TAG: "brain"

UCSF launches online registry to drive brain disease research


Brain Health Registry brings promise of speeding advances.

A new online project led by researchers at UC San Francisco promises to dramatically cut the time and cost of conducting clinical trials for brain diseases, while also helping scientists analyze and track the brain functions of thousands of volunteers over time.

With easy online registration, the Brain Health Registry is designed to create a ready pool of research subjects for studies on neurological diseases, such as Alzheimer’s and Parkinson’s, as well as depression, post-traumatic stress disorder and many other brain ailments. About one third of the cost of running a clinical trial comes from having to recruit patients, and many trials fail or are delayed because of it.

Michael Weiner, UC San Francisco

The Brain Health Registry is the first neuroscience project to use the Internet on such a scale to advance clinical research, according to Michael Weiner, M.D., founder and principal investigator of the initiative and a professor of radiology, biomedical engineering, medicine, psychiatry and neurology at UCSF. One of his roles is serving as principal investigator of the Alzheimer’s Disease Neuroimaging Initiative, the largest observational study of Alzheimer’s.

“This registry is an innovative 21st century approach to science with tremendous potential,” Weiner said. “The greatest obstacles to finding a cure for Alzheimer’s and other brain disorders are the cost and time involved in clinical trials. This project aims to cut both and greatly accelerate the search for cures.”

Leading funders for the project include the Rosenberg Alzheimer’s Project, the Ray and Dagmar Dolby Family Fund and Kevin and Connie Shanahan. The initial focus will be on the San Francisco Bay Area, and the goal is to recruit 100,000 people by the end of 2017. Nearly 2,000 people already signed up during the online registry’s beta phase.

Volunteers will provide a brief personal history and take online neuropsychological tests in an online game format. The games give the Brain Health Registry scientific team a snapshot of the participant’s brain function. The data collected will help scientists study brains as they age, identify markers for diseases, develop better diagnostic tools to stop disease before it develops and increase the ready pool of pre-qualified clinical trial participants.

A select number of volunteers will be asked by researchers to do more, such as providing saliva or blood samples, or participating in clinical trials to test potential cures. Volunteers can participate as little or as much as they like. All information will be gathered in accordance with federal privacy laws under the Health Insurance Portability and Accountability Act (HIPAA), as well as the highest standards of medical ethics.

“For those of us who know people suffering from Parkinson’s, Alzheimer’s, PTSD and other brain disorders, this is a way we can be involved in the search for a cure,” said Douglas Rosenberg, of the Rosenberg Alzheimer’s Project, which is helping to fund the project. “We’ve worked to make the process very easy and very fulfilling for our volunteers.”

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Cancer drugs block dementia-linked brain inflammation


Research represents novel approach to lessening impact of Alzheimer’s, Parkinson’s.

Kim Green, UC Irvine

A class of drugs developed to treat immune-related conditions and cancer – including one currently in clinical trials for glioblastoma and other tumors – eliminates neural inflammation associated with dementia-linked diseases and brain injuries, according to UC Irvine researchers.

In their study, assistant professor of neurobiology & behavior Kim Green and colleagues discovered that the drugs, which can be delivered orally, eradicated microglia, the primary immune cells of the brain. These cells exacerbate many neural diseases, including Alzheimer’s and Parkinson’s, as well as brain injury.

“Because microglia are implicated in most brain disorders, we feel we’ve found a novel and broadly applicable therapeutic approach,” Green said. “This study presents a new way to not just modulate inflammation in the brain but eliminate it completely, making this a breakthrough option for a range of neuroinflammatory diseases.”

The researchers focused on the impact of a class of drugs called CSF1R inhibitors on microglial function. In mouse models, they learned that inhibition led to the removal of virtually all microglia from the adult central nervous system with no ill effects or deficits in behavior or cognition. Because these cells contribute to most brain diseases – and can harm or kill neurons – the ability to eradicate them is a powerful advance in the treatment of neuroinflammation-linked disorders.

Green said his group tested several selective CSF1R inhibitors that are under investigation as cancer treatments and immune system modulators. Of these compounds, they found the most effective to be a drug called PLX3397, created by Plexxikon Inc., a Berkeley-based biotechnology company and member of the Daiichi Sankyo Group. PLX3397 is currently being evaluated in phase one and two clinical trials for multiple cancers, including glioblastoma, melanoma, breast cancer and leukemia.

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Bioengineer studying how the brain controls movement


UC San Diego research aims to help patients with Parkinson’s disease.

Jim Bell is a Parkinson's patient who is working with researchers to better understand the brain dynamics of motor control in Parkinson's disease. The team is working to develop non-invasive therapies. (Photo by National Science Foundation)

A UC San Diego research team led by bioengineer Gert Cauwenberghs is working to understand how the brain circuitry controls how we move. The goal is to develop new technologies to help patients with Parkinson’s disease and other debilitating medical conditions navigate the world on their own. Their research is funded by the National Science Foundation’s Emerging Frontiers of Research and Innovation program.

“Parkinson’s disease is not just about one location in the brain that’s impaired. It’s the whole body. We look at the problems in a very holistic way, combine science and clinical aspects with engineering approaches for technology,” explains Cauwenberghs, a professor at the Jacobs School of Engineering and co-director of the Institute for Neural Computation at UC San Diego. “We’re using advanced technology, but in a means that is more proactive in helping the brain to get around some of its problems — in this case, Parkinson’s disease — by working with the brain’s natural plasticity, in wiring connections between neurons in different ways.”

Outcomes of this research are contributing to the system-level understanding of human-machine interactions, and motor learning and control in real world environments for humans, and are leading to the development of a new generation of wireless brain and body activity sensors and adaptive prosthetics devices. Besides advancing our knowledge of human-machine interactions and stimulating the engineering of new brain/body sensors and actuators, the work is directly influencing diverse areas in which humans are coupled with machines. These include brain-machine interfaces and telemanipulation.

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New test makes Parkinson’s-like disorder detectable in young adults


Brain abnormalities may begin to develop two decades before symptoms might occur.

UC Davis MIND Institute

The very earliest signs of a debilitating neurodegenerative disorder, in which physical symptoms are not apparent until the fifth decade of life, are detectable in individuals as young as 30 years old using a new, sophisticated type of neuroimaging, researchers at UC Davis, the University of Illinois and UCLA have found.

People with the condition — fragile X-associated tremor/ataxia syndrome (FXTAS) — experience tremors, poor balance, cognitive impairments and Parkinsonism. The genetic condition results from a mutation in the fragile X mental retardation gene (FMR1). FXTAS develops in about 40 percent of male and 15 percent of female carriers of the mutated FMR1 gene.

“Our findings suggest that the brain abnormalities of FXTAS may begin to develop about two decades before symptoms might occur,” said Tony J. Simon, study senior author and professor, Department of Psychiatry and Behavioral Sciences.

“Altered Structural Brain Connectome in Young Adult Fragile X Premutation Carriers,” is published in Human Brain Mapping.

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Study shows evidence that autism begins during pregnancy


Finding gives insight into the nature of autism.

Eric Courchesne, UC San Diego

Researchers at the UC San Diego School of Medicine and the Allen Institute for Brain Science have published a study that gives clear and direct new evidence that autism begins during pregnancy.

The study will be published in the March 27 online edition of the New England Journal of Medicine.

The researchers – Eric Courchesne, Ph.D., professor of neurosciences and director of the Autism Center of Excellence at UC San Diego; Ed S. Lein, Ph.D., of the Allen Institute for Brain Science in Seattle; and first author Rich Stoner, Ph.D., of the UC San Diego Autism Center of Excellence – analyzed 25 genes in post-mortem brain tissue of children with and without autism. These included genes that serve as biomarkers for brain cell types in different layers of the cortex, genes implicated in autism and several control genes.

“Building a baby’s brain during pregnancy involves creating a cortex that contains six layers,” Courchesne said. “We discovered focal patches of disrupted development of these cortical layers in the majority of children with autism.” Stoner created the first three-dimensional model visualizing brain locations where patches of cortex had failed to develop the normal cell-layering pattern.

“The most surprising finding was the similar early developmental pathology across nearly all of the autistic brains, especially given the diversity of symptoms in patients with autism, as well as the extremely complex genetics behind the disorder,” explained Lein.

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Brain differences found in college-aged occasional drug users


UC San Diego findings point to potential biomarkers for early detection of at-risk youth.

Martin Paulus, UC San Diego

Researchers at the UC  San Diego School of Medicine have discovered impaired neuronal activity in the parts of the brain associated with anticipatory functioning among occasional 18- to 24-year-old users of stimulant drugs, such as cocaine, amphetamines and prescription drugs such as Adderall.

The brain differences, detected using functional magnetic resonance imaging (fMRI), are believed to represent an internal hard wiring that may make some people more prone to drug addiction later in life.

Among the study’s main implications is the possibility of being able to use brain activity patterns as a means of identifying at-risk youth long before they have any obvious outward signs of addictive behaviors.

The study is published in the March 26 issue of the Journal of Neuroscience.

“If you show me 100 college students and tell me which ones have taken stimulants a dozen times, I can tell you those students’ brains are different,” said Martin Paulus, M.D., professor of psychiatry and a co-senior author with Angela Yu, Ph.D., professor of cognitive science at UC San Diego. “Our study is telling us, it’s not ‘this is your brain on drugs,’ it’s ‘this is the brain that does drugs.’”

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Brain insights


UCSF’s Neuroscape Lab vividly displays brain activity as tool to develop targeted therapies.

In Adam Gazzaley’s new lab, the brain is a kaleidoscope of colors, bursting and pulsing in real time to the rhythm of electronic music.

The mesmerizing visual on the screen is a digital masterpiece – but the UC San Francisco neuroscientist has a much bigger aspiration than just creating art. He wants this to lead to treatments for a variety of brain diseases, including Alzheimer’s, autism and multiple sclerosis.

Gazzaley, M.D., Ph.D., opened the Neuroscape lab this month at UCSF’s Mission Bay campus, where he’s developed a way to display a person’s brain activity while it’s thinking, sensing and processing information, allowing researchers to see what areas of the person’s brain are being triggered – or, in the case of certain diseases, not triggered.

Until recently, it was impossible to study brain activity without immobilizing the person inside a big, noisy machine or tethering him or her to computers. At the Neuroscape lab, subjects can move freely to simulate real-world conditions.

One of its first projects was the creation of new imaging technology called GlassBrain, in collaboration with the Swartz Center at UC San Diego and Nvidia, which makes high-end computational computer chips. Brain waves are recorded through electroencephalography (EEG), which measures electrical potentials on the scalp, and projected onto the structures and connecting fibers of a brain image created with magnetic resonance imaging and diffusion tensor imaging.

To demonstrate the technology at the lab’s opening, Grateful Dead drummer Mickey Hart donned an Oculus Rift virtual reality headset and played a drumming video game designed to enhance brain function, while colorful images of his brain in action showed on the screen. Video games like NeuroDrummer are an entertaining and accessible way that Gazzaley is developing to train the brain.

“I want us to have a platform that enables us to be more creative and aggressive in thinking how software and hardware can be a new medicine to improve brain health,” said Gazzaley, an associate professor of neurology, physiology and psychiatry and director of the UCSF neuroimaging center. “Often, high-tech innovations take a decade to move beyond the entertainment industry and reach science and medicine. That needs to change.”

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Anti-psychotic medications offer new hope vs. glioblastoma


Researchers use shRNA platform to test how genes contribute to glioblastoma growth.

Clark Chen, UC San Diego

Researchers at the UC San Diego School of Medicine have discovered that FDA-approved anti-psychotic drugs possess tumor-killing activity against the most aggressive form of primary brain cancer, glioblastoma. The finding was published in this week’s online edition of Oncotarget.

The team of scientists, led by principal investigator, Clark C. Chen, M.D., Ph.D., vice chairman of UC San Diego School of Medicine’s Division of Neurosurgery, used a technology platform called shRNA to test how each gene in the human genome contributed to glioblastoma growth. The discovery that led to the shRNA technology won the Nobel Prize in Physiology/Medicine in 2006.

“ShRNAs are invaluable tools in the study of what genes do. They function like molecular erasers,” said Chen. “We can design these ‘erasers’ against every gene in the human genome. These shRNAs can then be packaged into viruses and introduced into cancer cells. If a gene is required for glioblastoma growth and the shRNA erases the function of that gene, then the cancer cell will either stop growing or die.”

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New high-tech lab records the brain, body in action


UCSF’s Neuroscape Lab seeks to understand, treat brain disease.

How does an autistic child take in information when he sits in a classroom abuzz with social activity? How long does it take someone with multiple sclerosis, which slows activity in the brain, to process the light bouncing off the windshield while she drives?

Until recently, the answers to basic questions of how diseases affect the brain – much less the ways to treat them – were lost to the limitations on how scientists could study brain function under real-world conditions. Most technology immobilized subjects inside big, noisy machines or tethered them to computers that made it impossible to simulate what it’s really like to live and interact in a complex world.

But now UC San Francisco neuroscientist Adam Gazzaley, M.D., Ph.D., is hoping to paint a fuller picture of what is happening in the minds and bodies of those suffering from brain disease with his new lab, Neuroscape, which bridges the worlds of neuroscience and high-tech.

In the Neuroscape lab, wireless and mobile technologies set research participants free to move around and interact inside 3-D environments, while scientists make functional recordings with an array of technologies. Gazzaley hopes this will bring his field closer to understanding how complex neurological and psychiatric diseases really work and help doctors like him repurpose technologies built for fitness or fun into targeted therapies for their patients.

“I want us to have a platform that enables us to be more creative and aggressive in thinking how software and hardware can be a new medicine to improve brain health,” said Gazzaley, an associate professor of neurology, physiology and psychiatry and director of the UCSF Neuroscience Imaging Center. “Often, high-tech innovations take a decade to move beyond the entertainment industry and reach science and medicine. That needs to change.”

As a demonstration of what Neuroscape can do, Gazzaley’s team created new imaging technology that he calls GlassBrain, in collaboration with the Swartz Center at UC San Diego and Nvidia, which makes high-end computational computer chips. GlassBrain creates vivid, color visualizations of the structures of the brain and the white matter that connects them, as they pulse with electrical activity in real time.

These brain waves are recorded through electroencephalography (EEG), which measures electrical potentials on the scalp. Ordinary EEG recordings look like wavy horizontal lines, but GlassBrain turns the data into bursts of rhythmic activity that speed along golden spaghetti-like connections threading through a glowing, multi-colored glass-like image of a brain. Gazzaley is now looking at how to feed this information back to his subjects, for example by using the data from real-time EEG to make video games that adapt as people play them to selectively challenge weak brain processes.

Gazzaley has already used the technology to image the brain of former Grateful Dead drummer Mickey Hart as he plays a hypnotic, electronic beat on a Roland digital percussion device with NeuroDrummer, a game the Gazzaley Lab is designing to enhance brain function through rhythmic training. Hart, whose brain is healthy, is collaborating with Gazzaley to develop the game and performed on NeuroDrummer while immersed in virtual reality on an Oculus Rift at the Neuroscape lab opening today (March 5).

The Neuroscape lab will be available to all UCSF researchers who study the brain. And Gazzaley ultimately hopes it will aid in the development of therapies to treat diseases as various as Alzheimer’s, post-traumatic stress disorder, attention deficit and hyperactivity disorder, schizophrenia, autism, depression and multiple sclerosis.

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Cigarette smoking may cause physical changes in brains of young smokers


These changes can occur in those who have been smoking for a relatively short time.

The young, it turns out, smoke more than any other age group in America. Unfortunately, the period of life ranging from late adolescence to early adulthood is also a time when the brain is still developing.

Now, a small study from UCLA suggests a disturbing effect: Young adult smokers may experience changes in the structures of their brains due to cigarette smoking, dependence and craving. Even worse, these changes can occur in those who have been smoking for a relatively short time. Finally, the study suggests that neurobiological changes that may result from smoking during this critical period could explain why adults who began smoking at a young age stay hooked on cigarettes.

The study appears in today’s (March 3) online edition of the journal Neuropsychopharmacology.

“Although we are not certain whether the findings represent the effects of smoking or a genetic risk factor for nicotine dependence, the results may reflect the initial effects of cigarette smoking on the brain,” said senior author Edythe London, a professor of psychiatry and of molecular and medical pharmacology at UCLA’s Semel Institute for Neuroscience and Human Behavior and David Geffen School of Medicine. “This work may also contribute to the understanding of why smoking during this developmental stage has such a profound impact on lifelong smoking behavior.”

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Motion-sensing cells in eye let brain ‘know’ about directional changes


Study provides first direct link between direction-sensing cells in the retina and the cortex.

How do we “know” from the movements of speeding car in our field of view if it’s coming straight toward us or more likely to move to the right or left?

Scientists have long known that our perceptions of the outside world are processed in our cortex, the six-layered structure in the outer part of our brains. But how much of that processing actually happens in the cortex? Do the eyes tell the brain a lot or a little about the content of the outside world and the objects moving within it?

In a detailed study of the neurons linking the eyes and brains of mice, biologists at UC San Diego discovered that the ability of our brains and those of other mammals to figure out and process in our brains directional movements is a result of the activation in the cortex of signals that originate from the direction-sensing cells in the retina of our eyes.

“Even though direction-sensing cells in the retina have been known about for half a century, what they actually do has been a mystery — mostly because no one knew how to follow their connections deep into the brain,” said Andrew Huberman, an assistant professor of neurobiology, neurosciences and ophthalmology at UC San Diego, who headed the research team, which also involved biologists at the Salk Institute for Biological Sciences. “Our study provides the first direct link between direction-sensing cells in the retina and the cortex and thereby raises the new idea that we ‘know’ which direction things are moving specifically because of the activation of these direction-selective retinal neurons.” The study, recently published online, will appear in the March 20 print issue of Nature.

The discovery of the link between direction-sensing cells in the retina and the cortex has a number of practical implications for neuroscientists who treat disabilities in motion processing, such as dysgraphia, a condition sometimes associated with dyslexia that affects direction-oriented skills.

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MRI-guided laser treatment for brain cancer a first in state


Technology helps treat malignant tumor deep inside a patient’s brain.

Neurosurgeon Clark Chen treats recurrent brain cancer with MRI-guided laser technology at UC San Diego Health System.

Using a novel magnetic resonance imaging (MRI)-guided laser technology, neurosurgeons at UC San Diego Health System have successfully treated a malignant tumor deep inside a patient’s brain. This is the first time that this FDA-approved laser-based treatment has been performed in California.

“The patient’s brain tumor was located in the thalamus. Normally, to access a tumor in this region, the surgeon would have to remove considerable healthy brain tissue, thus subjecting the patient to significant neurologic injury,” said neurosurgeon Clark C. Chen, M.D., Ph.D., vice chairman of research, UC San Diego Division of Neurosurgery.  “This MRI-guided laser technology helps neurosurgeons preserve healthy brain tissues while allowing treatment of tumors that would otherwise be inoperable.”

Chen and his team used a technique called laser interstitial thermal therapy. The procedure is performed inside an MRI machine while the patient is under general anesthesia.  A dime-size hole is created in the patient’s skull to access the tumor. A laser probe is then inserted into the tumor under real-time MRI monitoring and computer guidance. When the tumor is reached, the laser beam is activated, heating and destroying tumor cells.

“It is well-known that MRI can be used to generate detailed images of the brain. What is less known is that MRI can also be used to measure the internal temperature of the brain,” said Chen. “With this application, I can view the tumor in real time as it is being destroyed while customizing the effects of the laser to the tumor without injuries to the surrounding normal brain. This incredible visualization allows neurosurgeons to preserve billions of neuronal connections that are essential for normal brain function.”

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