Anxiolytic actions of oxytocin, unlike those of benzodiazepines, involve brain regions outside the amygdala

From Kreuder et al.:

Significance

A potential new target for anxiolytic drug development is the oxytocin (OXT) neuropeptide system. An emerging question is whether OXT has similar effects on the neural microcircuitry of fear compared with clinically established compounds such as benzodiazepines. The present functional MRI study showed that both OXT and its benzodiazepine comparator lorazepam (LZP) reduced centromedial amygdala responses to fear signals. OXT, but not LZP, increased extra-amygdalar connectivity between the centromedial amygdala and frontoparietal regions. Thus, while both compounds inhibited the centromedial amygdala, OXT, but not LZP, elicited large-scale connectivity changes of potential therapeutic relevance.

Abstract

Benzodiazepines (BZDs) represent the gold standard of anxiolytic pharmacotherapy; however, their clinical benefit is limited by side effects and addictive potential. Consequently, there is an urgent need to develop novel and safe anxiolytics. The peptide hormone oxytocin (OXT) exhibits anxiolytic-like properties in animals and humans, but whether OXT and BZDs share similar effects on the neural circuitry of fear is unclear. Therefore, the rationale of this ultra-high-field functional MRI (fMRI) study was to test OXT against the clinical comparator lorazepam (LZP) with regard to their neuromodulatory effects on local and network responses to fear-related stimuli. One hundred twenty-eight healthy male participants volunteered in this randomized double-blind, placebo-controlled, between-group study. Before scanning using an emotional face-matching paradigm, participants were randomly administered a single dose of OXT (24 IU), LZP (1 mg), or placebo. On the behavioral level, LZP, but not OXT, caused mild sedation, as evidenced by a 19% increase in reaction times. On the neural level, both OXT and LZP inhibited responses to fearful faces vs. neutral faces within the centromedial amygdala (cmA). In contrast, they had different effects on intra-amygdalar connectivity; OXT strengthened the coupling between the cmA and basolateral amygdala, whereas LZP increased the interplay between the cmA and superficial amygdala. Furthermore, OXT, but not LZP, enhanced the coupling between the cmA and the precuneus and dorsomedial prefrontal cortex. These data implicate inhibition of the cmA as a common denominator of anxiolytic action, with only OXT inducing large-scale connectivity changes of potential therapeutic relevance.

Your voice carries information about your upper body movements.

Fascinating observations by Pouw et al.:

Significance

We show that the human voice carries an acoustic signature of muscle 
tensioning during upper limb movements which can be detected by 
listeners. Specifically, we find that human listeners can synchronize 
their own movements to very subtle wrist movements of a vocalizer only 
by listening to their vocalizations and without any visual contact. This
study shows that the human voice contains information about dynamic 
bodily states, breaking ground for our understanding of the evolution of
spoken language and nonverbal communication. The current findings are 
in line with other research on nonhuman animals, showing that 
vocalizations carry information about bodily states and capacities.

Abstract
We show that the human voice has complex acoustic qualities that are 
directly coupled to peripheral musculoskeletal tensioning of the body, 
such as subtle wrist movements. In this study, human vocalizers produced
a steady-state vocalization while rhythmically moving the wrist or the 
arm at different tempos. Although listeners could only hear and not see 
the vocalizer, they were able to completely synchronize their own 
rhythmic wrist or arm movement with the movement of the vocalizer which 
they perceived in the voice acoustics. This study corroborates recent 
evidence suggesting that the human voice is constrained by bodily 
tensioning affecting the respiratory–vocal system. The current results 
show that the human voice contains a bodily imprint that is directly 
informative for the interpersonal perception of another’s dynamic 
physical states.

An "Apostle's Creed" for the humanistic scientific materialist?

(Note: I have begun to slowly go though the posts on MindBlog, which began in Feb. of 2006, over 14 years ago.  Here I repeat the post that appeared on March 14, 2006.  I could have written it yesterday, without changing a word.)

The classical Christian apostle's creed, over 1600 years old and formulated soon after the writing of the New Testament, is a series of "I believe....." statements. Without thinking too much about it, I've decided to quickly write down a few sentences to suggest the very different creed that I follow. Here they are:

I believe the most fundamental content of our minds to be the sensed physical breathing and moving body, a quiet awareness that underlies our surface waves of emotions and thoughts.

I believe that this awareness can begin to experience a larger process, closer to the machinery that is generating a self, a process that observes rather than being completely defined by the current narrative "I" chatter of who-I-am or what-it-is-I-do.

I believe that this awareness can expand to feel its part in a a drama of evolving life on this planet and an evolving universe - a theater much more universal than conventional cultural or religious myths.

I believe that this awareness can enhance the depth, sanity, and sensed completion of each moment. It provides a sense of wholeness and sufficiency from which actions rise. It makes contact with other humans more sane and whole.

Brain connectivity fingerprinting of complex human personality traits - another tool for the surveillance state?

A group of researchers in the Department of Radiology, Anhui Medical University, Hefei, China, find that resting-state functional connectivity patterns of whole-brain large-scale networks can effectively and reliably predict complex human personality traits, including agreeableness, openness, conscientiousness and neuroticism, at the individual level. Fascinating work, but one wonders whether this might become yet another tool that might be used by a government to assess its citizens? :

Neuroimaging studies have linked inter-individual variability in the brain to individualized personality traits. However, only one or several aspects of personality have been effectively predicted based on brain imaging features. The objective of this study was to construct a reliable prediction model of personality in a large sample by using connectome-based predictive modeling (CPM), a recently developed machine learning approach. High-quality resting-state functional magnetic resonance imaging data of 810 healthy young participants from the Human Connectome Project dataset were used to construct large-scale brain networks. Personality traits of the five-factor model (FFM) were assessed by the NEO Five Factor Inventory. We found that CPM successfully and reliably predicted all the FFM personality factors (agreeableness, openness, conscientiousness and neuroticism) other than extraversion in novel individuals. At the neural level, we found that the personality-associated functional networks mainly included brain regions within default mode, frontoparietal executive control, visual and cerebellar systems. Although different feature selection thresholds and parcellation strategies did not significantly influence the prediction results, some findings lost significance after controlling for confounds including age, gender, intelligence and head motion. Our finding of robust personality prediction from an individual’s unique functional connectome may help advance the translation of ‘brain connectivity fingerprinting’ into real-world personality psychological settings.

An explanation for human synesthesia

Fascinating work from Maurer et al.:

Synesthesia is a neurologic trait in which specific inducers, such as sounds, automatically elicit additional idiosyncratic percepts, such as color (thus “colored hearing”). One explanation for this trait—and the one tested here—is that synesthesia results from unusually weak pruning of cortical synaptic hyperconnectivity during early perceptual development. We tested the prediction from this hypothesis that synesthetes would be superior at making discriminations from nonnative categories that are normally weakened by experience-dependent pruning during a critical period early in development—namely, discrimination among nonnative phonemes (Hindi retroflex /d̪a/ and dental /ɖa/), among chimpanzee faces, and among inverted human faces. Like the superiority of 6-mo-old infants over older infants, the synesthetic groups were significantly better than control groups at making all the nonnative discriminations across five samples and three testing sites. The consistent superiority of the synesthetic groups in making discriminations that are normally eliminated during infancy suggests that residual cortical connectivity in synesthesia supports changes in perception that extend beyond the specific synesthetic percepts, consistent with the incomplete pruning hypothesis.

Social animals need connection for health and survival

Snyder-Mackler et al. have reviewed the relationships between social environment and many aspects of health and well-being across nonhuman mammals and investigated the similarities between these and patterns in humans. They found many of the same threats and responses across social mammals.

From their introduction:

The relationship between the social environment and mortality risk has been known in humans for some time, but studies in other social mammals have only recently been able to test for the same general phenomenon. These studies reveal that measures of social integration, social support, and, to a lesser extent, social status independently predict life span in at least four different mammalian orders. Despite key differences in the factors that structure the social environment in humans and other animals, the effect sizes that relate social status and social integration to natural life span in other mammals align with those estimated for social environmental effects in humans. Also like humans, multiple distinct measures of social integration have predictive value, and in the taxa examined thus far, social adversity in early life is particularly tightly linked to later-life survival.

Animal models have also been key to advancing our understanding of the causal links between social processes and health. Studies in laboratory animals indicate that socially induced stress has direct effects on immune function, disease susceptibility, and life span. Animal models have revealed pervasive changes in the response to social adversity that are detectable at the molecular level. Recent work in mice has also shown that socially induced stress shortens natural life spans owing to multiple causes, including atherosclerosis. This result echoes those in humans, in which social adversity predicts increased mortality risk from almost all major causes of death.

A comparative perspective on the social determinants of health (click to enlarge).

The obsolescence of three core operating systems that have shaped civilization for the past 350 years

I want to pass on a quotations from the beginning and end of Roger Cohen's essay on how honestly - on the 75th anniversary of the end of World War II in Europe - Germany is facing its fractured past:

“The nation-state alone does not have a future,” Angela Merkel, the German chancellor, said this week. It was a direct challenge to President Trump’s “America First,” the slogan whose poison keeps on giving. His United States has become the most unserious of nations.

Stephen Heintz, the president of the Rockefeller Brothers Fund, has written of a crisis “that stems from the growing obsolescence of three core operating systems that have shaped civilization for the past 350 years: capitalism, fueled by carbon since the dawn of the Industrial Age and increasingly driven by global financialization; the nation-state system, formalized by the Treaty of Westphalia in 1648; and representative democracy, a system of self-rule based on Enlightenment ideals of freedom, fairness, justice and equality.”

The problem is that “our practice of capitalism is both putting the planetary ecosystem at risk and generating vast economic inequality.” The nation-state is “inadequate for managing transnational challenges like global warming.” And “representative democracy is neither truly representative nor very democratic as citizens feel that self-rule has given way to rule by corporations, special interests and the wealthy.”

The virus and accompanying economic collapse have only redoubled the urgency of these reflections. This is the Age of Undoing — of world order, of international law, of truth, of America’s word. It is a dangerous time, as Germany knows better than any nation. Autocracy feeds on fear, misery, resentment and lies. It did in the 1930s; it does now. Better to love your country with a broken heart than to love it blind.

Rules for identifying your life's work.

During this time of virtual or postponed college graduations, Arthur Brooks does a relevant installment in his bi-weekly series for Atlantic Magazine. I'm going to pass on just sentence or two of each of his rules for graduates in finding your calling, and suggest you read the whole article:  

Rule 1. The work has to be the reward.

One of the biggest mistakes people make in their careers is to treat work primarily as a means to an end. Whether that end is money, power, or prestige, this instrumentalization of work leads to unhappiness.

Rule 2. An interesting career is better than a fun career.

Interest is considered by many neuroscientists to be a positive primary emotion, processed in the limbic system of the brain. Something that truly interests you is intensely pleasurable; it also must have meaning in order to hold your interest. Thus, “Is this work deeply interesting to me?” is a helpful litmus test of [for] a job.

Rule 3. A career doesn’t have to be a straight line.

Scholars at the University of Southern California have studied career patterns and come up with four broad categories. The first are linear careers, which climb steadily upward, with everything building on everything else...There are three others. Steady-state careers involve staying at one job and growing in expertise. Transitory careers are ones in which people jump from job to job or even field to field, looking for new challenges. Spiral careers, the last category, are more like a series of mini careers—people spend many years developing in a profession, then shift fields seeking not just for novelty, but for work that builds on the skills of their previous mini careers.

Rule 4. Beware of unhealthy passions.

This rule refines Rule 3. Yes, look for something in which you are intensely interested. But go further and ask, “Is my interest obsessive, or harmonious? Does this job or career bring out the best in me? Does it make me a happier, better person, or, in pursuing it, am I neglecting other important things life has to offer?”

AI for social good: Well meaning gobbledegook

I pass on this link to a my-eyes-glaze-over open access perspective on international efforts to use artificial intelligence for social good. The effort is a noble one, and indeed tries to deal with a very complex domain. Here is the abstract, which introduces the first of an array of acronyms:

Advances in machine learning (ML) and artificial intelligence (AI) present an opportunity to build better tools and solutions to help address some of the world’s most pressing challenges, and deliver positive social impact in accordance with the priorities outlined in the United Nations’ 17 Sustainable Development Goals (SDGs). The AI for Social Good (AI4SG) movement aims to establish interdisciplinary partnerships centred around AI applications towards SDGs. We provide a set of guidelines for establishing successful long-term collaborations between AI researchers and application-domain experts, relate them to existing AI4SG projects and identify key opportunities for future AI applications targeted towards social good.

Added note: I almost never respond positively to emails requesting that I link to a particular advocacy or commercial site, but I make an exception on receiving this morning email on 8/12/2020:

My name is Sean from Don’t Panic. We’re a Creative Advertising agency in London passionate about creating cause-related advertising campaigns for charities and brands.

I am a fan of your website and I noticed that you linked to a Nature resource discussing social good on this page https://mindblog.dericbownds.net/2020/05/ai-for-social-good-well-meaning.html.

I have put together an article exploring what social good is. I think that your readers would find this very useful. You can find it here: https://www.dontpaniclondon.com/what-is-social-good/

I’d be very grateful if you considered linking to my article in addition to the Nature resource.

Ketogenic diet enhances brain network stability, a biomarker of aging

Mujica-Parodi et al. make observations suggesting that diets that changes the predominant dietary fuel from glucose (from carbohydrates) to ketones (from fats) increase available energy and enhance functional communication between brain regions, thus showing potential in protecting the aging brain. 

Significance

To better understand how diet influences brain aging, we focus here on the presymptomatic period during which prevention may be most effective. Large-scale life span neuroimaging datasets show functional communication between brain regions destabilizes with age, typically starting in the late 40s, and that destabilization correlates with poorer cognition and accelerates with insulin resistance. Targeted experiments show that this biomarker for brain aging is reliably modulated with consumption of different fuel sources: Glucose decreases, and ketones increase the stability of brain networks. This effect replicated across both changes to total diet as well as fuel-specific calorie-matched bolus, producing changes in overall brain activity that suggest that network “switching” may reflect the brain’s adaptive response to conserve energy under resource constraint.

Abstract

Epidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether dietary changes are capable of modulating sustained functional communication between brain regions (network stability) by changing their predominant dietary fuel from glucose to ketones. We first established network stability as a biomarker for brain aging using two large-scale (n = 292, ages 20 to 85 y; n = 636, ages 18 to 88 y) 3 T functional MRI (fMRI) datasets. To determine whether diet can influence brain network stability, we additionally scanned 42 adults, age < 50 y, using ultrahigh-field (7 T) ultrafast (802 ms) fMRI optimized for single-participant-level detection sensitivity. One cohort was scanned under standard diet, overnight fasting, and ketogenic diet conditions. To isolate the impact of fuel type, an independent overnight fasted cohort was scanned before and after administration of a calorie-matched glucose and exogenous ketone ester (d-β-hydroxybutyrate) bolus. Across the life span, brain network destabilization correlated with decreased brain activity and cognitive acuity. Effects emerged at 47 y, with the most rapid degeneration occurring at 60 y. Networks were destabilized by glucose and stabilized by ketones, irrespective of whether ketosis was achieved with a ketogenic diet or exogenous ketone ester. Together, our results suggest that brain network destabilization may reflect early signs of hypometabolism, associated with dementia. Dietary interventions resulting in ketone utilization increase available energy and thus may show potential in protecting the aging brain.

How Social Networks are destroying democracy.

In the December 2019 issue of The Atlantic Haidt and Rose-Stockwell offer a must-read article titled "The Dark Psychology of Social Networks." It begins with a thought experiment asks us to imagine what chaos would result if God became bored and decided to double the gravitational constant. Birds would falls from the sky, buildings would collapse, etc.

Let’s rerun this thought experiment in the social and political world, rather than the physical one. The U.S. Constitution was an exercise in intelligent design. The Founding Fathers knew that most previous democracies had been unstable and short-lived. But they were excellent psychologists, and they strove to create institutions and procedures that would work with human nature to resist the forces that had torn apart so many other attempts at self-governance...James Madison wrote about his fear of the power of “faction,” by which he meant strong partisanship or group interest that “inflamed [men] with mutual animosity” and made them forget about the common good...The Constitution included mechanisms to slow things down, let passions cool, and encourage reflection and deliberation.

Madison’s design has proved durable. But what would happen to American democracy if, one day in the early 21st century, a technology appeared that—over the course of a decade—changed several fundamental parameters of social and political life? What if this technology greatly increased the amount of “mutual animosity” and the speed at which outrage spread? Might we witness the political equivalent of buildings collapsing, birds falling from the sky, and the Earth moving closer to the sun?

What Social Media Changed....The problem may not be connectivity itself but rather the way social media turns so much communication into a public performance...social psychologist Mark Leary coined the term sociometer to describe the inner mental gauge that tells us, moment by moment, how we’re doing in the eyes of others...Social media, with its displays of likes, friends, followers, and retweets, has pulled our sociometers out of our private thoughts and posted them for all to see...Human beings evolved to gossip, preen, manipulate, and ostracize. We are easily lured into this new gladiatorial circus, even when we know that it can make us cruel and shallow...In other words, social media turns many of our most politically engaged citizens into Madison’s nightmare: arsonists who compete to create the most inflammatory posts and images, which they can distribute across the country in an instant while their public sociometer displays how far their creations have traveled...Citizens are now more connected to one another, on platforms that have been designed to make outrage contagious.

Is There Any Way Back?...Social media has changed the lives of millions of Americans with a suddenness and force that few expected...citizens are now more connected to one another, in ways that increase public performance and foster moral grandstanding, on platforms that have been designed to make outrage contagious, all while focusing people’s minds on immediate conflicts and untested ideas, untethered from traditions, knowledge, and values that previously exerted a stabilizing effect. This, we believe, is why many Americans—and citizens of many other countries, too—experience democracy as a place where everything is going haywire...It doesn’t have to be this way...Many researchers, legislators, charitable foundations, and tech-industry insiders are now working together in search of ... improvements. We suggest three types of reform that might help:

(1) Reduce the frequency and intensity of public performance. If social media creates incentives for moral grandstanding rather than authentic communication, then we should look for ways to reduce those incentives. One such approach already being evaluated by some platforms is “demetrication,” the process of obscuring like and share counts so that individual pieces of content can be evaluated on their own merit, and so that social-media users are not subject to continual, public popularity contests.

(2) Reduce the reach of unverified accounts. Bad actors—trolls, foreign agents, and domestic provocateurs—benefit the most from the current system, where anyone can create hundreds of fake accounts and use them to manipulate millions of people. Social media would immediately become far less toxic, and democracies less hackable, if the major platforms required basic identity verification before anyone could open an account—or at least an account type that allowed the owner to reach large audiences. (Posting itself could remain anonymous, and registration would need to be done in a way that protected the information of users who live in countries where the government might punish dissent. For example, verification could be done in collaboration with an independent nonprofit organization.)

(3) Reduce the contagiousness of low-quality information. Social media has become more toxic as friction has been removed. Adding some friction back in has been shown to improve the quality of content. For example, just after a user submits a comment, AI can identify text that’s similar to comments previously flagged as toxic and ask, “Are you sure you want to post this?” This extra step has been shown to help Instagram users rethink hurtful messages. The quality of information that is spread by recommendation algorithms could likewise be improved by giving groups of experts the ability to audit the algorithms for harms and biases.

If we want our democracy to succeed—indeed, if we want the idea of democracy to regain respect in an age when dissatisfaction with democracies is rising—we’ll need to understand the many ways in which today’s social-media platforms create conditions that may be hostile to democracy’s success. And then we’ll have to take decisive action to improve social media.

Closing the gap between mind and brain - The dynamic connectome and psilocybin

Quiroga summaries elegant work by Kringelbach et al.,

...who provide a framework for incorporating into the connectome the dynamic variations caused by neuromodulatory systems...The main tenet of [their work] is that neurotransmitters’ systems can modulate the connectome over time, thus enabling a plethora of behaviors with the same underlying structural connectivity. To this end, a modeling approach is presented, in which the structural connectivity is estimated through diffusion MRI, and is coupled to the neurotransmitter system, estimated from positron electron tomography data. Both systems are portrayed by a set of mutually coupled dynamic equations, which are used to fit the functional connectivity, obtained from functional MRI. This approach was tested by exploring the effects that a psychedelic drug (psilocybin) had on neuronal activity, showing that the dynamically coupled neuronal and neuromodulatory systems give a significantly better fit to the measured data, compared to alternative models in which both systems were uncoupled, or in which the neuromodulatory system, rather than being dynamically updated, was frozen in time.

I pass on the Kringelbach et al. significance statement (not distinguished by its modesty) and abstract. The article is open source,and has excellent graphics and figures.  

Significance

In a technical tour de force, we have created a framework demonstrating the underlying fundamental principles of bidirectional coupling of neuronal and neurotransmitter dynamical systems. Specifically, in the present study, we combined multimodal neuroimaging data to causally explain the functional effects of specific serotoninergic receptor (5-HT2AR) stimulation with psilocybin in healthy humans. Longer term, this could provide a better understanding of why psilocybin is showing considerable promise as a therapeutic intervention for neuropsychiatric disorders including depression, anxiety, and addiction.

Abstract

Remarkable progress has come from whole-brain models linking anatomy and function. Paradoxically, it is not clear how a neuronal dynamical system running in the fixed human anatomical connectome can give rise to the rich changes in the functional repertoire associated with human brain function, which is impossible to explain through long-term plasticity. Neuromodulation evolved to allow for such flexibility by dynamically updating the effectivity of the fixed anatomical connectivity. Here, we introduce a theoretical framework modeling the dynamical mutual coupling between the neuronal and neurotransmitter systems. We demonstrate that this framework is crucial to advance our understanding of whole-brain dynamics by bidirectional coupling of the two systems through combining multimodal neuroimaging data (diffusion magnetic resonance imaging [dMRI], functional magnetic resonance imaging [fMRI], and positron electron tomography [PET]) to explain the functional effects of specific serotoninergic receptor (5-HT2AR) stimulation with psilocybin in healthy humans. This advance provides an understanding of why psilocybin is showing considerable promise as a therapeutic intervention for neuropsychiatric disorders including depression, anxiety, and addiction. Overall, these insights demonstrate that the whole-brain mutual coupling between the neuronal and the neurotransmission systems is essential for understanding the remarkable flexibility of human brain function despite having to rely on fixed anatomical connectivity.

Anti-Intellectualism, Populism, and Motivated Resistance to Expert Consensus

I want to pass on the abstract from Eric Merkley's article in Public Opinion Quarterly. I fervently hope that the anti-intellectuals he describes do not form a majority of those voting in the November election.

Scholars have maintained that public attitudes often diverge from expert consensus due to ideology-driven motivated reasoning. However, this is not a sufficient explanation for less salient and politically charged questions. More attention needs to be given to anti-intellectualism—the generalized mistrust of intellectuals and experts. Using data from the General Social Survey and a survey of 3,600 Americans on Amazon Mechanical Turk, I provide evidence of a strong association between anti-intellectualism and opposition to scientific positions on climate change, nuclear power, GMOs, and water fluoridation, particularly for respondents with higher levels of political interest. Second, a survey experiment shows that anti-intellectualism moderates the acceptance of expert consensus cues such that respondents with high levels of anti-intellectualism actually increase their opposition to these positions in response. Third, evidence shows anti-intellectualism is connected to populism, a worldview that sees political conflict as primarily between ordinary citizens and a privileged societal elite. Exposure to randomly assigned populist rhetoric, even that which does not pertain to experts directly, primes anti-intellectual predispositions among respondents in the processing of expert consensus cues. These findings suggest that rising anti-elite rhetoric may make anti-intellectual sentiment more salient in information processing.

Meet the psychobiome

Elizabeth Pennisi does a piece on the search for new brain drugs in human poop, generated by the ~ 2 kilograms of bacteria, fungi, viruses, and archaea that live in our gut.

..with as many as 20 million genes among them, those microbes pack a genomic punch that our measly 20,000 genes can't match. Gut bacteria can make and use nutrients and other molecules in ways the human body can't — a tantalizing source of new therapies.

Holobiome, a small startup company,...plans to capitalize on growing evidence from epidemiological and animal studies that link gut bacteria to conditions as diverse as autism, anxiety, and Alzheimer's disease. Since its founding a mere 5 years ago, Holobiome has created one of the world's largest collections of human gut microbes...A growing number of researchers see a promising alternative in microbe-based treatments, or “psychobiotics,”... the targeted ailments include depression and insomnia, as well as constipation, and visceral pain like that typical of irritable bowel syndrome—conditions that may have neurological as well as intestinal components.

One interesting approach involves finding bacteria that secrete the inhibitory neurotransmitter GABA.

One growth factor Strandwitz identified turned out to be the key to launching his entrepreneurial dreams. He and colleagues isolated a bacterium that couldn't survive on typical culture media and required an amino acid called gamma-aminobutyric acid (GABA) to thrive. GABA is a neurotransmitter that inhibits neural activity in the brain, and its misregulation has been linked to depression and other mental health problems.

The researchers reasoned that if this gut microbe had to have GABA, some other microbe must be making it. Such GABA producers might be a psychobiotic gold mine. Strandwitz and colleagues began to add gut microbes one at a time to petri dishes containing the GABA eater. If the GABA eater thrived, the scientists would know they'd found a GABA producer. They discovered such producers among three groups of bacteria, including Bactereroides. They quickly filed a patent for packaging those bacteria—or their products—to treat people with depression or other mental disorders.

Before publishing those findings, the group teamed up with researchers at Weill Cornell Medicine who were doing a brain scan study of 23 people diagnosed with depression. They found that people with fewer Bacteroides bacteria had a stronger pattern of hyperactivity in the prefrontal cortex, which some researchers have associated with severe depression. The collaboration reported its findings on 10 December 2018 in Nature Microbiology, along with the discovery of GABA-producing bacteria.

GABA is too big to reach the brain by slipping across the blood-brain barrier, a cellular defense wall that limits the size and types of molecules that can get into the brain from blood vessels. Instead, the molecule may act through the vagus nerve or the enteroendocrine cells. Some researchers might question why bacteria would be any more beneficial than GABA-boosting drugs. But Strandwitz says the bacteria may do more than simply boost GABA. He notes that they produce molecules that may have other effects on the brain and body, thereby addressing other symptoms of depression.

Arthur Brooks on "The Hero's Journey" and retirement

In the most recent installment of Arthur Brooks’ biweekly column in The Atlantic, which I suggest that you read, he talks about the classical hero's journey in literature, described by Carl Jung and Joseph Campbell as a lens through which many people see their lives:

It’s a nice narrative, especially if you’ve worked hard and done pretty well in life. The problem is the real-life ending, after the triumphant return...The hero’s journey is great when you’re in the middle of it. The trouble comes when your strengths start to wane, because now you’re off script...Joseph Campbell...notes that...“The first problem of the returning hero is to accept as real, after an experience of the soul-satisfying vision of fulfillment, the passing joys and sorrows, banalities and noisy obscenities of life.” In other words, the end of the true hero’s journey is coming home and finding a battle to be waged not with an external enemy, but with one’s own demons...your skills will decline, and life’s problems will intrude. If you try to hang on to glory, or lash out when it fades, it will squander your victories and mark an unhappy end to your journey.

Plan to spend the last part of your life serving others, loving your family and friends, and being a good example to those still in the first three stages of their own hero’s journey. Happiness in retirement depends on your choice of narrative.

Young blood plasma reverses the epigenetic aging clock.

Perhaps the best molecular biomarker of aging at present is the epigenetic clock, developed by Horvath and others, based on measurements of DNA methylation. Josh Mitteldorf points to experiments by Horvath et al. recently posted in a preprint (not yet reviewed) in bioRxiv. noting how methylation patterns characteristic of aging can be reversed.

...plasma treatment of the old rats [109 weeks] reduced the epigenetic ages of blood, liver and heart by a very large and significant margin, to levels that are comparable with the young rats [30 weeks]….According to the final version of the epigenetic clocks, the average rejuvenation across four tissues was 54.2%. In other words, the treatment more than halved the epigenetic age.

Their abstract:

Young blood plasma is known to confer beneficial effects on various organs in mice. However, it was not known whether young plasma rejuvenates cells and tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly-accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=593 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain-, liver-, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n=850 human tissue samples to the training data. We employed these six clocks to investigate the rejuvenation effects of a plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers and behavioral responses to assess cognitive functions. Cellular senescence, which is not associated with epigenetic aging, was also considerably reduced in vital organs. Overall, this study demonstrates that a plasma-derived treatment markedly reverses aging according to epigenetic clocks and benchmark biomarkers of aging.

Take the shutdown skeptics seriously.

I have been holding back from doing posts on the current pandemic, since it completely dominates the popular press. However, I want to pass on this link to one sane piece done by Conor Friedersdorf, a staff writer at The Atlantic. I will just paste in one key paragraph here, and urge you to read the whole piece.

If we knew that a broadly effective COVID-19 treatment was imminent, or that a working vaccine was months away, minimizing infections through social distancing until that moment would be the right course. At the other extreme, if we will never have an effective treatment or vaccine and most everyone will get infected eventually, then the costs of social distancing are untenable. We don’t know where we sit on that spectrum. So we cannot know what the best way forward is even if we place the highest possible value on preserving life and protecting the vulnerable.

That uncertainty means, at the very least, that Americans should carefully consider the potential costs of prolonged shutdowns lest they cause more deaths or harm to the vulnerable than they spare.

Self, purpose, and tribal mentality as Darwinian adaptations (or…Why why aren’t we all enlightened?)

This is a post like the one I offered on March 13 that passes on a bit of writing that I think might develop into a longer piece of work. I hope the following ideas and assertions make some sense to readers:

One ultimate cause of human behaviors is the endless cycling of a “Darwin machine,” operating at the level of cells, individuals, and groups of humans. As entities - from the most simple virus particles to complex human cultures - reproduce or renew themselves to persist through time, small errors or variations that end up enhancing reproductive fitness become dominant in the population. The grand master is multilevel selection, and there is a conflict between individual-level selection (individuals competing with other individuals in the same group) and group-level selection (competition between groups). Within groups selfish individuals beat altruistic individuals, but groups of altruists beat groups of selfish individuals. E.O. Wilson risks the oversimplification of suggesting that individual selection promoted sin, while group selection promoted virtue.

The array of social emotions supporting tribal cultures that have occupied most of human history, as well as the more recent emergence of language, thought, and material culture, can be rationalized with this model. Taken together, they have enabled formation of large complex societies bonded together by laws, religions, and assumptions about purpose, meaning, and self that are unique to modern humans.

Nations and religions link language and meaning to more ancient evolved instinctive social emotional behaviors that bond groups of humans and other primates. This link is revealed when logic and language are turned inward (by both ancient meditative traditions as well as modern neuroscience) in a way that reveals that our common experiences of self or purpose are confabulations, or illusions - illusions nevertheless that have been necessary for forming complex human linguistic cultures, illusions which our emotional hormones and nerve circuitry have evolved to support.

Given the clear scientific evidence, why don’t we transcend these evolved linkages between our biology and our illusions? Why have those regarded as spiritually ‘enlightened’ throughout history remained a small minority of the population? Perhaps it is because those who become enlightened or awakened to the illusory nature of the self are granted a perspective on basic emotional drives that can divests them of much of their power. Enlightenment is subtle, not noisy, it doesn't engage the passions as well as blind devotion to nations and gods. This is why secular humanism, with its more muted versions of spirituality (‘I’m spiritual but not religious’) finds it difficult to compete with the ego-rich passions of nationalism and theism.

Because our evolved social brains incline us to cling to a complex array of nations, religions, and tribal identities that parse the world into ‘us’ and ‘them,’ we find it difficult to accept that we are a common humanity that would most effectively face our current pandemic and environmental crises by joining together.

Infant behavioral inhibition predicts personality and social outcomes three decades later

From Tang et al.:

Significance

Children show different temperamental styles early in development. Whether temperament predicts who children become as adults and how early we can predict these outcomes have been long-standing questions of interest to the scientific and public community. The current study used rigorous methods to characterize an inhibited temperament by 14 mo of age in a cohort of infants and followed them for three decades. We provide the strongest and earliest evidence showing that infants with an inhibited temperament at 14 mo became introverted adults, with poorer functioning in some social and mental health domains. Also, brain activity underlying cognitive control in adolescence was associated with adult mental health. These findings highlight the lasting influence of early temperament on social-emotional development.

Abstract

Does infant temperament predict adult personality and life-course patterns? To date, there is scant evidence examining relations between child temperament and adult outcomes, and extant research has relied on limited methods for measuring temperament such as maternal report. This prospective longitudinal study followed a cohort of infants (n = 165) for three decades to examine whether infant behavioral inhibition, a temperament characterized by cautious and fearful behaviors to unfamiliar situations, shapes long-term personality, social relationships, vocational/education, and mental health outcomes in adulthood. At age 14 mo, behavioral inhibition was assessed using an observation paradigm. In adolescence (15 y; n = 115), error monitoring event-related potentials were measured in a flanker task. In adulthood (26 y; n = 109), personality, psychopathology, and sociodemographics were self-reported using questionnaires. We found that infants with higher levels of behavioral inhibition at 14 mo grew up to become more reserved and introverted adults (β = 0.34) with lower social functioning with friends and family (β = −0.23) at age 26. Infant behavioral inhibition was also a specific risk factor for adult internalizing (i.e., anxiety and depression, β = 0.20) psychopathology, rather than a transdiagnostic risk for general and externalizing psychopathology. We identified a neurophysiologic mechanism underlying risk and resilience for later psychopathology. Heightened error monitoring in adolescence moderated higher levels of adult internalizing psychopathology among behaviorally inhibited individuals. These findings suggest meaningful continuity between infant temperament and the development of adult personality. They provide the earliest evidence suggesting that the foundation of long-term well-being is rooted in individual differences in temperament observed in infancy.

Future of the Human climate niche

Sobering analysis from Xu et al. :

Significance

We show that for thousands of years, humans have concentrated in a surprisingly narrow subset of Earth’s available climates, characterized by mean annual temperatures around ∼13 °C. This distribution likely reflects a human temperature niche related to fundamental constraints. We demonstrate that depending on scenarios of population growth and warming, over the coming 50 y, 1 to 3 billion people are projected to be left outside the climate conditions that have served humanity well over the past 6,000 y. Absent climate mitigation or migration, a substantial part of humanity will be exposed to mean annual temperatures warmer than nearly anywhere today.

Abstract

All species have an environmental niche, and despite technological advances, humans are unlikely to be an exception. Here, we demonstrate that for millennia, human populations have resided in the same narrow part of the climatic envelope available on the globe, characterized by a major mode around ∼11 °C to 15 °C mean annual temperature (MAT). Supporting the fundamental nature of this temperature niche, current production of crops and livestock is largely limited to the same conditions, and the same optimum has been found for agricultural and nonagricultural economic output of countries through analyses of year-to-year variation. We show that in a business-as-usual climate change scenario, the geographical position of this temperature niche is projected to shift more over the coming 50 y than it has moved since 6000 BP. Populations will not simply track the shifting climate, as adaptation in situ may address some of the challenges, and many other factors affect decisions to migrate. Nevertheless, in the absence of migration, one third of the global population is projected to experience a MAT >29 °C currently found in only 0.8% of the Earth’s land surface, mostly concentrated in the Sahara. As the potentially most affected regions are among the poorest in the world, where adaptive capacity is low, enhancing human development in those areas should be a priority alongside climate mitigation.