Memory fading? Try some dopamine...

From Chowdhury et al. in the Journal of Neuroscience:

Activation of the hippocampus is required to encode memories for new events (or episodes). Observations from animal studies suggest that, for these memories to persist beyond four to six hours, a release of dopamine generated by strong hippocampal activation is needed. This predicts that dopaminergic enhancement should improve human episodic memory persistence also for events encoded with weak hippocampal activation. Here, using pharmacological functional MRI (fMRI) in an elderly population in which there is a loss of dopamine neurons as part of normal aging, we show this very effect. The dopamine precursor levodopa led to a dose-dependent (inverted U-shape) persistent episodic memory benefit for images of scenes when tested after six hours, independent of whether encoding-related hippocampal fMRI activity was weak or strong (U-shaped dose–response relationship). This lasting improvement even for weakly encoded events supports a role for dopamine in human episodic memory consolidation, albeit operating within a narrow dose range.

A revolution in understanding our genetics, personality, and disease.

A revolution is taking place. It challenges the basic genetic orthodoxy of the past century, changing what all of us thought we knew. This is dense material, but very important, and I would urge general readers to try to have a go at it. (Few MindBlog readers would be up for taking on the Wonkish details of Nelson et al.'s paper on 'epigenetic effects of…cytidine deaminase deficiency…etc.' - so I want to pass on edited and rearranged clips from a commentary by Mattick that shows (still Wonkish, but less so) the context and importance of this and similar studies):

Nelson et al. present intriguing evidence that challenges the fundamental tenets of genetics. It has long been assumed that the inherited contribution to phenotype is embedded in DNA sequence variations in, and interactions between, the genes endogenous to the organism, i.e., alleles derived from parents with some degree of de novo variation. This assumption underlies most genetic analysis, including the fleet of genome-wide association studies launched in recent years to identify genomic loci that influence complex human traits and diseases....the perplexing and much debated surprise has been that most genome-wide association studies have superficially failed to locate more than a small percentage of the inherited component of complex traits. This may be a result of a number of possibilities...including... intergenerational epigenetic inheritance, which is not polled by DNA sequence. However, the latter has not thus far been paid much attention or given much credence as a major factor.

Now Nelson et al. provide data suggesting that epigenetic inheritance may be far more important and pervasive than expected. (Mechanistically, epigenetic memory is embedded in DNA methylation and/or histone modifications, which are thought to be erased in germ cells, but may not be, at least completely, as some chromatin structure appears to be preserved. Some information may also be cotransmitted by RNA.) Their findings add to a growing list of studies indicating that genetic influence of ancestral variants can commonly reach through multiple generations and rival conventional inheritance in strength. These include the demonstrations, with considerable molecular and genetic detail, of epigenetic inheritance (i.e., “paramutation”) in plants, and, although still somewhat controversial, in animals.

Although the genetics are complex, Nelson et al.show in an elegant and comprehensive series of analyses that grand-maternal (but not grand-paternal) heterozygosis for a null allele of the Apobec1 cytidine deaminase gene modulates testicular germ cell tumor susceptibility and embryonic viability in male (mouse) descendants that do not carry the null allele, an effect that persists for at least three generations.

...here is now good evidence that epigenetic inheritance is RNA-mediated...as it is becoming clear that a major function of the large numbers of noncoding RNAs that are differentially expressed from the genome is to direct chromatin-modifying complexes to their sites of action. This conclusion is consistent with the recent findings of the ENCODE project, suggesting that much if not most of the human genome may be functional, and explains the informational basis of the extraordinary precision and complexity of the epigenetic superstructure of the genome in different cells required to specify developmental architecture.

The available evidence not only suggests an intimate interplay between genetic and epigenetic inheritance, but also that this interplay may involve communication between the soma and the germline. This idea contravenes the so-called Weismann barrier, sometimes referred to as Biology’s Second Law, which is based on flimsy evidence and a desire to distance Darwinian evolution from Lamarckian inheritance at the time of the Modern Evolutionary Synthesis. However, the belief that the soma and germline do not communicate is patently incorrect—as demonstrated by the multigenerational inheritance of RNAi-mediated phenotypes delivered to somatic cells in Caenorhabditis elegans.

Thus, if RNA editing can alter hardwired genetic information in a context-dependent manner, and thereby alter epigenetic memory, it is feasible that not only allelic but also environmental history may shape phenotype, and provide a far more plastic and dynamic inheritance platform than envisaged by the genetic orthodoxy of the past century. Morever...RNA, more than DNA, may be the computational engine of the evolution and ontogeny of developmentally complex and cognitively advanced organisms

Learning new information during sleep.

Arzi et al. do an ingenious experiment to show that we can do associative learning during our sleep. We can associate a sound with a pleasant or unpleasant odor and react, both while still asleep and after waking, with a deeper or shallower breath. This does not, however, represent the kind of 'sleep learning' long sought by students who unsuccessfully try to remember scientific or literary facts needed for an exam by playing a tape softly during sleep. Here is the abstract:

During sleep, humans can strengthen previously acquired memories, but whether they can acquire entirely new information remains unknown. The nonverbal nature of the olfactory sniff response, in which pleasant odors drive stronger sniffs and unpleasant odors drive weaker sniffs, allowed us to test learning in humans during sleep. Using partial-reinforcement trace conditioning, we paired pleasant and unpleasant odors with different tones during sleep and then measured the sniff response to tones alone during the same nights' sleep and during ensuing wake. We found that sleeping subjects learned novel associations between tones and odors such that they then sniffed in response to tones alone. Moreover, these newly learned tone-induced sniffs differed according to the odor pleasantness that was previously associated with the tone during sleep. This acquired behavior persisted throughout the night and into ensuing wake, without later awareness of the learning process. Thus, humans learned new information during sleep.

The Neurochemistry of Storytelling.

Having in the previous post just made an ill-tempered dump on one kind of popularization, I decide to be inconsistent and now pass on this nice piece with a little less pizazz from the Brain Pickings Newsletter, on how storytelling can engage our brain neurochemistry associated with stress and empathy. It is a very effective and touching piece, and I recommend that you watch the video below:

Brain Showbiz...

Put me down as a curmudgeonly old fart, but I'm not getting a 'gee whiz' response to a recent promotional email asking for publicity on a rhythm and the brain project. It's cute, the graphics are kewl, but the science is out to lunch - it seems to me more like publicity seeking and self promotion masquerading as brain science.

Conscious awareness not required for our placebo or nocebo responses.

Interesting observations from Jensen et al. They first condition a placebo (beneficial) or nocebo (adverse) reponse to a thermal pain stimulus, and then find subliminal (non-conscious) presentation of the conditioning cues elicits the same responses. Their abstract:

The dominant theories of human placebo effects rely on a notion that consciously perceptible cues, such as verbal information or distinct stimuli in classical conditioning, provide signals that activate placebo effects. However, growing evidence suggest that behavior can be triggered by stimuli presented outside of conscious awareness. Here, we performed two experiments in which the responses to thermal pain stimuli were assessed. The first experiment assessed whether a conditioning paradigm, using clearly visible cues for high and low pain, could induce placebo and nocebo responses. The second experiment, in a separate group of subjects, assessed whether conditioned placebo and nocebo responses could be triggered in response to nonconscious (masked) exposures to the same cues. A total of 40 healthy volunteers (24 female, mean age 23 y) were investigated in a laboratory setting. Participants rated each pain stimulus on a numeric response scale, ranging from 0 = no pain to 100 = worst imaginable pain. Significant placebo and nocebo effects were found in both experiment 1 (using clearly visible stimuli) and experiment 2 (using nonconscious stimuli), indicating that the mechanisms responsible for placebo and nocebo effects can operate without conscious awareness of the triggering cues. This is a unique experimental verification of the influence of nonconscious conditioned stimuli on placebo/nocebo effects and the results challenge the exclusive role of awareness and conscious cognitions in placebo responses.

Clever crows! Now shown to reason about hidden causes.

Behavioral studies on New Caledonian crows, especially over the past twenty years, continue to yield amazing results. (A video I first posted for my Biology of Mind course over ten years ago showing some of this earlier work has received 125,000 viewings!). Taylor et al. now demonstrate reasoning about hidden causes:

The ability to make inferences about hidden causal mechanisms underpins scientific and religious thought. It also facilitates the understanding of social interactions and the production of sophisticated tool-using behaviors. However, although animals can reason about the outcomes of accidental interventions, only humans have been shown to make inferences about hidden causal mechanisms. Here, we show that tool-making New Caledonian crows react differently to an observable event when it is caused by a hidden causal agent. Eight crows watched two series of events in which a stick moved. In the first set of events, the crows observed a human enter a hide, a stick move, and the human then leave the hide. In the second, the stick moved without a human entering or exiting the hide. The crows inspected the hide and abandoned probing with a tool for food more often after the second, unexplained series of events. This difference shows that the crows can reason about a hidden causal agent. Comparative studies with the methodology outlined here could aid in elucidating the selective pressures that led to the evolution of this cognitive ability.

Kids as little scientists - early academics can be misguided

A review article by Gopnik offers an interesting perspective:

New theoretical ideas and empirical research show that very young children’s learning and thinking are strikingly similar to much learning and thinking in science. Preschoolers test hypotheses against data and make causal inferences; they learn from statistics and informal experimentation, and from watching and listening to others. The mathematical framework of probabilistic models and Bayesian inference can describe this learning in precise ways. These discoveries have implications for early childhood education and policy. In particular, they suggest both that early childhood experience is extremely important and that the trend toward more structured and academic early childhood programs is misguided.

Opps! Sex does decrease human male lifespan.

Animal studies have suggested that castration increases lifespan in males, and now Korean researchers have examined genealogy records and lifespan of 81 Korean eunuchs to find that their average lifespan is ~14-19 years longer than that of non-castrated men of similar class. (I doubt this finding will lead to an uptick in voluntary male castrations, the trade off of minus fifteen years for what our male sex hormones make possible doesn’t seem so bad...) The abstract:

Although many studies have shown that there are trade-offs between longevity and reproduction, whether such trade-offs exist in humans has been a matter of debate. In many species, including humans, males live shorter than females, which could be due to the action of male sex hormones. Castration, which removes the source of male sex hormones, prolongs male lifespan in many animals, but this issue has been debated in humans. To examine the effects of castration on longevity, we analyzed the lifespan of historical Korean eunuchs. Korean eunuchs preserved their lineage by adopting castrated boys. We studied the genealogy records of Korean eunuchs and determined the lifespan of 81 eunuchs. The average lifespan of eunuchs was 70.0 ± 1.76 years, which was 14.4–19.1 years longer than the lifespan of non-castrated men of similar socio-economic status. Our study supports the idea that male sex hormones decrease the lifespan of men.

Followup on evolutionary psychology as ' just so stories'

A comment on my Sept. 28 post has passed on a number of excellent response to the book review I was noting in that post. I was remiss (lazy) in not taking to task one absurd contention of the reviewer, namely that "you don’t have to know about the evolution of an organ in order to understand it." (a third of my Biology of Mind Book argued the contrary.) After Jabr notes in his Scientific American comments several examples of how understanding the evolution of different brain areas has enhanced understanding and medical practice, he gives this nice analogy:

Studying the brain and mind in ignorance of its vast evolutionary tale does not make sense. It would be equivalent to an archaeologist discovering the remains of an enormous tapestry, slicing out a particular figure from the cloth and claiming that he could learn everything he needs to know by examining that figure in isolation. Even if the archaeologist described the figure in exquisite detail, taking it apart thread by thread and sewing it back together, he would remain willfully oblivious of the whole story. In the same way, disregarding the human brain’s history limits psychology and neuroscience to a paltry understanding of our brains and minds.

The comment also points to Kurzban and Gottschall as offering further commentary.

Also, let me note this comment on the Sept 28 post by Jim Birch:

I'm a little surprised by the animosity directed at evolutionary psychology. For me, it has provided revolutionary insights and understanding. In particular, the general notion that in biology, energy is not wasted, it is utilized adaptively. Under evolution, "adaptive" is not local in time and space but statistically selected over a period and range of the species' evolution.

This gives, or actually requires, a new way of interpreting any human behaviour: as statistically adaptive. And in doing so, it blasts away the incoherent mass of narrative explanations that have been conventionally applied. Our "craziest" tendencies like dying on Everest or blowing life savings on poker machines are no longer down to Freudian death wishes or moral failings (etc) but can be seen as adaptive behaviours operating badly, or even just out of context.

Of course, no one was around in the Pleistocene recording behaviours and survival rates so there's a need for speculation, modelling and indirect evidence. It is this that opens the field up to "just-so stories" charge. There is also the potential for use of selective evidence - to simplistically support preferred moral positions, eg, tooth-and-claw v. cooperative vision of "human nature". However, this is not a problem that is peculiar to evolutionary psychology, it's a perenial problem for science, especially new fields. No doubt the situation will improve as things develop and there's a lot of baby in the bathwater of evolutionary psychology.

Young children and adults: intrinsically motivated to see others helped

This interesting piece from Tomasello and collaborators:

Young children help other people, but it is not clear why. In the current study, we found that 2-year-old children’s sympathetic arousal, as measured by relative changes in pupil dilation, is similar when they themselves help a person and when they see that person being helped by a third party (and sympathetic arousal in both cases is different from that when the person is not being helped at all). These results demonstrate that the intrinsic motivation for young children’s helping behavior does not require that they perform the behavior themselves and thus “get credit” for it, but rather requires only that the other person be helped. Thus, from an early age, humans seem to have genuine concern for the welfare of others.

And, Rand et al. use economic games with adult subjects to demonstrate that cooperation is intuitive, because cooperative heuristics are developed in daily life where cooperation is typically advantageous. This data adds to Kahneman's recent summary of evidence that much of human decision-making is governed by fast and automatic intuitions, rather than by slow, effortful thinking (see Kahneman, D. Thinking, Fast and Slow, Allen Lane, 2011). The Rand et al. abstract

Cooperation is central to human social behaviour. However, choosing to cooperate requires individuals to incur a personal cost to benefit others. Here we explore the cognitive basis of cooperative decision-making in humans using a dual-process framework. We ask whether people are predisposed towards selfishness, behaving cooperatively only through active self-control; or whether they are intuitively cooperative, with reflection and prospective reasoning favouring ‘rational’ self-interest. To investigate this issue, we perform ten studies using economic games. We find that across a range of experimental designs, subjects who reach their decisions more quickly are more cooperative. Furthermore, forcing subjects to decide quickly increases contributions, whereas instructing them to reflect and forcing them to decide slowly decreases contributions. Finally, an induction that primes subjects to trust their intuitions increases contributions compared with an induction that promotes greater reflection. To explain these results, we propose that cooperation is intuitive because cooperative heuristics are developed in daily life where cooperation is typically advantageous. We then validate predictions generated by this proposed mechanism. Our results provide convergent evidence that intuition supports cooperation in social dilemmas, and that reflection can undermine these cooperative impulses.

MRI of reading Jane Austen

Another totally annoying example of science by press release sans any reference to an original research article offers a glimpse at what looks like fascinating work, showing brain correlates of a kind of deep attention going with reading literature that is very different from the kind of deep attention that is focused on mastering a particular task.

In an innovative interdisciplinary study, neurobiological experts, radiologists and humanities scholars are working together to explore the relationship between reading, attention and distraction – by reading Jane Austen. Surprising preliminary results reveal a dramatic and unexpected increase in blood flow to regions of the brain beyond those responsible for "executive function," areas which would normally be associated with paying close attention to a task, such as reading, said Natalie Phillips, the literary scholar leading the project. During a series of ongoing experiments, functional magnetic resonance images track blood flow in the brains of subjects as they read excerpts of a Jane Austen novel. Experiment participants are first asked to leisurely skim a passage as they might do in a bookstore, and then to read more closely, as they would while studying for an exam. Phillips said the global increase in blood flow during close reading suggests that "paying attention to literary texts requires the coordination of multiple complex cognitive functions." Blood flow also increased during pleasure reading, but in different areas of the brain. Phillips suggested that each style of reading may create distinct patterns in the brain that are "far more complex than just work and play."

A commentary by Alan Jacobs on this work makes a further point, that we might do well to exercise various parts of our minds just as we do well to exercise various parts of our bodies. Otherwise we could end up like Charles Darwin, who felt that over time he had lost certain mental functions:

My mind seems to have become a kind of machine for grinding general laws out of large collections of facts, but why this should have caused the atrophy of that part of the brain alone, on which the higher tastes depend, I cannot conceive. A man with a mind more highly organised or better constituted than mine, would not, I suppose, have thus suffered; and if I had to live my life again, I would have made a rule to read some poetry and listen to some music at least once every week; for perhaps the parts of my brain now atrophied would thus have been kept active through use. The loss of these tastes is a loss of happiness, and may possibly be injurious to the intellect, and more probably to the moral character, by enfeebling the emotional part of our nature.

Rethinking sleep - brief wakeful resting boosts new memories over the long term.

Two recent articles point out that the prevailing notion that an eight hour chunk of sleep is required for optimum health and function is a relatively recent invention that doesn't take into account the usefulness of many varieties of sleep. Randall notes historical and contemporary evidence that other patterns are useful, and here is an abstract from Dewar et al. on how wakeful rest enhances long term consolidation of new memories:

A brief wakeful rest after new verbal learning enhances memory for several minutes. In the research reported here, we explored the possibility of extending this rest-induced memory enhancement over much longer periods. Participants were presented with two stories; one story was followed by a 10-min period of wakeful resting, and the other was followed by a 10-min period during which participants played a spot-the-difference game. In Experiment 1, wakeful resting led to significant enhancement of memory after a 15- to 30-min period and also after 7 days. In Experiment 2, this striking enhancement of memory 7 days after learning was demonstrated even when no retrievals were imposed in the interim. The degree to which people can remember prose after 7 days is significantly affected by the cognitive activity that they engage in shortly after new learning takes place. We propose that wakeful resting after new learning allows new memory traces to be consolidated better and hence to be retained for much longer.

Regulators of prosocial and empathetic behavior.

Two pieces in the September issue of Psychological Science deal with empathetic or prosocial behavior. Grant and Dutton make observations showing that prosocial behavior is boosted more by reflecting on giving than on receiving; and Lewis et al.'s experiments give a example of how stereotypes enhance empathetic accuracy.

Grant and Dutton:

Research shows that reflecting on benefits received can make people happier, but it is unclear whether or not such reflection makes them more helpful. Receiving benefits can promote prosocial behavior through reciprocity and positive affect, but these effects are often relationship-specific, short-lived, and complicated by ambivalent reactions. We propose that prosocial behavior is more likely when people reflect on being a benefactor to others, rather than a beneficiary. The experience of giving benefits may encourage prosocial behavior by increasing the salience and strength of one’s identity as a capable, caring contributor. In field and laboratory experiments, we found that participants who reflected about giving benefits voluntarily contributed more time to their university, and were more likely to donate money to natural-disaster victims, than were participants who reflected about receiving benefits. When it comes to reflection, giving may be more powerful than receiving as a driver of prosocial behavior.

Lewis et al.:

An ideal empathizer may attend to another person’s behavior in order to understand that person, but it is also possible that accurately understanding other people involves top-down strategies. We hypothesized that perceivers draw on stereotypes to infer other people’s thoughts and that stereotype use increases perceivers’ accuracy. In this study, perceivers (N = 161) inferred the thoughts of multiple targets. Inferences consistent with stereotypes for the targets’ group (new mothers) more accurately captured targets’ thoughts, particularly when actual thought content was also stereotypic. We also decomposed variance in empathic accuracy into thought, target, and perceiver variance. Although past research has frequently focused on variance between perceivers or targets (which assumes individual differences in the ability to understand other people or be understood, respectively), the current study showed that the most substantial variance was found within targets because of differences among thoughts.

Idle Minds - why are our brains so active when doing ‘nothing’?

Kerri Smith does a review on the resting or default activity of our brains, what is happening when we are not focused on anything in particular, but letting our minds just rest or wander at random: After initial observations in the mid-1990s showed that the brain never really takes a break,

...studies of the resting state in its own right began to emerge. A team led by Marcus Raichle characterized activity in one such network as the brain's default mode — what they considered its baseline setting. During tasks, default-mode activity actually dropped, coming back online when the brain was no longer focusing so intensely.

The default-mode network has been joined by dozens of other flavors of resting-state network — some of which resemble the circuitry that contributes to attention, vision, hearing or movement. They seem very similar across study participants but are also dynamic, changing over time.

One idea is that the brain is running several models of the world in the background, ready for one of them to turn into reality.

Raichle favors the idea that activity in the resting state helps the brain to stay organized. The connections between neurons are continually shifting as people age and learn, but humans maintain a sense of self throughout the upheaval. Spontaneous activity might play a part in maintaining that continuity. “Connections between neurons turn over in minutes, hours, days and weeks,...The structure of the brain will be different tomorrow but we will still remember who we are.” …the brain replays and consolidates new memories at any chance it gets — even when awake.

…perhaps the activity is part of the reshaping process, tweaking connections while we idle. Several teams have reported changes in resting connectivity after language and memory tasks and motor learning… suggesting that the brain is not only thinking about supper coming up, but it's also processing the recent past and converting some of that into long-term memories. The network changes are specific to the tasks performed.

Interpersonal closeness and brain social reward processing

I'm passing on a graphic from Vrticka's comments on recent work by Farei et al., who have observed brain activation patterns associated with sharing positive outcomes with a friends, that are also mirrored in high subjective ratings of excitement and high skin conductance responses during the same condition, reflecting increased biological arousal.

Illustration of the dynamic “push–pull” between social approach and aversion in the affective processing module of human social interaction. According to the phylogenetic perspective of social engagement and attachment proposed by Porges, human social functioning is determined by two opposite emotional brain systems representing positive (social approach; purple) versus negative (social aversion; blue) information. Whereas the social approach module mainly includes dopaminergic pathways (ventral tegmental area, striatum, ventral medial orbitofrontal cortex), as well as the pituitary/hypothalamus as the main site of oxytocin synthesis, the social aversion module operates through brain areas involved in fear/threat (amygdala), stress (hippocampus), disgust/empathy for pain/social rejection (insula and anterior cingulate cortex), and sadness (anterior temporal pole).

Here is the Farei et al. abstract:

Everyday goals and experiences are often shared with others who may hold different places within our social networks. We investigated whether the experience of sharing a reward differs with respect to social network. Twenty human participants played a card guessing game for shared monetary outcomes with three partners: a computer, a confederate (out of network), and a friend (in network). Participants subjectively rated the experience of sharing a reward more positively with their friends than the other partners. Neuroimaging results support participants' subjective reports, as ventral striatal BOLD responses were more robust when sharing monetary gains with a friend as compared to the confederate or computer, suggesting a higher value for sharing with an in-network partner. Interestingly, ratings of social closeness covaried with this activity, resulting in a significant partner × closeness interaction; exploratory analysis showed that only participants reporting higher levels of closeness demonstrated partner-related differences in striatal BOLD response. These results suggest that reward valuation in social contexts is sensitive to distinctions of social network, such that sharing positive experiences with in-network others may carry higher value.

Want to be unhappy? Trying to be happy will do it!

I'm finding the "Anxiety" topic in the Opinionator series at the NYTimes to be a real treat. This entry by British expatriate Ruth Whippman brings back memories of a my signing on several years ago to be a talking head neuroscience expert on the  California "Make Me Happy!" Radio Show (I don't think they were all that pleased with their dyspeptic guest!). Whippman notes the American obsession with, and anxiety over, being "happy", and contrasts this with the attitudes of more stoic Britishers:

Happiness in America has become the overachiever's ultimate trophy. A vicious trump card, it outranks professional achievement and social success, family, friendship and even love…this elusive MacGuffin is creating a nation of nervous wrecks. Despite being the richest nation on earth, the United States is, according to the World Health Organization, by a wide margin, also the most anxious, with nearly a third of Americans likely to suffer from an anxiety problem in their lifetime. America's precocious levels of anxiety are not just happening in spite of the great national happiness rat race, but also perhaps, because of it.

The British are generally uncomfortable around the subject, and as a rule, don't subscribe to the happy-ever-after. It's not that we don't want to be happy, it just seems somehow embarrassing to discuss it, and demeaning to chase it, like calling someone moments after a first date to ask them if they like you….Even the recent grand spectacle of the London 2012 Olympic Games told this tale. The opening ceremony, traditionally a sparklefest of perkiness, was, with its suffragist and trade unionists, mainly a celebration of dissent, or put less grandly, complaint…Our queen, despite the repeated presence of a stadium full of her subjects urging in song that she be both happy and glorious, could barely muster a smile, staring grimly through her eyeglasses and clutching her purse on her lap as if she might be mugged.

Cynicism is the British shtick. When happiness does come our way, it is entirely without effort, as unmeritocratic as a hereditary peerage. By contrast, in America, happiness is work. Intense, nail-biting work, slogged out in motivational seminars and therapy sessions, meditation retreats and airport bookstores. For the left there's yoga, for the right, there's Jesus. For no one is there respite…The people taking part in "happiness pursuits," as a rule, don't seem very happy…The happy person would be more likely to be off doing something fun, like sitting in the park drinking.

Happiness should be serendipitous, a by-product of a life well lived, and pursuing it in a vacuum doesn't really work. This is borne out by a series of slightly depressing statistics. The most likely customer of a self-help book is a person who has bought another self-help book in the last 18 months. The General Social Survey, a prominent data-based barometer of American society, shows little change in happiness levels since 1972, when such records began. Every year, with remarkable consistency, around 33 percent of Americans report that they are "very happy." It's a fair chunk, but a figure that remains surprisingly constant, untouched by the uptick in Eastern meditation or evangelical Christianity, by Tony Robbins or Gretchen Rubin or attachment parenting. For all the effort Americans are putting into happiness, they are not getting any happier. It is not surprising, then, that the search itself has become a source of anxiety.

So here's a bumper sticker: despite the glorious weather and spectacular landscape, the people of California are probably less happy and more anxious than the people of Grimsby. So they may as well stop trying so hard.

Just so stories about the evolution of our minds.

I want to point to a very nicely done review in The New Yorker by Anthony Gottlieb, who notes a number of recent books dealing with evolutionary psychology, but mainly comments on “Homo Mysterious: Evolutionary Puzzles of Human Nature” (Oxford), a new book by David Barash, a professor of psychology and biology at the University of Washington, Seattle. The main point of critics is that most evolutionary theories purporting to explain our sexual or other behaviors as evolved adaptations to conditions faced by our paleolithic ancestors have no more validity than Rudyard Kipling's "just so" stories about how the camel got his hump or the rhinoceros his wrinkly folds of skin. One clip from the review:

A review of the methods of evolutionary psychology, published last summer in a biology journal, underlined a point so simple that its implications are easily missed. To confirm any story about how the mind has been shaped, you need (among other things) to determine how people today actually think and behave, and to test rival accounts of how these traits function. Once you have done that, you will, in effect, have finished the job of explaining how the mind works. What life was really like in the Stone Age no longer matters. It doesn’t make any practical difference exactly how our traits became established. All that matters is that they are there.

Voting patterns: “I” value competence but “we” value social competence

(Chen et al. ask whether judgments of candidates' social competence—defined as the capacity for effective functioning in social interactions—are related to outcomes in an individualistic society (the United States) and a collectivist society (Taiwan). They replicate the earlier result that a judgment of competence does predict winners in the United States, as it does in Taiwan, and they find that judgments of social competence are also predictive, though only for elections in Taiwan. Their abstract:

This investigation distinguishes interpersonally oriented social competence from intrapersonally oriented competence. It examines the influence of voters' individualism and collectivism orientation in affecting the roles of these two dimensions in predicting electoral outcomes. Participants made judgments of personality traits based on inferences from faces of political candidates in the U.S. and Taiwan. Two social outcomes were examined: actual election results and voting support of the participants. With respect to actual electoral success, perceived competence is more important for the candidates in the U.S. than for those in Taiwan, whereas perceived social competence is more important for the candidates in Taiwan than for those in the U.S. With respect to subjective voting support, within cultural findings mirror those found cross-culturally. Competence is valued more among voters who are more individualistic, and social competence is valued more among voters who are more collectivistic. These results highlight important omissions in the social perception/judgment literature.

(excuse a techie note irrelevant to this post: I confirm the subscription of this blog to the Paperblog service under the username mdbownds)

Combat stress causes long term changes in brain connectivity.

Sobering results from Wingen et al.:

Prolonged stress can have long-lasting effects on cognition. Animal models suggest that deficits in executive functioning could result from alterations within the mesofrontal circuit. We investigated this hypothesis in soldiers before and after deployment to Afghanistan and a control group using functional and diffusion tensor imaging. Combat stress reduced midbrain activity and integrity, which was associated to compromised sustained attention. Long-term follow-up showed that the functional and structural changes had normalized within 1.5 y. In contrast, combat stress induced a persistent reduction in functional connectivity between the midbrain and prefrontal cortex. These results demonstrate that combat stress has adverse effects on the human mesofrontal circuit and suggests that these alterations are partially reversible.

Legend (click figure to enlarge) - Combat stress reduces functional connectivity of the midbrain with the lateral prefrontal cortex. The reduction from baseline to short-term follow-up is presented in blue. The persistent reduction from baseline to long-term follow-up at 1.5 y after military deployment is presented in green. The overlap between the short-term and long-term effects is presented in cyan.

A bit more expanded summary in their discussion:

These results show that the adverse effects of combat stress on sustained attention are related to functional and structural changes in the midbrain. These alterations normalize within 1.5 y in soldiers without psychiatric complaints, which may explain why long-term cognitive deficits following combat are mainly observed in soldiers with posttraumatic stress symptoms. In contrast to the reversible effects on the midbrain itself, its reduced interaction with the prefrontal cortex persists for at least 1.5 y. Taken together, these results suggest that the human brain can largely recover from the adverse effects of stress, supporting the view that neural plasticity in response to prolonged stress is adaptive. However, the results also reveal long-term changes within the mesofrontal network that may increase the vulnerability to subsequent stressors and lead to long-lasting cognitive deficits.

Male sex hormones alter the brain after exercise.

Numerous experiments have shown that exercise enhances our ability to remember and think, and causes formation of new nerve cells. A collaboration that includes McEwen's Laboratory of Neuroendocrinology at Rockefeller now shows (in rats) that brain (not gonadal) production of the testosterone derivative dihydroxtestosterone (DHT) is required for this effect. The amount of exercise required is quite mild (McEwen: "the equivalent of jogging at a pace at which someone could speak (or squeak) to a companion."). In castrated rats blocking the action of testosterone levels that have been enhanced by exercise (by blocking testosterone receptors in the brain) also blocks the formation of new nerve cells. The chemical details are given by their abstract:

Mild exercise activates hippocampal neurons through the glutamatergic pathway and also promotes adult hippocampal neurogenesis (AHN). We hypothesized that such exercise could enhance local androgen synthesis and cause AHN because hippocampal steroid synthesis is facilitated by activated neurons via N-methyl-D-aspartate receptors. Here we addressed this question using a mild-intense treadmill running model that has been shown to be a potent AHN stimulator. A mass-spectrometric analysis demonstrated that hippocampal dihydrotestosterone increased significantly, whereas testosterone levels did not increase significantly after 2 wk of treadmill running in both orchidectomized (ORX) and sham castrated (Sham) male rats. Furthermore, analysis of mRNA expression for the two isoforms of 5α-reductases (srd5a1, srd5a2) and for androgen receptor (AR) revealed that both increased in the hippocampus after exercise, even in ORX rats. All rats were injected twice with 5′-bromo-2′deoxyuridine (50 mg/kg body weight, i.p.) on the day before training. Mild exercise significantly increased AHN in both ORX and Sham rats. Moreover, the increase of doublecortin or 5′-bromo-2′deoxyuridine/NeuN-positive cells in ORX rats was blocked by s.c. flutamide, an AR antagonist. It was also found that application of an estrogen receptor antagonist, tamoxifen, did not suppress exercise-induced AHN. These results support the hypothesis that, in male animals, mild exercise enhances hippocampal synthesis of dihydrotestosterone and increases AHN via androgenenic mediation.

In commenting on this work in the NYTimes, Gretchen Reynolds raises an interesting question for women:

But while those findings may be salutary for men who are active and fit, or planning to become so, they seem potentially troubling for those of us without testes. If DHT is necessary for neurogenesis after exercise and women produce far less of it than men, do women gain less brain benefit from exercise than men?

On being nothing...

The "Opinionater" feature of the New York Times has "Anxiety" as one of its topics inviting online essays. I wanted to pass on a piece submitted by Brian Jay Stanley that notes how at every stage of our lives we desire to be noticed and affirmed by others, and in the absence of notice can easily become anxious, feeling insignificant and insubstantial. His last two paragraphs are a treat:

Society is adroit at disillusioning newcomers, and many self-assured children grow up to be bitter adults. But bitterness, instead of a form of disillusionment, is really the refusal to give up your childhood illusions of importance. Ignored instead of welcomed by the world, you fault the world as blind and evil in order not to fault yourself as naïve. Bitterness is a child’s coddling narcissism within the context of an adult’s harsh life. Instead, I know that the world only tramples me as a street crowd does an earthworm — not out of malice or stupidity, but because no one sees it. Thus my pain is not to feel wrongly slighted, but to feel rightly slighted.

There must be a Copernican revolution of the self. Instead of pointlessly cursing the sun to go around me, my chance of contentment is learning to orbit, being the world’s audience instead of demanding the world be mine. If the world is a stage, then everyone’s an extra, acting minor roles in simultaneous scenes in which no one has the lead. With so much happening, society is poorly made to satisfy pride, but well made to satisfy interest, if we will only let go of our vanity and join the swirl of activity.

Signing beforehand increases honesty.

Here is a fascinating simple study by Shu et al. Simply signing a statement of honesty at the top rather the bottom of a form makes you more honest. They outline the problem:

The annual tax gap between actual and claimed taxes due in the United States amounts to roughly $345 billion. The Internal Revenue Service estimates more than half this amount is due to individuals misrepresenting their income and deductions (1). Insurance is another domain burdened by the staggering cost of individual dishonesty; the Coalition Against Insurance Fraud estimated that the overall magnitude of insurance fraud in the United States totaled $80 billion in 2006 (2). The problem with curbing dishonesty in behaviors such as filing tax returns, submitting insurance claims, claiming business expenses or reporting billable hours is that they primarily rely on self-monitoring in lieu of external policing.

Here is their abstract:

Many written forms required by businesses and governments rely on honest reporting. Proof of honest intent is typically provided through signature at the end of, e.g., tax returns or insurance policy forms. Still, people sometimes cheat to advance their financial self-interests—at great costs to society. We test an easy-to-implement method to discourage dishonesty: signing at the beginning rather than at the end of a self-report, thereby reversing the order of the current practice. Using laboratory and field experiments, we find that signing before, rather than after, the opportunity to cheat makes ethics salient when they are needed most and significantly reduces dishonesty.

The experimental design used several different measures of cheating: self-reported earnings (income) on a math puzzles task wherein university participants could cheat for financial gain, self reported travel expenses to the laboratory (deductions) claimed on a tax return form on research earnings. Another experiment was done in the field with an insurance company in the southeastern United States asking some of their existing customers to report their odometer reading. They examined the effect of requiring the signature at the top of the form, the bottom, or the control of requiring no signature.

A personal history.

I thought I would mention that in response to several requests from friends and family I have now posted a personal history on my dericbownds.net website at http://www.dericbownds.net/DericHistory.html.

Distinct prefrontal areas regulating cognitive control and value decisions.

A massive study involving workers at five different universities has utilized a dataset on brain lesions accumulated over many decades to reveal two distinct functional-anatomical networks within the prefrontal cortex (PFC), one associated with cognitive control and the other associated with value-based decision-making. They used lesion-symptom mapping in 344 participants who were assessed by using a large battery of standardized neuropsychological tasks. Of these participants, 165 had damage in the frontal lobes that included sectors of the PFC, supplementary motor area (SMA), or premotor cortex (PM). Here is their abstract, followed by some details:

A considerable body of previous research on the prefrontal cortex (PFC) has helped characterize the regional specificity of various cognitive functions, such as cognitive control and decision making. Here we provide definitive findings on this topic, using a neuropsychological approach that takes advantage of a unique dataset accrued over several decades. We applied voxel-based lesion-symptom mapping in 344 individuals with focal lesions (165 involving the PFC) who had been tested on a comprehensive battery of neuropsychological tasks. Two distinct functional-anatomical networks were revealed within the PFC: one associated with cognitive control (response inhibition, conflict monitoring, and switching), which included the dorsolateral prefrontal cortex and anterior cingulate cortex and a second associated with value-based decision-making, which included the orbitofrontal, ventromedial, and frontopolar cortex. Furthermore, cognitive control tasks shared a common performance factor related to set shifting that was linked to the rostral anterior cingulate cortex. By contrast, regions in the ventral PFC were required for decision-making. These findings provide detailed causal evidence for a remarkable functional-anatomical specificity in the human PFC.

Here is a description of the array of tests used (edited to simplify):

The four cognitive control tasks were as follows: the Trail-Making Test (TMT), a measure of executive response switching; the Perseverative Errors score from the Wisconsin Card Sorting Test (WCST), which measures impairments in set switching; the Color-Word Interference score from the Stroop Test (STROOP), a measure of response inhibition; and the Number of Words score from the Controlled Oral Word Association Test (COWA), which measures verbal fluency, divergent thinking, and response creativity. As an index of value-based decision-making and reward learning, we used the Net Score (advantageous minus disadvantageous choices) from the Iowa Gambling Task (IGT). All these tasks have been extensively used and well standardized, and they have been shown to detect impairments reliably in clinical populations such as ours. As expected, the cognitive control-related tasks were all weakly, but positively intercorrelated, whereas their correlation with the IGT was generally lower, a pattern that remained even after the covariates were statistically removed from the data.

And here is a summary graphic:

Results from the lesion overlap analysis of different tests of cognitive control and value-based decision making.

Motivation influences how time flies when you’re having fun.

Numerous studies have shown that a positive state, relative to a negative state, makes time appear to pass more quickly and causes assessments of elapsed time to be shorter. Gable and Pool examine how the degree of motivation - as distinguished from positive or negative valence (as in approach versus withdrawal) - influences subjective time:

Time flies when you’re having fun, but what is it about pleasant experiences that makes time seem to go by faster? In the experiments reported here, we tested the proposal that approach motivation causes perceptual shortening of time during pleasant experiences. A first experiment showed that, relative to a neutral state or a positive state with low approach motivation, a positive state with high approach motivation shortened perceptions of time. Also, individual differences in approach motivation predicted shorter perceptions of time. In a second experiment we manipulated approach motivation independently of the affective state and showed that increasing approach motivation caused time to be perceived as passing more quickly. Finally we showed that positive approach motivation, as opposed to arousal, shortens perception of time by comparing a highly arousing positive state with a highly arousing negative state. Shortening of time perception in appetitive states may prolong approach-motivated behavior and increase the likelihood of acquiring appetitive objects or goals.

Neural signature of affiliative emotions.

Moll et al. do an interesting study to experimentally disentangle affiliative experience from general emotional valence, by demonstrating that brain areas distinctive to expression of affiliative (bonding) emotions engage an ensemble of basal forebrain structures that is conserved in mammals, and can be distinguished from areas reflecting the positive or negative emotional valence that accompanies the subjective affiliative experience. Here is their abstract, following by one of the illustrations from the paper:

Comparative studies have established that a number of structures within the rostromedial basal forebrain are critical for affiliative behaviors and social attachment. Lesion and neuroimaging studies concur with the importance of these regions for attachment and the experience of affiliation in humans as well. Yet it remains obscure whether the neural bases of affiliative experiences can be differentiated from the emotional valence with which they are inextricably associated at the experiential level. Here we show, using functional MRI, that kinship-related social scenarios evocative of affiliative emotion induce septal–preoptic–anterior hypothalamic activity that cannot be explained by positive or negative emotional valence alone. Our findings suggest that a phylogenetically conserved ensemble of basal forebrain structures, especially the septohypothalamic area, may play a key role in enabling human affiliative emotion. Our finding of a neural signature of human affiliative experience bears direct implications for the neurobiological mechanisms underpinning impaired affiliative experiences and behaviors in neuropsychiatric conditions.

Figure Legend - Activation of the septal/preoptic-anterior hypothalamic and medial FPC, predicted a priori, as well as in the left posterior superior temporal sulcus region (data not shown) and precuneus (Prec), observed in the affiliative versus nonaffiliative contrast.

Figure Legend - Brain regions associated with positive versus negative conditions (red-yellow) and negative versus positive contrasts (blue-green). Activation of the ventral striatum (VStr) and medial orbitofrontal cortex (medOFC; BA11/32) was observed in the positive versus negative contrast. For the negative versus positive contrast, activation of dorsomedial prefrontal cortex (dmPFC; BA 8/9) and lateral frontal cortex, including the lateral orbitofrontal cortex and inferior frontal gyrus (latFC), as well as the adjoining anterior insula (antIns) was observed (BA 45/47/48).

Do implicit attitudes predict actual voting behavior?

How can psychologists and pollsters predict the voting behavior of undecided voters? Is there is any hope for us Obama supporters who worry about the effectiveness of the clever framing of the conservative marketing aimed at undecided voters that pushes emotional buttons with complete disregard for rationality or facts? Friese et al. show that explicit attitudes predict voting behavior better than implicit attitudes for both decided and undecided voters, while implicit attitudes predict voting behavior better for decided than undecided voters. While this is not to say that explicit attitudes can't also be based on irrationality, it does argue against the power of implicit attitudes of which the voter is unaware. Here is their abstract:

The prediction of voting behavior of undecided voters poses a challenge to psychologists and pollsters. Recently, researchers argued that implicit attitudes would predict voting behavior particularly for undecided voters whereas explicit attitudes would predict voting behavior particularly for decided voters. We tested this assumption in two studies in two countries with distinct political systems in the context of real political elections. Results revealed that (a) explicit attitudes predicted voting behavior better than implicit attitudes for both decided and undecided voters, and (b) implicit attitudes predicted voting behavior better for decided than undecided voters. We propose that greater elaboration of attitudes produces stronger convergence between implicit and explicit attitudes resulting in better predictive validity of both, and less incremental validity of implicit over explicit attitudes for the prediction of voting behavior. However, greater incremental predictive validity of implicit over explicit attitudes may be associated with less elaboration.

Psychological distance enhances conformity to group norms.

In yet another of one of those studies that give what would appear to be a generally applicable result, but is based on experiments carried out on two rather selective population represented by undergraduate psychology students at a U.S. college (UC-Davis, and NYU), Ledgerwood and Callahan demonstrate that psychological distance can enhance conformity to group norms, contra the usual association of the distanced or abstracted thinker (think Spock or Obama) with reasoned opinions that resist group pressure.

In the first study noted in their abstract below. they manipulated the temporal distance of a policy by varying whether it would be implemented in the near or distant future. They then provided participants with information about the majority opinion before asking them to report their own attitudes toward the policy. (The study's 67 participants (72% female) completed a study described as an online student opinion survey. All participants read an article excerpt (ostensibly from an online campus newsletter), which stated that the Davis City Council was considering whether to approve a proposal that would require all bicycles - the primary mode of student transportation in Davis - to use rear bicycle lights for nighttime travel.) Participants tended to conform to group opinion when the policy would be implemented in the relatively distant future, expressing more favorable attitudes when the group favored the policy than when the group opposed it.

The second study, a bit more complicated, asked students who had been primed in a diversionary task that required thinking in either concrete or abstract terms, to vote on a previously defined affirmation action issue. They did this by privately placing a number of 'yes' or 'no' tokens proportional to how strongly they felt in boxes that already contained tokens placed by the group of previous voters (actually the experimenters). Participants conformed to the group norm after they had been led to think abstractly, voting more strongly in favor of affirmative action when the group seemed to support it rather than oppose it.

Here is the abstract:

Intuition suggests that a distanced or abstract thinker should be immune to social influence, and on its surface, the current literature could seem to support this view. The present research builds on recent theorizing to suggest a different possibility. Drawing on the notion that psychological distance regulates the extent to which evaluations incorporate context-specific or context-independent information, we suggest that psychological distance should actually increase susceptibility to sources of social influence that tend to be consistently encountered across contexts, such as group norms. Consistent with this hypothesis, two studies showed that psychological distance and abstraction increased conformity to group opinion and that this effect persisted in a novel voting-booth paradigm in which participants believed their voting behavior was both anonymous and consequential. We discuss implications of these findings for understanding the social side of abstraction as well as the conditions under which different types of social influence are likely to be most influential.

Zero effect of caloric restriction on lifespan

I would be very surprised if there were any blog readers who are unaware of this material, released two weeks ago with saturation coverage by the popular press, but because human aging has been a continuous topic in this blog I thought I should pass on reference to the results of an exhaustive study by Mattison et al. that has failed to confirm an effect of dietary caloric restriction on longevity in rhesus monkeys, even though some beneficial health effects are noted. This takes the edge off my motivation to do occasional fits of dieting with the assurance that this might influence how long this 70-year old body continues to hang around.

Calorie restriction (CR), a reduction of 10–40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7–14 years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.

Cognitive load disrupts implicit theory of mind processing.

I'm passing this on because I was totally unaware of the implicit theory of mind (TOM) system that is explained in these clips from the article by Schneider et al.. They test whether this implicit TOM system is independent of domain-general, capacity-limited, cognitive resources (e.g., working memory.) First the abstract:

Eye movements in Sally-Anne false-belief tasks appear to reflect the ability to implicitly monitor the mental states of other individuals (theory of mind, or ToM). It has recently been proposed that an early-developing, efficient, and automatically operating ToM system subserves this ability. Surprisingly absent from the literature, however, is an empirical test of the influence of domain-general executive processing resources on this implicit ToM system. In the study reported here, a dual-task method was employed to investigate the impact of executive load on eye movements in an implicit Sally-Anne false-belief task. Under no-load conditions, adult participants displayed eye movement behavior consistent with implicit belief processing, whereas evidence for belief processing was absent for participants under cognitive load. These findings indicate that the cognitive system responsible for implicitly tracking beliefs draws at least minimally on executive processing resources. Thus, even the most low-level processing of beliefs appears to reflect a capacity-limited operation.

And here, slightly edited, is some essential background material from their introduction:

A key paradigm for assessing ToM abilities is the Sally-Anne false-belief task: In still images, movies, or “live” performance (with puppets, actors, or both), “Sally” sees an object (e.g., a ball) being placed in a container. Sally then leaves the room. Next, “Anne” hides the object in a different container. When Sally returns to the room, participants are required to identify the location where they think Sally will first look for the object. To succeed at the task, participants must select (e.g., point to) the location that is consistent with Sally’s belief, as opposed to the actual, known location of the object.

Passing this explicit Sally-Anne task is thought to reflect a developmental milestone, which is typically achieved by the age of 4 years. Such findings suggest that children understand other people’s beliefs by this age. However, recent research using a variety of implicit ToM tasks suggests that children as young as 7 months may be able to register other individuals’ beliefs. For example, monitoring of eye movement behavior in free-viewing false-belief scenarios has demonstrated that 2-year-olds preferentially look toward the location at which the actor believes the ball to be.

Do humans fail to understand other individuals’ internal mental states until the age of 4, or is this fundamental ability already present during the 1st year of life? To accommodate these seemingly incongruent findings, Apperly and Butterfill proposed that throughout the life span, ToM is subserved by two distinct systems. According to this framework, an earlier-developing system, which operates implicitly and is independent of the development of language and executive function (e.g., working memory), is responsible for efficient monitoring of belief-like states. A later-developing system, which is dependent on domain-general cognitive functions (e.g., executive function), allows conscious (explicit) ToM inferences. Evidence supporting this framework includes a dissociation found in adults with Asperger’s syndrome, who can pass explicit false-belief tasks but do not display eye movement patterns consistent with implicit ToM in a Sally-Anne free-viewing paradigm.

Why the sex gap in affective disorders?

Here is an abstract from Hu et al., which I pass on to you even though it is rather technical, that shows that an increase in negative affective behavior in stressed female versus male mice that correlates with a decrease (vs increase in males) in their hippocampal NO (nitric oxide) levels. If the hippocampal NO levels are equalized in male and females, their affective behaviors become similar.

Mechanisms underlying the female preponderance in affective disorders are poorly understood. Here we show that hippocampal nitric oxide (NO) plays a role in the sex difference of depression-like behaviors in rodents. Female mice had substantially lower NO production in the hippocampus and were significantly more likely to display negative affective behaviors than their male littermates. Eliminating the difference in the basal hippocampal NO level between male and female mice mended the sex gap of affective behaviors. Estradiol exerted a positive control on hippocampal NO production via estrogen receptor-β–mediated neuronal NO synthase expression. Thus, low estrogen in the female hippocampus accounts for lower local NO than in the male hippocampus. Although estrogen has important significance in modulating affective behaviors, it is not estrogen but NO in the hippocampus that mediates the sex difference of affective behaviors directly, because hippocampal NO was necessary for the behavioral effects of estradiol, and NO was an independent factor in modulating behaviors. Stress promoted hippocampal NO production in males because of glucocorticoid release, thus leading to local NO excess. In contrast, stress suppressed NO production in females because of decreased estrogen, thereby resulting in hippocampal NO shortage. Whereas activating cAMP response element binding protein (CREB) rescued the depression-like effects of the intrahippocampal NO donor diethylenetriamine/nitric oxide adduct (DETA/NONOate), inactivating CREB abolished the antidepressant-like effects of the intrahippocampal NO donor DETA/NONOate. Our findings suggest a molecular mechanism underlying the sex difference of affective behaviors.

Investing in Karma - When Wanting Promotes Helping

An interesting piece from Converse et al. provides reliable evidence that people do good deeds when they want something beyond their control. This suggests that they act in accord with a karmic tenet rooted in immanent justice (but doesn't necessarily imply pervasive explicit belief in karma.) Here is the abstract slightly edited:

People often face outcomes of important events that are beyond their personal control, such as when they wait for an acceptance letter, job offer, or medical test results. We suggest that when wanting and uncertainty are high and personal control is lacking, people may be more likely to help others, as if they can encourage fate’s favor by doing good deeds proactively. Four experiments support this karmic-investment hypothesis. The first two experiments show that when people want an outcome over which they have little control, their donations of time and money increase, but their participation in other rewarding activities does not. A third experiment shows that, in addition, at a job fair, job seekers who feel the process is outside (vs. within) their control make more generous pledges to charities. A final experiment shows that karmic investments increase optimism about a desired outcome. We conclude by discussing the role of personal control and magical beliefs in this phenomenon.

Some clips from their discussion:

Past research has found that people automatically anticipate negative outcomes following behaviors that tempt fate, and that people associate positive outcomes with virtuous behaviors. Thus, people may develop a basic good-behavior—good-outcome association, such that hoping for good outcomes activates the cognitive script to do good deeds...whether based on explicit or implicit belief, some version of a karmic belief system must be at least momentarily activated when people face important, uncontrollable outcomes...our findings fit with the notion that people turn to external sources of control, such as gods and governments, when internal control is lacking, and may even turn to apparently magical systems when necessary...rather than increasing selfishness, wanting can increase helping...people may not only pursue reciprocal exchanges interpersonally, but may also attempt to bargain with the universe.

Alcohol and group formation.

Sayette et al. do what looks like a thorough piece of work, but I also have a "Duh...tell us something else we didn't already know" kind of reaction. This is why evidence of human grape fermentation is found very early in the archeological record, and probably extends beyond it.

We integrated research on emotion and on small groups to address a fundamental and enduring question facing alcohol researchers: What are the specific mechanisms that underlie the reinforcing effects of drinking? In one of the largest alcohol-administration studies yet conducted, we employed a novel group-formation paradigm to evaluate the socioemotional effects of alcohol. Seven hundred twenty social drinkers (360 male, 360 female) were assembled into groups of 3 unacquainted persons each and given a moderate dose of an alcoholic, placebo, or control beverage, which they consumed over 36 min. These groups’ social interactions were video recorded, and the duration and sequence of interaction partners’ facial and speech behaviors were systematically coded (e.g., using the Facial Action Coding System). Alcohol consumption enhanced individual- and group-level behaviors associated with positive affect, reduced individual-level behaviors associated with negative affect, and elevated self-reported bonding. Our results indicate that alcohol facilitates bonding during group formation. Assessing nonverbal responses in social contexts offers new directions for evaluating the effects of alcohol.

Where thinking about thinking happens in the brain.

We evaluate and alter the cognitive functions we perform, as when we revise or edit our writing or speaking. This monitoring and controlling is usually referred to as metacognition. Middlebrooks and Sommer have recently done an elegant study of metacognition in Macaque monkeys, using a simple betting paradigm:

Humans are metacognitive: they monitor and control their cognition. Our hypothesis was that neuronal correlates of metacognition reside in the same brain areas responsible for cognition, including frontal cortex. Recent work demonstrated that nonhuman primates are capable of metacognition, so we recorded from single neurons in the frontal eye field, dorsolateral prefrontal cortex, and supplementary eye field of monkeys (Macaca mulatta) that performed a metacognitive visual-oculomotor task. The animals made a decision and reported it with a saccade, but received no immediate reward or feedback. Instead, they had to monitor their decision and bet whether it was correct. Activity was correlated with decisions and bets in all three brain areas, but putative metacognitive activity that linked decisions to appropriate bets occurred exclusively in the SEF. Our results offer a survey of neuronal correlates of metacognition and implicate the SEF in linking cognitive functions over short periods of time.

Highlight points:

-Monkeys made decisions and wagered on their performance in a metacognitive task

-Single neurons were recorded in three frontal cortical region

-Only supplementary eye field (SEF) neuronal activity correlated with metacognition

-The SEF metacognitive signal provided a temporal “bridge” between decision and bet

The unimaginable complexity of our evolved human systems.

In the face of all the current hubris about redesigning and engineering humans using modern genetic and biochemical tools, trying to reverse engineer brain systems that were never engineered in the first place, Randolph Nesse offers a very therapeutic essay. Here is a slightly edited version:

The products of natural selection are … not merely complicated in the way that machines are complicated, they are organically complex in ways that are fundamentally different from any product of design. This makes them difficult for human minds to fully describe or comprehend. So, we use that grand human gambit for understanding, a metaphor, in this case, the body as machine…it easy to portray the systems that mediate cell division, immune responses, glucose regulation, and all the rest, using boxes for the parts, and arrows to indicate causes what. Such diagrams summarize important information in ways we can grasp. .. But, they fundamentally misrepresent the nature of organic complexity.

Thinking about the body as a machine was a grand advance in the 16th century, when it offered an alternative to vitalism and vague notions of the life force. Now it is outmoded. It distorts our view of biological systems by fostering thinking about them as simpler and more sensibly "designed" than they are. Experts know better. They recognize that the mechanisms that regulate blood clotting are represented only crudely by the neat diagrams medical students memorize; most molecules in the clotting system interact with many others. Experts on the amygdala know that it does not have one or two functions, it has many, and they are mediated by scores of pathways to other brain loci. Serotonin exists not mainly to regulate mood and anxiety, it is essential to vascular tone, intestinal motility, and bone deposition. Leptin is not mainly a fat hormone, it has many functions, serving different ones at different time, even in the same cell. The reality of organic systems is vastly untidy. If only their parts were all distinct, with specific functions for each! Alas, they are not like machines. Our human minds have as little intuitive feeling for organic complexity as they do for quantum physics.

Recent progress in genetics confronts the problem. Naming genes according to postulated functions is as natural as defining chairs and boats by their functions. If each gene were a box on a blueprint labeled with its specific function, biology would be so much more tractable! However, it is increasingly clear that most traits are influenced by many genes, and most genes influence many traits. For instance, about 80% of the variation in human height is accounted for by genetic variation. It would seem straightforward to find the responsible genes. But looking for them has revealed that the 180 loci with the largest effects together account for only about 10% of the phenotypic variation. Recent findings in medical genetics are more discouraging. Just a decade ago, hope was high that we would soon find the variations that account for highly heritable diseases, such as schizophrenia and autism. But scanning the entire genome has revealed that there are no common alleles with large effects on these diseases. Some say we should have known. Natural selection would, after all, tend to eliminate alleles that cause disease. But, thinking about the body as a machine aroused unrealistic hopes.

The grand vision for some neuroscientists is to trace every molecule and pathway to characterize all circuits in order to understand how the brain works. Molecules, loci, and pathways do serve differentiated functions, this is real knowledge with great importance for human health. But, understanding how the brain works by drawing a diagram that describes all the components and their connections and functions is a dream that may be unfulfillable. The problem is not merely fitting a million items on a page, the problem is that no such diagram can adequately describe the structure of organic systems. They are products of miniscule changes, from diverse mutations, migration, drift, and selection, which develop into systems with incompletely differentiated parts and incomprehensible interconnections, that, nonetheless, work very well indeed. Trying to reverse engineer brain systems focuses important attention on functional significance, but it inherently limited, because brain systems were never engineered in the first place.

If bodies are not like machines, what are they like? They are more like Darwin's "tangled bank" with its "elaborately constructed forms, so different from each other, and dependent upon each other in so complex a manner." Lovely. But, can an ecological metaphor replace the metaphor of body as machine? Not likely. Perhaps someday understanding how natural selection shapes organic complexity will be so widely and deeply understood that scientists will be able to say "A body is like…a living body," and everyone will know exactly what that means. 

Mapping discrete and dimensional emotions onto the brain.

Here I am passing on the abstract and one summary figure from a useful recent review article by Stephan Hamann:

A longstanding controversy in the field of emotion research has concerned whether emotions are better conceptualized in terms of discrete categories, such as fear and anger, or underlying dimensions, such as arousal and valence. In the domain of neuroimaging studies of emotion, the debate has centered on whether neuroimaging findings support characteristic and discriminable neural signatures for basic emotions or whether they favor competing dimensional and psychological construction accounts. This review highlights recent neuroimaging findings in this controversy, assesses what they have contributed to this debate, and offers some preliminary conclusions. Namely, although neuroimaging studies have identified consistent neural correlates associated with basic emotions and other emotion models, they have ruled out simple one-to-one mappings between emotions and brain regions, pointing to the need for more complex, network-based representations of emotion.

Figure - Levels of mapping between emotion models and the brain. The left panel illustrates the most commonly proposed one-to-one mappings between elements of emotion theories and individual brain regions. For example, amygdala activation typically correlates with emotional arousal, whereas activation in the orbitofrontal cortex correlates with emotional valence. As noted in the text, these one-to-one mappings run afoul of numerous experimental findings that show that, for example, fear consistently activates regions other than the amygdala, and the amygdala in turn is associated with several emotion processes. Such difficulties with one-to-one mappings have motivated a shift to more complex interrelationships, such as functional networks. For example, in the right panel, network mappings may involve individual brain regions (small rectangles) participating in networks that carry out the processing mediating different emotions. An individual region, such as the amygdala (red rectangle) can participate in multiple networks and that region's role can be modulated according to the currently active network configuration. These network dynamics have important implications for evaluating the neuroimaging evidence for different emotion theories.

How childhood musical training shapes the adult brain.

From Skoe and Kraus:

Playing a musical instrument changes the anatomy and function of the brain. But do these changes persist after music training stops? We probed this question by measuring auditory brainstem responses in a cohort of healthy young human adults with varying amounts of past musical training. We show that adults who received formal music instruction as children have more robust brainstem responses to sound than peers who never participated in music lessons and that the magnitude of the response correlates with how recently training ceased. Our results suggest that neural changes accompanying musical training during childhood are retained in adulthood. These findings advance our understanding of long-term neuroplasticity and have general implications for the development of effective auditory training programs.

Scientific basis of a psychotherapy.

I've been wanting to pass on elements of a nice essay written by Eric Kandel for last year's Edge question, which describes Aaron Beck's development of cognitive behavioral therapy, a systematic psychological treatment for depression that focuses on distorted thinking rather than presumed unconscious conflicts. This is a pragmatic relatively value-neutral approach that avoids considerations of, and lacks the richness of, dealing with object relations, morality, or origins. (A random aside: I remember from my postdoctoral years at Harvard Medical School's Neurobiology Department (1967-68) that Eric Kandel, trained as a psychiatrist, would drop by at our communal lunch time to talk about his new work on a strange sea slug named Aplysia, work which was the basis of his later Nobel prize for uncovering a neuronal basis for memory. He was quizzed by Hubel and Wiesel, also to win the prize for their work in vision.) Kandel describes Beck's basic innovations:

First, he introduced instruments for measuring mental illness..beginning with a Depression Inventory, a Hopelessness Scale, and a Suicide Intent Scale. These scales helped to objectify research in psychopathology and facilitated the establishment of better clinical outcome trials.

Second, Beck introduced a new short-term, evidence-based therapy he called Cognitive Behavioral Therapy.

Third, Beck manualized the treatments. He wrote a cookbook so method could be reliably taught to others. You and I could in principle learn to do Cognitive Behavioral Therapy.

Fourth, he carried out with the help of several colleagues, progressively better controlled studies which documented that Cognitive Behavioral Therapy worked more effectively than placebo and as effectively as antidepressants in mild and moderate depression. In severe depression it did not act as effectively as an anti-depressant but acted synergistically with them to enhance recovery.

Fifth and finally, Beck's work was picked up by Helen Mayberg, another one of my heroes in psychiatry. She carried out FMRI studies of depressed patients and discovered that Brodmann area 25 was a focus of abnormal activity in depression. She went on to find that if—and only if—a patient responded to cognitive behavior therapy or to antidepressants SSRI's (selective serotonin reuptake inhibitors) this abnormality reverted to normal.

Freud, the tea party, and deluded individualism.

A nice piece by DeBrabander in The Stone forum on the NYTimes has an interesting take on how it is that stalwart red state tea party supporters who admit they could not survive with government support nevertheless profess a robust individualism, and anger at sustaining others with their tax dollars. I think the basic point is that they perform the same cognitive illusion that was clearly perceived by Spinoza and Freud, the illusion that I provide an updated description of in my "I-Illusion" web/lecture. We imagine ourselves to be the master of our actions while ignoring evidence to the contrary. Some clips from DeBrabander's article:

By Freud's account, conscious autonomy is a charade. "We are lived," as he puts it, and yet we don't see it as such…I was reminded of Freud's paradox by…a study from Dartmouth political science professor Dean Lacy, which revealed that, though Republicans call for deep cuts to the safety net, their districts rely more on government support than their Democratic counterparts…In Chisago County, Minn., The Times's reporters spoke with residents who supported the Tea Party and its proposed cuts to federal spending, even while they admitted they could not get by without government support. Tea Party aficionados, and many on the extreme right of the Republican party for that matter, are typically characterized as self-sufficient middle class folk, angry about sustaining the idle poor with their tax dollars. Chisago County revealed a different aspect of this anger: economically struggling Americans professing a robust individualism and self-determination, frustrated with their failures to achieve that ideal.

Why the stubborn insistence on self-determination, in spite of the facts? One might say there is something profoundly American in this. It's our fierce individualism shining through. Residents of Chisago County are clinging to notions of past self-reliance before the recession, before the welfare state. It's admirable in a way. Alternately, it evokes the delusional autonomy of Freud's poor ego…These people, like many across the nation, rely on government assistance, but pretend they don't. They even resent the government for their reliance. If they looked closely though, they'd see that we are all thoroughly saturated with government assistance in this country: farm subsidies that lower food prices for us all, mortgage interest deductions that disproportionately favor the rich, federal mortgage guarantees that keep interest rates low, a bloated Department of Defense that sustains entire sectors of the economy and puts hundreds of thousands of people to work. We can hardly fathom the depth of our dependence on government, and pretend we are bold individualists instead.

Thanks to a decades-long safety net, we have forgotten the trials of living without it. This is why, the historian Tony Judt argued, it's easy for some to speak fondly of a world without government: we can't fully imagine or recall what it's like. We can't really appreciate the horrors Upton Sinclair witnessed in the Chicago slaughterhouses before regulation, or the burden of living without Social Security and Medicare to look forward to. Thus, we can entertain nostalgia for a time when everyone pulled his own weight, bore his own risk, and was the master of his destiny. That time was a myth. But the notion of self-reliance is also a fallacy.

Spinoza greatly influenced Freud, and he adds a compelling insight we would do well to reckon with. Spinoza also questioned the human pretense to autonomy…There is no such thing as a discrete individual, Spinoza points out. This is a fiction. The boundaries of 'me' are fluid and blurred. We are all profoundly linked in countless ways we can hardly perceive. My decisions, choices, actions are inspired and motivated by others to no small extent. The passions, Spinoza argued, derive from seeing people as autonomous individuals responsible for all the objectionable actions that issue from them. Understanding the interrelated nature of everyone and everything is the key to diminishing the passions and the havoc they wreak…In this, Spinoza and President Obama seem to concur: we're all in this together.

Wednesday morning music: Faure Barcarolle No. 1

I keep stopping recordings and starting over if I make a mistake, and I finally decided the hell with it, and just recorded a run through, minor glitches and all.

The quotable Gore Vidal.

I just can't resist passing on these wonderful quotes from Gore Vidal,  from the PBS website:

1. “It is not enough to succeed. Others must fail.”
2. “Style is knowing who you are, what you want to say and not giving a damn.”
3. “First coffee, then a bowel movement. Then the Muse joins me.” – from The Paris Review Interviews: Writers at Work, interview by Gerald Clarke, 1974
4. “Write what you know will always be excellent advice for those who ought not to write at all.” – from The Second American Revolution, 1983
5. “…American society, literary or lay, tends to be humorless. What other culture could have produced someone like [Ernest] Hemingway and not seen the joke?” – from United States – Essays 1952-1992
6. “To speak today of a famous novelist is like speaking of a famous cabinetmaker or speedboat designer. Adjective is inappropriate to noun.” – from Screening History
7. “The more money an American accumulates the less interesting he himself becomes.” – from Homage to Daniel Shays: Collected Essays
8. “Whenever a friend succeeds, a little something in me dies.” – from The Sunday Times Magazine, 1973
9. “Andy Warhol is the only genius I’ve ever known with an I.Q. of 60″
10. “I am at heart a propagandist, a tremendous hater, a tiresome nag, complacently positive that there is no human problem which could not be solved if people would simply do as I advise.” – from Homage to Daniel Shays: Collected Essays, 1972
11. “The four most beautiful words in our common language: I told you so.”
12. “Sex is. There is nothing more to be done about it. Sex builds no roads, writes no novels, and sex certainly gives no meaning to anything in life but itself.”
13. “You hear all this whining going on, ‘Where are our great writers?’ The thing I might feel doleful about is: Where are the readers?” – from Esquire, 2008
14. “Never pass up a chance to have sex or appear on television.”
15. “A narcissist is someone better looking than you are.” – from The New York Times, 1981
16. “History is nothing but gossip about the past, with the hope that it might be true.” – from Butt, 2007
17. “The United States was founded by the brightest people in the country — and we haven’t seen them since.” – from Matters of Fact and Fiction: Essays 1973 – 1976
18. “Celebrities are invariably celebrity-mad, just as liars always believe liars.” – from Palimpsest: A Memoir
19. “I do many different things rather better than most people do one thing.” – from The Paris Review Interviews: Writers at Work, interview by Gerald Clarke, 1974
20. “The usual question everybody asks now is: What are you proudest of, Mr. Vidal, of all your great achievements? To which I answer: ‘Despite intense provocations over the course of what is becoming a rather long life, I have never killed anybody. That is my greatest achievement.’ A little negative maybe, but that’s it.” – from Vanity Fair, 2009

Effect of early institutionalization on brain development.

Sheridan et al. do further studies on the effects of Rumanian institutionalization of children, finding some reversibility its deleterious effects. From their introduction:

UNICEF estimates that there are at least 8 million children who live in institutional settings. Institutional rearing of young children represents a severe form of early psychological and physical neglect, and as such, serves as a model system for understanding how early experience—or the lack of thereof—impacts brain and behavioral development...In most forms of institutional rearing, the ratio of caregivers-to-children is low (e.g., in our sample ∼1:12), care is highly regimented, and caregiver investment in children is low. Children raised in institutions are more likely than children raised in families to have deficits in cognitive function and in language production and comprehension. Relative to noninstitutionalized children, children reared in institutional settings experience a wide range of developmental problems including markedly elevated rates of attention-deficit/hyperactivity disorder and other forms of psychopathology and difficulties with social functioning.

The abstract:

We used structural MRI and EEG to examine brain structure and function in typically developing children in Romania (n = 20), children exposed to institutional rearing (n = 29), and children previously exposed to institutional rearing but then randomized to a high-quality foster care intervention (n = 25). In so doing, we provide a unique evaluation of whether placement in an improved environment mitigates the effects of institutional rearing on neural structure, using data from the only existing randomized controlled trial of foster care for institutionalized children. Children enrolled in the Bucharest Early Intervention Project underwent a T1-weighted MRI protocol. Children with histories of institutional rearing had significantly smaller cortical gray matter volume than never-institutionalized children. Cortical white matter was no different for children placed in foster care than never-institutionalized children but was significantly smaller for children not randomized to foster care. We were also able to explain previously reported reductions in EEG α-power among institutionally reared children compared with children raised in families using these MRI data. As hypothesized, the association between institutionalization and EEG α-power was partially mediated by cortical white matter volume for children not randomized to foster care. The increase in white matter among children randomized to an improved rearing environment relative to children who remained in institutional care suggests the potential for developmental “catch up” in white matter growth, even following extreme environmental deprivation.