Reading the drug side-effects label can make you sick.

An interesting article from the Wall Street Journal on the nocebo effect, which I have mentioned before, the opposite of the placebo effect. Numerous studies report that negative side effects of a medical condition or drug treatment are reported to occur more frequently by those who are aware of them than by those who are not.

Another herbal miracle drug fails to pan out....

The largest clinical trial to date finds no effect of ginkgo biloba on slowing memory loss or dementia in Alzheimer's.

Reversal of fear in the human brain

Schiller et al. do work on learned fear responses and their reversal:

Fear learning is a rapid and persistent process that promotes defense against threats and reduces the need to relearn about danger. However, it is also important to flexibly readjust fear behavior when circumstances change. Indeed, a failure to adjust to changing conditions may contribute to anxiety disorders. A central, yet neglected aspect of fear modulation is the ability to flexibly shift fear responses from one stimulus to another if a once-threatening stimulus becomes safe or a once-safe stimulus becomes threatening. In these situations, the inhibition of fear and the development of fear reactions co-occur but are directed at different targets, requiring accurate responding under continuous stress. To date, research on fear modulation has focused mainly on the shift from fear to safety by using paradigms such as extinction, resulting in a reduction of fear. The aim of the present study was to track the dynamic shifts from fear to safety and from safety to fear when these transitions occur simultaneously. We used functional neuroimaging in conjunction with a fear-conditioning reversal paradigm. Our results reveal a unique dissociation within the ventromedial prefrontal cortex between a safe stimulus that previously predicted danger and a "naive" safe stimulus. We show that amygdala and striatal responses tracked the fear-predictive stimuli, flexibly flipping their responses from one predictive stimulus to another. Moreover, prediction errors associated with reversal learning correlated with striatal activation. These results elucidate how fear is readjusted to appropriately track environmental changes, and the brain mechanisms underlying the flexible control of fear.


Figure: Striatum and amygdala BOLD responses throughout the discrimination and reversal task. A, Mean differential striatal (left and right caudate) and amygdala percent BOLD signal change in the different phases of the task. The differential responding is calculated as [face A – face B]. Positive scores correspond to stronger responses to face A, which was paired with the shock during acquisition (CS+). Negative scores correspond to stronger responses to face B, which was paired with the shock during reversal (new CS+). These BOLD responses were extracted from the CS+ greater than CS– in early acquisition contrast. B, Striatal activation is denoted by yellow circle. C, Left amygdala activation is denoted by yellow circle.

How we learn to value others

Behrens et al. use a combination of computational and neuroimaging techniques to address a key question in social neuroscience: how we learn to value some individuals more than others. The work demonstrates that demonstrates that social valuation is achieved using the same mechanisms that underlie the reward-based learning — that is, by associative learning. Their abstract:

Our decisions are guided by information learnt from our environment. This information may come via personal experiences of reward, but also from the behaviour of social partners. Social learning is widely held to be distinct from other forms of learning in its mechanism and neural implementation; it is often assumed to compete with simpler mechanisms, such as reward-based associative learning, to drive behaviour. Recently, neural signals have been observed during social exchange reminiscent of signals seen in studies of associative learning. Here we demonstrate that social information may be acquired using the same associative processes assumed to underlie reward-based learning. We find that key computational variables for learning in the social and reward domains are processed in a similar fashion, but in parallel neural processing streams. Two neighbouring divisions of the anterior cingulate cortex were central to learning about social and reward-based information, and for determining the extent to which each source of information guides behaviour. When making a decision, however, the information learnt using these parallel streams was combined within ventromedial prefrontal cortex. These findings suggest that human social valuation can be realized by means of the same associative processes previously established for learning other, simpler, features of the environment.

Potential flaws in unconscious bias tests

An interesting article by John Tierney notes controversy over the way researchers have been using split-second reactions on a computer test (the Implicit Association Test, or I.A.T.) to diagnose an epidemic of racial bias. Critic Hart Blanton notes:

One can decrease racial bias scores on the I.A.T. by simply exposing people to pictures of African-Americans enjoying a picnic...Yet respondents who take this test on the Web are given feedback suggesting that some enduring quality is being assessed...People receiving feedback about their ‘strong’ racial biases are encouraged in sensitivity workshops to confront these tendencies as some ugly reality that has meaning in their daily lives. But unbeknownst to respondents who take this test, the labels given to them were chosen by a small group of people who simply looked at a distribution of test scores and decided what terms seemed about right. This is not how science is done.

However,

In a new a meta-analysis of more than 100 studies, Dr. Greenwald, Dr. Banaji (two of the leading I.A.T. researchers) and fellow psychologists conclude that scores on I.A.T. reliably predict people’s behavior and attitudes, and that the test is a better predictor of interracial behavior than self-description. Their critics reach a different conclusion after reanalyzing the data in some of those studies, which they say are inconsistent and sometimes demonstrate the reverse of what has been reported. They have suggested addressing the scientific dispute over bias — and the researchers’ arguments about the legal implications for affirmative-action policies — by having the two sides join in an “adversarial collaboration.”

One critic, Philip Tetlock, a psychologist at the University of California, Berkeley, said he had found prominent research groups and scholars willing to mediate joint experiments. But so far nothing has happened — and each side blames the other. Dr. Greenwald says he tried proposing a joint experiment to Dr. Tetlock only to have it rejected. Dr. Tetlock says that he tried a counterproposal and offered to work out a compromise, but that the I.A.T. researchers had refused two invitations to sit down with independent mediators.

After all the mutual invective in the I.A.T. debate, maybe it’s unrealistic to expect the two sides to collaborate. But these social scientists are supposed to be experts in overcoming bias and promoting social harmony. If they can’t figure out how to get along with their own colleagues, how seriously should we take their advice for everyone else?

Cultural specificity in amygdala response to fear faces

From Chiao et al. :

The human amygdala robustly activates to fear faces. Heightened response to fear faces is thought to reflect the amygdala's adaptive function as an early warning mechanism. Although culture shapes several facets of emotional and social experience, including how fear is perceived and expressed to others, very little is known about how culture influences neural responses to fear stimuli. Here we show that the bilateral amygdala response to fear faces is modulated by culture. We used functional magnetic resonance imaging to measure amygdala response to fear and nonfear faces in two distinct cultures. Native Japanese in Japan and Caucasians in the United States showed greater amygdala activation to fear expressed by members of their own cultural group. This finding provides novel and surprising evidence of cultural tuning in an automatic neural response.

The innovative brain

Lawrence et al. present preliminary neurocognitive data from matched groups of entrepreneurs and managerial controls that suggests that entrepreneurs represent an example of highly adaptive risk-taking behavior, with positive functional outcomes in the context of stressful economic decision-making. They suggest this 'functional impulsivity' may have evolutionary value as a means of seizing opportunities in a rapidly changing environment. Their neurocognitive tests distinguished the involvement of distinct processes in risky and risk-free decision-making. Referred to as 'hot' and 'cold' processes, these appear to be localized to distinct regions of the brain's frontal lobes. Risk-taking performance in the entrepreneurs was accompanied by elevated scores on personality impulsiveness measures and superior cognitive-flexibility performance. They conclude that entrepreneurs and managers do equally well when asked to perform cold decision-making tasks, but differences emerge in the context of risky or emotional decisions.

The pattern of performance seen on a gambling task in entrepreneurs reflects a behavioral index of risk-seeking or risk tolerance. Greater rewards (as well as greater losses) are available for those who bet more. If these impulsive risk-taking traits can be beneficial, can they be taught or otherwise imparted to the potential entrepreneur? What does it take to make an entrepreneur — is it an inherited, inbuilt characteristic, or is it acquired, and if so, can it be acquired by anyone? These cognitive processes are intimately linked to brain neurochemistry, particularly to the neurotransmitter dopamine. Using single-dose psychostimulants to manipulate dopamine levels, we have seen modulation of risky decision-making on this task9. Therefore, it might be possible to enhance entrepreneurship pharmacologically.

Alexithymia

I just learned a new word: Alexithymia, the inability to express feelings with words, or more generally deficiency in understanding, processing, or describing emotions. The condition is associated with less activation of the anterior cingulate cortex, involved in cognitive and emotional processing. Gu et al. show that the trait is also associated with less efficient voluntary control.

Mozart's Symphony No. 40 in G minor - a new version

I just have to pass this on (from Andrews Sullivan's blog):

Towards a Moral Neuropolitics

Gary Olson writes an article on the neuroscience of empathy and mirror neuron systems, arguing that the morality that leads to progressive political possibilities is grounded in biology.

Making your tennis racquet part of your brain's body representation

Interesting work from Fourkas et al. in Cerebral Cortex:

Specific physical or mental practice may induce short- and long-term neuroplastic changes in the motor system and cause tools to become part of one's own body representation. Athletes who use tools as part of their practice may be an excellent model for assessing the neural correlates of possible bodily representation changes that are specific to extensive practice. We used single-pulse transcranial magnetic stimulation to measure corticospinal excitability in forearm and hand muscles of expert tennis players and novices while they mentally practiced a tennis forehand, table tennis forehand, and a golf drive. The muscles of expert tennis players showed increased corticospinal facilitation during motor imagery of tennis but not golf or table tennis. Novices, although athletes, were not modulated across sports. Subjective reports indicated that only in the tennis imagery condition did experts differ from novices in the ability to form proprioceptive images and to consider the tool as an extension of the hand. Neurophysiological and subjective data converge to suggest a key role of long-term experience in modulating sensorimotor body representations during mental simulation of sports.

Why do intelligent people live longer?

Ian Deary offers an interesting essay in Nature. Here are some clips:

Scores from cognitive-ability tests (intelligence tests or IQ tests) have validity that is almost unequalled in psychology. A general cognitive-ability factor emerges from measures of diverse mental tasks, something that hundreds of data sets since 1904 have replicated. People's rankings on intelligence tests show high stability across almost the whole lifespan, are substantially heritable and are associated with important life outcomes — including educational achievements, occupational success and morbidity and mortality. More thumping confirmatory studies of the link between intelligence and mortality have appeared...One of these contains nearly a million Swedish men tested at around age 19 during military induction and followed for almost 20 years. It shows a clear association: as intelligence test scores go up the scale, so too does the likelihood of survival over those two decades...Intelligence can predict mortality more strongly than body mass index, total cholesterol, blood pressure or blood glucose, and at a similar level to smoking4. But the reasons for this are still mysterious.

The field has focused on four non-exclusive possibilities for the link between intelligence and death. First, what occurs to many people as an obvious pathway of explanation, is that intelligence is associated with more education, and thereafter with more professional occupations that might place the person in healthier environments. Statistical adjustment for education and adult social class can make the association between early-life intelligence and mortality lessen or disappear. But not always.

Second, people with higher intelligence might engage in more healthy behaviours. Evidence is accruing that people with higher intelligence in early life are more likely to have better diets, take more exercise, avoid accidents, give up smoking, engage in less binge drinking and put on less weight in adulthood. But this too doesn't seem to be the whole story.

Third, mental test scores from early life might act as a record of insults to the brain that have occurred before that date. These insults — perinatal events, or the result of illnesses, accidents or deprivations before the mental testing — might be the fundamental cause behind both intelligence test scores and mortality risk. So far, little evidence supports this.

Fourth, mental test scores obtained in youth might be an indicator of a well-put-together system. It is hypothesized that a well-wired body is more able to respond effectively to environmental insults. This 'system integrity' idea has a parallel in the field of ageing, where some data suggest that bodily and cognitive functions age in concert. Some supporting evidence comes from the finding that simple reaction speed — the time taken to press a button when a stimulus appears — can displace intelligence test scores as an even better predictor of mortality risk.

There is also a search for other, non-cognitive psychological characteristics that are associated with living longer. For example, it seems that, independently of any association with intelligence, being more dependable or conscientious in childhood is also significantly protective to health. Children who scored in the top 50% of the population for intelligence and dependability were in one study more than twice as likely to survive to their late sixties as children scoring in the bottom half for both.

Religion and visual attention

Colzato et al. report a quirky study in PLoS ONE: "Losing the Big Picture: How Religion May Control Visual Attention"

Despite the abundance of evidence that human perception is penetrated by beliefs and expectations, scientific research so far has entirely neglected the possible impact of religious background on attention. Here we show that Dutch Calvinists and atheists, brought up in the same country and culture and controlled for race, intelligence, sex, and age, differ with respect to the way they attend to and process the global and local features of complex visual stimuli: Calvinists attend less to global aspects of perceived events, which fits with the idea that people's attentional processing style reflects possible biases rewarded by their religious belief system.

The way we age

I find myself returning again and again to a New Yorker article by Atul Gawande, "The Way We Age Now." (PDF here). It was the subject of a May 2007 post which included a few clips from the article. His descriptions of the natural processes that underlie changes in teeth, hair, skin, bones, muscles, joints, etc during agin are the most concise and clear that I have read.

Massive reorganization of visual cortex at the level of dendritic spines..

Keck et al. do elegant experiments to directly observe spine replacement in individual apical dendritic tufts of layer-5 pyramidal neurons, replacement that correlates with functional recovery over a period of months after lesioning the retinal input:

The cerebral cortex has the ability to adapt to altered sensory inputs. In the visual cortex, a small lesion to the retina causes the deprived cortical region to become responsive to adjacent parts of the visual field. This extensive topographic remapping is assumed to be mediated by the rewiring of intracortical connections, but the dynamics of this reorganization process remain unknown. We used repeated intrinsic signal and two-photon imaging to monitor functional and structural alterations in adult mouse visual cortex over a period of months following a retinal lesion. The rate at which dendritic spines were lost and gained increased threefold after a small retinal lesion, leading to an almost complete replacement of spines in the deafferented cortex within 2 months. Because this massive remodeling of synaptic structures did not occur when all visual input was removed, it likely reflects the activity-dependent establishment of new cortical circuits that serve the recovery of visual responses.

A novel theory of mental disorders

Benedict Carey writes a useful article on a radical new theory for explaining the psychotic spectrum:

...that an evolutionary tug of war between genes from the father’s sperm and the mother’s egg can, in effect, tip brain development in one of two ways. A strong bias toward the father pushes a developing brain along the autistic spectrum, toward a fascination with objects, patterns, mechanical systems, at the expense of social development. A bias toward the mother moves the growing brain along what the researchers call the psychotic spectrum, toward hypersensitivity to mood, their own and others’. This, according to the theory, increases a child’s risk of developing schizophrenia later on, as well as mood problems like bipolar disorder and depression.

In short: autism and schizophrenia represent opposite ends of a spectrum that includes most, if not all, psychiatric and developmental brain disorders. The theory has no use for psychiatry’s many separate categories for disorders, and it would give genetic findings an entirely new dimension.

The theory leans heavily on the work of David Haig of Harvard. It was Dr. Haig who argued in the 1990s that pregnancy was in part a biological struggle for resources between the mother and unborn child. On one side, natural selection should favor mothers who limit the nutritional costs of pregnancy and have more offspring; on the other, it should also favor fathers whose offspring maximize the nutrients they receive during gestation, setting up a direct conflict.

I strongly recommend that you read the article, which goes on to give a lucid explanation of how gene imprinting regulates this competition.

Language evolution embedded in cooperative social context

Another installment in the Nature series "Being Human" is offered by Szathmáry and Számadó , who put the case that language evolved in a highly social, cooperative context as one of a suite of uniquely human traits, meriting special status because of the opportunities that it opened up.

The subliminal power of logos

An interesting article by Rob Walker in the New York Times Magazine: "The Brand-ness of Strangers."

In one study, each subject was shown 20 photographs of people in various situations and instructed to focus on facial expressions. Afterward, each subject was offered a bottle of water from a selection of four brands. The experiment had nothing to do with facial expressions and everything to do with which kind of water they chose: the subjects had been divided into groups, based on how many of the photos they viewed incidentally included a bottle of Dasani water. Among those who looked at Dasani-free pictures, about 17 percent chose that brand. But about 40 percent of those who viewed a group of pictures that included 12 with a Dasani presence made the brand their pick. Since subjects who actually noticed the brand in the pictures were eliminated from the results, that spike in popularity evidently came from exposure that the subjects weren’t even aware of.

He discusses the very successful Ralph Lauren logo

Needless to say, a successful logo like Polo’s isn’t easy to create. But having attained and maintained such a level of familiarity, that logo may now be as effective as any of Ralph Lauren’s seductive ads — and for exactly the opposite reason: Not because it catches our attention, but because it doesn’t.

Is the financial meltdown a guy thing?

Dobrzynski asks whether traders have become prisoners of their endocrine systems — ruled by testosterone, the elixir of male aggressiveness, during a bull market; and by cortisol, a steroid that helps the body deal with stress, when the bears take over.

From Genes to Social Behavior

The Nov. 7 issue of Science Magazine is a gold mine of articles on genetics and behavior. I'm giving you here a clip from from the introduction to this special issue by Jasny et al. that contains links to the individual articles.

When it comes to behavior, we have moved beyond genetic determinism. Our genes do not lock us into certain ways of acting; rather, genetic influences are complicated and mutable and are only one of many factors affecting behavior. In their editorial, Landis and Insel (p. 821) elaborate on this idea, explaining that proteins encoded by genes direct the formation of multicomponent neural circuits, which are the true substrates of behavior, as these circuits respond to internal and outside stimuli.

Why do we study the genetic underpinnings of behavior? One reason is to understand how certain behaviors evolve. Conserved neural pathways can be tied to the evolution of social behaviors (Robinson et al., p. 896), and the conserved peptides oxytocin and vasopressin regulate social cognition and reproductive behaviors in many species (Donaldson and Young, p. 900). In a News story, Pennisi focuses on a region of chromosome 17 that has a complicated pattern of evolution in humans and other primates and is linked in unexpected ways to various disorders, including mental retardation, learning disabilities, and dementias.

Genetics can help us understand why identical circumstances can elicit different behavioral responses among individuals. Genetic differences are reflected in variations in behavior; activation of distinct versions of a hormone receptor gene, an example Donaldson and Young present, results in monogamous behavior in one species of vole but not in another. Conversely, as Robinson et al. describe, insights from recent work show that perceiving social information--such as bird songs or dominance behavior from cichlid fish--from another individual of the same species can itself alter gene expression in the brain, with downstream effects on physiology and behavior.

The potent genetic tools available for Drosophila have uncovered many genes that, when deleted, disrupt behaviors. This, in turn, has allowed dissection of the neural circuits that control essential behaviors. One of the best understood is a social activity necessary for reproduction--stereotypical mating behavior--as outlined by Dickson (p. 904). Genetic methods have also led to the understanding of another class of behaviors: those driven by the circadian clock. The genetic basis of the clock was elegantly worked out in Drosophila, followed by a similar achievement in mice. The reasons for these successes are outlined by Takahashi in his Perspective (p. 909), in which he also explains what tools will be needed to attain similar advances for other behaviors in mice.

Humans are not as genetically tractable as mice or flies, and human behavior is not as stereotypical. Holden's News story on the strengths and shortcomings of genetic studies of personality illustrates this point (p. 892). So do Cotton and some members of the Human Variome Project community in a Policy Forum (p. 861) that describes how the genes and loci associated with disorders of the nervous system are a particular challenge to geneticists and clinical neurologists in need of reliable diagnostic tests. And in a Perspective on a critical human social activity--politics--Fowler and Schreiber (p. 912) argue that genetics and neurobiology have much to teach us about how our leaders are chosen.

Some believe that psychology is the last frontier of genetic analysis. This special section provides a sampling of our early explorations.