intellectual vanities… about close to everything

It often seems that certain aspects of our personalities are influenced by events that occurred in our childhoods. A recent study by Dr. Akaysha Tang’s research team from the University of New Mexico Psychology Department and collaborators at Rockefeller University examined how early life experience influences social skills and ability to handle stressful situations using a rat model.

In this study, Dr. Tang and colleagues examined whether rats that experienced greater novelty by spending three minutes a day away from their familiar home environment during infancy had a greater ability to compete against other rats for exclusive access to chocolate reward compared to their siblings that stayed in the home environment during infancy. They found that novelty-exposed rats were able to “beat out” their competitors more often than their home-staying siblings. They also found that across repeated sessions of competition, novelty-exposed rats decreased their release of stress hormones into the bloodstream, suggesting that they adapted faster to the stressful situation.

These findings were made among rats that were 24 months of age—considered old age for a rat. Perhaps most remarkably, the differences in early experience were induced by approximately 60 minutes of cumulative differential treatment carried out during the first 3 weeks of life. This means that very brief exposures to a novel environment during infancy can have a life-long influence on social competitive ability and the stress response.

Another question asked by Dr. Tang and colleagues was whether the differences between siblings depended on the care received from their mothers during infancy. They measured how much mother rats licked and groomed their pups after the novelty exposure procedure and how consistently they provided this care from day to day. They discovered that the mother rats that delivered more care to their pups on average were inconsistent in their amount of care from day to day. This led to the surprising finding that the novelty-exposed rats with the most adaptive stress responses had mothers that gave highly consistent, but lesser amounts, of care.

In translating possible significance of these findings to the human species, although it is sometimes assumed that the overall amount of care from the mother is one of the most important influences on her children’s development, this study by Dr. Tang and colleagues provides a different view—that the consistency of maternal care may be more important than the amount of maternal care and that other sources of influences, such as environmental novelty can play an important role in shaping a child’s development.

PLoS ONE, 2008; 3 (7): e2840 DOI: 10.1371/journal.pone.0002840
Social Competitiveness and Plasticity of Neuroendocrine Function in Old Age: Influence of Neonatal Novelty Exposure and Maternal Care Reliability
Katherine G. Akers, Zhen Yang1, Dominic P. DelVecchio, Bethany C. Reeb, Russell D. Romeo, Bruce S. McEwen, Akaysha C. Tang

Early experience is known to have a profound impact on brain and behavioral function later in life. Relatively few studies, however, have examined whether the effects of early experience remain detectable in the aging animal. Here, we examined the effects of neonatal novelty exposure, an early stimulation procedure, on late senescent rats’ ability to win in social competition. During the first 3 weeks of life, half of each litter received daily 3-min exposures to a novel environment while the other half stayed in the home cage. At 24 months of age, pairs of rats competed against each other for exclusive access to chocolate rewards. We found that novelty-exposed rats won more rewards than home-staying rats, indicating that early experience exerts a life-long effect on this aspect of social dominance. Furthermore, novelty-exposed but not home-staying rats exhibited habituation of corticosterone release across repeated days of social competition testing, suggesting that early experience permanently enhances plasticity of the stress response system. Finally, we report a surprising finding that across individual rat families, greater effects of neonatal novelty exposure on stress response plasticity were found among families whose dams provided more reliable, instead of a greater total quantity of, maternal care.

Researchers at Yale School of Medicine have found the brain’s appetite center uses fat for fuel by involving oxygen free radicals—molecules associated with aging and neurodegeneration. The findings, reported in the journal Nature, suggest that antioxidants could play a role in weight control.

The study’s lead authors were Sabrina Diano and Tamas Horvath, who are an associate professor and professor, respectively, in the Departments of Obstetrics, Gynecology & Reproductive Sciences and Neurobiology. Horvath is also chair of the Section of Comparative Medicine.

“In contrast to the accepted view, the brain does use fat as fuel,” said Horvath. “Our study shows that the minute-by-minute control of appetite is regulated by free radicals, implying that if you interfere with free radicals, you may affect eating and satiety.”

The results also imply, added Horvath, “that each time a feeling of fullness or satiety is reached during a meal, you may be chipping away some time from your maximum lifespan as the most free radicals are produced when satiety-promoting brain cells are active.”

Diano, Horvath and colleagues conducted the study in mice to better understand how the brain mediates neuronal activation in response to ghrelin, a hormone produced in the stomach and previously associated with growth hormone release, appetite, learning and memory.

They found that ghrelin-induced increase in appetite is driven by burning fat in hypothalamic mitochondria, which produces free radicals that are scavenged by a mitochondrial protein called uncoupling protein 2 (UCP2)

“The timing of taking antioxidants may be critical for the control of appetite,” said Diano. “If taken on an empty stomach antioxidants may further increase appetite, however when taken with food, they may affect satiety. Further studies are needed to determine whether any regiment of orally taken antioxidants could be used to control appetite in animals and humans.”

Nature advance online publication 30 July 2008 | doi:10.1038/nature07181
UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Zane B. Andrews, Zhong-Wu Liu, Nicholas Walllingford, Derek M. Erion, Erzsebet Borok, Jeffery M. Friedman, Matthias H. Tschöp, Marya Shanabrough, Gary Cline, Gerald I. Shulman, Anna Coppola, Xiao-Bing Gao, Tamas L. Horvath & Sabrina Diano

The gut-derived hormone ghrelin exerts its effect on the brain by regulating neuronal activity. Ghrelin-induced feeding behaviour is controlled by arcuate nucleus neurons that co-express neuropeptide Y and agouti-related protein (NPY/AgRP neurons). However, the intracellular mechanisms triggered by ghrelin to alter NPY/AgRP neuronal activity are poorly understood. Here we show that ghrelin initiates robust changes in hypothalamic mitochondrial respiration in mice that are dependent on uncoupling protein 2 (UCP2). Activation of this mitochondrial mechanism is critical for ghrelin-induced mitochondrial proliferation and electric activation of NPY/AgRP neurons, for ghrelin-triggered synaptic plasticity of pro-opiomelanocortin-expressing neurons, and for ghrelin-induced food intake. The UCP2-dependent action of ghrelin on NPY/AgRP neurons is driven by a hypothalamic fatty acid oxidation pathway involving AMPK, CPT1 and free radicals that are scavenged by UCP2. These results reveal a signalling modality connecting mitochondria-mediated effects of G-protein-coupled receptors on neuronal function and associated behaviour.

The tendency toward obesity is directly related to the brain system that is involved in food reward and addictive behaviors, according to a new study. Researchers at Tufts University School of Medicine (TUSM) and colleagues have demonstrated a link between a predisposition to obesity and defective dopamine signaling in the mesolimbic system in rats.

The mesolimbic system is a system of neurons in the brain that secretes dopamine, a neurotransmitter or chemical messenger, which mediates emotion and pleasure. The release of the neurotransmitter dopamine in the mesolimbic system is traditionally associated with euphoria and considered to be the major neurochemical signature of drug addiction.

“Baseline dopamine levels were 50 percent lower and stimulated dopamine release was significantly attenuated in the brain reward systems of obesity-prone rats, compared with obesity-resistant rats. Defects in brain dopamine synthesis and release were evident in rats immediately after birth,” said Emmanuel Pothos, PhD, assistant professor in the department of pharmacology and experimental therapeutics at TUSM and member of the neuroscience program faculty of the Sackler School of Graduate Biomedical Sciences.

“Previous research has demonstrated that food intake leads to an increase in the release of dopamine, in the circuits that mediate the pleasurable aspects of eating,” Pothos explains. “Also, chronic food deprivation resulting in decreased body weight leads to decreased dopamine levels. Therefore, increased food intake may represent a compensatory attempt to restore baseline dopamine levels.”

Pothos says, “These findings have important implications in our understanding of the obesity epidemic. The notion that decreased dopamine signaling leads to increased feeding is compatible with the finding from human studies that obese individuals have reduced central dopamine receptors.” He speculates that an attenuated dopamine signal may interfere with satiation, leading to overeating.

Pothos and colleagues conducted their research using obesity-prone and obesity-resistant rats. Adult obesity-prone rats consumed more food and were 20% heavier than obesity-resistant rats.

The researchers measured electrically-evoked dopamine release from nerve terminals. “We also measured regulators of dopamine synthesis and release in midbrain dopamine pathways,” explains Brenda Geiger, first author and graduate student in the pharmacology and experimental therapeutics department at TUSM. “Our molecular analysis suggests that the central dopamine deficits are most likely caused by reduced expression of the genes encoding two proteins, one that is involved in dopamine synthesis, and another that is a transporter responsible for packaging dopamine into vesicles from which it is later released upon stimulation.”

“Obesity has so far been approached mostly as a metabolic rather than as an addictive disorder; and obesity research has primarily focused on brain systems that regulate body weight through the maintenance of energy balance. The current study challenges this approach by focusing on brain pathways implicated in pleasure and reward. These pathways could override energy balance and induce hyperphagia and obesity by altering the reward value of food, particularly palatable high-energy food, very early in life,” says Pothos, who is the study’s corresponding and senior author.

According to Gerald Weissmann, MD, editor-in-chief of The FASEB Journal, “Now we know why so many people stay addicted to food: it fuels the mid-brain pleasure machinery. We eat not only for nourishment, but also for pleasure. This study provides the molecular link between eating and mental health.”

The FASEB Journal, Published online before print May 13, 2008; DOI: 10.1096/fj.08-110759
Evidence for defective mesolimbic dopamine exocytosis in obesity-prone rats
Brenda M. Geiger, Gerald G. Behr, Lauren E. Frank, Angela D. Caldera-Siu, Margery C. Beinfeld, Efi G. Kokkotou, and Emmanuel N. Pothos

The association between dietary obesity and mesolimbic systems that regulate hedonic aspects of feeding is currently unresolved. In the present study, we examined differences in baseline and stimulated central dopamine levels in obesity-prone (OP) and obesity-resistant (OR) rats. OP rats were hyperphagic and showed a 20% weight gain over OR rats at wk 15 of age, when fed a standard chow diet. This phenotype was associated with a 50% reduction in basal extracellular dopamine, as measured by a microdialysis probe in the nucleus accumbens, a projection site of the mesolimbic dopamine system that has been implicated in food reward. Similar defects were also observed in younger animals (4 wk old). In electrophysiology studies, electrically evoked dopamine release in slice preparations was significantly attenuated in OP rats, not only in the nucleus accumbens but also in additional terminal sites of dopamine neurons such as the accumbens shell, dorsal striatum, and medial prefrontal cortex, suggesting that there may be a widespread dysfunction in mechanisms regulating dopamine release in this obesity model. Moreover, dopamine impairment in OP rats was apparent at birth and associated with changes in expression of several factors regulating dopamine synthesis and release: vesicular monoamine transporter-2, tyrosine hydroxylase, dopamine transporter, and dopamine receptor-2 short-form. Taken together, these results suggest that an attenuated central dopamine system would reduce the hedonic response associated with feeding and induce compensatory hyperphagia, leading to obesity.

CD4+ T lymphocytes, or simply CD4 T cells, are the “brains” of the immune system, coordinating its activity when the body comes under attack. They are also the cells that are attacked by HIV, the devastating virus that causes AIDS and has infected roughly 40 million people worldwide. The virus slowly eats away at CD4 T cells, weakening the immune system.

But the immune systems of HIV/AIDS patients face another enemy as well — stress, which can accelerate CD4 T cell declines. Now, researchers at UCLA report that the practice of mindfulness meditation stopped the decline of CD4 T cells in HIV-positive patients suffering from stress, slowing the progression of the disease. The study was just released in the online edition of the journal Brain, Behavior, and Immunity.

Mindfulness meditation is the practice of bringing an open and receptive awareness of the present moment to experiences, avoiding thinking of the past or worrying about the future. It is thought to reduce stress and improve health outcomes in a variety of patient populations.

“This study provides the first indication that mindfulness meditation stress-management training can have a direct impact on slowing HIV disease progression,” said lead study author David Creswell, a research scientist at the Cousins Center for Psychoneuroimmunology at UCLA. “The mindfulness program is a group-based and low-cost treatment, and if this initial finding is replicated in larger samples, it’s possible that such training can be used as a powerful complementary treatment for HIV disease, alongside medications.”

Creswell and his colleagues ran an eight-week mindfulness-based stress-reduction (MBSR) meditation program and compared it to a one-day MBSR control seminar, using a stressed and ethnically diverse sample of 48 HIV-positive adults in Los Angeles. Participants in the eight-week group showed no loss of CD4 T cells, indicating that mindfulness meditation training can buffer declines. In contrast, the control group showed significant declines in CD4 T cells from pre-study to post-study. Such declines are a characteristic hallmark of HIV progression.

Creswell also noted that researchers found a “dose-response” relationship between MBSR class attendance and CD4 T cells, meaning, said Creswell, “the more mindfulness meditation classes people attended, the higher the CD4 T cells at the study’s conclusion.”

The researchers were also encouraged because the overall CD4 T cell effects remained even after controlling for a number of factors that could have skewed the study results. Most notably, they found equivalent protective effects for participants whether or not they were on antiretroviral medications for HIV. Even participants taking HIV medications showed the CD4 T cell buffering effect after the mindfulness meditation class, Creswell said.

There is emerging evidence from other studies that shows that behavioral stress-management programs can buffer HIV declines in HIV-positive people, Creswell noted. And while there has been an exponential increase of interest in and practice of mindfulness meditation in the West over the past 10 years, this study, he said, is the first to show an HIV disease protective effect with mindfulness meditation training.

In order to understand the health benefits of mindfulness meditation, Creswell and his colleagues at UCLA are now examining the underlying pathways through which mindfulness meditation reduces stress, using brain imaging, genetics and immune system measurements.

“Given the stress-reduction benefits of mindfulness meditation training, these findings indicate there can be health protective effects not just in people with HIV but in folks who suffer from daily stress,” Creswell said.

Brain, Behavior, and Immunity Volume 22, Issue 6 – selected
pp. 797-1008 (August 2008)
Effect of mindfulness based stress reduction on immune function, quality of life and coping in women newly diagnosed with early stage breast cancer
Pages 969-981
Linda Witek-Janusek, Kevin Albuquerque, Karen Rambo Chroniak, Christopher Chroniak, Ramon Durazo-Arvizu, Herbert L. Mathews

This investigation used a non-randomized controlled design to evaluate the effect and feasibility of a mindfulness based stress reduction (MBSR) program on immune function, quality of life (QOL), and coping in women recently diagnosed with breast cancer. Early stage breast cancer patients, who did not receive chemotherapy, self-selected into an 8-week MBSR program or into an assessment only, control group. Outcomes were evaluated over time. The first assessment was at least 10 days after surgery and prior to adjuvant therapy, as well as before the MBSR start-up. Further assessments were mid-MBSR, at completion of MBSR, and at 4-week post-MBSR completion. Women with breast cancer enrolled in the control group (Non-MBSR) were assessed at similar times. At the first assessment (i.e., before MBSR start), reductions in peripheral blood mononuclear cell NK cell activity (NKCA) and IFN-γ production with increases in IL-4, IL-6, and IL-10 production and plasma cortisol levels were observed for both the MBSR and Non-MBSR groups of breast cancer patients. Over time women in the MBSR group re-established their NKCA and cytokine production levels. In contrast, breast cancer patients in the Non-MBSR group exhibited continued reductions in NKCA and IFN-γ production with increased IL-4, IL-6, and IL-10 production. Moreover, women enrolled in the MBSR program had reduced cortisol levels, improved QOL, and increased coping effectiveness compared to the Non-MBSR group. In summary, MBSR is a program that is feasible for women recently diagnosed with early stage breast cancer and the results provide preliminary evidence for beneficial effects of MBSR; on immune function, QOL, and coping.

We’ve all heard it. Many of us in fact believe it. Girls just aren’t as good at math as boys.

But is it true? After sifting through mountains of data – including SAT results and math scores from 7 million students who were tested in accordance with the No Child Left Behind Act – a team of scientists says the answer is no. Whether they looked at average performance, the scores of the most gifted children or students’ ability to solve complex math problems, girls measured up to boys.

“There just aren’t gender differences anymore in math performance,” says University of Wisconsin-Madison psychology professor Janet Hyde, the study’s leader. “So parents and teachers need to revise their thoughts about this.”

Though girls take just as many advanced high school math courses today as boys, and women earn 48 percent of all mathematics bachelor’s degrees, the stereotype persists that girls struggle with math, says Hyde. Not only do many parents and teachers believe this, but scholars also use it to explain the dearth of female mathematicians, engineers and physicists at the highest levels.

Cultural beliefs like this are “incredibly influential,” she says, making it critical to question them. “Because if your mom or your teacher thinks you can’t do math, that can have a big impact on your math self concept.”

To carry out its query, the team acquired math scores from state exams now mandated annually under No Child Left Behind (NCLB), along with detailed statistics on test takers, including gender, grade level and ethnicity, in 10 states.

Using data from more than 7 million students, they then calculated the “effect size,” a statistic that reports the degree of difference between girls’ and boys’ average math scores in standardized units.

The effect sizes they found – ranging from 0.01 and 0.06 – were basically zero, indicating that average scores of girls and boys were the same.

“Boys did a teeny bit better in some states, and girls did a teeny bit better in others,” says Hyde. “But when you average them all, you essentially get no difference.”

Some critics argue, however, that even when average performance is equal, gender discrepancies may still exist at the highest levels of mathematical ability. So the team searched for those, as well. For example, they compared the variability in boys’ and girls’ math scores, the idea being that if more boys fell into the top scoring percentiles than girls, the variance in their scores would be greater.

Again, the effort uncovered little difference, as did a comparison of how well boys and girls did on questions requiring complex problem solving. What the researchers did find, though, was a disturbing lack of questions that tested this ability. In fact, they found none whatsoever on the state assessments for NCLB, requiring them to turn to another data source for this part of the study.

What this suggests, says Hyde, is that if teachers are gearing instruction toward these assessments, the performance of both boys and girls in complex problem solving may drop in the future, leaving them ill-prepared for careers in math, science and engineering.

“This skill can be taught in the classroom,” she says, “but we need to motivate teachers to do so by including those items on the tests.”

The study’s final piece was a review of the granddaddy of all high school math tests, the SAT. The fact that boys score better on it than girls has been widely publicized, contributing to the public’s notion that boys truly are better at math. But Hyde and her co-authors think there’s another explanation: sampling artifact.

For one thing, because it’s administered only to college-bound seniors, the SAT is hardly a random sample of all students. What’s more, greater numbers of girls take the test now than boys, because more girls are going to college.

“So you’re dipping farther down into the distribution of female talent, which brings down the average score,” says Hyde. “That may be the explanation for (the results), rather than girls aren’t as good as math.”

Still, will all of this be enough to finally shift this long-held attitude? Hyde can’t say, but she remains determined to do so.

“Stereotypes are very, very resistant to change,” she says, “but as a scientist I have to challenge them with data.”

Science 25 July 2008 321: 494-495 DOI: 10.1126/science.1160364
DIVERSITY: Gender Similarities Characterize Math Performance
Janet S. Hyde, Sara M. Lindberg, Marcia C. Linn, Amy B. Ellis, and Caroline C. Williams

Standardized tests in the U.S. indicate that girls now score just as well as boys in math.

Although state lotteries, on average, return just 53 cents for every dollar spent on a ticket, people continue to pour money into them — especially low-income people, who spend a larger percentage of their incomes on lottery tickets than do the wealthier segments of society.

A new Carnegie Mellon University study sheds light on the reasons why low-income lottery players eagerly invest in a product that provides poor returns.

In the study, published in the July issue of the Journal of Behavioral Decision Making, participants who were made to feel subjectively poor bought nearly twice as many lottery tickets as a comparison group that was made to feel subjectively more affluent. The Carnegie Mellon findings point to poverty’s central role in people’s decisions to buy lottery tickets.

“Some poor people see playing the lottery as their best opportunity for improving their financial situations, albeit wrongly so,” said the study’s lead author Emily Haisley, a doctoral student in the Department of Organizational Behavior and Theory at Carnegie Mellon’s Tepper School of Business. “The hope of getting out of poverty encourages people to continue to buy tickets, even though their chances of stumbling upon a life-changing windfall are nearly impossibly slim and buying lottery tickets in fact exacerbates the very poverty that purchasers are hoping to escape.”

The researchers influenced participants’ perceptions of their relative wealth — or lack thereof — by having them complete a survey on their opinions of the city of Pittsburgh that included an item on annual income. The group made to feel poor was asked to provide its income on a scale that began at “less than $100,000″ and went upward from there in $100,000 increments, ensuring that most respondents would be in the lowest income category. The group made to feel subjectively wealthier was asked to report income on a scale that began with “less than $10,000″ and increased in $10,000 increments, leading most respondents to be in a middle or upper tier.

Participants, who were recruited at Pittsburgh’s Greyhound Bus terminal, were paid $5 for completing the survey and given the opportunity to buy as many as five scratch-off lottery tickets. The experimental group purchased an average of 1.27 lottery tickets, compared with 0.67 tickets bought by the members of the control group.

A second experiment reported in the paper found that indirectly reminding participants that, while different income groups face unequal outcomes in education, jobs and housing, everyone has equal chances of winning the lottery induced an increase in the number of lottery tickets purchased. The group given this reminder purchased 1.31 tickets, compared with 0.54 for the group not given such a reminder.

In the study, the researchers note that lotteries set off a vicious cycle that not only exploits low-income individuals’ desires to escape poverty but also directly prevents them from improving upon their financial situations. They recommend that state lottery administrators explore strategies that balance the economic burdens faced by low-income households with the need to maintain important funding streams for state governments.

“State lotteries are popular revenue sources that are unlikely to go away anytime soon,” said George Loewenstein, a study co-author and Herbert A. Simon professor of economics and psychology at Carnegie Mellon. “However, it is possible to implement measures that can actually benefit low-income lottery players and lead to fairer outcomes.” Loewenstein noted that one such potential method for addressing income inequality, which has shown promise in other countries, is tying lottery tickets to savings accounts.

Journal of Behavioral Decision Making, 2008; 21 (3) p 283-295 DOI: 10.1002/bdm.588
Subjective relative income and lottery ticket purchases
Haisley, Emily; Mostafa, Romel; Loewenstein, George

Despite a return of only $.53 on the dollar, state lotteries are extremely popular, especially among the poor, who play the most but can least afford to play. In two experiments conducted with low-income participants, we examine how implicit comparisons with other income classes increase low-income individuals’ desire to play the lottery. In Experiment 1, participants were more likely to purchase lottery tickets when they were primed to perceive that their own income was low relative to an implicit standard. In Experiment 2, participants purchased more tickets when they considered situations in which rich people or poor people receive advantages, implicitly highlighting the fact that everyone has an equal chance of winning the lottery.

No one enjoys being told that their behavior is harmful to themselves or others. In fact, most people respond defensively when confronted with evidence that their behavior is irrational, irresponsible, or unhealthy. Fortunately, research has shown that just a few minutes of writing about an important value can reduce defensiveness.

Previous research by David Sherman at the University of California at Santa Barbara and his collaborators have shown that coffee drinkers are more willing to accept information that drinking coffee harms their health if they first write a few sentences about their most important value.

Although researchers have known for decades that reflecting on important values reduces defensiveness, they have not identified why this simple practice opens people to unpleasant facts they would rather avoid. For decades, scientists assumed that writing about important values boosts self-esteem, or makes people feel good about themselves, and this makes them less defensive. Yet, many studies failed to support the idea that boosts to self-esteem or positive mood explains why writing about important values reduces defensiveness.

In a new experiment, Jennifer Crocker and Yu Niiya from the University of Michigan and Dominik Mischkowski from the University of Konstanz, suggest that previous researchers have it wrong; writing about important values doesn’t reduce defensiveness by boosting the self; instead, it enables people to transcend the self by focusing on people or things they care about beyond themselves. In two experiments, they found that writing about important values makes people feel loving and connected, and that these other-directed feelings account for reduced defensiveness.

In the first study, the researchers asked participants to rank six values — social life, religion/morality, science, business, arts, and government. One group later wrote for 10 minutes about why their most important value was important to them, while the control group wrote for 10 minutes about how their least important value might be important to others. Afterwards, they rated how much writing the essay made them feel love, empathy or other emotions.

In the second study, participants were smokers and nonsmokers. Like the first study, participants wrote about an important or unimportant value. This time, however, they next read a fake article claiming that smoking increases the risk of abdominal aortic aneurysms, a bulge in the main artery of the heart, and the quality of the research described in the article.

The results for both studies were very strong. In both studies, those who wrote about an important value felt more loving and connected after writing the essays than those who wrote about an unimportant value. And specifically in the second study, writing about an important value made smokers less defensive — they were more accepting of the article’s claim that smoking harms health if they wrote about an important value instead of an unimportant value.

“These studies raise the prospect that reminding people what they love or care about may enable them to transcend the self and may foster learning under difficult circumstances,” the authors explain in the July issue of Psychological Science, a journal of the Association for Psychological Science.

The researchers speculate that the love and connection people feel after writing about important values could affect hormones related to care giving, such as oxytocin. Because oxytocin increases trust, it might account for reduced defensiveness in people who take a few minutes to reflect on their important values.

Psychological Science Volume 19, Issue 7, Date: July 2008, Pages: 740-747
Why Does Writing About Important Values Reduce Defensiveness? Self-Affirmation and the Role of Positive Other-Directed Feelings

An experiment examined the buffering effects of a learning orientation following failure in a domain of contingent self-worth. Participants’ academic contingencies of self-worth (CSW) and priming with theories of intelligence interacted to affect vulnerability of self-esteem to failure. Participants who had high academic CSW and were primed with an entity theory of intelligence experienced lower self-esteem and higher negative affect following failure than following success on an academic test, but these effects were eliminated when participants with high academic CSW were primed with an incremental theory of intelligence. This study shows that endorsing a learning orientation is an effective way to minimize threat to self-esteem among students whose self-worth is highly contingent on academics and may allow them to persist in the face of challenges and to learn from failure.

In a major step in understanding how the nervous system and the immune system interact, scientists at The Feinstein Institute for Medical Research have identified a new anatomical path through which the brain and the spleen communicate.

The spleen, once thought to be an unnecessary bit of tissue, is now regarded as an organ where important information from the nervous reaches the immune system. Understanding this process could ultimately lead to treatments that target the spleen to send the right message when fighting human disease.

Mauricio Rosas-Ballina, MD, working with colleagues in the laboratory of Kevin J. Tracey, MD, figured out that macrophages in the spleen were making tumor necrosis factor, a powerful inflammation-producing molecule. When they stimulated the vagus nerve, a long nerve that goes from the base of the brain into thoracic and abdominal organs, tumor necrosis factor (TNF) production in the spleen decreased. This study complements previous research performed in Dr. Tracey’s laboratory, which showed that stimulation of the vagus nerve increases survival in laboratory models of sepsis.

The findings were published July 22 in the Proceedings of the National Academy of Sciences. Many laboratories at The Feinstein Institute study the immune system in health and in disease. Every year, about 500,000 people develop severe sepsis, a syndrome triggered when the body’s immune system wages an attack on the body that is well beyond its normal response to an invader. Sepsis kills about 225,000 deaths in the United States each year.

A hundred years ago, the spleen (located in the upper quadrant of the abdomen) was thought to be only reservoir for blood. It has only been in recent years that scientists discovered that the spleen is a manufacturing plant for immune cells, and a site where immune cells and nerves interact. The spleen defends the body against infection, particularly encapsulated bacteria that circulate through the blood.

The hope is to modulate other immune functions like antibody production through the spleen (via vagus nerve stimulation) as a way to modify the course of infections and possibly some autoimmune disorders.

Dr. Rosas-Ballina began following the winding path of the vagus nerve to establish the route it follows to reach the spleen. He was trying, without much luck, to find fibers of the vagus nerve in this organ. And then he went a little further south to the splenic nerve, the nerve that innervates the spleen. Their results indicate that the vagus nerve inherently communicates with the splenic nerve to suppress TNF production by macrophages in the spleen.

According to the prevailing paradigm, the autonomic nervous system is anatomically and functionally divided in sympathetic and parasympathetic branches, which act in opposition to regulate organ function. “The division between the parasympathetic and sympathetic nervous systems is not clear cut,” said Dr. Rosas-Ballina, explaining that the vagus nerve (the major parasympathetic nerve) acts through the splenic nerve to modulate immune function. He said that results of this study suggest that there may be two separate ways the brain communicates with the spleen to regulate immune function. This points the way to a possible solution for treating sepsis. It may be more effective to take advantage of the central nervous system to control cells of the spleen. This way, “you know where the treatment is going,” said Dr. Rosas-Ballina.

Brain Behav Immun. 2008 Jun 27. [Epub ahead of print]
Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway.
Pavlov VA, Parrish WR, Rosas-Ballina M, Ochani M, Puerta M, Ochani K, Chavan S, Al-Abed Y, Tracey KJ.

The excessive release of cytokines by the immune system contributes importantly to the pathogenesis of inflammatory diseases. Recent advances in understanding the biology of cytokine toxicity led to the discovery of the “cholinergic anti-inflammatory pathway,” defined as neural signals transmitted via the vagus nerve that inhibit cytokine release through a mechanism that requires the alpha7 subunit-containing nicotinic acetylcholine receptor (alpha7nAChR). Vagus nerve regulation of peripheral functions is controlled by brain nuclei and neural networks, but despite considerable importance, little is known about the molecular basis for central regulation of the vagus nerve-based cholinergic anti-inflammatory pathway. Here we report that brain acetylcholinesterase activity controls systemic and organ specific TNF production during endotoxemia. Peripheral administration of the acetylcholinesterase inhibitor galantamine significantly reduced serum TNF levels through vagus nerve signaling, and protected against lethality during murine endotoxemia. Administration of a centrally-acting muscarinic receptor antagonist abolished the suppression of TNF by galantamine, indicating that suppressing acetylcholinesterase activity, coupled with central muscarinic receptors, controls peripheral cytokine responses. Administration of galantamine to alpha7nAChR knockout mice failed to suppress TNF levels, indicating that the alpha7nAChR-mediated cholinergic anti-inflammatory pathway is required for the anti-inflammatory effect of galantamine. These findings show that inhibition of brain acetylcholinesterase suppresses systemic inflammation through a central muscarinic receptor-mediated and vagal- and alpha7nAChR-dependent mechanism. Our data also indicate that a clinically used centrally-acting acetylcholinesterase inhibitor can be utilized to suppress abnormal inflammation to therapeutic advantage.

For the first time, Weill Cornell scientists have learned important details illustrating how neuronal cells in the brain communicate at a microcellular level. Such knowledge may help in the development of drug compounds used to treat disorders caused by malfunctions in communication between brain cells, such as schizophrenia, epilepsy, Parkinson’s and Alzheimer’s disease.

To communicate between cells, tiny transport vesicles package and ship neurotransmitter-chemicals to the end (terminals) of the cell and then across synapses, or gaps in-between neurons. Adjacent neurons then receive the signal. To do this, these transport-vesicles must be recycled quickly — especially during boosts in brain activity, but it has never been understood exactly how such critical recycling works.

Observing proteins within cellular vesicles labeled with a fluorescent marker in the lab, for easy identification, the researchers saw that about 20 vesicles can be simultaneously manufactured right at the end of the neuron — like milk bottles, lined up and waiting to be filled for shipment. The new findings show that calcium ions, which help to send the signal across the synapse to another neuron, also control the cell’s ability to rebuild the vesicles at the cell’s terminal end.

According to the researchers, the explanation for this cellular feat is a simple matter of distance. “Think of the cell body as New York City and the axon [the long narrow stretch between the cell body and cell terminal] as a highway leading to Boston,” explains lead researcher, Dr. Tim Ryan, from the Department of Biochemistry at Weill Cornell Medical College.

“It takes far too long for the vesicles to move from all the way in the cell body to another cell. These vesicles are made in New York and slowly transported to the cell’s terminal end, but some are made right in Boston for immediate use.” Dr. Ryan hopes that by understanding the mechanics of the cellular trafficking machine, he and other scientists will ultimately be able to identify and repair numerous neurologic malfunctions.

J Neurosci. 2008 Jun 25;28(26):6742-9.
Calcium control of endocytic capacity at a CNS synapse.
Balaji J, Armbruster M, Ryan TA.

The ability to recycle synaptic vesicles is a crucial property of nerve terminals that allows maintenance of synaptic transmission. Using high-sensitivity optical approaches at hippocampal nerve terminals in dissociated neurons in culture, we show that modulation of endocytosis can be achieved by expansion of the endocytic capacity. Our experiments indicate that the endocytic capacity, the maximum number of synaptic vesicles that can be internalized in parallel at individual synapses, is tightly controlled by intracellular calcium levels. Increasing levels of intracellular calcium, which occurs as firing frequency increases, significantly increases the endocytic capacity. At physiological temperature after 30 Hz firing, these synapses are capable of endocytosing at least approximately 28 vesicles in parallel, each with a time constant of approximately 6 s. This calcium-dependent control of endocytic capacity reveals a potentially useful adaptive response to high-frequency activity to increase endocytic rates under conditions of vesicle pool depletion.

Anyone who has seen an optical illusion can recall the quirky moment when you realize that the image being perceived is different from objective reality. Now, a team of scientists from MIT, Harvard and McGill has designed a new illusion involving the sense of touch, which is helping to glean new insights into perception and how different senses–such as touch and sight–work together.

Anyone who has seen an optical illusion can recall the quirky moment when you realize that the image being perceived is different from objective reality. Now, a team of scientists from MIT, Harvard and McGill has designed a new illusion involving the sense of touch, which is helping to glean new insights into perception and how different senses–such as touch and sight–work together. (Credit: iStockphoto/Allister Clark)

Ambiguous visual images are fascinating because it is often difficult to imagine seeing them any other way–until something flips within the brain and the alternative perception is revealed. This phenomenon, known as perceptual rivalry, is of great interest to neuroscience. Because rivalrous illusions produce changes in perception that are independent of changes in the stimulus itself, they may help to understand how the brain gives rise to conscious experience.

“The most familiar illusions involve vision,” explains Christopher Moore, a principal investigator at the McGovern Institute for Brain Research at MIT and an assistant professor in MIT’s Department of Brain and Cognitive Sciences. “But we’re interested in discovering general principles of perception, and we wanted to see whether similar illusions can occur in the tactile domain.”

Moore is senior author of a paper on the new illusion published on the Current Biology web site on July 17.

In the visual illusion known as the apparent motion quartet, two dots are presented at diagonally opposite corners of an imaginary square. When the pattern alternates between the two diagonals–top left/bottom right followed by top right/bottom left–people perceive the dots as moving back and forth either horizontally or vertically. After a period of time, typically a minute or two, most observers report that the axis of motion appears to flip from vertical to horizontal or vice versa.

An example of the illusion can be seen at http://web.mit.edu/~tkonkle/www/AmbiguousQuartet.html.

To create a tactile version of this illusion, Olivia Carter, a postdoctoral researcher at Harvard University, and Talia Konkle, a graduate student in Moore’s MIT lab, used a new piezoelectric stimulator device developed by Qi Wang and Vincent Hayward at McGill University. This device, originally designed as a computer Braille display, uses a centimeter-square array composed of 60 “tactors” to deliver precisely controlled touch stimuli to the finger tips of volunteer subjects.

When volunteer subjects were given the diagonally alternating stimuli, they perceived them as moving smoothly back and forth–and just as with the visual illusion, the direction of apparent motion flipped back and forth from vertical to horizontal, on average about twice per minute, even though there was no change in the stimulus itself.

The authors went on to show that after a period of adaptation to an unambiguous horizontal or vertical stimulation (produced by activating a row of tactors in succession), subjects were more likely to perceive a subsequent ambiguous stimulus as being in the orthogonal direction. Similar after-effects are common in vision and were once thought to reflect fatigue in the brain circuits responsible for a particular perceptual interpretation, but are now thought to reflect a continual recalibration of the brain to its sensory environment. In another experiment, an ambiguous touch stimulus was interrupted by a three-second break, after which subjects tended to experience the same direction as before the break, suggesting that the prior interpretation was somehow retained in memory and used to reinterpret the ambiguous stimulus.

Real-world objects often stimulate multiple senses simultaneously, and our brains must combine these disparate stimuli into a unified interpretation of the world. The authors used their tactile illusion to explore the interaction between touch and vision. They instructed their subjects to make vertical or horizontal eye movements during the ambiguous touch stimuli. Subjects perceived that the direction of tactile motion shifted into alignment with the direction of the eye movements, but only if the head and finger were also aligned. Tilting the head sideways 90 degrees produced a shift to the other direction–suggesting that the tactile and visuomotor systems are somehow aligned with respect to the external world.

“We don’t yet understand what’s happening in the brain during these illusions,” says Konkle. “But we think this illusion will be a useful new tool to understand more about the similarities between different sensory modalities and how they all work together.”

Curr Biol. 2008 Jul 15. [Epub ahead of print]
Tactile Rivalry Demonstrated with an Ambiguous Apparent-Motion Quartet.
Carter O, Konkle T, Wang Q, Hayward V, Moore C.

When observers view ambiguous visual stimuli, their perception will often alternate between the possible interpretations, a phenomenon termed perceptual rivalry [1]. To induce perceptual rivalry in the tactile domain, we developed a new tactile illusion, based on the visual apparent-motion quartet [2]. Pairs of 200 ms vibrotactile stimuli were applied to the finger pad at intervals separated by 300 ms. The location of each successive stimulus pair alternated between the opposing diagonal corners of the approximately 1 cm(2) stimulation array. This stimulation sequence led all participants to report switches between the perception of motion traveling either up and down or left and right across their fingertip. Adaptation to tactile stimulation biased toward one direction caused subsequent ambiguous stimulation to be experienced in the opposing direction. In contrast, when consecutive trials of ambiguous stimulation were presented, motion was generally perceived in the direction consistent with the motion reported in the previous trial. Voluntary eye movements induced shifts in the tactile perception toward a motion axis aligned along a world-centered coordinate frame. Because the tactile quartet results in switching perceptual states despite unvaried sensory input, it is ideally suited to future studies of the neural processes associated with conscious tactile perception