In the Brain: 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. …

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Peer pressure’s influence calculated by mathematician

Oct. 9, 2013 — A mathematician has calculated how peer pressure influences society.Professor Ernesto Estrada, of the University of Strathclyde’s Department of Mathematics and Statistics, examined the effect of direct and indirect social influences — otherwise known as peer pressure — on how decisions are reached on important issues. Using mathematical models, he analysed data taken from 15 networks — including US school superintendents and Brazilian farmers — to outline peer pressure’s crucial role in society.Professor Estrada said: “Our modern society is a highly-interconnected one — and social groups have become ever-more interconnected as time has progressed, with the evolution from the cavemen to today’s technology-driven society.”Reaching consensus about vital topics — such as global warming, the cost of health care and insurance systems, and healthy habits — is crucial for the evolution of our society.”That is why the study of consensus has attracted the attention of scholars in a variety of disciplines, ranging from social to natural sciences, who have documented examples of peer pressure’s influence on popular cultural styles — such as changing fashions over time and the behavior of crowds at football matches — as well as collective decision-making, and even pedestrians’ walking behavior.”Professor Estrada’s research into how decisions are reached found that the process begins when individuals directly connected to each other first reach agreement, then — under the influence of peers not directly connected to them — the entire social group eventually tips into a collective consensus. He said: “Consider a teenager who is pressed by her friends into binge-drinking on a Saturday night — this corresponds to the direct pressure exerted by the peers connected to that individual.”However, she is also under indirect pressure, by seeing that many teenagers are doing the same every Saturday. Thus, this indirect pressure could make the difference in that individual to copy a given attitude.”Professor Estrada’s study, being published today in the Nature journal Scientific Reports, also examined the extent to which a small number of leaders can guide and dictate the behavior — and decisions — of an entire social group.He said: “Think about the existence of groups in different organisations, such as industries. Every organisation has one or more leaders who might, for example, be trying to convince the group to go to — or indeed not attend — a demonstration about a contentious issue.”The group can reach a consensus about the topic only by considering the direct pressure exerted by the members of the group and that of the leaders. However, if the individuals in the group observe that many other workers from external places have joined the demonstration, they can take a decision to join — regardless of the pressure exerted by their leaders.”In social groups in which indirect peer pressure is largely absent, the extent to which its leaders share the same views plays a critical role in the length of time it takes to reach agreement on issues. However, when there is strong indirect peer pressure, the role of the local leaders vanishes and individuals with no important positions in their networks can become the leaders of the group.Professor Estrada said: “Think about, for instance, the change of attitudes in respect to the smoking habit. In the 70s, it was very cool to smoke and you would see actors lighting cigarettes all the time on TV — and movie stars were always smoking at decisive moments in films.”Back then, individuals were not only directly pressed by their colleagues and friends to smoke but they also saw that people of the same social class, age and gender were doing the same. In this way, the combination of both direct and indirect peer pressure influenced the individuals to take up smoking.”What is happening right now is the reverse. …

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Researchers discover how inhibitory neurons behave during critical periods of learning

Aug. 25, 2013 — We’ve all heard the saying “you can’t teach an old dog new tricks.” Now neuroscientists are beginning to explain the science behind the adage.For years, neuroscientists have struggled to understand how the microcircuitry of the brain makes learning easier for the young, and more difficult for the old. New findings published in the journal Nature by Carnegie Mellon University, the University of California, Los Angeles and the University of California, Irvine show how one component of the brain’s circuitry — inhibitory neurons — behave during critical periods of learning.The brain is made up of two types of cells — inhibitory and excitatory neurons. Networks of these two kinds of neurons are responsible for processing sensory information like images, sounds and smells, and for cognitive functioning. About 80 percent of neurons are excitatory. Traditional scientific tools only allowed scientists to study the excitatory neurons.”We knew from previous studies that excitatory cells propagate information. We also knew that inhibitory neurons played a critical role in setting up heightened plasticity in the young, but ideas about what exactly those cells were doing were controversial. Since we couldn’t study the cells, we could only hypothesize how they were behaving during critical learning periods,” said Sandra J. Kuhlman, assistant professor of biological sciences at Carnegie Mellon and member of the joint Carnegie Mellon/University of Pittsburgh Center for the Neural Basis of Cognition.The prevailing theory on inhibitory neurons was that, as they mature, they reach an increased level of activity that fosters optimal periods of learning. But as the brain ages into adulthood and the inhibitory neurons continue to mature, they become even stronger to the point where they impede learning.Newly developed genetic and imaging technologies are now allowing researchers to visualize inhibitory neurons in the brain and record their activity in response to a variety of stimuli. …

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Scientists help explain visual system’s remarkable ability to recognize complex objects

July 2, 2013 — How is it possible for a human eye to figure out letters that are twisted and looped in crazy directions, like those in the little security test internet users are often given on websites?It seems easy to us — the human brain just does it. But the apparent simplicity of this task is an illusion. The task is actually so complex, no one has been able to write computer code that translates these distorted letters the same way that neural networks can. That’s why this test, called a CAPTCHA, is used to distinguish a human response from computer bots that try to steal sensitive information.Now, a team of neuroscientists at the Salk Institute for Biological Studies has taken on the challenge of exploring how the brain accomplishes this remarkable task. Two studies published within days of each other demonstrate how complex a visual task decoding a CAPTCHA, or any image made of simple and intricate elements, actually is to the brain.The findings of the two studies, published June 19 in Neuron and June 24 in the Proceedings of the National Academy of Sciences (PNAS), take two important steps forward in understanding vision, and rewrite what was believed to be established science. The results show that what neuroscientists thought they knew about one piece of the puzzle was too simple to be true.Their deep and detailed research — -involving recordings from hundreds of neurons — -may also have future clinical and practical implications, says the study’s senior co-authors, Salk neuroscientists Tatyana Sharpee and John Reynolds.”Understanding how the brain creates a visual image can help humans whose brains are malfunctioning in various different ways — -such as people who have lost the ability to see,” says Sharpee, an associate professor in the Computational Neurobiology Laboratory. “One way of solving that problem is to figure out how the brain — -not the eye, but the cortex — — processes information about the world. If you have that code then you can directly stimulate neurons in the cortex and allow people to see.”Reynolds, a professor in the Systems Neurobiology Laboratory, says an indirect benefit of understanding the way the brain works is the possibility of building computer systems that can act like humans.”The reason that machines are limited in their capacity to recognize things in the world around us is that we don’t really understand how the brain does it as well as it does,” he says.The scientists emphasize that these are long-term goals that they are striving to reach, a step at a time.Integrating parts into wholesIn these studies, Salk neurobiologists sought to figure out how a part of the visual cortex known as area V4 is able to distinguish between different visual stimuli even as the stimuli move around in space. V4 is responsible for an intermediate step in neural processing of images.”Neurons in the visual system are sensitive to regions of space — — they are like little windows into the world,” says Reynolds. “In the earliest stages of processing, these windows — -known as receptive fields — -are small. …

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Biomedical research revealing secrets of cell behavior

July 1, 2013 — Knowing virtually everything about how the body’s cells make transitions from one state to another — for instance, precisely how particular cells develop into multi-cellular organisms — would be a major jump forward in understanding the basics of what drives biological processes.Such a leap could open doors to far-reaching advances in medical science, bioengineering and related areas.An interdisciplinary team of researchers at Arizona State University, with a partner at Imperial College London, report on taking at least a step toward better comprehension of the fundamentals of “cell fate determination” in the prominent research journal Proceedings of the National Academy of Sciences (PNAS).Cell fate determination relates to the mechanisms by which a cell “decides” in what direction it will go in moving through transitional phases into a final state.Using mathematical modeling and synthetic biology techniques the team is manufacturing artificial gene networks (a collection of DNA segments in a cell that interact with each other) and introducing them into cells in the laboratory.From there, the researchers are able to closely observe through microscopic imaging what is happening with particular cells at their “tipping point,” a stage of rest right before they transition into other states.By learning what takes place at that point, “We can get closer to a fundamental insight about all biology,” says biomedical engineer and synthetic biologist Xiao Wang.Once the mechanisms determining the fate of cells are better understood, Wang says, “We could make gene networks or devices that do what we want them to do,” such as create cells that produce medicinal drugs or that kill diseased cells, or create cells that act as sensors to detect environmental hazards.Wang is an assistant professor in the School of Biological and Health Systems Engineering, one of ASU’s Ira A. Fulton Schools of Engineering. He is the senior author of the PNAS paper.Wang’s fellow authors are: biomedical engineering research scientists Min Wu and Xiaohui Li, who work in Wang’s lab; electrical engineering graduate student Ri-Qi Su; Ying-Cheng Lai, a professor in ASU’s School of Electrical, Computer and Energy Engineering; and synthetic biologist Tom Ellis from Imperial College London.Their article, “Engineering of regulated stochastic cell fate determination,” is available online.The research team is studying the molecular-level interactions within the DNA sequences of cells, through which the products of one gene affect those of other genes. This helps to trace the lineages of cell development and reveal what drives them in the direction of what kinds of cells they will be in their final states.Within deeper knowledge of the workings of such processes lays the key to more effectively engineering cells and gene networks.Wang’s team is focused on investigating the intricate properties of gene networks with the goal of learning new ways of regulating the mechanisms behind cell fate determination.”Our research could be built upon to look at more complicated gene networks and more complex cellular behavior,” paving the way for expanding the capabilities of bioengineering to protect and maintain human health, Wang says.Support for the team’s research has come from the National Science Foundation and the American Heart Association.

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Social networks shape monkey ‘culture’ too

June 27, 2013 — Of course Twitter and Facebook are all the rage, but the power of social networks didn’t start just in the digital age. A new study on squirrel monkeys reported in Current Biology, a Cell Press publication, on June 27 finds that monkeys with the strongest social networks catch on fastest to the latest in foraging crazes. They are monkey trendsters.The researchers, led by Andrew Whiten of the University of St Andrews, made the discovery by combining social network analysis with more traditional social learning experiments. By bringing the two together, they offer what they say is the first demonstration of how social networks may shape the spread of new cultural techniques. It’s an approach they hope to see adopted in studies of other social animals.”Our study shows that innovations do not just spread randomly in primate groups but, as in humans, are shaped by the monkeys’ social networks,” Whiten said.Whiten, along with Nicolas Claidière, Emily Messer, and William Hoppitt, traced the monkeys’ social networks by recording which monkeys spent time together in the vicinity of “artificial fruits” that could be manipulated to extract tempting food rewards. Sophisticated statistical analysis of those data revealed the monkeys’ social networks, with some individuals situated at the heart of the network and others more on the outside. The researchers rated each of the monkeys on their “centrality,” or social status in the network, with the highest ratings going to monkeys with the most connections to other well-connected individuals.The artificial fruits could be opened in two different ways, either by lifting a little hatch on the front or by pivoting it from side to side. The researchers trained the alpha male in one group of monkeys on the lift technique, while the leader in another group was trained on the pivot method. They then sent them back to their groups and watched to see how those two methods would catch on in the two groups.More central monkeys with the strongest social ties picked up the new methods more successfully, the researchers found. They were also more likely than peripheral monkeys to learn the method demonstrated by their trained alpha leaders.Whiten said the squirrel monkeys are a good species for these studies because of their natural inquisitiveness. …

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Social networks could help prevent disease outbreaks in endangered chimpanzees

June 5, 2013 — Many think of social networks in terms of Facebook friends and Twitter followers, but for recent University of Georgia doctoral graduate Julie Rushmore, social networks are tools in the fight against infectious diseases.Rushmore, who completed her doctorate in the Odum School of Ecology in May, analyzed the social networks of wild chimpanzees to determine which individuals were most likely to contract and spread pathogens. Her findings, published in the Journal of Animal Ecology on June 5, could help wildlife managers target their efforts to prevent outbreaks and potentially help public health officials prevent disease in human populations as well.Effective disease intervention for this species is important for a number of reasons. Wild chimpanzees are highly endangered, and diseases — including some that also infect humans — are among the most serious threats to their survival. And due to habitat loss, chimpanzees increasingly overlap with human populations, so disease outbreaks could spread to people and livestock, and vice versa.Disease prevention in wildlife is logistically challenging, and resources are scarce, Rushmore explained. Even when vaccines are available, it is impractical to vaccinate every individual in a wildlife population. She and her colleagues decided to use social network analysis to pinpoint individuals most important in disease transmission.”Modeling studies in humans have shown that targeting central individuals for vaccination is significantly more effective than randomly vaccinating,” Rushmore said. “There have been a few social network studies in wildlife systems — bees, lions, meerkats, lizards and giraffes — but this is the first paper to map out social networks in the context of disease transmission and conservation for wild primates.”Rushmore observed a community of wild chimpanzees in Kibale National Park in Uganda, recording the interactions of individuals and family groups over a nine-month period to determine which individuals — and which types of individuals — were most central.”Chimpanzees are ideal for this study because to collect this observational behavioral data, you don’t need to collar them or use any invasive methods. You can essentially just observe chimpanzees in their natural environment and identify them individually based on their facial features,” she said.Rushmore collected information about the traits of individual chimpanzees including age, sex, rank and family size. Rank for adult males was based on dominance, while for adult females and juveniles it was based on location: Those that lived and foraged in the interior of the community’s territory were considered of higher rank than those that roamed its edges.From December 2009 to August 2010, Rushmore recorded the interactions of chimpanzees in the community at 15-minute intervals between 6 a.m. and 7:30 p.m., four to six days per week. …

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PET finds increased cognitive reserve levels in highly educated pre-Alzheimer’s patients

June 3, 2013 — Highly educated individuals with mild cognitive impairment that later progressed to Alzheimer’s disease cope better with the disease than individuals with a lower level of education in the same situation, according to research published in the June issue of The Journal of Nuclear Medicine. In the study “Metabolic Networks Underlying Cognitive Reserve in Prodromal Alzheimer Disease: A European Alzheimer Disease Consortium Project,”neural reserve and neural compensation were both shown to play a role in determining cognitive reserve, as evidenced by positron emission tomography (PET).Cognitive reserve refers to the hypothesized capacity of an adult brain to cope with brain damage in order to maintain a relatively preserved functional level. Understanding the brain adaptation mechanisms underlying this process remains a critical question, and researchers of this study sought to investigate the metabolic basis of cognitive reserve in individuals with higher (more than 12 years) and lower (less than 12 years) levels of education who had mild cognitive impairment that progressed to Alzheimer’s disease, also known as prodromal Alzheimer’s disease.”This study provides new insight into the functional mechanisms that mediate the cognitive reserve phenomenon in the early stages of Alzheimer’s disease,” said Silvia Morbelli, MD, lead author of the study. “A crucial role of the dorso-lateral prefrontal cortex was highlighted by demonstrating that this region is involved in a wide fronto-temporal and limbic functional network in patients with Alzheimer’s disease and high education, but not in poorly educated Alzheimer’s disease patients.”In the study, 64 patients with prodromal Alzheimer’s disease and 90 control subjects — coming from the brain PET project (chaired by Flavio Nobili, MD, in Genoa, Italy) of the European Alzheimer Disease Consortium — underwentbrain 18F-FDG PET scans. Individuals were divided into a subgroup with a low level of education (42 controls and 36 prodromal Alzheimer’s disease patients) and a highly educated subgroup (40 controls and 28 prodromal Alzheimer’s disease patients). Brain metabolism was compared between education-matched groups of patients and controls, and then between highly and poorly educated prodromal Alzheimer’s disease patients.Higher metabolic activity was shown in the dorso-lateral prefrontal cortex for prodromal Alzheimer’s disease patients. More extended and significant correlations of metabolism within the right dorso-lateral prefrontal cortex and other brain regions were found with highly educated than less educated prodromal Alzheimer’s disease patients or even highly educated controls.This result suggests that neural reserve and neural compensation are activated in highly educated prodromal Alzheimer’s disease patients. Researchers concluded that evaluation of the implication of metabolic connectivity in cognitive reserve further confirms that adding a comprehensive evaluation of resting 18F-FDG PET brain distribution to standard inspection may allow a more complete comprehension of Alzheimer’s disease pathophysiology and possibly may increase 18F-FDG PET diagnostic sensitivity.”This work supports the notion that employing the brain in complex tasks and developing our own education may help in forming stronger ‘defenses’ against cognitive deterioration once Alzheimer knocks at our door,” noted Morbelli.”It’s possible that, in the future, a combined approach evaluating resting metabolic connectivity and cognitive performance can be used on an individual basis to better predict cognitive decline or response to disease-modifying therapy.”

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