Killing old cells to stay young.

I want to pass on one of Science Magazine's choices for the top ten scientific breakthroughs of the year.

Pricey plastic surgery won't stop you from getting old. Nor will dietary supplements, testosterone injections, or those wrinkle creams that imply they'll make you look 21 again. But this year, researchers demonstrated one way to postpone some ravages of time—at least in mice. When they selectively weeded out rundown cells, the animals lived longer and remained healthier as they aged.

The infirm cells the scientists targeted had undergone a partial shutdown known as senescence, in which they lose the ability to divide. Researchers think senescence may prevent worn-out, cancer-prone cells from initiating tumors, but it may also promote aging. As we grow older, more and more cells stop reproducing, potentially robbing our tissues of the ability to replace dead or injured cells. Senescent cells also discharge molecules that can cause problems such as abnormal cell growth and inflammation.

The first study showing that eliminating senescent cells can produce health and longevity benefits, at least in middle-aged mice, came out in February. Deterioration of the animals' hearts and kidneys slowed, and they didn't sprout tumors until later in their lives. Some age-related declines, such as in memory and muscle coordination, didn't abate. Nonetheless, the rodents outlived their contemporaries by more than 20%.

In October, the same research team took aim at senescent cells from the immune system that amass in artery-clogging plaques and may drive their formation. Removing these cells from mice that are prone to atherosclerosis reduced the amount of fatty buildup in the animals' arteries by 60%, even though the rodents gorged on fat-laden food.

The multibillion-dollar question: Will taking out senescent cells help humans stay young longer? Both studies used genetically modified mice that clear away their senescent cells in response to a particular compound—a technique that isn't feasible in humans. But researchers have created several so-called senolytic drugs that slay senescent cells without genetic tinkering. Next year, scientists will launch the first clinical trial of one of those drugs in people who have arthritis.

References:

D. J. Baker et al., “Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders,” Nature 479, 232 (2 November 2016)

D. J. Baker et al., “Naturally occurring p16Ink4a-positive cells shorten healthy lifespan,,” Nature 530, 184 (11 February 2016)

B. G. Childs et al., “Senescent intimal foam cells are deleterious at all stages of atherosclerosis,” News from Science 354, 472 (28 October 2016)

Creative versus destructive chaos in Trump-land. Is there a ray of hope?

I am a member of the professional intelligentsia bubble still feeling post-traumatic stress from the presidential election. I grasp at any small reassurances that the sky may not in fact be falling, and so point to this piece by David Ignatius noting the current influence of Robert Gates, who has worked in senior national security positions for the past five presidents. Some clips:

At the top of Gates’s to-do list is striking the right balance between improving relations with Russia and appearing too cooperative with a belligerent President Vladimir Putin...“I think the challenge for any new administration would have been how to thread the needle — between stopping the downward spiral in U.S.-Russian relations, which had real dangers, and pushing back on Putin’s aggressiveness and general thuggery,” Gates said.

Gates has shared the role of informal counselor to the Trump transition team with two other veterans of the Bush administration, former secretary of state Condoleezza Rice, who talks regularly with Vice President-elect Mike Pence, and former national security adviser Stephen Hadley. The three have a consulting firm, RiceHadleyGates, which has proposed candidates for Cabinet and sub-Cabinet jobs, including Rex Tillerson and retired Marine Gen. James N. Mattis, the choices for State and Defense, respectively.

Gates, Hadley and Rice have also talked with foreign governments that are puzzled about how to approach Trump. In an interview this week, Hadley summarized his basic advice:..“We’ve never had a populist movement or political insurgency quite like this — that actually captured the White House. That means there will be more discontinuities in our foreign policy. I’m telling people: ‘Give us some space here and have some strategic patience. And don’t overreact — even to Trump’s tweets.’ ”

One issue that worries Gates is the multiplicity of people surrounding Trump in the White House, seeking to influence an undisciplined chief executive. “What happens when someone tries to get in to see the president with a proposal or initiative and is rebuffed by one gatekeeper — and simply goes through another door? It’s a formula for a disjointed process.”

“There will be a rough break-in period,” Gates predicted. Part of the challenge is that Trump believes his success stems from his freewheeling, undisciplined style, and personal messaging through Twitter — which makes him resist limits.

Artificial intelligence ups its game

I pass on this description by John Bohannon in Science Magazine of a recent triumph of A.I.:

This year, artificial intelligence (AI) passed a significant milestone when a computer program called AlphaGo beat the world's No. 2 Go player in a five-game match. It's not the first time that AI has surpassed human mastery of a game. After all, it was 20 years ago that IBM's Deep Blue first beat Garry Kasparov in a game of chess, toppling the world champion the following year in a six-game match. But that is where the similarity ends.

The rules of Go are more straightforward than those of chess: You simply place identical stones on a grid, capturing territory by surrounding your opponent's positions. But that simplicity and openness result in an explosion in the number of possible moves for a player to consider—far more than there are atoms in the known universe. That makes it impossible for AI to beat Go masters with an approach like that used by Deep Blue, which relies on handcoded strategies from chess experts to evaluate each possible move.

Instead, AlphaGo, designed by the London-based Google subsidiary DeepMind, studied hundreds of thousands of online Go games played between humans, using those sequences of moves as data for a machine-learning algorithm. Then AlphaGo played against itself—or, rather, slightly different versions of itself—over and over, finetuning its strategies with a technique called deep reinforcement learning. The final result is AI that wins not just with brute-force calculation, but with something that looks strikingly like human intuition.

Most of the things we want AI to master involve a seemingly unmanageable number of possible decisions—walking a robot safely through a crowded room, routing driverless cars, making small talk with passengers. Because hard-coded rules fail for such tasks, AlphaGo's triumph shows just how powerful deep reinforcement learning can be.

References
D. Mackenzie, “Update: Why this week’s man-versus-Go match doesn’t matter (and what does,” News from Science (15 March 2016)
D. Silver, “Mastering the game of Go with deep neural networks and tree search,” Nature 589, 224 (28 January 2016)

Making the world nicer is a tough slog - two organizations trying.

The end of 2016 approaches, I am thinking about charitable donations I have made or might make in this angry and uncertain time of huge political changes. Angry voters in Europe and America are turning back the clock, and the paradigm of America may be irreversibly changing. A collective trauma is being generated by the severing of ties that previously have bound Americans together. How might we try to be more kind, gentle, and understanding with each other?

I've decided to make year end contributions to two university associated organizations trying to promote the greater good through research, teaching, and understanding - trying to find ways to spread and promote the virtues of altruism, compassion, gratitude, empathy, forgiveness, and mindfulness. One is the Greater Good Science Center at the University of California, Berkeley, founded by Dacher Keltner. The other is the Center for Healthy Minds at the University of Wisconsin, Madison, led by my former colleague Richard Davidson. I would encourage MindBlog readers to check out their websites, and consider donations to both.

Our automated jobless future.

Elizabeth Kolbert offers an interesting review of ideas in several recent books dealing with our automated future. How long will it be before you lose your job to a robot? Here are a few clips:

Imagine a matrix with two axes, manual versus cognitive and routine versus nonroutine. Jobs can then be arranged into four boxes: manual routine, manual nonroutine, and so on…Jobs on an assembly line fall into the manual-routine box, jobs in home health care into the manual-nonroutine box. Keeping track of inventory is in the cognitive-routine box; dreaming up an ad campaign is cognitive nonroutine.

The highest-paid jobs are clustered in the last box; managing a hedge fund, litigating a bankruptcy, and producing a TV show are all cognitive and nonroutine. Manual, nonroutine jobs, meanwhile, tend to be among the lowest paid—emptying bedpans, bussing tables, cleaning hotel rooms (and folding towels). Routine jobs on the factory floor or in payroll or accounting departments tend to fall in between. And it’s these middle-class jobs that robots have the easiest time laying their grippers on.

How much technology has contributed to the widening income gap in the U.S. is a matter of debate; some economists treat it as just one factor, others treat it as the determining factor. In either case, the trend line is ominous. Facebook is worth two hundred and seventy billion dollars and employs just thirteen thousand people. In 2014, Facebook acquired Whatsapp for twenty-two billion dollars. At that point, the messaging firm had a grand total of fifty-five employees. When a twenty-two-billion-dollar company can fit its entire workforce into a Greyhound bus, the concept of surplus labor would seem to have run its course.

Martin Ford (author of “Rise of the Robots: Technology and the Threat of a Jobless Future”) worries that we are headed toward an era of “techno-feudalism,” He imagines a plutocracy shut away “in gated communities or in elite cities, perhaps guarded by autonomous military robots and drones.” Under the old feudalism, the peasants were exploited; under the new arrangement, they’ll merely be superfluous. The best we can hope for, he suggests, is a collective form of semi-retirement. He recommends a guaranteed basic income for all, to be paid for with new taxes, levelled, at least in part, on the new gazillionaires.

To one degree or another, just about everyone writing on the topic shares this view. Jerry Kaplan proposes that the federal government create a 401(k)-like account for every ten-year-old in the U.S. Those who ultimately do find jobs could contribute some of their earnings to the accounts; those who don’t could perform volunteer work in return for government contributions.

...if it’s unrealistic to suppose that smart machines can be stopped, it’s probably just as unrealistic to imagine that smart policies will follow. Which brings us ... to Trump. The other day, during his “victory lap” through the Midwest, the President-elect vowed to “usher in a new Industrial Revolution,” apparently unaware that such a revolution is already under way, and that this is precisely the problem. The pain of dislocation he spoke to during the campaign is genuine; the solutions he offers are not.

A stark graphic - the income gap continues to widen.

The NYTimes piece by Patricia Cohen and graphic summaries by Ashkenas are worth reading. The top 1% and the bottom 50% have swapped their relative shares of the national income. Forty years ago, the top 1 percent of earners took home 10.5 percent of the total national income, and the bottom half earned 20 percent of it. By 2014, those percentages effectively flipped, with the top 1 percent earning a 20 percent share and the bottom half dropping to 12.5 percent.

Our Arthropod housemates.

Now I know more about what is in the haze of particles I see illuminated by the horizontal rays of the rising sun flowing through my Fort Lauderdale condo in early morning.  I pass on, under the "random curious stuff" MindBlog category,  an accounting by Madden et al. that shows the ubiquity of insects detected in settled dust samples collected from inside homes. They used a DNA-based method for investigating the arthropod diversity in homes via high-throughput marker gene sequencing of home dust. Settled dust samples were collected by citizen scientists from both inside and outside more than 700 homes across the United States, yielding the first continental-scale estimates of arthropod diversity associated with our residences. Here is a graphic (click to enlarge), in which (A) shows the Genera detected, (B) shows orders detected in at least 5% of homes. The Y-axes indicate the percentage of homes (of 651 homes with arthropods detected) where those arthropods were detected.

Reducing future fears by suppressing episodic simulation in the brain.

Benoit et al. offer some findings relevant to understanding the heightened anxiety many are feeling in the Age of Trump.

An edited summary that starts the discussion section of their paper:

Recurrently imagining dreaded future situations potentiates fears and can even support the development and maintenance of anxiety disorders. We tested the hypothesis that such simulations can be suppressed with the opposite effect of down-regulating apprehensiveness. Our data indicate that future suppression is based on a brain mechanism that is remarkably similar to a system implicated in the voluntary suppression of past experiences. This mechanism recruits right dorsolateral prefrontal cortex, which originates an inhibitory signal that down-regulates activation in brain regions supporting both retrieval and episode-construction processes. Paralleling the suppression of recently acquired memories, the regions targeted by future suppression included the hippocampus, a structure that is fundamental for the retrieval of past episodes and the construction of coherent future and fictitious events. Critically, the suppression of recurring fears of the future differs from suppressing past events in that it also involved modulating the vmPFC (ventromedial prefrontal cortex). The mPFC fosters the integration of overlapping memories into a common representation.

A clip describing their procedure:

To examine future suppression, we adapted the “Think/No-Think” procedure, used to study the suppression of past events, to create the new “Imagine/No-Imagine” paradigm. The procedure first asked participants to describe their fears. Importantly, they only provided recurrent future fears—that is, those that they had already worried might happen before entering the experiment. Participants then gave one key detail for each fear that was typical to their recurring imaginings of it. (These typical event details served as a dependent measure; see below.) Afterward, they entered the critical Imagine/No-Imagine phase, which was composed of trials that presented reminders to these fears. For some trials, participants were asked to imagine the feared event as vividly as possible in response to the reminder (Imagine condition); for others, participants were asked to suppress their imagining of the event, upon seeing the reminder (Suppress condition). (A third of the originally provided episodes, the Baseline items, were set aside and were not cued during this phase.) Over the course of the Imagine/No-Imagine phase, participants either imagined or suppressed a feared event 12 times. Following this phase, we gave participants each reminder again and asked them to recall the typical feature of its corresponding fear. Once all typical details were tested, participants were then asked to freely imagine each episode aloud in detail for 2 min. Finally, we assessed the impact of suppression on participants’ apprehensiveness toward these future events.

Here are the significance and abstract section of their paper:

Significance 

Humans possess the remarkable ability to recombine details of divergent memories into imaginings of future events. Such imaginings are useful, for example, because they foster planning and motivate farsighted decisions. Importantly, recurrently imagining feared situations can also undermine our well-being and may even contribute to the development of anxiety. Here, we demonstrate that fearful imaginings about the future can be inhibited by neural mechanisms that help to suppress the past. Importantly, suppression reduces later apprehensiveness about the feared events, a benefit that was diminished in individuals with greater trait anxiety. This pattern suggests that the observed inhibition mechanism serves to control people’s future fears and its disruption may foster psychological disorders characterized by intrusive prospective thoughts. 

Abstract 

Imagining future events conveys adaptive benefits, yet recurrent simulations of feared situations may help to maintain anxiety. In two studies, we tested the hypothesis that people can attenuate future fears by suppressing anticipatory simulations of dreaded events. Participants repeatedly imagined upsetting episodes that they feared might happen to them and suppressed imaginings of other such events. Suppressing imagination engaged the right dorsolateral prefrontal cortex, which modulated activation in the hippocampus and in the ventromedial prefrontal cortex (vmPFC). Consistent with the role of the vmPFC in providing access to details that are typical for an event, stronger inhibition of this region was associated with greater forgetting of such details. Suppression further hindered participants’ ability to later freely envision suppressed episodes. Critically, it also reduced feelings of apprehensiveness about the feared scenario, and individuals who were particularly successful at down-regulating fears were also less trait-anxious. Attenuating apprehensiveness by suppressing simulations of feared events may thus be an effective coping strategy, suggesting that a deficiency in this mechanism could contribute to the development of anxiety.

Can evolution have a 'higher purpose'?

I want to point to this essay by Robert Wright, author of "The Moral Animal," who makes the point that arguments that life on earth may have some larger purpose do not necessarily have to depart from a scientific worldview, invoke supernatural beings, or depart from the model of evolution by natural selection. Among these arguments are:

... “simulation” scenarios, which hold that our seemingly tangible world is actually a kind of projection emanating from some sort of mind-blowingly powerful computer; and the history of our universe, including evolution on this planet, is the unfolding of a computer algorithm...When an argument for higher purpose is put this way — that is, when it doesn’t involve the phrase “higher purpose” and, further, is cast more as a technological scenario than a metaphysical one — it is considered intellectually respectable. I don’t mean there aren’t plenty of people who dismiss it. I’m talking about how people dismiss it. [Neil deGrasse Tyson and Elon Musk find this view plausible.]

Wright quotes from a conversation with William Hamilton, who says:

There’s one theory of the universe that I rather like — I accept it in an almost joking spirit — and that is that Planet Earth in our solar system is a kind of zoo for extraterrestrial beings who dwell out there somewhere. And this is the best, the most interesting experiment they could set up: to set up the evolution on Planet Earth going in such a way that it would produce these really interesting characters — humans who go around doing things — and they watch their experiment, interfering hardly at all so that almost everything we do comes out according to the laws of nature. But every now and then they see something which doesn’t look quite right — this zoo is going to kill itself off if they let you do this or that.” So, he continued, these extraterrestrials “insert a finger and just change some little thing. And maybe those are the miracles which the religious people like to so emphasize.” He reiterated: “I put it forward in an almost joking spirit. But I think it

Another scenario:

...emerges from one version of physicist Lee Smolin’s theory of “cosmological natural selection.” Smolin thinks our universe may itself be a product of a kind of evolution: maybe universes can replicate themselves via black holes, so over time — over a lot of time — you get universes whose physical laws are more and more conducive to replication. (So that’s why our universe is so good at black-hole making!) In some variants of Smolin’s theory — such as those developed by the late cosmologist Edward Harrison and the mathematician Louis Crane — intelligent beings can play a role in this replication once their technology reaches a point where they can produce black holes. So through cosmological natural selection you’d get universes whose physical properties were more and more conducive to the evolution of intelligent life. This might explain the much-discussed observation that the physical constants of this universe seem “fine-tuned” to permit the emergence of life.

Wilson's ending points:

I think discussion of higher purpose should be respectable even in a scientific age. I don’t mean I buy the simulation scenario in particular, or the space alien scenario, or the cosmological natural selection scenario. But I do think there’s reason to suspect that there’s some point to this exercise we Earthlings are engaged in, some purpose imbued by something — and that, even if identifying that something is for now hopeless, there are grounds for speculating about what the point of the exercise is.

I won’t elaborate much on this, since I’ve done that elsewhere, arguing that higher purpose can be framed as a hypothesis, and that evidence for or against the hypothesis can be marshaled. But I will say that the evidence I see for purpose includes not just the direction of biological evolution, but the direction of technological evolution and of the broader social and cultural evolution it drives — the evolution that has carried us from hunter-gatherer bands to the brink of a cohesive global community. And if the purpose involves sustaining this direction — becoming a true global community — then it would seem to include moral progress. In particular, our purpose would involve transcending the psychology of tribalism that can otherwise divide people along ethnic, national, religious and ideological lines. Which would mean — in light of recent political and social developments in the United States and abroad — that our work is cut out for us.

Political tribes, and the psychology of liberals and conservatives.

I am using this post to pass on to MindBlog readers some background material I just sent out to members of a senior current topics discussion group that we have recently formed in Fort Lauderdale, and named "The Round Table." The session on Monday Dec. 19 is on the topic indicated by the title of this post.

Where do tribes come from? Evolutionary origins   

http://mindblog.dericbownds.net/2014/12/eo-wilson-and-meaning-of-human-existence.html

http://mindblog.dericbownds.net/2011/03/beginning-and-middle-of-human-history.html

What is essential human nature? Where do religion and morality come from?  How do  religious and non-religious people differ?  

http://www.moralfoundations.org/

http://mindblog.dericbownds.net/2007/02/human-nature-redux_20.html

http://mindblog.dericbownds.net/2007/10/moral-universals.html

http://mindblog.dericbownds.net/2014/08/origins-of-good-and-evil-in-human-babies.html

http://mindblog.dericbownds.net/2015/09/birth-of-moralizing-gods.htm

http://mindblog.dericbownds.net/2016/02/moralistic-gods-enhance-sociality.html

http://mindblog.dericbownds.net/2008/10/evolution-of-religious-prosociality.html

http://mindblog.dericbownds.net/2014/09/morality-how-theists-and-non-theists.html

What dynamics regulate in-group and out-group interactions and conflicts?

http://www.nytimes.com/2016/12/09/opinion/sunday/the-roots-of-implicit-bias.html

http://mindblog.dericbownds.net/2014/11/a-mechanism-underlying-intractable.html

http://mindblog.dericbownds.net/2012/05/blog-post.html  brain correlates of whether we help someone suffering

http://mindblog.dericbownds.net/2014/09/norm-enforcement-is-biased-from-its.html

What kinds of political tribes do people belong to today?

http://mindblog.dericbownds.net/2016/07/the-myth-of-cosmopolitanism.html

http://mindblog.dericbownds.net/2011/02/bias-within-politics-of-professoriat.html

http://www.nytimes.com/2016/12/10/opinion/sunday/the-dangers-of-echo-chambers-on-campus.html

https://www.washingtonpost.com/opinions/democrats-need-to-focus-on-the-gut-not-the-head/2016/12/01/dfbe7782-b803-11e6-a677-b608fbb3aaf6_story.html

http://www.alternet.org/print/election-2016/rural-america-understanding-isnt-problem

https://www.amazon.com/Strangers-Their-Own-Land-Mourning/dp/1620972255/ref=as_li_ss_tl

http://mindblog.dericbownds.net/2016/01/our-strongest-prejudice-partisan.html

What distinguishes liberals and conservatives?

http://mindblog.dericbownds.net/2009/12/more-on-psychology-of-liberals-and.html

http://mindblog.dericbownds.net/2008/10/political-attitudes-vary-with.html

http://mindblog.dericbownds.net/2009/06/liberals-and-conservatives-feel.html

http://mindblog.dericbownds.net/2015/12/negative-evaluation-of.html

http://mindblog.dericbownds.net/2013/02/red-brain-blue-brain.html

http://mindblog.dericbownds.net/2008/06/why-are-conservatives-happier-than.html

How do people sustain their tribal identities, what psychological shortcuts or errors help?

http://mindblog.dericbownds.net/2010/08/metacognitive-deficits-in-public.html

http://mindblog.dericbownds.net/2016/04/a-succinct-list-of-some-of-our-common.html

http://www.huffingtonpost.com/dr-travis-bradberry/13-cognitive-biases-that_b_13355298.html

http://mindblog.dericbownds.net/2008/06/seeing-ourselves-seeing-others-built-in.html

http://mindblog.dericbownds.net/2015/02/the-neuroscience-of-motivated-cognition.html

How can tribal animosities and conflicts be ameliorated?

http://www.nytimes.com/2016/12/10/opinion/sunday/im-prejudiced-he-said-then-we-kept-talking.html

http://mindblog.dericbownds.net/2016/06/confronting-prejudiced-brain.html

http://mindblog.dericbownds.net/2016/11/how-to-get-beyond-our-tribal-politics.html

http://mindblog.dericbownds.net/2010/04/internet-enhancing-not-diminishing.html

http://mindblog.dericbownds.net/2016/05/the-key-to-political-persuasion.html

http://mindblog.dericbownds.net/2013/05/the-limits-of-empathy.html

http://mindblog.dericbownds.net/2016/04/how-to-change-prejudicefor-real-this.html

http://mindblog.dericbownds.net/2016/01/how-learning-shapes-empathic-brain.html

Bad things that happen to annoyingly happy people...

There is abundant evidence that being or appearing to be happy confers lots of advantages in life, both in personal health, relationships and in the workplace. On the down side, however, Ana Swanson points to work by Barasch et al. showing that very happy people are more likely to get ripped off:

Highlights

• We examine how the magnitude of expressed happiness influences social perception. 

• Very happy people are perceived as more naïve than moderately happy individuals. 

• Very happy people are believed to shelter themselves from negative information. 

• Very happy people are exploited in conflicts of interest and distributive negotiations. 

• We challenge prior work by identifying a disadvantage of expressing happiness.

Abstract

Across six studies, we examine how the magnitude of expressed happiness influences social perception and interpersonal behavior. We find that happiness evokes different judgments when expressed at high levels than when expressed at moderate levels, and that these judgments influence opportunistic behavior. Specifically, people perceive very happy individuals to be more naïve than moderately happy individuals. These perceptions reflect the belief that very happy individuals shelter themselves from negative information about the world. As a result of these inferences, very happy people, relative to moderately happy people, are more likely to receive biased advice from advisors with a conflict of interest and are more likely to be chosen as negotiation partners when the opportunity for exploitation is salient. Our findings challenge existing assumptions in organizational behavior and psychology by identifying a significant disadvantage of expressing happiness, and underscore the importance of examining emotional expressions at different magnitudes. We call for future work to explore how the same emotion, experienced or expressed at different levels, influences judgment and behavior.

Why does time fly when you’re having fun? Dopamine neurons…

Soares et al. find by observing timing behavior in mice that dopaminergic neurons control temporal judgments on a time scale of seconds.

Our sense of time is far from constant. For instance, time flies when we are having fun, and it slows to a trickle when we are bored. Midbrain dopamine neurons have been implicated in variable time estimation. However, a direct link between signals carried by dopamine neurons and temporal judgments is lacking. We measured and manipulated the activity of dopamine neurons as mice judged the duration of time intervals. We found that pharmacogenetic suppression of dopamine neurons decreased behavioral sensitivity to time and that dopamine neurons encoded information about trial-to-trial variability in time estimates. Last, we found that transient activation or inhibition of dopamine neurons was sufficient to slow down or speed up time estimation, respectively. Dopamine neuron activity thus reflects and can directly control the judgment of time.

Feeling confident that you know? fMRI correlates of metacognitive accuracy.

The more confident you are, the less likely you are to be correct! From Molenberghs et al:

One important aspect of metacognition is the ability to accurately evaluate one’s performance. People vary widely in their metacognitive ability and in general are too confident when evaluating their performance. This often leads to poor decision making with potentially disastrous consequences. To further our understanding of the neural underpinnings of these processes, this fMRI study investigated inter-individual differences in metacognitive ability and effects of trial-by-trial variation in subjective feelings of confidence when making metacognitive assessments. Participants (N = 308) evaluated their performance in a high-level social and cognitive reasoning task. The results showed that higher metacognitive accuracy was associated with a decrease in activation in the anterior medial prefrontal cortex, an area previously linked to metacognition on perception and memory. Moreover, the feeling of confidence about one’s choices was associated with an increase of activation in reward, memory and motor related areas including bilateral striatum and hippocampus, while less confidence was associated with activation in areas linked with negative affect and uncertainty, including dorsomedial prefrontal and bilateral orbitofrontal cortex. This might indicate that positive affect is related to higher confidence thereby biasing metacognitive decisions towards overconfidence. In support, behavioural analyses revealed that increased confidence was associated with lower metacognitive accuracy.

Oxytocin, moral judgement, and male social synchony

I pass on two interesting pieces of work. First, Bernhard et al. show a correlation between different forms of the oxytocin receptor gene (which would influence neurotransmitters in multiple neural systems) and the kind of judgements made in complex moral situations. The technical abstract:

Moral judgments are produced through the coordinated interaction of multiple neural systems, each of which relies on a characteristic set of neurotransmitters. Genes that produce or regulate these neurotransmitters may have distinctive influences on moral judgment. Two studies examined potential genetic influences on moral judgment using dilemmas that reliably elicit competing automatic and controlled responses, generated by dissociable neural systems. Study 1 (N = 228) examined 49 common variants (SNPs) within 10 candidate genes and identified a nominal association between a polymorphism (rs237889) of the oxytocin receptor gene (OXTR) and variation in deontological vs utilitarian moral judgment (that is, judgments favoring individual rights vs the greater good). An association was likewise observed for rs1042615 of the arginine vasopressin receptor gene (AVPR1A). Study 2 (N = 322) aimed to replicate these findings using the aforementioned dilemmas as well as a new set of structurally similar medical dilemmas. Study 2 failed to replicate the association with AVPR1A, but replicated the OXTR finding using both the original and new dilemmas. Together, these findings suggest that moral judgment is influenced by variation in the oxytocin receptor gene and, more generally, that single genetic polymorphisms can have a detectable effect on complex decision processes.

Second, Mu et al. find that oxytocin enhances inter-brain synchrony during social coordination among adult men.

Recent brain imaging research has revealed oxytocin (OT) effects on an individual's brain activity during social interaction but tells little about whether and how OT modulates the coherence of inter-brain activity related to two individuals' coordination behavior. We developed a new real-time coordination game that required two individuals of a dyad to synchronize with a partner (coordination task) or with a computer (control task) by counting in mind rhythmically. Electroencephalography (EEG) was recorded simultaneously from a dyad to examine OT effects on inter-brain synchrony of neural activity during interpersonal coordination. Experiment 1 found that dyads showed smaller interpersonal time lags of counting and greater inter-brain synchrony of alpha-band neural oscillations during the coordination (vs control) task and these effects were reliably observed in female but not male dyads. Moreover, the increased alpha-band inter-brain synchrony predicted better interpersonal behavioral synchrony across all participants. Experiment 2, using a double blind, placebo-controlled between-subjects design, revealed that intranasal OT vs placebo administration in male dyads improved interpersonal behavioral synchrony in both the coordination and control tasks but specifically enhanced alpha-band inter-brain neural oscillations during the coordination task. Our findings provide first evidence that OT enhances inter-brain synchrony in male adults to facilitate social coordination.

Exhaustion is not unique to our overstimulated age.

Anna Katharina Schaffner, author of the book "Exhaustion: A History (2016), does a precis of its arguments,

Is ours the most exhausting age ever?..The argument goes that human energy levels have basically remained static throughout history, while the cognitive, emotional and temporal demands on the modern subject have increased so sharply that a chronic deficit of inner resources ensues...

..anxieties about exhaustion are not peculiar to our age. Those who imagine that life in the past was simpler, slower and better are wrong...exhaustion and its effects have preoccupied thinkers since classical antiquity...Over the centuries, medical, cultural, literary and biographical sources have cast exhaustion as a biochemical imbalance, a somatic ailment, a viral disease and a spiritual failing. It has been linked to loss, the alignment of the planets, a perverse desire for death, and social and economic disruption.

Exhaustion theories often address questions of responsibility, agency and willpower. In some accounts, exhaustion is represented as a form of weakness and lack of willpower, or even as a grave spiritual failing manifest in a bad mental attitude. For instance, medieval theories centred around the notion of acedia and sin, while recent neoliberal theories blame individuals for the management of their physical and mental wellbeing...Acedia literally denotes a ‘state of non-caring’, and has also been described as ‘weariness of the heart’. It primarily affected monks in late antiquity and the early medieval period, and was thought to be the result of a weak spiritual disposition and giving in to demonic temptations.

In Greek antiquity, a surplus of black bile that wreaks havoc with the bodily humoral economy was blamed. In the 19th century, it was a lack of nerve-power, and in the 20th and 21st centuries, a cognitive system chronically overstrained by external stimuli and stressors.

The 19th-century American physician George M Beard invented the neurasthenia diagnosis, a vaguely defined nervous exhaustion, and declared it to be a disease of civilisation, triggered by characteristics of the modern age, including ‘steam-power, the periodical press, the telegraph, the sciences, and the mental activity of women’...A century before Beard, the Scottish physician George Cheyne (1671-1743) already theorised the ‘English Malady’, manifest in a ‘Lowness of Spirits, lethargick Dullness, Melancholy and Moping’, and which he blamed on the fast-growing wealth of the sea-faring English nation and the adverse consequences of immoderation, laziness and luxury lifestyles. Burnout theorists of the 21st century are still making similar arguments about the damaging effects of new communication technologies and the neoliberal workplace.

...the continual production of theories about the loss of human energy is also an expression of timeless anxieties about death, ageing and the dangers of waning engagement. Theorising about exhaustion, and proposing cures and therapeutics for its effects, is a tactic to counteract the awareness of our helplessness in the face of our mortality. It is, in other words, a terror-management strategy designed to hold at bay our most existential fears – fears that are in no way peculiar to today.

The rage against the elites...

Roger Cohen, always a perceptive commentator, really nails it in his recent Op-Ed Piece "The Rage of 2016". His closing paragraphs:

Western democracies are in the midst of an upheaval they only dimly grasp. Virtual direct democracy through social media has outflanked representative democracy. The impact of the smartphone on the human psyche is as yet scarcely understood; its addictiveness is treacherous and can be the enemy of thought. Mr. Trump hijacked the Republican Party like a man borrowing a dinner jacket for an evening. His campaign moved through Twitter to the aroused masses; it had no use or need for conventional channels. The major political parties in Britain and the United States will have to prove their relevance again.

Democracies, it is clear, have not been delivering to the less privileged, who were disenfranchised or discarded in the swirl of technology’s advance. A lot of thought is now needed to find ways to restore faith in liberal, free-market societies; to show that they can be fairer and more equitable and offer more opportunities across the social spectrum. Germany, with its successful balance of capitalism and solidarity, its respect for the labor force and its commitments to both higher education and technical training, offers one model. The rage of 2016 will not abate by itself.

The liberal elites’ arrogance and ignorance has been astounding. It is time to listen to the people who voted for change, be humble and think again. That, of course, does not mean succumbing to the hatemongers and racists among them: They must be fought every inch of the way. Nor does it mean succumbing to a post-truth society: Facts are the linchpins of progress. But so brutal a comeuppance cannot be met by more of the same. I fear for my children’s world, more than I ever imagined possible.

We should ask our elders how best to live.

I want to point to a brief essay by Pillemer in Aeon. His interviews with several thousand people in their 80s and 90s revealed that their common response to younger people seeking a goal or purpose in life was to tell them to relax...a life can have a number of purposes, which can shift and change as life situations, interests, and priorities change.

But how should you go about finding a direction? How to settle on a purpose that fits your current life stage? One technique turns out to be immensely valuable – and yet most people ignore it. If you are searching for a direction or purpose, interview your future self...when people are made to think in detail about their future selves, they are more likely to make better financial planning decisions, show altruistic behaviour, and make more ethical choices. But it’s hard to do.

He gives advice similar to that given by Daniel Gilbert in his book "Stumbling towards happiness," a book which I abstracted in a series of MindBlog posts June 29, 2006.

..it’s astonishing how few people do the next best thing: interview an older person who embodies the ‘self’ they would like to be...In any period where you feel directionless, wavering, stuck with one foot in two different worlds, and hearing in the back of your mind the song lyrics ‘Should I stay or should I go?’ – find your future self. He or she should be old – and preferably really old. You don’t want a 40-year-old if you are 20; you want someone in his or her 80s, 90s, or a centenarian if you can find one. You need your future self to have the truly long view, as well as the detachment that comes from a very long life.

This person also needs to be as close as possible to your imagined future self. Debating a career in medicine? Find a doctor who loved what she did. Worried about whether you can balance your values with a career in the financial services industry? Find an older person who struck that balance and made it to the end of life without regrets. Planning to work an undemanding day job so you have the energy to paint/write/act in your spare time? Some very old people did just that

Protecting and reactivating memories

I want to point to two recent Science Magazine articles on memory. From the magazine's summaries..

Protecting memories from stress

It is widely accepted that stress has a negative impact on memory retrieval. But specific approaches to learning can counteract this effect. Smith et al. found that when memory was tested immediately after the onset of stress, stress effects were reduced. Furthermore, when subjects learned novel material by using a highly effective learning technique involving practice tests, their memory was also protected against the negative effects of stress.

Smith et al. Abstract:

More than a decade of research has supported a robust consensus: Acute stress impairs memory retrieval. We aimed to determine whether a highly effective learning technique could strengthen memory against the negative effects of stress. To bolster memory, we used retrieval practice, or the act of taking practice tests. Participants first learned stimuli by either restudying or engaging in retrieval practice. Twenty-four hours later, we induced stress in half of the participants and assessed subsequent memory performance. Participants who learned by restudying demonstrated the typical stress-related memory impairment, whereas those who learned by retrieval practice were immune to the deleterious effects of stress. These results suggest that the effects of stress on memory retrieval may be contingent on the strength of the memory representations themselves.

How to reactivate forgotten memories

Sophisticated techniques can decode stimulus representations for items held in a person's working memory. However, when subjects shift their attention toward something else, the neural representation of the now unattended item drops to baseline, as though the item has been forgotten. Rose et al. used single-pulse transcranial magnetic stimulation (TMS) to briefly reactivate the representation of an unattended item. A short pulse of TMS enhanced recognition of “forgotten” stimuli, bringing an unattended item back into focal attention.

Rose et al. Abstract:

The ability to hold information in working memory is fundamental for cognition. Contrary to the long-standing view that working memory depends on sustained, elevated activity, we present evidence suggesting that humans can hold information in working memory via “activity-silent” synaptic mechanisms. Using multivariate pattern analyses to decode brain activity patterns, we found that the active representation of an item in working memory drops to baseline when attention shifts away. A targeted pulse of transcranial magnetic stimulation produced a brief reemergence of the item in concurrently measured brain activity. This reactivation effect occurred and influenced memory performance only when the item was potentially relevant later in the trial, which suggests that the representation is dynamic and modifiable via cognitive control. The results support a synaptic theory of working memory.

Reversing the effect of booze on the brain.

Assuming that data on female rats can be extrapolated to humans, a bit of work that makes me feel better about my daily habits of aerobic swimming and a robust happy hour...Maynard and Leasure show that loss of nerve cells caused by binge drinking can be reversed by exercise, which acts to promote natural self-repair processes.:

Binge drinking damages the brain, and although a significant amount of recovery occurs with abstinence, there is a need for effective strategies to maximize neurorestoration. In contrast to binge drinking, exercise promotes brain health, so the present study assessed whether it could counteract ethanol-induced damage by augmenting natural self-repair processes following one or more binge exposures. Adult female rats were exposed to 0 (control), 1 or 2 binges, using an established 4-day model of binge-induced neurodegeneration. Half of the animals in each group remained sedentary, or had running wheel access beginning 7 days after the final binge, and were sacrificed 28 days later. To assess binge-induced hippocampal damage and exercise restoration, we quantified volume of the dentate gyrus and number of granule neurons. We found that a single binge exposure significantly decreased the volume of the dentate gyrus and number of granule neurons. A second binge did not exacerbate the damage. Exercise completely restored baseline volume and granule neuron numbers. To investigate a potential mechanism of this restoration, we administered IdU (a thymidine analog) in order to label cells generated after the first binge. Previous studies have shown that neurogenesis in the dentate gyrus is decreased by binge alcohol exposure, and that the hippocampus responds to this insult by increasing cell genesis during abstinence. We found increased IdU labeling in binge-exposed animals, and a further increase in binged animals that exercised. Our results indicate that exercise reverses long-lasting hippocampal damage by augmenting natural self-repair processes.

The brain adapts to dishonesty.

From Garrett et al., some information on neural correlates of what might be going on in Donald Trump's brain....

Dishonesty is an integral part of our social world, influencing domains ranging from finance and politics to personal relationships. Anecdotally, digressions from a moral code are often described as a series of small breaches that grow over time. Here we provide empirical evidence for a gradual escalation of self-serving dishonesty and reveal a neural mechanism supporting it. Behaviorally, we show that the extent to which participants engage in self-serving dishonesty increases with repetition. Using functional MRI, we show that signal reduction in the amygdala is sensitive to the history of dishonest behavior, consistent with adaptation. Critically, the extent of reduced amygdala sensitivity to dishonesty on a present decision relative to the previous one predicts the magnitude of escalation of self-serving dishonesty on the next decision. The findings uncover a biological mechanism that supports a 'slippery slope': what begins as small acts of dishonesty can escalate into larger transgressions.