The whimsical décor at the Baby Lab at the University of California, San Diego (UCSD), is designed to appeal to its most important visitors: the 400-plus babies and toddlers who have visited the cozy space since 2002.

Paintings of trees with spindly brown branches and plump green leaves cover the walls. Books, plastic cars and coloring books spill out across the carpeted floor and fill several plastic bins.

The children who come here are as young as 3 months on their first visit, and return every few months to participate in a battery of tests of their social behavior and perceptual processing — the brain’s response to non-social stimuli, such as looking at an ordinary object.

About one in four of these children is particularly interesting to the researchers: They are the younger siblings of children with autism, and are much more likely to develop the disorder than are those without a family history of it. Over the past few years, scientists have gathered heaps of behavioral data from these so-called ‘baby sibs’, but the Baby Lab is among the first to look for distinct signatures of brain activity.

The lab’s studies are ongoing, but two published reports have uncovered surprising differences between baby sibs and age-matched controls. Previous imaging work on face processing in people with autism had found abnormalities, suggesting to many researchers that their brains are slow to process social information. But the Baby Lab team is finding that during tests of sensory or perceptual processing, baby sibs show abnormally fast brain responses, rather than a delay.

Lead investigator Karen Dobkins says these data suggest an alternate interpretation of autism’s origins. Instead of resulting from a disruption of the brain’s social behavior circuits, she says, the disorder could arise from early upsets in perceptual processing, which eventually cause more noticeable social problems.

“We know that the hallmarks of autism are social in nature, but social systems develop later than sensory systems,” says Dobkins, professor of psychology at UCSD. “How on earth are you supposed to respond appropriately, behave appropriately, if you don’t perceive your world properly?”

This hypothesis agrees with previous reports from other labs conducting baby sib research, which converge on the idea that there is no fundamental social problem in autism, but rather gradual deficits in several different perceptual and sensory systems, according to a review of these studies published in June.

Chicken or egg?
The Baby Lab tests children for different abilities as they grow up. At 3 and 6 months of age, for instance, the infants sit on their mothers’ laps and watch gray lines flash on a computer screen — allowing researchers to assess how well they detect visual contrast. At 10 and 18 months, the toddlers wear electrodes on their scalp, allowing researchers to record brain activity during perceptual tasks, such as looking at pictures of faces or objects, and social ones, such as playing with a new toy along with their mothers.

The lab’s newest study, to be published in the 15 November issue of Biological Psychiatry, found that 10-month-old baby sibs produce brain-wave responses to pictures of toys significantly faster than do controls.

The findings support a 2007 report from the researchers in which they found that, compared with healthy controls, 6-month-old baby sibs show twice as much sensitivity to black-and-white visual contrast. The researchers say this heightened ability stems from unusual robustness in an early visual brain pathway — one that feeds into brain areas responsible for processing emotions and facial expressions.

But others are skeptical, saying the heightened processing does not necessarily indicate that perceptual glitches are the root cause of the disorder.

“If that were true, then you wouldn’t have something so specific happening in the social domain. They would have visual problems, and more global forms of intellectual disability,” notes Ami Klin, director of the Autism Program at the Yale Child Study Center.

A fundamental social deficit also makes more sense from an evolutionary perspective, Klin adds. “The things in the world that are important to an infant’s survival are people, not objects. Why should they pay more attention to objects?”

In his own studies, Klin has found that, unlike healthy controls, toddlers with autism show no preference for human motion, and tend to look at other people’s mouths instead of their eyes.

The question of which deficits come first “is very much a ‘chicken or egg’ problem,” says Mayada Elsabbagh, scientific coordinator of the British Autism Study of Infant Siblings. “What’s going on is actually affecting multiple systems at the same time, in a way that we don’t see very clearly within the first year.”

…read the rest of my latest feature at SFARI

This is quite a week for sensational headlines on da blog: Last post was about scientists reading minds; now, they’re making the blind see.

To the right is Barbara Campbell, a New Yorker who lost her vision slowly over the course of her youth. Now 56, she’s been completely blind for 26 years. Until, that is, she got her artificial retina. Now she can see her stove top turn hot and computer monitor glow. From the New York Times:

With the artificial retina, a sheet of electrodes is implanted in the eye. The person wears glasses with a tiny camera, which captures images that the belt-pack video processor translates into patterns of light and dark, like the “pixelized image we see on a stadium scoreboard,” said Jessy D. Dorn, a research scientist at Second Sight Medical Products, which produces the device, collaborating with the Department of Energy.

The video processor directs each electrode to transmit signals representing an object’s contours, brightness and contrast, which pulse along optic neurons into the brain.

Currently, “it’s a very crude image,” Dr. Dorn said, because the implant has only 60 electrodes; many people see flashes or patches of light.

Brian Mech, Second Sight’s vice president for business development, said the company was seeking federal approval to market the 60-electrode version, which would cost up to $100,000 and might be covered by insurance. Also planned are 200- and 1,000-electrode versions; the higher number might provide enough resolution for reading.

Many of the most noticeable symptoms of autism involve trouble with the five senses. Sometimes people with the disorder are extremely sensitive — cowering from sudden noises or bright lights, for example, or reacting aggressively to being touched. Others seek out extra sensation, such as through hand flapping.

Surprisingly, though, most experts don’t consider these issues core features of the disorder. One reason is that no one has definitively calculated the extent to which these behaviors crop up in people with autism. Even if a high prevalence were confirmed, sensory impairments could simply be secondary consequences of a more fundamental deficit, such as a problem with attention or an aversion to social interactions.

But last week, a group of Australian researchers reported that these symptoms are probably universal among children on the autism spectrum. Their study also found that some children show both high and low sensitivities, and that specific combinations of sensory symptoms tend to arise more frequently than others.

For the study, the parents of 54 young children with autism filled out the Short Sensory Profile, a 38-item questionnaire designed to measure abnormal function of each sense.

Almost 90 percent of the kids in the study showed some kind of sensory difficulty. The most common were related to auditory filtering, such as responding to their name being called, and low tactile sensitivity, such as not noticing when their face or hands are messy.

Perhaps the study’s most interesting finding is that the types of sensory issues tended to cluster in distinct ways. One group of kids, for instance, showed extreme sensitivity to taste and smell, but normal reaction to sudden movements; another had fairly normal sensing, except that they were distracted easily by noises or sights, excessively touched things, and couldn’t stay focused on a task.

An obvious drawback of this study is that it’s based on parental reports, which may be incomplete or inaccurate. Still, if confirmed using different methods, it should spur more basic research on the brain circuitry behind these striking sensory patterns.

In February, I wrote about a controversial report claiming that people with autism have ‘eagle-eye’ vision. Now, four scientists have published rebuttals to that study, citing major flaws in the way the experiment was carried out.

In the original paper, Emma Ashwin used a computer program to measure how well people with autism can see super-small pictures. Controlled experiments of this kind hadn’t been done before, but there are many anecdotal stories of people with autism noticing tiny details of a scene (sometimes at the expense of seeing the ‘big picture’).

Ashwin’s experiment, published in Biological Psychiatry, found that adults with autism have off-the-charts scores of visual acuity: 2.79 — meaning they can resolve images at 2.79 times the distance of average adults — compared with 1.44 for the control group. She suggested that this super vision may stem from an unusually large number of densely packed eye cells.

These numbers are striking, but might be meaningless. Ashwin’s group mangled the settings of the computer program, says its creator, Michael Bach. In a letter to the editor of Biological Psychiatry, he lists many problems with the researchers’ setup. Most notably, participants sat too close to the computer screen. With the shorter distance, the program cannot accurately measure acuities larger than 1.44.

Another letter, submitted to the journal by two researchers from Swinburne University of Technology in Australia, chides the idea that people with autism have densely packed eye cells. Apparently, in hawks — known for their fantastic eyesight — better vision comes not from the density of retinal cells, but from bigger eyes.

Ashwin admits that technological problems could have affected her data. But she also defends her work by pointing out that inflated acuity values would be similar in all participants, and so couldn’t account for the large difference between the autism and control groups.

Of course, the only way to definitively resolve these issues is to repeat the experiments. Happily, Ashwin is doing just that — this time collaborating with Bach.

New Scientist pointed me to a contest, run by neuroscientists, of the best new visual illusions. Definitely worth checking out if you have some procrastinating to do today. This one’s my favorite. It was created by Richard Russell, a psychology postdoc at Harvard:

In the Illusion of Sex, two faces are perceived as male and female. However, both faces are actually versions of the same androgynous face. One face was created by increasing the contrast of the androgynous face, while the other face was created by decreasing the contrast. The face with more contrast is perceived as female, while the face with less contrast is perceived as male. The Illusion of Sex demonstrates that contrast is an important cue for perceiving the sex of a face, with greater contrast appearing feminine, and lesser contrast appearing masculine.

There’s no denying that, in the past two decades, functional magnetic resonance imaging (fMRI) has revolutionized neuroscience. Its colorful, fine-resolution pictures allow scientists to compare patterns of activity in different brain regions during specific tasks.

Every technique has its drawbacks, of course, and many of fMRI’s flaws — such as the fact that it measures blood flow, an indirect measure of neuron activity — are often mentioned in papers and discussed at conferences. 

But one flaw is rarely brought up and is apparently more widespread than anyone realized: when choosing from the enormous amounts of data generated from an fMRI experiment, scientists often ‘double dip’, or use the same subset for setting up a hypothesis and for confirming it.

So says a group led by Chris Baker of the National Institutes of Health. In this month’s Nature Neuroscience, Baker reports that at least 57 of the 134 fMRI-based studies published in the top five journals last year based their conclusions on this kind of biased data.

For instance, researchers might first look to see which region of the brain lights up when someone sees a particular facial emotion and mine the same data set for patterns, instead of generating fresh data from that region.

Given how much fMRI is used in autism research, I wrote to Baker to ask how many of the studies he analyzed are about autism, schizophrenia and related disorders.

Frustratingly, Baker won’t reveal the list of papers he used. Doing so would be unfair, he wrote, because he only looked at a year’s worth of studies from a small set of journals. “The problem is much broader than this,” he added.

Instead, he calls upon specialists in each field to examine the literature themselves, and “make their own decisions about which results to trust.”

Withholding this information doesn’t seem to me to be the best approach to fixing the problem. Of course researchers in each field will have to investigate the literature on their own, but why not give them a head start? After all, meaningful scientific discourse depends on experts being able to scrutinize published results.

The word schizophrenia comes from the Greek skhizein, meaning ‘to split’ and phren, which means ‘mind’.

Schizophrenia now refers to the apparent separation of memory, thinking and perceptual abilities that trigger a disjointed personality in those with the disorder. But this split may also grant those individuals unusual abilities.

The disconnection between what the eyes see and what the brain perceives may be the reason that people with schizophrenia aren’t fooled by some visual illusions, according to a new study published in March in NeuroImage.

In the ‘hollow-mask illusion’, a well known test of visual ability, a mask of a human face rotates slowly around a vertical axis. When the mask has turned 180 degrees — and the inside of the mask is what’s visible — most people still see it as normal. It’s as if their brain refuses to see the face as hollow, presumably because that’s an extremely improbable sight in the real world.

In contrast, several studies have found that people with schizophrenia easily distinguish between normal and inverted photos of a face – something that has baffled scientists until now.

In the new study, the researchers found that confronted with an inverted face, the brains of healthy people, but not of those with schizophrenia, show more activity in the fronto-parietal network. This brain region is involved in ‘high-level’ thinking processes, such as perceiving a combination of lines and shadings as a human face.

Increased activity in the region suggests that when a healthy brain receives unusual visual information from the eyes — the curved lines of an inverted nose, say — high-level regions such as the fronto-parietal network send out commands to low-level regions, such as the primary visual cortex, to ignore the strange sight, and still perceive what it sees as a nose.

In those with schizophrenia, those high- and low-level regions may not be properly connected, the researchers suggest. The study is small, and tested just 13 people with the disorder, but it’s still an intriguing look at the mysterious split.

A new way of analyzing the data gathered from electroencephalography (EEG) — a non-invasive technique that measures brain waves through the scalp — provides much more information about how brain regions coordinate with one another than standard EEG analysis.

The new approach may be particularly useful for researchers who propose that autism is a consequence of poor temporal coordination among brain regions.

“The which brain areas, the where, has been a powerful focus” of research on autism and other psychiatric diseases, says Scott Kelso, professor of complex systems and brain sciences at Florida Atlantic University. “But if you don’t have a theory of how things are coordinated in time, you’re going to be missing something very essential.”

In 2007, Kelso and colleagues recorded EEG waves from two people in the same room who had been instructed to move one finger up and down. The researchers observed a specific wave frequency — or ‘neural signature’ — when the pair’s finger movements were synchronized. They concluded that social interaction is at least partly encoded by precise temporal patterns in the brain.

Brain activity that is subtly coordinated between different brain regions can be difficult to measure using EEG, however, because scientists normally average brain wave data from many trials and participants across a relatively large time window.

What’s more, once a brain wave leaves its origin, it meets electrical resistance — in other brain tissues, cerebral spinal fluid, and in the skull — before reaching the electrodes at the scalp. The electrodes may therefore be sensing distorted signals or ‘false’ instances of synchrony.

Scientists who use standard EEG analyses “cannot do fine discriminations because they have [included] a lot of things which are unrelated to this pure mechanism of interactions between brain areas,” says Emmanuelle Tognoli, research assistant professor at Florida Atlantic University who collaborated with Kelso on both studies.

In contrast, Tognoli and Kelso’s new ‘4D colorimetric’ method of EEG analysis, published in the January issue of Progress in Neurobiology, first uses physical laws to map the signals recorded at the skull back onto brain space, and only then looks for instances of synchrony between brain regions.

Also, rather than averaging waves of the same frequency from many participants, the method looks at how individual brain waves change over time. Finally, the method plots the waves in different colors, making it easier for the researchers to visualize how their frequencies coordinate with one another.

Distinguishing between true and false synchronization is one of the most important problems facing EEG analysis, notes Michael Murias, research assistant professor of psychiatry at the University of Washington in Seattle. Murias has used simpler EEG analyses to study how brain regions interact in people with autism. The new approach is “something that I would be interested in applying myself,” he adds.

…Read the rest of my latest article at SFARI

…was spent skipping around the Salk Institute, in beautiful La Jolla, California:

I was immediately struck by the contrasting elements of the campus: cold, looming cement architecture set against manicured green lemon trees and that beautiful blue Pacific Ocean. A brochure in the lobby explained it a bit. In 1965, founder Jonas Salk commissioned world-famous architect Louis Kahn to build a structure:

…that was adaptable to the ever-changing needs of science. The building materials had to be simple and strong — able to withstand the tests of time, without costly attention to maintenance. Above all else, the laboratory environments had to meet the researchers’ functional, humanistic and aesthetic needs…Salk said: “Create a facility worthy of a visit by Pablo Picasso.”

Indeed, the labs are spacious and filled with light, and the buildings have needed very little maintenance in the last 50 years. Still, I couldn’t quite shake the feeling of being in a bomb shelter…

When children with autism look at these 'Gabor patches', their brain response is about 20 milliseconds faster than in controls.

In the 1970s, when animal scientist Temple Grandin began her research on livestock behavior in Tempe, Arizona, she noticed that cattle are often spooked by seemingly insignificant visual details, such as a yellow hose on the ground or light reflecting off a piece of metal.

Grandin, who was diagnosed with autism in 1950, says that she has always had extraordinary vision, but “never really thought anything of it”. When she sits at a boring meeting, for instance, she says she often studies the tiny pattern variations in the carpet beneath her; when she drives at night, she sees so clearly that she sometimes forgets to turn on the headlights.

This ‘eagle-eyed’ vision, characteristic of many people on the autism spectrum, stems at least in part from abnormal variations in the early stages of visual processing, according to two reports published in the January issue of Biological Psychiatry.

The first report, published by researchers at the University of Sheffield in England, found that when children with autism look at simple line diagrams, the aggregated response of all of their brain cells occurs fractions of a second sooner than in healthy controls.

In the second study, psychologists at the University of Cambridge’s Autism Research Centre found that compared with healthy controls, high-functioning adults with autism score twice as high on standard tests of visual acuity — the ability to resolve fine detail in an image.

“When a person with autism walks into a room, the first thing they see is a stain on the coffee table and 17 floor boards,” says Elizabeth Milne, a lecturer in cognitive neuroscience at the University of Sheffield who led the first study. These new studies agree with previous work showing that people with autism have “a tendency to focus more on local details, often at the expense of the bigger picture,” she says.

Many anecdotal reports have described extra-sharp vision among people with autism but, so far, no large epidemiological study has estimated its prevalence.

Previous research on visual perception in autism focused almost entirely on ‘high-level’ visual perception — the use of visual information to solve relatively complicated cognitive tasks.

“Now people are starting to show more of an interest in the lower level,” says Milne, referring to early aspects of visual processing, such as the response of retinal cells to a light stimulus, or a brain cell’s first response to a single black line.

The autism field needs more work in low-level visual processing, but the findings must be integrated with previous work on higher levels of visual processing, other experts add.

“There really is room for more of this kind of low-level visual testing in people with autism, but that has to be done in collaboration with visual psychophysicists,” says Steven Dakin, a reader in visual psychophysics at University College London’s Institute of Ophthalmology who was not involved in either study.

“The balance of evidence of there being a difference in visual processing in people with autism is overwhelming,” he says. “But the story is almost certainly more complicated than a simple difference in acuity.”

…Read the rest of my latest article at SFARI

Photo Credit: Tony Zador, CSHL

In the past year, researchers have debuted a growing number of mouse models that they say exhibit the subtle behaviors of autism. In the midst of controversy over whether these mouse models represent autism, one team of scientists is looking for quirks in the animals’ neural circuits.

In October 2007, a high-profile report unveiled mice that carry a mutation in neuroligin-3, which has been associated with autism in people. Since then, about a dozen other models have been proposed, showcasing a grab bag of genetic mutations: some are pivotal players in the development of nerve cell axons, others in synapse formation. One mutation, PTEN, has a strong role in cancer.

As the list of candidate genes for autism grows, experts estimate that at least 30 mouse models of autism will surface within the next couple of years.

“With all of these models, the question now becomes: What do you do once you have the mouse?” asks neurophysiologist Tony Zador of Cold Spring Harbor Laboratory (CSHL).

Although much has been made of the mice’s autism-like behaviors — hovering alone in a corner of their cage or repeatedly sniffing the same spot — no one has yet compared the brain physiology, such as connections between neurons or firing patterns, of these mutant mice to that of normal mice. One study published in June claimed that the neuroligin-3 mouse model of autism behaves no differently than normal mice.

“These autistic mouse models present only more questions,” says Pavel Osten, assistant professor of physiology at Northwestern University. “At the moment, they are the most interesting thing in all of neurobiology.”

Zador, Osten, and CSHL neurobiologist Josh Huang say the common link among the growing number of mouse models of autism is likely to be found not in their social behaviors or communicative abilities, but in the way neurons in different brain regions communicate with one another.

The trio is looking for quantifiable markers of disease, or ‘endophenotypes’, in the brain wiring of two mouse models of autism. “Our goal is to understand the gene mutations that eventually lead to autism or Rett syndrome at the level of brain circuitry: what connections, and what cell types, do they disrupt?” says Huang.

The researchers are also developing techniques to rapidly image an entire mouse brain within a few hours. Standard methods can take about a week, creating a bottleneck between genetic and behavioral research.

“Genetics research has a very high throughput,” says Osten, noting that genome-wide analyses can scan for thousands of genes at a time. Ideally, he says, neurophysiologists would screen various mouse models of these genetic variations at a similar pace. “That may be possible eventually, but at the moment we’d be happy to increase by ten-fold the speed you can look at mouse models,” he says.

Geneticists are optimistic about the approach, even though the team’s first experiments are still months away from publication.

“Right now you have a lot of people like me who are deeply invested in genetic manipulation. But our expertise doesn’t run to the behavioral and systems analysis,” says developmental neurobiologist Gordon Fishell of New York University, who is not involved in the research.

Fishell is working on yet another mouse model of autism by knocking out genes that code for interneurons, cells that dampen electrical signaling in the brain. “Guys like Tony are just such obvious partners for people like me, because they can take [the research] so much further.”

…read the rest of my latest at Simons

So far, researchers have identified five taste receptors on the human tongue that sense the following tastes: sweet, salty, sour, bitter, and umami. The latter, which gives us that hearty mmmeaty taste, was discovered almost a century ago by Kikunae Ikeda of Tokyo Imperial University. But that there was a unique umami receptor wasn’t confirmed until the 1980s. Now, neuroscientists at NYC’s very own Mount Sinai have found the T1R3 “sweet” taste receptor, but in an unusual place: the gut.

These gut taste cells regulate secretion of insulin and hormones that regulate appetite, according to the paper published in the August 20 Early Edition of PNAS. Because sensing sugar in the gastrointestinal tract is the first step in regulating blood sugar levels, head researcher Robert Margolskee says the findings may help in designing new drugs for diabetes and obesity.

Now a related question for my reader-experts: When I was a neuroscience student, my professors taught me that the five receptors were found in patches in different parts of the tongue—sweet on the tip, bitter in the back, etc. But this surely doesn’t mean that if I put a chunk of salt on the tip of my tongue I won’t be able to taste it right away? Are the receptors actually found everywhere, but just clumped mostly in those areas?