Neuroscience

In an Australian first, researchers are studying Magnetic Seizure Therapy (MST) as an alternative treatment for the 30 per cent of patients suffering from depression who don’t respond to traditional treatment.

The treating team; Anne Maree Clinton, Dr Kate Hoy and Professor Paul Fitzgerald with the MST machine

The study, led by researchers from the Monash Alfred Psychiatry Research Centre (MAPrc) and funded by beyondblue and the National Health and Medical Research Council (NHMRC), has been published in two leading journals: Psychiatry Research: Neuroimaging and Depression and Anxiety. Both papers are a result of the same study.

MAPrc Deputy Director Professor Paul Fitzgerald, who led the study, said depression was a common and disabling disorder, affecting up to one in five Australians during their lifetime.

“Electroconvulsive Therapy (ECT) is one of the only established interventions for treatment resistant depression,” Professor Fitzgerald said.

“But use of ECT is limited due to the presence of memory-related side effects and associated stigma.”

For this reason, the MAPrc researchers began exploring new treatment options. MST is a brain-stimulation technique that may have similar clinical effects to ECT without the unwanted side effects.

“In MST, a seizure is induced through the use of magnetic stimulation rather than a direct electrical current like ECT. Magnetic fields are able to pass freely into the brain, making it possible to more precisely focus stimulation,” Professor Fitzgerald said.

“By avoiding the use of direct electrical currents and inducing a more focal stimulation, it is thought that MST will result in an improvement of depressive symptoms without the memory difficulties seen with ECT.”

Research is still at an early stage and MST is only available in a handful of locations worldwide. The MAPrc is the only centre in Australia conducting trials with this therapy.

The study found that MST resulted in an overall significant reduction in depression symptoms; 40 per cent showed overall improvement and 30 per cent showed some improvement. None of the trial participants complained of cognitive side effects.

“MST shows antidepressant efficacy without apparent cognitive side effects. However, substantial research is required to understand the optimal conditions for stimulation and to compare MST to established treatments, including ECT,” Professor Fitzgerald said.

“In order to accurately assess the comparable efficacy of MST to ECT, large-scale randomised controlled trials are required. There remains considerable work to be done before statements of the relative efficacy of these treatments can be made.”

Professor Fitzgerald and his team have received more funding from beyondblue and the NHMRC to carry out a large-scale trial on MST as an alternative treatment for depression.

TAU researcher discovers that family history of schizophrenia is a risk factor for autism

Autism Spectrum Disorders (ASD), a category that includes autism, Asperger Syndrome, and Pervasive Developmental Disorder, are characterized by difficulty with social interaction and communication, or repetitive behaviors. The U.S. Centers for Disease Control and Management says that one in 88 children in the US is somewhere on the Autism spectrum — an alarming ten-fold increase in the last four decades.

New research by Dr. Mark Weiser of Tel Aviv University’s Sackler Faculty of Medicine and the Sheba Medical Center has revealed that ASD appears share a root cause with other mental illnesses, including schizophrenia and bipolar disorder. At first glance, schizophrenia and autism may look like completely different illnesses, he says. But closer inspection reveals many common traits, including social and cognitive dysfunction and a decreased ability to lead normal lives and function in the real world.

Studying extensive databases in Israel and Sweden, the researchers discovered that the two illnesses had a genetic link, representing a heightened risk within families. They found that people who have a schizophrenic sibling are 12 times more likely to have autism than those with no schizophrenia in the family. The presence of bipolar disorder in a sibling showed a similar pattern of association, but to a lesser degree.

A scientific leap forward, this study sheds new light on the genetics of these disorders. The results will help scientists better understand the genetics of mental illness, says Dr. Weiser, and may prove to be a fruitful direction for future research. The findings have been published in the Archives of General Psychiatry.

All in the family

Researchers used three data sets, one in Israel and two in Sweden, to determine the familial connection between schizophrenia and autism. The Israeli database alone, used under the auspices of the ethics committees of both the Sheba Medical Center and the Israeli Defense Forces, included anonymous information about more than a million soldiers, including patients with schizophrenia and ASD.

"We found the same results in all three data sets," he says, noting that the ability to replicate the findings across these extensive databases is what makes this study so significant.Understanding this genetic connection could be a missing link, Dr. Weiser says, and provides a fresh direction for study. The researchers are now taking this research in a clinical direction. For now, though, the findings shouldn’t influence the way that doctors treat patients with either illness, he adds.

People with perfect pitch seem to possess their own inner pitch pipe, allowing them to sing a specific note without first hearing a reference tone. This skill has long been associated with early and extensive musical training, but new research suggests that perfect pitch may have as much to do with genetics as it does with learning an instrument or studying voice.

Previous research does draw a connection between early musical training and the likelihood of a person developing perfect pitch, which is also referred to as absolute pitch. This is especially true among speakers of tonal languages, such as Mandarin. Speakers of English and other non-tonal languages are far less likely to develop perfect pitch, even if they were exposed to early and extensive musical training.

“We have wondered if perfect pitch is as much about nature or nurture,” said Diana Deutsch, a professor of psychology at the University of California, San Diego. “What is clear is that musically trained individuals who speak a non-tone language can acquire absolute pitch, but it is still a remarkably rare talent. What has been less clear is why most others with equivalent musical training do not.” Deutsch and her colleague Kevin Dooley present their findings at the 164th meeting of the Acoustical Society of America (ASA), held Oct. 22 – 26 in Kansas City, Missouri.

To shine light on this question, the researchers studied 27 English speaking adults, 7 of whom possessed perfect pitch. All began extensive musical training at or before the age of 6. The researchers tested the subjects’ memory ability using a test known as the digit span, which measures how many digits a person can hold in memory and immediately recall in correct order. They presented the digits either visually or auditorily; for the auditory test, the subject listened to the numbers through headphones, and for the visual test the digits were presented successively at the center of a computer screen.

The people with perfect pitch substantially outperformed the others in the audio portion of the test. In contrast, for the visual test, the two groups exhibited very similar performance, and their scores were not significantly different from each other. This is significant because other researchers have shown previously that auditory digit span has a genetic component.

“Our finding therefore shows that perfect pitch is associated with an unusually large memory span for speech sounds,” said Deutsch, “which in turn could facilitate the development of associations between pitches and their spoken languages early in life.”

A new study shows that electrical stimulation of a small patch of the brain causes illusions that only affect the perception of faces. (Matt Cardy/Getty Images)

Ron Blackwell didn’t enter the hospital expecting to see his doctor’s face melt before his eyes. But that’s exactly what happened when researchers electrically stimulated a small part of his brain, according to a study published Tuesday in the Journal of Neuroscience.

The doctor’s face did not actually melt, of course. Instead, the researchers argue, the stimulation short-circuited a brain area called the fusiform gyrus. Previous studies have linked a part of that area to face processing by showing that it becomes active when people perceive faces. But it’s hard to know just how important the area is for facial processing unless you can actually change its activity level while someone views faces.

Blackwell, an epileptic, turned out to be the perfect test case. He was in Stanford’s hospital so that doctors — including the study author, Dr. Josef Parvizi — could study his epilepsy and decide whether they could perform surgery to remove the part of the brain responsible for his seizures. As part of that procedure, Parvizi laid down a strip of electrodes on the surface of the brain. That gave him the capacity to painlessly and harmlessly stimulate the part of the brain they covered, and one of those electrodes was right over the fusiform gyrus.

Along with collaborators led by Stanford psychologist Kalanit Grill-Spector, Parvizi stimulated the area to see whether it would affect Blackwell’s perception of the doctor’s face. When he performed a sham stimulation — counting down from three and pressing a button that did nothing — Blackwell reported no change.

But when Parvizi applied voltage, strange things suddenly began to happen to Blackwell’s face perception. “You just turned into somebody else,” Blackwell said in a video that was recorded as part of the experiment. “Your face metamorphosed. Your nose got saggy, went to the left. You almost looked like somebody I’d seen before, but somebody different. That was a trip.” As soon as the electricity was turned off, Blackwell’s visualization of Parvizi’s face returned to normal.

Later, Blackwell confirmed that it was only the doctor’s face that changed — his body and hands remained the same.

Though only a single case, the experiment provides strong confirmatory evidence that the fusiform gyrus is indeed directly involved in processing face perception, and that the area is specialized for doing so.

New imaging techniques are mapping the locations of our aesthetic response

In Michelangelo’s Expulsion from Paradise, a fresco panel on the ceiling of the Sistine Chapel, the fallen-from-grace Adam wards off a sword-wielding angel, his eyes averted from the blade and his wrist bent back defensively. It is a gesture both wretched and beautiful. But what is it that triggers the viewer’s aesthetic response—the sense that we’re right there with him, fending off blows?

Recently, neuroscientists and an art historian asked ten subjects to examine the wrist detail from the painting, and—using a technique called trans­cranial magnetic stimulation (TMS)—monitored what happened in their brains. The researchers found that the image excited areas in the primary motor cortex that controlled the observers’ own wrists.

“Just the sight of the raised wrist causes an activation of the muscle,” reports David Freedberg, the Columbia University art history professor involved in the study. This connection explains why, for instance, viewers of Degas’ ballerinas sometimes report that they experience the sensation of dancing—the brain mirrors actions depicted on the canvas.

Freedberg’s study is part of the new but growing field of neuroaesthetics, which explores how the brain processes a work of art. The discipline emerged 12 years ago with publication of British neuroscientist Semir Zeki’s book, Inner Vision: An Exploration of Art and the Brain. Today, related studies depend on increasingly sophisticated brain-imaging techniques, including TMS and functional magnetic resonance imaging (fMRI), which maps blood flow and oxygenation in the brain. Scientists might monitor an observer’s reaction to a classical sculpture, then warp the sculpture’s body proportions and observe how the viewer’s response changes. Or they might probe what occurs when the brain contemplates a Chinese landscape painting versus an image of a simple, repetitive task.

Ulrich Kirk, a neuroscientist at the Virginia Tech Carilion Research Institute, is also interested in artworks’ contexts. Would a viewer respond the same way to a masterpiece enshrined in the Louvre if he beheld the same work displayed in a less exalted setting, such as a garage sale? In one experiment, Kirk showed subjects a series ofimages—some, he explained, were fine artwork; others were created by Photoshop. In reality, none were Photoshop-generated; Kirk found that different areas of viewers’ brains fired up when he declared an image to be “art.”

Kirk also hopes one day to plumb the brains of artists themselves. “You might be able to image creativity as it happens, by putting known artists in the fMRI,” he says.

Others, neuroscientists included, worry that neuroscience offers a reductionist perspective. Vilayanur Ramachandran, a neuroscientist at the University of California at San Diego, says that neuro­aesthetics undoubtedly “enriches our understanding of human aesthetic experience.” However, he adds, “We have barely scratched the sur­face…the quintessence of art, and of genius, still eludes us—and may elude us forever.”

Analysis of specific biomarkers in a cerebrospinal fluid sample can differentiate patients with Alzheimer’s disease from those with other types of dementia. The method, which is being studied by researchers at Sahlgrenska Academy, may eventually permit earlier detection of Alzheimer’s disease.

Due to the similarity of the symptoms, differentiating patients with Alzheimer’s from those with other types of dementia – or patients with Parkinson disease from those with other motor disorders – is often difficult.

Making a proper diagnosis is essential if proper treatment and medication are to commence at an early stage. A research team at Sahlgrenska Academy, University of Gothenburg, is developing a new method to differentiate patients with Alzheimer’s disease or Parkinson disease by analyzing a cerebrospinal fluid sample.

The study, led by Professor Kaj Blennow and conducted among 450 patients at Skåne University Hospital and Sahlgrenska University Hospital, involved testing five proteins that serve as biomarkers for the two diseases.

“Previous studies have shown that Alzheimer’s disease is associated with biochemical changes in specific proteins of the brain,” says Annika Öhrfelt, a researcher at Sahlgrenska Academy. “This study has found that the inclusion of a new protein can differentiate patients with Alzheimer’s disease from those with Lewy body dementia, Parkinson disease dementia and other types of dementia.”

Similarly, the biomarkers can differentiate patients with Parkinson disease from those with atypical Parkinsonian disorders.

“Additional studies are needed before the biomarkers can be used in clinical practice during the early stages of disease,” says Öhrfelt, “but these results represent an important step along the way.”

Researchers at Washington University School of Medicine in St. Louis have found a key difference in the brains of people with Alzheimer’s disease and those who are cognitively normal but still have brain plaques that characterize this type of dementia.

“There is a very interesting group of people whose thinking and memory are normal, even late in life, yet their brains are full of amyloid beta plaques that appear to be identical to what’s seen in Alzheimer’s disease,” says David L. Brody, MD, PhD, associate professor of neurology. “How this can occur is a tantalizing clinical question. It makes it clear that we don’t understand exactly what causes dementia.”

Hard plaques made of a protein called amyloid beta are always present in the brain of a person diagnosed with Alzheimer’s disease, according to Brody. But the simple presence of plaques does not always result in impaired thinking and memory. In other words, the plaques are necessary – but not sufficient – to cause Alzheimer’s dementia.

The new study, available online in Annals of Neurology, still implicates amyloid beta in causing Alzheimer’s dementia, but not necessarily in the form of plaques. Instead, smaller molecules of amyloid beta dissolved in the brain fluid appear more closely correlated with whether a person develops symptoms of dementia. Called amyloid beta “oligomers,” they contain more than a single molecule of amyloid beta but not so many that they form a plaque.

Oligomers floating in brain fluid have long been suspected to have a role in Alzheimer’s disease. But they are difficult to measure. Most methods only detect their presence or absence, or very large quantities. Brody and his colleagues developed a sensitive method to count even small numbers of oligomers in brain fluid and used it to compare amounts in their samples.

The researchers examined samples of brain tissue and fluid from 33 deceased elderly subjects (ages 74 to 107). Ten subjects were normal – no plaques and no dementia. Fourteen had plaques, but no dementia. And nine had a diagnosis of Alzheimer’s disease – both plaques and dementia.

They found that cognitively normal patients with plaques and Alzheimer’s patients both had the same amount of plaque, but the Alzheimer’s patients had much higher oligomer levels.

But even oligomer levels did not completely distinguish the two groups. For example, some people with plaques but without dementia still had oligomers, even in similar quantity to some patients with Alzheimer’s disease. Where the two groups differed completely, according to Brody and his colleagues, was the ratio of oligomers to plaques. They measured more oligomers per plaque in patients with dementia, and fewer oligomers per plaque in the samples from cognitively normal people.

In people with plaques but no dementia, Brody speculates that the plaques could serve as a buffer, binding with free oligomers and keeping them tied down. And in dementia, perhaps the plaques have exceeded their capacity to capture the oligomers, leaving them free to float in the brain’s fluid, where they can damage or interfere with neurons.

Brody cautions that, due to the difficulty in getting samples, oligomer levels have never been measured in living people. Therefore, it’s possible these floating clumps of amyloid beta only form after death. Even so, he says, there is still a clear difference between the two groups.

“The plaques and oligomers appear to be in some kind of equilibrium,” Brody says. “What happens to shift the relationship between the oligomers and plaques? Like much Alzheimer’s research, this study raises more questions than it answers. But it’s an important next piece of the puzzle.”

Blood-circulating immune cells can take over the essential immune surveillance of the brain, this is shown by scientists of the German Center for Neurodegenerative Diseases (DZNE) and the Hertie Institute for Clinical Brain Research in Tübingen. Their study, now published in PNAS, might indicate new ways of dealing with diseases of the nervous system.

The immune system is comprised of multiple cell types each capable of specialized functions to protect the body from invading pathogens and promote tissue repair after injury. One cell type, known as monocytes, circulates throughout the organism in the blood and enters tissues to actively phagocytose (eat!) foreign cells and assist in tissue healing. While monocytes can freely enter most bodily tissues, the healthy, normal brain is different as it is sequestered from circulating blood by a tight network of cells known as the blood brain barrier. Thus, the brain must maintain a highly specialized, resident immune cell, known as microglia, to remove harmful invaders and respond to tissue damage.

In certain situations, such as during disease, monocytes can enter the brain and also contribute to tissue repair or disease progression. However, the potential for monocytes to actively replace old or injured microglia is under considerable debate. To address this, Nicholas Varvel, Stefan Grathwohl and colleagues from the German Center for Neurodegenerative Diseases (DZNE) Tübingen and the Hertie Institute for Clinical Brain Research in Tübingen used a transgenic mouse model in which almost all brain microglia cells (>95%) can be removed within two weeks. This was done by introducing a so-called suicide gene into microglia cells and administering a pharmaceutical agent that leads to acute death of the cells. Surprisingly, after the ablation of the microglia, the brain was rapidly repopulated by blood-circulating monocytes. The monocytes appeared similar, but not identical to resident microglia. The newly populated monocytes, evenly dispersed throughout the brain, responded to acute neuronal injury and other stimuli — all activities normally assumed by microglia. Most interestingly, the monocytes were still present in the brain six months - nearly a quarter of the life of a laboratory mouse - after initial colonization.

These studies now published in PNAS provide evidence that blood-circulating monocytes can replace brain resident microglia and take over the essential immune surveillance of the brain. Furthermore, the findings highlight a strong homeostatic mechanism to maintain a resident immune cell within the brain. The observation that the monocytes took up long-term residence in the brain raises the possibility that these cells can be utilized to deliver therapeutic agents into the diseased brain or replace microglia when they become dysfunctional. Can monocytes be exploited to combat the consequences of Alzheimer’s disease and other neurodegenerative diseases? The scientists and their colleagues in the research groups headed by Mathias Jucker are now following exactly this research avenue.

In 1906, when Alois Alzheimer discovered the neurodegenerative disease that would later be named for him, he saw amyloid-beta plaques and neurofibrillary tangles inside the brain. Several decades later, abnormal protein structures called Hirano bodies also were frequently observed in patients with neurodegenerative diseases.

A hundred years and many millions of suffering patients and families later, scientists still don’t know what these structures do. They do know, thanks to new research from the University of Georgia, that Hirano bodies may have a protective role in the brain of Alzheimer’s patients.

Matthew Furgerson, a doctoral candidate in the UGA Franklin College of Arts and Sciences department of biochemistry and molecular biology, used cell culture models to study the role of Hirano bodies in cell death induced by AICD, or a fragment of AICD called c31, that are released inside the cell during cleavage of the amyloid precursor protein. This cleavage also produces amyloid-beta, which forms extracellular plaques.

Furgerson found mixtures of amyloid precursor protein, c31 and tau-the protein that forms the intracellular neurofibrillary tangles-or of AICD and tau cause synergistic cell death that is significantly higher than cell death from amyloid precursor protein, c31, AICD or tau alone.

"This synergistic cell death is very exciting," Furgerson said. "Other groups have shown synergy between extracellular amyloid beta or amyloid precursor protein with tau, but these new results show that there may be an important interaction that occurs inside the cells."

The results of this study were published in the September issue of PLoS One. Ruth Furukawa, associate research scientist, and Marcus Fechheimer, University Professor in cellular biology, are co-authors on the paper.

Furgerson also found cell death is significantly reduced in cells that contain Hirano bodies compared to cells without Hirano bodies. The protective effect of Hirano bodies was observed in cell cultures in both the presence and absence of tau. The findings reveal that Hirano bodies may have a protective role during the progression of Alzheimer’s disease.

While this research offers no cure for the disease, it does offer some understanding about how the disease operates. The lab has been a leader of Hirano body research for more than a decade due to their development of cell culture and mouse model systems.

Before the development of model systems, the only way to study these abnormal structures was in post-mortem brain tissue. The recently developed Hirano body mouse model is currently being used with an Alzheimer’s model mouse to investigate whether cell culture results can translate to a complex animal.

"I feel privileged to lead a team that might be able to contribute knowledge to help us understand Alzheimer’s disease processes," Fechheimer said. "Other groups have focused on plaques and tangles, and we don’t know as much about Hirano bodies. Results from the cell culture studies are exciting and reveal the protective role of Hirano bodies. Our ongoing studies with mouse models are essential to defining the role of Hirano bodies in Alzheimer’s disease progression in a whole animal."

Perceive first, act afterwards. The architecture of most of today’s robots is underpinned by this control strategy. The eSMCs project has set itself the aim of changing the paradigm and generating more dynamic computer models in which action is not a mere consequence of perception but an integral part of the perception process. It is about improving robot behaviour by means of perception models closer to those of humans.

"The concept of how science understands the mind when it comes to building a robot or looking at the brain is that you take a photo, which is then processed as if the mind were a computer, and a recognition of patterns is carried out. There are various types of algorithms and techniques for identifying an object, scenes, etc. However, organic perception, that of human beings, is much more active. The eye, for example, carries out a whole host of saccadic movements -small rapid ocular movements- that we do not see. Seeing is establishing and recognising objects through this visual action, knowing how the relationship and sensation of my body changes with respect to movement," explains Xabier Barandiaran, a PhD-holder in Philosophy and researcher at IAS-Research (UPV/EHU) which under the leadership of Ikerbasque researcher Ezequiel di Paolo is part of the European project eSMCs (Extending Sensorimotor Contingencies to Cognition).

Until now, the belief has been that sensations were processed, and the perception was created, and this in turn then led to reasoning and action. As Barandiaran sees it, action is an integral part of perception:”Our basic idea is that when we perceive, what is there is active exploration, a particular co-ordination with the surroundings, like a kind of invisible dance than makes vision possible.”

The eSMCs project aims to apply this idea to the computer models used in robots, improve their behaviour and thus understand the nature of the animal and human mind. For this purpose, the researchers are working on sensorimotor contingencies: regular relationships existing between actions and changes in the sensory variations associated with these actions.

An example of this kind of contingency is when you drink water and speak at the same time, almost without realising it. Interaction with the surroundings has taken place “without any need to internally represent that this is a glass and then compute needs and plan an action,” explains Barandiaran, “seeing the glass draws one’s attention, it is coordinated with thirst while the presence of the water itself on the table is enough for me to coordinate the visual-motor cycle that ends up with the glass at my lips.”The same thing happens in the robots in the eSMCs project, “they are moving the whole time, they don’t stop to think; they think about the act using the body and the surroundings,” he adds.

The researchers in the eSMCs project maintain that actions play a key role not only in perception, but also in the development of more complex cognitive capacities. That is why they believe that sensorimotor contingencies can be used to specify habits, intentions, tendencies and mental structures, thus providing the robot with a more complex, fluid behaviour.

So one of the experiments involves a robot simulation (developed by Thomas Buhrmann, who is also a member of this team at the UPV/EHU) in which an agent has to discriminate between what we could call an acne pimple and a bite or lump on the skin.”The acne has a tip, the bite doesn’t. Just as people do, our agent stays with the tip and recognises the acne, and when it goes on to touch the lump, it ignores it. What we are seeking to model and explain is that moment of perception that is built with the active exploration of the skin, when you feel ‘ah! I’ve found the acne pimple’ and you go on sliding your finger across it,” says Barandiaran. The model tries to identify what kind of relationship is established between the movement and sensation cycles and the neurodynamic patterns that are simulated in the robot’s “mini brain”.

In another robot, built at the Artificial Intelligence Laboratory of Zürich University, Puppy, a robot dog, is capable of adapting and “feeling” the texture of the terrain on which it is moving (slippery, viscous, rough, etc.) by exploring the sensorimotor contingencies that take place when walking.

The work of the UPV/EHU’s research team is focusing on the theoretical part of the models to be developed.”As philosophers, what we mostly do is define concepts. Our main aim is to be able to define technical concepts like the sensorimotor habitat, or that of the pattern of sensorimotor co-ordination, as well as that of habit or of mental life as a whole. “Defining concepts and giving them a mathematical form is essential so that the scientist can apply it to specific experiments, not only with robots, but also with human beings. The partners at the University Medical Centre Hamburg-Eppendorf, for example, are studying in dialogue with the theoretical development of the UPV/EHU team how the perception of time and space changes in Parkinson’s patients.

Researchers identify brain mechanisms that regulating cocaine-seeking behavior

Researchers from the University of Wisconsin-Milwaukee (UWM) have identified mechanisms in the brain responsible for regulating cocaine-seeking behavior, providing an avenue for drug development that could greatly reduce the high relapse rate in cocaine addiction.

The research reveals that stimulation of certain brain receptors promotes inhibition of cocaine-associated memories, helping addicts to stop drug use. This inhibition is achieved through enhancing a process called “extinction learning,” in which cocaine-associated memories are replaced with associations that have no drug “reward.” This reduces drug-seeking behavior in rats.

The work was presented at the annual meeting of the Society for Neuroscience in New Orleans by Devin Mueller, UWM assistant professor of psychology, and doctoral student James Otis.

There are currently no FDA-approved medications to treat cocaine abuse, only treatments that address withdrawal symptoms, says Mueller. Abuse is maintained, in part, through exposure to environmental cues that trigger cocaine-related memories which lead to craving and relapse in recovering addicts. Currently, exposure therapy is used to help recovering addicts suppress their drug-seeking behavior, but with limited success. In exposure therapy, a patient is repeatedly exposed to stimuli that provoke craving. With repeated exposure, the patient experiences extinction, leading to reduced craving when presented with those stimuli.

If extinction could be strengthened, it would increase the effectiveness of exposure therapies in preventing relapse.

Isolating the receptor

The team found that a specific variant of the NMDA receptor, those which contain the NR2B subunit, are critical for extinction learning. They also discovered that drugs known to enhance NR2B function strengthened extinction because they act specifically in a region of the brain that regulates learned behaviors. In their investigation, researchers conditioned rats to associate one distinct chamber, but not another, with cocaine. Following conditioning, the rats were tested for a place preference by allowing drug-free access to both chambers. Rats demonstrating cocaine-seeking behavior spent significantly more time in the previously cocaine-associated chamber. Over several cocaine-free test sessions, addicted rats lost their place preference through extinction learning.

To examine the neural mechanisms of extinction, the researchers administered ifenprodil, which blocks NR2B-containing NMDA receptors, immediately after an extinction test. Ifenprodil-treated rats continued to spend more time in the cocaine-associated chamber even in the absence of cocaine, while saline-treated rats did not. These results were also replicated through specific infusion of ifenprodil into the brain’s infralimbic cortex, localizing a key brain structure in arresting cocaine-seeking.

Other avenues

The results indicate that enhancing NR2B function would boost the effectiveness of extinction-based exposure therapies. Although there are currently no NR2B-enhancing drugs, the NR2B containing receptor can be stimulated using other molecular pathways, says Mueller.

An example is the brain derived neurotrophic factor (BDNF) signaling cascade, which is implicated in neuron survival and growth. The authors targeted this cascade by directly administering BDNF into the infralimbic cortex. In extinction tests, administration of BDNF caused rats to lose their preference for the cocaine-associated chamber faster than rats given a placebo.

Mueller and Otis took these findings even further toward possible therapeutic intervention for addicts.

One issue with giving BDNF to humans is that it is unable to reach the brain through the bloodstream. Therefore, researchers next targeted the TrkB receptor, which is where BDNF normally binds. They did so with a newly synthesized drug that is able to reach the brain due to its small molecular size. This TrkB receptor agonist, known as 7,8 dihydroxyflavone, also strengthened extinction when given to rats during extinction training. The authors conclude that combining TrKB receptor stimulation simultaneously with exposure therapy could be an effective treatment for cocaine abuse, reducing craving and the potential for relapse.

You glimpse a stranger standing in the street. The light is hazy and the person’s face and clothing are indistinct. Who is it? Chances are you will think it is a man—and the reason for this is a survival reflex, according to an unusual study published on Wednesday.

Psychologists at the University of California at Los Angeles delved into our quest for visual clues when we assess other people.

They asked male and female students to look at 21 human silhouettes, all of them the same height, but with a progressively changing waist-to-hip ratio. The figures began with an obviously female “hourglass” figure and, after incremental changes, ended with an obviously male “hunk” figure. The volunteers were asked to say whether each of the 21 silhouettes was male or female, the idea being to identify the point where they saw a shift in gender.

What was striking, said researcher Kerri Johnson, was a preference for the volunteers to deem a shape to be a man whenever it was ambiguous—or could readily have been taken for a woman. “I was surprised by the size of the effect. It was a much stronger effect than I ever imagined,” Johnson said in a phone interview.

In the natural world, the demarcation between a woman’s shape and man’s shape comes when the ratio of the waist and hip circumferences is 0.8. But the volunteers, on average, placed the boundary at 0.68. In other words, an identifiable female shape for them was close to the idealised curves of a pinup.

Johnson’s team carried out three further studies, using a slightly different methods to see whether their approach had been skewed, and found that the bias in favour of men was unchanged. Are these errors in perception? Not so, said Johnson, who believes it to be an ancestral survival mechanism.

A man is likelier than a woman to be a bigger physical threat and our default perception is to prepare for risk: it’s better to be safe than sorry. “We suspect that this might be for a self-protective reason,” she said. “If you are walking down a dark alley at night, a woman poses no great physical threat to you in general, but if you encounter an unknown man, he’s more likely to have a physical formidability that could pose some risks.”

Johnson conceded that there could be cultural or ethnic factors which influence judgement but argued that the same kind of bias would prevail anywhere. “I think it’s entirely likely that if we were to test this in different populations we would probably have the same basic effect, the same pattern of judgement, although the strength of the judgement might vary,” she said.

The findings show how gender stereotypes can be reinforced, sometimes dangerously so, said the study. A woman could struggle if she has a body shape that is perceived as masculine and thus unattractive. “Consistent with other research, this is likely to produce preferences for extreme body shapes, particularly for women,” said the study.

The paper appears in the British journal Proceedings of the Royal Society B

Electrical stimulation of the visual cortex may one day give image perception to blind people.

Work presented at the Society for Neuroscience meeting in New Orleans today suggests a way to create a completely new kind of visual prosthetic—one that restores vision by directly activating the brain.

In a poster session, researchers presented results showing how electrical stimulation of the visual cortex can evoke the sensation of simple flashes of light—including spatial information about those flashes.

While other researchers are trying to develop artificial retinas that feed visual signals into existing sensory pathways (see “A Retinal Prosthetic Powered by Light" and "Now I See You" for instance), the team behind the new work, from the Baylor College of Medicine and the University of Texas Health Science Center in Houston, is exploring the possibility of bypassing those routes all together. This could be vital for those whose retinas are unable to receive retinal stimulation.

The researchers used electrodes to stimulate the brains of three patients who were already undergoing brian surgery to treat epilepsy. All three were able to detect bright spots of light, called phosphenes, when certain regions of their brains were stimulated. And, in seven out of eight trials, the patients were able to correctly see the orientation of a phosphene—in one of two orientations, depending on the stimulation they received. 

The work builds upon a study published by the same team in Nature Neuroscience this summer. In that study, the researchers defined which areas of the brain produce phosphene perception when patients’ brains were electrically stimulated.

A press release related to the earlier work says that the researchers “plan to conduct a larger patient study and create multiple flashes of light at the same time. Twenty-seven or so simultaneous flashes might allow participants to see the outline of a letter.”