Thursday, February 17, 2011

WHAT BLAME CAN TELL US ABOUT AUTISM

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In the mid-1980s, a team of autism researchers theorized that one of the major features of autism is an inability to infer the thoughts of other people. This skill, known as theory of mind, comes naturally to most people — we are constantly evaluating other people’s mental states and trying to determine what they know, what they want and why they are happy or sad, angry or scared.

Though there is much anecdotal evidence that this skill is impaired in autistic people, it has been difficult to show it experimentally in adults. Now, a study from MIT neuroscientists reveals that high-functioning autistic adults appear to have trouble using theory of mind to make moral judgments in certain situations.

Specifically, the researchers found that autistic adults were more likely than non-autistic subjects to blame someone for accidentally causing harm to another person. This shows that their judgments rely more on the outcome of the incident than on an understanding of the person’s intentions, says Liane Young, an MIT postdoctoral associate and one of the lead authors of the study, which appears in the Jan. 31 online edition of the Proceedings of the National Academy of Sciences.

For example, in one scenario, “Janet” and a friend are kayaking in a part of the ocean with many jellyfish. The friend asks Janet if she should go for a swim. Janet has just read that the jellyfish in the area are harmless, and tells her friend to go for a swim. The friend is stung by a jellyfish and dies.

In this scenario, the researchers found that people with autism are more likely than non-autistic people to blame Janet for her friend’s death, even though she believed the jellyfish were harmless.

Young notes that such scenarios tend to elicit a broad range of responses even among non-autistic people. “There’s no normative truth as to whether accidents should be forgiven. The pattern with autistic patients is that they are at one end of the spectrum,” she says. Young’s co-lead author on the paper is former MIT postdoctoral associate Joseph Moran, now at Harvard.

Most children develop theory-of-mind ability around age 4 or 5, which can be demonstrated experimentally with “false-belief” tests. In the classic example, a child is shown two dolls, “Sally” and “Anne.” The experimenter puts on a skit in which Sally puts a marble in a basket and then leaves the scene. While Sally is away, Anne moves the marble from the basket to a box. The experimenter asks the child where Sally will look for the marble when she returns. Giving the correct answer — that Sally will look in the basket — requires an understanding that others have beliefs that may differ from our own knowledge of the world, and from reality.

Previous studies have shown that autistic children develop this ability later than non-autistic children, if ever, depending on the severity of the autism, says the study's senior author, John Gabrieli, the Grover Herman Professor of Health Sciences and Technology.

“High-functioning” autistic people — for example, those with a milder form of autism such as Asperger’s syndrome — often develop compensatory mechanisms to deal with their difficulties in understanding other people’s thoughts. The details of these mechanisms are unknown, says Young, but they allow autistic people to function in society and to pass simple experimental tests such as determining whether someone has committed a societal “faux pas.”

However, the scenarios used in the new MIT study were constructed so that there is no easy way to compensate for impaired theory of mind. The researchers tested 13 autistic adults and 13 non-autistic adults on about 50 scenarios similar to the jellyfish example.

Uta Frith, professor of psychology at the University College London’s Institute of Cognitive Neuroscience, was part of the team of scientists who published research in 1985 suggesting that children with autism have impairments of theory of mind. Frith says the new study offers strong support for that hypothesis.

“The study uses a novel test, the judgment of intentions in moral vignettes, to probe the theory. It is an excellent test because it detects poor mentalizing even in individuals with mild autism spectrum disorder who have learned to compensate for their difficulties in understanding mental states,” she says.

In a 2010 study, Young used the same hypothetical scenarios to test the moral judgments of a group of patients with damage to the ventromedial prefrontal cortex (VMPC), a part of the prefrontal cortex (where planning, decision-making and other complex cognitive tasks occur).

Those patients understand other people’s intentions, but they lack the emotional outrage that usually occurs in cases where someone tries (but fails) to harm someone else. For example, they would more easily forgive someone who offers mushrooms he believes to be poisonous to an acquaintance, if the mushrooms turn out to be harmless.

“While autistic individuals are unable to process mental state information and understand that individuals can have innocent intentions, the issue with VMPC patients is that they could understand information but did not respond emotionally to that information,” says Young.

Putting these two pieces together could help neuroscientists come up with a more thorough picture of how the brain constructs morality. Previous studies by MIT assistant professor Rebecca Saxe (also an author of the new PNAS paper) have shown that theory of mind appears to be seated in a brain region called the right temporoparietal junction (TPJ). In ongoing studies, the researchers are studying whether autistic patients have irregular activity in the right TPJ while performing the moral judgment tasks used in the PNAS study.

(Photo: Christine Daniloff)

MIT

A CLEARER PICTURE OF VISION

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The human retina — the part of the eye that converts incoming light into electrochemical signals — has about 100 million light-sensitive cells. So retinal images contain a huge amount of data. High-level visual-processing tasks — like object recognition, gauging size and distance, or calculating the trajectory of a moving object — couldn’t possibly preserve all that data: The brain just doesn’t have enough neurons. So vision scientists have long assumed that the brain must somehow summarize the content of retinal images, reducing their informational load before passing them on to higher-order processes.

At the Society of Photo-Optical Instrumentation Engineers’ Human Vision and Electronic Imaging conference on Jan. 27, Ruth Rosenholtz, a principal research scientist in the Department of Brain and Cognitive Sciences, presented a new mathematical model of how the brain does that summarizing. The model accurately predicts the visual system’s failure on certain types of image-processing tasks, a good indication that it captures some aspect of human cognition.

Most models of human object recognition assume that the first thing the brain does with a retinal image is identify edges — boundaries between regions with different light-reflective properties — and sort them according to alignment: horizontal, vertical and diagonal. Then, the story goes, the brain starts assembling these features into primitive shapes, registering, for instance, that in some part of the visual field, a horizontal feature appears above a vertical feature, or two diagonals cross each other. From these primitive shapes, it builds up more complex shapes — four L’s with different orientations, for instance, would make a square — and so on, until it’s constructed shapes that it can identify as features of known objects.

While this might be a good model of what happens at the center of the visual field, Rosenholtz argues, it’s probably less applicable to the periphery, where human object discrimination is notoriously weak. In a series of papers in the last few years, Rosenholtz has proposed that cognitive scientists instead think of the brain as collecting statistics on the features in different patches of the visual field.

On Rosenholtz’s model, the patches described by the statistics get larger the farther they are from the center. This corresponds with a loss of information, in the same sense that, say, the average income for a city is less informative than the average income for every household in the city. At the center of the visual field, the patches might be so small that the statistics amount to the same thing as descriptions of individual features: A 100-percent concentration of horizontal features could indicate a single horizontal feature. So Rosenholtz’s model would converge with the standard model.

But at the edges of the visual field, the models come apart. A large patch whose statistics are, say, 50 percent horizontal features and 50 percent vertical could contain an array of a dozen plus signs, or an assortment of vertical and horizontal lines, or a grid of boxes.

In fact, Rosenholtz’s model includes statistics on much more than just orientation of features: There are also measures of things like feature size, brightness and color, and averages of other features — about 1,000 numbers in all. But in computer simulations, storing even 1,000 statistics for every patch of the visual field requires only one-90th as many virtual neurons as storing visual features themselves, suggesting that statistical summary could be the type of space-saving technique the brain would want to exploit.

Rosenholtz’s model grew out of her investigation of a phenomenon called visual crowding. If you were to concentrate your gaze on a point at the center of a mostly blank sheet of paper, you might be able to identify a solitary A at the left edge of the page. But you would fail to identify an identical A at the right edge, the same distance from the center, if instead of standing on its own it were in the center of the word “BOARD.”

Rosenholtz’s approach explains this disparity: The statistics of the lone A are specific enough to A’s that the brain can infer the letter’s shape; but the statistics of the corresponding patch on the other side of the visual field also factor in the features of the B, O, R and D, resulting in aggregate values that don’t identify any of the letters clearly.

Rosenholtz’s group has also conducted a series of experiments with human subjects designed to test the validity of the model. Subjects might, for instance, be asked to search for a target object — like the letter O — amid a sea of “distractors” — say, a jumble of other letters. A patch of the visual field that contains 11 Q’s and one O would have very similar statistics to one that contains a dozen Q’s. But it would have much different statistics than a patch that contained a dozen plus signs. In experiments, the degree of difference between the statistics of different patches is an extremely good predictor of how quickly subjects can find a target object: It’s much easier to find an O among plus signs than it is to find it amid Q’s.

Rosenholtz, who has a joint appointment to the Computer Science and Artificial Intelligence Laboratory, is also interested in the implications of her work for data visualization, an active research area in its own right. For instance, designing subway maps with an eye to maximizing the differences between the summary statistics of different regions could make them easier for rushing commuters to take in at a glance.

In vision science, “there’s long been this notion that somehow what the periphery is for is texture,” says Denis Pelli, a professor of psychology and neural science at New York University. Rosenholtz’s work, he says, “is turning it into real calculations rather than just a side comment.” Pelli points out that the brain probably doesn’t track exactly the 1,000-odd statistics that Rosenholtz has used, and indeed, Rosenholtz says that she simply adopted a group of statistics commonly used to describe visual data in computer vision research. But Pelli also adds that visual experiments like the ones that Rosenholtz is performing are the right way to narrow down the list to “the ones that really matter.”

(Photo: Christine Daniloff)

MIT

SECRETS OF DINOSAUR FOOTPRINTS REVEALED, THANKS TO GOLDILOCKS

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Terrain thought to be ruled by only the largest dinosaurs to inhabit the earth could have in fact been home to dozens of other creatures, ground-breaking research from The University of Manchester has found.

Writing in the journal of the Royal Society Interface, Dr Peter Falkingham has discovered that dinosaurs only created lasting footprints if the soil conditions were perfect to do so – and entirely depending on the animal’s weight.

Dubbed the ‘Goldilocks Effect’ – as all conditions have to be ‘just right’ for a print to be created – this work could help to bring ancient environments to life, by showing how a great number of animals can walk over an area, but only a few leave behind tracks.

The findings mean that hugely-significant prehistoric dinosaur track sites, such as Paluxy River in Texas, USA, or Fumanya, Spain could have been host to a much larger number of dinosaurs and other animals than the tracks themselves show.

Dr Falkingham, from the University’s School of Earth, Atmospheric and Environmental Sciences, led a team using detailed computer modelling to recreate the process of large dinosaurs making footprints in different types of mud.

The team incorporated scientists from a range of disciplines, including vertebrate palaeontologist Dr Phil Manning and Geotechnical engineer Dr Lee Margetts, both from The University of Manchester, and biomechanicist Dr Karl Bates (University of Liverpool).

By using computer modelling to simulate dinosaurs making tracks, the scientists were able for the first time to run dozens of simulations in order to systematically change the conditions of the mud.

As dinosaurs ranged vastly in weight, from Brachiosaurus, weighing around 30 tonnes, to Compsognathus, which was the size and weight of a chicken, Dr Falkingham worked out that only the heaviest creatures would leave prints in certain mud conditions.

Equally, in other areas where the mud was deep and soft, only lighter, nimbler dinosaurs would be able to walk over it and therefore leave prints; larger animals would become stuck and die.

These insights give palaeontologists the chance to re-evaluate the ecosystems which existed more than 100 million years ago.

Dr Falkingham said: “By using computer modelling, we were able to recreate the conditions involved when a 30-tonne animal makes a track.

“That’s very hard to do with physical modelling, more so when you need to do it 20 times in 20 different types of mud.

“But the real advantage of computer modelling is that everything is controllable. We were able to ensure that in every simulation we could look at the effects of each variable (for instance, the shape of the foot, or the weight of the animal) independently.

“As with most scientific papers, this isn’t the end of research, this is the beginning.

“Now we can use this “Goldilocks” effect as a baseline for exploring more complicated factors such as the way dinosaurs moved their legs, or what happens to tracks when a mud is drying out.”

In Paluxy River, site of one of the most famous sets of dinosaur footprints which seem to show a sauropod being chased by a carnivorous theropod, there are only footprints recording large dinosaurs.

But Dr Falkingham’s findings suggest that many more species probably lived there, walking over the same mud, but their footprints either made no impression or have disappeared over time.

The computer method was based on a technique common in engineering, known as finite element analysis.

This method lets scientists simulate the deformation of a material under load. Whilst in engineering this may be an aeroplane wing supporting the aircraft, Dr Falkingham and his co-authors applied the method to mud supporting a dinosaur.

(Photo: U. Manchester)

University of Manchester

A BETTER WAY TO DIAGNOSE PNEUMONIA

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Researchers from the Georgia Institute of Technology have created a new sampling device that could prevent thousands of people worldwide from dying of pneumonia each year.

Called PneumoniaCheck, the device created at Georgia Tech is a solution to the problem of diagnosing pneumonia, which is a major initiative of the U.S. Centers for Disease Control and Prevention (CDC).

Pneumonia, an inflammation of the lungs, kills about 2.4 million people each year. The problem is particularly devastating in Africa, Southeast Asia and the Eastern Mediterranean, where a child dies of pneumonia every 15 seconds.

Developed by mechanical engineering students, graduate business students and faculty at Georgia Tech, PneumoniaCheck will be commercially launched this month to healthcare professionals through the startup company, MD Innovate Inc.

“Georgia Tech created a simple and new device to detect the lung pathogens causing pneumonia, “ said David Ku, Georgia Tech Regents’ Professor of Mechanical Engineering, L.P. Huang Chair Professor for Engineering Entrepreneurship in the College of Management, and Professor of Surgery at Emory University. “It has the potential to save more lives than any other medical device.”

Last year, Ku was asked by the head of virology at the CDC to develop a quick and economical way to diagnose pneumonia, particularly in developing nations where it is a leading cause of death among children.

Ku challenged a group of mechanical engineering and bioengineering graduate students to develop an accurate device for diagnosing pneumonia. Current sampling methods using the mouth and nose are only 40 percent effective. The samples are typically contaminated by bacteria in the mouth, which leads to misdiagnosis and an incorrect prescription of antibiotics.

In developing nations, many children with respiratory infections fail to receive adequate care, and the overuse of antibiotics has led to an increase in drug-resistant bacteria. An accurate, easy-to-use and widely available new diagnostic test could improve identification of bacterial respiratory infection in children, reducing the inappropriate use of antibiotics and the long-term negative impacts of drug resistance, according to a recent article in Nature titled “Reducing the global burden of acute lower respiratory infections in children: The contributions of new diagnostics.”

As a Tech graduate student, Tamera Scholz and her peers developed the solution – PneumoniaCheck.

The device contains a plastic tube with a mouthpiece. A patient coughs into the device to fill up a balloon-like upper airway reservoir before the lung aerosols go into a filter. Using fluid mechanics, PneumoniaCheck separates the upper airway particles of the mouth from the lower airway particles coming from the lungs.

“It’s interesting because it’s so simple,” said Scholz (M.S. ’10 Mechanical Engineering), who is now an engineer for Newell Rubbermaid. “It’s not a fancy contraption. It’s a device that patients cough into and through fluid mechanics it separates upper and lower airway aerosols. Through each iteration, it got simpler. … I like that I will be able to see it make a difference in my lifetime.”

Once the device was developed, Taylor Bronikowski and a group of Georgia Tech M.B.A. students from the College of Management started developing a business plan for PneumoniaCheck that starts locally and grows globally. They used the device as a test case to develop a Triple Bottom Line company in India that could result in financial profits, environmental sustainability and social benefits, such as jobs and healthcare.

“Our goal is to provide better medicine at a cost savings to patients and hospitals,” Bronikowski said. “We wanted a worldwide solution, so patients in developing nations can afford it.”

Bronikowksi, Ku and Sarah Ku formed the startup company, MD Innovate Inc., in 2010 to manufacture the device in large quantities and organize distribution and commercialization. The device is now being used in pneumonia studies at Grady Memorial Hospital in downtown Atlanta and the Atlanta Veterans Administration Medical Center, Ku said.

The FDA has cleared PneumoniaCheck for sale in the U.S. The device is licensed but its patent is pending. The company will start selling PneumoniaCheck in the U.S. in January and it could hit other countries in two years, Ku said.

“It’s a great feeling, working on something that has the potential to save thousands of lives,” Bronikowski said.

On the horizon, Ku and future Georgia Tech graduate students will be developing a simple and effective method for diagnosing pneumonia in regions without healthcare facilities or basic infrastructure.

(Photo: GIT)

Georgia Institute of Technology

GENDER AND HYGIENE: COULD CLEANLINESS BE HURTING GIRLS?

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Little girls growing up in western society are expected to be neat and tidy – “all ribbon and curls” – and one researcher who studies science and gender differences thinks that emphasis may contribute to higher rates of certain diseases in adult women.

The link between increased hygiene and sanitation and higher rates of asthma, allergies and autoimmune disorders is known as the “hygiene hypothesis” and the link is well-documented. Yet the role of gender is rarely explored as part of this phenomenon.

Oregon State University philosopher Sharyn Clough thinks researchers need to dig deeper. In her new study, published in the journal Social Science & Medicine, she points out that women have higher rates of allergies and asthma, and many autoimmune disorders. However, there is no agreed-upon explanation for these patterns. Clough offers a new explanation.

Clough documents a variety of sociological and anthropological research showing that our society socializes young girls differently from young boys. In particular, she notes, girls are generally kept from getting dirty compared to boys.

“Girls tend to be dressed more in clothing that is not supposed to get dirty, girls tend to play indoors more than boys, and girl’s playtime is more often supervised by parents,” said Clough, adding that this is likely to result in girls staying cleaner. “There is a significant difference in the types and amounts of germs that girls and boys are exposed to, and this might explain some of the health differences we find between women and men.”

However, that doesn’t mean that parents should let their daughters go out into the back yard and eat dirt, Clough points out.

“What I am proposing is new ways of looking at old studies,” she said. “The hygiene hypothesis is well-supported, but what I am hoping is that the epidemiologists and clinicians go back and examine their data through the lens of gender.”

The “hygiene hypothesis” links the recent rise in incidence of asthma, allergies, and autoimmune disorders such as Crohn’s disease and rheumatoid arthritis, with particular geographical and environmental locations, in particular urban, industrialized nations. Many scholarly studies have noted that as countries become more industrial and urban, rates of these diseases rise. For instance, the rate of Crohn’s disease is on the rise in India as sanitation improves and industrialization increases.

The Centers for Disease Control and Prevention has noted that asthma prevalence is higher among females (8.9 percent compared to 6.5 percent in males) and that women are more likely to die from asthma. The National Institutes of Health statistics show that autoimmune diseases strike women three times more than men.

A report by the Task Force on Gender, Multiple Sclerosis, and Autoimmunity shows that among people with multiple sclerosis and rheumatoid arthritis, the female to male ratio is between 2:1 and 3:1. With the disease lupus, nine times as many women are affected as men.

Clough is a philosopher of science and epistemology, with a particular focus on feminist theory and gender differences. The focus of her work is to study scientific research and look for the implicit or hidden assumptions that guide that research.

She believes the link between hygiene, gender and disease is not just a fluke.

“We are just now beginning to learn about the complex relationship between bacteria and health,” she said. “More than 90 percent of the cells in our body are microbial rather than human. It would seem that we have co-evolved with bacteria. We need to explore this relationship more, and not just in terms of eating ‘pro-biotic’ yogurt.”

That’s why Clough does not recommend that parents feed their daughters spoonfuls of dirt. Just one gram of ordinary uncontaminated soil contains 10 billion microbial cells, so the effects of ingesting dirt are unknown.

“We obviously do not yet know enough to differentiate between helpful and harmful bacteria,” she said.

However, Clough said she can easily join in the chorus of voices of health experts who say that more outdoor time for kids is good – even if that means the kids get a little dirty.

“Getting everyone, both boys and girls, from an early age to be outdoors as much as possible is something I can get behind,” she said.

Oregon State University

MODERATE AEROBIC EXERCISE IN OLDER ADULTS SHOWN TO IMPROVE MEMORY

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A new study shows that one year of moderate physical exercise can increase the size of the brain's hippocampus in older adults and lead to an improvement in spatial memory.

The project -- conducted by researchers at the University of Pittsburgh, University of Illinois, Rice University and Ohio State University -- is considered the first study of its kind to focus on older adults who are already experiencing atrophy of the hippocampus, the brain structure involved in all forms of memory formation. The study, funded through the National Institute on Aging, was published in the Jan. 31 Proceedings of the National Academy of Sciences (PNAS).

"A moderate exercise regimen may not only improve physical health in the elderly by reducing the risk of diabetes, obesity and high cholesterol; it can also improve cognitive abilities, such as memory," said Chandramallika Basak, assistant professor of psychology at Rice and co-author of the study.

The scientists recruited more than 120 sedentary older people without dementia and randomly placed them in one of two groups -- those who began an exercise regimen of walking around a track for 40 minutes a day, three days a week, and those limited to stretching and toning exercises. Magnetic resonance images were collected before the intervention, after six months and at the end of the one-year study.

The aerobic exercise group demonstrated an increase in volume of the left and right hippocampus of 2.12 percent and 1.97 percent, respectively. The same regions of the brain in those who did stretching exercises decreased in volume by 1.40 and 1.43 percent, respectively.

Spatial memory tests were conducted for all participants at the three intervals. Those in the aerobic exercise group showed improved memory function when measured against their performance at the start of the study. This improvement was associated with the increased size of the hippocampus. The authors also examined several biomarkers associated with brain health, including brain-derived neurotrophic factor (BDNF), a small molecule that is involved in learning and memory. They found that the increases in hippocampal size were associated with increased amounts of BDNF.

"We think of the atrophy of the hippocampus in later life as almost inevitable," said Kirk Erickson (http://www.psychology.pitt.edu/people/faculty/faculty.php?fc_id=83), professor of psychology at the University of Pittsburgh and the paper's lead author. "But we've shown that even moderate exercise for one year can increase the size of that structure. The brain at that stage remains modifiable."

"The results of our study are particularly interesting in that they suggest that even modest amounts of exercise by sedentary older adults can lead to substantial improvements in memory and brain health," said Art Kramer (http://www.beckman.illinois.edu/directory/a-kramer), director of the Beckman Institute at the University of Illinois and the senior author. "Such improvements have important implications for the health of our citizens and the expanding population of older adults worldwide."

Rice University

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