Brain & Behavior Research Foundation Announces 10 Major Research Achievements of 2012

In 2012, the Brain & Behavior Research Foundation funded more than 200 new promising ideas through its NARSAD Grants to identify the causes, improve treatments and develop prevention strategies for mental illness. Many research projects also came to fruition in 2012, and the Foundation highlights ten significant findings.

Monkey See, Monkey Do: Visual Feedback Is Necessary for Imitating Facial Expressions

Studies of the chameleon effect confirm what salespeople, tricksters, and Lotharios have long known: Imitating another person’s postures and expressions is an important social lubricant.

But how do we learn to imitate with any accuracy when we can’t see our own facial expressions and we can’t feel the facial expressions of others?

Richard Cook of City University London, Alan Johnston of University College London, and Cecilia Heyes of the University of Oxford investigate possible mechanisms underlying our ability to imitate in two studies published in Psychological Science, a journal of the Association for Psychological Science.

In the first experiment, the researchers videotaped participants as they recited jokes and then asked them to imitate four randomly selected facial expressions from their videos. When they achieved what they perceived to be the target expression, the participants recorded the attempt with the click of a computer mouse.

A computer program evaluated the accuracy of participants’ imitation attempts against a map of the target expression. In contrast to previous studies that relied on subjective assessments, this new technology allowed for automated and objective measurement of imitative accuracy.

In one experiment, the researchers found that participants who were able to see their imitation attempts through visual feedback improved over successive attempts. But participants who had to rely solely on proprioception – sensing the relative position of their facial features – got progressively worse.

These results are consistent with the associative sequence-learning model, which holds that our ability to imitate accurately depends on learned associations between what we see (in the mirror or through feedback from others) and what we feel.

Cook and colleagues conclude that contingent visual feedback may be a useful component of rehabilitation and skill-training programs that are designed to improve individuals’ ability to imitate facial gestures.

A New Focus on the ‘Post’ in Post-Traumatic Stress

Psychological trauma dims tens of millions of lives around the world and helps create costs of at least $42 billion a year in the United States alone. But what is trauma, exactly?

Both culturally and medically, we have long seen it as arising from a single, identifiable disruption. You witness a shattering event, or fall victim to it — and as the poet Walter de la Mare put it, “the human brain works slowly: first the blow, hours afterward the bruise.” The world returns more or less to normal, but you do not.

In 1980, the Diagnostic and Statistical Manual of Mental Disorders defined trauma as “a recognizable stressor that would evoke significant symptoms of distress in almost everyone” — universally toxic, like a poison.

But it turns out that most trauma victims — even survivors of combat, torture or concentration camps — rebound to live full, normal lives. That has given rise to a more nuanced view of trauma — less a poison than an infectious agent, a challenge that most people overcome but that may defeat those weakened by past traumas, genetics or other factors.

Now, a significant body of work suggests that even this view is too narrow — that the environment just after the event, particularly other people’s responses, may be just as crucial as the event itself.

The idea was demonstrated vividly in two presentations this fall at the Interdisciplinary Conference on Culture, Mind and Brain at the University of California, Los Angeles. Each described reframing a classic model of traumatic experience — one in lab rats, the other in child soldiers.

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Birdsong study pecks at theory that music is uniquely human

A bird listening to birdsong may experience some of the same emotions as a human listening to music, suggests a new study on white-throated sparrows, published in Frontiers of Evolutionary Neuroscience.

“We found that the same neural reward system is activated in female birds in the breeding state that are listening to male birdsong, and in people listening to music that they like,” says Sarah Earp, who led the research as an undergraduate at Emory University.

For male birds listening to another male’s song, it was a different story: They had an amygdala response that looks similar to that of people when they hear discordant, unpleasant music.

The study, co-authored by Emory neuroscientist Donna Maney, is the first to compare neural responses of listeners in the long-standing debate over whether birdsong is music.

“Scientists since the time of Darwin have wondered whether birdsong and music may serve similar purposes, or have the same evolutionary precursors,” Earp notes. “But most attempts to compare the two have focused on the qualities of the sound themselves, such as melody and rhythm.”

Earp reviewed studies that mapped human neural responses to music through brain imaging.

She also analyzed data from the Maney lab on white-throated sparrows. The lab maps brain responses in the birds by measuring Egr-1, part of a major biochemical pathway activated in cells that are responding to a stimulus.

The study used Egr-1 as a marker to map and quantify neural responses in the mesolimbic reward system in male and female white-throated sparrows listening to a male bird’s song. Some of the listening birds had been treated with hormones, to push them into the breeding state, while the control group had low levels of estradiol and testosterone.

During the non-breeding season, both sexes of sparrows use song to establish and maintain dominance in relationships. During the breeding season, however, a male singing to a female is almost certainly courting her, while a male singing to another male is challenging an interloper.

For the females in the breeding state every region of the mesolimbic reward pathway that has been reported to respond to music in humans, and that has a clear avian counterpart, responded to the male birdsong. Females in the non-breeding state, however, did not show a heightened response.

And the testosterone-treated males listening to another male sing showed an amygdala response, which may correlate to the amygdala response typical of humans listening to the kind of music used in the scary scenes of horror movies.

“The neural response to birdsong appears to depend on social context, which can be the case with humans as well,” Earp says. “Both birdsong and music elicit responses not only in brain regions associated directly with reward, but also in interconnected regions that are thought to regulate emotion. That suggests that they both may activate evolutionarily ancient mechanisms that are necessary for reproduction and survival.”

A major limitation of the study, Earp adds, is that many of the regions that respond to music in humans are cortical, and they do not have clear counterparts in birds. “Perhaps techniques will someday be developed to image neural responses in baleen whales, whose songs are both musical and learned, and whose brain anatomy is more easily compared with humans,” she says.

MRI Can Screen Patients for Alzheimer’s Disease or Frontotemporal Lobar Degeneration, Using Penn-designed Model

When trying to determine the root cause of a person’s dementia, using an MRI can effectively and non-invasively screen patients for Alzheimer’s disease or Frontotemporal Lobar Degeneration (FTLD), according to a new study by researchers from the Perelman School of Medicine at the University of Pennsylvania. Using an MRI-based algorithm effectively differentiated cases 75 percent of the time, according to the study, published in the December 26th, 2012, issue of Neurology, the medical journal of the American Academy of Neurology. The non-invasive approach reported in this study can track disease progression over time more easily and cost-effectively than other tests, particularly in clinical trials testing new therapies.

Researchers used the MRIs to predict the ratio of two biomarkers for the diseases - the proteins total tau and beta-amyloid - in the cerebrospinal fluid. Cerebrospinal fluid analyses remain the most accurate method for predicting the disease cause, but requires a more invasive lumbar puncture. “Using this novel method, we obtain a single biologically meaningful value from analyzing MRI data in this manner and then we can derive a probabilistic estimate of the likelihood of Alzheimer’s or FTLD,” said the study’s lead author, Corey McMillan, PhD, of the Perelman School of Medicine and Frontotemporal Degeneration Center at the University of Pennsylvania.

Using the MRI prediction method was 75 percent accurate at identifying the correct diagnosis in both patients with pre-confirmed disease diagnoses and those with biomarker levels confirmed by lumbar punctures, which shows comparable overlap between accuracy of the MRI and lumbar puncture methods. “For those remaining 25 percent of cases that are borderline, a lumbar puncture testing spinal fluid may provide a more accurate estimate of the pathological diagnosis.”

Accurate tests to measure disease progression are very important in neurodegenerative diseases, especially as clinical trials test new therapies to slow or stop the progression or the disease. Biomarkers for neurodegenerative diseases have been steadily improving, with new developments including spinal fluid tests detecting tau and amyloid-beta protein levels and other neuroimaging techniques developed at Penn Medicine, as part of the Alzheimer’s Disease Neuroimaging Initiative. While a spinal fluid test can be used to accurately pinpoint whether disease-specific proteins are present, the test requires a more invasive lumbar puncture making it more difficult to repeat over time. And for studies using other imaging techniques, such as test measuring whole brain volume, reduced sensitivity of the measurement requires more patients to be enrolled in clinical trials for statistical power to be achieved.

“Since this method yields a single biological value, it is possible to use MRI to screen patients for inclusion in clinical trials in a cost-effective manner and to provide an outcome measure that  optimizes power in drug treatment trials,” the authors concluded.

Does Einstein’s brain hold the secret to his genius?

Albert Einstein’s brain fascinates scientists and the general public alike, because it may provide clues to the neurological basis of his extraordinary intellectual abilities. The latest study of the great physicist’s grey matter was published last month. The researchers analyzed previously unpublished photographs of the great physicist’s cerebral cortex, and claim to have identified unusual, and hitherto unknown, features. But some are sceptical about how the findings have been interpreted.

Shortly after Einstein’s death on 18th April, 1955, pathologist Thomas Harvey removed his brain and dissected it into 240 blocks, taking dozens of photographs while he did so. He then sent some of the tissue samples and photographs to a handful of researchers, and eventually, a small number of studies emerged. The early ones showed that Einstein’s brain was, in fact, slightly smaller, and weighed about 200 grams less, than average, but subsequent investigations revealed several unusual features, which were, it was claimed, somehow related to his visuo-spatial skills.

For the new study, anthropologist Dean Falk of Florida State University and her colleagues analyzed 14 of the’s photographs from the museum collection, which together reveal the entire surface of Einstein’s cerebral cortex for the first time, enabling the researchers to examine the pattern of grooves and ridges and in detail and compare them to those seen in other brains.

"The new photographs reveal parts of Einstein’s brain that have not previously been seen in published images," says Falk. "We have identified most of the external details of his cerebral cortex, [and] the complexity and pattern of convolutions on certain parts of Einstein’s cerebral cortex is striking and unusual in comparison to brains from normal individuals."

"This is especially noticeable in the prefrontal cortex, which is important for advanced cognition, the parietal lobes, which are important for spatial and arithmetic reasoning, and the visual cortex. The primary sensory and motor cortices are also extraordinarily expanded in certain parts."

Some argue that any conclusions drawn from such findings could be meaningless. “Studying Einstein’s brain is like studying the writings of Nostradamus,” says Chris Chambers, a cognitive neuroscientist at Cardiff University. “You can read them backwards, forward, or even sideways, and draw whatever conclusions you like.”

"We inevitably end up committing logical fallacies of reverse inference and faulty generalisation: that certain parts of Einstein’s brain may look a bit different to other brains, and that this explains his abilities. But the differences might have no functional importance whatsoever, and this makes any kind of conclusion extremely weak."

Chambers adds that there is enormous variability in human brain structure, and that this poses another problem when trying to interpret such findings. “We’re dealing with just one brain and this makes it impossible to draw any firm conclusions about the population at large. Human brains come in all shapes and sizes and there is no known relationship to cognition. Very few people have the ‘normal’ brain we see in textbooks, and neither did Einstein.”

Clinical neurologist Frederick Lepore, a co-author of the new study, made similar arguments in 2001, and in an interview published online earlier this month, he is quoted as saying that the new study confirms Einstein’s brain “was very different,” but that “we face an insurmountable explanatory gap if we attempt to use our neuroanatomical findings to account for the mind that envisioned the curvature of the universe.”

He goes on to say that the next logical step would be to try to generate Einstein’s connectome, a comprehensive map of the connections in his brain, and that a comparison of the brain to those of other geniuses is another possible avenue of research.

Falk believes that the photographs could help researchers to map Einstein’s connectome. “[We have published]… the ‘roadmap’ that provides a key between these areas and recently emerged histological slides of Einstein’s brain, which may allow scientists to study its internal connectivity. These photographs should become more meaningful in the future, as more is learned about the functions of various regions.”

PredictAD software promises early diagnosis of Alzheimer’s

Scientists at VTT Technical Research Centre in Finland have developed new software called PredictAD that could significantly boost the early diagnosis of Alzheimer’s disease.

The comparative software contrasts patient’s measurements with those of other patients kept in large databases, then visualizes the status of the patient with an index and graphics.

The support system and imaging methods were developed by VTT and Imperial College London.

The researchers used material compiled in the U.S. by the Alzheimer’s Disease Neuroimaging Initiative based on the records of 288 patients with memory problems. Nearly half of them, or 140 individuals, were diagnosed with Alzheimer’s disease on average 21 months after the initial measurements, which is about the same as the current European average of 20 months.

The researchers concluded that half of the patients could have been diagnosed with the disease around a year earlier, or nine months after the initial measurements. They say the accuracy of the predictions was comparable to clinical diagnosis.

There are several advantages of an early diagnosis of Alzheimer’s. It can delay institutionalization and slow down the progress of the disease. It is also advantageous from the clinical trials perspective because if patients caught early can be included in the trials, treatment is likely to be more effective.

Working towards the same goal, researchers at Lancaster University in the U.K. recently developed an eye test method to detect early signs of Alzheimer’s.

The VTT researchers will spend the next five years carrying out the test at memory clinics in Europe. They also hope to expand its scope to include other illnesses that cause dementia. According to 2010 figures, an estimated 35.6 people live with dementia worldwide, and that number is expected to rise to 65.7 million by 2030.

The findings of the research were published in the Journal of Alzheimer’s Disease in November 2012. VTT cooperated with the University of Eastern Finland and Copenhagen University Hospital Rigshospitalet on this project.

How Excess Holiday Eating Disturbs Your ‘Food Clock’

If the sinful excess of holiday eating sends your system into butter-slathered, brandy-soaked overload, you are not alone: People who are jet-lagged, people who work graveyard shifts and plain-old late-night snackers know just how you feel.

All these activities upset the body’s “food clock,” a collection of interacting genes and molecules known technically as the food-entrainable oscillator, which keeps the human body on a metabolic even keel. A new study by researchers at UCSF is helping to reveal how this clock works on a molecular level.

Published this month in the journal Proceedings of the National Academy of Sciences, the UCSF team has shown that a protein called PKCγ is critical in resetting the food clock if our eating habits change.

The study showed that normal laboratory mice given food only during their regular sleeping hours will adjust their food clock over time and begin to wake up from their slumber, and run around in anticipation of their new mealtime. But mice lacking the PKCγ gene are not able to respond to changes in their meal time – instead sleeping right through it.

The work has implications for understanding the molecular basis of diabetes, obesity and other metabolic syndromes because a desynchronized food clock may serve as part of the pathology underlying these disorders, said Louis Ptacek, MD, the John C. Coleman Distinguished Professor of Neurology at UCSF and a Howard Hughes Medical Institute Investigator.

It may also help explain why night owls are more likely to be obese than morning larks, Ptacek said.

“Understanding the molecular mechanism of how eating at the “wrong” time of the day desynchronizes the clocks in our body can facilitate the development of better treatments for disorders associated with night-eating syndrome, shift work and jet lag,” he added.

Resetting the Food Clock

Look behind the face of a mechanical clock and you will see a dizzying array of cogs, flywheels, reciprocating counterbalances and other moving parts. Biological clocks are equally complex, composed of multiple interacting genes that turn on or off in an orchestrated way to keep time during the day.

In most organisms, biological clockworks are governed by a master clock, referred to as the “circadian oscillator,” which keeps track of time and coordinates our biological processes with the rhythm of a 24-hour cycle of day and night.

Life forms as diverse as humans, mice and mustard greens all possess such master clocks. And in the last decade or so, scientists have uncovered many of their inner workings, uncovering many of the genes whose cycles are tied to the clock and discovering how in mammals it is controlled by a tiny spot in the brain known as the “superchiasmatic nucleus.”

Scientists also know that in addition to the master clock, our bodies have other clocks operating in parallel throughout the day. One of these is the food clock, which is not tied to one specific spot in the brain but rather multiple sites throughout the body.

The food clock is there to help our bodies make the most of our nutritional intake. It controls genes that help in everything from the absorption of nutrients in our digestive tract to their dispersal through the bloodstream, and it is designed to anticipate our eating patterns. Even before we eat a meal, our bodies begin to turn on some of these genes and turn off others, preparing for the burst of sustenance – which is why we feel the pangs of hunger just as the lunch hour arrives.

Scientist have known that the food clock can be reset over time if an organism changes its eating patterns, eating to excess or at odd times, since the timing of the food clock is pegged to feeding during the prime foraging and hunting hours in the day. But until now, very little was known about how the food clock works on a genetic level.

What Ptacek and his colleagues discovered is the molecular basis for this phenomenon: the PKCγ protein binds to another molecule called BMAL and stabilizes it, which shifts the clock in time.