Feeling pleasure from music - brain correlates of why people differ

From Martínez-Molina et al.:

SIGNIFICANCE

Music is one of the most important sources of pleasure for many people, but at the same time there are important individual differences in the sensitivity to musical reward. Previous studies have revealed the critical involvement of the functional connectivity between perceptual and subcortical brain areas in the enjoyment of music. However, it is unknown whether individual differences in music sensitivity might arise from variability in the structural connectivity among these areas. Here we show that structural connectivity between supratemporal and orbitofrontal cortices, and between orbitofrontal and nucleus accumbens, predict individual differences in sensibility to music reward. These results provide evidence for the critical involvement of the interaction between the subcortical reward system and higher-order cortical areas in music-induced pleasure.

Abstract

People show considerable variability in the degree of pleasure they experience from music. These individual differences in music reward sensitivity are driven by variability in functional connectivity between the nucleus accumbens (NAcc), a key structure of the reward system, and the right superior temporal gyrus (STG). However, it is unknown whether a neuroanatomical basis exists for this variability. We used diffusion tensor imaging and probabilistic tractography to study the relationship between music reward sensitivity and white matter microstructure connecting these two regions via the orbitofrontal cortex (OFC) in 38 healthy human participants (24 females and 14 males). We found that right axial diffusivity (AD) in the STG–OFC connectivity inversely correlated with music reward sensitivity. Additionally, right mean diffusivity and left AD in the NAcc-OFC tract also showed an inverse correlation. Further, AD in this tract also correlated with previously acquired BOLD activity during music listening, but not for a control monetary reward task in the NAcc. Finally, we used mediation analysis to show that AD in the NAcc–OFC tract explains the influence of NAcc activation during a music task on music reward sensitivity. Overall, our results provide further support for the idea that the exchange of information among perceptual, integrative, and reward systems is important for musical pleasure, and that individual differences in the structure of the relevant anatomical connectivity influences the degree to which people are able to derive such pleasure.

Can an uprising of decency win the next presidential election?

I want to point to this massively cogent piece by David Brooks, and also pass on a video done by the democratic presidential candidate he mentions, Marianne Williamson. He credits her with being the only candidate who most effectively cuts to the real heart of what is at issue in the next presidential election: who we are as a people, our national character, and the moral atmosphere in which we raise our children.

It is no accident that the Democratic candidate with the best grasp of this election is the one running a spiritual crusade, not an economic redistribution effort. Many of her ideas are wackadoodle, but Marianne Williamson is right about this: “This is part of the dark underbelly of American society: the racism, the bigotry and the entire conversation that we’re having here tonight. If you think any of this wonkiness is going to deal with this dark psychic force of the collectivized hatred that this president is bringing up in this country, then I’m afraid that the Democrats are going to see some very dark days.”

And she is right about this: “We’ve never dealt with a figure like this in American history before. This man, our president, is not just a politician; he’s a phenomenon. And an insider political game will not be able to defeat it. … The only thing that will defeat him is if we have a phenomenon of equal force, and that phenomenon is a moral uprising of the American people.”

They are unready for it, but it falls on the Democrats to rebuild the moral infrastructure of our country. That does not mean standing up and saying, “Donald Trump is a racist!” 500 times a day. It means reminding Americans of the values we still share, and the damage done when people are not held accountable for trampling on them. The values are pretty basic and can be simply expressed:

Unity: We’re one people. Our leader represents all the people. He doesn’t go around attacking whole cities and regions.

Honesty: We can’t have deliberative democracy without respect for the truth. None of us want congenital liars in our homes or our workplaces.

Pluralism: Human difference makes life richer and more interesting. We treasure members of all races and faiths for what they bring to the mosaic.

Sympathy: We want to be around people with good hearts, who feel for those who are suffering, who are faithful friends, whose daily lives are marked by kindness.

Opportunity: We want all children to have an open field and a fair chance in the great race of life.

Trump has put himself on the wrong side of all these values. So Democrats, go ahead and promote your plans. But also lead an uprising of decency. There must be one Democrat who, in word and deed, can do that.

Here is the Williamson video:

What can we do when facts don't matter?

Some of Trump’s most ardent supporters are those whose lives are most diminished and compromised by his actions. They do not let facts cloud their beliefs. A similar situation is seen in the anti-science denial of the scientifically proven benefits of vaccinations or genetically modified foods. The Dunning Kruger effect is in force. Those who know the least think they are experts. As Carroll points out in his NYTimes opinion piece, only subtle persuasion can be used to nudge those who are immune to factual knowledge. Some clips:

In a paper published early this year in Nature Human Behavior, scientists asked 500 Americans what they thought about foods that contained genetically modified organisms.

The vast majority, more than 90 percent, opposed their use. This belief is in conflict with the consensus of scientists. Almost 90 percent of them believe G.M.O.s are safe — and can be of great benefit.

The second finding of the study was more eye-opening. Those who were most opposed to genetically modified foods believed they were the most knowledgeable about this issue, yet scored the lowest on actual tests of scientific knowledge.

Carroll points out that...

A great deal of science communication still relies on the “knowledge deficit model,” an idea that the lack of support for good policies, and good science, merely reflects a lack of scientific information.

The problem is that experts have been giving accurate information for years to little effect.

In 2016, a number of researchers argued in an essay that those in the sciences needed to realize that the public may not process information in the same way they do. Scientists need to be formally trained in communication skills, they said, and they also need to realize that the knowledge deficit model makes for easy policy, but not necessarily good results.

It seems important to engage the public more, and earn their trust through continued, more personal interaction, using many different platforms and technologies. Dropping knowledge from on high — which is still the modus operandi for most scientists — doesn’t work.

Politics are in our DNA - why societies evolved to have both conservatives and liberals.

Sebastian Junger points out an evolutionary rationale for the presence of both liberals and conservatives within a group - that over our evolutionary history such heterogeneity has proven to enhance a group's ability to compete with other groups. One could wish that respect for these deep roots of our current political polarization might ameliorate the culture of contempt that currently prevails between red and blue America. There are now numerous studies correlating conservative or liberal orientation with basic biological differences, notably studies on young adults showing correlations between political orientation, brain structures, and genetics. Such differences can be shaped by different socialization processes (such as strict versus nurturant family values). Yudkin reviews differences in core beliefs (on how dangerous the world is, on personal responsibility, on parenting philosophy, etc.) between conservatives and liberals to suggest that the sides are more aligned on many issues than they realize.

Here is a clip from Junger's article:

If liberalism and conservatism are partly rooted in genetics, then those worldviews had to have been adaptive — and necessary — in our evolutionary past. That means that neither political party can accuse the other of being illegitimate or inherently immoral; we are the way we are for good reason. Every human society must do two things: It must be strong enough to protect itself from outside groups, and it must be fair enough to avoid internal conflict. A society entirely composed of liberals risks being overrun by enemies, and a society entirely composed of conservatives risks breaking apart over issues of inequality — “social justice,” as it’s now termed.

Put those groups together, however, and you have addressed the two greatest threats to human welfare: enemies and discord. The task for every society, from the earliest Homo sapiens of Africa to Americans of the 21st century, is to accommodate different values and worldviews into one ethos. It’s not easy to do, but our own genetic diversity clearly demonstrates that it’s possible. Otherwise, one set of values would have gradually dominated the other until there was no political discord at all, just a broad, flat uniformity. That may sound appealing at the moment. But in the long term, what a great loss that would be.

Re-skilling the brain.

For the first time, Oby et al (open source, nice graphics) observe the new neural activity patterns that cause a new learned behavior.

Significance

Consider a skill you would like to learn, like playing the piano. How do you progress from “Chopsticks” to Chopin? As you learn to do something new with your hands, does the brain also do something new? We found that monkeys learned new skilled behavior by generating new neural activity patterns. We used a brain–computer interface (BCI), which directly links neural activity to movement of a computer cursor, to encourage animals to generate new neural activity patterns. Over several days, the animals began to exhibit new patterns of neural activity that enabled them to control the BCI cursor. This suggests that learning to play the piano and other skills might also involve the generation of new neural activity patterns.

Abstract

Learning has been associated with changes in the brain at every level of organization. However, it remains difficult to establish a causal link between specific changes in the brain and new behavioral abilities. We establish that new neural activity patterns emerge with learning. We demonstrate that these new neural activity patterns cause the new behavior. Thus, the formation of new patterns of neural population activity can underlie the learning of new skills.

Deindividuation of outgroup faces occurs at the earliest stages of visual perception.

From Hughes et al:

A hallmark of intergroup biases is the tendency to individuate members of one’s own group but process members of other groups categorically. While the consequences of these biases for stereotyping and discrimination are well-documented, their early perceptual underpinnings remain less understood. Here, we investigated the neural mechanisms of this effect by testing whether high-level visual cortex is differentially tuned in its sensitivity to variation in own-race versus other-race faces. Using a functional MRI adaptation paradigm, we measured White participants’ habituation to blocks of White and Black faces that parametrically varied in their groupwise similarity. Participants showed a greater tendency to individuate own-race faces in perception, showing both greater release from adaptation to unique identities and increased sensitivity in the adaptation response to physical difference among faces. These group differences emerge in the tuning of early face-selective cortex and mirror behavioral differences in the memory and perception of own- versus other-race faces. Our results suggest that biases for other-race faces emerge at some of the earliest stages of sensory perception.

Facial muscles in dogs evolved for interactions with humans.

From Kaminski et al. (check out the videos in the article):

Domestication shaped wolves into dogs and transformed both their behavior and their anatomy. Here we show that, in only 33,000 y, domestication transformed the facial muscle anatomy of dogs specifically for facial communication with humans. Based on dissections of dog and wolf heads, we show that the levator anguli oculi medialis, a muscle responsible for raising the inner eyebrow intensely, is uniformly present in dogs but not in wolves. Behavioral data, collected from dogs and wolves, show that dogs produce the eyebrow movement significantly more often and with higher intensity than wolves do, with highest-intensity movements produced exclusively by dogs. Interestingly, this movement increases paedomorphism and resembles an expression that humans produce when sad, so its production in dogs may trigger a nurturing response in humans. We hypothesize that dogs with expressive eyebrows had a selection advantage and that “puppy dog eyes” are the result of selection based on humans’ preferences.

Around the globe, financial temptation increases civic honesty.

Shalvi does a commentary on work by Cohn et al. Here is the Cohn et al. abstract:

Civic honesty is essential to social capital and economic development but is often in conflict with material self-interest. We examine the trade-off between honesty and self-interest using field experiments in 355 cities spanning 40 countries around the globe. In these experiments, we turned in more than 17,000 lost wallets containing varying amounts of money at public and private institutions and measured whether recipients contacted the owners to return the wallets. In virtually all countries, citizens were more likely to return wallets that contained more money. Neither nonexperts nor professional economists were able to predict this result. Additional data suggest that our main findings can be explained by a combination of altruistic concerns and an aversion to viewing oneself as a thief, both of which increase with the material benefits of dishonesty.

It’s never simple...The tidy textbook story about the primary visual cortex is wrong.

When I was a postdoc in the Harvard Neurobiology department in the mid-1960’s I used to have afternoon tea with the Hubel and Weisel group. These are the guys who got a Nobel prize for, among other things, finding that the primary visual cortex is organized into cortical columns of cells that responded to lines that prefer different orientations. Another grouping of columns, called ‘blobs’ responded selectively to color and brightness but not orientation. These two different kinds of groups sent their outputs to higher visual areas that were supposed to integrate the information. My neurobiology course lectures and my Biology of Mind book showed drawings illustrating these tidy distinctions.

Sigh… now Garg et al. come along with two-photon calcium imaging to probe a very large spatial and chromatic visual stimulus space and map functional microarchitecture of thousands of neurons with single-cell resolution. They show that processing of orientation and color is combined at the earliest stages of visual processing, totally challenging the existing model. Their abstract:

Previous studies support the textbook model that shape and color are extracted by distinct neurons in primate primary visual cortex (V1). However, rigorous testing of this model requires sampling a larger stimulus space than previously possible. We used stable GCaMP6f expression and two-photon calcium imaging to probe a very large spatial and chromatic visual stimulus space and map functional microarchitecture of thousands of neurons with single-cell resolution. Notable proportions of V1 neurons strongly preferred equiluminant color over achromatic stimuli and were also orientation selective, indicating that orientation and color in V1 are mutually processed by overlapping circuits. Single neurons could precisely and unambiguously code for both color and orientation. Further analyses revealed systematic spatial relationships between color tuning, orientation selectivity, and cytochrome oxidase histology.

An anti-aging pill with some credibility....

An AARP article points to studies on the new drug RTB101, which boosts immune function in older people and lowers risk for respiratory diseases. By virtue of it's inhibition of the multiprotein complex TORC1, which mediates temporal control of cell growth, it is also a potential anti-aging drug. Below is text from the anti-aging website lifespan.io:

resTORbio, Inc. is developing RTB101, an oral medication that inhibits target of rapamycin complex 1 (TORC1). Using a combination of RTB101 and everolimus, another TORC1 inhibitor, the company is testing a comprehensive immunotherapy program to fight respiratory tract infections in the elderly, improving the immune system rather than attempting to target individual infectious agents.

The mammalian target of rapamycin (mTOR) pathway uses the multiprotein complexes TORC1 and TORC2 to conduct signaling. While inhibiting TORC2 has been observed to decrease lifespan, TORC1 inhibition has been shown to have multiple positive effects, including enhanced brain functions, reduction of adipose tissue, and delaying the onset of age-related pathology. Inhibiting TORC1 with both RTB101 and everolimus decreases S6K while increasing 4EBP1 and Atg; affecting each of these downstream products in this way is reported to enhance lifespan.

In 2018, the company reported that a phase 2b trial of RTB101 has returned positive results for boosting the immune system to respond better to respiratory infections. The trial saw 652 aged people with increased risk of RTIs enroll and compared to the control group, there were significantly fewer patients treated with RTB101 who suffered from one or more RTIs during a 16-week trial period. The next step for resTORbio is to conduct a study of its effects on other infections, heart failure, or autophagy-related diseases later in 2018.

Concluding the successful Phase 2 and 2b studies the company has agreed with the FDA to proceed to a large scale phase 3 clinical trial scheduled to begin later in 2019...resTORbio has licensed the worldwide rights for its product from Novartis Limited, a major pharmaceutical company...Website: resTORbio

Correlating our our physical and mental experiences of stress linked to psychological and physical well-being

Davidson and colleagues at the Univ. of Wisconsin show that individual differences in the ability to associate subjective stress and heart rate are related to psychological and physical well being. Here is a description of the work from a newsletter, followed by the abstract from Psychological Sciences. They:

...analyzed data from 1,065 participants in the Midlife in the United States (MIDUS) study, a longitudinal effort looking at well-being as adults age. Participants completed a series of stressful computer tasks, including a mental math task and a color identification task.

Before, during and after the tasks, researchers measured participants’ heart rate and asked them to rate their stress on a scale of one to 10 throughout the study.

After the participants completed the stress tests, researchers compared each person’s heart rate to the stress levels they reported — a measure called “stress-heart rate coherence”— and found that some people’s stress levels aligned with their heart rate better than others.

To examine the link between stress-heart rate coherence and people’s emotional well-being, researchers used psychological questionnaires focused on well-being, depression, anxiety and coping as well as blood samples measuring inflammation markers. Researchers found that people with greater stress-heart rate coherence had fewer symptoms of anxiety and depression, greater overall psychological well-being and lower levels of inflammation.

Here is the journal article's abstract:

The physiological response to stress is intertwined with, but distinct from, the subjective feeling of stress, although both systems must work in concert to enable adaptive responses. We investigated 1,065 participants from the Midlife in the United States 2 study who completed a self-report battery and a stress-induction procedure while physiological and self-report measures of stress were recorded. Individual differences in the association between heart rate and self-reported stress were analyzed in relation to measures that reflect psychological well-being (self-report measures of well-being, anxiety, depression), denial coping, and physical well-being (proinflammatory biomarkers interleukin-6 and C-reactive protein). The within-participants association between heart rate and self-reported stress was significantly related to higher psychological well-being, fewer depressive symptoms, lower trait anxiety, less use of denial coping, and lower levels of proinflammatory biomarkers. Our results highlight the importance of studying individual differences in coherence between physiological measures and subjective mental states in relation to well-being.

And here is a PDF of the article.

The Problem With ‘Sharenting’

An article in the NYTimes 'Privacy Project' by Kamenetz resonates with my own experience of very mixed reactions to viewing some of what I consider the most private and intimate details of the lives of my 5 and 7 year old grandsons occasionally revealed in some of the Facebook posts by their parents. I feel embarrassed for the boys, and sometimes how they would feel in their 20s and 30s if they were to look back at these posts on their childhood. (A pre-facebook version of the situation from my childhood is a photograph of two legs - five year old Deric - protruding from under a newspaper sitting on the toilet...how cute!). Some clips from the Kamenetz piece:

Today, many children’s social media presence starts with a sonogram, posted, obviously, without consent. One study from Britain found that nearly 1,500 images of the average child had been placed online by their fifth birthday. Parents get a lot of gratification from telling kids’ stories online...It’s less clear what our children have to gain from their lives being broadcast in this way. ..parents’ rights to free speech and self-expression are at odds with children’s rights to privacy when they are young and vulnerable...This is especially true when the information is potentially damaging. Imagine a child who has behavior problems, learning disabilities or chronic illness. Mom or Dad understandably want to discuss these struggles and reach out for support. But those posts live on the internet, with potential to be discovered by college admissions officers and future employers, friends and romantic prospects. A child’s life story is written for him before he has a chance to tell it himself.

Even if you confine your posts about your children to sunny days and birthday parties, any information you provide about them — names, dates of birth, geographic location — could be acquired by data brokersClose X, companies that collect personal information and sell it to advertisers.

Finally, there’s display and commodification. In 2018, the top earner on YouTube, according to Forbes, was a 7-year-old boy who brought in $22 million by playing with toys. It’s never seemed more accessible to become famous at a wee age, and the type of children who used to sing into a hairbrush in the mirror are often clamoring to start their own channels today.

The most egregious abuses are just the tip of the iceberg, though. For every moneymaking influencer, there are millions of less-successful stage parents and wannabes scratching for followers on YouTube and Instagram. They’re out there shoving cameras in children’s faces, using up their free time, killing spontaneity, warping the everyday rituals of childhood into long working shoots.

When it comes to childhood and technology, we adults are the horror show.

Looking for a dose of optimism?

I want to point to a recent NYTimes Op-Ed piece by David Brooks that is a bit more upbeat than his frequent hand wringing over the dissolution of old verities. A few clips from its later paragraphs:

The reality and challenge is that America has become radically pluralistic. We used to be unipolar — one dominant majority culture and a lot of minority groups that defined themselves against it. Now we’re multipolar. We’re all minorities now.

That could blow us to smithereens. But who knows? We could learn to be minorities together, to be what Rabbi Jonathan Sacks calls creative minorities. In a brilliant 2013 lecture, Sacks noted that when Solomon’s temple was destroyed and the Jews were cast into exile, the prophet Jeremiah had a surprising message: Go to new lands. Build houses. Plant gardens. Seek the peace and prosperity of the cities in which you settle.

In a world of radical pluralism, we are all Jews. We have no choice but to build a mass multicultural democracy, a society that has no dominant center but is a collection of creative minorities...Nearly 200 years ago, Tocqueville wrote that democracy was creating a new sort of man. Pluralism today is creating a new sort of person, especially among the young. They don’t just relish diversity; they embody it. Many have mixed roots — say, half-French/half-Dominican. Many are border stalkers; they live between cultures, switch back and forth, and work hard to build a multiplicity of influences into a single coherent life. They’re Whitmanesque, containing multitudes, holding opposite ideas in their minds at the same time.

Radical pluralism also necessitates retelling the nation’s history. We’ve always been a universal nation, a crossroads nation, a nation whose very identity is defined by the fact that it is a hub for a dense network of minorities and subgroups, and the distinct way of life they fashion to interact and flourish together.

I used to think that America had to find a new unifying national narrative. Now I wonder if not having a single national narrative will become our national narrative.

Subgroups of gay men correspond to different biodevelopmental pathways

Swift-Gallant et al. consider three established biomarkers of sexual orientation and suggest they reflect distinct biodevelopmental pathways influencing same-sex sexual orientation in men. They describe these biomarkers in their introduction:

A well-established biomarker of sexual orientation is familiality of male same-sex sexual orientation. Same-sex sexual orientation clusters in families, twin studies show greater sexual orientation concordance among monozygotic than dizygotic twins, and molecular genetic studies have identified candidate genes associated with sexual orientation.

A second well-studied biomarker of sexual orientation is handedness. Although the biological underpinnings of handedness are not yet clear, increasing evidence suggests that handedness is a marker of cerebral lateralization determined prenatally by genetic, immunological, and endocrine mechanisms and/or by developmental instability... it is estimated that men have 20% greater odds of non−right-handedness than women, and gay men have 34% greater odds of being non−right-handed than heterosexual men.

A third well-established biomarker of sexual orientation is the fraternal birth order effect). Across a diverse range of cultures and sample types, studies have shown that older brothers increase the odds of androphilia in later-born males. The maternal immune hypothesis is the best-developed explanation of the fraternal birth order effect. It argues that male antigens enter maternal circulation during the gestation and birthing of male offspring, promoting an immune response to these male-specific antigens that increases with each successive male fetus gestated; thus, with each successive pregnancy with a male fetus, the odds increase that these maternal antibodies will affect sexual differentiation of the brain and behavior, including sexual preferences.

Their Significance and Abstract statements:  

Significance

Studying individual differences in gender and sexual orientation provides insight into how early-life biology shapes brain and behavior. The literature identifies multiple biodevelopmental influences on male sexual orientation, but these influences are generally studied individually, and the potential for association or interaction between them remains largely unexplored. We hypothesized that distinct biodevelopmental pathways correspond to specific subgroups of nonheterosexual men. We present evidence that nonheterosexual men can be categorized into at least four subgroups based on established biomarkers, and these biodevelopmental pathways differentially relate to gender expression and personality traits. These findings indicate individual differences in biodevelopmental pathways of male sexual orientation. They also illustrate the value of latent profile analyses for studying individual differences.

Abstract

Several biological mechanisms have been proposed to influence male sexual orientation, but the extent to which these mechanisms cooccur is unclear. Putative markers of biological processes are often used to evaluate the biological basis of male sexual orientation, including fraternal birth order, handedness, and familiality of same-sex sexual orientation; these biomarkers are proxies for immunological, endocrine, and genetic mechanisms. Here, we used latent profile analysis (LPA) to assess whether these biomarkers cluster within the same individuals or are present in different subgroups of nonheterosexual men. LPA defined four profiles of men based on these biomarkers: 1) A subgroup who did not have these biomarkers, 2) fraternal birth order, 3) handedness, and 4) familiality. While the majority of both heterosexual and nonheterosexual men were grouped in the profile that did not have any biomarker, the three profiles associated with a biomarker were composed primarily of nonheterosexual men. We then evaluated whether these subgroups differed on measures of gender nonconformity and personality that reliably show male sexual orientation differences. The subgroup without biomarkers was the most gender-conforming whereas the fraternal birth order subgroup was the most female-typical and agreeable, compared with the other profiles. Together, these findings suggest there are multiple distinct biodevelopmental pathways influencing same-sex sexual orientation in men.

Social Media - no effect on adolescent life satisfaction?

Orben et al. (open source article) provide a study whose results contest a common opinion, reinforced by several previous studies, that adolescents who use social media extensively are more likely to be depressed and have low self esteem. They used...

...large-scale representative panel data to disentangle the between-person and within-person relations linking adolescent social media use and well-being. We found that social media use is not, in and of itself, a strong predictor of life satisfaction across the adolescent population. Instead, social media effects are nuanced, small at best, reciprocal over time, gender specific, and contingent on analytic methods.

They note limitations of current published research:

Focused on cross-sectional relations, scientists have few means of parsing longitudinal effects from artifacts introduced by common statistical modeling methodologies. Furthermore, the volume of data under analysis, paired with unchecked analytical flexibility, enables selective research reporting, biasing the literature toward statistically significant effects. Nevertheless, trivial trends are routinely overinterpreted by those under increasing pressure to rapidly craft evidence-based policies.

The UK study examined data on 12,672 10-15 year old. Two summary graphics are provided. One clip:

...the importance of gender was apparent: Only 16% of significant models arose from male data.

The last two paragraphs:

The relations linking social media use and life satisfaction are, therefore, more nuanced than previously assumed: They are inconsistent, possibly contingent on gender, and vary substantively depending on how the data are analyzed. Most effects are tiny—arguably trivial; where best statistical practices are followed, they are not statistically significant in more than half of models. That understood, some effects are worthy of further exploration and replication: There might be small reciprocal within-person effects in females, with increases in life satisfaction predicting slightly lower social media use, and increases in social media use predicting tenuous decreases in life satisfaction.

With the unknowns of social media effects still substantially outnumbering the knowns, it is critical that independent scientists, policymakers, and industry researchers cooperate more closely. Scientists must embrace circumspection, transparency, and robust ways of working that safeguard against bias and analytical flexibility. Doing so will provide parents and policymakers with the reliable insights they need on a topic most often characterized by unfounded media hype. Finally, and most importantly, social media companies must support independent research by sharing granular user engagement data and participating in large-scale team-based open science. Only then will we truly unravel the complex constellations of effects shaping young people in the digital age.

Think twice about metformin as an anti-aging drug.

Gretchen Reynolds points to work suggesting that use of metformin (the most commonly used Type 2 diabetes drug) as an anti-aging agent by healthy active people (because it reduces inflammation and causes other cellular effects that alter aging) may have a downside. Konopka et al. report that it suppresses the anti-aging effects of exercise, notably exercise-related gains in muscle-cell mitochondrial respiration. There is the usual caveat that this is a single study with a relatively small number of subjects (53). Here is their technical abstract:

Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow aging. However, recent evidence indicates that adding metformin to exercise antagonizes the exercise‐induced improvement in insulin sensitivity and cardiorespiratory fitness. The purpose of this study was to test the hypothesis that metformin diminishes the improvement in insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) by inhibiting skeletal muscle mitochondrial respiration and protein synthesis in older adults (62 ± 1 years). In a double‐blinded fashion, participants were randomized to placebo (n = 26) or metformin (n = 27) treatment during 12 weeks of AET. Independent of treatment, AET decreased fat mass, HbA1c, fasting plasma insulin, 24‐hr ambulant mean glucose, and glycemic variability. However, metformin attenuated the increase in whole‐body insulin sensitivity and VO2max after AET. In the metformin group, there was no overall change in whole‐body insulin sensitivity after AET due to positive and negative responders. Metformin also abrogated the exercise‐mediated increase in skeletal muscle mitochondrial respiration. The change in whole‐body insulin sensitivity was correlated to the change in mitochondrial respiration. Mitochondrial protein synthesis rates assessed during AET were not different between treatments. The influence of metformin on AET‐induced improvements in physiological function was highly variable and associated with the effect of metformin on the mitochondria. These data suggest that prior to prescribing metformin to slow aging, additional studies are needed to understand the mechanisms that elicit positive and negative responses to metformin with and without exercise.

Your professional decline.

Arthur Brooks, former president of the conservative American Enterprise Institute think tank and New York Times Op-Ed writer, does an essay in the Atlantic in which he contemplates his professional decline, making points that are universally relevant. Some clips:

...happiness of most adults declines through their 30s and 40s, then bottoms out in their early 50s...Almost all studies of happiness over the life span show that, in wealthier countries, most people’s contentment starts to increase again in their 50s, until age 70 or so. That is where things get less predictable, however. After 70, some people stay steady in happiness; others get happier until death. Others—men in particular—see their happiness plummet. Indeed, depression and suicide rates for men increase after age 75...A few researchers have looked at this cohort to understand what drives their unhappiness. It is, in a word, irrelevance.

This is especially an issue in gifted and accomplished people.

...accomplishment is a well-documented source of happiness. If current accomplishment brings happiness, then shouldn’t the memory of that accomplishment provide some happiness as well?...Though the literature on this question is sparse, giftedness and achievements early in life do not appear to provide an insurance policy against suffering later on...abundant evidence suggests that the waning of ability in people of high accomplishment is especially brutal psychologically...Call it the Principle of Psychoprofessional Gravitation: the idea that the agony of professional oblivion is directly related to the height of professional prestige previously achieved, and to one’s emotional attachment to that prestige...the memory of remarkable ability, if that is the source of one’s self-worth, might, for some, provide an invidious contrast to a later, less remarkable life.

In some professions, early decline is inescapable. No one expects an Olympic athlete to remain competitive until age 60. But in many physically nondemanding occupations, we implicitly reject the inevitability of decline before very old age. Sure, our quads and hamstrings may weaken a little as we age. But as long as we retain our marbles, our quality of work as a writer, lawyer, executive, or entrepreneur should remain high up to the very end, right? ...The data are shockingly clear that for most people, in most fields, decline starts earlier than almost anyone thinks...if you start a career in earnest at 30, expect to do your best work around 50 and go into decline soon after that...the most common age for producing a magnum opus is the late 30s...the likelihood of a major discovery increases steadily through one’s 20s and 30s and then declines through one’s 40s, 50s, and 60s. Are there outliers? Of course. But the likelihood of producing a major innovation at age 70 is approximately what it was at age 20—almost nonexistent.

In sum, if your profession requires mental processing speed or significant analytic capabilities—the kind of profession most college graduates occupy—noticeable decline is probably going to set in earlier than you imagine...Whole sections of bookstores are dedicated to becoming successful. The shelves are packed with titles like The Science of Getting Rich and The 7 Habits of Highly Effective People. There is no section marked “Managing Your Professional Decline.”

Brooks contrasts the declines of Charles Darwin, who became embittered and inactive after his younger most creative period had passed, with Johann Sebastian Bach, who redesigned his life - as baroque music was being replaced by the "classical" style - moving from being an innovator to being a teacher and instructor.

The lesson for you and me, especially after 50: Be Johann Sebastian Bach, not Charles Darwin...How does one do that? A potential answer lies in the work of the British psychologist Raymond Cattell, who in the early 1940s introduced the concepts of fluid and crystallized intelligence. Cattell defined fluid intelligence as the ability to reason, analyze, and solve novel problems—what we commonly think of as raw intellectual horsepower. ...It is highest relatively early in adulthood and diminishes starting in one’s 30s and 40s...Crystallized intelligence, in contrast, is the ability to use knowledge gained in the past. Think of it as possessing a vast library and understanding how to use it. It is the essence of wisdom. Because crystallized intelligence relies on an accumulating stock of knowledge, it tends to increase through one’s 40s, and does not diminish until very late in life...poets—highly fluid in their creativity—tend to have produced half their lifetime creative output by age 40 or so. Historians—who rely on a crystallized stock of knowledge—don’t reach this milestone until about 60...No matter what mix of intelligence your field requires, you can always endeavor to weight your career away from innovation and toward the strengths that persist, or even increase, later in life...teaching is an ability that decays very late in life, a principal exception to the general pattern of professional decline over time...the most profound insights tend to come from those in their 30s and early 40s. The best synthesizers and explainers of complicated ideas—that is, the best teachers—tend to be in their mid-60s or older, some of them well into their 80s.

Most Eastern philosophy warns that focusing on acquisition leads to attachment and vanity, which derail the search for happiness by obscuring one’s essential nature. As we grow older, we shouldn’t acquire more, but rather strip things away to find our true selves—and thus, peace.

At some point, writing one more book will not add to my life satisfaction; it will merely stave off the end of my book-writing career. The canvas of my life will have another brushstroke that, if I am being forthright, others will barely notice, and will certainly not appreciate very much. The same will be true for most other markers of my success.

What I need to do, in effect, is stop seeing my life as a canvas to fill, and start seeing it more as a block of marble to chip away at and shape something out of. I need a reverse bucket list. My goal for each year of the rest of my life should be to throw out things, obligations, and relationships until I can clearly see my refined self in its best form.

Hindu philosophy—and indeed the wisdom of many philosophical traditions—suggests that you should be prepared to walk away from the rewards of success before you feel ready. Even if you’re at the height of your professional prestige, you probably need to scale back your career ambitions in order to scale up your metaphysical ones.

David Brooks talks about the difference between “résumé virtues” and “eulogy virtues,”...Résumé virtues are professional and oriented toward earthly success. They require comparison with others. Eulogy virtues are ethical and spiritual, and require no comparison. Your eulogy virtues are what you would want people to talk about at your funeral. As in He was kind and deeply spiritual, not He made senior vice president at an astonishingly young age and had a lot of frequent-flier miles....To move from résumé virtues to eulogy virtues is to move from activities focused on the self to activities focused on others.

..an abundance of research strongly suggests that happiness—not just in later years but across the life span—is tied directly to the health and plentifulness of one’s relationships. Pushing work out of its position of preeminence—sooner rather than later—to make space for deeper relationships can provide a bulwark against the angst of professional decline.

The aspen tree is an excellent metaphor for a successful person—but not, it turns out, for its solitary majesty. Above the ground, it may appear solitary. Yet each individual tree is part of an enormous root system, which is together one plant...The secret to bearing my decline—to enjoying it—is to become more conscious of the roots linking me to others. If I have properly developed the bonds of love among my family and friends, my own withering will be more than offset by blooming in others.

Perception as controlled hallucination - predictive processing and the nature of conscious experience

I've now read several times through a fascinating Edge.org conversation with philosopher Andy Clark. I suggest you read the piece, and here pass on some edited clips. First, his comments on most current A.I. efforts:

There's something rather passive about the kinds of artificial intelligence ...[that are]...trained on an objective function. The AI tries to do a particular thing for which it might be exposed to an awful lot of data in trying to come up with ways to do this thing. But at the same time, it doesn't seem to inhabit bodies or inhabit worlds; it is solving problems in a disembodied, disworlded space. The nature of intelligence looks very different when we think of it as a rolling process that is embedded in bodies or embedded in worlds. Processes like that give rise to real understandings of a structured world.

Then, his ideas on how our internal and external worlds are a continuum:

Perception itself is a kind of controlled hallucination. You experience a structured world because you expect a structured world, and the sensory information here acts as feedback on your expectations. It allows you to often correct them and to refine them. But the heavy lifting seems to be being done by the expectations. Does that mean that perception is a controlled hallucination? I sometimes think it would be good to flip that and just think that hallucination is a kind of uncontrolled perception.

The Bayesian brain, predictive processing, hierarchical predictive coding are all, roughly speaking, names for the same picture in which experience is constructed at the shifting borderline between sensory evidence and top-down prediction or expectation. There's been a big literature out there on the perceptual side of things. It's a fairly solid literature. What predictive processing did that I found particularly interesting—and this is mostly down to a move that was made by Karl Friston—was apply the same story to action. In action, what we're doing is making a certain set of predictions about the shape of the sensory information that would result if I were to perform the action. Then you get rid of prediction errors relative to that predicted flow by making the action.

There's a pleasing symmetry there. Once you've got action on the table in these stories—the idea is that we bring action about by predicting sensory flows that are non actual and then getting rid of prediction errors relative to those sensory flows by bringing the action about—that means that epistemic action, as it's sometimes called, is right there on the table. Systems like that cannot just act in the world to fulfill their goals; they can also act in the world so as to get better information to fulfill their goals. And that's something that active animals do all the time. The chicken, when it bobs its head around, is moving its sensors around to get information that allows it to do depth perception that it can't do unless it bobs its head around...Epistemic action, and practical action, and perception, and understanding are now all rolled together in this nice package.

An upshot here is that there's no experience without the application of some model to try to sift what is worthwhile for a creature like you in the signal and what isn't worthwhile for a creature like you.

Apart from the exteroceptive signals that we take in from vision, sound, and so on, and apart from the proprioceptive signals from our body that are what we predict in order to move our body around, there's also all of the interoceptive signals that are coming from the heart and from the viscera, et cetera...being subtly inflected by interoception information is part of what makes our conscious experience of the world the kind of experience that it is. So, artificial systems without interoception could perceive their world in an exteroceptive way, they could act in their world, but they would be lacking what seems to me to be one important dimension of what it is to be a conscious human being in the world.

Implicit racial bias is preserved by historical roots of social environments.

Payne et al. note that geographic differences in implicit racial bias correlate with the number of slaves in those areas in 1860.

Significance

Geographic variation in implicit bias is associated with multiple racial disparities in life outcomes. We investigated the historical roots of geographical differences in implicit bias by comparing average levels of implicit bias with the number of slaves in those areas in 1860. Counties and states more dependent on slavery in 1860 displayed higher pro-White implicit bias today among White residents and less pro-White bias among Black residents. Mediation analyses suggest that historical oppression may be transmitted into contemporary biases through structural inequalities, including disparities in poverty and upward mobility. Given the importance of contextual factors, efforts to reduce unintended discrimination might focus on modifying social environments that cue implicit biases in the minds of individuals.

Abstract

Implicit racial bias remains widespread, even among individuals who explicitly reject prejudice. One reason for the persistence of implicit bias may be that it is maintained through structural and historical inequalities that change slowly. We investigated the historical persistence of implicit bias by comparing modern implicit bias with the proportion of the population enslaved in those counties in 1860. Counties and states more dependent on slavery before the Civil War displayed higher levels of pro-White implicit bias today among White residents and less pro-White bias among Black residents. These associations remained significant after controlling for explicit bias. The association between slave populations and implicit bias was partially explained by measures of structural inequalities. Our results support an interpretation of implicit bias as the cognitive residue of past and present structural inequalities.

Over 50-fold difference between individuals in circadian melatonin sensitivity to evening light.

Phillips et al. probe how our high sensitivity to artificial light after dusk perturbs the circadian rhythm of our sleep hormone melatonin:

Significance

Electric lighting has fundamentally altered how the human circadian clock synchronizes to the day/night cycle. Exposure to light after dusk is pervasive in the modern world. We examined group-level sensitivity of the circadian system to evening light and the degree to which sensitivity varies between individuals. We found that, on average, humans are highly sensitive to evening light. Specifically, 50% suppression of melatonin occurred at less than 30 lux, which is comparable to or lower than typical indoor lighting used at night, as well as light produced by electronic devices. Significantly, there was a greater than 50-fold difference in sensitivity to evening light across individuals. Interindividual differences in light sensitivity may explain differential vulnerability to circadian disruption and subsequent impact on human health.

Abstract

Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (less than 30 lux) environmental light—stimuli at extreme ends of the circadian system’s dose–response curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30–300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose–response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18–30) were exposed to a dim control (less than 1 lux) and a range of experimental light levels (10–2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED₅₀) was computed at individual and group levels. The group-level fitted ED₅₀ was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED₅₀ values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock’s role in human health and disease.