Deficits in Brain's Reward System Observed in ADHD Patients

A brain-imaging study conducted at Brookhaven National Laboratory provides the first definitive evidence that patients suffering from attention deficit hyperactivity disorder (ADHD) have lower-than-normal levels of certain proteins essential for experiencing reward
and motivation.

"These deficits in the brain's reward system may help explain clinical symptoms of ADHD, including inattention and reduced motivation, as well as the propensity for complications such as drug abuse and obesity among ADHD patients," says lead author Nora Volkow, director of the National Institute on Drug Abuse and a long-time collaborator on neuroimaging research at Brookhaven Lab.

The study, published in the September 9, 2009, issue of the Journal of the American Medical Association, also has important implications for treatment. "Finding ways to address the underlying reward-system deficit could improve the direct clinical outcome of ADHD, and potentially reduce the likelihood of other negative consequences of this condition," says study co-author Gene-Jack Wang, chair of Brookhaven's medical department.

Prior to this study, it was not clear whether people with ADHD had abnormalities in the brain's dopamine-mediated motivation/reward system. Previous studies were relatively small and may have been complicated by the fact that some ADHD patients had undergone treatments, or had a history of drug abuse or other conditions that can affect the dopamine system.

To strengthen the statistics and control for these factors, the current study looked at 53 adult ADHD patients who had never received treatment and 44 healthy control subjects -- all of whom had been carefully screened to eliminate potentially confounding variables.

The scientists used positron emission tomography (PET) to measure two markers of the dopamine system -- dopamine receptors, to which the chemical messenger binds to propagate the "reward" signal, and dopamine transporters, which take up and recycle excess dopamine after the signal is sent.

Lying in a PET scanner, each patient was injected with a minute amount of a "radiotracer" compound -- a chemical labeled with a radioactive form of carbon and designed to bind specifically to one of the targets. Different tracers were used for each target, and patients were scanned for each at separate times. By detecting the signal from the radiotracers, the PET machine can measure the receptor and transporter locations and concentrations in various parts of the brain.

The results clearly showed that, relative to the healthy control subjects, the ADHD patients had lower levels of dopamine receptors and transporters in the accumbens and midbrain -- two key regions of the brain directly involved in processing motivation and reward. In addition, the measurements of dopamine markers correlated with measures of behavior and clinical observations of ADHD symptoms, such as reduced levels of attention as measured by standard
psychological tests.

"Our findings imply that these deficits in the dopamine reward pathway play a role in the symptoms of inattention in ADHD and could underlie these patients' abnormal responses to reward," Volkow says.

"This pathway plays a key role in reinforcement, motivation, and in learning how to associate various stimuli with rewards," she adds. "Its involvement in ADHD supports the use of interventions to enhance the appeal and relevance of school and work tasks to improve performance.

"Our results also support the continued use of stimulant medications - the most common pharmacological treatment for ADHD -- which have been shown to increase attention to cognitive tasks by elevating brain dopamine," she says.

The findings may also help explain why ADHD patients are more likely than control subjects to develop drug-abuse disorders and conditions such as obesity.

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Video of the Day - Brain Study: "Use It or Lose It"

New research is changing the understanding of the relationship between getting older and keeping the mind healthy. The key - according to scientists - is exercise. Mental exercise.

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Video of the Day: Honey, I Love You With All My Medial Insula

If that special someone makes your heart go pitter-patter, you should see what's happening with your medial insula, anterior cingulate and hippocampus.

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Brain Starvation as We Age Appears to Trigger Alzheimer's

A slow, chronic starvation of the brain as we age appears to be one of the major triggers of a biochemical process that causes some forms of Alzheimer's disease.

A new study from Northwestern University's Feinberg School of Medicine has found when the brain doesn't get enough sugar glucose -- as might occur when cardiovascular disease restricts blood flow in arteries to the brain -- a process is launched that ultimately produces the sticky clumps of protein that appear to be a cause of Alzheimer's.

Robert Vassar, lead author, discovered a key brain protein is altered when the brain has a deficient supply of energy. The altered protein, called elF2alpha, increases the production of an enzyme that, in turn, flips a switch to produce the sticky protein clumps. Vassar worked with human and mice brains in his research.

The study is published in the December 26 issue of the journal Neuron.

"This finding is significant because it suggests that improving blood flow to the brain might be an effective therapeutic approach to prevent or treat Alzheimer's," says Vassar, a professor of cell and molecular biology at the Feinberg School.

A simple preventive strategy people can follow to improve blood flow to the brain is getting exercise, reducing cholesterol and managing hypertension.

"If people start early enough, maybe they can dodge the bullet," Vassar says. For people who already have symptoms, vasodilators, which increase blood flow, may help the delivery of oxygen and glucose to the brain, he added.

Vassar said it also is possible that drugs could be designed to block the elF2alpha protein that begins the formation of the protein clumps, known as amyloid plaques.

An estimated 10 million baby boomers will develop Alzheimer's in their lifetime, according to the Alzheimer's Association. The disease usually begins after age 60, and risk rises with age. The direct and indirect cost of Alzheimer's and other dementias is about $148 billion a year.

The initial trigger of Alzheimer's has long been a mystery.

Ten years ago, it was Vassar who discovered the enzyme, BACE1, that was responsible for making the sticky, fiber-like clumps of protein that form outside neurons and disrupt their ability to send messages.

But the cause of the high levels of the protein in people with the disease has been unknown. Vassar's study now shows that energy deprivation in the brain might be the trigger starting the process that forms plaques in Alzheimer's.

Vassar said his work suggests that Alzheimer's disease may result from a less severe type of energy deprivation than occurs in a stroke. Rather than dying, the brain cells react by increasing BACE1, which may be a protective response in the short term, but harmful in the long term.

"A stroke is a blockage that prevents blood flow and produces cell death in an acute, dramatic event," Vassar says. "What we are talking about here is a slow, insidious process over many years where people have a low level of cardiovascular disease or atherosclerosis in the brain. It's so mild, they don't even notice it, but it has an effect over time because it's producing a chronic reduction in the blood flow."

Vassar says when people reach a certain age, some may get increased levels of the enzymes that cause a build-up of the plaques. "Then they start falling off the cliff," he says.

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Methamphetamine Enters Brain Quickly and Lingers

Using positron emission tomography (PET) to track tracer doses of methamphetamine in humans' brains, scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory find that the addictive and long-lasting effects of this increasingly prevalent drug can be explained in part by its pharmacokinetics -- the rate at which it enters and clears the brain, and its distribution. This study in 19 healthy, non-drug-abusing volunteers includes a comparison with cocaine and also looked for differences by race. It will appear in the November 1, issue of Neuroimage.

"Methamphetamine is one of the most addictive and neurotoxic drugs of abuse," says Brookhaven chemist Joanna Fowler, lead author on the study. "It produces large increases in dopamine, a brain chemical associated with feelings of pleasure and reward - both by increasing dopamine's release from nerve cells and by blocking its reuptake."

Studies by Fowler and others have shown that drugs that produce greater elevations in brain dopamine tend to be more addictive. But other factors, including the speed with which a drug enters and clears the brain and its distribution within the brain, can also be important in determining its addictive and toxic potential.

In undertaking this first study of methamphetamine pharmacokinetics, the researchers also wanted to know if there were differences between Caucasians and African Americans. "Reports that the rate of methamphetamine abuse among African Americans is lower than for Caucasians led us to question whether biological or pharmacokinetic differences might explain this difference," Fowler says.

The scientists measured brain uptake, distribution, and clearance of methamphetamine by injecting 19 normal healthy men (9 Caucasian, 10 African American) with a radioactively tagged form of the drug in "trace" doses too small to have any psychoactive effects. They used PET scanning cameras to monitor the concentration and distribution of the tagged methamphetamine in the subjects' brains. On the same day, the same subjects were injected with trace
doses of cocaine and scanned for comparison. The scientists also used PET to measure the number of dopamine reuptake proteins, known as dopamine transporters, available in each research subject's brain.

Like cocaine, methamphetamine entered the brain quickly, a finding consistent with both drugs' highly reinforcing effects. Methamphetamine, however, lingered in the brain significantly longer than cocaine, which cleared quickly. In fact, some brain regions, particularly white matter, still showed signs of tracer methamphetamine at the end of the 90-minute scanning session, by which time all cocaine had been cleared. The distribution of methamphetamine in the brain was
remarkably different from that of cocaine. Whereas cocaine was concentrated only in the 'reward' center and cleared rapidly, methamphetamine was concentrated all over the brain, where it remained throughout the study.

"This slow clearance of methamphetamine from such widespread brain regions may help explain why the drug has such long-lasting behavioral and neurotoxic effects," Fowler says. Methamphetamine is known to produce lasting damage not only to dopamine cells but also to other brain regions, including white matter, that are not part of the dopamine network.

Surprisingly, the researchers found significant differences in cocaine pharmacokinetics between African Americans and Caucasians, with the African Americans exhibiting higher uptake of cocaine, a later rise to peak levels, and slower clearance. In contrast, the scientists found no differences in methamphetamine pharmacokinetics between these groups.

"This suggests that variables other than pharmacokinetics and bioavailability account for the lower prevalence of methamphetamine abuse in African Americans," Fowler says. "The differences observed for cocaine pharmacokinetics are surprising considering there are no differences in cocaine abuse prevalence between these two ethnic groups." These differences may merit further study, and also suggest the need to match subjects by ethnic group in future studies to avoid interference from this potentially confounding variable.

Another interesting finding was that across all research subjects, the level of dopamine transporters was directly related to the level of methamphetamine taken up by the brain. This finding suggests that transporter proteins somehow play a role in regulating the brain's uptake of this drug.

This research was funded by the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism Intramural Program, and by the Office of Biological and Environmental Research within DOE's Office of Science. Brain-imaging studies such as PET are a direct outgrowth of DOE's long-standing investment in basic research in chemistry, physics, and nuclear medicine. The ongoing neuroimaging research at Brookhaven is a prime example of how DOE's national laboratories bring together the expertise of chemists, physicists, and
medical scientists to address questions of profound significance for society.

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Direct Recording Shows Brain Signal Persists Even in Dreamless Sleep

Neuroscientists at Washington University School of Medicine in St. Louis have taken one of the first direct looks at one of the human brain's most fundamental "foundations": a brain signal that never switches off and may support many cognitive functions.

The results, appearing online this week in the Proceedings of the National Academy of Sciences, are an important step forward for efforts to outline what neuroscientists call the functional architecture of the brain. Better understanding of this architecture will aid efforts to treat brain injury and mental disorders, the researchers say.

Although the brain's different specialized regions can be considered as a collection of physical structures, functional architecture instead focuses on metaphorical structures formed by brain processes and interactions among different brain regions. The "foundation" highlighted in the new study is a low-frequency signal created by neuronal activity throughout the brain. This signal doesn't switch off even in dreamless sleep, possibly to help maintain basic structure and facilitate offline housekeeping activities.

"A different, more labile and higher-frequency signal known as the gamma frequency activity has been the focus of much brain research in recent years," says first author Biyu He, a graduate student. "But we found that signal loses its large-scale structure in deep sleep, while the low-frequency signal does not, suggesting that the low-frequency signal may be more fundamental."

"What we've been finding is reorienting the way we think about how the brain works," says senior author Dr. Marcus Raichle, M.D., professor of radiology, of neurology and of neurobiology. "We're starting to see the brain as being in the prediction business, with ongoing, organized carrier frequencies within the systems of the brain that keep them prepared for the work they need to do to perform mental tasks."

Neurologists have already spent many years exploring the upper levels of the brain's functional architecture. In these studies, researchers typically ask volunteers to perform specific mental tasks as their brains are scanned using functional magnetic resonance imaging (fMRI). Such "goal-oriented" tasks might include looking for or studying a visual stimulus, moving an arm or leg, reading a word or listening for a sound. As the subjects perform these tasks, the scans reveal increases in blood flow to different parts of the brain, which researchers take as indications that the brain areas are contributing to the mental task.

In the past decade, though, scientists have realized that deeper structures underlie goal-oriented mental processes. These underlying brain processes continue to occur even when subjects aren't consciously using their brain to do anything, and the energies that the brain puts into them seem to be much greater than those used for goal-oriented tasks.

"The brain consumes a tremendous amount of the body's energy resources—it's only 2 percent of body weight, but it uses about 20 percent of the energy we take in," says Raichle. "When we started to ask where all those resources were being spent, we found that the goal-oriented tasks we had studied previously only accounted for a tiny portion of that energy budget. The rest appears to go into activities and processes that maintain a state of readiness in the brain."

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Some Brain Injuries May Reduce Likelihood of Post-Traumatic Stress

A new study of combat-exposed Vietnam War veterans shows that those with injuries to certain parts of the brain were less likely to develop post-traumatic stress disorder (PTSD). The findings, from the National Institutes of Health (NIH) and the National Naval Medical Center, suggest that drugs or pacemaker-like devices aimed at dampening activity in these brain regions might be effective treatments for PTSD.

PTSD involves the persistent reliving of a traumatic experience through nightmares and flashbacks that may seem real. Twenty percent to 30 percent of Vietnam vets (more than 1 million) have been diagnosed with PTSD, and a similar rate has been reported among Hurricane Katrina survivors in New Orleans. Public health officials are currently tracking the disorder among soldiers returning from Iraq. Yet, while war and natural disasters tend to call the greatest attention to PTSD, it's estimated that millions of Americans suffer from it as a result of assault, rape, child abuse, car accidents, and other traumatic events.

Previous studies have shown that PTSD is associated with changes in brain activity, but those studies couldn't determine whether the changes were contributing to the disorder or merely occurring because of it.

Jordan Grafman, a senior investigator at the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH, turned to the Vietnam Head Injury Study (VHIS) to make that distinction. The VHIS is a registry of Vietnam veterans who sustained penetrating brain injuries (which are less common in Iraq compared to concussion brain injuries). It has received support from the Department of Defense, the Department of Veterans of Affairs and NIH, and is currently supported by NINDS.

"If we could show that lesions in a specific brain region eliminated PTSD, we knew we could say that the region is critical to developing the disorder," says Grafman. The results of his study appear online in Nature Neuroscience.

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Further Evidence Genetics Has Role in Determining Sexual Orientation in Men

Canadian scientists have uncovered new evidence which shows genetics has a role to play in determining whether an individual is homosexual or heterosexual.

The research was conducted by Dr. Sandra Witelson, a neuroscientist in the Michael G. DeGroote School of Medicine at McMaster University, and colleagues at Sunnybrook Health Sciences Centre in Toronto who studied the brains of healthy, right-handed, 18- to 35-year-old homosexual and heterosexual men using structural Magnetic Resonance Imaging (MRI).

About 10 years ago, Witelson and Dr. Cheryl McCormick, then a student of Witelson’s, demonstrated there is a higher proportion of left-handers in the homosexual population than in the general population – a result replicated in subsequent studies which is now accepted as fact.
Handedness is a sign of how the brain is organized to represent different aspects of intelligence. Language, for example, is usually on the left - music on the right.

In other research, Witelson and research associate Debra Kigar, had found that left-handers have a larger region of the posterior corpus callosum – the thick band of nerve fibers connecting the two hemispheres of the brain – than right handers.

This raised the hypothesis for the current study – whether the anatomy of the brain of the sub-group of right-handed homosexual men is similar to that of left-handers.

They found that the posterior part of the corpus callosum is larger in homosexual than heterosexual men.

The size of the corpus callosum is largely inherited suggesting a genetic factor in sexual orientation, says Witelson. “Our results do not mean that heredity is destiny but they do indicate that environment is not the only player in the field,” she says.

While this is not a litmus test for sexual orientation, Witelson said this finding could prove to be one additional valuable piece of information for physicians and individuals who are trying to determine their sexual orientation. “Sometimes people aren’t sure of their sexual orientation.”

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Use of Techniques From Neuroscience in Today's Marketing

Using knowledge from neurosciences to market to consumers is nothing new but scanning consumers' brains to gauge their response to commercials is gaining in popularity.

Esteban Ribero, senior strategic planner at Lapiz says there are dangers in looking for answers to consumer behaviors using these techniques but there is tremendous value in using them as part of the overall strategic planning process. In his presentation to account planners at the Association of Hispanic Advertising Agencies 23rd Semi-Annual Conference, Ribero shared with an audience of account planners that opening the black box - the brain - is not the ultimate solution to effectively
market to consumers.

Account planners seek to understand the motivation behind consumer behavior and use insight and consumer perspective to provide the foundation for innovative concepts and creative execution. Borrowing the techniques and tools from neuroscientists to get to know the consumer better may offer some direction but it's not that easy, according to Ribero. "Scanning consumers' brainwaves while they watch ads and discuss concepts is a new fad and some are suggesting it is a way to bypass focus groups," Ribero says. "I want to open up the debate for account planners who are searching for the truth. I think there are huge dangers in basing our campaigns
solely on this type of information."

Ribero's presentation and interactive discussion with account planners from the Hispanic marketing industry was part of AHAA's skill-building workshops planned to challenge creative thinking and approaches. The conference was designed to spark ideas and debate, and maybe create a little controversy according to Jackie Bird, AHAA chairwoman and president of Wing Latino.

"It is imperative that we keep on top of trends that will continue to propel our industry forward," Bird says. "Our planners, and frankly all of the professionals in our business, need to understand new tools so they can use them effectively in delivering exceptional work to our clients. We can't rely on what's been done in the past to communicate with Latino consumers of today. It takes bold thinking and a willingness to listen to, and experiment with, new ideas to succeed as a professional, as a Latino agency and as an industry."

Ribero wants planners to be better informed about neuromarketing. Rather than asking consumers to identify the reasons for their behaviors, Ribero believes planners should infer that by studying humans and understanding why humans like certain things. "Humans behave the way they do but they don't know why," Ribero says. "And we won't get to the truth by asking them. By studying, reading and observing human behavior we will become better planners. As we become more strategic, our brands will become more connected with their consumers and not just sell stuff but fulfill
desires and needs that we can help them identify."

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Alzheimer's-associated Enzyme Can Disrupt Brain Activity

An enzyme involved in the formation of the amyloid-beta protein associated with Alzheimer’s disease can also alter the mechanism by which signals are transmitted between brain cells, the disruption of which can cause seizures. These findings from researchers at the MassGeneral Institute for Neurodegenerative Disorders (MGH-MIND) may explain the increased incidence of seizures in Alzheimer’s patients and suggest that potential treatments that block this enzyme – called beta-secretase or BACE – may alleviate their occurrence. The report will appear in the journal Nature Cell Biology and is receiving early online release.

“We have found a molecular pathway by which BACE can modulate the activity of sodium channels on neuronal cell membranes,” says study leader Dora Kovacs, director of the Neurobiology of Disease Laboratory in the Genetics and Aging Research Unit at MGH-MIND. “That implies that elevated BACE activity may be responsible for the seizures frequently observed in Alzheimer’s patients.”

Alzheimer's disease is characterized by plaques within the brain of the toxic amyloid-beta protein. Amyloid-beta is formed when the larger amyloid precursor protein (APP) is clipped by two enzymes – BACE and gamma-secretase – which releases the amyloid-beta fragment.
Signaling impulses in nerve cells are transmitted via voltage-gated sodium channels, structures on the cell membrane that transmit electrochemical signal by admitting charged sodium particles into the cell’s interior. Sodium channels consist of an alpha subunit, which makes up the body of the channel, and one or two beta subunits that help to regulate the channels’ activity.

Previous studies from Kovacs’ team and others showed that the BACE and gamma-secretase enzymes that release amyloid-beta from APP also act on the beta2 subunit of neuronal sodium channels. The current study was designed to examine how this processing of the beta2 subunit may alter neuronal function.

Lead author Doo Yeon Kim, and colleagues first confirmed that the beta2 subunit, similar to APP, can be acted on by BACE and gamma-secretase, releasing a portion of the beta2 molecule from the cell membrane. A series of experiments using brain tissue from animal models and from Alzheimer’s patients revealed the following series of cellular events: Elevated levels of the free beta2 segment within the cell appear to increase production of the alpha subunits, but those molecules are not incorporated into new sodium channels on the cell surface. The resulting deficit of membrane sodium channels inhibits the passage of neuronal signals into and through the cells.

Neuronal sodium-channel dysfunction is known to cause seizures in both mice and humans. In a supplement to the current paper the investigators present evidence that sodium channel metabolism is altered in the brains of Alzheimer’s patients compared with non-demented individuals of similar age.

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Why We Learn From Our Mistakes

Psychologists from the University of Exeter have identified an 'early warning signal' in the brain that helps us avoid repeating previous mistakes. Published in the Journal of Cognitive Neuroscience, their research identifies, for the first time, a mechanism in the brain that reacts in just 0.1 seconds to things that have resulted in us making errors in the past.

Previous research has shown that we learn more about things for which we initially make incorrect predictions than for things for which our initial predictions are correct. The element of surprise in discovering we are wrong is conducive to learning, but this research is the first to show how amazingly rapid our brain’s response can be. This discovery was made possible through the use of electrophysiological recordings, which allow researchers to detect processes in the brain at the instant they occur.

'It's a bit of a cliché to say that we learn more from our mistakes than our successes,' says psychologist Andy Wills of the University of Exeter, 'but for the first time we’ve established just how quickly the brain works to help us avoid repeating errors. By monitoring activity in the brain as it occurs, we were able to identify the moment at which this mechanism kicks in.’

For this study, a group of volunteers took part in a computerised task, which involved them making predictions based on information they were given. New information was then introduced, which made many of their predictions incorrect, so they needed to learn from this in order to avoid repeating the error. While they did this, their brain activity was recorded via 58 electrodes placed on their scalp. The researchers identified activity in the lower temporal region of the brain, the area closest to the temples. This occurred almost immediately after the person was presented with the visual object that had previously made them make an error, and before there was time for conscious consideration.

Most previous research in this field has focused on the frontal lobes of the brain, which are the areas associated with sophisticated human thought processes such as planning, analysis and conscious decision-making. The lower temporal region of the brain, which was the focus for this activity, is responsible for the recognition of visual objects.

’This brain signal could help us in many different kinds of situations,’ says Wills. ‘For example, when driving abroad the rules of the road sometimes differ. We may make a mistake the first time we misinterpret a situation, for example not realising that in the States cars can turn right on a red light. The next time we’re driving out there and see a red light, this early warning signal will immediately alert us to our previous mistake to prevent us from repeating it.’


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Sex on the Brain

New evidence on sex differences in people’s brains and behaviors emerges with the publication of results from the British Broadcasting Corporation’s (BBC) Sex ID Internet Survey. Survey questions and tests focused on participants’ sex-linked cognitive abilities, personality traits, interests, sexual attitudes and behavior, as well as physical traits.

The Archives of Sexual Behavior has devoted a special section in its April issue to research papers based on the BBC data. BBC Science, in collaboration with researchers in the United Kingdom and North America, designed their research project on psychological sex differences in conjunction with their TV documentary, Secrets of the Sexes.

The project culminated in the creation of the BBC Internet Survey, which was posted on the BBC Science and Nature website. In just three months (February-May 2005), more than 250,000 people from all over the world responded to the full survey. Some initial results were presented in July 2005 in the program, Secrets of the Sexes. The complete dataset has been analyzed since, with key findings published in the current issue of the Archives of Sexual Behavior.

The BBC summaries of the articles are available online at http://www.bbc.co.uk/science/humanbody/sex/articles/results/.

Included in the April issue of the Archives of Sexual Behavior is a paper on methodology, describing the study’s history, rationale, ethics and methodological considerations, namely the advantages and limitations of internet-based research.

Stian Reimers, from the Department of Psychology at University College London in the UK, says in this paper, “Much is made of the different agendas of science and the media, and the tensions that can occur when the two interact. Although this tension is not likely to disappear in the near future, it is hoped that this project can serve as an example of how positive interaction between the two professions can have beneficial consequences for both.”


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The Formation of Social Memories

Is there a specific memory for events involving people? Researchers in the Vulnerability, Adaptation and Psychopathology Laboratory (CNRS/University Paris VI France) and a Canadian team at Douglas Hospital, McGill University (Montreal), have identified the internal part of the prefrontal cortex as being the key structure for memorizing social information.

Social events such as a party with friends, a work meeting or an argument with a partner form an integral part of daily life. Our ability to remember these events, and more precisely to remember the people and the relationships we had with them, is essential to ensure satisfactory adaptation to our social existence. At a cerebral level, various regions of the brain, and particularly the hippocampus, are directly involved in learning and memory. Some of these regions are specialised in learning certain types of information, such as the amygdale and our memory for emotions.

The Canadian and French teams (the latter led by Philippe Fossati) have recently identified a precise region in the frontal cortex which may be specialised in recording and learning social information. Using a functional magnetic resonance imaging technique, the scientists measured cerebral activity in 17 volunteers while they accomplished a memory task involving pictures of social scenes (interacting individuals) and non-social scenes (landscapes with no people). They thus identified the internal part of the prefrontal cortex, called the medial prefrontal cortex, as being the key structure in memorizing social information from a picture.

Previous studies performed by the same research teams had associated this prefrontal region with thinking processes about self and others. Their work suggested that in addition to emotions, the analysis of specifically human information could facilitate learning and
memorisation, involving cerebral structures specialised in analysing mental states and empathy.
This work opens important perspectives regarding our understanding of the mechanisms of human recollections and mental disorders (schizophrenia, autism) which affect social and relational skills.


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Googling Brain Proteins With 3-D Goggles

The Allen Brain Atlas, a genome-wide map of the mouse brain on the Internet, has been hailed as "Google of the brain." The atlas now has a companion of the brain's working molecules, a sort of pop-up book of the proteins, or proteome map, that those genes express.

The protein map is "the first to apply quantitative proteomics to imaging," says Richard Smith, Battelle fellow at the US Department of Energy's Pacific Northwest National Laboratory, who led the mapping effort with Desmond Smith of UCLA's David Geffen School of Medicine.
"Proteins are the lead actors, the most important part of the picture," PNNL's Smith says. "They are the molecules that do the work of the cells."

Fine-tuning such proteome maps will enable comparisons of healthy brains with others whose protein portraits look different. Contrasts in location and abundance of proteins may display the earliest detectable stages of Alzheimer's, Parkinson's and other neurological diseases. They hope such diseases might be curbed if caught and treated early enough.

The National Institutes of Health-funded study, performed at DOE's Environmental Molecular Sciences Laboratory on PNNL's campus, is published in the advance online edition of Genome Research and featured in current Nature online Neuroscience Gateway.

To produce the map, the team characterized center-brain slices as scores of 1 millimeter cubes, or "voxels," to "show us where proteins appear in the brain and where they vary in abundance," PNNL's Smith says. "We labeled all the proteins so we would have reference points so we know we're looking at the same protein between different parts of the brain and from one mouse to another."

Until now, proteomics, which enlists a specially modified instrument called a mass spectrometer for the task of identifying proteins and tallying them, has been akin to flying blind over a lake of proteins. The abundance and protein type could be discerned from a given sample, but "knowing their location and how the abundances change in different cases is important for understanding what they do," PNNL's Smith says.

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