Re-energizing the aged brain

Alderton does a brief summary of work by Brakedal et al.:

Nicotinamide adenine dinucleotide (NAD) is an important cofactor in numerous metabolic reactions. NAD concentrations decline with age, which may contribute to age-associated conditions such as Parkinson’s disease. Preclinical studies show that replenishing NAD by supplementation with nicotinamide riboside (NR), a biosynthetic precursor to NAD, can promote health span and neuroprotection. Brakedal et al. performed a randomized, double-blind phase 1 clinical trial of NR supplementation in 30 patients newly diagnosed with Parkinson’s disease. They found that NR supplementation was safe and that concentrations of NAD in the brain increased in most patients receiving NR. These patients had signs of altered cerebral metabolism and mild clinical improvement, although further testing is needed with a larger cohort to confirm any clinical benefit.

Added note: I realized I had bought a jar of nicotinamide riboside some time ago ("TRU - Niagen" at an outrageious price), decided not to take it after reading about possible side effects, but relented after reading the Brakedal et al. article. I've been taking a 150 mg capsule daily for the past 10 days, half the recommended dosage. I haven't detected any noticable effects on my general energy levels.

Abnormal hemispheric interactions of Autism Spectrum Disorder present in 1st year of life.

From Rolison et al.:

Autism spectrum disorder (ASD) is characterized by atypical connectivity lateralization of functional networks. However, previous studies have not directly investigated if differences in specialization between ASD and typically developing (TD) peers are present in infancy, leaving the timing of onset of these differences relatively unknown. We studied the hemispheric asymmetries of connectivity in children with ASD and infants later meeting the diagnostic criteria for ASD. Analyses were performed in 733 children with ASD and TD peers and in 71 infants at high risk (HR) or normal risk (NR) for ASD, with data collected at 1 month and 9 months of age. Comparing children with ASD (n = 301) to TDs (n = 432), four regions demonstrated group differences in connectivity: posterior cingulate cortex (PCC), posterior superior temporal gyrus, extrastriate cortex, and anterior prefrontal cortex. At 1 month, none of these regions exhibited group differences between ASD (n = 10), HR-nonASD (n = 15), or NR (n = 18) infants. However, by 9 months, the PCC and extrastriate exhibited atypical connectivity in ASD (n = 11) and HR-nonASD infants (n = 24) compared to NR infants (n = 22). Connectivity did not correlate with symptoms in either sample. Our results demonstrate that differences in network asymmetries associated with ASD risk are observable prior to the age of a reliable clinical diagnosis.

Trust is needed to run the world, and crypto can make trusting easier

I want to pass on a few clips from a recent screed by Mark Manson in his usual explitive-rich style. I regret that he doesn't make clear the central point that it is the blockchain concept underlying various cryptocurrencies that is responsible for generating trustworthy transactions, without requiring the intervention of third parties like banks, inspectors, and regulators to certify trustworthiness. Here are my clips and pastings:

The problem is that trust-building institutions are human. And humans are, uh, not really trustworthy....there are millions of people in the world whose entire jobs are to verify trustworthiness. Insurance companies, banks, legal firms, universities, regulatory agencies, and government programs have massive office buildings full of nothing but people doing this trustworthy verification thing, all day every day... because we have not other better way to do it...and the process is corruptible because it is human.

The way Uber automated away taxi drivers, crypto will automate away millions of these trust verifiers...you can shake your fist and make please about job security and income inequality or whatever, but at the end of the day...we will all love it and use it for the same reason we love and use Uber...because it makes our lives a hundred times easier...dealing with human-led institution to constantly verify trust is a never-ending nightmare...submissionsw of hundreds of pages of paperwork...All it takes is one pissed off guy at the DMV to literally prevent you from being able to legally drive. All it takes is one asshoel banker on a power trip to fuck up your ability to buy a home.

That is why I believe crypto is inevitable...but messy...crypto is market-testing hundreds of different types of governance models, security protocols, capitalization allocations, wealth redistribution, brand-building. What happend in 100 years in the real world happens in a couple months in the crypto world...eventually, it will catch up. The governance systems will be better, faster, more reliable, more secure, and censorship-proof. But part of that market-testing is subjecting itself to hundreds of hacks, ponzis, rug pulls, saboteurs, scam artists, rip-offs, and dum dog coins. ...in order to automate and upgrade trust-verifying institutions, you must rebuild and/or replace those institutions. And those institutions are unlikely to go quietly.

Neurons in the brain that respond mainly to singing

New work from Norman-Haignere et al. describes a population of cells in our auditory cortex, located between the music and speech-selective areas, that is responsive to singing, but not to instrumental music or speech. (Their experiments were done on patients who were in hospital with electrodes implanted into their heads for epilepsy treatment, allowing more precise location data than can be obtained from fMRI scans.) Their result is consonant with a popular theory that singing has an important role in the evolution of music and language. Their abstract:  

Highlights

• Neural population responsive to singing, but not instrumental music or speech 

• New statistical method infers neural populations from human intracranial responses 

• fMRI used to map the spatial distribution of intracranial responses 

• Intracranial responses replicate distinct music- and speech-selective populations

Summary

How is music represented in the brain? While neuroimaging has revealed some spatial segregation between responses to music versus other sounds, little is known about the neural code for music itself. To address this question, we developed a method to infer canonical response components of human auditory cortex using intracranial responses to natural sounds, and further used the superior coverage of fMRI to map their spatial distribution. The inferred components replicated many prior findings, including distinct neural selectivity for speech and music, but also revealed a novel component that responded nearly exclusively to music with singing. Song selectivity was not explainable by standard acoustic features, was located near speech- and music-selective responses, and was also evident in individual electrodes. These results suggest that representations of music are fractionated into subpopulations selective for different types of music, one of which is specialized for the analysis of song.

Mellow Mice - Why deep breathing can keep us calm

How we are breathing is usally a good indicator of whether we are calm or aroused. When we become anxious or aroused, usually the best thing we can do is stop and take a deep breath. Gretchen Reynolds points to interesting work in mice that suggests that taking deep breaths is calming because it does not activate neurons in the brain's breathing center that communicate with the brain's arousal center (breathing pacemakers in humans closely resemble those in mice). Here is the abstract from Yackle et al.:

Slow, controlled breathing has been used for centuries to promote mental calming, and it is used clinically to suppress excessive arousal such as panic attacks. However, the physiological and neural basis of the relationship between breathing and higher-order brain activity is unknown. We found a neuronal subpopulation of about 350 neurons in the mouse preBötzinger complex (preBötC), the primary breathing rhythm generator, which regulates the balance between calm and arousal behaviors. Conditional, bilateral genetic ablation of the ~175 Cdh9/Dbx1 double-positive preBötC neurons in adult mice left breathing intact but increased calm behaviors and decreased time in aroused states. These neurons project to, synapse on, and positively regulate noradrenergic neurons in the locus coeruleus, a brain center implicated in attention, arousal, and panic that projects throughout the brain.

Difference in knowledge production by global north and south

Torres et al. do an interesting analysis:

Significance

Contemporary social sciences aim to be diverse and inclusive, but traces of the historical dominance of Western European and North American academic institutions persist in scientific practices. One such practice is the phrasing of article titles. Our analysis shows that articles studying the global North are systematically less likely to mention the name of the country they study in their title compared to articles on the global South. This constitutes, potentially, an unwarranted claim on universality and may lead to lesser recognition of global South studies. Social and behavioral scientists must reflect on the phrasing of their article titles to avoid reproducing harmful relations of intellectual domination which limit inclusivity and constitute a barrier to the generalizability of scientific knowledge.

Abstract

The legacy of Eurocentrism continues to affect knowledge production in the social sciences. Evidence produced in and about the global North is assumed to be more “universal,” whereas evidence from or produced in the global South is considered valid only for specific contexts (i.e., “localized”). We argue that these dynamics are evident in the phrasing of articles’ titles based on the examination of more than half a million social science research articles indexed by Scopus (1996 to 2020). We find that empirical articles written by authors affiliated to institutions of the global North, using data from these countries, are less likely to include a concrete geographical reference in their titles. When authors are affiliated to global South institutions, and use evidence from global South countries, the names of these countries are more likely to be part of the article’s title. We confirm this overarching pattern by looking at 1) differences between world regions, 2) differences within world regions, and 3) patterns in 23 social science subfields. These gaps are large and consistent, yet article naming conventions are merely the “tip of the iceberg” of the imbalances in knowledge production between the global North and South.

How exercise supports the brain

From Leiter et al. "Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging":

Highlights 

• Selenium mediates the exercise-induced increase in adult hippocampal neurogenesis 

• Selenium increases hippocampal precursor proliferation and adult neurogenesis 

• Selenium reverses cognitive decline in aging and in hippocampal injury 

Summary 

Although the neurogenesis-enhancing effects of exercise have been extensively studied, the molecular mechanisms underlying this response remain unclear. Here, we propose that this is mediated by the exercise-induced systemic release of the antioxidant selenium transport protein, selenoprotein P (SEPP1). Using knockout mouse models, we confirmed that SEPP1 and its receptor low-density lipoprotein receptor-related protein 8 (LRP8) are required for the exercise-induced increase in adult hippocampal neurogenesis. In vivo selenium infusion increased hippocampal neural precursor cell (NPC) proliferation and adult neurogenesis. Mimicking the effect of exercise through dietary selenium supplementation restored neurogenesis and reversed the cognitive decline associated with aging and hippocampal injury, suggesting potential therapeutic relevance. These results provide a molecular mechanism linking exercise-induced changes in the systemic environment to the activation of quiescent hippocampal NPCs and their subsequent recruitment into the neurogenic trajectory.

Addicted to dreaming.

Dopamine (DA) is usually associated with pleasure and addiction. Now Hasegawa et al. show that release of DA in the basolateral amygdala (BLA), a brain structure associated with emotional processing, can trigger rapid eye movement (REM) dreaming sleep in mice.

The sleep cycle is characterized by alternating non–rapid eye movement (NREM) and rapid eye movement (REM) sleeps. The mechanisms by which this cycle is generated are incompletely understood. We found that a transient increase of dopamine (DA) in the basolateral amygdala (BLA) during NREM sleep terminates NREM sleep and initiates REM sleep. DA acts on dopamine receptor D2 (Drd2)–expressing neurons in the BLA to induce the NREM-to-REM transition. This mechanism also plays a role in cataplectic attacks—a pathological intrusion of REM sleep into wakefulness—in narcoleptics. These results show a critical role of DA signaling in the BLA in initiating REM sleep and provide a neuronal basis for sleep cycle generation.

The manly art of self-promotion

Exley and Kessler suggest that gender wage gaps may have roots in men being more self-promoting than women:

We run a series of experiments involving over 4,000 online participants and over 10,000 school-aged youth. When individuals are asked to subjectively describe their performance on a male-typed task relating to math and science, we find a large gender gap in self-evaluations. This gap arises when self-evaluations are provided to potential employers, and thus measure self-promotion, and when self-evaluations are not driven by incentives to promote. The gender gap in self-evaluations proves to be persistent and arises as early as the sixth grade. No gender gap arises if individuals are asked about their performance on a more female-typed task.

Genes for loving nature.

From Chang et al.:

Nature experiences have been linked to mental and physical health. Despite the importance of understanding what determines individual variation in nature experience, the role of genes has been overlooked. Here, using a twin design (TwinsUK, number of individuals = 2,306), we investigate the genetic and environmental contributions to a person’s nature orientation, opportunity (living in less urbanized areas), and different dimensions of nature experience (frequency and duration of public nature space visits and frequency and duration of garden visits). We estimate moderate heritability of nature orientation (46%) and nature experiences (48% for frequency of public nature space visits, 34% for frequency of garden visits, and 38% for duration of garden visits) and show their genetic components partially overlap. We also find that the environmental influences on nature experiences are moderated by the level of urbanization of the home district. Our study demonstrates genetic contributions to individuals’ nature experiences, opening a new dimension for the study of human–nature interactions.

The Life Cycle of Outrage

 I have to pass on this great piece by Mark Manson on the life cycle of a 'significant event'.  

A feeling of loss in the abstraction of all those beautiful things into streams and algorithms...

I pass on a single paragraph from A.O.Scott's recent essay "Shelf Life: Our Collections and the Passage of Time" and suggest you read the whole piece, an engaging illustrated commentary on generational and cultural change:

And that is the substance, so to speak, of Klosterman’s (author of "The Nineties") relentless cataloging and Aksel’s (a character in "The Worst Person in the World" comedy series) lamentation for lost record stores. The digitization of culture — the abstraction of all those beautiful things into streams and algorithms — feels to many of us like a permanent loss. What kind of a loss can be hard to specify, since there is also clearly a benefit. In the old days, Aksel might not have been able to watch “Dog Day Afternoon” over and over again. He might have had to wait until it showed up at a revival house, or until the previous customer returned the only VHS copy to the video store. Now he can stream “Back to Dungaree High” on a playlist with his other favorites. Klosterman can watch any episode of “Seinfeld” or “The Simpsons” any time he wants.

Listening to our bodies can make us more resilient to stress

Jane Brody points to work from Haas et al. suggesting that resilience is more about body awareness than rational thinking. In their experiments subjects who had more subjective awareness of their internal feelings were less emotionally reactive to stress (showing less heart rate increase, shallow breathing, blood adrenaline increase), and recovered more quickly from it. Increased awareness of interoceptive stress signals from the body appears to enable stronger top-down suppression of the stress response. Here is the abstract from the Haas et al. article:

This study examined neural processes of resilience during aversive interoceptive processing. Forty-six individuals were divided into three groups of resilience Low (LowRes), high (HighRes), and normal (NormRes), based on the Connor-Davidson Resilience Scale (2003). Participants then completed a task involving anticipation and experience of loaded breathing during functional magnetic resonance imaging (fMRI) recording. Compared to HighRes and NormRes groups, LowRes self-reported lower levels of interoceptive awareness and demonstrated higher insular and thalamic activation across anticipation and breathing load conditions. Thus, individuals with lower resilience show reduced attention to bodily signals but greater neural processing to aversive bodily perturbations. In low resilient individuals, this mismatch between attention to and processing of interoceptive afferents may result in poor adaptation in stressful situations.

AI-synthesized faces are indistinguishable from real faces and more trustworthy

A sobering open source aricle from Nightingale and Farid than suggests the impossibility of sorting our the real from the fake. Synthesized faces tend to look more like average faces which themselves are deemed more trustworthy.

Artificial intelligence (AI)–synthesized text, audio, image, and video are being weaponized for the purposes of nonconsensual intimate imagery, financial fraud, and disinformation campaigns. Our evaluation of the photorealism of AI-synthesized faces indicates that synthesis engines have passed through the uncanny valley and are capable of creating faces that are indistinguishable—and more trustworthy—than real faces.

Seven Habits That Lead to Happiness in Old Age

I want to point to this self-help article by Arthur Brooks in The Atlantic, part of his 'How to Build a Life' series. It's bottom line, derived from data in the famous Harvard Study of Adult Development begun in 1938, is that Happy-well seniors accumulate resources and habits in their Happiness 401(k)s during their younger lives by practicing the following injunctions. 

1. Don't smoke 

2. Watch your drinking 

3. Maintain a healthy body weight 

4. Prioritize physical movement in your life 

5. Practice coping mechanisms 

6 Keep learning 

 7 Cultivate stable long term relationships.

Reconsidering evidence of moral contagion in online social networks

Burton et al. raise some cautions about recent studies seeming to show that inclusion of emotional terms in social media text messages increases message diffusion. Here is a clip from their text, followed by the article abstract:

...we created an absurd factor for illustrative purposes, what we call XYZ contagion, and tested whether the number of X’s, Y’s and Z’s included in messages’ text predicted diffusion...Our analysis found XYZ contagion to be present in four of our six corpora such that the presence of the letters X, Y and Z predicted an increase in message diffusion: COVID-19 tweets...#MeToo tweets...#MuellerReport tweets...2016 US Election tweets...While there was no positive relationship between the presence of X, Y and Z and message diffusion in the #WomensMarch and Post-Brexit tweets, the finding that XYZ contagion passes a key test of robustness, viz. out-of-sample prediction, demonstrates the potential of large-scale social media datasets to contain spurious correlations

Abstract

The ubiquity of social media use and the digital data traces it produces has triggered a potential methodological shift in the psychological sciences away from traditional, laboratory-based experimentation. The hope is that, by using computational social science methods to analyse large-scale observational data from social media, human behaviour can be studied with greater statistical power and ecological validity. However, current standards of null hypothesis significance testing and correlational statistics seem ill-suited to markedly noisy, high-dimensional social media datasets. We explore this point by probing the moral contagion phenomenon, whereby the use of moral-emotional language increases the probability of message spread. Through out-of-sample prediction, model comparisons and specification curve analyses, we find that the moral contagion model performs no better than an implausible XYZ contagion model. This highlights the risks of using purely correlational evidence from large observational datasets and sounds a cautionary note for psychology’s merge with big data.

Predictions help neurons, and the brain, learn

From the PNAS Journal Club, a review of a publication by Luczak et. al. that suggest that neurons might be able to predict their own future activity, and learn to improve the accuracy of those predictions. The review expands on the Luczak et al abstract, which I pass on here:

Understanding how the brain learns may lead to machines with human-like intellectual capacities. It was previously proposed that the brain may operate on the principle of predictive coding. However, it is still not well understood how a predictive system could be implemented in the brain. Here we demonstrate that the ability of a single neuron to predict its future activity may provide an effective learning mechanism. Interestingly, this predictive learning rule can be derived from a metabolic principle, whereby neurons need to minimize their own synaptic activity (cost) while maximizing their impact on local blood supply by recruiting other neurons. We show how this mathematically derived learning rule can provide a theoretical connection between diverse types of brain-inspired algorithm, thus offering a step towards the development of a general theory of neuronal learning. We tested this predictive learning rule in neural network simulations and in data recorded from awake animals. Our results also suggest that spontaneous brain activity provides ‘training data’ for neurons to learn to predict cortical dynamics. Thus, the ability of a single neuron to minimize surprise—that is, the difference between actual and expected activity—could be an important missing element to understand computation in the brain.

Consciousness is supported by near-critical slow cortical electrodynamics

An open source offering from Toker et al. that has a nice summary graphic.:  

Significance

What changes in the brain when we lose consciousness? One possibility is that the loss of consciousness corresponds to a transition of the brain’s electric activity away from edge-of-chaos criticality, or the knife’s edge in between stability and chaos. Recent mathematical developments have produced tools for testing this hypothesis, which we apply to cortical recordings from diverse brain states. We show that the electric activity of the cortex is indeed poised near the boundary between stability and chaos during conscious states and transitions away from this boundary during unconsciousness and that this transition disrupts cortical information processing.

Abstract

Mounting evidence suggests that during conscious states, the electrodynamics of the cortex are poised near a critical point or phase transition and that this near-critical behavior supports the vast flow of information through cortical networks during conscious states. Here, we empirically identify a mathematically specific critical point near which waking cortical oscillatory dynamics operate, which is known as the edge-of-chaos critical point, or the boundary between stability and chaos. We do so by applying the recently developed modified 0-1 chaos test to electrocorticography (ECoG) and magnetoencephalography (MEG) recordings from the cortices of humans and macaques across normal waking, generalized seizure, anesthesia, and psychedelic states. Our evidence suggests that cortical information processing is disrupted during unconscious states because of a transition of low-frequency cortical electric oscillations away from this critical point; conversely, we show that psychedelics may increase the information richness of cortical activity by tuning low-frequency cortical oscillations closer to this critical point. Finally, we analyze clinical electroencephalography (EEG) recordings from patients with disorders of consciousness (DOC) and show that assessing the proximity of slow cortical oscillatory electrodynamics to the edge-of-chaos critical point may be useful as an index of consciousness in the clinical setting.

Illusory faces are more likely to be perceived as male than female

Interesting observations from Wardle et al.:

Despite our fluency in reading human faces, sometimes we mistakenly perceive illusory faces in objects, a phenomenon known as face pareidolia. Although illusory faces share some neural mechanisms with real faces, it is unknown to what degree pareidolia engages higher-level social perception beyond the detection of a face. In a series of large-scale behavioral experiments (ntotal = 3,815 adults), we found that illusory faces in inanimate objects are readily perceived to have a specific emotional expression, age, and gender. Most strikingly, we observed a strong bias to perceive illusory faces as male rather than female. This male bias could not be explained by preexisting semantic or visual gender associations with the objects, or by visual features in the images. Rather, this robust bias in the perception of gender for illusory faces reveals a cognitive bias arising from a broadly tuned face evaluation system in which minimally viable face percepts are more likely to be perceived as male.

Our brains store concepts as sensory-motor and affective information

Fascinating work from Fernandino et al., who show that concept representations are not independent of sensory-motor experience: 

Significance

The ability to identify individual objects or events as members of a kind (e.g., “knife,” “dog,” or “party”) is a fundamental aspect of human cognition. It allows us to quickly access a wealth of information pertaining to a newly encountered object or event and use it to guide our behavior. How is this information represented in the brain? We used functional MRI to analyze patterns of brain activity corresponding to hundreds of familiar concepts and quantitatively characterized the informational structure of these patterns. Our results indicate that conceptual knowledge is stored as patterns of neural activity that encode sensory-motor and affective information about each concept, contrary to the long-held idea that concept representations are independent of sensory-motor experience.

Abstract

The nature of the representational code underlying conceptual knowledge remains a major unsolved problem in cognitive neuroscience. We assessed the extent to which different representational systems contribute to the instantiation of lexical concepts in high-level, heteromodal cortical areas previously associated with semantic cognition. We found that lexical semantic information can be reliably decoded from a wide range of heteromodal cortical areas in the frontal, parietal, and temporal cortex. In most of these areas, we found a striking advantage for experience-based representational structures (i.e., encoding information about sensory-motor, affective, and other features of phenomenal experience), with little evidence for independent taxonomic or distributional organization. These results were found independently for object and event concepts. Our findings indicate that concept representations in the heteromodal cortex are based, at least in part, on experiential information. They also reveal that, in most heteromodal areas, event concepts have more heterogeneous representations (i.e., they are more easily decodable) than object concepts and that other areas beyond the traditional “semantic hubs” contribute to semantic cognition, particularly the posterior cingulate gyrus and the precuneus.