TAG: "brain"

‘Dimmer switch’ discovered for mood disorders


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

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

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

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

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

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

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Brain scans used to forecast early reading difficulties


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

Fumiko Hoeft, UC San Francisco

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

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

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

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

The research is published online in Psychological Science.

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


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

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

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

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

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

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

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Study shows evidence that sleep apnea hurts brain


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

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

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

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

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

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

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Brain inflammation disrupts memory retrieval networks


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

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

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

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

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

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

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

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

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

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

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

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Study ties honesty to prefrontal region of brain


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

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

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

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

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

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Colds may temporarily increase stroke risk in kids


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

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

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

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

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

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

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

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UC scientists awarded 8 grants in support of BRAIN Initiative


Projects seek to gain understanding of the brain.

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

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

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

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

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

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

UC early concept grant awardees include:

UC Berkeley
Ehud Isacoff

UC Davis
Martin Usrey
Karen Zito

UC San Diego
Brenda Bloodgood
Andrea Chiba
David Kleinfeld
Charles Stevens

UC San Francisco
Steven Finkbeiner

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Mapping the infant brain


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

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

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

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

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

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Single-cell analysis holds promise for stem cell, cancer research


UCSF researchers use microfluidic technology to probe human brain development.

Arnold Kriegstein, UC San Francisco

UC San Francisco researchers have identified cells’ unique features within the developing human brain, using the latest technologies for analyzing gene activity in individual cells, and have demonstrated that large-scale cell surveys can be done much more efficiently and cheaply than was previously thought possible.

“We have identified novel molecular features in diverse cell types using a new strategy of analyzing hundreds of cells individually,” said Arnold Kriegstein, M.D., Ph.D., director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. “We expect to use this approach to help us better understand how the complexity of the human cortex arises from cells that are spun off through cell division from stem cells in the germinal region of the brain.”

The research team used technology focused on a “microfluidic” device in which individual cells are captured and flow into nanoscale chambers, where they efficiently and accurately undergo the chemical reactions needed for DNA sequencing. The research showed that the number of reading steps needed to identify and spell out unique sequences and to successfully identify cell types is 100 times fewer than had previously been assumed. The technology, developed by Fluidigm Corp., can be used to individually process 96 cells simultaneously.

“The routine capture of single cells and accurate sampling of their molecular features now is possible,” said Alex Pollen, Ph.D., who along with fellow Kriegstein-lab postdoctoral fellow Tomasz Nowakowski, Ph.D., conducted the key experiments, in which they analyzed the activation of genes in 301 cells from across the developing human brain. Their results were published online August 3 in Nature Biotechnology.

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Gaining insights into the nervous system


Rita Allen Foundation Scholarship supports brain imaging studies.

Neuron picture: synaptic terminal of cortical layer2/3 neurons labeled with targeted genetically encoded sensors of neural activity.

Lin Tian’s fascination with neuroscience stems from a deep curiosity about the complexity and elegance of the human brain. As one of only five scientists in the U.S. and Canada — and the first at UC Davis — to be named a 2014 Rita Allen Foundation Scholar, Tian will be developing optical sensors and applications to acquire fundamental insights about how the nervous system functions in health and disease.

“The functioning brain receives thousands of chemical and electrical signals at the synapse, the area of connection between neurons,” Tian said. “Understanding how neurons integrate these multiple inputs to transmit information and to shape and refine the neural circuitry itself is an important area of research that can shed light on an array of neurological disorders, including depression, addiction, autism, schizophrenia and epilepsy.”

With a five-year, $500,000 grant from the Rita Allen Foundation, Tian will develop imaging tools to obtain a comprehensive view of both excitatory and inhibitory synapses in action at the cellular, tissue and whole-animal levels. She also will apply these tools to uncover the functional organization of cortical layer1 (L1) interneurons in shaping long-range interactions and their link to behavior, which can’t be done with current technology, Tian said.

“Understanding how information is transferred across neural circuitry and systems is the key to innovation in the treatment of neurological disorders,” she said.

Tian is an assistant professor of biochemistry and molecular medicine at UC Davis. She holds a bachelor’s degree in neuroscience from the University of Science and Technology of China and a doctorate in biochemistry, molecular and cell biology from Northwestern University. She completed her postdoctoral training at Howard Hughes Medical Institute Janelia Farm.

Since 1976, more than one hundred young leaders in biomedical science have been selected as Rita Allen Foundation Scholars. The program embraces innovative research with above-average risk and promise. Scholars have gone on to win the Nobel Prize in Physiology or Medicine, the National Medal of Science, the Wolf Prize in Medicine, and the Breakthrough Prize in Life Sciences.

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Kids with autism, SPD show brain wiring differences


UCSF study builds on its research showing kids with SPD have measurable brain differences.

Pratik Mukherjee, UC San Francisco

Researchers at UC San Francisco have found that children with sensory processing disorders have decreased structural brain connections in specific sensory regions different than those in autism, further establishing SPD as a clinically important neurodevelopmental disorder.

The research, published in the journal PLOS ONE, is the first study to compare structural connectivity in the brains of children with an autism diagnosis versus those with an SPD diagnosis, and with a group of typically developing boys. This new research follows UCSF’s groundbreaking study published in 2013 that was the first to find that boys affected with SPD have quantifiable regional differences in brain structure when compared to typically developing boys. This work showed a biological basis for the disease but prompted the question of how these differences compared with other neurodevelopmental disorders.

“With more than 1 percent of children in the U.S. diagnosed with an autism spectrum disorder, and reports of 5 to 16 percent of children having sensory processing difficulties, it’s essential we define the neural underpinnings of these conditions, and identify the areas they overlap and where they are very distinct,” said senior author Pratik Mukherjee, M.D., Ph.D., a professor of radiology and biomedical imaging and bioengineering at UCSF.

SPD can be hard to pinpoint, as more than 90 percent of children with autism also are reported to have atypical sensory behaviors, and SPD has not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists.

Elysa Marco, UC San Francisco

“One of the most striking new findings is that the children with SPD show even greater brain disconnection than the kids with a full autism diagnosis in some sensory-based tracts,” said Elysa Marco, M.D., cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital San Francisco and the study’s corresponding author. “However, the children with autism, but not those with SPD, showed impairment in brain connections essential to the processing of facial emotion and memory.”

Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with emotional regulation. Furthermore, a sound that is an irritant one day can be tolerated the next. The disease can be baffling for parents and has been a source of much controversy for clinicians who debate whether it constitutes its own disorder, according to the researchers.

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