Have we met before? Scientists show why the brain has the answer

ScienceDaily (Aug. 4, 2011) — Have you ever been approached by someone whose face you recognize but whose name you can't remember? Neuroscientists at the University of Bristol have identified the reasons behind why we are, at times, unable to link a face to a name.

The research, led by Dr Clea Warburton and Dr Gareth Barker in the University's School of Physiology and Pharmacology and published in the Journal of Neuroscience, has investigated why we can recognise faces much better if we have extra clues as to where or indeed when we encountered them in the first place.

The study found that when we need to remember that a particular object, for example a face, occurred in a particular place, or at a particular time, multiple brain regions have to work together -- not independently.

It has been known for some time that three brain regions appear to have specific roles in memory processing. The perirhinal cortex seems to be critical for our ability to recognise whether an individual object is novel or familiar, the hippocampus is important for recognising places and for navigation, while the medial prefrontal cortex is associated with higher brain functions.

These most recent studies, however, are the first to look at situations where these brain regions interact all together, rather than considering each one individually.

Dr Warburton said: "We are very excited to discover this important brain circuit. We're now studying how memory information is processed within it, in the hope we can then understand how our own 'internal library' system works."

The researchers investigated the neural basis of our ability to recognise different types of stimuli under different conditions. Of specific interest were two types of recognition memory: 'object-in-place recognition memory' (remembering where we put our keys), and 'temporal order recognition memory' (when we last had them).

Neither 'object-in-place' or 'temporal order recognition' memories could be formed if communication between the hippocampus and either the perirhinal cortex, or the medial prefrontal cortex, was broken. In other words, disconnecting the regions prevented the ability to remember both where objects had been, and in which order.

Finding that these regions must all act together has important implications for understanding memory and helping treat people with memory disorders such as Alzheimer's disease.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Bristol, via EurekAlert!, a service of AAAS.

Journal Reference:

G. R. I. Barker, E. C. Warburton. When Is the Hippocampus Involved in Recognition Memory? Journal of Neuroscience, 2011; 31 (29): 10721 DOI: 10.1523/JNEUROSCI.6413-10.2011

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here sciencedaily.com

Think healthy, eat healthy: Scientists show link between attention and self-control

ScienceDaily (July 26, 2011) — You're trying to decide what to eat for dinner. Should it be the chicken and broccoli? The super-sized fast-food burger? Skip it entirely and just get some Rocky Road?

Making that choice, it turns out, is a complex neurological exercise. But, according to researchers from the California Institute of Technology (Caltech), it's one that can be influenced by a simple shifting of attention toward the healthy side of life. And that shift may provide strategies to help us all make healthier choices -- not just in terms of the foods we eat, but in other areas, like whether or not we pick up a cigarette.

Their research is described in a paper published in the July 27 issue of the Journal of Neuroscience.

When you decide what to eat, not only does your brain need to figure out how it feels about a food's taste versus its health benefits versus its size or even its packaging, but it needs to decide the importance of each of those attributes relative to the others. And it needs to do all of this more-or-less instantaneously.

Antonio Rangel, professor of economics and neuroscience at Caltech, has been studying this value-deriving and decision-making process for years now. Along with Todd Hare -- a former postdoc at Caltech who is now an assistant professor of neuroeconomics at the University of Zurich in Switzerland -- he published a paper in Science in 2009 describing differences in the brains of people who are better at exercising self-control than others. What they found was that while everyone uses the same area of the brain -- the ventral medial prefrontal cortex, or vmPFC -- to make value-laden decisions like what to munch on, there's a second brain area -- the dorsolateral prefrontal cortex, or dlPFC -- that seems to come to life when a person is using self-control during the decision-making process.

In other words, when the dlPFC is active, it allows the vmPFC to take into account health benefits as well as taste when it assigns a value to a particular food.

The new study goes a step further, showing that there seem to be ways to help kickstart the dlPFC through the use of what Hare calls "external cues" that allow us to exhibit more self-control than we might have otherwise.

The researchers came to their conclusions based on data from a brain-imaging experiment conducted with 33 adult volunteers, none of whom were following a specific diet or trying to lose weight for any reason. Each of the volunteers was shown 180 different food items -- from chips and candy bars to apples and broccoli -- through a set of video goggles while in a functional magnetic resonance imaging (fMRI) machine.

The hungry subjects -- they were asked to fast for at least three hours prior to the experiment -- were given up to three seconds to respond to each picture with a decision about whether or not they'd want to eat the food shown after the experiment was over. They could either give the food a "strong no," a "no," a "yes," or a "strong yes." Once all of the images had been flipped through, a single food image was chosen at random; if the volunteer had said "yes" or "strong yes" to the idea of eating that food, he or she was served that item.

"Because only one random trial was selected to 'count,'" says Rangel, "the optimal strategy for subjects is to treat each decision as if it were the only one."

Simple, right? But here's the catch: before every 10 food choices, an instruction would come on the screen for five seconds telling the subjects either to "consider the healthiness," "consider the tastiness," or "make decisions naturally." This meant that of the 180 decisions, the subjects made 60 in each of the three "instruction conditions."

What this was meant to do, Rangel explains, is shift the subject's attention during the experiment and, potentially, shift the way in which they made decisions.

Afterward -- outside the scanner -- the subjects were asked to rate the same foods on both a tastiness scale (very untasty, untasty, tasty, very tasty) and a healthiness scale (very unhealthy, unhealthy, healthy, very healthy). That way, the researchers were able to associate the choices the subjects made during the brain scan with their stated perceptions of those foods' attributes -- showing that a subject who chose broccoli during the "consider the healthiness" portion of the test might think of it nonetheless as untasty.

The researchers then classified the foods for each subject based on that subject's ratings: unhealthy-untasty, healthy-untasty, unhealthy-tasty, and healthy-tasty. Unsurprisingly, people chose healthy-tasty foods no matter where their attention had been directed.

Things got interesting when the researchers looked at the other three categories, however. Among their findings:

When thinking about healthiness, subjects were less likely to eat unhealthy foods, whether or not they deemed them to be tasty, and more likely to eat healthy-untasty foods.Being asked to think about healthiness led subjects to say "no" to foods more often than they did when asked to make decisions naturally.There were no real differences between the choices made during the "consider the tastiness" and "make decisions naturally" portions of the experiment.

When the researchers turned to the fMRI results, they found that the vmPFC was, as predicted, "more responsive to the healthiness of food in the presence of health cues," says Rangel. And, as they'd seen previously, the robustness of that response was due to the influence of the dlPFC -- that bastion of self-control -- which was much quieter when the study's subjects were thinking about taste or their own personal choice than when they were asked to throw healthiness into the equation.

"This increased influence of the health signals on the vmPFC results in an overall value for the food that is based more on its health properties than is the case when the subject's attention is not focused on healthiness," says Hare.

These results are most likely not limited just to choices about food, Hare says. "Our findings are also relevant to the current changes to cigarette warnings many governments have started to make," he notes. "These changes include adding graphical images of the health risks of smoking. It remains to be seen whether these images will be more effective in drawing attention to the unhealthiness of smoking than the text warnings. If the graphical warnings do increase attention to health, then our results suggest that they could decrease the desire to smoke."

Jonathan Malmaud, a former research assistant at Caltech who is now a graduate student at MIT, was also an author on the Journal of Neuroscience paper, "Focusing attention on the health aspects of foods changes value signals in the vmPFC and improves dietary choice." The scientists' work was funded by a grant from the National Science Foundation.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by California Institute of Technology.

Journal Reference:

T. A. Hare, J. Malmaud, A. Rangel. Focusing Attention on the Health Aspects of Foods Changes Value Signals in vmPFC and Improves Dietary Choice. Journal of Neuroscience, 2011; 31 (30): 11077 DOI: 10.1523/JNEUROSCI.6383-10.2011

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Scientists create vaccine against heroin high

ScienceDaily (July 21, 2011) — Researchers at The Scripps Research Institute have developed a highly successful vaccine against a heroin high and have proven its therapeutic potential in animal models.

The new study, published recently online ahead of print by the American Chemical Society's Journal of Medicinal Chemistry, demonstrates how a novel vaccine produces antibodies (a kind of immune molecule) that stop not only heroin but also other psychoactive compounds metabolized from heroin from reaching the brain to produce euphoric effects.

"In my 25 years of making drug-of-abuse vaccines, I haven't seen such a strong immune response as I have with what we term a dynamic anti-heroin vaccine," said the study's principal investigator, Kim D. Janda, the Ely R. Callaway, Jr. Chair in Chemistry and a member of The Skaggs Institute for Chemical Biology at Scripps Research. "It is just extremely effective. The hope is that such a protective vaccine will be an effective therapeutic option for those trying to break their addiction to heroin."

"We saw a very robust and specific response from this heroin vaccine," said George F. Koob, chair of the Scripps Research Committee on the Neurobiology of Addictive Disorders and a co-author of the new study. "I think a humanized version could be of real help to those who need and want it."

A Worldwide Epidemic

While injection drug abuse is a debilitating worldwide epidemic, heroin abuse and addiction are especially destructive, with costs estimated at $22 billion in the United States due to loss of productivity, criminal activity, medical care, and social welfare, the authors say in their study.

Heroin abuse and addiction are also driving forces in the spread of HIV through needle sharing.

Using an approach termed "immunopharmacotherapy," Janda and his Scripps Research colleagues previously created vaccines that used immune molecules to blunt the effects of other abused drugs such as cocaine, methamphetamine, and nicotine. Human clinical trials are under way for the cocaine and nicotine vaccines.

Attempts by other researchers over the past four decades to create a clinically viable heroin vaccine, however, have fallen short, in part due to the fact that heroin is an elusive target metabolized into multiple substances each producing psychoactive effects.

An Innovative Approach

To overcome this problem, in the new study the Scripps Research team used a "dynamic" approach, targeting not only heroin itself, but also the chemical it quickly degrades into, 6-acetylmorphine (6AM), and morphine.

"Heroin is lipophilic and is rapidly degraded to 6AM," said G. Neil Stowe, a research associate in Janda's laboratory who is first author of the new study. "Both readily cross the blood-brain barrier and gain access to the opioid receptors in the brain."

The researchers linked a heroin-like hapten (a small molecule that elicits an immune response) to a generic carrier protein called keyhole limpet hemocyanin or KLH, and mixed it with Alum, an adjuvant (vaccine additive), to create a vaccine "cocktail." This mixture slowly degraded in the body, exposing the immune system to different psychoactive metabolites of heroin such as 6AM and morphine.

"Critically, the vaccine produces antibodies to a constantly changing drug target," said Stowe. "Such an approach has never before been engaged with drug-of-abuse vaccines."

To compare the results of a non-dynamic approach, the team also prepared a vaccine simply targeting morphine, a substance related to heroin. Both vaccines were then injected into rats and the effects were examined in Koob's laboratory.

Promising Results

The results showed that the rats rapidly generated robust polyclonal antibodies in response to the dynamic heroin vaccine.

In addition, the study found that addicted rats were less likely to "self-administer" heroin by pressing on a lever after several booster shots of the vaccine. Only three of the seven rats that received the heroin vaccine self-administered heroin. In contrast, all of the control rats, including those given the morphine vaccine, self-administered the drug.

The effect of the heroin vaccine "was very dramatic; as dramatic as we have ever seen in experiments of this kind," said Koob. "To have an animal vaccinated and not show a response to heroin is pretty amazing."

The team also found that the heroin vaccine was highly specific, meaning that it only produced an antibody response to heroin and 6AM, and not to the other opioid-related drugs tested, such as oxycodone as well as drugs used for opioid dependence -- methadone, naltrexone, and naloxone. "The importance of this," said Janda, "is that it indicates these vaccines could be used in combination with other heroin rehabilitation therapies."

The Scripps Research team has recently begun an exciting collaboration with researchers at the Walter Reed Army Institute of Research to see if it is feasible to develop a dual-purpose vaccine against HIV and for the treatment of heroin addiction in a single shot, Janda said.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Scripps Research Institute, via EurekAlert!, a service of AAAS.

Journal Reference:

G. Neil Stowe, Leandro F. Vendruscolo, Scott Edwards, Joel E. Schlosburg, Kaushik K. Misra, Gery Schulteis, Alexander V. Mayorov, Joseph S. Zakhari, George F. Koob, Kim D. Janda. A Vaccine Strategy that Induces Protective Immunity against Heroin. Journal of Medicinal Chemistry, 2011; 110630091316074 DOI: 10.1021/jm200461m

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Scientists discover potential stroke treatment that may extend time to prevent brain damage

ScienceDaily (July 25, 2011) — A naturally occurring substance shrank the size of stroke-induced lesions in the brains of experimental mice -- even when administered as much as 12 hours after the event, Stanford University School of Medicine researchers have shown. The substance, alpha-B-crystallin, acts as a brake on the immune system, lowering levels of inflammatory molecules whose actions are responsible for substantial brain damage above and beyond that caused by the initial oxygen deprivation of a stroke.

The finding, which will be published online July 25 in Proceedings of the National Academy of Sciences, is of great potential significance. Every year brings nearly 800,000 new stroke patients in North America. "That's one every 40 seconds," said Gary Steinberg, MD, PhD, director of Stanford's Institute for Neuro-Innovation and Translational Neurosciences and one of the study's two senior authors. Steinberg is also the Bernard and Ronni Lacroute-William Randolph Hearst Professor of Neurosurgery and the Neurosciences, and chair of neurosurgery at the medical school.

The largest single cause of severe neurological disability and the third-leading cause of death in the United States, stroke accounts for an estimated $74 billion annually in related costs, including treatment and additional assistance for the three of every four stroke patients whose ability to perform the activities of daily life is impaired. Strokes are caused by a sudden drop in the flow of blood to the brain resulting from a clot or, less often, bleeding. One of every three stroke patients is under the age of 65. In all, there are 5.4 million stroke survivors in the United States and 15 million worldwide.

The only currently approved drug for stroke -- tissue plasminogen activator, or tPA -- dissolves clots that keep oxygenated blood from reaching brain tissue. To be effective, tPA must be administered within about 4.5 hours after the stroke. But patients' brains must first be scanned to rule out the possibility that the stroke was caused by bleeding, which tPA would exacerbate, rather than by blockage.

Moreover, tPA does nothing to counter the stroke's insidious inflammatory aftershock: a flood of noxious chemicals secreted by angry immune cells that rush in to the affected area, causing significant further damage.

Alpha-B-crystallin appears to act as a sponge, sopping up those bad actors and stopping inflammation from making a bad situation worse.

Alpha-B-crystallin is a major structural protein in the eye's lens. It is also constantly made in the heart. In other tissues, including the brain, its production can be triggered by stressful events, such as oxygen deprivation or excessive heat or cold. Growing evidence suggests that alpha-B-crystallin can help curb inflammatory activity in the brain.

"The brain doesn't roll over and play dead when it's under attack," said Lawrence Steinman, MD, the other senior author of the new study, who is the George A. Zimmermann Professor of Neurology and Neurological Sciences and Pediatrics as well as chair of Stanford's interdepartmental program in immunology.

In an earlier study, published in Nature in 2007, Steinman and his colleagues found that the presence of alpha-B-crystallin could help reduce the severity of brain damage caused by multiple sclerosis, a chronic, debilitating autoimmune disease of the brain. Other studies published this year by his group have shown that alpha-B-crystallin limits the damage caused by blood-supply cutoffs to heart tissue and the retina.

It seemed logical to see if this protein could mitigate the effects of a stroke. "We made a jump from its relevance in inflammatory diseases such as multiple sclerosis," Steinberg said. "To my knowledge, nobody had looked at concentrations of alpha-B-crystallin after a stroke, either in people or in an experimental animal model before."

So, along with first authors Ahmet Arac, MD, a postdoctoral scholar in Steinberg's lab, and Steinman's former graduate student Sarah Brownell, PhD, Steinberg and Steinman turned to a standard animal model: the laboratory mouse. They found that, in mice bioengineered to lack alpha-B-crystallin, experimentally induced stroke lesions were more massive than those induced in otherwise genetically similar mice whose cells were capable of making the protein. The alpha-B-crystallin-deficient mice had worse neurological function after the stroke than did the normal mice.

The researchers also found that supplying synthetic alpha-B-crystallin to the deficient mice reduced brain-lesion sizes after a stroke, even when the substance was administered 12 hours after the stroke was induced. And they saw elevated alpha-B-crystallin levels in blood plasma from both human patients and mice after a stroke. (The human samples were obtained from study co-author Gregory Albers, MD, the Coy Foundation Professor of Neurology and Neurological Sciences and the director of the Stanford Stroke Center).

"In younger patients, the larger the stroke, the higher the concentration of alpha-B-crystallin," said Steinberg. Interestingly, increased alpha-B-crystallin levels were not detected in plasma from patients over the age of 80, whose strokes typically have worse consequences than those affecting younger patients.

Finally, the investigators demonstrated that alpha-B-crystallin-treated mice produce fewer inflammatory immune-signaling molecules and more anti-inflammatory ones than untreated mice.

At the doses given to the mice in this study, alpha-B-crystallin appeared to be nontoxic. "This is a naturally occurring molecule the body is already producing, although maybe just not enough of it," said Steinberg. "We're just supplementing it." If further studies by other labs and in other models confirm and extend the findings, alpha-B-crystallin may be an excellent candidate for clinical trials in stroke, Steinman and Steinberg both said.

"This is the first demonstration of an efficacious brain-protecting agent that targets the inflammatory aspect of stroke in a novel way, and it can be given at quite a delay," said Thomas Carmichael, MD, PhD, professor and vice chair of neurology at the David Geffen School of Medicine at UCLA. Carmichael, a stroke expert, did not participate in the study but is familiar with its methodology and results. "Tissue plasminogen activator has a fairly narrow risk-to-benefit ratio. The longer you wait, the more likely it is to stimulate a hemorrhage."

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Stanford University Medical Center. The original article was written by Bruce Goldman.

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here