The Dance of Sleep

Sleep and wakefulness are characterized by unique intrinsic activity patterns and are usually thought to be two distinct global states, with the preoptic area of the hypothalamus being the regulator of brain state changes. Yamagata et al. find that this area also affects within-state changes of sleep and wake intensity.  

Significance

Our current understanding of how sleep is regulated is based upon the model of sleep homeostasis, which defines a variable called Process S as a measure of sleep need, and a so-called “flip-flop” model of state switching, which builds on a notion of a mutually antagonistic relationship between subcortical sleep-promoting and wake-promoting circuits. The neurobiological substrates of the interaction between the sleep switch and Process S are unknown. Our study identifies a previously unrecognized role of hypothalamic circuitry in tuning within-state brain activity or levels of arousal, which in turn determine the homeostatic drive for sleep.

Abstract

Sleep and wakefulness are not simple, homogenous all-or-none states but represent a spectrum of substates, distinguished by behavior, levels of arousal, and brain activity at the local and global levels. Until now, the role of the hypothalamic circuitry in sleep–wake control was studied primarily with respect to its contribution to rapid state transitions. In contrast, whether the hypothalamus modulates within-state dynamics (state “quality”) and the functional significance thereof remains unexplored. Here, we show that photoactivation of inhibitory neurons in the lateral preoptic area (LPO) of the hypothalamus of adult male and female laboratory mice does not merely trigger awakening from sleep, but the resulting awake state is also characterized by an activated electroencephalogram (EEG) pattern, suggesting increased levels of arousal. This was associated with a faster build-up of sleep pressure, as reflected in higher EEG slow-wave activity (SWA) during subsequent sleep. In contrast, photoinhibition of inhibitory LPO neurons did not result in changes in vigilance states but was associated with persistently increased EEG SWA during spontaneous sleep. These findings suggest a role of the LPO in regulating arousal levels, which we propose as a key variable shaping the daily architecture of sleep–wake states.

The road to our larger brains

Bertrand et al. address the question of how and why mammals evolved large brain sizes relative to their body mass by characterizing the timing and pattern of mammal brain development across the Early Jurassic to the middle Cenozoic (∼200 million to 30 million years ago) when the ecological niches vacated by the extinction of large reptiles were being filled by large mammals. Here is their abstract:

Mammals are the most encephalized vertebrates, with the largest brains relative to body size. Placental mammals have particularly enlarged brains, with expanded neocortices for sensory integration, the origins of which are unclear. We used computed tomography scans of newly discovered Paleocene fossils to show that contrary to the convention that mammal brains have steadily enlarged over time, early placentals initially decreased their relative brain sizes because body mass increased at a faster rate. Later in the Eocene, multiple crown lineages independently acquired highly encephalized brains through marked growth in sensory regions. We argue that the placental radiation initially emphasized increases in body size as extinction survivors filled vacant niches. Brains eventually became larger as ecosystems saturated and competition intensified.

Humans don’t have culture because we’re smart, we’re smart because we have culture.

The title of this post is a sentence taken from the final paragraph of Henrich's Perspective article in Science on the work of Thompson et al. which notes that Thompson et al.'s results

...highlight a deeper point: Humans don’t have culture because we’re smart, we’re smart because we have culture. The selective processes of cultural evolution not only generate more sophisticated practices and technologies but also produce new cognitive tools—algorithms—that make humans better adapted to the ecological and institutional challenges that we confront. Thompson et al.’s results underline the need for the psychological sciences to abandon their implicit reliance on a digital computer metaphor of the mind (hardware versus software) and transform into a historical science that considers not just how cultural evolution shapes what we think (our mental contents) but also how we think [our cognitive processes].

Here I pass on the introductory paragraphs and then the abstract of the Thompson et al. article. Motivated readers can obtain the full text by emailing me.

Reading, counting, cooking, and sailing are just some of the human abilities passed from generation to generation through social learning... Complex abilities like these often depend on learned cognitive algorithms: procedural representations of a problem that coordinate memory, attention, and perception into sequences of useful computations and actions. Accumulation of complex algorithms—from ancient tool-making techniques to bread making, boat building, or horticulture—is central to human adaptation yet challenging to explain because algorithmic concepts can be difficult to discover, communicate, and learn from observation, making them vulnerable to loss. Theories of cultural evolution suggest that human social learning may help overcome this fragility. For example, mathematical models predict that choosing to learn from successful or prestigious individuals can prevent the loss of rare innovations. However, this potential link between sociality and complex abilities is challenging to establish.

We conducted large-scale simulations of cultural evolution with human participants to assess how selective social learning influenced the evolution of cognitive algorithms. Prior research shows that social learning can improve decisions in multiple-choice tasks, perceptual judgments, and search problems and can improve artifacts such as physical structures or computer programs. However, the evolution of cognitive algorithms at the population level has been difficult to study. We developed custom software to recruit large numbers of participants online and organize them into evolving societies facing a common problem. Twenty populations tackled a sequential decision problem... Presented with six images, participants attempted to establish hidden arbitrary orderings using pairwise comparisons. Out-of-order pairs swapped positions when compared. Participants were rewarded for establishing the ordering using fewer comparisons. This task poses a sorting problem, requiring a strategy for executing appropriate sequences of actions, analogous to culturally evolved strategies for making tools or food.

Abstract:

Many human abilities rely on cognitive algorithms discovered by previous generations. Cultural accumulation of innovative algorithms is hard to explain because complex concepts are difficult to pass on. We found that selective social learning preserved rare discoveries of exceptional algorithms in a large experimental simulation of cultural evolution. Participants (N = 3450) faced a difficult sequential decision problem (sorting an unknown sequence of numbers) and transmitted solutions across 12 generations in 20 populations. Several known sorting algorithms were discovered. Complex algorithms persisted when participants could choose who to learn from but frequently became extinct in populations lacking this selection process, converging on highly transmissible lower-performance algorithms. These results provide experimental evidence for hypothesized links between sociality and cognitive function in humans.

The Science of Consciousness - Tucson 2022

For junkies of consciousness and altered states thereof, as in anesthesia or psychedelic-induced states, a browsing of the abstracts submitted for The Science of Consciousness 2022 in Tucson April 18-22 makes for stimulating reading (though I found pauses to recover from input overload to be necessary.) I attended the first “Towards a Science of Consciousness” - now known as TSC “The Science of Consciousness” - in 1994, as well as a number of subsequent meetings, and it was encouragement from several then luminaries in the field that emboldened me to turn the lecture notes from my “Biology of Mind” course at the University of Wisconsin into a book of that title which was published in 1999. There are numerous bon-bons to be found in this year's set of abstracts, one example from many being Huang’s noting of his work on how the anterior insula, situated between unimodal and transmodal cortical areas along the brain’s primary functional gradient, regulates the default mode – dorsal attention network transitions, and gates conscious access of sensory information.

Magic mind therapy….. Moving your body.

Gretchen Reynolds interviews Jennifer Heisz about the contents of her new book "Move the Body, Heal the Mind," which details the latest science about exercise and mental health, especially its potential to reduce anxiety and stress. The brief reprieve from anxiety than can sometimes be experienced after a workout is due to the release of neuropeptide Y, known to dampen hyperactivity of the anxious amygdala. Exercise also can reduce stress-induced body inflammation that damages cells and affects mood. These effects require only about a quarter of the normally recommended 150 minutes of moderate to vigorous exercise a week, so the exercise prescription for mental health seems to be less than that for physical health.

Losing sleep with age.

Jacobson and Hoyer summarize experiments of Li et al.:

Humans spend approximately one-third of their lives asleep, but this is not distributed equally across their life span. Sleep quantity and quality decline as age advances, and insomnia and sleep fractionation are common in older people. Sleep is essential for vitality and health. At any age, chronic sleep deprivation causes a range of issues, including disrupted cognition and memory. Correspondingly, sleep complaints in older people are associated with increased risks of impaired physical and mental health and with mortality. Beyond evidence of degenerating subcortical nuclei in age-associated sleep disturbances, the underlying mechanisms remain unclear despite decades of awareness of the problem and its consequences...Li et al.report the hyperexcitability of hypocretin neurons as a core mechanism underlying sleep disruption in aged mice, explaining why sleep is punctuated by intruding wakefulness despite the loss of wake-promoting neurons.

A few clips from the Li et al. article: 

RATIONALE

We hypothesized that the decline in sleep quality could be due to malfunction of the neural circuits associated with sleep/wake control. It has been established that hypocretin/orexin (Hcrt/OX) neuronal activity is tightly associated with wakefulness and initiates and maintains the wake state. In this study, we investigated whether the intrinsic excitability of Hcrt neurons is altered, leading to a destabilized control of sleep/wake states during aging.

RESULTS

Aged mice exhibited sleep fragmentation and a significant loss of Hcrt neurons. Hcrt neurons manifested a more frequent firing pattern, driving wake bouts and disrupting sleep continuity in aged mice. Aged Hcrt neurons were capable of eliciting more prolonged wake bouts upon optogenetic stimulations. These results suggested that hyperexcitability of Hcrt neurons emerges with age. Patch clamp recording in genetically identified Hcrt neurons revealed distinct intrinsic properties between the young and aged groups. Aged Hcrt neurons were hyperexcitable with depolarized membrane potentials (RMPs) and a smaller difference between RMP and the firing threshold.

CONCLUSION

Aged mice exhibited sleep fragmentation and a significant loss of Hcrt neurons. Hcrt neurons manifested a more frequent firing pattern, driving wake bouts and disrupting sleep continuity in aged mice. Aged Hcrt neurons were capable of eliciting more prolonged wake bouts upon optogenetic stimulations. These results suggested that hyperexcitability of Hcrt neurons emerges with age. Patch clamp recording in genetically identified Hcrt neurons revealed distinct intrinsic properties between the young and aged groups. Aged Hcrt neurons were hyperexcitable with depolarized membrane potentials (RMPs) and a smaller difference between RMP and the firing threshold.

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.