Resveratrol promotes repair of DNA breaks that occur on aging

Nicholas Wade reports on work of Sinclair and collaborators (reported in Cell) that sirtulin, an enzyme activated by the red wine compound resveratrol, promotes the repair of breaks in DNA that occur on aging. (Ten previous MindBlog posts on resveratrol can be retrieved by entering "resveratrol" in the search box in the left column.) Resveratrol has many different effects, only some of which are exerted through sirtuin. While some people have been taking resveratrol with no apparent side effects, Mindblog's self-experiment found it causing arthritic symptoms, and that experience was reported by several who commented on that post.

Ventral and dorsal pathways for language

Finding an analogy to our visual system's partition of visual information into dorsal 'where' and ventral 'what' streams, Saur et al combine MRI and diffusion tensor imaging to provide support for a language processing model in which a dorsal stream is involved in mapping sound to articulation, and a ventral stream in mapping sound to meaning. Here is their abstract:

Built on an analogy between the visual and auditory systems, the following dual stream model for language processing was suggested recently: a dorsal stream is involved in mapping sound to articulation, and a ventral stream in mapping sound to meaning. The goal of the study presented here was to test the neuroanatomical basis of this model. Combining functional magnetic resonance imaging (fMRI) with a novel diffusion tensor imaging (DTI)-based tractography method we were able to identify the most probable anatomical pathways connecting brain regions activated during two prototypical language tasks. Sublexical repetition of speech is subserved by a dorsal pathway, connecting the superior temporal lobe and premotor cortices in the frontal lobe via the arcuate and superior longitudinal fascicle. In contrast, higher-level language comprehension is mediated by a ventral pathway connecting the middle temporal lobe and the ventrolateral prefrontal cortex via the extreme capsule. Thus, according to our findings, the function of the dorsal route, traditionally considered to be the major language pathway, is mainly restricted to sensory-motor mapping of sound to articulation, whereas linguistic processing of sound to meaning requires temporofrontal interaction transmitted via the ventral route.

Destroying memories to strengthen them

Lee reports work with rats showing that the core mechanisms that strengthen memories have more in common with the mechanisms that support memory reconsolidation than those that participate in initial memory storage. Memories are dynamic, rather than static, in nature. The reactivation of a memory through re-exposure to salient training stimuli results in its destabilization, necessitating a restabilization process known as reconsolidation, a disruption of which leads to amnesia. He finds that one normal function of hippocampal memory reconsolidation in rats is to modify the strength of a contextual-fear memory as a result of further learning.

A summary figure from Rudy's review of the article:

(a) The contextual-fear conditioning procedures that were used to study reconsolidation and memory strengthening are very similar. Note that the only difference between them is that the shock unconditioned stimulus was presented in phase II of the memory strengthening procedure, but the subject was only exposed to the context in the reconsolidation procedure. (b) Exposure to just a retrieval cue or a second conditioning trial will retrieve the established memory trace from long-term memory. This will result in the activation of the UPS, which will uncouple the synapses that support the trace, and the activation of Zip268 and the subsequent production of molecules, protein synthesis (PS), needed to rebuild or strengthen the trace.

The idea that retrieval can disrupt the synaptic basis of an established memory trace is counterintuitive. Nevertheless, the ubiquitin-proteasome system (UPS) has recently been identified as a key component of this process. Ubiquitin tags proteins for degradation and the proteasome degrades them. Retrieval of a contextual-fear memory is associated with polyubiquitinization of important postsynaptic density scaffolding proteins in the hippocampus.If proteolysis is prevented, then the memory trace should not degrade and would not have to be rebuilt from new protein.

Measuring the real-time chemistry of reward and aversion

fMRI studies suggest that nucleus accumbens (NAc) activation increases in response to stimuli of different hedonic valence, whereas physiological evidence suggests that NAc neurons show increases in activity for rewarding stimuli and pauses for aversive stimuli. Using cyclic voltammetry, Roitman et al. find that patterns of dopamine release and metabolic activity differentiate between rewarding and aversive stimuli. From their text:

It is controversial whether dopamine release in the NAc exclusively signals aspects of reward or serves a more broad purpose for signaling novelty or salience regardless of hedonic value...To dissociate salience or novelty from hedonic valence, we delivered brief intra-oral infusions of sucrose and quinine solutions to naive behaving rats and measured changes in dopamine concentration and pH in the NAc every 100 ms using fast-scan cyclic voltammetry. The pH measurements provide a measure of metabolic activity and thus an indirect measure of general neuronal activity.Appetitive (0.3 M sucrose) and aversive (0.001 M quinine) stimuli were delivered intra-orally to ensure equal exposure and transduction via the same sensory modality: the taste system. Each animal received both appetitive and aversive stimuli at unpredictable times to ensure comparable novelty and salience but opposing hedonic valence. This design elicited strong and consistent behavioral differences in hedonic expression with no evidence of anticipatory or conditioned responses. Voltammetric recordings permitted real-time detection of dopamine release and NAc activity, elucidating their role in signaling hedonic valence. The work makes clear that dopamine signaling and general activity in the NAc is exquisitely sensitive to both rewarding and aversive taste stimuli.

Teaching robots right from wrong

Cornelia Dean writes a brief article on people trying to develop intelligent battle robots that can behave more ethically in the battlefield than humans currently can. It focuses on the work of Ronald Arkin at Georgia Tech.

In the heat of battle, their minds clouded by fear, anger or vengefulness, even the best-trained soldiers can act in ways that violate the Geneva Conventions or battlefield rules of engagement. Now some researchers suggest that robots could do better...some of the potential benefits of autonomous fighting robots: For one thing, they can be designed without an instinct for self-preservation and, as a result, no tendency to lash out in fear. They can be built without anger or recklessness, Dr. Arkin wrote, and they can be made invulnerable to what he called “the psychological problem of ‘scenario fulfillment,’ ” which causes people to absorb new information more easily if it agrees with their pre-existing ideas.

Dr. Arkin’s approach involves creating a kind of intellectual landscape in which various kinds of action occur in particular “spaces.” In the landscape of all responses, there is a subspace of lethal responses. That lethal subspace is further divided into spaces for ethical actions, like firing a rocket at an attacking tank, and unethical actions, like firing a rocket at an ambulance....because rules like the Geneva Conventions are based on humane principles, building them into the machine’s mental architecture endows it with a kind of empathy. He added, though, that it would be difficult to design “perceptual algorithms” that could recognize when people were wounded or holding a white flag or otherwise “hors de combat.”

Noel Sharkey, a computer scientist at the University of Sheffield in Britain, has written that this is not a ‘Terminator’-style science fiction but grim reality. He would ban lethal autonomous robots until they demonstrate they will act ethically, a standard he said he believes they are unlikely to meet. Meanwhile, he said, he worries that advocates of the technology will exploit the ethics research to allay political opposition.

Daniel C. Dennett, a philosopher and cognitive scientist at Tufts University:

“If we talk about training a robot to make distinctions that track moral relevance, that’s not beyond the pale at all,” he said. But, he added, letting machines make ethical judgments is “a moral issue that people should think about.”

The Psychology of Transcending the Present

Liberman and Trope suggest an underlying similarity in all of our mental operations that are not dealing with the here and now:

People directly experience only themselves here and now but often consider, evaluate, and plan situations that are removed in time or space, that pertain to others' experiences, and that are hypothetical rather than real. People thus transcend the present and mentally traverse temporal distance, spatial distance, social distance, and hypotheticality. We argue that this is made possible by the human capacity for abstract processing of information. We review research showing that there is considerable similarity in the way people mentally traverse different distances, that the process of abstraction underlies traversing different distances, and that this process guides the way people predict, evaluate, and plan near and distant situations.

Here is one clip from the article on the interrelations among psychological distance dimensions:

Try to complete the sentence "A long time ago, in a ____ place." The tendency to complete it with "far away" rather than with "nearby" reflects not only a literary convention but also an automatic tendency of the human mind. Indeed, people use spatial metaphors to represent time in everyday language and reasoning. More generally, if psychological distance is reflected in different dimensions, then these dimensions should be mentally associated. Remote locations should bring to mind the distant rather than the near future, other people rather than oneself, and unlikely rather than likely events. Initial support for this hypothesis comes from a set of studies in which participants viewed landscape photographs containing an arrow that was pointing to either a proximal or a distal point on the landscape. Each arrow contained a word denoting either psychological proximity (e.g., tomorrow, we, sure) or psychological remoteness (e.g., year, others, maybe) (Figure below). Participants had to respond by pressing one of two keys as quickly and as accurately as possible. In one version of the task, they had to indicate whether the arrow pointed to a proximal or distal location. In another version, they had to identify the word printed in the arrow [Stroop task]. In both versions, participants responded faster to (i.e., processed more efficiently) distance-congruent stimuli (in which the spatially distant arrow contained a word that denoted large temporal distance, large social distance, or low likelihood and the spatially proximal arrow contained words that denoted temporal proximity, social proximity or high likelihood) than to distance-incongruent stimuli (in which spatially distal arrows contained words denoting proximity and spatially proximal arrows contained words denoting remoteness).

Figure: Two examples of incongruent visual stimuli: a word denoting social proximity, "us," located far from the observer, and a word denoting social remoteness, "them," located near the observer. Because spatial distance is associated with temporal distance, social distance, and hypotheticality, participants are slower to indicate the location of the arrow and to identify the word on it with incongruent stimuli than with congruent stimuli "us" located near the observer and "them" located far from the observer.

Superorganisms

Steve Jones writes an interesting review of E.O. Wilson's latest book, a collaboration with Bert Hölldobler: "THE SUPERORGANISM -The Beauty, Elegance, and Strangeness of Insect Societies"

Social insects have often been co-opted as models of human society. The right uses them to celebrate the power of hierarchy, the left that of community. Bees attract the liberal and optimistic (the spirit of the beehive), ants the conservative and the anything but (the city as ant heap).

Hölldobler and Wilson’s central conceit is that a colony is a single animal raised to a higher level. Each insect is a cell, its castes are organs, its queens are its genitals, the wasps that stung me are an equivalent of an immune system. In the same way, the foragers are eyes and ears, and the colony’s rules of development determine its shape and size. The hive has no brain, but the iron laws of cooperation give the impression of planning. Teamwork pays; in a survey of one piece of Amazonian rain forest, social insects accounted for 80 percent of the total biomass, with ants alone weighing four times as much as all its mammals, birds, lizards, snakes and frogs put together. The world holds as much ant flesh as it does that of humans.

A few simple rules produce what appears to be intelligence, but is in fact entirely mindless. Individuals are automatons. An ant stumbles on a tasty item and brings a piece back to the nest, wandering as it does and leaving a trail of scent. A second ant tracks that pathway back to the source, making random swerves of its own. A third, a fourth, and so on do the same, until soon the busy creatures converge on the shortest possible route, marked by a highway of pheromones. This phenomenon has some useful applications for the social animals who study it. Computer scientists fill their machines with virtual ants and task them with finding their way through a maze, leaving a coded signal as they pass until the fastest route emerges. That same logic helps plan efficient phone networks and the best use of the gates at J.F.K. In the phone system each message leaves a digital “pheromone” as it passes through a node, and the fastest track soon emerges. Swarm intelligence does wondrous things.

Neurotech

Virginia Gewin offers a report on the growing neurotechnology industry.

Last year, global neurotechnology industry revenues rose 8.3% to US$130.5 billion, says NeuroInsights, a market-analysis firm based in San Francisco, California. Its Neurotechnology Industry 2008 Report, which profiled 500 public and private companies, divided the industry into three sectors: neuropharmaceuticals, neurodevices and neurodiagnostics.

Medtronic in Minneapolis, Minnesota...is developing deep-brain stimulation devices, the latest ones for epilepsy and depression.

The budding area of neurogenesis research..has prompted drug companies to look to start-ups and academia for talent... the development of small molecules to encourage neurogenesis — in which endogenous stem cells mature into neurons — is a "breakthrough area". Swiss-based drug giant AstraZeneca announced last month that it will collaborate with Columbia University's René Hen to explore novel neurogenesis-related depression and anxiety treatments.

What happy people don't do.

Rabin notes the work of John Robinson, who finds that:

Although people who describe themselves as happy enjoy watching television, it turns out to be the single activity they engage in less often than unhappy people.

The study relied primarily on the responses of 45,000 Americans collected over 35 years by the University of Chicago’s General Social Survey, and on published “time diary” studies recording the daily activities of participants.

“We looked at 8 to 10 activities that happy people engage in, and for each one, the people who did the activities more — visiting others, going to church, all those things — were more happy,” Dr. Robinson said. “TV was the one activity that showed a negative relationship. Unhappy people did it more, and happy people did it less.”

Slow Blogging....

From an article by Sharon Otterman:

The practice is inspired by the slow food movement, which says that fast food is destroying local traditions and healthy eating habits. Slow food advocates, like the chef Alice Waters of Chez Panisse in Berkeley, Calif., believe that food should be local, organic and seasonal...A Slow Blog Manifesto, written in 2006 by Todd Sieling, a technology consultant from Vancouver, British Columbia, laid out the movement’s tenets. “Slow Blogging is a rejection of immediacy,” he wrote. “It is an affirmation that not all things worth reading are written quickly.” ...Some slow bloggers like to push the envelope of their readers’ attention even further. Academics post lengthy pieces about literature and teaching styles, while techies experiment to see how infrequently they can post before readers desert them.

This approach is a deliberate smack at the popular group blogs like Huffington Post, the Daily Beast, Valleywag and boingboing, which can crank out as many as 50 items a day. On those sites, readers flood in and advertisers sign on. Spin and snark abound. Earnest descriptions of the first frost of the season are nowhere to be found.

Andrew Sullivan, perhaps the world’s best-read political blogger, talked about the burnout factor in an article in November’s Atlantic magazine called “Why I Blog.” He said in an interview posted on the magazine’s Web site that during the election, his readers became so addicted to his stream of posts that he sometimes set his blog to post automatically so he could go to lunch. When he took two days off to make sense of “the whole Sarah Palin thing,” his audience flipped, thinking he was dead or silenced.

“You can’t stop,” Mr. Sullivan said in the online interview. “The readers act as if you’ve cut off their oxygen supply, and they just flap around like a goldfish out of water until you plop them back in.”

The Wall Street Bonus degrades rather than enhancing performance.

Dan Ariely, a professor of behavioral economics at Duke, reports interesting work showing that people perform better on tasks requiring cognitive skills when they are not offered huge rewards. Social pressure has the same effect that money has. It motivates people, especially when the tasks at hand require only effort and no skill. But it can provide stress, too, and at some point that stress overwhelms the motivating influence.

Contempt and disgust - sexual differences in brain responses

Aleman and Swart use fMRI measurements to note (slightly edited clip from the abstract) that:

Men display stronger brain activation than women to facial expressions of contempt in the medial frontal gyrus, inferior frontal gyrus, and superior temporal gyrus. Conversely, women showed stronger neural responses than men to facial expressions of disgust. The effect of stimulus sex differed for men versus women. Specifically, women showed stronger responses to male contemptuous faces (as compared to female expressions) in the insula and middle frontal gyrus. Contempt has been conceptualized as signaling perceived moral violations of social hierarchy, whereas disgust would signal violations of physical purity.

They suggest that the results indicate a neural basis for sex differences in moral sensitivity regarding hierarchy on the one hand and physical purity on the other.

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.