Posts tagged science

Posts tagged science
Brain Scans Show We Take Risks Because We Can’t Stop Ourselves
A new study correlating brain activity with how people make decisions suggests that when individuals engage in risky behavior, such as drunk driving or unsafe sex, it’s probably not because their brains’ desire systems are too active, but because their self-control systems are not active enough.
This might have implications for how health experts treat mental illness and addiction or how the legal system assesses a criminal’s likelihood of committing another crime.
Researchers from The University of Texas at Austin, UCLA and elsewhere analyzed data from 108 subjects who sat in a magnetic resonance imaging (MRI) scanner — a machine that allows researchers to pinpoint brain activity in vivid, three-dimensional images — while playing a video game that simulates risk-taking.
The researchers used specialized software to look for patterns of activity across the whole brain that preceded a person’s making a risky choice or a safe choice in one set of subjects. Then they asked the software to predict what other subjects would choose during the game based solely on their brain activity. The software accurately predicted people’s choices 71 percent of the time.
“These patterns are reliable enough that not only can we predict what will happen in an additional test on the same person, but on people we haven’t seen before,” said Russell Poldrack, director of UT Austin’s Imaging Research Center and professor of psychology and neuroscience.
When the researchers trained their software on much smaller regions of the brain, they found that just analyzing the regions typically involved in executive functions such as control, working memory and attention was enough to predict a person’s future choices. Therefore, the researchers concluded, when we make risky choices, it is primarily because of the failure of our control systems to stop us.
“We all have these desires, but whether we act on them is a function of control,” said Sarah Helfinstein, a postdoctoral researcher at UT Austin and lead author of the study that appears online this week in the journal Proceedings of the National Academy of Sciences.
Helfinstein said that additional research could focus on how external factors, such as peer pressure, lack of sleep or hunger, weaken the activity of our brains’ control systems when we contemplate risky decisions.
“If we can figure out the factors in the world that influence the brain, we can draw conclusions about what actions are best at helping people resist risks,” said Helfinstein.
To simulate features of real-world risk-taking, the researchers used a video game called the Balloon Analogue Risk Task (BART) that past research has shown correlates well with self-reported risk-taking such as drug and alcohol use, smoking, gambling, driving without a seatbelt, stealing and engaging in unprotected sex.
While playing the BART, the subject sees a balloon on the screen and is asked to make either a risky choice (inflate the balloon a little and earn a few cents) or a safe choice (stop the round and “cash out,” keeping whatever money was earned up to that point). Sometimes inflating the balloon causes it to burst and the player loses all the cash earned from that round. After each successful balloon inflation, the game continues with the chance of earning another standard-sized reward or losing an increasingly large amount. Many health-relevant risky decisions share this same structure, such as when deciding how many alcoholic beverages to drink before driving home or how much one can experiment with drugs or cigarettes before developing an addiction.
The data for this study came from the Consortium for Neuropsychiatric Phenomics at UCLA, which recruited adults from the Los Angeles area for researchers to examine differences in response inhibition and working memory between healthy adults and patients diagnosed with bipolar disorder, schizophrenia, or adult attention deficit hyperactivity disorder (ADHD). Only data collected from healthy participants were included in the present analyses.

Image caption: Stem cells in the cortex of a mouse embryo (cell nuclei: blue). © MPI f. Molecular Cell Biology and Genetics/ D. Stenzel
Brain development - the pivotal role of the stem cell environment
Higher mammals, such as humans, have markedly larger brains than other mammals. Scientists from the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden recently discovered a new mechanism governing brain stem cell proliferation. It serves to boost the production of neurons during development, thus causing the enlargement of the cerebral cortex – the part of the brain that enables us humans to speak, think and dream. The surprising discovery made by the Dresden-based researchers: two components in the stem cell environment – the extracellular matrix and thyroid hormones – work together with a protein molecule found on the stem cell surface, a so-called integrin. This likely explains why iodine deficiency in pregnant women has disastrous consequences for the unborn child, affecting its brain development adversely – without iodine, no thyroid hormones are produced. “Our study highlights this relationship and provides a potential explanation for the condition neurologists refer to as cretinism”, says Wieland Huttner, Director at the Max Planck Institute in Dresden. This neurological disorder severely impairs the mental abilities of a person.
In the course of evolution, certain mammals, notably humans, have developed larger brains than others, and therefore more advanced cognitive abilities. Mice, for example, have brains that are around a thousand times smaller than the human one. In their study, which was conducted in cooperation with the Fritz Lipmann Institute in Jena, the researchers in Dresden wanted to identify factors that determine brain development, and understand how larger brains have evolved.
A cosy bed for brain stem cells
Brain neurons are generated from stem cells called basal progenitors that are able to proliferate in humans, but not in mice. In humans, basal progenitors are surrounded by a special environment, a so-called extracellular matrix (ECM), which is produced by the progenitors themselves. Like a cosy bed, it accommodates the proliferating cells. Mice lack such ECM, which means that they generate fewer neurons and have a smaller brain.
The scientists therefore conducted tests to see whether in mice, basal progenitors start to proliferate if a comparable cell environment is simulated. The result: “We simulated an extracellular matrix for the brain stem cells using a stimulating antibody. This antibody activates an integrin on the cell surface of basal progenitors and thus stimulates their proliferation”, explains Denise Stenzel, who headed the experiments.
Because a requirement of thyroid hormones for proper brain development was previously known, the researchers blocked the production of these hormones in pregnant rats to see if their absence would inhibit basal progenitor proliferation in the embryos. Indeed, fewer progenitors and, consequently, neurons were produced, likely explaining the abnormal brain development in the absence of thyroid hormones. When the action of these hormones on the integrin was blocked, the ECM-simulating antibody alone was no longer able to induce basal progenitor proliferation.
A combination of ECM and thyroid hormones thus appears necessary for basal progenitors to proliferate and produce enough neurons for brain development. Human brain stem cells produce the suitable environment naturally. “That is probably how, in the course of evolution, we humans developed larger brains”, says Wieland Huttner, summing up the study. The research produced another important finding: “We were able to explain the role of iodine in embryonic brain development at the cellular level”, says Denise Stenzel. Iodine is essential for the production of thyroid hormones, and an iodine deficiency in pregnant women is known to have adverse effects on the brain development of the unborn child.
Studies have shown that certain pesticides can increase people’s risk of developing Parkinson’s disease. Now, UCLA researchers have found that the strength of that risk depends on an individual’s genetic makeup, which, in the most pesticide-exposed populations, could increase a person’s chance of developing the debilitating disease two- to six-fold.

In an earlier study, published January 2013 in Proceedings of the National Academy of Sciences, the UCLA team discovered a link between Parkinson’s and the pesticide benomyl, a fungicide that has been banned by the U.S. Environmental Protection Agency. That study found that benomyl prevents the enzyme aldehyde dehydrogenase (ALDH) from converting aldehydes — organic compounds that are highly toxic to dopamine cells in the brain — into less toxic agents, thereby contributing to the risk of Parkinson’s.
For the current study, UCLA researchers tested a number of additional pesticides and found 11 that also inhibit ALDH and increase the risk of Parkinson’s — and at levels much lower than they are currently being used, said the study’s lead author, Jeff Bronstein, a professor of neurology and director of the movement disorders program at UCLA.
Bronstein said the team also found that people with a common genetic variant of the ALDH2 gene are particularly sensitive to the effects of ALDH-inhibiting pesticides and are two to six times more likely to develop Parkinson’s when exposed to these pesticides than those without the variant.
The results of the new epidemiological study appear Feb. 5 in the online issue of Neurology, the medical journal of the American Academy of Neurology.
"We were very surprised that so many pesticides inhibited ALDH and at quite low concentrations — concentrations that were way below what was needed for the pesticides to do their job," Bronstein said. "These pesticides are pretty ubiquitous and can be found on our food supply. They are used in parks and golf courses and in pest control inside buildings and homes. So this significantly broadens the number of people at risk."
The study compared 360 patients with Parkinson’s disease in three agriculture-heavy Central California counties and 816 people from the same area who did not have Parkinson’s. The researchers focused their analyses on individuals with ambient exposures to pesticides at work and at home, using information from the California Department of Pesticide Regulation.
In the previous PNAS study, Bronstein and his team had determined the mechanism that leads to increased risk. Exposure to pesticides starts a cascade of cellular events, preventing ALDH from keeping a lid on the aldehyde DOPAL, a toxin that naturally occurs in the brain. When ALDH does not detoxify DOPAL sufficiently, it accumulates, damages neurons and increases an individual’s risk of developing Parkinson’s.
"ALDH inhibition appears to be an important mechanism by which these environmental toxins contribute to Parkinson’s pathogenesis, especially in genetically vulnerable individuals," said study author Beate Ritz, a professor of epidemiology at UCLA’s Fielding School of Public Health. "This suggests several potential interventions to reduce Parkinson’s occurrence or to slow its progression."
In the current study, the research team developed a lab test to determine which pesticides inhibited ALDH. They then found that those participants in the epidemiologic study who had a genetic variant in the ALDH gene were at increased risk of Parkinson’s when exposed to these pesticides. Just having the variant alone, however, did not increase risk of the disease, Bronstein noted.
"This report provides evidence for the relevance of ALDH inhibition in Parkinson’s disease pathogenesis, identifies pesticides that should be avoided to reduce the risk of developing Parkinson’s disease and suggests that therapies modulating ALDH enzyme activity or otherwise eliminating toxic aldehydes should be developed and tested to potentially reduce Parkinson’s disease occurrence or slow its progression, particularly for patients exposed to pesticides," the study states.
(Source: newsroom.ucla.edu)

Blue light may fight fatigue around the clock
Researchers from Brigham and Women’s Hospital (BWH) have found that exposure to short wavelength, or blue light, during the biological day directly and immediately improves alertness and performance. These findings are published in the February issue of Sleep.
"Our previous research has shown that blue light is able to improve alertness during the night, but our new data demonstrates that these effects also extend to daytime light exposure," said Shadab Rahman, PhD, a researcher in BWH’s Division of Sleep Medicine and lead author of this study. "These findings demonstrate that prolonged blue light exposure during the day has an an alerting effect."
In order to determine which wavelengths of light were most effective in warding off fatigue, the BWH researchers teamed with George Brainard, PhD, a professor of neurology at Thomas Jefferson University, who developed the specialized light equipment used in the study. Researcherscompared the effects of blue light with exposure to an equal amount of green light on alertness and performance in 16 study participants for 6.5 hours over a day. Participants then rated how sleepy they felt, had their reaction times measured and wore electrodes to assess changes in brain activity patterns during the light exposure.
The researchers found that participants exposed to blue light consistently rated themselves as less sleepy, had quicker reaction times and fewer lapses of attention during the performance tests compared to those who were exposed to green light. They also showed changes in brain activity patterns that indicated a more alert state.
"These results contribute to our understanding of how light impacts the brain and open up a new range of possibilities for using light to improve human alertness, productivity and safety," explained Steven Lockley, PhD, neuroscientist at BWH and senior investigator of the study. "While helping to improve alertness in night workers has obvious safety benefits, day shift workers may also benefit from better quality lighting that would not only help them see better but also make them more alert."
Researchers note that the next big challenge is to figure out how to deliver better lighting. While natural light is ideal, many people do not have access to daylight in their schools, homes or work places. In addition to improvements in daylight access, the advent of new, more controllable lighting technologies may help enable researchers to develop ‘smart’ lighting systems designed to maximize the beneficial effects of light for human health, productivity and safety.
In the brain, the number of neurons in a network may not matter
Last spring, President Obama established the federal BRAIN Initiative to give scientists the tools they need to get a dynamic picture of the brain in action.
To do so, the initiative’s architects envision simultaneously recording the activity of complete neural networks that consist of thousands or even millions of neurons. However, a new study indicates that it may be possible to accurately characterize these networks by recording the activity of properly selected samples of 50 neurons or less – an alternative that is much easier to realize.
The study was performed by a team of cognitive neuroscientists at Vanderbilt University and reported in a paper published the week of Feb. 3 in the online Early Edition of the Proceedings of the National Academy of Sciences.
The paper describes the results of an ambitious computer simulation that the team designed to understand the behavior of the networks of hundreds of thousands of neurons that initiate different body movements: specifically, how the neurons are coordinated to trigger a movement at a particular point in time, called the response time.
The researchers were surprised to discover that the range of response times produced by the simulated population of neurons did not change with size: A network of 50 simulated neurons responded with the same speed as a network with 1,000 neurons.
For decades, response time has been a core measurement in psychology. “Psychologists have developed powerful models of human responses that explain the variation of response time based on the concept of single accumulators,” said Centennial Professor of Psychology Gordon Logan. In this model, the brain acts as an accumulator that integrates incoming information related to a given task and produces a movement when the amount of information reaches a preset threshold. The model explains random variations in response times by how quickly the brain accumulates the information it needs to act.
Meanwhile, neuroscientists have related response time to measurements of single neurons. “Twenty years ago we discovered that the activity of particular neurons resembles the accumulators of psychology models. We haven’t understood until now how large numbers of these neurons can act collectively to initiate movements,” said Ingram Professor of Neuroscience Jeffrey Schall.
No one really knows the size of the neural networks involved in initiating movements, but researchers estimated that about 100,000 neurons are involved in launching a simple eye movement.
“One of the main questions we addressed is how ensembles of 100,000 neuron accumulators can produce behavior that is also explained by a single accumulator,” Schall said.
“The way that the response time of these ensembles varies with ensemble size clearly depends on the ‘stopping rules’ that they follow,” explained co-author Thomas Palmeri, associate professor of psychology. For example, if an ensemble doesn’t respond until all of its member neurons have accumulated enough activity, then its response time would be slower for larger networks. On the other hand, if the response time is determined by the first neurons that react, then the response time in larger networks would be shorter than those of smaller networks.
Another important factor is the degree to which the ensemble is coordinated. “The more the ensemble is coordinated, the more the collective resembles a single accumulator. What has been unknown is how much coordination is necessary for the ensemble to act in unison, ” said Bram Zandbelt, a post-doctoral fellow and lead author on the paper.
To address this problem, the researchers developed a new type of computer simulation, one that models the collective behavior of different numbers of accumulators given different amounts of variation in the rates of accumulation. The simulation took a tremendous amount of computer power. Even using Vanderbilt’s in-house supercomputer at the Advanced Computing Center for Research & Education, Zandbelt was limited to modeling networks containing 1,000 neurons.
The researchers found that the networks did not produce realistic response times if responses were initiated when only a few or almost all of the simulated neurons finished accumulating, or if the simulated neurons had very different accumulation rates. However, the networks produced realistic response times over a broad range of stopping rules and similarity in accumulation rates, showing that within these broad constraints, size doesn’t matter. “We were surprised to discover that the networks behaved with a remarkable uniformity except under extreme assumptions,” said Schall.
“As far as the response time goes, the bottom line is that we found that the size of the neural network doesn’t matter under a large set of conditions. If this is true for networks ranging from 10 to 1,000 neurons, it should also hold for networks of 10,000 to 100,000 neurons,” Palmeri said.
In many people with autism and other neurodevelopmental disorders, different parts of the brain don’t talk to each other very well. Scientists have now identified, for the first time, a way in which this decreased functional connectivity can come about. In a study published online today in Nature Neuroscience, scientists at the European Molecular Biology Laboratory (EMBL) in Monterotondo, Italy, and collaborators at the Istituto Italiano di Tecnologia (IIT), in Rovereto, and La Sapienza University in Rome, demonstrate that it can be caused by cells called microglia failing to trim connections between neurons.
“We show that a deficit in microglia during development can have widespread and long-lasting effects on brain wiring and behaviour,” says Cornelius Gross, who led the study. “It leads to weak brain connectivity, decreased social behaviour, and increased repetitive behaviour, all hallmarks of autism.”
The findings indicate that, by trimming surplus connections in the developing brain, microglia allow the remaining links to grow stronger, like high-speed fibre-optic cables carrying strong signals between brain regions. But if these cells fail to do their job at that crucial stage of development, those brain regions are left with a weaker communication network, which in turn has lifelong effects on behaviour.
Yang Zhan, a postdoctoral fellow in Gross’ lab at EMBL, analysed the strength of connections between different areas of brain in mice that were genetically engineered to have fewer microglia during development. Working with Alessandro Gozzi’s lab at IIT and Davide Ragozzino at La Sapienza University, the EMBL scientists combined this approach with high-resolution fMRI (functional Magnetic Resonance Imaging) scans of the mice’s brains, taking full advantage of a novel technique developed at IIT, which enables scientists to obtain detailed, three-dimensional maps of the brain’s functional connections. The team found that mice with fewer microglia had weaker connections between neurons, and less cross-talk between different brain regions. When Rosa Paolicelli, a PhD student in Gross’ lab, studied the mice’s behaviour, she discovered that mice with fewer microglia and decreased connectivity displayed behaviours commonly associated with autism spectrum disorders. These mice spent more time repeatedly grooming themselves, and avoided social interactions.
“This is an exciting time to be studying microglia,” Gross concludes: “they’re turning out to be major players in how our brain gets wired up.”
University of Queensland researchers have made a surprise discovery about how the brain plans movement that may lead to more targeted treatments for patients with Parkinson’s disease.

The discovery was made by UQ’s Queensland Brain Institute (QBI) researcher Professor Pankaj Sah in collaboration with neurologist Professor Peter Silburn and neurosurgeon Associate Professor Terry Coyne from the UQ Centre for Clinical Research.
Professor Sah said the team examined the brains of 10 patients with Parkinson’s disease while the patients were awake during deep brain stimulation surgery, and found more than one part of the brain is responsible for planning movement.
“This study aimed to improve understanding of how different parts of the brain are involved in planning movement and controlling gait,” Professor Sah said.
The team was particularly interested in a part of the brain stem known as the pedunculopontine nucleus (PPN), which lies in the deepest part of the brain.
The PPN has previously been targeted as a treatment point for people with advanced Parkinson’s disease who are unable to walk.
“To date, we have known that walking is generally controlled by the outer part of the brain known as the cortex,” Professor Sah said.
“When you decide to walk, the cortex sends signals to your brain stem which in turn signals the spinal cord to initiate movement.
“We have also known that neurons in the PPN are activated during limb movement, but our study has shown they were also activated when patients were simply thinking about walking.
“This is a complete surprise, because general thinking has been that movement planning takes place in the cortex, but this study indicates it might be happening in the brain stem as well.”
Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting more than six million people globally, and about 1 in 350 Australians.
Professor Sah said improved understanding of how the brain plans movement could lead to more targeted treatments for people with Parkinson’s.
“The cells involved in these networks seem to be one type of cell, so when thinking about drug treatments for Parkinson’s, maybe we should be targeting these cells,” Professor Sah said.
All the patients treated with deep brain stimulation also recorded positive outcomes with improvements with gait, highlighting the importance of neuroscientists working with clinicians.
Findings of the research are published in the Nature Neuroscience journal.
(Source: uq.edu.au)

Stanford researchers may have solved a riddle about the inner workings of the brain, which consists of billions of neurons, organized into many different regions, with each region primarily responsible for different tasks.
The various regions of the brain often work independently, relying on the neurons inside that region to do their work. At other times, however, two regions must cooperate to accomplish the task at hand. The riddle is this: what mechanism allows two brain regions to communicate when they need to cooperate yet avoid interfering with one another when they must work alone?
In a paper published today in Nature Neuroscience, a team led by Stanford electrical engineering professor Krishna Shenoy reveals a previously unknown process that helps two brain regions cooperate when joint action is required to perform a task.
“This is among the first mechanisms reported in the literature for letting brain areas process information continuously but only communicate what they need to,” said Matthew T. Kaufman, who was a postdoctoral scholar in the Shenoy lab when he co-authored the paper.
(Source: engineering.stanford.edu)

Your Brain Is Fine-Tuning Its Wiring Throughout Your Life
The white matter microstructure, the communication pathways of the brain, continues to develop/mature as one ages. Studies link age-related differences in white matter microstructure to specific cognitive abilities in childhood and adulthood.
Most prior studies, however, did not include individuals from the entire life span or evaluated a limited section of white matter tracts. This knowledge gap prompted a new study published this week in Biological Psychiatry.
Dr. Bart Peters, of the Zucker Hillside Hospital, and his colleagues investigated the relationship of age and neurocognitive performance to nine white matter tracts from childhood to late adulthood.
To accomplish this, they recruited 296 healthy volunteers who ranged from 8 to 68 years of age. The participants completed a comprehensive battery of tests designed to measure their cognitive functioning, including speed, attention, memory, and learning. They also underwent a non-invasive diffusion tensor imaging scan, a technology that allowed the researchers to create maps of the 9 major white matter tracts under investigation.
The combination of this data allowed them to identify the neurocognitive correlates of each white matter tract in relation to its unique aging pattern.
They found that, from childhood into early adulthood, differences in fractional anisotropy – a measure of connectivity – of the cingulum were associated with executive functioning, whereas fractional anisotropy of the inferior fronto-occipital fasciculus was associated with visual learning and global cognitive performance via speed of processing.
"Our study identified key brain circuits that develop during adolescence and young adulthood that are associated with the growth of learning, memory and planning abilities. These findings suggest that young people may not have full capacity of these functions until these connections have completed their normal trajectory of maturation beyond adolescence," explained Peters.
"Our brain is changing throughout our lives. These changes underlie the capacities that emerge and are refined through adulthood," commented Dr. John Krystal, Editor of Biological Psychiatry. “There are clues that the steps that we take to preserve our medical health and stimulate our minds also serve to further refine and maintain these connections. For good reasons, attending to brain health is increasingly a focus of healthy aging.”
In addition, many individuals diagnosed with psychiatric disorders suffer with neurocognitive dysfunction as part of their illness, which is particularly difficult to alleviate with currently available treatments. Studies such as this may help to identify specific brain circuits/pathways that could serve as potential targets for treatment interventions.
Drugs that modify DNA structure may be beneficial for treating Alzheimer’s Disease
In a study published this week in Nature Neuroscience, Bess Frost, PhD, and co-authors, identify abnormal expression of genes, resulting from DNA relaxation, that can be detected in the brain and blood of Alzheimer’s patients.
The protein tau is involved in a number of neurodegenerative disorders, including Alzheimer’s disease. Previous studies have implicated DNA damage as a cause of neuron, or cell, death in Alzheimer’s patients. Given that DNA damage can change the structure of DNA within cells, the researchers examined changes in DNA structure in tau-induced neurodegeneration. They used transgenic flies and mice expressing human tau to show that DNA is more relaxed in tauopathy. They then identified that the relaxation of tightly wound DNA and resulting abnormal gene expression are central events that cause neurons to die in Alzheimer’s disease.
The authors write, “Our work suggests that drugs that modify DNA structure may be beneficial for treating Alzheimer’s Disease.” The authors recommend, “A greater understanding of the pathway of DNA relaxation in tauopathies will allow us to identify the optimal target and explore the therapeutic potential of epigenetic-based drugs.”
(Source: eurekalert.org)