Training your working memory increases your cortical Dopamine D1 receptors

McNab et al demonstrate training-induced brain changes that indicate an unexpectedly high level of plasticity of our cortical dopamine D1 system and illustrate the mutual interdependence of our behavior and the underlying brain biochemistry. The training included a visuo-spatial working memory task, a backwards digit span task and a letter span task. These are similar to the n-back tests that I have mentioned in previous posts. The authors had previously shown increased prefrontal and parietal activity after training of working memory. Their abstract:

Working memory is a key function for human cognition, dependent on adequate dopamine neurotransmission. Here we show that the training of working memory, which improves working memory capacity, is associated with changes in the density of cortical dopamine D1 receptors. Fourteen hours of training over 5 weeks was associated with changes in both prefrontal and parietal D1 binding potential. This plasticity of the dopamine D1 receptor system demonstrates a reciprocal interplay between mental activity and brain biochemistry in vivo.

A clip from their methods description:

Participants performed working memory (WM) tasks with a difficulty level close to their individual capacity limit for about 35 min per day over a period of 5 weeks (8–10). Thirteen volunteers (healthy males 20 to 28 years old) performed the 5-week WM training. Five computer-based WM tests (three visuospatial and two verbal) were used to measure each participant's WM capacity before and after training, and they showed a significant improvement of overall WM capacity (paired t test, t = 11.1, P less than 0.001). The binding potential (BP) of D1 and D2 receptors was measured with positron emission tomography (PET) while the participants were resting, before and after training, using the radioligands [11C]SCH23390 and [11C]Raclopride, respectively.

Malthusian information famine

A view of our information future from Charles Seife:

...Vast amounts of digital memory will change the relationship that humans have with information....For the first time, we as a species have the ability to remember everything that ever happens to us. For millennia, we were starving for information to act as raw material for ideas. Now, we are about to have a surfeit.

Alas, there will be famine in the midst of all that plenty. There are some hundred million blogs, and the number is roughly doubling every year. The vast majority are unreadable. Several hundred billion e-mail messages are sent every day; most of it—current estimates run around 70%—is spam. There seems to be a Malthusian principle at work: information grows exponentially, but useful information grows only linearly. Noise will drown out signal. The moment that we, as a species, finally have the memory to store our every thought, etch our every experience into a digital medium, it will be hard to avoid slipping into a Borgesian nightmare where we are engulfed by our own mental refuse.

Some Chopin for a Monday morning.

This is Chopin's Nocture Op. 9 No. 1, which I recorded last May. I miss my Steinway B grand piano back in Wisconsin during my current snowbird period in Fort Lauderdale Florida. I will probably do a burst of pent-up recordings when I get back in April.

How we decide how big a reward is...

Furlong and Opfer do a nice set of experiments showing that we can be lured into making decisions by numbers that seem bigger than they really are. We apparently go with numerical values rather than real economic values. They asked volunteers to take part in the prisoner’s dilemma behavioral test, in which two partners are offered various rewards to either work together or defect. The idea is that in the long term, the participants earn the most money by cooperating. But in any given round of play, they make the most if they decide to turn against their partner while he stays loyal. (The reward is lowest when both partners defect.) When the reward for cooperation was increased to 300 cents from 3 cents, the researchers found, the level of cooperation went up. But when the reward went from 3 cents to $3, it did not. Here is their abstract:

Cooperation often fails to spread in proportion to its potential benefits. This phenomenon is captured by prisoner's dilemma games, in which cooperation rates appear to be determined by the distinctive structure of economic incentives (e.g., $3 for mutual cooperation vs. $5 for unilateral defection). Rather than comparing economic values of cooperating versus not ($3 vs. $5), we tested the hypothesis that players simply compare numeric values (3 vs. 5), such that subjective numbers (mental magnitudes) are logarithmically scaled. Supporting our hypothesis, increasing only numeric values of rewards (from $3 to 300¢) increased cooperation, whereas increasing economic values increased cooperation only when there were also numeric increases. Thus, changing rewards from 3¢ to 300¢ increased cooperation rates, but an economically identical change from 3¢ to $3 elicited no gains. Finally, logarithmically scaled reward values predicted 97% of variation in cooperation, whereas the face value of economic rewards predicted none. We conclude that representations of numeric value constrain how economic rewards affect cooperation.

Similar risk assessment in man and mouse.

In an open access article Balci et al. devise a simple and clever timing task which captures the essence of temporal decision making that confronts human and nonhuman animal subjects in everyday life, and show that men are no better than mice in assessing a simple kind of uncertainty. This suggests that mechanisms for near-optimal risk assessment in many everyday contexts evolved long ago. Their abstract:

Human and mouse subjects tried to anticipate at which of 2 locations a reward would appear. On a randomly scheduled fraction of the trials, it appeared with a short latency at one location; on the complementary fraction, it appeared after a longer latency at the other location. Subjects of both species accurately assessed the exogenous uncertainty (the probability of a short versus a long trial) and the endogenous uncertainty (from the scalar variability in their estimates of an elapsed duration) to compute the optimal target latency for a switch from the short- to the long-latency location. The optimal latency was arrived at so rapidly that there was no reliably discernible improvement over trials. Under these nonverbal conditions, humans and mice accurately assess risks and behave nearly optimally. That this capacity is well-developed in the mouse opens up the possibility of a genetic approach to the neurobiological mechanisms underlying risk assessment.

How cute is that baby's face - hormones regulate the answer.

Sprengelmeyer et al. make some interesting observations suggesting that female reproductive hormones increase sensitivity to variations in the cuteness of baby faces. Their abstract:

We used computer image manipulation to develop a test of perception of subtle gradations in cuteness between infant faces. We found that young women (19–26 years old) were more sensitive to differences in infant cuteness than were men (19–26 and 53–60 years old). Women aged 45 to 51 years performed at the level of the young women, whereas cuteness sensitivity in women aged 53 to 60 years was not different from that of men (19–26 and 53–60 years old). Because average age at menopause is 51 years in Britain, these findings suggest the possible involvement of reproductive hormones in cuteness sensitivity. Therefore, we compared cuteness discrimination in pre- and postmenopausal women matched for age and in women taking and not taking oral contraceptives (progestogen and estrogen). Premenopausal women and young women taking oral contraceptives (which raise hormone levels artificially) were more sensitive to variations of cuteness than their respective comparison groups. We suggest that cuteness sensitivity is modulated by female reproductive hormones.

Modulation of the brain's emotion circuits by facial muscle feedback

Several studies have shown that facial muscle contractions associated with various emotions can induce or enhance the correlated emotional feelings, or counter them if the facial movements and central feelings are in opposition (as in forcing a smile while angry.) The late senator Proxmire of Wisconsin wrote a self help book that included instruction for making a 'happy face' to improve your mood. Hennenlotter et al. now do an interesting bit of work in which they observe that blocking the feedback of frown muscles to the brain lowers the level of amygdala activation during a subject's imitiation of an angry facial expression:

Afferent feedback from muscles and skin has been suggested to influence our emotions during the control of facial expressions. Recent imaging studies have shown that imitation of facial expressions is associated with activation in limbic regions such as the amygdala. Yet, the physiological interaction between this limbic activation and facial feedback remains unclear. To study if facial feedback effects on limbic brain responses during intentional imitation of facial expressions, we applied botulinum toxin (BTX)–induced denervation of frown muscles in combination with functional magnetic resonance imaging as a reversible lesion model to minimize the occurrence of afferent muscular and cutaneous input. We show that, during imitation of angry facial expressions, reduced feedback due to BTX treatment attenuates activation of the left amygdala and its functional coupling with brain stem regions implicated in autonomic manifestations of emotional states. These findings demonstrate that facial feedback modulates neural activity within central circuitries of emotion during intentional imitation of facial expressions. Given that people tend to mimic the emotional expressions of others, this could provide a potential physiological basis for the social transfer of emotion.

The smell of fear modulates our perception of threat in faces

This is kind of neat: Zhou and Chen collected gauze pads that had absorbed sweat from the armpit apocrine glands of men (because they sweat more) watching a horror movie or a happy or neutral movie. Women sniffed the extracted smells (versus neutral controls) while watching a face morph from happy to frightened (women have more sensitive sense of smell and sensitivity to emotional signals). The chemosignal of fearful sweat biased the women toward interpreting ambiguous expressions as more fearful, but had no effect when the facial emotion was more discernible. This shows that fear-related chemosignals modulate humans' visual emotion perception in an emotion-specific way

Men tolerate their peers better than women

This study by Benenson et al. was conducted to examine the often-cited conclusion that human females are more sociable than males. Its results certainly correlate with my own university experience. In studying students at a Northeastern university they concluded that:

Males were more likely than females to be satisfied with their roommates and were less bothered by their roommates' style of social interaction, types of interests, values, and hygiene, regardless of whether or not the roommates were selected for study because they were experiencing conflicts. Furthermore, males were less likely than females to switch roommates over the course of a year at three collegiate institutions. Finally, violation of a friendship norm produced a smaller negative effect on friendship belief in males than in females.

They authors maintain (this surprises me, if true) that their studies are the first to demonstrate that males, compared with females, display higher levels of tolerance for genetically unrelated same-sex individuals.

When losing control can be useful.

Apfelbaum and Sommers do a simple experiment that suggests that diminished executive control can facilitate positive outcomes in contentious intergroup interactions. Here is their abstract, followed by a description of how the subject's sense of executive control was manipulated:

Across numerous domains, research has consistently linked decreased capacity for executive control to negative outcomes. Under some conditions, however, this deficit may translate into gains: When individuals' regulatory strategies are maladaptive, depletion of the resource fueling such strategies may facilitate positive outcomes, both intra- and interpersonally. We tested this prediction in the context of contentious intergroup interaction, a domain characterized by regulatory practices of questionable utility. White participants discussed approaches to campus diversity with a White or Black partner immediately after performing a depleting or control computer task. In intergroup encounters, depleted participants enjoyed the interaction more, exhibited less inhibited behavior, and seemed less prejudiced to Black observers than did control participants—converging evidence of beneficial effects. Although executive capacity typically sustains optimal functioning, these results indicate that, in some cases, it also can obstruct positive outcomes, not to mention the potential for open dialogue regarding divisive social issues.

Now, the following dinking with executive control to generate 'depleted' participants sort of makes sense to me, but I'm not sure I really get it...

The Attention Network Test is a computer-based measure of attention. We modified the ANT component typically used to gauge executive control into a manipulation of executive capacity. Across multiple trials, participants were presented with a string of five arrows and instructed to quickly and accurately indicate the direction of the center arrow (i.e., whether the arrow was pointing left or right). The center arrow was either congruent (i.e., ←←←←←, →→→→→) or incongruent (i.e., →→←→→, ←←→←←) with its flankers; correct responses to incongruent trials thus required executive control to override the natural tendency to follow the flankers. Participants in the depletion condition were presented with congruent and incongruent stimuli, whereas participants in the control condition viewed congruent stimuli only.

If it is difficult to pronounce, it must be risky.

Song and Schwartz make the observation that low processing fluency (as with names that are difficult to pronounce) fosters the impression that a stimulus is unfamiliar, which in turn results in perceptions of higher risk. Ostensible food additives were rated as more harmful when their names were difficult to pronounce than when their names were easy to pronounce, and amusement-park rides were rated as more likely to make one sick (an undesirable risk) and also as more exciting and adventurous (a desirable risk) when their names were difficult to pronounce than when their names were easy to pronounce.

Brain imaging can reflect expected, rather than actual, nerve activity

Work by Sirotin and Das illustrates how the brain thinks ahead. Electrical signalling among brain cells summons the local delivery of extra blood — the basis of functional brain imaging. And the usual assumption is that an increase in blood flow means an increase in electrical activity. The experiments by Sirotin and Das show that blood can be sent to the brain's visual cortex in the absence of any stimulus, priming the neural tissue in apparent anticipation of future events. (They observed this mismatch in alert rhesus monkeys by simultaneously measuring vascular and neural responses in the same region of the visual cortex. Changes in the blood supply were monitored by a sensitive video camera peering at the surface of the brain through a transparent window in the animal's skull, and local electrical responses of neurons were measured with a microelectrode.) Their results show that cortical blood flow can depart wildly from what is expected on the basis of local neural activity. Blood can be sent in anticipation of neural events that never take place.

Knowledge about how we know changes everything.

The essay by Boroditsky in the Edge series has the following interesting comments:

In the past ten years, research in cognitive science has started uncovering the neural and psychological substrates of abstract thought, tracing the acquisition and consolidation of information from motor movements to abstract notions like mathematics and time. These studies have discovered that human cognition, even in its most abstract and sophisticated form, is deeply embodied, deeply dependent on the processes and representations underlying perception and motor action. We invent all kinds of complex abstract ideas, but we have to do it with old hardware: machinery that evolved for moving around, eating, and mating, not for playing chess, composing symphonies, inventing particle colliders, or engaging in epistemology for that matter. Being able to re-use this old machinery for new purposes has allowed us to build tremendously rich knowledge repertoires. But it also means that the evolutionary adaptations made for basic perception and motor action have inadvertently shaped and constrained even our most sophisticated mental efforts. Understanding how our evolved machinery both helps and constrains us in creating knowledge, will allow us to create new knowledge, either by using our old mental machinery in yet new ways, or by using new and different machinery for knowledge-making, augmenting our normal cognition.

So why will knowing more about how we know change everything? Because everything in our world is based on knowledge. Humans, leaps and bounds beyond any other creatures, acquire, create, share, and pass on vast quantities of knowledge. All scientific advances, inventions, and discoveries are acts of knowledge creation. We owe civilization, culture, science, art, and technology all to our ability to acquire and create knowledge. When we study the mechanics of knowledge building, we are approaching an understanding of what it means to be human—the very nature of the human essence. Understanding the building blocks and the limitations of the normal human knowledge building mechanisms will allow us to get beyond them. And what lies beyond is, well, yet unknown...

Robocop and cello scrotum

I thought these two items in the Random Samples section of the Feb. 6 Science Magazine were a hoot:

FIDDLE WITHOUT FEAR:

Elaine Murphy was just starting her medical career in 1974 when she and her husband, John, pulled a fast one on the editors of the British Medical Journal (BMJ). The joke's long run ended last week when the Murphys confessed that a medical condition, "cello scrotum," they coined in a letter to the journal 35 years ago doesn't exist.

Now a baroness and member of the British House of Lords, Murphy and her partner in crime admitted the hoax in a letter published 27 January in BMJ. The couple came up with the prank after reading a letter to BMJ in April 1974 on "guitar nipple," an alleged chest inflammation that the couple assumed was fake. In the spirit of one-upmanship, the pair wrote a short note on "cello scrotum," an inflammation on a fabricated patient who played the cello for hours each day. "We never expected our spoof letter to be published," Murphy says. "We probably wrote it after a glass of wine or two."

The Murphys came clean after finding a reference to cello scrotum in a December 2008 issue of the journal. Although journal editors disapprove of dishonesty in science, Tony Delamothe, a deputy editor at BMJ, says that the Murphys' joke was harmless. "All of my colleagues, from the editor down, think it's a hoot," Delamothe says. Murphy adds that she's received no negative fallout. "I was worried the House of Lords would think I was bringing them into disrepute," she says, "but so far, everyone wants to enjoy the joke."

NEW SHERIFF IN TOWN:

It's not RoboCop, but Japanese robotmaker Tmsuk believes its T-34 security robot can fight crime by snaring intruders in an entangling net. The 60-centimeter-tall robot sends real-time video of its surroundings to a remote operator's mobile phone over Japan's advanced mobile phone service, eliminating the need for cables or wireless networks. On command, the T-34 fires a weighted net capable of enveloping a human target up to 3.5 meters away, holding the suspected criminal until security officers arrive. Tmsuk, which worked with security service provider Alacom in developing the T-34, says the robot could confront dangerous intruders while keeping human guards at a safe distance. "We think this could serve the needs of the security industry," says company spokesperson Mariko Ishikawa. The company recently demonstrated a working prototype and says a commercial model could be on the market in a few years for about $5000.

Brain correlates of dealing with risk versus ambiguity

Because it is relevant to last friday's post on the economic situation, I thought I would bring forward this bit of work which I had been planning to mention soon. It is yet another interesting study from the group at Wellcome Center group at University College associated with Ray Dolan - cognitive neuroscience that is directly relevant to our current economic and political reality:

In economic decision making, outcomes are described in terms of risk (uncertain outcomes with certain probabilities) and ambiguity (uncertain outcomes with uncertain probabilities). Humans are more averse to ambiguity than to risk, with a distinct neural system suggested as mediating this effect. However, there has been no clear disambiguation of activity related to decisions themselves from perceptual processing of ambiguity. In a functional magnetic resonance imaging (fMRI) experiment, we contrasted ambiguity, defined as a lack of information about outcome probabilities, to risk, where outcome probabilities are known, or ignorance, where outcomes are completely unknown and unknowable. We modified previously learned pavlovian CS+ stimuli such that they became an ambiguous cue and contrasted evoked brain activity both with an unmodified predictive CS+ (risky cue), and a cue that conveyed no information about outcome probabilities (ignorance cue). Compared with risk, ambiguous cues elicited activity in posterior inferior frontal gyrus and posterior parietal cortex during outcome anticipation. Furthermore, a similar set of regions was activated when ambiguous cues were compared with ignorance cues. Thus, regions previously shown to be engaged by decisions about ambiguous rewarding outcomes are also engaged by ambiguous outcome prediction in the context of aversive outcomes. Moreover, activation in these regions was seen even when no actual decision is made. Our findings suggest that these regions subserve a general function of contextual analysis when search for hidden information during outcome anticipation is both necessary and meaningful.

The authors also comment on previous work emphasizing the amygdala:

In contrast to the present experiment, a previous fMRI study has suggested that the amygdala and dorsomedial prefrontal and orbitofrontal cortex underlie decision making under ambiguity (Hsu et al., 2005). ... Although it is obvious that the amygdala responds to some kinds of uncertainty [e.g., temporal unpredictability], different forms of uncertainty have not been formally compared with regard to such responses. The kind of outcome uncertainty described in the aforementioned work is likely to be different from the economic definition applied in the present study (e.g., the lack of knowledge about CS–UCS contingencies in fear conditioning paradigms corresponds to the ignorance and not the ambiguity condition in the present study). The study by Hsu et al. (2005), although concerned with an economic definition of ambiguity, in fact collapsed different kinds of "ambiguous" situations for analysis of fMRI data, that is, monetary gambles following a strict economic definition, but also quizzes, and uninformed gambles against an informed opponent. Together, the data indicate that there is no entirely convincing empirical evidence that the amygdala responds to ambiguity as defined in a strict economic sense, an inference upheld by our present findings, although such a role of the amygdala cannot be discounted entirely (Seymour and Dolan, 2008).

Placebos, curing within...

I wanted to pass on two pieces on self curing and the placebo effect pointed out to me by a mindblog reader. Amanda Schaffer offers a review in Slate on Anne Harrington's new book "The Cure Within", which maps the history of mind-body medicine. Also, a recent study testing pain relief from analgesics shows that merely telling people that a novel form of codeine they were taking (actually a placebo) was worth $2.50 rather than 10 cents increased the proportion of people who reported pain relief from 61% to 85.4%.1 When the "price" of the placebo was reduced, so was the pain relief.

Run for the hills.....

Three items in today's New York Times are sufficienly pungent to warrant mention. Lohr's article gives a clear exposition of the fact that the nation's banking system is effectively insolvent, it's debts being greater than its assets. Krugman again notes the futility of current plans which avoid shutting down the bad banks (and wiping out their investors) and saving the solvent ones. And Brooks, in an OpEd piece that motivated me to go ahead with this post, paints a pessimistic imagined future scenario for 2010 influenced by his reading of current cognitive neuroscience (Here, for example, is a relevant article, more recent than the work that Brooks was aware of, showing structures that appear to be more important than the amygdala in dealing with uncertainty). From Brooks' piece:

The problem was this: The policy makers knew how to pull economic levers, but they did not know how to use those levers to affect social psychology.

The crisis was labeled an economic crisis, but it was really a psychological crisis. It was caused by a mood of fear and uncertainty, which led consumers to not spend, bankers to not lend and entrepreneurs to not risk. No amount of federal spending could change this psychology because uncertainty about the future remained acute.

Essentially, Americans had migrated from one society to another — from a society of high trust to a society of low trust, from a society of optimism to a society of foreboding, from a society in which certain financial habits applied to a society in which they did not. In the new world, investors had no basis from which to calculate risk. Families slowly deleveraged. Bankers had no way to measure the future value of assets.

Cognitive scientists distinguish between normal risk-assessment decisions, which activate the reward-prediction regions of the brain, and decisions made amid extreme uncertainty, which generate activity in the amygdala. These are different mental processes using different strategies and producing different results. Americans were suddenly forced to cope with this second category, extreme uncertainty.

Economists and policy makers had no way to peer into this darkness. Their methods were largely based on the assumption that people are rational, predictable and pretty much the same. Their models work best in times of equilibrium. But in this moment of disequilibrium, behavior was nonlinear, unpredictable, emergent and stubbornly resistant to Keynesian rationalism.

...The nation had essentially bet its future on economic models with primitive views of human behavior. The government had tried to change social psychology using the equivalent of leeches and bleeding.

(A friend of mine claims to know a former hedge fund manager who has converted his assets to gold coins, and bought a safe, and a shotgun!)

Faster evolution means more ethnic differences.

Some interesting thoughts from Jonathan Haidt:

...a betting person would have to predict that as we decode the genomes of people around the world, we're going to find deeper differences than most scientists now expect...A wall has long protected respectable evolutionary inquiry from accusations of aiding and abetting racism. That wall is the belief that genetic change happens at such a glacial pace that there simply was not time, in the 50,000 years since humans spread out from Africa, for selection pressures to have altered the genome in anything but the most trivial way (e.g., changes in skin color and nose shape were adaptive responses to cold climates). ...But the writing is on the wall. Russian scientists showed in the 1990s that a strong selection pressure (picking out and breeding only the tamest fox pups in each generation) created what was — in behavior as well as body — essentially a new species in just 30 generations. That would correspond to about 750 years for humans.

Humans may never have experienced such a strong selection pressure for such a long period, but they surely experienced many weaker selection pressures that lasted far longer, and for which some heritable personality traits were more adaptive than others. It stands to reason that local populations (not continent-wide "races") adapted to local circumstances by a process known as "co-evolution" in which genes and cultural elements change over time and mutually influence each other. The best documented example of this process is the co-evolution of genetic mutations that maintain the ability to fully digest lactose in adulthood with the cultural innovation of keeping cattle and drinking their milk. This process has happened several times in the last 10,000 years, not to whole "races" but to tribes or larger groups that domesticated cattle.

...traits that led to Darwinian success in one of the many new niches and occupations of Holocene life — traits such as collectivism, clannishness, aggressiveness, docility, or the ability to delay gratification — are often seen as virtues or vices. Virtues are acquired slowly, by practice within a cultural context, but the discovery that there might be ethnically-linked genetic variations in the ease with which people can acquire specific virtues is — and this is my prediction — going to be a "game changing" scientific event. (By "ethnic" I mean any group of people who believe they share common descent, actually do share common descent, and that descent involved at least 500 years of a sustained selection pressure, such as sheep herding, rice farming, exposure to malaria, or a caste-based social order, which favored some heritable behavioral predispositions and not others.)

I believe that the "Bell Curve" wars of the 1990s, over race differences in intelligence, will seem genteel and short-lived compared to the coming arguments over ethnic differences in moralized traits. I predict that this "war" will break out between 2012 and 2017...There are reasons to hope that we'll ultimately reach a consensus that does not aid and abet racism. I expect that dozens or hundreds of ethnic differences will be found, so that any group — like any person — can be said to have many strengths and a few weaknesses, all of which are context-dependent. Furthermore, these cross-group differences are likely to be small when compared to the enormous variation within ethnic groups and the enormous and obvious effects of cultural learning. But whatever consensus we ultimately reach, the ways in which we now think about genes, groups, evolution and ethnicity will be radically changed by the unstoppable progress of the human genome project.

Caloric restriction improves memory

From Witte et al:

Animal studies suggest that diets low in calories and rich in unsaturated fatty acids (UFA) are beneficial for cognitive function in age. Here, we tested in a prospective interventional design whether the same effects can be induced in humans. Fifty healthy, normal- to overweight elderly subjects (29 females, mean age 60.5 years, mean body mass index 28 kg/m2) were stratified into 3 groups: (i) caloric restriction (30% reduction), (ii) relative increased intake of UFAs (20% increase, unchanged total fat), and (iii) control. Before and after 3 months of intervention, memory performance was assessed under standardized conditions. We found a significant increase in verbal memory scores after caloric restriction (mean increase 20%; P less than 0.001), which was correlated with decreases in fasting plasma levels of insulin and high sensitive C-reactive protein, most pronounced in subjects with best adherence to the diet (all r values less than −0.8; all P values less than 0.05). Levels of brain-derived neurotrophic factor remained unchanged. No significant memory changes were observed in the other 2 groups. This interventional trial demonstrates beneficial effects of caloric restriction on memory performance in healthy elderly subjects. Mechanisms underlying this improvement might include higher synaptic plasticity and stimulation of neurofacilitatory pathways in the brain because of improved insulin sensitivity and reduced inflammatory activity. Our study may help to generate novel prevention strategies to maintain cognitive functions into old age.

Pavlovian conditioning can transfer from the virtual world to the real world

McCabe et al. offer an intriguing experiment showing that conditioning-dependent motivational properties can transfer from a computer game to the real world and also be expressed in terms of brain responses measured using functional magnetic resonance imaging (fMRI). They studied healthy participants conditioned with aversive and appetitive drinks in the context of a virtual cycling race. Three days after conditioning, participants returned for a fMRI session. They used this opportunity to observe the impact of incidental presentation of conditioned stimuli on a real-world decision (seat choice, see the figures below). They found a significant influence of conditioning on seat choice and, moreover, noted that individual susceptibility to this influence was reflected in differential insula cortex responses during subsequent scanning. Thus a stimulus in a virtual environment can acquire motivational properties that persist and modify behavior in the real world.

Figure - Day 1: Pavlovian conditioning in virtual environment. Participants in the virtual cycle race were overtaken by competitors. The stimuli on the competitors' jerseys acted as CSs predicting the delivery of either pleasant or unpleasant juice. The stimulus-to-juice assignment was counterbalanced across participants.

Figure - Day 4: Real-world decision when asked to take a seat in an unoccupied waiting room before scanning. Sixteen participants chose the seat bearing a towel with the CS+app.