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News Article | April 17, 2017
Site: www.newscientist.com

It tastes foul and makes people vomit. But ayahuasca, a hallucinogenic concoction that has been drunk in South America for centuries in religious rituals, may help people with depression that is resistant to antidepressants. Tourists are increasingly trying ayahuasca during holidays to countries such as Brazil and Peru, where the psychedelic drug is legal. Now the world’s first randomised clinical trial of ayahuasca for treating depression has found that it can rapidly improve mood. The trial, which took place in Brazil, involved administering a single dose to 14 people with treatment-resistant depression, while 15 people with the same condition received a placebo drink. A week later, those given ayahuasca showed dramatic improvements, with their mood shifting from severe to mild on a standard scale of depression. “The main evidence is that the antidepressant effect of ayahuasca is superior to the placebo effect,” says Dráulio de Araújo of the Brain Institute at the Federal University of Rio Grande do Norte in Natal, who led the trial. Shamans traditionally prepare the bitter, deep-brown brew of ayahuasca using two plants native to South America. The first, Psychotria viridis, is packed with the mind-altering compound dimetheyltryptamine (DMT). The second, the ayahuasca vine (Banisteriopsis caapi), contains substances that stop DMT from being broken down before it crosses the gut and reaches the brain. To fool placebo recipients into thinking they were getting the real thing, de Araújo and his team concocted an equally foul tasting brown-coloured drink. They also carefully selected participants who had never tried ayahuasca or other psychedelic drugs before. A day before their dose, the participants filled in standard questionnaires to rate their depression. The next day, they spent 8 hours in a quiet, supervised environment, where they received either the placebo or the potion, which produces hallucinogenic effects for around 4 hours. They then repeated filling in the questionnaires one, two and seven days later. Both groups reported substantial improvements one and two days after the treatment, with placebo scores often as high as those of people who had taken the drug. In trials of new antidepressant drugs, it is common for as many as 40 per cent of participants to respond positively to placebos, says de Araújo. But a week into this trial, 64 per cent of people who had taken ayahuasca felt the severity of their depression reduce by 50 per cent or more. This was true for only 27 per cent of those who drank the placebo. “The findings suggest a rapid antidepressant benefit for ayahuasca, at least for the short term,” says David Mischoulon of Massachusetts General Hospital in Boston. “But we need studies that follow patients for longer periods to see whether these effects are sustained.” “There is clearly potential to explore further how this most ancient of plant medicines may have a salutary effect in modern treatment settings, particularly in patients who haven’t responded well to conventional treatments,” says Charles Grob at the University of California, Los Angeles. If the finding holds up in longer studies, it could provide a valuable new tool for helping people with treatment-resistant depression. An estimated 350 million people worldwide experience depression, and between a third to a half of them don’t improve when given standard antidepressants. Ayahuasca isn’t the only psychedelic drug being investigated as a potential treatment for depression. Researchers have also seen some benefits with ketamine and psilocybin, extracted from magic mushrooms, although psilocybin is yet to be tested against a placebo.


News Article | April 25, 2017
Site: www.sciencedaily.com

Anna Gunby can't run around as smoothly as most 4-year-olds because her wobbly legs are affected by a rare brain disease that also hinders her intellect. She can't identify colors. She can't count objects. Her attention span is short. "But there's definitely hope," said Anna's mother, Courtney Gunby. "Maybe one day she'll be able to live on her own, operate a vehicle or go swimming by herself. There's hope that she could have some sense of normalcy to her life." A study led by investigators in UT Southwestern's Peter O'Donnell Jr. Brain Institute offers novel insight into how a newly designed diet can help children like Anna cope with Glut1 deficiency -- a rare disease that severely inhibits learning and muscle control by starving the brain of glucose, its main energy source. And scientists are already beginning to expand on the findings published in JAMA Neurology by testing an edible oil that smaller studies indicate can improve cognitive abilities in patients. Combining the new diet with the supplemental oil derived from castor beans could provide a life-changing treatment that trail blazes a brighter future for thousands of children in the U.S. who otherwise face a lifetime of stunted brain function. Patients with Glut1 deficiency usually can't learn beyond an elementary school level and often can't live independently as adults. "We're talking about helping people be independent from their parents. The question every parent asks is, 'Will my child be able to have an independent life when we're gone?' Right now it's very questionable whether they'll be able to achieve independence," said Dr. Juan Pascual, Associate Professor of Neurology and Neurotherapeutics, Pediatrics, and Physiology at UT Southwestern Medical Center. Dr. Pascual led the JAMA study that relied on data from a worldwide registry he created in 2013 for Glut1 deficiency patients. The research tracked 181 patients for three years, finding that a modified Atkins diet that includes less fat and slightly more carbohydrates than the standard ketogenic diet helped reduce seizures and improved the patients' long-term health. The study also found earlier diagnosis and treatment of the disease improved their prognosis. In addition, Dr. Pascual is overseeing national clinical trials that are testing whether triheptanoin (C7) oil improves the intellect of patients by providing their brains an alternative fuel to glucose. The trials will last five years and are funded with more than $3 million from the National Institutes of Health.


News Article | April 5, 2017
Site: www.medicalnewstoday.com

Picking up a slice of pizza or sending a text message: Scientists long believed that the brain signals for those and related movements originated from motor areas in the frontal lobe of brain, which control voluntary movement. But that may not always be true. A new brain pathway has been identified by neuroscientists at the University of Pittsburgh School of Medicine and the University of Pittsburgh Brain Institute (UPBI) that could underlie our ability to make the coordinated hand movements needed to reach out and manipulate objects in our immediate surroundings. The discovery was made in a non-human primate model, but researchers believe that a similar pathway is likely to be present in humans as well. The results, published in the journal Proceedings of the National Academy of Sciences, show that the neural pathway originates not from the frontal lobe, but from the posterior parietal cortex (PPC), a brain region that scientists previously thought was involved only in associating sensory inputs and building a representation of extrapersonal space. "The findings break the hard and fast rule that a furrow in the brain called the central sulcus--a Mississippi River-like separation--splits up the areas controlling sensory and motor function," said senior author Peter Strick, Ph.D., Thomas Detre Professor of Neuroscience, Distinguished Professor and chair of neurobiology, Pitt School of Medicine, and scientific director of UPBI. "This has implications for how we understand hand movement and may help us develop better treatments for patients in whom motor function is affected, such as those who have had a stroke. Our study also will have a direct impact on the efforts of researchers studying neural prosthetics and brain computer interfaces." More than three decades ago, renowned neuroscientist Vernon Mountcastle proposed the presence of a movement control center in the PPC and termed it a 'command apparatus' for operation of the limbs, hands and eyes within immediate extrapersonal space. In the current study, Strick and his team confirm that such a command apparatus exists and demonstrate a new pathway that connects the PPC directly to neurons in the spinal cord that control hand movement. The research team conducted three separate experiments in a non-human primate model to make the discovery. They first showed that electrical stimulation in a region of the PPC called "lateral area 5" evoked finger and wrist movements in the animal. When they injected a protein marker into lateral area 5, they found that the marker made its way to the spinal cord and ended in the same location where the neurons controlling hand muscles are known to be present, suggesting a connection. "The wiring and the connections from the PPC to the spinal cord and the hand look extremely similar to those from the frontal lobe that have been extensively studied. Similar form suggests similar function in controlling movement," said Jean-Alban Rathelot, Ph.D., a research associate in Strick's laboratory and the lead author of the new study. For their final experiment, they used a strain of rabies virus as a 'tracker' since it has the ability to jump across connected neurons. The team found that when they injected the virus into a hand muscle, it was indeed transported back to neurons in the same region of PPC where stimulation evoked hand movements. This result demonstrated the existence of a direct pathway from lateral area 5 to spinal cord regions that control hand muscles. "We know from previous research that individuals who have suffered brain injuries in this area have trouble with dexterous finger movements like finding keys in a bag containing many other things, which strongly supports our findings," said Richard Dum, Ph.D., a research associate professor in neurobiology and a co-author of the study. Strick and his team believe that the multiple pathways for controlling hand movement from the frontal lobe and the PPC could work together to execute one complex hand task or could work in parallel to speed up movement, much like multiple processors in a computer can enhance efficacy. The research was supported by National Institutes of Health grants R01 NS24328 and P40 OD010996, and the Pennsylvania Department of Health. Article: Posterior parietal cortex contains a command apparatus for hand movements, Jean-Alban Rathelot, Richard P. Dum, and Peter L. Strick, Proceedings of the National Academy of Sciences, doi: 10.1073/pnas.1608132114, published online 3 April 2017.


News Article | April 29, 2017
Site: www.techtimes.com

Diabetes is a troublesome disease that causes complications that increase the chances of contracting other serious health conditions. A study published on April 27 provides proof that diabetes, along with excess weight, damages the brain. The study suggests that people diagnosed with type 2 diabetes should keep their weight at normal levels because overweight diabetics are more at risk for cognitive decline and psychiatric illnesses. The researchers assembled a group of 50 overweight individuals aged 30 to 60 who were in the early stages of type 2 diabetes. Two other groups were gathered to match the original group according to age and sex. The second group was composed of 50 normal-weight type 2 diabetics who were also in the early stages, while the third, a control group, consisted of 50 healthy individuals. The researchers focused their attention on brain functions that usually affect type 2 diabetics and noted that obesity also attacks the same areas in the brain. "So, if you have both, will it be worse than if you have them alone? That's what we looked at in this particular study," endocrinologist and study co-author Dr. Donald C. Simonson said. The participants underwent a magnetic resonance imaging scan and were given psychological examinations that tested their memory, executive function (cognition and planning), and psychomotor speed (reaction time). By studying the MRI scan results and psychological tests taken by the three subgroups, the researchers discovered that a significant thinning of the cerebral cortex, as well as increased presence of white matter abnormalities, occurred in overweight diabetic participants. "Cortical thickness was decreased in several regions of the diabetic brains. Further thinning of the temporal lobes found in overweight/obese individuals with type 2 diabetes suggests that these regions are specifically vulnerable to combined effects of obesity and type 2 diabetes," said Dr. In Kyoon Lyoo, the study's senior author and the director of the Brain Institute in South Korea's Ewha University. Type 2 diabetics with a normal body mass index also showed similar results but the damage was not as advanced as that in overweight participants. "Most of the things we looked at, you could see that there was a progression, and the obese patients with diabetes were worse than the lean patients with diabetes, and they were both worse than the age-matched controls," Simonson explained. The study notes that the damaged areas in the brain cater to language comprehension and long-term memory. What is more significant in the findings is that the combined obesity and type 2 diabetes damage is only a milder form of the abnormalities that show up in Alzheimer's disease patients, leading the researchers to believe that diabetes may be a risk factor in the development of Alzheimer's disease. The research, titled "Brain changes in overweight/obese and normal-weight adults with type 2 diabetes mellitus," was published in the journal Diabetologia. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


News Article | October 31, 2016
Site: www.sciencedaily.com

The distinct structures of toxic protein aggregates that form in degenerating brains determine which type of dementia will occur, which regions of brain will be affected, and how quickly the disease will spread, according to a study from the Peter O'Donnell Jr. Brain Institute. The research helps explain the diversity of dementias linked to tau protein aggregation, which destroys brain cells of patients with Alzheimer's and other neurodegenerative syndromes. The study also has implications for earlier and more accurate diagnoses of various dementias through definition of the unique forms of tau associated with each. "In addition to providing a framework to understand why patients develop different types of neurodegeneration, this work has promise for the development of drugs to treat specific neurodegenerative diseases, and for how to accurately diagnose them. The findings indicate that a one-size-fits-all strategy for therapy may not work, and that we have to approach clinical trials and drug development with an awareness of which forms of tau we are targeting," said study author Dr. Marc Diamond, founding Director of the Center for Alzheimer's and Neurodegenerative Diseases, and Professor of Neurology and Neurotherapeutics with the O'Donnell Brain Institute at UT Southwestern Medical Center. Researchers used special cell systems to replicate distinct tau aggregate conformations. These different forms of pathological tau were then inoculated into the brains of mice. Each form created different pathological patterns, recapitulating the variation that occurs in diseases such as Alzheimer's, frontotemporal dementias, and traumatic encephalopathy. The different forms of tau caused pathology that spread at different rates through the brain, and affected specific brain regions. This experiment demonstrated that the structure of pathological tau aggregates alone is sufficient to account for most if not all the variation seen in human neurodegenerative diseases that are linked to this protein. The finding, published in Neuron, could have a notable impact on widespread efforts at the O'Donnell Brain Institute and elsewhere to develop treatments that eliminate tau and other toxic proteins from the brains of dementia patients. "The challenge for us now is to figure out how to rapidly and efficiently determine the forms of tau that are present in individual patients, and simultaneously, to develop specific therapies. This work says that it should be possible to predict patterns of disease in patients and responses to therapy based on knowledge of tau aggregate structure," said Dr. Diamond, who holds the Distinguished Chair in Basic Brain Injury and Repair. Dr. Diamond's lab, at the forefront of many notable findings relating to tau, had previously determined that tau acts like a prion -- an infectious protein that can self-replicate and spread like a virus through the brain. The lab has determined that tau protein in human brain can form many distinct strains, or self-replicating structures, and developed methods to reproduce them in the laboratory. This research led Dr. Diamond's team to the latest study to test whether these strains might account for different forms of dementia. To make this link, 18 distinct tau aggregate strains were replicated in the lab from human neurodegenerative disease brain samples, or were created from mouse models or other artificial sources. Researchers inoculated the strains into different brain regions of mice and found striking differences among them. While some strains had far reaching and rapid effects, others replicated only in limited parts of the brain, or caused widespread disease but did so very slowly. This surprising result answered a fundamental question that has dogged the field of neurodegenerative disease: Why are brain regions vulnerable in certain cases but not others, and why do some diseases progress more rapidly than others? For instance, in Alzheimer's disease, problems begin in brain memory centers before spreading to other areas that control functions such as language. Conversely, due to initial degeneration of frontal and temporal brain regions in frontotemporal dementia, the memory centers are relatively spared, and patients often first show changes in personality and behavior. The new study implies that with knowledge of tau aggregate structure in patients, or possibly even in healthy individuals, it should be possible to predict the brain regions most vulnerable to degeneration and the rate of disease progression. The study was funded by the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, National Institute on Aging, the Tau Consortium, and the Cure Alzheimer's Fund. At UT Southwestern the work was facilitated with help from the Neuro-Models Facility, Whole Brain Microscopy Facility, and the Moody Foundation Flow Cytometry Facility.


News Article | October 28, 2016
Site: www.eurekalert.org

DALLAS - Oct.28, 2016 - The distinct structures of toxic protein aggregates that form in degenerating brains determine which type of dementia will occur, which regions of brain will be affected, and how quickly the disease will spread, according to a study from the Peter O'Donnell Jr. Brain Institute. The research helps explain the diversity of dementias linked to tau protein aggregation, which destroys brain cells of patients with Alzheimer's and other neurodegenerative syndromes. The study also has implications for earlier and more accurate diagnoses of various dementias through definition of the unique forms of tau associated with each. "In addition to providing a framework to understand why patients develop different types of neurodegeneration, this work has promise for the development of drugs to treat specific neurodegenerative diseases, and for how to accurately diagnose them. The findings indicate that a one-size-fits-all strategy for therapy may not work, and that we have to approach clinical trials and drug development with an awareness of which forms of tau we are targeting," said study author Dr. Marc Diamond, founding Director of the Center for Alzheimer's and Neurodegenerative Diseases, and Professor of Neurology and Neurotherapeutics with the O'Donnell Brain Institute at UT Southwestern Medical Center. Researchers used special cell systems to replicate distinct tau aggregate conformations. These different forms of pathological tau were then inoculated into the brains of mice. Each form created different pathological patterns, recapitulating the variation that occurs in diseases such as Alzheimer's, frontotemporal dementias, and traumatic encephalopathy. The different forms of tau caused pathology that spread at different rates through the brain, and affected specific brain regions. This experiment demonstrated that the structure of pathological tau aggregates alone is sufficient to account for most if not all the variation seen in human neurodegenerative diseases that are linked to this protein. The finding, published in Neuron, could have a notable impact on widespread efforts at the O'Donnell Brain Institute and elsewhere to develop treatments that eliminate tau and other toxic proteins from the brains of dementia patients. "The challenge for us now is to figure out how to rapidly and efficiently determine the forms of tau that are present in individual patients, and simultaneously, to develop specific therapies. This work says that it should be possible to predict patterns of disease in patients and responses to therapy based on knowledge of tau aggregate structure," said Dr. Diamond, who holds the Distinguished Chair in Basic Brain Injury and Repair. Dr. Diamond's lab, at the forefront of many notable findings relating to tau, had previously determined that tau acts like a prion - an infectious protein that can self-replicate and spread like a virus through the brain. The lab has determined that tau protein in human brain can form many distinct strains, or self-replicating structures, and developed methods to reproduce them in the laboratory. This research led Dr. Diamond's team to the latest study to test whether these strains might account for different forms of dementia. To make this link, 18 distinct tau aggregate strains were replicated in the lab from human neurodegenerative disease brain samples, or were created from mouse models or other artificial sources. Researchers inoculated the strains into different brain regions of mice and found striking differences among them. While some strains had far reaching and rapid effects, others replicated only in limited parts of the brain, or caused widespread disease but did so very slowly. This surprising result answered a fundamental question that has dogged the field of neurodegenerative disease: Why are brain regions vulnerable in certain cases but not others, and why do some diseases progress more rapidly than others? For instance, in Alzheimer's disease, problems begin in brain memory centers before spreading to other areas that control functions such as language. Conversely, due to initial degeneration of frontal and temporal brain regions in frontotemporal dementia, the memory centers are relatively spared, and patients often first show changes in personality and behavior. The new study implies that with knowledge of tau aggregate structure in patients, or possibly even in healthy individuals, it should be possible to predict the brain regions most vulnerable to degeneration and the rate of disease progression. The study was funded by the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, National Institute on Aging, the Tau Consortium, and the Cure Alzheimer's Fund. At UT Southwestern the work was facilitated with help from the Neuro-Models Facility, Whole Brain Microscopy Facility, and the Moody Foundation Flow Cytometry Facility. DALLAS - Recent efforts to develop a treatment for Alzheimer's disease and other dementias have focused heavily on removing toxic proteins from the brain. Here's a look at the tau protein and what we know about its role in the progression of dementia. A. The tau protein is known to bind microtubules in neurons. These structures enable transport of cellular components. But the protein becomes toxic in patients with Alzheimer's and other dementias, forming aggregates that progressively accumulate and lead to loss of neuron function and eventually to neurodegeneration. Q. How does tau spread in Alzheimer's patients? A. When the tau protein begins to form aggregates, it is toxic to neurons. It is unknown how these aggregates can escape cells. They may be released from living cells, or they may rupture the cell after causing its death. Once outside of cells the aggregates can be taken up by nearby cells. Once inside, they cause normal tau to begin to aggregate, and the process repeats itself. Remarkably, tau aggregates, which are highly ordered assemblies, can have different structures that will be precisely replicated over time within cells. These structures are referred to as "strains." A new study from the Peter O'Donnell Jr. Brain Institute shows the three-dimensional structure of a tau aggregate will determine which neurons are vulnerable to it, how readily it will create more pathology, and how quickly it will spread throughout the brain. A. Although no cure has been found for Alzheimer's or other dementias, many researchers believe removing toxic tau aggregates can help slow or stop the deterioration of the brain. Consequently, this is now a focus of drug development for most of the major pharmaceutical companies. Amyloid beta is another protein that also builds up in the brains of patients with Alzheimer's disease, and is thought to cause the accumulation of tau. Many clinical trials are now underway to test the protective effects of drugs designed to prevent the accumulation of each protein. It is hoped that they will slow or prevent cognitive decline. Q. How can people prevent tau from turning toxic? A. Scientists aren't sure, but since there is not yet a specific therapy, many believe the best course is to reduce the risk factors for dementia, which include high blood pressure, cholesterol and a sedentary lifestyle. Studies have shown cardiovascular health somehow affects the brain and that healthy diet and regular exercise can reduce the incidence of toxic protein buildup. An ongoing national study led by the O'Donnell Brain Institute is testing the combination of cholesterol-lowering medication and exercise on preserving brain function. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. . To automatically receive news releases from UT Southwestern via email, subscribe at http://www.


PITTSBURGH--For as long as scientists have been listening in on the activity of the brain, they have been trying to understand the source of its noisy, apparently random, activity. In the past 20 years, "balanced network theory" has emerged to explain this apparent randomness through a balance of excitation and inhibition in recurrently coupled networks of neurons. A team of scientists has extended the balanced model to provide deep and testable predictions linking brain circuits to brain activity. Lead investigators at the University of Pittsburgh say the new model accurately explains experimental findings about the highly variable responses of neurons in the brains of living animals. On Oct. 31, their paper, "The spatial structure of correlated neuronal variability," was published online by the journal Nature Neuroscience. The new model provides a much richer understanding of how activity is coordinated between neurons in neural circuits. The model could be used in the future to discover neural "signatures" that predict brain activity associated with learning or disease, say the investigators. "Normally, brain activity appears highly random and variable most of the time, which looks like a weird way to compute," said Brent Doiron, associate professor of mathematics at Pitt, senior author on the paper, and a member of the University of Pittsburgh Brain Institute (UPBI). "To understand the mechanics of neural computation, you need to know how the dynamics of a neuronal network depends on the network's architecture, and this latest research brings us significantly closer to achieving this goal." Earlier versions of the balanced network theory captured how the timing and frequency of inputs--excitatory and inhibitory--shaped the emergence of variability in neural behavior, but these models used shortcuts that were biologically unrealistic, according to Doiron. "The original balanced model ignored the spatial dependence of wiring in the brain, but it has long been known that neuron pairs that are near one another have a higher likelihood of connecting than pairs that are separated by larger distances. Earlier models produced unrealistic behavior--either completely random activity that was unlike the brain or completely synchronized neural behavior, such as you would see in a deep seizure. You could produce nothing in between." In the context of this balance, neurons are in a constant state of tension. According to co-author Matthew Smith, assistant professor of ophthalmology at Pitt and a member of UPBI, "It's like balancing on one foot on your toes. If there are small overcorrections, the result is big fluctuations in neural firing, or communication." The new model accounts for temporal and spatial characteristics of neural networks and the correlations in the activity between neurons--whether firing in one neuron is correlated with firing in another. The model is such a substantial improvement that the scientists could use it to predict the behavior of living neurons examined in the area of the brain that processes the visual world. After developing the model, the scientists examined data from the living visual cortex and found that their model accurately predicted the behavior of neurons based on how far apart they were. The activity of nearby neuron pairs was strongly correlated. At an intermediate distance, pairs of neurons were anticorrelated (When one responded more, the other responded less.), and at greater distances still they were independent. "This model will help us to better understand how the brain computes information because it's a big step forward in describing how network structure determines network variability," said Doiron. "Any serious theory of brain computation must take into account the noise in the code. A shift in neuronal variability accompanies important cognitive functions, such as attention and learning, as well as being a signature of devastating pathologies like Parkinson's disease and epilepsy." While the scientists examined the visual cortex, they believe their model could be used to predict activity in other parts of the brain, such as areas that process auditory or olfactory cues, for example. And they believe that the model generalizes to the brains of all mammals. In fact, the team found that a neural signature predicted by their model appeared in the visual cortex of living mice studied by another team of investigators. "A hallmark of the computational approach that Doiron and Smith are taking is that its goal is to infer general principles of brain function that can be broadly applied to many scenarios. Remarkably, we still don't have things like the laws of gravity for understanding the brain, but this is an important step for providing good theories in neuroscience that will allow us to make sense of the explosion of new experimental data that can now be collected," said Nathan Urban, associate director of UPBI. In addition to Doiron and Smith, Jonathan Rubin, professor of mathematics at Pitt; Robert Rosenbaum, a former postdoctoral scholar at Pitt and now an assistant professor at the University of Notre Dame; and Adam Kohn from the Albert Einstein College of Medicine contributed to this work. The research was funded by National Science Foundation grants awarded as part of the federal BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative. Additional support was provided by the National Eye Institute, Research to Prevent Blindness, the Eye and Ear Foundation of Pittsburgh, and the Simons Foundation. With more than 150 faculty members, the University of Pittsburgh Brain Institute seeks to unlock the mysteries of normal and abnormal brain function and then translate discoveries into new approaches for overcoming brain disorders. The institute employs multiple levels of analysis, from molecular and cellular approaches to whole systems and behavioral analysis, and incorporates research across disciplines including neuroscience, bioengineering, computer science, and robotics.


News Article | October 26, 2016
Site: www.eurekalert.org

DALLAS - Oct.24, 2016 - Carol White can't help but worry when she misplaces keys or can't recall a name ever since relatives have been diagnosed with early onset Alzheimer's. "I live with the possibility Alzheimer's might also touch my life," she said. "You just take a deep breath and wonder." But the 69-year-old doesn't plan to sit around waiting to find out. She's joined a study at the UT Southwestern Peter O'Donnell Jr. Brain Institute to determine whether regular aerobic exercise and taking specific medications to reduce high blood pressure and cholesterol levels can help preserve brain function. "There is plenty of evidence to suggest that what is bad for your cardiovascular system is bad for your brain, but the body is one machine and you cannot separate the heart from the brain," said Dr. Rong Zhang, Associate Professor of Neurology and Neurotherapeutics at UT Southwestern Medical Center. Dr. Zhang is Principal Investigator for the 5-year study being carried out at six medical centers around the nation. They plan to enroll more than 600 older adults at high risk to develop Alzheimer's disease and measure whether certain interventions can be linked to slower brain decline. Participants will take part in regular aerobic exercise and take specific medications to reduce high blood pressure and cholesterol levels. Information on this study is available on the rrAD trail website or contact Tammy Lewis at 214-345-4665 or ieembrain@texashealth.org">ieembrain@texashealth.org. Other trial sites include Texas Health Resources in Dallas, the University of Kansas Medical Center, Washington University School of Medicine, Pennington Biomedical Research Center at Louisiana State University, and Michigan State University. There is compelling evidence that hypertension is linked to development of dementia later in life, according to a statement from the American Heart Association issued earlier this month. But more data are needed to determine whether treating high blood pressure can preserve the brain's function. Doctors also need to know what kind of exercise or which medications or blood pressure levels will benefit at-risk patients the most. "That's the point of this study. People are looking for a silver bullet to stop the disease. But Alzheimer's is a multi-factorial disease. You have to do A, B, C, and D together, which will hopefully make the difference," said Dr. Zhang, Director of the Cerebrovascular Laboratory in the Institute for Exercise and Environmental Medicine (IEEM) at Texas Health Presbyterian Hospital Dallas, where the Dallas arm of the study will be carried out. The IEEM, a joint program between Texas Health Presbyterian Hospital Dallas and UT Southwestern, is among the most sophisticated human physiology laboratories in the world. Researchers there are working to find treatments and contribute to the development of cures for many of society's most debilitating and chronic diseases, including hypertension, diabetes, congestive heart failure, Alzheimer's disease, Obstructive Sleep Apnea (OSA), and obesity. This new study builds upon prior research linking healthy lifestyles to better brain function. That includes a 2013 study from Dr. Zhang's team that found neuronal messages are more efficiently relayed in brains of older adults who exercise, and a recent UCLA study that found a healthy diet and regular exercise can reduce the incidence of toxic protein buildup associated with Alzheimer's. Other teams at the O'Donnell Brain Institute are designing tests for the early detection of patients who will develop dementia, and seeking methods to slow or stop the spread of toxic proteins associated with the disease such as beta-amyloid and tau, which are blamed for destroying certain groups of neurons in the brain. In the current study, supported by funding from the National Institutes on Aging, researchers will measure the effectiveness of various combinations of intervention in four groups of participants, including those who receive both aerobic training and medication that aggressively targets cardiovascular risks, and others that only receive some or none of these interventions. Researchers will watch for changes in the participants' memory and other functions using cognitive testing and MRIs that will monitor brain cell communication and blood flow, which is important for prevention of any buildup of toxic proteins. They will also measure brain volume and other factors to help them assess which combinations of interventions are most effective in slowing the decline in brain function. Ms. White was the first to sign up. "I'm just interested in doing anything that I can that might help in some small way to find a cure," said Ms. White, who does government and public affairs contract work in the Dallas area. "It's not a pleasant thing to see your relatives go through." Join the Friends of the Alzheimer's Disease Center for "From Astronauts to Alzheimer's Disease: How Understanding the Heart-Brain Connection May Prevent Cognitive Impairment," presented by Benjamin Levine, M.D., and Rong Zhang, Ph.D. Seating is limited for this free public event. RSVP today at rsvp@utsouthwestern.edu or call 214-648-2344.


News Article | November 2, 2016
Site: www.eurekalert.org

DALLAS - November 2, 2016 - Researchers have identified the first two core genes that regulate the amount of deep sleep and dreaming, a key development they believe will lead to the discovery of a network of related genes controlling sleep. The study from the Peter O'Donnell Jr. Brain Institute demonstrates in mice that a single gene controls the amount of non-REM (rapid eye movement) sleep, which includes deep sleep. A second gene controls the amount or need for REM sleep, associated with vivid dreaming. The findings provide a critical molecular entry point to explain how sleep works and to identify potential targets to better treat sleep disorders. "This research is just the beginning. We believe that these two genes are the first of many that regulate sleep," said study co-author Dr. Joseph S. Takahashi, Chairman of Neuroscience with the O'Donnell Brain Institute at UT Southwestern Medical Center and Investigator in the Howard Hughes Medical Institute. Previous research has identified genes that regulate the switch between wakefulness and sleep. But until this latest study in Nature, scientists have not known what mechanisms control the drive or need for non-REM sleep, nor the amount of REM sleep. To find out, researchers used a forward-genetic approach in which they screened for sleep disorders in 8,000 mice using electroencephalogy (EEG) to monitor brain waves. They found two distinct pedigrees of note: Researchers introduced these same mutations into normal mice and saw their sleep behaviors change accordingly. "We hope this is the entry door to the black box that explains how our sleep is regulated," said the senior co-author Dr. Masashi Yanagisawa, an Adjunct Professor of Molecular Genetics at UT Southwestern and former HHMI Investigator. He now directs the International Institute for Integrative Sleep Medicine (IIIS) at the University of Tsukuba in Japan, where most of the mice were screened. Normal sleep patterns include short durations of REM sleep surrounded by longer stretches of non-REM sleep and account for about a quarter of a night's rest in most young adults. Many forms of sleep disorder distort these patterns. Because the Sik3 and Nalcn genes have just been identified, no evidence yet exists to link them directly to known sleep disturbances in humans. However, while the role and importance of REM sleep remains a point of debate, many scientists agree this stage of rest is involved in the formation of emotional memories and coping with negative experiences. Thus, a lack of REM sleep may contribute to conditions such as posttraumatic stress disorder (PTSD). "At least in theory, this study opens up future possibilities to create new sleep-regulating drugs, but doing so will occur in the distant future," said Dr. Yanagisawa, noting that the proteins produced by Sik3 and Nalcn could possibly be molecular targets for new medicines. Dr. Takahashi used a forward-genetic approach two decades ago to make a landmark discovery of the Clock gene that regulates the body's biological clock. The finding led his team to discover a network of more than 20 other related genes. Dr. Takahashi said he expects the screen for sleep genes will lead to more genes, forming perhaps a much larger group than the clock genes because sleep affects more parts of the brain. What's unclear is how big a part the other genes in that network play in regulating sleep. The Takahashi lab found that only a handful of the clock genes have a crucial role in the larger network. "If the same is true for sleep, this is going to be a simplifying, illuminating discovery," said Dr. Takahashi, holder of the Loyd B. Sands Distinguished Chair in Neuroscience and 2016 recipient of the Peter Farrell Prize in Sleep Medicine. Dr. Takahashi said he had wanted to conduct such a genetic screen for sleep mutants for many years but had to overcome logistical issues to conduct a large-scale effort. Most mouse studies involve no more than a few dozen animals, but Dr. Yanagisawa rapidly scaled up and optimized his lab's ability to screen large numbers of mice initially at UT Southwestern and now at his institute in Japan. "To be able to screen 8,000 mice is something that most people would say is too much work," said Dr. Takahashi, explaining that each mouse had to be surgically wired for the EEG readings, among other steps. "Technically, this project was very challenging." About UT Southwestern Medical Center UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. . To automatically receive news releases from UT Southwestern via email, subscribe at http://www. A study from the Peter O'Donnell Jr. Brain Institute has identified the first two core genes that regulate the amount of deep sleep and dreaming. While normal sleep patterns include short durations of rapid eye movement (REM) sleep surrounded by longer stretches of non-REM sleep, the study published in Nature demonstrates how one gene can alter these patterns. Here's a look at the stages of sleep: REM: Rapid eye movement sleep, associated with vivid dreaming. Brain waves are similar to those experienced during wakefulness. Breathing, heart rate and blood pressure increase. Muscles become paralyzed, protecting the person from acting out dreams. Person is more likely to wake from REM than non-REM sleep, though the awakenings usually last only a few seconds. While the role and importance of REM sleep remains a point of debate, many scientists agree it is involved in the formation of emotional memories and coping with negative experiences. Stage 1: Between wakefulness and sleep. The heart rate begins to slow and breathing becomes regular. Dreaming is relatively rare. The person may be aware of sounds and may have quick body jerks. If awakened, the person will often believe they were not asleep. Brain waves begin to transition from beta/gamma to slower alpha waves, then theta waves. Stage 2: Muscle activity decreases and awareness of outside sounds recedes. Sigma waves, or sleep spindles, provide short bursts of brain activity that combine with other low and high voltage peaks. These protect the person's sleeping state from outside disruptions and help with processing memory and other information. The person passes through this stage several times each night, usually accounting for about half the total sleep. Stage 3: Deep sleep. The person is completely removed from outside stimuli and will feel groggy if awakened. Heart rate, breathing and blood pressure are at their lowest levels. Dreaming is more common at this stage than other non-REM stages, though not as common as during REM sleep. Like in stage 2, memory and information processing occur during this stage. Sleep walking or talking may also occur.


News Article | November 2, 2016
Site: www.sciencedaily.com

For as long as scientists have been listening in on the activity of the brain, they have been trying to understand the source of its noisy, apparently random, activity. In the past 20 years, "balanced network theory" has emerged to explain this apparent randomness through a balance of excitation and inhibition in recurrently coupled networks of neurons. A team of scientists has extended the balanced model to provide deep and testable predictions linking brain circuits to brain activity. Lead investigators at the University of Pittsburgh say the new model accurately explains experimental findings about the highly variable responses of neurons in the brains of living animals. On Oct. 31, their paper, "The spatial structure of correlated neuronal variability," was published online by the journal Nature Neuroscience. The new model provides a much richer understanding of how activity is coordinated between neurons in neural circuits. The model could be used in the future to discover neural "signatures" that predict brain activity associated with learning or disease, say the investigators. "Normally, brain activity appears highly random and variable most of the time, which looks like a weird way to compute," said Brent Doiron, associate professor of mathematics at Pitt, senior author on the paper, and a member of the University of Pittsburgh Brain Institute (UPBI). "To understand the mechanics of neural computation, you need to know how the dynamics of a neuronal network depends on the network's architecture, and this latest research brings us significantly closer to achieving this goal." Earlier versions of the balanced network theory captured how the timing and frequency of inputs -- excitatory and inhibitory -- shaped the emergence of variability in neural behavior, but these models used shortcuts that were biologically unrealistic, according to Doiron. "The original balanced model ignored the spatial dependence of wiring in the brain, but it has long been known that neuron pairs that are near one another have a higher likelihood of connecting than pairs that are separated by larger distances. Earlier models produced unrealistic behavior -- either completely random activity that was unlike the brain or completely synchronized neural behavior, such as you would see in a deep seizure. You could produce nothing in between." In the context of this balance, neurons are in a constant state of tension. According to co-author Matthew Smith, assistant professor of ophthalmology at Pitt and a member of UPBI, "It's like balancing on one foot on your toes. If there are small overcorrections, the result is big fluctuations in neural firing, or communication." The new model accounts for temporal and spatial characteristics of neural networks and the correlations in the activity between neurons -- whether firing in one neuron is correlated with firing in another. The model is such a substantial improvement that the scientists could use it to predict the behavior of living neurons examined in the area of the brain that processes the visual world. After developing the model, the scientists examined data from the living visual cortex and found that their model accurately predicted the behavior of neurons based on how far apart they were. The activity of nearby neuron pairs was strongly correlated. At an intermediate distance, pairs of neurons were anticorrelated (When one responded more, the other responded less.), and at greater distances still they were independent. "This model will help us to better understand how the brain computes information because it's a big step forward in describing how network structure determines network variability," said Doiron. "Any serious theory of brain computation must take into account the noise in the code. A shift in neuronal variability accompanies important cognitive functions, such as attention and learning, as well as being a signature of devastating pathologies like Parkinson's disease and epilepsy." While the scientists examined the visual cortex, they believe their model could be used to predict activity in other parts of the brain, such as areas that process auditory or olfactory cues, for example. And they believe that the model generalizes to the brains of all mammals. In fact, the team found that a neural signature predicted by their model appeared in the visual cortex of living mice studied by another team of investigators. "A hallmark of the computational approach that Doiron and Smith are taking is that its goal is to infer general principles of brain function that can be broadly applied to many scenarios. Remarkably, we still don't have things like the laws of gravity for understanding the brain, but this is an important step for providing good theories in neuroscience that will allow us to make sense of the explosion of new experimental data that can now be collected," said Nathan Urban, associate director of UPBI.

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