 professional papers.

McGaugh joined UCI in 1964, a year before classes began. Over the ensuing decades, he served as executive vice chancellor, vice chancellor of academic affairs, dean of biological sciences and department chair, in addition to founding and directing the Center for the Neurobiology of Learning & Memory.

UCI named McGaugh Hall after him in 2001 and also awarded him the UCI Medal and established a neurobiology & behavior graduate research award of excellence in his name.

Among McGaugh’s many other honors are the Association for Psychological Science’s William James Fellow Award, the American Psychological Association’s Award for Distinguished Scientific Contributions, the American Philosophical Society’s Karl Spencer Lashley Award, the Society of Experimental Psychologists’ Norman Anderson Lifetime Achievement Award, the American Association for the Advancement of Science’s John McGovern Lecture award, and the Western Psychological Association’s Lifetime Achievement Award.

A former president of the Association for Psychological Science, McGaugh is a member of the National Academy of Sciences, the Society for Neuroscience, the International Brain Research Organization, the American College of Neuropsychopharmacology, the Society of Experimental Psychologists and the World Academy of Art & Science.

He also is a fellow of the American Academy of Arts & Sciences.

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Research aims to help veterans with hearing loss


UC Riverside team tries crowdfunding to support project.

Alison Smith, a disabled veteran and UC Riverside graduate student, is part of a research team that is developing a brain-training game to help veterans suffering combat-related hearing loss.

By Bettye Miller, UC Riverside

Many combat veterans suffer hearing loss from blast waves that makes it difficult to understand speech in noisy environments — a condition called auditory dysfunction — which may lead to isolation and depression. There is no known treatment.

Building on promising brain-training research at UC Riverside related to improving vision, researchers at UC Riverside and the National Center for Rehabilitative Auditory Research are developing a novel approach to treat auditory dysfunction by training the auditory cortex to better process complex sounds.

The team is seeking public support to raise the estimated $100,000 needed to fund research and develop a computer game they believe will improve the brain’s ability to process and distinguish sounds.

“This is exploratory research, which is extremely hard to fund,” said Aaron Seitz, UCR professor of neuropsychology. “Most grants fund basic science research. We are creating a brain-training game based on our best understanding of auditory dysfunction. There’s enough research out there to tell us that this is a solvable problem. These disabled veterans are a patient population that has no other resource.”

Seitz said the research team is committed to the project regardless of funding, but donations will accelerate development of the brain-training game by UCR graduate and undergraduate students in computer science and neuroscience; pilot studies on UCR students with normal hearing; testing the game with veterans; and refining the game to the point that it can be released for public use.

Auditory dysfunction is progressive, said Alison Smith, a graduate student in neuroscience studying hearing loss in combat vets who is a disabled veteran. Nearly 8 percent of combat veterans who served in Afghanistan and Iraq suffer from traumatic brain injury, she said. Of those, a significant number complain about difficulty understanding speech in noisy environments, even though they show no external hearing loss.

“Approximately 10 percent of the civilian population is at risk for noise-induced hearing loss, and there have been more than 20,000 significant cases of hearing loss per year since 2004,” added Smith, who served in the Army National Guard as a combat medic for five years.

This research also may help many other hearing-impaired populations, including musicians, mechanics and machinists; reduce the effects of age-related hearing loss; and aid individuals with hearing aids and cochlear implants.

“This kind of training has never been done before,” Seitz said. “We’re taking what we know about the building blocks of speech and what we know about the auditory cortex and the building blocks of hearing, and developing a way to retrain the auditory cortex to process complex sounds.”

The goal is to revive the auditory processing system that was damaged by blast waves and improve hearing, he said. “They may not hear as well as they did before the damage occurred, but we’re hoping to get them to a more normal point.”

UC Riverside launched the research project after audiologists at the Veterans Administration hospital in Loma Linda approached UCR neuroscientist Khaleel Razak about the hearing difficulties faced by returning combat veterans after he presented a seminar on age-related hearing loss. Razak is a consultant on the project.

In addition to Seitz and Smith, team members include Frederick J. Gallun, a researcher at the National Center for Rehabilitative Auditory Research and associate professor in otolaryngology and the Neuroscience Graduate Program at Oregon Health and Science University; Victor Zordan, UCR associate professor of computer science who specializes in video game design and intelligent systems; and Dominique Simmons, a cognitive psychology graduate student studying audiovisual speech perception.

Seitz said he hopes to begin testing the game on veterans by summer 2015.

“Whether or not you agree with the war, these are people who have gone overseas to serve their country,” he said. “When they come back, it’s our responsibility to care for them. We have to find a way to help our disabled vets. Right now, there’s nothing out there for veterans who are suffering this kind of hearing loss. This is our best shot.”

Contributions made through experiment.com are not tax-deductible. Individuals who wish to make a tax-deductible donation may give to the UCR Brain Game Center through UCR Online Giving and use the “special instructions” field to designate the gift for the “Can brain training help soldiers with brain injury regain hearing?” project.

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Study puts more natural movement for artificial limbs within reach


Providing simple neural signals to brain implants could stand in for body’s own feedback system.

By Pete Farley, UC San Francisco

In new research that brings natural movement by artificial limbs closer to reality, UC San Francisco scientists have shown that monkeys can learn simple brain-stimulation patterns that represent their hand and arm position, and can then make use of this information to precisely execute reaching maneuvers.

Goal-directed arm movements involving multiple joints, such as those we employ to extend and flex the arm and hand to pick up a coffee cup, are guided both by vision and by proprioception — the sensory feedback system that provides information on the body’s overall position in three-dimensional space. Previous research has shown that movement is impaired when either of these sources of information is compromised.

The most sophisticated artificial limbs, which are controlled via brain-machine interfaces (BMIs) that transmit neural commands to robotic mechanisms, rely on users’ visual guidance and do not yet incorporate proprioceptive feedback. These devices, though impressive, lack the fluidity and accuracy of skilled natural reaching movements, said Philip Sabes, Ph.D., senior author of the new study, published today (Nov. 24) in the Advance Online Edition of Nature Neuroscience.

“State-of-the-art BMIs generate movements that are slow and labored — they veer around a lot, with many corrections,” said Sabes, whose research to improve prosthetics has been funded by the REPAIR (Reorganization and Plasticity to Accelerate Injury Recovery) initiative of the Defense Advanced Projects Research Agency (DARPA). “Achieving smooth, purposeful movements will require proprioceptive feedback.”

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Tolman, behavior and academic freedom


UC Berkeley day of talks honors pioneering professor.

In Tolman Hall, Seth Rosenfeld, author of "Subversives," connected the dots from Edward Tolman's stand against the UC loyalty oath to the Free Speech Movement. (Photo by Barry Bergman, UC Berkeley)

If you’ve ever been to Tolman Hall, you probably reached it not by rigid adherence to a series of mechanical steps — start at West Circle, go up Hilgard Way, first right to the end of Morgan Hall, then first left and voila — but by navigating via the map in your head. That is, you pictured its location, and figured out a suitable route.

If you’d made the trip Monday, you would have learned it was the man who lent the aging psychology building his name, longtime UC Berkeley professor Edward Tolman, whose pre-World War II work with rats in mazes changed how we think about how we think. His groundbreaking insights laid the foundation for the discovery of what’s been called “the brain’s GPS” — the underlying neural machinery of the cognitive map — and this year’s Nobel Prize in Physiology or Medicine.

Edward Moser, who shared the 2014 Nobel with his wife, May-Britt Moser, and John O’Keefe, gave the keynote address at Monday’s daylong celebration of Tolman’s legacy. While Moser and fellow neuroscientist David Foster, of Johns Hopkins University, gave technical presentations on their clinical research — with due credit to Tolman’s pioneering work in psychology — others highlighted his role as a pioneer in the realm of academic freedom.

In 1949, as McCarthyism raged, Tolman took a high-profile stand against the special “loyalty oath” demanded of UC employees by President Robert Gordon Sproul and the Board of Regents. Although he was fired, he not only won back his faculty position but was instrumental in winning the fight against the oath, which was ultimately found to be unconstitutional.

“The issue I am concerned with involves not communists but liberals,” explained Tolman, reading a letter to Sproul at a meeting of the Academic Senate. “For, when one reads the second part of the oath again, one discovers certain ambiguities of statement and meaning which would make it very difficult for many of us liberals to be certain just what we were being asked to commit ourselves to.”

He further objected that because only individuals can “believe,” it was dangerous to require faculty to disavow membership in organizations that “believe in” the overthrow of the U.S. government. This, he said, was “neither good psychology nor good civil rights.”

In 1963, the year before the Free Speech Movement — whose support from the Berkeley faculty, said author and journalist (and one-time Daily Cal reporter) Seth Rosenfeld, was an extension of the loyalty-oath fight — Berkeley’s new psychology building was dedicated in his name.

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