A bit of science fiction...a brain implant that allows mind-controlled gene expression.

The experiments by Folcher et al. are done with optogenetic implants in mouse brains that are wirelessly controlled by human brain waves. This is the proof of concept step, preliminary to trying the implants in humans to control the expression of engineered light sensitive regulators of genes for therapeutic proteins. Here is their cartoon summary of the procedure:

The mind-controlled transgene expression device consisted of (a) an EEG headset that captured brain-wave activities (the encephalogram), identified mental state-specific electrical patterns (biofeedback, concentration, meditation) and processed discrete meditation-meter values (0–100; meditation-meter value plot), which were transmitted via Bluetooth to (b) the Arduino single-board microcontroller with a time-relay device and switching the (c) field generator ON and OFF. This BCI (a–c) controlled (d) the TC (c,d) of the field generator, which inductively coupled with the (d,e) receiver coil (RC) of the (e) wireless-powered optogenetic implant. (e) The NIR light LED illuminated the culture chamber of the wireless-powered optogenetic implant and programmed the designer cells to produce ​SEAP, which diffused through the semi-permeable membrane. The blood ​SEAP (human ​secreted alkaline phosphatase) levels of mice with subcutaneous wireless-powered optogenetic implants containing designer cells that were freely moving on the field generator could be modulated by the human subject’s mindset in a wireless, remote-controlled manner.

Impact of literacy on visual processing

From Pegado et al., a clear demonstration of how learning the act of reading enhances our visual processing:

How does learning to read affect visual processing? We addressed this issue by scanning adults who could not attend school during childhood and either remained illiterate or acquired partial literacy during adulthood (ex-illiterates). By recording event-related brain responses, we obtained a high-temporal resolution description of how illiterate and literate adults differ in terms of early visual responses. The results show that learning to read dramatically enhances the magnitude, precision, and invariance of early visual coding, within 200 ms of stimulus onset, and also enhances later neural activity. Literacy effects were found not only for the expected category of expertise (letter strings), but also extended to other visual stimuli, confirming the benefits of literacy on early visual processing.

Cross-species evidence that adaptive training diminishes distractibility in Aging.

Another fascinating study from Gazzaley's productive research group. A video clip is offered in the abstract. Here are the highlights and summary:

Highlights

•Adaptive distractor training selectively suppresses sensory distractor responses 

•Training enhances spectral and spatial tuning of sensory receptive fields in older rats 

•Top-down frontal theta is selectively restrained for distractors in trained humans 

•Training in older humans generalizes to enhanced aspects of cognitive control

Summary

Aging is associated with deficits in the ability to ignore distractions, which has not yet been remediated by any neurotherapeutic approach. Here, in parallel auditory experiments with older rats and humans, we evaluated a targeted cognitive training approach that adaptively manipulated distractor challenge. Training resulted in enhanced discrimination abilities in the setting of irrelevant information in both species that was driven by selectively diminished distraction-related errors. Neural responses to distractors in auditory cortex were selectively reduced in both species, mimicking the behavioral effects. Sensory receptive fields in trained rats exhibited improved spectral and spatial selectivity. Frontal theta measures of top-down engagement with distractors were selectively restrained in trained humans. Finally, training gains generalized to group and individual level benefits in aspects of working memory and sustained attention. Thus, we demonstrate converging cross-species evidence for training-induced selective plasticity of distractor processing at multiple neural scales, benefitting distractor suppression and cognitive control.

How to bridge the respective bubbles of our ideological tribes?

A number of recent mindblog posts have engaged the issue of the individual versus the collective good (for example, here, here, and here), a creative tension that has been central in human evolution. This has led me to mull a bit about the current apparent drift in the direction of more extreme individualism and rejection of the state’s concern for common interests.

I sometimes feel guilty for not being more evangelistic about promoting a rational scientific ideology that encompasses creationists, conservatives, and libertarians in a more broad evolutionary view, I wonder how it might be possible to induce these groups to admit a broader swath of reality than they currently seem willing to engage.

Concrete personal steps I might take? The expression of my ideas or those of others in writing is relatively easy, that is what this blog is about.

The problem is that MindBlog exists as one instance in the array of similarly minded sites that largely mirror each other’s views. I suspect that it is quite invisible to those following websites that deal with Creationism , conservatism, the libertarian or tea party movements that extoll individualism, etc. Those sites, in turn, are unlikely to be viewed by followers of atheist, agnostic, skeptic, or humanist sites more sympathetic to collective views of the individual in society.

I am a person who is timid about robust personal visceral engagement with those of opposing religious or political views, so I quail at the prospect of showing up at meetings of evangelical or ultra-conservative groups to ask questions like “you say you want the government off our backs...do you accept your social security or medicare payments? If so, do you see any inconsistency in your beliefs and actual practices?” Or, “You indicate you believe the biblical account that earth was created about 6,000 years ago. Do you accept the validity of the physical laws that permit your computer and iPhone to function? If so, how do you account for the fact that these same laws governing the physical properties of atoms prove that life on this planet began 3-4 billion years ago?”

I do hope that the a devout creationist or extreme individualist who occasionally stumbles on to a MindBlog post has his or her mental horizons slightly expanded.

Critique of the Nature paper on dishonest bankers,

I wanted to pass on to MindBlog readers this item analyzing the paper noted in my recent post "Banking - a culture of dishonesty", Statistician Salil Mehta argues that the article is misleading, missing data, and mathematically inaccurate.

Several nuggets on the individual vs. the collective.

Following yesterday's post on the evolution of prosocial religions, I pass on a random set of links to articles also relevant to the individual and the collective.

Terrell notes that the current political schism between Republicans and Democrats has a foundation in different views about the whether an individual's primary purpose is to look out for communal or self interests.

...modern evolutionary research, anthropology, cognitive psychology and neuroscience have come down on the side of the philosophers who have argued that the basic unit of human social life is not and never has been the selfish, self-serving individual. Contrary to libertarian and Tea Party rhetoric, evolution has made us a powerfully social species, so much so that the essential precondition of human survival is and always has been the individual plus his or her relationships with others.

Luhrman does a piece "Wheat people versus rice people" which references the same work mentioned in MindBlog's May 21st post, and notes several other studies on individualistic versus collective cultures.

Rand et al. offer economic game experiments to illustrate how static network structure stabilizes human cooperation

Finally Crockett et al. do an experiment relevant to social cohesion, showing that harm to others outweighs harm to self in moral decision making - most people sacrifice more money to reduce a stranger’s pain than their own pain (the pain being delivered by electric shocks).

The Cultural Evolution of Prosocial Religions

Having been an author in an issue of "Behavioral and Brain Biology" published by Cambridge University Press, I receive notice of forthcoming articles inviting reviewers comments. The articles are then published with the reviewer's comments and authors' responses to the comments.

As a followup to my recent MindBlog post on E.O. Wilson's new book, I am passing on this interesting abstract of such a forthcoming article by Norenzayan et al.  (Motivated readers can email me if they wish to obtain a PDF of this article.)

We develop a cultural evolutionary theory of the origins of prosocial religions, and apply it to resolve two puzzles in human psychology and cultural history: 1) the rise of large-scale cooperation among strangers in the last twelve millennia, and 2) the spread of prosocial religions during the same period. We argue that these two developments were importantly linked. We explain how a package of culturally evolved religious beliefs and practices characterized by increasingly potent, moralizing supernatural agents, credible displays of faith, and other psychologically active elements conducive to social solidarity promoted internal harmony, large-scale cooperation, and high fertility, often leading to success in intergroup competition. In turn, prosocial religious beliefs and practices spread and aggregated as these successful groups expanded, or were copied by less successful groups. This synthesis is grounded in the idea that although religious beliefs and practices originally arose as non-adaptive byproducts of innate cognitive functions, particular cultural variants were then selected for their prosocial effects in a long-term cultural evolutionary process. This framework (1) reconciles key aspects of the adaptationist and byproduct approaches to the origins of religion, (2) explains a variety of empirical observations that have not received adequate attention, and (3) generates novel predictions. Converging lines of evidence drawn from diverse disciplines provide empirical support while at the same time encouraging new research directions and opening up new questions for exploration and debate.

The new surveillance state and our robotic future.

Isreal et al. examine one of the many uses to which individual credit scores are being put - to determine our cardiovascular risk (useful information for health insurance companies). They also note that credit scores are also used by employers, utility companies, and automobile insurers to index high-risk behavior; and by life insurance companies that incorporate credit scores into actuarial models.) Here is the abstract:

Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions.

Also, the well known futuristic author Margaret Atwood offers an essay, well worth giving a read, on our growing efforts to craft a robotic future. One clip:

Why do we dream up such things? Because, deep down, we desire them...If we were technologically capable mice, we’d be perfecting deadly cat harpoons, or bird-exploding rockets, or cheese-on-demand molecular assemblers...To understand Homo sapiens’ primary wish list, go back to mythology. We endowed the gods with the abilities we wished we had ourselves: immortality and eternal youth, flight, resplendent beauty, total power, climate control, ultimate weapons, delicious banquets minus the cooking and washing up — and artificial creatures at our beck and call.

And just one more:

...people are dreaming up robotic prostitutes, complete with sanitary self-flushing features. Will there be a voice feature, and, if so, what will it say?...If the prospect of getting painfully stuck due to a malfunction keeps you from test-driving a full-body prostibot, you may soon be able to avail yourself of a remote kissing device that transmits the sensation of your sweetie’s kiss to your lips via haptic feedback and an apparatus that resembles a Silly Putty egg. (Just close your eyes.) Or you could venture all the way into the emerging world of “teledildonics” — essentially, remote-controlled vibrators. Push the game-controller levers, watch the effect on screen. Germ-free! Wait for Google or Skype to snatch this up.

Why elders smile, and wisdom in social signals.

Two articles relevant to becoming a senior person:
From Rijsbergen et al. (open access), a piece of work that reminds me of the book recently read by my book group here in Fort Lauderdale, the classic John Rechy novel about male hustlers, "City of Night", in which two age classes existed - 'young man' and 'old man.' Their abstract:

In an increasingly aging society, age has become a foundational dimension of social grouping broadly targeted by advertising and governmental policies. However, perception of old age induces mainly strong negative social biases. To characterize their cognitive and perceptual foundations, we modeled the mental representations of faces associated with three age groups (young age, middle age, and old age), in younger and older participants. We then validated the accuracy of each mental representation of age with independent validators. Using statistical image processing, we identified the features of mental representations that predict perceived age. Here, we show that whereas younger people mentally dichotomize aging into two groups, themselves (younger) and others (older), older participants faithfully represent the features of young age, middle age, and old age, with richer representations of all considered ages. Our results demonstrate that, contrary to popular public belief, older minds depict socially relevant information more accurately than their younger counterparts.

Also, David Brooks cites several books on the practical wisdom that comes with aging, and notes on the famous U-curve experiments in which people generally assess their own well being as high in their 20's and decreasing until about age 50 and then rising again until people rate themselve most happy at ages 82 to 85. A sample clip:

...experienced heads have intuitive awareness of the landscape of reality, a feel for what other people are thinking and feeling, an instinct for how events will flow. In “The Wisdom Paradox,” Elkhonon Goldberg details the many ways the brain deteriorates with age: brain cells die, mental operations slow. But a lifetime of intellectual effort can lead to empathy and pattern awareness. “What I have lost with age in my capacity for hard mental work,” Goldberg writes, “I seem to have gained in my capacity for instantaneous, almost unfairly easy insight.”

Physics, Emergence, and the Connectome - From the connectome to brain function

A special issue of Neuron on connectomics has a special open source section of articles with different views of the problems we face in relating details of brain structure to brain function. I would in particular recommend, Robert B. Laughlin's rather deep article on Physics, Emergence, and the Connectome, whose final paragraphs I copy in below:

It is not controversial that neurons do playful things. They deploy themselves somewhat haphazardly in glial matter, exhibiting no lateral crystalline order. They arborize with each other in ways that resemble tree branches and roots. They possess on-board memory that responds to incoming signals in an agent-based way and changes the signals they themselves generate.

What Might Be Missing

If we suspend disbelief for a moment and consider the possibility that play might be a design principle rather than a higher emergent phenomenon, a simple idea presents itself as to why making sense of the connectome might be so difficult. The latter includes things like obtaining the entire map of C. elegans and finding that it still doesn’t make any sense, and that it even has no action potentials. It is a small step from systems that play without direction to systems that play with rules, and from there to systems that play games with each other. Were that to happen, it could easily account for something as complicated as the brain, for it is well known from the study of automata that simple systems playing games can create enormously complex structures with very sophisticated functions. It is also known that small changes in the rule base can make enormous changes in the structures that develop. There is also the obvious example of the human economy, a thing that grows out of simple rules of money exchange that transcends anyone’s attempt to understand and manage it. One of the economy’s physical manifestations is a great network of highways with mighty cities at its hubs. It would obviously be a fool’s errand to try understanding the economy by mapping its roads.

There is nothing supernatural or unscientific in the concept of gaming making a brain, or for that matter an entire organism. All that is required is an intermediate stage of organization that is unstable, like the weather. Physical science tells us that unstable development can be perfectly deterministic yet difficult, if not impossible, to follow by experiment, among other reasons because unstable evolution is functionally the same thing as cryptography. Thus the scientific resolution of the whole mystery might simply be that the genome instructs the system to go wild and generate a bag of tools and parts it might need to construct something interesting, and then sends a subsequent instruction to go out and play. Emergent self-organization then finishes the job.

Psilocybin changes brain connectivity.

Petri et al. show that "the brain's functional patterns undergoes a dramatic change post-psilocybin, characterized by the appearance of many transient structures of low stability and of a small number of persistent ones that are not observed in the case of placebo." A simple reading of their results is that the effect of psilocybin is to relax constraints on brain function, ascribing cognition a more flexible quality. This may account for the transient synesthesia reported by many with psilocybin, hearing colors or seeing sounds.

Simplified visualization of the persistence homological scaffolds. a.) placebo baseline b.) with psilocybin

A review of the work by Bone notes:

When ingested, psilocybin metabolizes to psilocin, which resembles the chemical structure of serotonin — a neurotransmitter that regulates mood, appetite, sleep, cognitive functions like memory and learning and feelings of pleasure. Psilocin may simulate serotonin, and stimulate serotonin receptors in the brain...psilocybin therapy could be useful in treating disorders like depression, in which people get stuck in a spiral of negative thoughts. Like electric shock therapy, psilocybin might act like tripping a circuit breaker or rebooting your computer.

The Bone review also give links to studies on psilocybin effects on other psychological syndromes.

We search for meaning at the start of each chronological decade.

Recent soulful introspection by my husband, who moves from age 59 to 60 in late December, motivates me to point to this study by Alter and Hershfield, who perform six cross cultural studies to show the same thing I recall from my own experience when I was 49, 59 and 69: that people renew their search for meaning as they face a new decade. The studies aggregated data available on several major survey data websites relevant to values, search for meaning, extramarital affairs, suicide rates, and marathon sign-ups and performance. The summary from their significance and abstract sections:

...people audit the meaningfulness of their lives as they approach a new decade in chronological age, further suggesting that people across dozens of countries and cultures are prone to making significant decisions as they approach each new decade...Six studies show that adults undertake a search for existential meaning when they approach a new decade in age (e.g., at ages 29, 39, 49, etc.) or imagine entering a new epoch, which leads them to behave in ways that suggest an ongoing or failed search for meaning (e.g., by exercising more vigorously, seeking extramarital affairs, or choosing to end their lives).

Banking - a culture of dishonesty

Kelland points to work by Cohn et al., who have studied bank workers and other professionals in experiments in which they won more money if they cheated. They found that bankers were more dishonest when they were made particularly aware of their professional role. Employees in other sectors - manufacturing, telecoms, pharmaceuticals - did not show more dishonest behavior when their professional identity or banking-related information was emphasized. Honesty was tested by having participants toss a coin 10 times, unobserved, and report the results, knowing whether heads or tails would yield a $20 reward. They were told they could keep their winnings if they were more than or equal to those of a randomly selected subject from a pilot study. The control group reported ~50% winning tosses, and bankers who banking identity had been emphasized to them reported ~58% as wins. The authors conclude that the prevailing business culture in the banking industry weakens and undermines the honesty norm, suggesting a need for measures that re-establish an honest culture.

The ecology of religious beliefs

Botero et al. do a fascinating survey of 583 societies to show that religions with moralizing high gods that promote cooperation between humans are more prevalent among societies that inhabit poorer environments and are more prone to ecological duress:

Although ecological forces are known to shape the expression of sociality across a broad range of biological taxa, their role in shaping human behavior is currently disputed. Both comparative and experimental evidence indicate that beliefs in moralizing high gods promote cooperation among humans, a behavioral attribute known to correlate with environmental harshness in nonhuman animals. Here we combine fine-grained bioclimatic data with the latest statistical tools from ecology and the social sciences to evaluate the potential effects of environmental forces, language history, and culture on the global distribution of belief in moralizing high gods (n = 583 societies). After simultaneously accounting for potential nonindependence among societies because of shared ancestry and cultural diffusion, we find that these beliefs are more prevalent among societies that inhabit poorer environments and are more prone to ecological duress. In addition, we find that these beliefs are more likely in politically complex societies that recognize rights to movable property. Overall, our multimodel inference approach predicts the global distribution of beliefs in moralizing high gods with an accuracy of 91%, and estimates the relative importance of different potential mechanisms by which this spatial pattern may have arisen. The emerging picture is neither one of pure cultural transmission nor of simple ecological determinism, but rather a complex mixture of social, cultural, and environmental influences. Our methods and findings provide a blueprint for how the increasing wealth of ecological, linguistic, and historical data can be leveraged to understand the forces that have shaped the behavior of our own species.

E.O. Wilson and "The Meaning of Human Existence"

I've just read through E.O. Wilson's new and admirably brief and terse book (~200 pages) that gives a distillation of his previous writings on our human condition, and in particular the relationship between the sciences and the humanities. I pass on here a few clips from the first section of the book, but start with his statement in the final section where he gives his version of what the meaning of human existence is. (It conforms to my own opinion that experiencing ourselves as part of biological evolution suffices as a complete spiritual path.)

So, what is the meaning of human existence? I suggest that it is the epic of the species, begun in biological evolution and prehistory, passed into recorded history, and urgently now, day by day, faster and faster into the indefinite future, it is also what we will choose to become.

From Section I "The Reason We Exist":

In ordinary usage the word “meaning” implies intention, intention implies design, and design implies a designer. Any entity, any process, or definition of any word itself is put into play as a result of an intended consequence in the mind of the designer. This is the heart of the philosophical worldview of organized religions, and in particular their creation stories. Humanity, it assumes, exists for a purpose. Individuals have a purpose in being on Earth. Both humanity and individuals have meaning.

There is a second, broader way the word “meaning” is used and a very different worldview implied. It is that the accidents of history, not the intentions of a designer, are the source of meaning. There is no advance design, but instead overlapping networks of physical cause and effect. The unfolding of history is obedient only to the general laws of the Universe. Each event is random yet alters the probability of later events. During organic evolution, for example, the origin of one adaptation by natural selection makes the origin of certain other adaptations more likely. This concept of meaning, insofar as it illuminates humanity and the rest of life, is the worldview of science.

We are about to abandon natural selection , the process that created us, in order to direct our own evolution by volitional selection— the process of redesigning our biology and human nature as we wish them to be.

Humanity, I argue, arose entirely on its own through an accumulated series of events during evolution. We are not predestined to reach any goal, nor are we answerable to any power but our own. Only wisdom based on self-understanding, not piety, will save us.

...the grand master is multilevel selection . This formulation recognizes two levels at which natural selection operates: individual selection based on competition and cooperation among members of the same group, and group selection, which arises from competition and cooperation between groups. Group selection can occur through violent conflict or by competition between groups in the finding and harvesting of new resources.

Probably ... during the habiline period, a conflict ensued between individual-level selection, with individuals competing with other individuals in the same group, on the one side, and group-level selection , with competition among groups, on the other. The latter force promoted altruism and cooperation among all the group members. It led to innate group-wide morality and a sense of conscience and honor. The competition between the two forces can be succinctly expressed as follows: Within groups selfish individuals beat altruistic individuals, but groups of altruists beat groups of selfish individuals. Or, risking oversimplification, individual selection promoted sin, while group selection promoted virtue.

So it came to pass that humans are forever conflicted by their prehistory of multilevel selection. They are suspended in unstable and constantly changing positions between the two extreme forces that created us. We are unlikely to yield completely to either force as the ideal solution to our social and political turmoil. To give in completely to the instinctual urgings born from individual selection would be to dissolve society. At the opposite extreme, to surrender to the urgings from group selection would turn us into angelic robots— the outsized equivalents of ants.

Varieties of poverty - money, time, and bandwidth

We usually think of money when the word poverty is employed. But, just like getting caught in a high interest loan cycle, we can get in trouble by borrowing too much time, having a list of deadlines we continually fall behind on, forcing us to focus on the immediate next deadline, just like the next loan payment due. Konnikova points to the consequence of situations like these, bandwidth poverty:

If I’m focused on the immediate deadline, I don’t have the cognitive resources to spend on mundane tasks or later deadlines. If I’m short on money, I can’t stop thinking about today’s expenses — never mind those in the future. In both cases, I end up making decisions that leave me worse off because I lack the ability to focus properly on anything other than what’s staring me in the face right now, at this exact moment... 

She quotes a Princeton psychologist:

Under scarcity, you devote a lot of resources to the thing you’re lacking...When people are juggling time, they are doing something very similar to when they’re juggling finances. It is all scarcity juggling. You borrow from tomorrow, and tomorrow you have less time than you have today, and tomorrow becomes more costly. It’s a very costly loan.

Further clips:

When you get overloaded and you feel this deadline is overwhelming, you can say, I’ll take a vacation, I’ll focus on work-life balance...Poor people can’t say, ‘I’ll take a vacation from being poor.’ It’s the same mental process, but a different feedback loop.The poor are under a deadline that never lifts, pressure that can’t be relieved. If I am poor, I work or I churn until decisions like buying lottery tickets begin to seem like attractive alternatives. I lack the time to calculate the odds and think of alternative uses for my money...the mental bandwidth tax is powerful enough to make the overall problem run deeper. The poor... are so taxed they don’t even realize they have a problem...AND of course how much money you have affects how much time you have. If you keep busyness constant, the rich have it much easier...they can buy nannies and drivers and lawyers and the like. It’s easy to give yourself time if you have money.

If poverty is about time and mental bandwidth as well as money, how does this change how we combat its effects? When we think about programs for the poor, we don’t ever think, hey, let’s give them programs that don’t use a lot of bandwidth...Instead, we fault people for failing to sign up for programs that are ostensibly available, even though we don’t factor in the time and cognitive capacity they need to get past even the first step...Take something like the Fafsa” — the Free Application for Federal Student Aid — Why is pickup for the low-income families less than 30 percent? People are already overwhelmed, and you go and give them an incredibly complicated form...One study found that if you offer help with filling out the Fafsa form, pickup goes up significantly.

My iPad is masturbating!

As I have read the New York Times or Kindle Apps on my iPad over the past few weeks, the tablet has seemed to take on a mind of its own, opening articles or turning pages when I haven't touched it. Going by a techie store I am asked whether the screen has ever been broken and replaced, and indeed, this happened several months ago. It appears that if the job isn't done properly, or the screen is a poor quality one, it can start spontaneous touching or stroking in the absence of a human finger. To turn pages I am now gingerly stroking parts of the screen that don't seem to get its g-spots excited..... (I don't want to buy a new iPad because I am waiting for the larger one to come out, it will be more useful for displaying musical scores.)

The peripheral immune system and stress susceptibility.

Using a social stress model in mice, Hoades et al. find preexisting individual differences in the sensitivity of the peripheral immune system that predict and promote vulnerability to social stress. Finding that the emotional response to stress can be generated or blocked outside the brain suggest a new route for treating stress disorders, perhaps by controlling the peripheral level of the cytokine IL-6.

Significance

Depression and anxiety have been linked to increased inflammation. However, we do not know if inflammatory status predates onset of disease or whether it contributes to depression symptomatology. We report preexisting individual differences in the peripheral immune system that predict and promote stress susceptibility. Replacing a stress-naive animal’s peripheral immune system with that of a stressed animal increases susceptibility to social stress including repeated social defeat stress (RSDS) and witness defeat (a purely emotional form of social stress). Depleting the cytokine IL-6 from the whole body or just from leukocytes promotes resilience, as does sequestering IL-6 outside of the brain. These studies demonstrate that the emotional response to stress can be generated or blocked in the periphery, and offer a potential new form of treatment for stress disorders.

Abstract

Depression and anxiety disorders are associated with increased release of peripheral cytokines; however, their functional relevance remains unknown. Using a social stress model in mice, we find preexisting individual differences in the sensitivity of the peripheral immune system that predict and promote vulnerability to social stress. Cytokine profiles were obtained 20 min after the first social stress exposure. Of the cytokines regulated by stress, IL-6 was most highly up-regulated only in mice that ultimately developed a susceptible behavioral phenotype following a subsequent chronic stress, and levels remained elevated for at least 1 mo. We confirmed a similar elevation of serum IL-6 in two separate cohorts of patients with treatment-resistant major depressive disorder. Before any physical contact in mice, we observed individual differences in IL-6 levels from ex vivo stimulated leukocytes that predict susceptibility versus resilience to a subsequent stressor. To shift the sensitivity of the peripheral immune system to a pro- or antidepressant state, bone marrow (BM) chimeras were generated by transplanting hematopoietic progenitor cells from stress-susceptible mice releasing high IL-6 or from IL-6 knockout (IL-6−/−) mice. Stress-susceptible BM chimeras exhibited increased social avoidance behavior after exposure to either subthreshold repeated social defeat stress (RSDS) or a purely emotional stressor termed witness defeat. IL-6−/− BM chimeric and IL-6−/− mice, as well as those treated with a systemic IL-6 monoclonal antibody, were resilient to social stress. These data establish that preexisting differences in stress-responsive IL-6 release from BM-derived leukocytes functionally contribute to social stress-induced behavioral abnormalities.

Does exercise really make us smarter?

A NYTimes Well piece by Gretchen Reynolds points to an interesting study by Stothart et al., who decided to address a basic deficiency in most studies of the effects of aerobic training on cognition, they don't control for a possible placebo effect. If we expect to be smarter after training, our brains might just respond correspondingly. Stothart et al. found that people queried in an online survey expected a muscle stretching and toning program to have a greater effect on measures of thinking than a regular walking program. In actual experiments, stretching and toning regimens generally have been shown to have little if any impact on people’s cognitive skills. Walking, on the other hand, seems to substantially improve thinking ability. This lack of correlation between expectations and actual outcome suggests that a placebo effect does not explain the improved cognition observed after exercise.

The usefulness of spite.

Angier reviews a number of studies suggesting that the evolution of human cooperation can be assisted by spite, a certain degree of "altruistic" punishment, when some individuals are willing to punish rule breakers even when the infraction does not directly affect them. From Forber and Smead:

The presence of apparently irrational fair play in the ultimatum game remains a focal point for studies in the evolution of social behaviour. We investigate the role of negative assortment in the evolution of fair play in the ultimatum game. Spite-social behaviour that inflicts harm with no direct benefit to the actor-can evolve when it is disproportionally directed at individuals playing different strategies. The introduction of negative assortment alters the dynamics in a way that increases the chance fairness evolves, but at a cost: spite also evolves. Fairness is usually linked to cooperation and prosocial behaviour, but this study shows that it may have evolutionary links to harmful antisocial behaviour.

And, from Marlowe et al.:

We analyse generosity, second-party ('spiteful') punishment (2PP), and third-party ('altruistic') punishment (3PP) in a cross-cultural experimental economics project. We show that smaller societies are less generous in the Dictator Game but no less prone to 2PP in the Ultimatum Game. We might assume people everywhere would be more willing to punish someone who hurt them directly (2PP) than someone who hurt an anonymous third person (3PP). While this is true of small societies, people in large societies are actually more likely to engage in 3PP than 2PP. Strong reciprocity, including generous offers and 3PP, exists mostly in large, complex societies that face numerous challenging collective action problems. We argue that 'spiteful' 2PP, motivated by the basic emotion of anger, is more universal than 3PP and sufficient to explain the origins of human cooperation.

Brain's inflammatory response may contribute to brain disorders.

This post is just a pointer to a press release from the Society for Neuroscience meetings in Washington, DC. It outlines several studies on the link between brain inflammation and the progression of many common brain illnesses and disorders, suggesting possible targets for future treatments.

In older people, moderate alcohol intake improves memory.

Articles like this work from Downer et al. make me worry less about the possible deleterious effects of the happy hour cocktail that is part of my daily ritual. Several studies have shown that light and moderate alcohol consumption during late life is associated with higher cognitive functioning among older adults and a decreased risk of dementia, and they now document relevant correlations with the volume of the hippocampus, which is important in memory. Their abstract, slightly edited:

This study utilized data from the Framingham Heart Study Offspring Cohort to examine the relationship between midlife and late-life alcohol consumption, cognitive functioning, and regional brain volumes among older adults without dementia or a history of abusing alcohol. The results from multiple linear regression models indicate that late life, but not midlife, alcohol consumption status is associated with episodic memory and hippocampal volume. Compared to late life abstainers, moderate consumers had larger hippocampal volume, and light consumers had higher episodic memory. The differences in episodic memory according to late life alcohol consumption status were no longer significant when hippocampal volume was included in the regression model (This suggests that the observed relationship between alcohol consumption and episodic memory and alcohol consumption during old age may be due to larger hippocampal volume.) The findings from this study provide new evidence that hippocampal volume may contribute to the observed differences in episodic memory among older adults and late life alcohol consumption status.

The authors note that findings from animal studies suggest that moderate alcohol consumption may contribute to preserved hippocampal volume by promoting the generation of new neurons in the hippocampus. In addition, exposing the brain to moderate amounts of alcohol may increase the release of acetylcholine and other neurotransmitters that are involved in cognitive functioning.

How to dampen that urge to buy.

A brief post appropriate to the season: Seeing DeSteno's recent OpEd piece in the NYTimes make me think this is a relevant time to point back to my June post on his work. His OpEd piece is trying to broadcast to a larger audience possibly revving up for Black Friday's shopping madness. Exercising self-control to resist impulse buying takes a lot of energy, which is easily depleted. The DeSteno et al. experiments show that there is an easier way: cultivating the emotion of gratitude enhances patience and self-control. They asked asked 75 people to recall and describe in writing one of three events: a time they felt grateful, a time they felt amused or a typical day. Those describing a time of feeling greatful were twice as likely to be able to defer an immediate gratification in favor of a longer term reward. The take home message is that feeling grateful can sometimes temporarily enhance self-control by decreasing desires for immediate gratification.  (And, guess who just ordered a larger flat screen TV from Amazon's Black Friday sale, being delivered this Friday....)

Can brain science be dangerous?

Mindblog has done a number of posts on long terms brain and behavioral effects of early adverse environments. This OpEd piece by Anna North on the possible uses and misuses of such information is well worth a read.

How our prefrontal cortex explores and exploits options.

Hare describes work by Donoso et al:

Inferring the best response from a large range of possible actions frequently involves difficult computations that the brain is unlikely to perform rapidly. Nevertheless, humans often do well in such situations. Donoso et al. demonstrate that a computational model designed to integrate reward learning with probabilistic inference (i.e., computing the odds) and a form of hypothesis testing can approximate the optimal solution in a neurobiologically plausible manner. Moreover, the model provides a good fit to human behavior and, as seen by functional magnetic resonance imaging (fMRI), is represented in the activity patterns of specific prefrontal and striatal brain regions. 

Figure - Reasoning regions - Activity in specific brain regions tracks the reliability of executed strategies (medial prefrontal cortex), alternative strategies (frontopolar cortex, not shown), the need to explore new strategies (dorsal anterior cingulate cortex), and the confimation of strategies as valid (ventral striatum).

The Donoso et al abstract:

The prefrontal cortex (PFC) subserves reasoning in the service of adaptive behavior. Little is known, however, about the architecture of reasoning processes in the PFC. Using computational modeling and neuroimaging, we show here that the human PFC has two concurrent inferential tracks: (i) one from ventromedial to dorsomedial PFC regions that makes probabilistic inferences about the reliability of the ongoing behavioral strategy and arbitrates between adjusting this strategy versus exploring new ones from long-term memory, and (ii) another from polar to lateral PFC regions that makes probabilistic inferences about the reliability of two or three alternative strategies and arbitrates between exploring new strategies versus exploiting these alternative ones. The two tracks interact and, along with the striatum, realize hypothesis testing for accepting versus rejecting newly created strategies.

Art in a whiskey glass, the physics explained.

Here's a random bit that provides a tonic for the day. Ernie Button, a photographer in Phoenix, started taking pictures of the interesting patterns he noticed forming as the last bit of his single malt aged Scotch whiskey dried in the glass he had used.

The article describes the findings of some physicists he contacted, who determined what was going on.

Wealth is especially bad for the wealthy.

Michael Lewis reviews Darrell West's new book "Billionaires: Reflections on the Upper Crust" in The New Republic. The review starts with a marvellous story about breakfast at a tennis camp for children of the East Coast elite:

Jack Kenney’s assault on teenaged American inequality began at breakfast the first morning...On each table were small boxes of cereal, enough for each kid to have one box, but not enough that everyone could have the brand of cereal he wanted. There were Fruit Loops and Cheerios, but also more than a few boxes of the deadly dark bran stuff consumed willingly only by old people suffering from constipation...By the third morning, it was clear that, in the race to the Fruit Loops, some kids had a natural advantage...Some kids would always get the Fruit Loops, and others would always get the laxative. Life was now officially unfair.

After that third breakfast, Kenney called an assembly, saying...“You all live in important places surrounded by important people...When I’m in the big city, I never understand the faces of the people, especially the people who want to be successful. They look so worried! So unsatisfied!...In the city you see people grasping, grasping, grasping. Taking, taking, taking. And it must be so hard! To be always grasping-grasping, and taking-taking. But no matter how much they have, they never have enough. They’re still worried. About what they don’t have. They’re always empty.”

“You have a choice. You don’t realize it, but you have a choice. You can be a giver or you can be a taker. You can get filled up or empty. You make that choice every day. You make that choice at breakfast when you rush to grab the cereal you want so others can’t have what they want.” And then he moved on to why no one should ever hit a two-handed backhand—while every kid on the hill squirmed and reddened and glanced at each other, wondering if everyone else realized what an asshole he’d been.

On the fourth morning, no one ate the Fruit Loops. Kids were thrusting the colorful boxes at each other and leaping on the constipation cereal like war heroes jumping on hand grenades. In a stroke, the texture of life in this tennis camp had changed, from a chapter out of Lord of the Flies to the feeling between the lines of Walden.

Lewis follows with a discussion of the increase in wealth inequality, and whether rich people are significantly determining political outcomes. The evidence is not clear.

If these billionaires are seeking, as a class, to minimize the sums they return to society, they are not doing a very good job of it. But of course they aren’t seeking anything, as a class: it’s not even clear they can agree on what their collective interests are. The second richest American billionaire, Warren Buffett, has been quite vocal about his desire for higher tax rates on the rich. The single biggest donor to political campaigns just now is Tom Steyer, a Democrat with a passion for climate change. And for every rich person who sets off on a jag to carve California into seven states, or to defeat Barack Obama, there are many more who have no interest in politics at all except perhaps, in a general way, to prevent them from touching their lives. Rich people, in my experience, don’t want to change the world. The world as it is suits them nicely.

Lewis cites Dacher Keltner's work, which has been the subject of several mindblog posts (see here and here).

What is clear about rich people and their money...is how it changes them...Keltner and his colleague Paul Piff installed note-takers and cameras at city street intersections with four-way stop signs. The people driving expensive cars were four times more likely to cut in front of other drivers than drivers of cheap cars. The researchers then followed the drivers to the city’s cross walks and positioned themselves as pedestrians, waiting to cross the street. The drivers in the cheap cars all respected the pedestrians’ right of way. The drivers in the expensive cars ignored the pedestrians 46.2 percent of the time...the Berkeley researchers invited a cross section of the population into their lab and marched them through a series of tasks. Upon leaving the laboratory testing room the subjects passed a big jar of candy. The richer the person, the more likely he was to reach in and take candy from the jar—and ignore the big sign on the jar that said the candy was for the children who passed through the department.

Other studies show that a person, as he grows richer, becomes more likely to violate the rules of the road, to cheat, shoplift, and give less to charity.

A UCLA neuroscientist named Keely Muscatell has published an interesting paper showing that wealth quiets the nerves in the brain associated with empathy: if you show rich people and poor people pictures of kids with cancer, the poor people’s brains exhibit a great deal more activity than the rich people’s...The problem is caused by the inequality itself: it triggers a chemical reaction in the privileged few. It tilts their brains. It causes them to be less likely to care about anyone but themselves or to experience the moral sentiments needed to be a decent citizen...Or even a happy one...The evidence overwhelmingly suggests that money, above a certain modest sum, does not have the power to buy happiness, and yet even very rich people continue to believe that it does: the happiness will come from the money they don’t yet have. To the general rule that money, above a certain low level, cannot buy happiness there is one exception...While spending money upon oneself does nothing for one’s happiness,spending it on others increases happiness.

(By the way, I dug up the Muscatell paper, which does fMRI studies to show that individuals lower in social status are more likely to engage neural circuitry involved in thinking about others' thought and feelings.)

If the Harvard Business School is now making a home for research exposing the folly of a life devoted to endless material ambition, something in the world has changed—or is changing. And I think it is: there is a growing awareness that the yawning gap between rich and poor is no longer a matter of simple justice but also the enemy of economic success and human happiness. It’s not just bad for the poor. It’s also bad for the rich. It’s funny, when you think about it, how many rich people don’t know this. But they are not idiots; they can learn. Many even possess the self-awareness to correct for whatever tricks their brain chemicals seek to play on them; some of them already do it. When you control a lot more than your share of the Fruit Loops, there really isn’t much doubt about what you should do with them, for your own good. You just need to be reminded, loudly and often.

Genes that turned wildcats into kitty cats.

Reaction of my Abyssinian cat, Melvin, to finding that his genome had been sequenced.

David Grimm summarizes work by Montague et al., who sequenced the genome of a female Abyssinian cat, a domestic breed, and compared it with genome assemblies of six other domestic breeds, two wild cat species, and four other mammals to find genomic differences that might underlie cat biology and domestication. The authors found that, compared with wild cat genomes, domestic cat genomes displayed evidence of natural selection in genes linked to memory, fear-conditioning behavior, and stimulus-reward learning, suggesting that the genetic changes may underlie the evolution of tameness.

Cooperating with the future - how to sustain resources.

From Hauser et al., an experiment showing that if resource extraction decision are made by vote rather than individually, the resource can be sustained. Voting is effective for two reasons. First, it allows a majority of cooperators to restrain defectors. Second, it reassures conditional cooperators that their efforts are not futile. Voting, however, only promotes sustainability if it is binding for all involved. A summary of this work by Kerri Smith has a nice explanatory video. Here is the abstract:

Overexploitation of renewable resources today has a high cost on the welfare of future generations. Unlike in other public goods games, however, future generations cannot reciprocate actions made today. What mechanisms can maintain cooperation with the future? To answer this question, we devise a new experimental paradigm, the ‘Intergenerational Goods Game’. A line-up of successive groups (generations) can each either extract a resource to exhaustion or leave something for the next group. Exhausting the resource maximizes the payoff for the present generation, but leaves all future generations empty-handed. Here we show that the resource is almost always destroyed if extraction decisions are made individually. This failure to cooperate with the future is driven primarily by a minority of individuals who extract far more than what is sustainable. In contrast, when extractions are democratically decided by vote, the resource is consistently sustained. Voting is effective for two reasons. First, it allows a majority of cooperators to restrain defectors. Second, it reassures conditional cooperators16 that their efforts are not futile. Voting, however, only promotes sustainability if it is binding for all involved. Our results have implications for policy interventions designed to sustain intergenerational public goods.

Humor and Health

I want to point to this item by Jennifer Gibson that reminds me how useful it might be for me to "lighten up" just a little bit, try to get a daily laugh. Her article, with 11 article citations at its end, points to studies that suggest laughter, humor, or mirth improve short term memory and learning ability, lower stress hormone levels, improve immune function, lower blood pressure, etc.

Chemicals that delay or reverse effects of aging.

I scan for articles on aging in my wanderings through journals and pass on the following two, on chemical compounds that delay or reverse the effects of aging:

Mowia et al. suggest the prospect of an anti-aging pill that might extend life span and delay onset of age-related diseases. They fed mice a synthetic activator of SIRT1 (NAD-dependent deactylase sirtuin 1) from 6 months of age for the rest of their (∼3-year) life span. The treated mice had 5% and 10% increases in maximum and mean life span, respectively. They also resisted many problems associated with human aging. Here's the abstract:

Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age-related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean and maximal lifespan of mice fed a standard diet. This is accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density, and insulin sensitivity associated with higher mitochondrial content and decreased inflammation. Short-term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy. These results demonstrate it is possible to design a small molecule that can slow aging and delay multiple age-related diseases in mammals, supporting the therapeutic potential of SIRT1 activators in humans.

Gervain et al. find an instance of restoring brain plasticity characteristic of early life to an adult brain with valporate, a very simple organic structure (enter 'valporate' in google images to see the structure):

Absolute pitch, the ability to identify or produce the pitch of a sound without a reference point, has a critical period, i.e., it can only be acquired early in life. However, research has shown that histone-deacetylase inhibitors (HDAC inhibitors) enable adult mice to establish perceptual preferences that are otherwise impossible to acquire after youth. In humans, we found that adult men who took valproate (VPA) (a HDAC inhibitor) learned to identify pitch significantly better than those taking placebo—evidence that VPA facilitated critical-period learning in the adult human brain. Importantly, this result was not due to a general change in cognitive function, but rather a specific effect on a sensory task associated with a critical-period.

Big data in Neuroscience

I want to pass on an interesting graphic from a piece by Sejnowski, Churchland, and Movshon that introduces a "Focus on big data" series of articles in the November issue of Nature Neuroscience, on the challenges presented by the overwhelming flood of data on the brain being generated by new recording and visualization techniques, from the ultra-micro to the macro scale. (I'm afraid on looking at the whole ensemble of articles I quickly start seeing only gibble-gabble as my-eyes-glaze-over...) The graphic illustrates the spatial and temporal domain, and the increase in the number, of techniques that have appeared since 1988.

Each colored region represents the useful domain of spatial and temporal resolution for one method available for the study of the brain. Open regions represent measurement techniques; filled regions, perturbation techniques. Inset, a cartoon rendition of the methods available in 1988, notable for the large gaps where no useful method existed. The regions allocated to each domain are somewhat arbitrary and represent our own estimates. EEG, electroencephalography; MEG, magnetoencephalography; PET, positron emission tomography; VSD, voltage-sensitive dye; TMS, transcranial magnetic stimulation; 2-DG, 2-deoxyglucose.

The internet and the mind

This is a brief post to point to Jacob Silverman's quick reviews of four books that consider how enhanced connectivity might be altering us.

MDMA (ecstasy) enhances emotional empathy and prosocial behavior

Maybe a hit of NDMA, the party drug ecstasy (not to be confused with the methamphetamine of crystal meth, which is another derivative of the core amphetamine structure), would be good for the wingnuts in both political parties! From Hysek et al.:

3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) releases serotonin and norepinephrine. MDMA is reported to produce empathogenic and prosocial feelings. It is unknown whether MDMA in fact alters empathic concern and prosocial behavior. We investigated the acute effects of MDMA using the Multifaceted Empathy Test (MET), dynamic Face Emotion Recognition Task (FERT) and Social Value Orientation (SVO) test. We also assessed effects of MDMA on plasma levels of hormones involved in social behavior using a placebo-controlled, double-blind, random-order, cross-over design in 32 healthy volunteers (16 women). MDMA enhanced explicit and implicit emotional empathy in the MET and increased prosocial behavior in the SVO test in men. MDMA did not alter cognitive empathy in the MET but impaired the identification of negative emotions, including fearful, angry and sad faces, in the FERT, particularly in women. MDMA increased plasma levels of cortisol and prolactin, which are markers of serotonergic and noradrenergic activity, and of oxytocin, which has been associated with prosocial behavior. In summary, MDMA sex-specifically altered the recognition of emotions, emotional empathy and prosociality. These effects likely enhance sociability when MDMA is used recreationally and may be useful when MDMA is administered in conjunction with psychotherapy in patients with social dysfunction or post-traumatic stress disorder.

Trajectories of aging.

This post points to another of the articles in the Science special issue on aging. Lindenberger summarizes key features of human cognitive aging from the combined perspectives of life-span psychology and the cognitive neuroscience of aging, and notes a number of longitudinal studies that suggest that leading an intellectually challenging, physically active, and socially engaged life may mitigate losses and consolidate gains during cognitive aging. Here is a summary figure from the article:

Figure. An individual’s range of possible cognitive developmental trajectories from early to late adulthood.

The blue curve shows the most likely developmental path under normal circumstances. The fading of the background color indicates that more extreme paths are less likely. The functional threshold represents a level of functioning below which goal-directed action in the individual’s ecology will be severely compromised. The red curve represents the hope that changes in organism-environment interactions during adulthood move the individual onto a more positive trajectory. Beneficial changes may consist in the mitigation of risk factors, such as vascular conditions, metabolic syndrome, or chronic stress; the strengthening of enhancing factors, such as neuroplasticity; or both.

Are we really conscious?

I've done a post on Graziano's 'attention schema' theory of conscious, and thought I would pass on some clips from his recent exposition of the model in a NYTimes piece. In the title, and in the text below, a few qualifying phrases might have avoided the strong responses to Graziano in the letters to the editor that I also note below. I've added some qualifiers in brackets [ ]. For the inflammatory title "Are we really conscious?" what about adding [in the way we commonly suppose?].

...the argument here is that there is no subjective impression [in the way we commonly suppose]; there is only information in a data-processing device. When we look at a red apple, the brain computes information about color. It also computes information about the self and about a (physically incoherent) property of subjective experience. The brain’s cognitive machinery accesses that interlinked information and derives several conclusions: There is a self, a me; there is a red thing nearby; there is such a thing as subjective experience; and I have an experience of that red thing. Cognition is captive to those internal models. Such a brain would inescapably conclude it has subjective experience.

I concede that this approach is counterintuitive. One reason is that it seems to leave a gap in the logic: Why would the brain waste energy computing information about subjective awareness and attributing that property to itself, if the brain doesn’t in fact have this property?

This is where my own work comes in. In my lab at Princeton, my colleagues and I have been developing the “attention schema” theory of consciousness, which may explain why that computation is useful and would evolve in any complex brain. Here’s the gist of it:

Take again the case of color and wavelength. Wavelength is a real, physical phenomenon; color is the brain’s approximate, slightly incorrect model of it. In the attention schema theory, attention is the physical phenomenon and awareness is the brain’s approximate, slightly incorrect model of it. In neuroscience, attention is a process of enhancing some signals at the expense of others. It’s a way of focusing resources. Attention: a real, mechanistic phenomenon that can be programmed into a computer chip. Awareness: a cartoonish reconstruction of attention that is as physically inaccurate as the brain’s internal model of color.

In this theory, awareness is not an illusion. It’s a caricature. Something — attention — really does exist, and awareness is a distorted accounting of it.

One reason that the brain needs an approximate model of attention is that to be able to control something efficiently, a system needs at least a rough model of the thing to be controlled. Another reason is that to predict the behavior of other creatures, the brain needs to model their brain states, including their attention. This theory pulls together evidence from social neuroscience, attention research, control theory and elsewhere.

Almost all other theories of consciousness are rooted in our intuitions about awareness. Like the intuition that white light is pure [when it is in fact a spectrum of all colors], our intuitions about awareness come from information computed deep in the brain. But the brain computes models that are caricatures of real things. And as with color, so with consciousness: It’s best to be skeptical of intuition.

The letters in response to the above take Graziano to task for "explaining consciousness away" when what he is trying to do is not discount our experience of awareness or selfhood, but make a description of the physical process that actually constitutes them, a description that is counter-intuitive, but I think more likely to be correct than anything I've see thus far.

Antidepressant and nerve growth stimulating effects of exercise - a mechanism.

Yau et al. find that a hormone secreted by fat cells during exercise alleviates depression-like behaviors in mice and boosts new nerve cell synthesis in the hippocampus. The hormone, or compounds that enhance its effectiveness, are potential antidepressant drugs. I copy below their significance section and the abstract with some of the chemical details.

Significance

This study unmasks a previously unidentified functional role of adiponectin (a hormone secreted by adipocytes) in modulating hippocampal neurogenesis and alleviating depression-like behaviors. To our knowledge, this is the first report showing that adiponectin may be an essential factor that mediates the antidepressant effects of physical exercise on the brain by adiponectin receptor 1-mediated activation of AMP-activated protein kinase. Our results reveal a possible mechanism by which exercise increases hippocampal neurogenesis and also suggest a promising therapeutic treatment for depression.

Abstract

Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, anti-inflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood–brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression.

Aging: sit less and shape up your attitude

I'm continuing to clean out my queue of aging articles that have been languishing as potential posts...

Reynolds points to two studies. In one, Swedish researchers showed that a group of 68 year old couch potatoes who spent less time sitting and more time in an exercise program had longer telomere caps at the end of their DNA (the caps shorten with aging). The interesting finding was that this was related not to the exercise, but to simply not sitting down as much. A second article reviewed a large database of Canadian adults to find that longer amounts to time spent standing correlated with lower mortality rates.

Span does a review (linking to original articles) of work showing, for example that people who hold more positive views towards aging live 7.5 years longer on average than those who think negatively about aging, and recover more quickly from disabilities. Age stereotypes have a powerful effect, people become what they think. Thinking of older age as a time when one can feel capable, active, full of life, a time of wisdom, self-realization and satisfaction, is rather different from imagining it to be a time of becoming useless, helpless or devalued. A growing body of research shows that people with the latter attitudes are less likely to seek preventive medical care and die earlier, and more likely to suffer memory loss and poor physical functioning.

One interesting bit of work shows that subliminal intervention (flashing positive about aging on a screen so briefly that the brain registers them but they are not perceived) significantly strengthened positive age stereotypes and self-perceptions of age. The abstract:

Negative age stereotypes that older individuals assimilate from their culture predict detrimental outcomes, including worse physical function. We examined, for the first time, whether positive age stereotypes, presented subliminally across multiple sessions in the community, would lead to improved outcomes. Each of 100 older individuals (age = 61–99 years, M = 81) was randomly assigned to an implicit-positive-age-stereotype-intervention group, an explicit-positive-age-stereotype-intervention group, a combined implicit- and explicit-positive-age-stereotype-intervention group, or a control group. Interventions occurred at four 1-week intervals. The implicit intervention strengthened positive age stereotypes, which strengthened positive self-perceptions of aging, which, in turn, improved physical function. The improvement in these outcomes continued for 3 weeks after the last intervention session. Further, negative age stereotypes and negative self-perceptions of aging were weakened. For all outcomes, the implicit intervention’s impact was greater than the explicit intervention’s impact. The physical-function effect of the implicit intervention surpassed a previous study’s 6-month-exercise-intervention’s effect with participants of similar ages. The current study’s findings demonstrate the potential of directing implicit processes toward physical-function enhancement over time.

Mind wandering that makes effort more efficient.

MindBlog has done numerous posts on our brains' default mode and executive control networks, with the idea usually being that activating the default network or mind wandering during an attention demanding task can impair performance. Spreng et al. now do a study showing that it also can improve performance if the mind wandering is congruent with the task itself. In this case the default and executive control networks appear to relate external goals and internal meaning:

Substantial neuroimaging evidence suggests that spontaneous engagement of the default network impairs performance on tasks requiring executive control. We investigated whether this impairment depends on the congruence between executive control demands and internal mentation. We hypothesized that activation of the default network might enhance performance on an executive control task if control processes engage long-term memory representations that are supported by the default network. Using fMRI, we scanned 36 healthy young adult humans on a novel two-back task requiring working memory for famous and anonymous faces. In this task, participants (1) matched anonymous faces interleaved with anonymous face, (2) matched anonymous faces interleaved with a famous face, or (3) matched a famous faces interleaved with an anonymous face. As predicted, we observed a facilitation effect when matching famous faces, compared with anonymous faces. We also observed greater activation of the default network during these famous face-matching trials. The results suggest that activation of the default network can contribute to task performance during an externally directed executive control task. Our findings provide evidence that successful activation of the default network in a contextually relevant manner facilitates goal-directed cognition.

What is literature good for?

I pass on this fetching clutch of points on the usefulness of reading literature (rather than brief tweets, and blog posts like this) from Alain de Botton's School of Life, via Maria Popova's "Brain Pickings" (both are sites well worth checking out). Literature:

SAVES YOU TIME

It looks like it's wasting time, but literature is actually the ultimate time-saver – because it gives us access to a range of emotions and events that it would take you years, decades, millennia to try to experience directly. Literature is the greatest reality simulator – a machine that puts you through infinitely more situations than you can ever directly witness.

MAKES YOU NICER

Literature performs the basic magic of what things look like though someone else's point of view; it allows us to consider the consequences of our actions on others in a way we otherwise wouldn't; and it shows us examples of kindly, generous, sympathetic people.

Literature deeply stands opposed to the dominant value system – the one that rewards money and power. Writers are on the other side – they make us sympathetic to ideas and feelings that are of deep importance but can't afford airtime in a commercialized, status-conscious, and cynical world.

IS A CURE FOR LONELINESS

We're weirder than we like to admit. We often can't say what's really on our minds. But in books we find descriptions of who we genuinely are and what events, described with an honesty quite different from what ordinary conversation allows for. In the best books, it's as if the writer knows us better than we know ourselves – they find the words to describe the fragile, weird, special experiences of our inner lives... Writers open our hearts and minds, and give us maps to our own selves, so that we can travel in them more reliably and with less of a feeling of paranoia or persecution...

PREPARES YOU FOR FAILURE

All of our lives, one of our greatest fears is of failure, of messing up, of becoming, as the tabloids put it, "a loser." Every day, the media takes us into stories of failure. Interestingly, a lot of literature is also about failure – in one way or another, a great many novels, plays, poems are about people who messed up... Great books don't judge as harshly or as one-dimensionally as the media...

Why do we like sad music?

I have earlier noted work on how, in both Eastern and Western music and vocalization, major modes are associated with positive emotions, and minor modes with darker emotions, and I've also mentioned Kawakami's work on how music can be perceived as sad, but yet be accompanied by the experience of positive emotions. Now Taruffi and Koelsch have done an online survey with both Western and Eastern participants (N = 772) that probes the rewarding aspects of music-evoked sadness. Their results suggest four different rewards of music-evoked sadness: reward of imagination, emotion regulation, empathy, and no “real-life” implications:

This study explores listeners’ experience of music-evoked sadness. Sadness is typically assumed to be undesirable and is therefore usually avoided in everyday life. Yet the question remains: Why do people seek and appreciate sadness in music? We present findings from an online survey with both Western and Eastern participants (N = 772). The survey investigates the rewarding aspects of music-evoked sadness, as well as the relative contribution of listener characteristics and situational factors to the appreciation of sad music. The survey also examines the different principles through which sadness is evoked by music, and their interaction with personality traits. Results show 4 different rewards of music-evoked sadness: reward of imagination, emotion regulation, empathy, and no “real-life” implications. Moreover, appreciation of sad music follows a mood-congruent fashion and is greater among individuals with high empathy and low emotional stability. Surprisingly, nostalgia rather than sadness is the most frequent emotion evoked by sad music. Correspondingly, memory was rated as the most important principle through which sadness is evoked. Finally, the trait empathy contributes to the evocation of sadness via contagion, appraisal, and by engaging social functions. The present findings indicate that emotional responses to sad music are multifaceted, are modulated by empathy, and are linked with a multidimensional experience of pleasure. These results were corroborated by a follow-up survey on happy music, which indicated differences between the emotional experiences resulting from listening to sad versus happy music. This is the first comprehensive survey of music-evoked sadness, revealing that listening to sad music can lead to beneficial emotional effects such as regulation of negative emotion and mood as well as consolation. Such beneficial emotional effects constitute the prime motivations for engaging with sad music in everyday life.

Positive thinking can sabotage desired outcomes.

The point is a simple one - imagining success in attaining a goal can make one strive less diligently towards it. Gabriele Oettingen has summarized her research over the past 15-20 years on how this plays out in different areas of endeavour, in a new book “Rethinking Positive Thinking: Inside the New Science of Motivation.” (I know this because she has done what now seems imperative for for getting one's ideas to briefly rise about the noise level facing readers in the general public: she has done a marketing piece in The New York Times - another example of this is Graziano's piece on his theory of consciousness also in the "Gray Matter" NYTimes series - to which I devoted an extended MindBlog post ).

Oettingen's NYTimes piece gives links to her studies showing that women in a weight reduction program who imaged successful completion of the program lost fewer pounds than those who imagined themselves less positively, and that students instructed to imagine a great week ahead report feeling less energized and accomplish less than students instructed to write down any thoughts about the coming week. She then notes experiments on what she suggests as the most effective strategy, combining positive thinking with realism by mentally contrasting them.

A mechanism underlying intractable political conflicts.

Waytz et al. do an interesting piece of work directly relevant to the polarized mid-term election that just occurred, finding a cognitive bias that drives conflict between American Democrats and Republicans and ethnoreligious conflict between Israelis and Palestinians. (Note, "ingroup love" refers to compassion and empathy toward one's own group, and "outgroup hate" refers to dislike and animosity toward the opposing group.) I pass on both the significance statement and the abstract:

Significance

Political conflict between American Democrats and Republicans and ethnoreligious conflict between Israelis and Palestinians seem intractable, despite the availability of reasonable compromise solutions in both cases. This research demonstrates a fundamental cognitive bias driving such conflict intractability: Adversaries attribute their ingroup’s actions to ingroup love more than outgroup hate and attribute their outgroup’s actions to outgroup hate more than ingroup love. This biased attributional pattern increases beliefs and intentions associated with conflict intractability, including unwillingness to negotiate and unwillingness to vote for compromise solutions. In addition, offering financial incentives for accuracy in evaluating one’s outgroup mitigates this biased attributional pattern and its consequences. Understanding this bias and how to alleviate it can contribute to conflict resolution on a global scale.

Abstract

Five studies across cultures involving 661 American Democrats and Republicans, 995 Israelis, and 1,266 Palestinians provide previously unidentified evidence of a fundamental bias, what we term the “motive attribution asymmetry,” driving seemingly intractable human conflict. These studies show that in political and ethnoreligious intergroup conflict, adversaries tend to attribute their own group’s aggression to ingroup love more than outgroup hate and to attribute their outgroup’s aggression to outgroup hate more than ingroup love. Study 1 demonstrates that American Democrats and Republicans attribute their own party’s involvement in conflict to ingroup love more than outgroup hate but attribute the opposing party’s involvement to outgroup hate more than ingroup love. Studies 2 and 3 demonstrate this biased attributional pattern for Israelis and Palestinians evaluating their own group and the opposing group’s involvement in the current regional conflict. Study 4 demonstrates in an Israeli population that this bias increases beliefs and intentions associated with conflict intractability toward Palestinians. Finally, study 5 demonstrates, in the context of American political conflict, that offering Democrats and Republicans financial incentives for accuracy in evaluating the opposing party can mitigate this bias and its consequences. Although people find it difficult to explain their adversaries’ actions in terms of love and affiliation, we suggest that recognizing this attributional bias and how to reduce it can contribute to reducing human conflict on a global scale.

Aging - predictors of cognitive abilities.

The Oct. 31 issue of Science Magazine has a special section of articles on the aging brain. I point in particular to Underwood's article, "Starting young", which describes the followup on a Scottish national intelligence test performed on every 11 year old in the country in 1932 and 1947. The finding was that an individual's level of intelligence at age 11 is the most powerful predictor of late-life cognitive ability — not diet, social engagement, or any other virtuous activity. Scores at age 11 predicted about 50% of the variance in the IQs at age 77 in a cohort of individuals living in the Lothian region near Edinburgh (1641 of the original 5000 people tested were assessed.) Note the bottom line indicated in the final clip below:

By having an intelligence measure from even earlier in life, the Lothian studies are helping distinguish glitter from gold in the vast literature on factors correlated with cognition. A good recent example is Deary's analysis of the potential benefits of drinking, Thompson says. A smattering of correlational studies suggest that drinking small amounts of wine has positive effects on cognition late in life—indeed, Deary initially found a similar result when he first looked for a relationship between alcohol consumption and cognitive performance in the Lothian cohort. When he accounted for the participants' IQ scores on the Scottish Mental Survey, however, the perceived benefit dissolved. Rather than gaining cognitive benefit from drinking wine when they were older, “people who drank more were already likely to be smart,” Deary says.

The Lothian cohort has similarly challenged other reported influences on cognition, such as diet, body mass index, and caffeine consumption. None of those factors seems to have any effect on cognitive skills in the Lothian cohort when childhood intelligence is accounted for, Deary says. Even the effects of social and intellectual activity disappeared when he took into account how bright children were at age 11, possibly because those children are more likely to end up being socially and intellectually engaged.

And a final clip:

...the growing body of data from the Lothian Birth Cohort studies and other aging research supports a theory that some describe irreverently, and a little brutally, as the “water tank hypothesis”: The better put-together your brain is early on, thanks to good genes and, to some extent, a favorable early life environment, the more cognitive reserves you have to lose to neurodegeneration. In other words, Martin says, “the more you start out with in the tank, the longer it takes to draw down.”

Liberals and conservatives have different smell preferences.

A post faintly appropriate to this election day that is deciding the outcomes of very polarized contests of liberals and conservatives...Arthur Brooks points to an interesting article by McDermott et al. suggesting that our human mate preference - known to influenced more by political attitudes more than any other social, behavioral, or physical trait except religion - may be reflected in our smell preferences! Some clips from McDermott et al.:

Here we integrate extant studies of attraction, ideology, and olfaction and explore the possibility that assortation on political attitudes may result, in part, from greater attraction to the scent of those with shared ideology. We conduct a study in which individuals evaluated the body odor of unknown others, observing that individuals are more attracted to their ideological concomitants.

We conducted a study where participants rated the attractiveness of the body odor of unknown strong liberals and strong conservatives, hereafter referred to as “target” subjects; all “evaluator” subjects remained blind to the ideology of the target samples. One hundred forty-six participants between 18–40 years old were drawn from a large city in the northeast United States... Twenty-one target participants were selected for their high scores on opposite ends of the political spectrum (10 liberals and 11 conservatives) and provided body odor samples...Eleven of these target participants were female and 10 were male. Ideology was measured using the standard 7-point (strongly liberal to strongly conservative) American National Election Studies (ANES) self-report measure.

... individuals find the smell of those who are more ideologically similar to themselves more attractive than those endorsing opposing ideologies; recall that participants never saw the individuals whose smells they were evaluating, and the order of target subjects was randomized for each evaluator. Thus, the recognition of political alignment occurred through the medium of attraction, not recognition.

Some insight on the potency of odor might be gained from the participants’ comments and physical reactions during the study... a participant asked the experimenter if she could take one of the vials home with her because she thought it was “the best perfume I ever smelled”; the vial was from a male who shared an ideology similar to the evaluator. She was preceded by another respondent with an ideology opposite to the person who provided the exact same sample; this participant reported that that vial had “gone rancid” and suggested it needed to be replaced. In this way, different participants experienced the exact same stimulus in radically different ways only moments apart.