TAG: "brain"

Triathlete, actor share stories of recovery from traumatic brain injury

UCLA’s Brain Injury Research Center hosts symposium.

Greg Parks and Kathleen Pullen-Norris, a nurse at the Ronald Reagan UCLA Medical Center, were married for less than a year before Parks was in a bike accident and sustained a life-changing brain injury. (Photo courtesy of Greg Parks and Kathleen Pullen-Norris)

By Elaine Schmidt, UCLA

Triathlete Greg Parks never recalled the cause of the accident that left him lying unconscious in the road, still straddling the bicycle he’d been riding in Santa Clarita. But he will never forget what followed: four weeks of hospitalization and grueling rehabilitation. Then came another four months before he was able to resume his life as a newlywed husband and rocket-test engineer.

Actor Larry Miller was also able to pick up his life as the father of two after suffering a life-threatening head injury in 2012 and being on life support for a month. Well-known for the memorable characters he played in more than 100 films and TV shows, Miller also started back to work after his recovery.

Parks and Miller recently shared their experience of coming back from a life-changing brain injury at a public symposium hosted by the neurosurgery department’s Brain Injury Research Center at the Ronald Reagan UCLA Medical Center. Both men, as well as those who care for patients with traumatic brain injuries (TBI), talked about how to advocate for loved ones and how caregivers must also take time to tend to themselves.

“My accident was the best thing that could have happened to me,” said Miller, who has advocated for TBI patients before the California Senate. He opted to see the brighter side of his situation. “A brain injury wakes you up and makes you appreciate all that you have. Everything became funnier in my life.”

From her perspective as the wife of a patient, Kathleen Pullen-Norris, Parks’ wife, described the challenges she faced in obtaining proper treatment for her husband at the hospital where he was first taken and how she coped during his journey to recovery.

“Being the spouse of a TBI patient can be one of the world’s darkest places,” admitted Pullen-Norris, who happened to be a nurse at the Reagan UCLA Medical Center’s neuro-ICU unit, where her husband was eventually hospitalized. “You are not the injured, but you are the aching. Greg describes TBI as a fog. Being a TBI wife is like being a lighthouse — the best and brightest lighthouse I can muster.”

She emphasized the need for personal self-care. “Without the caregiver, the patient is lost,” she stressed. “That means taking time for yourself.”

Parks encouraged therapists to push their patients to recapture their mental and physical fitness. “My toughest therapist was my beautiful wife, Kathleen,” said Parks, who had married Pullen-Norris less than a year before his accident and raced in New Zealand’s Ironman competition together on their honeymoon.

“I am grateful to her for making fitness a priority and am living proof that a good support system is essential for surviving a brain injury,” Parks said.

Each year, an estimated 2.4 million Americans suffer a blow to the head that results in a traumatic brain injury, according to Dr. Paul Vespa, director of neurocritical care at the Reagan UCLA Medical Center and a professor of neurosurgery and neurology at the David Geffen School of Medicine.

“Swift treatment can prevent death and permanent brain damage, but not every hospital offers the trained specialists and sophisticated equipment required to treat TBIs effectively,” Vespa pointed out.  “As a result, tens of thousands of people die needlessly each year, and more than 5.3 million Americans live with a lifelong disability.”

Pullen-Norris echoed Vespa’s message. “Greg and I are deeply grateful to his UCLA physicians and nurses. Without their expertise and diligence, our work would be for nothing. They saved Greg and, in turn, saved me.”

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‘Gold standard’ method created for measuring key early sign of Alzheimer’s

UCLA helps validate first standardized protocol for measuring an early sign of Alzheimer’s.

Liana Apostolova, UCLA

By Mark Wheeler, UCLA

After six years of painstaking research, a UCLA-led team has validated the first standardized protocol for measuring one of the earliest signs of Alzheimer’s disease — the atrophy of the part of the brain known as the hippocampus.

The finding marks the final step in an international consortium’s successful effort to develop a unified and reliable approach to assessing signs of Alzheimer’s-related neurodegeneration through structural imaging tests, a staple in the diagnosis and monitoring of the disease. The study is published in the journal Alzheimer’s and Dementia.

Using brain tissue of deceased Alzheimer’s disease patients, a group headed by Dr. Liana Apostolova, director of the neuroimaging laboratory at the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA, confirmed that the newly agreed-upon method for measuring hippocampal atrophy in structural MRI tests correlates with the pathologic changes that are known to be hallmarks of the disease — the progressive development of amyloid plaques and neurofibrillary tangles in the brain.

“This hippocampal protocol will now become the gold standard in the field, adopted by many if not all research groups across the globe in their study of Alzheimer’s disease,” said Apostolova, who was invited to play a key role in the consortium because of her reputation as one of the world’s leading experts in hippocampal structural anatomy and atrophy. “It will serve as a powerful tool in clinical trials for measuring the efficacy of new drugs in slowing or halting disease progression.”

The brain is the least accessible and most challenging organ to study in the human body; as a result, Alzheimer’s disease can be diagnosed definitively only by examining brain tissue after death. In living patients, physicians diagnose Alzheimer’s by evaluating other health factors, known as biomarkers, in combination with memory loss and other cognitive symptoms.

The hippocampus is a small region of the brain that is associated with memory formation, and memory loss is the earliest clinical feature of Alzheimer’s disease. Its shrinkage or atrophy, as determined by a structural MRI exam, is a well-established biomarker for the disease and is commonly used in both clinical and research settings to diagnose the disease and monitor its progression.

But until now, the effectiveness of structural MRI has been limited because of the widely different approaches being used to identify the hippocampus and measure its volume — which has called into question the validity of this approach. A typical hippocampus is about 3,000 to 4,000 cubic millimeters in volume. But, Apostolova notes, two scientists analyzing the same structure can come up with a difference of as much as 2,000 cubic millimeters.

In addition, no previous study had verified whether estimates for the volume of the hippocampus using MRI corresponded to actual tissue loss.

To address these deficiencies, the European Alzheimer’s Disease Consortium–Alzheimer’s Disease Neuroimaging Initiative was established to develop a Harmonized Protocol for Hippocampal Segmentation, or HarP — an effort to establish a definitive method for measuring hippocampal shrinkage through structural MRI in a way that best corresponds to the Alzheimer’s disease process.

Once the HarP was established, Apostolova and four other experts were invited to develop the gold standard for measuring the hippocampus to be used by anyone employing the HarP protocol. The UCLA-led team then validated the technique and ensured the changes in the hippocampus corresponded to the hallmark pathologic changes associated with Alzheimer’s disease.

“The technique is meant to be used on scans of living human subjects, so it’s important that we are absolutely certain that this methodology measures what it is supposed to and captures disease presence accurately,” Apostolova said.

To do that, her group used a powerful 7 Tesla MRI scanner to take images of the brain specimens of 16 deceased individuals — nine who had Alzheimer’s disease and seven who were cognitively normal — each for 60 hours. This provided unprecedented visualization of the hippocampal tissue, Apostolova said.

After applying the protocol to measure the hippocampal structures, the researchers analyzed the tissues for two changes that signify the disease: a buildup of amyloid tau protein and loss of neurons. The team found a significant correlation between hippocampal volume and the Alzheimer’s disease indicators.

“As a result of the years of scientifically rigorous work of this consortium, hippocampal atrophy can finally be reliably and reproducibly established from structural MRI scans,” Apostolova said.

Although the technique can be used immediately in research settings such as clinical trials, the next step, Apostolova noted, will be to use the standardized protocol to validate automated techniques available for measuring the hippocampus so the approach could be used more widely — including for the diagnosis of the disease in doctor’s offices and other patient care settings.

Funding for the study was provided by the National Institute on Aging (P50 AG16570), the Jim Easton Consortium for Alzheimer’s Drug Discovery and Biomarker Development, the National Institutes of Health (R01 AG040770), and the Alzheimer’s Association (IIRG 10-174022). Please see the paper for a complete list of the study’s authors.

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Control switch for unfolded protein response may be key to multiple diseases

Discovery opens new drug development avenues for treating variety of diseases.

By Bonnie Ward, UC San Diego

Researchers at the UC San Diego School of Medicine have discovered a control switch for the unfolded protein response (UPR), a cellular stress relief mechanism drawing major scientific interest because of its role in cancer, diabetes, inflammatory disorders and several neural degenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), otherwise known as Lou Gehrig’s disease.

The normal function of the UPR pathway is to protect cells from stress but it can also trigger their death if the stress is not resolved. The researchers’ discovery of a control switch that acts on the UPR pathway, published today (March 25) in the online edition of EMBO Reports, opens new drug development avenues for treating a wide variety of diseases by modulating the UPR pathway to prevent excessive cell death.

“Our paper reports that two highly conserved pathways – the UPR and the nonsense-mediated RNA decay pathway – intersect with each other at a pivotal point in cell stress,” said Miles Wilkinson, Ph.D., senior author and professor in the Department of Reproductive Medicine and a member of the UC San Diego Institute for Genomic Medicine. “In essence, we’ve shown that the nonsense-mediated RNA decay pathway, typically referred to as ‘NMD,’ keeps the UPR in check to avoid the potentially dangerous consequences if the UPR pathway were allowed to mount an inadvertent response to innocuous stress.”

In cells, like people, too much stress can cause bad things to happen. In the case of cells, one such bad consequence is the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER), the cell’s protein-making factory. To carry out their many biological functions, proteins must be precisely folded in the correct shape. The body’s answer to excessive cell stress and accompanying misshapen proteins is the unfolded protein response. The UPR kicks in and restores normal ER-folding capacity by adjusting certain cellular processes. If this fails, the UPR instructs the cell to self-destruct, a process known as programmed cell death or apoptosis.

Wilkinson describes the UPR pathway as a double-edged sword. “In a large number of diseases, ranging from cancer to ALS, major stress occurs in the affected cells, leading the UPR pathway to be triggered,” he said. “And that’s meant to be helpful. But if the stress isn’t relieved in a timely fashion, it triggers cell death.  A limited amount of cell death is normal, but if too many cells die, especially critical cells, then it’s a problem. Chronic UPR activation and excessive cell death has been implicated in brain disorders like Alzheimer’s and Parkinson’s disease.”

In their study, Wilkinson, with first author Rachid Karam, Ph.D., and colleagues found that the NMD pathway plays a critical role in shaping the activities of UPR. Specifically, they discovered that NMD prevents inappropriate activation of the UPR and also promotes its timely termination to protect cells from prolonged ER stress.

“Because of the important role of UPR in regulating cell life/death decisions, it is critical that mechanisms are in place to prevent unnecessary UPR activation in response to innocuous or low-level stimuli,” said Wilkinson. “In this report we demonstrate that the NMD pathway serves in this capacity by raising the threshold for triggering UPR and also promoting its shut off at the appropriate time.”

He added that NMD doesn’t deter the UPR if an important stress comes along where more action is needed.

“Although NMD normally represses the UPR, our paper and previous work have shown that it gets out of the way if there’s a real problem,” Wilkinson noted.

Previous studies from the Wilkinson group and others have established that NMD has two broad roles. First, it is a quality control mechanism used by cells to eliminate faulty messenger RNA (mRNA) – molecules that are essential for transcribing genetic information into the construction of proteins critical for life. Second, NMD degrades a specific group of normal mRNAs.

The latest study shows that NMD suppresses inappropriate UPR activities by driving the rapid decay of several normal mRNAs encoding proteins critical for the UPR.

“We demonstrate that NMD directly targets the mRNAs encoding several UPR components, including the highly conserved UPR sensor, IRE1-alpha, whose NMD-dependent degradation partly underpins this process,” said Wilkinson.  “Our work not only sheds light on UPR regulation, but demonstrates the physiological relevance of NMD’s ability to regulate normal mRNAs.”

Co-authors include Chih-Hong Lou, Heike Kroeger, Jonathan H. Lin, all at UC San Diego; Lulu Huang, formerly of UC San Diego and now at ISIS Pharmaceuticals.

Funding for this research came, in part, from NIH grant (RO1 GM111838).

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ADHD program selected for new PEER patient portal by Genetic Alliance

‘This is citizen science at its best.’

Julie Schweitzer, UC Davis

By Phyllis Brown, UC Davis

The ADHD Program at the UC Davis MIND Institute has been selected to participate in an initiative that will link people with the condition in Sacramento and beyond with clinicians, researchers, advocates, support groups and each other, through an innovative privacy-assured online platform called Platform for Engaging Everyone Responsibly, or PEER.

The PEER program will create a customized portal for people with attention-deficit/hyperactivity disorder, funded by a $500,000 grant from the Robert Wood Johnson Foundation, which is underwriting the development of the ADHD site along with approximately 15 others.

PEER is a project of Genetic Alliance, which already has managed the development of portals for a wide array of diseases, many of which are rare genetic conditions, such as Gaucher disease or Joubert syndrome, and others that are more common, such as sickle cell disease and hepatitis.

The PEER platform creates a Web presence that allows people to share their health data, selecting privacy settings with which they are comfortable and that “strike a balance between the desire for solutions to their medical needs and their [concerns] about privacy.”

“The goal is to make the development of registries simple and easy,” said Sharon Terry, president and chief executive officer of Genetic Alliance and co-creator of PEER. “The members of community organizations will just sign up online, create their own instance of the software, and get to work. That is our plan for PEER.”

ADHD is one of several new PEER portals to be developed by PEER/Genetic Alliance. The condition is anything but rare. In fact, it is the most commonly diagnosed psychiatric disorder among children in the United States. Other new PEER collaborators will include the Asthma and Allergy Foundation of America, Celiac Support Association and the Center for Jewish Genetics.

“We’re grateful that the Genetic Alliance and PEER selected the ADHD Program and the MIND Institute as partners in this exciting endeavor,” said program Director Julie Schweitzer. “Through this partnership we can encourage families of people with ADHD to participate in research to help find treatments and possible preventive measures for the condition.”

The ADHD Program will partner with local and national ADHD support groups, including the Parent Education Network (PEN) and Children and Adults with Attention-Deficit Hyperactivity Disorder (CHADD).

“This is citizen science at its best,” Schweitzer said. “Families affected by ADHD will be able to learn information from one another by using a computer from their own homes. And, by sharing their health information, they will help researchers seeking improved treatments for people with ADHD.”

The ADHD Program offers clinical programs for people with ADHD across the lifespan, and conducts research into treatments for the condition.

Schweitzer will collaborate with Nick Anderson, UC Davis professor of informatics.

“We are very enthused to be partners in  this unique network – we greatly value advocacy groups’ participation, and the PEER platform provides the best privacy support currently available,” Anderson said.

More information about the institute is available on the Web at mindinstitute.ucdavis.edu.

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In anorexia nervosa, brain responds differently to hunger signals

Finding could lead to new treatment development efforts targeting specific brain pathways.

By Bonnie Ward, UC San Diego

Researchers at the UC San Diego School of Medicine have pinpointed differences in brain function that may help to explain how people with anorexia nervosa can continue to starve themselves, even when already emaciated. The finding adds to growing evidence about the role of brain mechanisms in eating disorders and could lead to new treatment development efforts targeting specific brain pathways.

“When most people are hungry, they are motivated to eat,” said Christina E. Wierenga, Ph.D., the study’s first author and UC San Diego associate professor of psychiatry. “Yet individuals with anorexia can be hungry and still restrict their food intake. We wanted to identify brain mechanisms that may contribute to their ability to ignore rewards, like food.”

Wierenga said their study showed differences in brain response to reward in women recovered from anorexia. “They showed decreased response to reward, even when hungry. This is opposite of healthy women without an eating disorder, who showed greater sensitivity to rewards when hungry,” added Wierenga.

The study is published in the current issue of the journal Biological Psychiatry.

Walter H. Kaye, M.D., a professor of psychiatry and director of the Eating Disorders Treatment and Research Program at UC San Diego and senior author, said the study’s results further support the view that neurobiology contributes to this disorder. “Our study suggests that brain circuitry differences in anorexics make them less sensitive to reward and the motivational drive of hunger. Put another way, hunger does not motivate them to eat.”

Anorexia nervosa is an eating disorder characterized by abnormally low body weight, fear of gaining weight and a skewed perception of body image. Up to 24 million Americans are estimated to suffer from anorexia and other eating disorders, including bulimia and binge-eating disorder. Women are much more likely to develop eating disorders, which are associated with many medical problems and can be life-threatening.

In their study, the research team analyzed brain function in 23 women who had recovered from anorexia and a control group of 17 healthy women who had never had the disease. Individuals were studied who had previously had anorexia nervosa and were at normal weight, rather than those in an active disease phase, to avoid the potential of malnutrition confounding their research results. Researchers analyzed participants’ brain circuitry related to motivation and reward during two distinct metabolic periods: when they were hungry and again when satiated.

Along with differences in brain response to reward, Kaye said the researchers saw greater activity in regions of the brain important for self-control among the recovered anorexics, regardless of metabolic state. This suggests these individuals may possess a higher degree of self-control than people without eating disorders, he said.

“We are using these new insights about brain mechanisms that contribute to disordered eating to guide the development of new treatment approaches in our Eating Disorders program at UC San Diego,” he said. “We’re very motivated to help advance efforts to better understand and address this life-threatening disorder.”

Co-authors include Amanda Bischoff-Grethe, A. James Melrose, Zoe Irvine, Laura Torres, Ursula F. Bailer, Alan Simmons, and Alice Ely, at UCSD; Julie L. Fudge, at the University of Rochester; and Samuel M. McClure at Stanford.

Funding for this research came, in part, from the National Institutes of Health (grants R01-MH042984-17A1, R01-MH042984-18S1) and the Price Foundation.

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Altering brain chemistry makes us more sensitive to inequality

Prolonging dopamine’s effects in brain causes people to be more sensitive to inequality.

By Thomas Levy, UC Berkeley

What if there were a pill that made you more compassionate and more likely to give spare change to someone less fortunate? UC Berkeley scientists have taken a big step in that direction.

A new study by UC Berkeley and UC San Francisco researchers finds that giving a drug that changes the neurochemical balance in the prefrontal cortex of the brain causes a greater willingness to engage in prosocial behaviors, such as ensuring that resources are divided more equally.

The researchers also say that future research may lead to a better understanding of the interaction between altered dopamine-brain mechanisms and mental illnesses, such as schizophrenia or addiction, and potentially light the way to possible diagnostic tools or treatments for these disorders.

“Our study shows how studying basic scientific questions about human nature can, in fact, provide important insights into diagnosis and treatment of social dysfunctions,” said Ming Hsu, a co-principal investigator and assistant professor at UC Berkeley’s Haas School of Business.

“Our hope is that medications targeting social function may someday be used to treat these disabling conditions,” said Andrew Kayser, a co-principal investigator on the study, an assistant professor of neurology at UC San Francisco and a researcher in the Helen Wills Neuroscience Institute at UC Berkeley.

In the study, published online today (March 19) in the journal Current Biology, participants on two separate visits received a pill containing either a placebo or tolcapone, a drug that prolongs the effects of dopamine, a brain chemical associated with reward and motivation in the prefrontal cortex. Participants then played a simple economic game in which they divided money between themselves and an anonymous recipient. After receiving tolcapone, participants divided the money with the strangers in a fairer, more egalitarian way than after receiving the placebo.

“We typically think of fair-mindedness as a stable characteristic, part of one’s personality,” said Hsu. “Our study doesn’t reject this notion, but it does show how that trait can be systematically affected by targeting specific neurochemical pathways in the human brain.”

In this double-blind study of 35 participants, including 18 women, neither participants nor study staff members knew which pills contained the placebo or tolcapone, an FDA-approved drug used to treat people with Parkinson’s disease, a progressive neurological disorder affecting movement and muscle control.

Computational modeling showed Hsu and his colleagues that under tolcapone’s influence, game players were more sensitive to and less tolerant of social inequity, the perceived relative economic gap between a study participant and a stranger.

By connecting to previous studies showing that economic inequity is evaluated in the prefrontal cortex, a core area of the brain that dopamine affects, this study brings researchers closer to pinpointing how prosocial behaviors such as fairness are initiated in the brain.

“We have taken an important step toward learning how our aversion to inequity is influenced by our brain chemistry,” said the study’s first author, Ignacio Sáez, a postdoctoral researcher at the Haas School of Business. “Studies in the past decade have shed light on the neural circuits that govern how we behave in social situations. What we show here is one brain ‘switch’ we can affect.”

In addition to Hsu, Sáez, and Kayser, co-authors include Eric Set of UC Berkeley and Lusha Zhu of the Virginia Tech Carilion Research Institute. The study was funded by grants from the Department of Defense, Institute for Molecular Neuroscience, National Institutes of Health and Hellman Family Faculty Fund.

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Heading off concussions

UC Irvine professor James Hicks leads novel probe of impact injuries in water polo.

By Tom Vasich, UC Irvine

As a result of ongoing probes into the short- and long-term effects of concussions in football, other sports are looking into whether additional steps can be taken to protect their athletes. Among them is water polo, and a novel research venture that includes UC Irvine scientists, coaches and athletes is helping.

The effort got rolling when James Hicks – a scientist, avid fan and father of three sons who played the sport – searched an NCAA database for concussion information related to water polo. But his inquiry came up empty.

“There was none,” says Hicks, professor of ecology & evolutionary biology at UC Irvine. “And given UCI’s historic place in the sport and the collaborative mission of the university, it became clear that we should take on this issue.”

Hicks’ research focuses on evolutionary physiology. While he’s best known in science circles for his work on alligator cardiovascular systems, he also directs UCI’s innovative Exercise Medicine & Sport Sciences Initiative, which unites an interdisciplinary cadre who share an interest in physical activity and its relationship to health. And he’s drawing on their expertise – with the assistance of USA Water Polo, the national governing body for the sport – to compile the first real data set on head impact injuries and concussions in water polo.

“Jim is the first in the world to look into these deeper issues in water polo, and it’s great,” says Dan Klatt, UCI women’s water polo head coach. “Our sport is a physical one, and we need to ask whether concussions are a real problem in the sport and if we’re using the proper equipment to protect our athletes. This study takes a giant step forward in order to answer that question.”

Although head injuries and concussions do happen in water polo, information about their prevalence is, so far, primarily anecdotal. Hicks and his collaborators aim to provide a factual basis for considering whether such injuries are sufficiently common that they need to be addressed and, if so, how best to do this.

“It’s a hard sport,” Hicks says. “Head butts, elbows, shoulders – and at the highest levels, players throw the ball as fast as 50 miles an hour at short distances. Goalies appear to be most at risk, but we want to obtain scientific data to assess that risk, as well as seeing what other positions in the pool may be prone to concussion injury.”

The study has three components. In one, Dr. Steven Small, professor and chair of neurology at UCI, and Robert Blumenfeld, assistant adjunct professor of neurology at UCI, will oversee an email survey of water polo players, who will be asked a number of questions about how long they’ve been in the sport, what positions they’ve played, and the number of serious head blows they’ve received. USA Water Polo will assist in the survey by inviting its 40,000 members to participate.

In the second project – now almost done – UCI engineering students shot water polo balls at a National Highway Traffic Safety Administration-certified crash-test dummy head to gauge the impact of blows at various speeds and levels of inflation. In addition, they measured the effectiveness of protective headgear. The results are currently being analyzed.

In the third component, Hicks will outfit UCI men’s and women’s water polo players with small G-force monitors incorporated into standard water polo caps to record the intensity of head impacts. “It’s challenging to understand what’s going on in the game, and the monitors will help,” he says.

The long-term goal is to broaden the study and outfit more college, high school and age-group teams with these devices. Several local water polo programs have expressed interest in the headgear monitoring, and Hicks is scheduled to give a presentation on it at Harvard-Westlake School in Los Angeles.

He notes that this is a particularly opportune time for the study, given water polo’s recent growth in popularity. According to Christopher Ramsey, CEO of USA Water Polo, participation is increasing dramatically, especially among women. Water polo is the fastest-growing sport in California high schools, and the NCAA administers an expanding number of men’s and women’s varsity teams across the nation. It’s a sport on the rise.

According to Klatt, the mecca of water polo is here in Orange County, where highly competitive high schools and club teams produce a steady stream of the world’s top talent. USA Water Polo is based in Huntington Beach, and the men’s and women’s national teams practice at Santa Ana’s Segerstrom High School and at the organization’s training center in Los Alamitos, respectively.

UCI holds a unique position in this epicenter. Its former men’s coach, the legendary Ted Newland, profoundly influenced the sport; his UCI teams won three NCAA championships and finished second seven times. And the Exercise Medicine & Sport Sciences Initiative allows UCI’s world-class researchers, coaches and athletes to collaborate in fresh and inventive ways.

“This is a great opportunity for a national governing body to assist a world-class university in groundbreaking research,” says USA Water Polo’s Ramsey. “Universities in the U.S. have a distinctive role with sport, and because there’s a close relationship between USA Water Polo and UCI, we start with a stronger bond to work on an issue like this. We both bring valuable perspectives to this enterprise.”

The crash-test dummy exercise is already providing some interesting – if preliminary – results. While Hicks stresses that more analysis is needed, he says the data indicates that ball inflation does matter, with less-inflated, softer balls absorbing more energy upon impact.

In addition, newly developed silicon-based protective headgear – the kind not approved for NCAA play – appears to reduce impact forces by as much as 25 percent. However, Hicks points out, the precise relationship between head impacts and concussion rates requires more study, both in the lab and in the pool.

“I love science, and I’m a fan of the game, and I want to see what we can do for water polo,” Hicks says. “This is exciting stuff.”

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UCLA opens center for brain and behavioral health

Gift from Staglin family will fund research on returning unhealthy brains to health.

Michael Fanselow’s research addresses fear, memory and anxiety disorders, including how traumatic memories lead to post-traumatic stress disorder, anxiety disorders and depression. (Photo by Reed Hutchinson, UCLA)

By Stuart Wolpert, UCLA

More than 30 percent of Americans will experience an anxiety disorder at some time in their lives. A new research center at UCLA will be dedicated to increasing our understanding of the brain and learning how to help the brain recover when those, and other malfunctions, occur.

The formation of the Staglin Family Music Festival Center for Brain and Behavioral Health, which is scheduled to open July 1, was announced today (March 17) by UCLA Life Sciences Dean Victoria Sork. Michael Fanselow, distinguished professor of psychology in the UCLA College, was appointed its director.

Genetic risk factors, combined with environmental experiences, can cause the brain to malfunction. The center’s researchers will seek to discover what those changes are and develop novel methods to address them.

“The center will focus on brain health and will develop novel methods to get the unhealthy brain back to the healthy state,” said Fanselow, who also holds a UCLA faculty appointment in psychiatry.

Fanselow said anxiety disorders are generally chronic and do not go away on their own. Some of these disorders, like post-traumatic stress, are devastating.

Understanding fear

Fanselow’s research addresses fear, memory and anxiety disorders, including how traumatic memories lead to post-traumatic stress disorder, anxiety disorders and depression. He has studied how fear works in the brain using rats and mice, whose fear systems work in remarkably similar ways to that of humans.

Fear serves an important function: to protect us from danger.

“When we’re in danger, it’s really adaptive to be afraid. When we’re not in danger, it’s adaptive not to be afraid,” Fanselow said. “But we can make mistakes. One mistake is when there’s true danger and I don’t defend myself. The other mistake, which is much less costly, is when there’s no danger and I do become afraid. That’s an anxiety disorder.”

Fanselow’s laboratory is identifying and learning about the brain circuits that give rise to inappropriate fear, with the goals of reducing — or even eliminating — unnecessary fear, while preserving healthy fear.

Fanselow also was appointed to the Staglin Family Chair in Psychology.

“We are delighted to have such a prominent scientist assume our Staglin Family Chair and the leadership of the Staglin Center,” said Shari Staglin.

Garen Staglin said, “UCLA is among the leading institutions studying brain health, and we applaud its approach to campus-wide collaborations to accelerate the science of the brain and resultant treatments.”

Getting the brain back to where it should be

Psychology and psychiatry professor Michelle Craske, an expert on fear and anxiety disorders, will be associate director of the center, which is being funded by the family of Shari and Garen Staglin through the Staglin Family Music Festival for Brain Health and their philanthropic organization, the International Mental Health Research Organization.

Fanselow and Craske are currently studying whether cognitive behavior therapy, combined with a pharmaceutical called scopolamine, will help suppress fear in people with anxiety. In cognitive behavior therapy, people with anxiety disorders are repeatedly exposed to the object or situation they fear, in a non-threatening environment, and eventually they learn not to be afraid.

“We want to get the brain back to where it should be, either by combining drugs with psychotherapy or by finding different drug approaches,” said Fanselow, whose research is funded by the National Institute of Mental Health, a branch of the National Institutes of Health.

Fanselow and colleagues reported in 2013 that at the right dose, scopolamine — which has been used to treat including nausea, motion sickness, depression and other conditions — might also be useful in treating anxiety disorders.

“UCLA and the UCLA College are extremely grateful to Shari and Garen Staglin and their family, for their extremely deep and long-standing commitment to fighting mental illness, and their generosity over many years to UCLA and the College,” Sork said.

The center will also provide seed money to interdisciplinary teams of scholars to advance our understanding of many areas in brain health, ranging from depression to memory loss to schizophrenia.

Dedicated philanthropists

“The Staglins are providing UCLA with wonderful opportunity to accelerate research, enhance treatment and lead to new approaches in combatting mental illness,” Fanselow said.

Garen Staglin, a UCLA alumnus and private equity investor, is co-chair of the $4.2 billion Centennial Campaign for UCLA. His wife, Shari, a UCLA alumna, has been a director of the UCLA Foundation and a member of UCLA’s Women and Philanthropy. The Staglins own the acclaimed Staglin Family Vineyard in Napa Valley. Shari Staglin is the vineyard’s CEO and the Staglins’ daughter, Shannon, also a UCLA alumna, is president.

The Staglins became active in supporting mental health research and treatment after their son, Brandon, was diagnosed with schizophrenia. Brandon has since graduated with honors from Dartmouth and is currently marketing communications director for both the Staglin Family Vineyard and IMHRO. He also is a member of the joint board of directors of IMHRO and One Mind.

The Staglins raise funds for brain health charities and research through a variety of major events including The Music Festival for Brain Health. All of the music festival’s expenses are underwritten by its sponsors, and all proceeds go to scientific research. They also serve as founders and board members of One Mind, where Garen is co-chairman.

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NASA awards UC Irvine $9M to study underlying mechanisms of ‘space brain’

Charles Limoli will lead effort to see how cosmic radiation affects astronauts’ cognition.

UC Irvine's Charles Limoli will lead a national effort to understand the early and long-term effects of space radiation on the central nervous system. (Photo by Steve Zylius, UC Irvine)

By Tom Vasich, UC Irvine

With $9 million in NASA funding, UC Irvine professor of radiation oncology Charles Limoli will lead a national effort to understand the early and long-term effects of space radiation on the central nervous system.

Exposure to the dangerous radiation fields in space has been shown to impair the cognitive abilities of rodents, and this data suggests that astronauts who spend extended time in space may suffer similar consequences. Limoli’s team will look into the behavioral impairments of rodents attributed to space radiation exposure and the underlying causes of these deficits, including studies to quantify the structural and functional alterations to nerve cells.

This “space brain” project is part of NASA’s Human Research Program, which is funding three new NASA Specialized Centers of Research on space radiation. Investigating how such radiation affects astronauts and learning ways to mitigate those effects are critical to further human exploration of space, and NASA has set its sights on exploring an asteroid and, ultimately, Mars.

Collectively, the three NSCOR teams comprise 25 investigators from 13 institutions in eight states and the District of Columbia. Limoli’s group includes researchers from UCI, Loma Linda University and the Eastern Virginia Medical School. The radiation exposure studies will take place at the NASA Space Radiation Laboratory, located at the Brookhaven National Laboratory in Long Island, New York.

“The space environment poses unique hazards to astronauts, since a range of potential central nervous system complications can result during and after actual space travel,” Limoli said. “We plan to conduct a comprehensive series of rodent studies to characterize the neurobiological mechanisms involved with radiation-induced cognitive impairment.”

Results will inform efforts to minimize the effects of solar and galactic cosmic radiation on the central nervous system.

As a member of the Chao Family Comprehensive Cancer Center at UCI, Limoli studies how cranial irradiation triggers DNA damage, oxidative stress and structural alterations to neurons – issues important to not just astronauts but also patients subjected to radiotherapy for brain cancer. In addition, he has advanced preclinical research showing that stem cell treatments can limit cognitive deficits after cranial radiotherapy or systemic chemotherapy.

Fellow UCI investigators on the NASA project are Ivan Soltesz, professor and chair of anatomy & neurobiology; Munjal Acharya, assistant professor of radiation oncology; and Janet Baulch and Vipan Kumar, project scientists in Limoli’s research group.

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Commentary: Study affirms varied factors contribute to cognitive decline

Editorial: ‘A call for new thoughts about what might influence brain aging.’

Charles DeCarli, UC Davis

By Phyllis Brown, UC Davis

A study published online today (March 16) in JAMA Neurology that finds associations between reduced hippocampal volume (HVa) and being male, but not the gene APOE ɛ4, suggests that there are multiple factors contributing to cognitive decline throughout adulthood, according to an accompanying commentary by UC Davis Alzheimer’s Disease Center Director Charles DeCarli.

The research, by Clifford R. Jack and colleagues at the Mayo Clinic and Foundation, compared age, sex and apolipoprotein E ɛ4 (APOE ɛ4) genotype effects on memory, brain structure and the amyloid brain plaques associated with Alzheimer’s disease, using positron emission tomography (PET) in 1,246 cognitively normal individuals between the ages of 30 and 95.

The study found:

  • Overall memory worsened from age 30 through the 90s.
  • HVa worsened gradually from age 30 to the mid-60s and more steeply after that with advancing age.
  • Median amyloid accumulation seen on PET scans was low until age 70 but increased after that.
  • Memory was worse in men than women overall, especially after 40.
  • The HVa was lower in men than women overall, especially after 60.
  • For both males and females, memory performance and HVa were not different by APOE ɛ4 carrier status at any age.

“If one ascribes religiously to the concept that a large proportion of cognitive differences with age are driven by incipient disease, then one might expect that memory performance — a cognitive ability that changes most dramatically with age and is common to Alzheimer’s disease — would follow increasing levels of associated cerebral amyloid and be strongly associated with hippocampal atrophy. In their article Jack et al present new information that challenges the notion that amyloid accumulation explains memory performance across the entire age range,” DeCarli says in his editorial.

“Importantly, this work does not only address the likely highly significant impact of cerebral amyloid accumulation on dementia risk, but also extends current knowledge relating to the impact of the aging process across the spectrum of ages 30 to 95 years to brain structure, amyloid accumulation and memory performance among cognitively normal individuals.”

DeCarli notes that “If one tenaciously holds to the notion that the insidious consequences of other diseases may be contributing to these earlier differences, vascular brain injury is an obvious candidate. Vascular risk factors, such as diabetes mellitus, are associated with subtle cognitive impairment among individuals aged 47 to 57 years and hypertension is associated with significantly greater cerebral atrophy among individuals 40 years on average.”

Other contributing factors include genetic influences, which include sex differences and the “major effects” of APOE ɛ4 genotype on amyloid retention beyond age 70 years.

“Understanding the basic biology of these early processes is likely to substantially inform us about ways in which we can maintain cognitive health and optimize resistance to late-life dementia. However, such work requires the necessary motivation found by seminal work, such as that of Jack et al, which tell us where and when to investigate these processes. Establishing what is normal creates avenues for new research, increasing the likelihood of discovering novel therapeutics for late-life disease states, which is a laudable goal indeed,” DeCarli says.

For more information, visit alzheimer.ucdavis.edu.

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Study reveals treatment for breast cancer patients with cognitive difficulties

Mental training exercises developed at UCLA shown to help mitigate effects of ‘chemo brain.’

Patricia Ganz, UCLA

By Reggie Kumar, UCLA

UCLA researchers have developed a program that could improve the day-to-day lives of women with breast cancer by addressing post-treatment cognitive difficulties, sometimes known as “chemo brain,” which can affect up to 35 percent of women after their treatments.

An estimated 1 in 8 women will develop invasive breast cancer in their lifetimes, and following treatment, a mental fogginess can prevent them from being able to concentrate, staying organized and completing everyday activities, such as sticking to a schedule or planning a family gathering.

The new study, led by breast cancer research pioneer and UCLA Jonsson Comprehensive Cancer Center member Dr. Patricia Ganz, builds upon her earlier research that found a statistically significant association between neuropsychological test performance and memory complaints among women with early stage breast cancer following treatment.

“We invited the women to participate in a research study that assigned them to early or delayed treatment with a five-week, two-hour group training session, where a psychologist taught them strategies to help them with their memory and maintaining their ability to pay attention to things,” said Ganz, director of prevention and control research at the cancer center. “These are activities we call executive function and planning, or the things all of us do in order to organize our day.”

Dr. Linda Ercoli, an associate clinical professor of health sciences at the UCLA Semel Institute for Neuroscience and Human Behavior, was responsible for the development of the cognitive rehabilitation intervention program and either delivered the training or supervised other clinicians who provided the group training sessions.

“We gave women exercises on, for example, how to remember a ‘to-do’ list, remembering to buy items at the store, or planning a party and deciding what type of food should be served to guests,” said Ercoli, a co-author of the study. “Participants were given real-life tasks to complete that would use these types of strategies to improve cognitive function.”

The intervention program also included homework and practice activities that they would discuss at the weekly sessions. These exercises were designed to improve memory and cognitive function.

Women in the delayed group were offered the intervention after completion of their two-month follow-up testing and this occurred when the researchers had enough women to form a group to provide them the intervention.

All of the women who participated in the study, whether they received the intervention early or at a delayed time point, completed questions about their mood and mental functioning. The women also had detailed neurocognitive testing three times: before learning which group they would be in, immediately after the end of the five weeks of training and then again two months later. Most of the women also had resting EEG (brain wave) testing to see if this could measure changes in how the women fared throughout the study.

Ganz and Ercoli found that the 32 women in the early intervention group reported improvement in memory complaints and test functioning, while the 16 women in the delayed intervention control group did not improve in either their cognitive complaints or test performance. The intervention group participants showed continued improvement two months after completion of the rehabilitation program.

“The brain wave pattern in the intervention group actually normalized,” Ganz said. “We hope that this might be an effective biologic way to assess the cognitive effects of cancer treatment in the future.”

The next steps are for other researchers to test this cognitive rehabilitation program in larger numbers of patients, and potentially to develop strategies to provide intervention much earlier in the course of breast cancer treatment to either prevent difficulties or hasten recovery.

“This study will be added to the growing body of literature demonstrating the validity of patient complaints,” Ganz said. “Furthermore, the intervention results provided important encouragement that these complaints can improve with appropriate training.”

The study was funded by the Breast Cancer Research Foundation and the Jonsson Comprehensive Cancer Center Foundation.

The randomized clinical trial results are available online in the journal of Psycho-Oncology.

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Study shows feasibility of blood-based test for diagnosing Alzheimer’s

An effective blood test would be safe, affordable and easy to administer.

Liana Apostolova, UCLA

By Mark Wheeler, UCLA

UCLA researchers have provided the first evidence that a simple blood test could be developed to confirm the presence of beta amyloid proteins in the brain, which is a hallmark of Alzheimer’s disease.

Although approximately 5 million Americans are living with Alzheimer’s, no reliable blood-based test currently exists for the neurodegenerative disorder that is the sixth-leading cause of death in the United States. Using blood-based biomarkers — a signature of proteins in the blood that indicate the presence of a disease — to diagnose Alzheimer’s could be a key advance.

“Blood-based biomarkers would have the important advantage of being safe, affordable and easy to administer in large groups or in rural areas, and therefore could have an enormous impact on clinical care and clinical trials alike,” said Dr. Liana Apostolova, director of the neuroimaging laboratory at the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA and head of the research team. Results of the study appeared in the journal Neurology.

Alzheimer’s disease can be diagnosed definitively only by examining brain tissue after death. While people are alive, physicians must rely on proxy measures, or biomarkers, along with cognitive symptoms such as memory loss.

Two current methods for determining the beta-amyloid formation characteristic of Alzheimer’s disease both have drawbacks. Cerebrospinal fluid can be obtained from patients, but that requires a spinal tap, an invasive procedure that carries the risk of nerve damage and other serious side effects. Another method, the amyloid PET scan, while effective, exposes subjects to radiation. The PET scan is also expensive and is not typically covered by insurance as a diagnostic test. Also, few medical centers have the technology.

For their study, the UCLA researchers developed a simple signature for predicting the presence of brain amyloidosis — the build-up of amyloid in the brain — including several blood proteins known to be associated with Alzheimer’s disease, along with information routinely obtained in the course of a clinical work-up for patients suspected to have the disease, such as results of memory testing and structural magnetic resonance imaging.

Using blood samples and other data from patients with mild cognitive impairment from the Alzheimer’s Disease Neuroimaging Initiative – a large public-private partnership that began in 2004 – the UCLA researchers found that their method could be used to predict the presence of amyloid in the brain with modest accuracy.

“Our study suggests that blood protein panels can be used to establish the presence of Alzheimer’s-type pathology of the brain in a safe and minimally invasive manner,” Apostolova said. “We need to further refine and improve on the power of this signature by introducing new disease-related metrics, but this indicates that such a test is feasible and could be on the market before long.”

Although there is no treatment that can halt or reverse the progression of Alzheimer’s disease, a non-invasive, inexpensive and reliable test for diagnosing the disease could spare people with dementia and their families the anxiety associated with uncertainty, direct them to support services earlier, and improve their likelihood of benefiting from current and future advances in treatment.

Such a test would also have a major impact on research. “With the advent of the amyloid PET scan we are learning that as many as 25-30 percent of subjects who enroll in Alzheimer’s disease clinical trials turn out not to have the disease,” said Apostolova. “That makes it difficult to measure the effects of the treatment being tested.”

Other authors of the study include Kristy Hwang, David Avila, Omid Kohannim, David Elashoff and Sophie Sokolow, all of UCLA; Edmond Teng from UCLA and Veterans Affairs Greater Los Angeles Healthcare System; Paul Thompson from the University of Southern California; Clifford Jack from the Mayo Clinic; William Jagust from the UC Berkeley; Leslie Shaw and Dr. John Trojanowski from the University of Pennsylvania School of Medicine; and Dr. Michael Weiner from the University of Pittsburgh and Department of Veterans Affairs Medical Center in San Francisco.

There were multiple funders for the study including the UCLA Easton Consortium for Alzheimer’s Drug Discovery and Biomarker Development, the National Institute of Mental Health (U01 AG024904), and the Alzheimer’s Disease Neuroimaging Initiative. Please see paper for complete list.

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