Possible mechanism of psychedelic therapeutic effects

From the latest issue of Science Magazine:  

The mechanism underlying psychedelic action

Psychedelic compounds promote cortical structural and functional neuroplasticity through the activation of serotonin 2A receptors. However, the mechanisms by which receptor activation leads to changes in neuronal growth are still poorly defined. Vargas et al. found that activation of intracellular serotonin 2A receptors is responsible for the plasticity-promoting and antidepressant-like properties of psychedelic compounds, but serotonin may not be the natural ligand for those intracellular receptors (see the Perspective by Hess and Gould). —PRS

Abstract

Decreased dendritic spine density in the cortex is a hallmark of several neuropsychiatric diseases, and the ability to promote cortical neuron growth has been hypothesized to underlie the rapid and sustained therapeutic effects of psychedelics. Activation of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) is essential for psychedelic-induced cortical plasticity, but it is currently unclear why some 5-HT2AR agonists promote neuroplasticity, whereas others do not. We used molecular and genetic tools to demonstrate that intracellular 5-HT2ARs mediate the plasticity-promoting properties of psychedelics; these results explain why serotonin does not engage similar plasticity mechanisms. This work emphasizes the role of location bias in 5-HT2AR signaling, identifies intracellular 5-HT2ARs as a therapeutic target, and raises the intriguing possibility that serotonin might not be the endogenous ligand for intracellular 5-HT2ARs in the cortex.

MindBlog picks some of its favorite posts on defining what a self is…

The following links are from a recent scan of what pops up if I click on items in ‘Selected MindBlog Categories’ in the right column of this page - to remind myself of some of the results of my personal reflections on the topics indicated. The chronological list starts with the most recent posts.

Enlightenment, Habituation, and Renewal - Or, Mindfulness as the opiate of the thinking classes?

The non-duality industry as a panacea for the anxieties of our times? 

I am not my problem

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

MindBlog passes on a note: on the relief of not being yourself.

Some rambling on "Selves" and “Purpose"

Why don’t we do what we know works better?

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

A fish passes the mirror self recognition test!

Our human abilities continue to found in more evolutionarily distant species. From Kohda et al.:

Some animals have the remarkable capacity for mirror self-recognition (MSR), yet any implications for self-awareness remain uncertain and controversial. This is largely because explicit tests of the two potential mechanisms underlying MSR are still lacking: mental image of the self and kinesthetic visual matching. Here, we test the hypothesis that MSR ability in cleaner fish, Labroides dimidiatus, is associated with a mental image of the self, in particular the self-face, like in humans. Mirror-naive fish initially attacked photograph models of both themselves and unfamiliar strangers. In contrast, after all fish had passed the mirror mark test, fish did not attack their own (motionless) images, but still frequently attacked those of unfamiliar individuals. When fish were exposed to composite photographs, the self-face/unfamiliar body were not attacked, but photographs of unfamiliar face/self-body were attacked, demonstrating that cleaner fish with MSR capacity recognize their own facial characteristics in photographs. Additionally, when presented with self-photographs with a mark placed on the throat, unmarked mirror-experienced cleaner fish demonstrated throat-scraping behaviors. When combined, our results provide clear evidence that cleaner fish recognize themselves in photographs and that the likely mechanism for MSR is associated with a mental image of the self-face, not a kinesthetic visual-matching model. Humans are also capable of having a mental image of the self-face, which is considered an example of private self-awareness. We demonstrate that combining mirror test experiments with photographs has enormous potential to further our understanding of the evolution of cognitive processes and private self-awareness across nonhuman animals.

Fundamentally rethinking what a mind is and how a brain works.

The February Issue of Trends in Cognitive Science has an open source Opinions article from Lisa Feldman Barrett and collaborators that suggests that new research approaches grounded in different ontological commitments will be required to properly describe brain-behavior relationships. Here is a clip of the introductory text and a graphic clip from the article. Finally, I pass on the concluding remarks on fundamentally rethinking what a mind is and how a brain works.

Most brain imaging studies present stimuli and measure behavioral responses in temporal units (trials) that are ordered randomly. Participants’ brain signals are typically aggregated to model structured variation that allows inferences about the broader population from which people were sampled. These methodological details, when used to study any phenomenon of interest, often give rise to brain-behavior findings that vary unexpectedly (across stimuli, context, and people). Such findings are typically interpreted as replication failures, with the observed variation discounted as error caused by less than rigorous experimentation (Box 1). Methodological rigor is of course important, but replication problems may stem, in part, from a more pernicious source: faulty assumptions (i.e., ontological commitments) that mis-specify the psychological phenomena of interest.

In this paper, we review three questionable assumptions whose reconsideration may offer opportunities for a more robust and replicable science: 

 (1) The localization assumption: the instances that constitute a category of psychological events (e.g., instances of fear) are assumed to be caused by a single, dedicated psychological process implemented in a dedicated neural ensemble (see Glossary). 

 (2) The one-to-one assumption: the dedicated neural ensemble is assumed to map uniquely to that psychological category, such that the mapping generalizes across contexts, people, measurement strategies, and experimental designs. 

 (3) The independence assumption: the dedicated neural ensemble is thought to function independently of contextual factors, such as the rest of the brain, the body, and the surrounding world, so the ensemble can be studied alone without concern for those other factors. Contextual factors might moderate activity in the neural ensemble but should not fundamentally change its mapping to the instances of a psychological category. 

 These three assumptions are rooted in a typological view of the mind, brain, and behavior [1. ] that was modeled on 19th century physics and continues to guide experimental practices in much of brain-behavior research to the present day. In this paper, we have curated examples from studies of human functional magnetic resonance imaging (fMRI) and neuroscience research using non-human animals that call each assumption into question. We then sketch the beginnings of an alternative approach to study brain-behavior relationships, grounded in different ontological commitments: (i) a mental event comprises distributed activity across the whole brain; (ii) brain and behavior are linked by degenerate (i.e., many-to-one) mappings; and (iii) mental events emerge as a complex ensemble of weak, nonlinearly interacting signals from the brain, body, and external world.

 

Concluding remarks

Scientific communities tacitly agree on assumptions about what exists (called ontological commitments), what questions to ask, and what methods to use. All assumptions are firmly rooted in a philosophy of science that need not be acknowledged or discussed but is practiced nonetheless. In this article, we questioned the ontological commitments of a philosophy of science that undergirds much of modern neuroscience research and psychological science in particular. We demonstrated that three common commitments should be reconsidered, along with a corresponding course correction in methods. Our suggestions require more than merely improved methodological rigor for traditional experimental design. Such improvements are important, but may aid robustness and replicability only when the ontological assumptions behind those methods are valid. Accordingly, a productive way forward may be to fundamentally rethink what a mind is and how a brain works. We have suggested that mental events arise from a complex ensemble of signals across the entire brain, as well as the from the sensory surfaces of the body that inform on the states of the inner body and outside world, such that more than one signal ensemble maps to a single instance of a single psychological category (maybe even in the same context. To this end, scientists might find inspiration by mining insights from adjacent fields, such as evolution, anatomy, development, and ecology , as well as cybernetics and systems theory. At stake is nothing less than a viable science of how a brain creates a mind through its constant interactions with its body, its physical environment, and with the other brains-in-bodies that occupy its social world.

The touch sensitive nerve cells that make mice (and probably us) horny.

From Elias et al. (open source) in the journal Cell:  

Highlights

• Activation of Mrgprb4-lineage touch neurons induces lordosis-like posture

• Activation of Mrgprb4-lineage touch neurons is rewarding

• Mrgprb4-lineage touch neurons are required for female sexual receptivity

• Mrgprb4-lineage touch neurons engage dopaminergic neurons during social behavior

Summary

Pleasurable touch is paramount during social behavior, including sexual encounters. However, the identity and precise role of sensory neurons that transduce sexual touch remain unknown. A population of sensory neurons labeled by developmental expression of the G protein-coupled receptor Mrgprb4 detects mechanical stimulation in mice. Here, we study the social relevance of Mrgprb4-lineage neurons and reveal that these neurons are required for sexual receptivity and sufficient to induce dopamine release in the brain. Even in social isolation, optogenetic stimulation of Mrgprb4-lineage neurons through the back skin is sufficient to induce a conditioned place preference and a striking dorsiflexion resembling the lordotic copulatory posture. In the absence of Mrgprb4-lineage neurons, female mice no longer find male mounts rewarding: sexual receptivity is supplanted by aggression and a coincident decline in dopamine release in the nucleus accumbens. Together, these findings establish that Mrgprb4-lineage neurons initiate a skin-to-brain circuit encoding the rewarding quality of social touch.

A.I. as a path towards mass lunacy

MindBlog wants to be part of the passing on of this elegantly stated clip from an article by novelist, literary critic, and essayist Walter Kirn:

What chatbots do is scrape the web, the library of texts already written, and learn from it how to add to the collection, which causes them to start scraping their own work in ever enlarging quantities, along with the texts produced by future humans. Both sets of documents will then degenerate. For as the adoption of A.I. relieves people of their verbal and mental powers and pushes them toward an echoing conformity, much as the mass adoption of map apps have abolished their senses of direction, the human writings from which the A.I. draws will decline in originality and quality along with their derivatives. Enmeshed, dependent, mutually enslaved, machine and man will unite their special weaknesses — lack of feeling and lack of sense — and spawn a thing of perfect lunacy, like the child of a psychopath and an idiot.

I can hear the objections to this dire scenario of a million gung-ho programmers as well as the ambitious A.I. itself, but I, a creative writer, am wed to it. I think dramatically first and scientifically second, such is my art. My ancient and possibly endangered art is imagining worst cases and playing them out to their bitter, tragic ends, as Sophocles did when he posited a king who unwittingly killed his father, married his mother, and then launched an inquiry into the matter after vowing to slay the perpetrator. See? See what writers were capable of then?

Now we have ‘Ant-Man.’ And worse, ‘Ant-Man’ sequels, enhanced by C.G.I.

An fMRI marker of drug and food craving

Koban et al. identify an fMRI-based neural signature of craving that is common to both food and drugs, predicts self-reported craving, distinguishes drug users from non-users, and tracks the efficacy of a cognitive therapy technique to reduce craving:

Craving is a core feature of substance use disorders. It is a strong predictor of substance use and relapse and is linked to overeating, gambling, and other maladaptive behaviors. Craving is measured via self-report, which is limited by introspective access and sociocultural contexts. Neurobiological markers of craving are both needed and lacking, and it remains unclear whether craving for drugs and food involve similar mechanisms. Across three functional magnetic resonance imaging studies (n = 99), we used machine learning to identify a cross-validated neuromarker that predicts self-reported intensity of cue-induced drug and food craving (P < 0.0002). This pattern, which we term the Neurobiological Craving Signature (NCS), includes ventromedial prefrontal and cingulate cortices, ventral striatum, temporal/parietal association areas, mediodorsal thalamus and cerebellum. Importantly, NCS responses to drug versus food cues discriminate drug users versus non-users with 82% accuracy. The NCS is also modulated by a self-regulation strategy. Transfer between separate neuromarkers for drug and food craving suggests shared neurobiological mechanisms. Future studies can assess the discriminant and convergent validity of the NCS and test whether it responds to clinical interventions and predicts long-term clinical outcomes.

Multigenerational Impacts of Childhood Access to the Safety Net.

In an open source article in the January issue of the American Economic Review East et al. show that early life exposure to Medicaid enhances the next generation's health.

We examine multigenerational impacts of positive in utero health interventions using a new research design that exploits sharp increases in prenatal Medicaid eligibility that occurred in some states. Our analyses are based on US Vital Statistics natality files, which enables linkages between individuals' early life Medicaid exposure and the next generation's health at birth. We find evidence that the health benefits associated with treated generations' early life program exposure extend to later offspring. Our results suggest that the returns on early life health investments may be substantively underestimated.

Shifting from foraging to farming, beginning ~12,000 years ago, changed everything.

A special Feature section in the Jan. 17 issue of PNAS offers a series of perspectives on the past 12,000 years of human behavior, adaptation, and evolution that shaped who we are today. An introduction to the special section by Larsen does an overview and brief summary of each of perspectives presented. I pass on the last paragraph (Conclusions) of that summary:

In evolutionary terms, the transition at the Pleistocene–Holocene boundary was extraordinary, especially in consideration of the beginning of a fundamental shift in dietary focus and the downstream effects of diets based on domesticated plants and animals. The transition provided the context for a remarkable increase in population. However, the costs for that success—elevated levels infectious diseases, undernutrition, and conflict—are still with us today. Our species will continue to adapt, to develop strategies for success, and to mitigate challenges. That is what we do. Once we began the shift to and intensification of farming, the remarkable changes seen in humans became critically important developments in recent human evolution. In view of conditions today, including climate change, overpopulation, and the rise in prevalence of infectious diseases, both old and newly emerging, it should come as no surprise that dependence on a few staple crops and shift to sedentary behavior will be with us for the foreseeable future. They are, after all, a legacy of our past, and forming and sharing of the dietary framework, behavioral patterns, and outcomes in health and well-being for all eight billion of us that occupy the world today.

Openness to spiritual experiences...with caution

After a Protestant Christian upbringing (I was a teenage organist in an Austin Lutheran Church, and took a course from theologian Paul Tillich at Harvard), my adult materialistic scientific Deric has never been able to fathom how an intellectual like Ross Douthat could be a devout Catholic. My irrational faith is in a materialism that is open to spiritual experiences and insights, but also strives to explain them in materialistic terms (as I think near-death experiences have been). I think Douthat’s recent opinion piece in the NYTimes very lucid, although I take exception to one of his pronouncements, and I would recommend that you read it. Here are some clips:

...the dissolution of the old order of American religion — the decline of churches and denominations and the rise of deinstitutionalized spirituality — means that more and more religious lives are lived in between worldviews, in experimental territory where it’s a mistake to expect coherence, theological consistency, a definite set of prior assumptions or beliefs...I want to defend the rationality of this kind of spiritual experimentation and then to warn about its dangers.

Douthat then offers three examples experimental style: magical thinking, experimenting with psychedelics, and pantheistic art that blurs spiritual traditions. And he continues:

For the stringent materialist, everything I’ve just described is reasonable as long as it's understood to be playacting, experience hunting, artistic experimentation. Only when it becomes serious does it offend against rationality.

However, stringent materialism is itself a weird late-modern superstition, and the kind of experimentation I’m describing is actually far more rational than a life lived as though the universe is random and indifferent and human beings are gene-transmission machines with an illusion of self-consciousness.

So... put me in the camp of irrational believers in stringent materialism. And... by what authority does Mr. Douthat get to declare spiritual experimentation or superstition is "far more rational than life lived as though the universe is random, etc." Superstition is superstition; irrational is irrational. What criteria are Mr. Douthat using for his "far more rational" judgment. Are they utilitarian?... as in "X diminishes or enhances the well being of humans more than Y"? He should explicitly state them.

Cryptocurrency isn't going away - any more that Gold is...

...as long as cryptocurrency maintains a core of true believers in the block chain concept for guaranteeing trustworthiness. All currencies are useful as tokens for exchange only to the extent that humans believe in them. The point of this brief post is just to pass on links to two recent screeds by Desai and Krugman that make entertaining reading: 

Mihir A. Desai - The Crypto Collapse and the End of the Magical Thinking That Infected Capitalism  

Paul Krugman - Wonking Out: Give Me That Gold Time Religion 

 

 

 

Market exposure and human morality

In the face of resurgent threats to place religion over the rest of civil society, and specious claims that we can't have a moral society without the (varying) moral injunctions of various religions, this recent article by Enke in Nature Human Behavior offers a nice explication of one of several other routes by which moral behaviors have evolved over time. Here is the abstract:

According to evolutionary theories, markets may foster an internalized and universalist prosociality because it supports market-based cooperation. This paper uses the cultural folklore of 943 pre-industrial ethnolinguistic groups to show that a society’s degree of market interactions, proxied by the presence of intercommunity trade and money, is associated with the cultural salience of (1) prosocial behaviour, (2) interpersonal trust, (3) universalist moral values and (4) moral emotions of guilt, shame and anger. To provide tentative evidence that a part of this correlation reflects a causal effect of market interactions, the analysis leverages both fine-grained geographic variation across neighbouring historical societies and plausibly exogenous variation in the presence of markets that arises through proximity to historical trade routes or the local degree of ecological diversity. The results suggest that the coevolutionary process involving markets and morality partly consists of economic markets shaping a moral system of a universalist and internalized prosociality.

How sleep shapes what we remember and forget.

I have found monitoring the quality of my sleep to be a fascinating and useful activity. I use both the Oura ring and Apple watch to monitor body temperature, body movement, heart rate, and heart rate variability, and then compare their different (but broadly similar) algorithmic estimates of deep sleep, REM sleep, non-REM sleep, and wake periods. I'm on the lookout for articles on sleep during my scans of journals' tables of contents, and have come upon this review by Sakai of what is happening in our sleep to be concise and useful. Below is a more general overview from edited and rearranged clips (The article goes into more electrophysiological and cellular details):

 

(image credit Dave Cutler)

...memory at the beginning of the consolidation process is very much anchored in hippocampal networks, and in the end of this process, it primarily resides in neocortical networks...New memories are rich with contextual clues such as the time, place, and sensory details of an experience...as memories get encoded in the cortex, many of those spatial and temporal details fade...forgetting—through weakening or loss of synapses—seems to play a key role in the process of memory consolidation, especially during sleep... What remains are the elements representing the essential core of the memory. When learning how to drive, for example, the movements needed to steer and brake are critical; the details of avoiding a specific car on a particular outing are not...sleep’s role in memory is not simply about passive storage. Rather..a more active process of consolidation that extracts key information and forms a generalized version of the overall memory that can later be accessed and applied to relevant situations.

Sleep in mammals has distinct phases as characterized by specific EEG patterns. These include brain-wide slow oscillations (less than 1 Hz in frequency), sharp-wave ripples (100-300 Hz) in the hippocampus, and spindles (10-15 Hz), which are related to the firing of neurons in the circuits connecting the thalamus and the cortex. Upon onset of sleep, the brain enters a non-rapid eye movement (non-REM) phase. During non-REM sleep, slow oscillations sweep across large regions of the brain, punctuated by swells of spindles and bursts of sharp wave-ripples. A period of rapid eye movement (REM) sleep follows, with characteristic bursts of its namesake eye movements and low-amplitude theta oscillations around 4-8 Hz. The brain cycles through these phases throughout the sleep period, with slow-wave, non-REM sleep dominating the early hours and REM sleep the late hours.

There are...

...distinct roles of different stages of sleep in memory formation. Non-REM sleep has been shown to be very important for consolidation of declarative memories—those based on recall of information—while REM sleep seems to play a larger part in procedural or task-based memories...this may relate to the degree of synaptic change required. For declarative memories, most of the foundational learning has already taken place; remembering a new fact likely requires only small changes in synaptic strengths. By contrast, procedural memories require a massive amount of synaptic change...If you want to learn how to ride a bike, or how to play capoeira … it's not like learning a new name...I’s weeks, months, years of work. And so it seems like REM sleep is really, really necessary to do this long-term persistent synaptic change.”

MindBlog's 2010 recital and lecture in Istanbul

I've been meandering back over old MindBlog posts and found an orphaned .mov file that I've reposted to my YouTube channel, quite a bit of nostalgia. The guy turning my pages was my handler and guide during my 10 day visit to Istanbul. He is now a Turkish Airlines pilot. 

 

The Evolution of Peace

I pass on the abstract of an article by Luke Glowacki that has been submitted to the network of Behavioral and Brain Science reviewers who might offer commentary on its arguments. Motivated readers can obtain a copy of the article from me.

Abstract: While some species have affiliative and even cooperative interactions between individuals of different social groups, humans are alone in having durable, positive-sum, interdependent relationships across unrelated social groups. Our capacity to have harmonious relationships that cross group boundaries is an important aspect of our species' success, allowing for the exchange of ideas, materials, and ultimately enabling cumulative cultural evolution. Knowledge about the conditions required for peaceful intergroup relationships is critical for understanding the success of our species and building a more peaceful world. How do humans create harmonious relationships across group boundaries and when did this capacity emerge in the human lineage? Answering these questions involves considering the costs and benefits of intergroup cooperation and aggression, for oneself, one's group, and one's neighbor. Taking a game theoretical perspective provides new insights into the difficulties of removing the threat of war and reveals an ironic logic to peace—the factors that enable peace also facilitate the increased scale and destructiveness of conflict. In what follows, I explore the conditions required for peace, why they are so difficult to achieve, and when we expect peace to have emerged in the human lineage. I argue that intergroup cooperation was an important component of human relationships and a selective force in our species history in the past 300 thousand years. But the preconditions for peace only emerged in the past 100 thousand years and likely coexisted with intermittent intergroup violence which would have also been an important and selective force in our species' history.

Our different styles of thinking.

An interesting recent article by Joshua Rothman, the ideas editor of newyorker.com, notes several recent books that describe different styles of thinking. A few clips:

In “Visual Thinking: The Hidden Gifts of People Who Think in Pictures, Patterns, and Abstractions,” Temple Grandin identifies a continuum of thought styles that’s roughly divisible into three sections. On one end are verbal thinkers, who often solve problems by talking about them in their heads or, more generally, by proceeding in the linear, representational fashion typical of language. (Estimating the cost of a building project, a verbal thinker might price out all the components, then sum them using a spreadsheet—an ordered, symbol-based approach.) On the other end of the continuum are “object visualizers”: they come to conclusions through the use of concrete, photograph-like mental images, as Grandin does when she compares building plans in her mind. In between those poles, Grandin writes, is a second group of visual thinkers—“spatial visualizers,” who seem to combine language and image, thinking in terms of visual patterns and abstractions.

Grandin proposes imagining a church steeple. Verbal people, she finds, often make a hash of this task, conjuring something like “two vague lines in an inverted V,” almost as though they’ve never seen a steeple before. Object visualizers, by contrast, describe specific steeples that they’ve observed on actual churches: they “might as well be staring at a photograph or photorealistic drawing” in their minds. Meanwhile, the spatial visualizers picture a kind of perfect but abstract steeple—“a generic New England-style steeple, an image they piece together from churches they’ve seen.” They have noticed patterns among church steeples, and they imagine the pattern, rather than any particular instance of it.

The imagistic minds in “Visual Thinking” can seem glamorous compared with the verbal ones depicted in “Chatter: The Voice in Our Head, Why It Matters, and How to Harness It,” by Ethan Kross. Kross is interested in what’s known as the phonological loop—a neural system, consisting of an “inner ear” and an “inner voice,” that serves as a “clearinghouse for everything related to words that occurs around us in the present.” If Grandin’s visual thinkers are attending Cirque du Soleil, then Kross’s verbal thinkers are stuck at an Off Broadway one-man show. It’s just one long monologue.

People with inner monologues, Kross reports, often spend “a considerable amount of time thinking about themselves, their minds gravitating toward their own experiences, emotions, desires, and needs.” This self-centeredness can spill over into our out-loud conversation. In the nineteen-eighties, the psychologist Bernard Rimé investigated what we’d now call venting—the compulsive sharing of negative thoughts with other people. Rimé found that bad experiences can inspire not only interior rumination but the urge to broadcast it. The more we share our unhappiness with others, the more we alienate them… Maybe it can pay to keep your thoughts to yourself.

Kross’s bottom line is that our inner voices are powerful tools that must be tamed. He ends his book with several dozen techniques for controlling our chatter. He advises trying “distanced self-talk”: by using “your name and the second-person ‘you’ to refer to yourself,” he writes, you can gain more command over your thinking. You might use your inner voice to pretend that you’re advising a friend about his problems; you might redirect your thoughts toward how universal your experiences are (It’s normal to feel this way), or contemplate how every new experience is a challenge you can overcome (I have to learn to trust my partner). The idea is to manage the voice that you use for self-management. Take advantage of the suppleness of dialogue. Don’t just rehearse the same old scripts; send some notes to the writers’ room.

If we can’t say exactly how we think, then how well do we know ourselves? In an essay titled “The Self as a Center of Narrative Gravity,” the philosopher Daniel Dennett argued that a layer of fiction is woven into what it is to be human. In a sense, fiction is flawed: it’s not true. But, when we open a novel, we don’t hurl it to the ground in disgust, declaring that it’s all made-up nonsense; we understand that being made up is actually the point. Fiction, Dennett writes, has a deliberately “indeterminate” status: it’s true, but only on its own terms. The same goes for our minds. We have all sorts of inner experiences, and we live through and describe them in different ways—telling one another about our dreams, recalling our thoughts, and so on. Are our descriptions and experiences true or fictionalized? Does it matter? It’s all part of the story.

A quick MindBlog riff on what a self is....

Spilling out what I was thinking at breakfast this morning, deciding to fire it off, probably incomprehensible to most readers, perhaps to attempt to clarify later (or delete!):

My self model or 'I' stands amongst my models of others, and during my early postnatal period I probably formed those other models prior to my own, a yet unknown self discovering and learning to predict the behavior of others to gain feeding and care, and only then composing my own self from parts of them. This is consonant with Graziano's take on consciousness as a perceptual construct ("Consciousness and the Social Brain"), also with Wegner's self as being the emotion of authorship ("The Illusion of Conscious Will") and with Metzenger's emotions as evolved virtual organs analogous to the hardware of the liver or kidney ("The Ego Tunnel"). Perhaps the closest we come to a 'real fundamental self' is the experience of occupancy of an expanded space (of non-dual consciousness) that feels to be the container for all of this.

Mindful attention enhances brain network control and uncouples past from the present

Zhou et al. (open source) do an interesting experiment on mindfulness and brain network control:  

Significance

Practicing mindfulness helps individuals regulate attention, thoughts, feelings, and behavior. In recognizing these benefits, various schools, workplaces, and clinics are increasingly teaching mindfulness. How does mindful attention change brain function to support self-regulation? Addressing this question could inform how we teach mindfulness and whom we expect to benefit. We modeled the defining components of mindful experience using tools that probe the structure and function of the brain’s network. In a randomized controlled study of alcohol consumption, we found that a brain network’s dynamic shape predicts individuals’ future alcohol consumption and explains otherwise elusive components of mindful experience, such as being present. Our results provide new understanding of how mindful attention affects brain function.

Abstract

Mindful attention is characterized by acknowledging the present experience as a transient mental event. Early stages of mindfulness practice may require greater neural effort for later efficiency. Early effort may self-regulate behavior and focalize the present, but this understanding lacks a computational explanation. Here we used network control theory as a model of how external control inputs—operationalizing effort—distribute changes in neural activity evoked during mindful attention across the white matter network. We hypothesized that individuals with greater network controllability, thereby efficiently distributing control inputs, effectively self-regulate behavior. We further hypothesized that brain regions that utilize greater control input exhibit shorter intrinsic timescales of neural activity. Shorter timescales characterize quickly discontinuing past processing to focalize the present. We tested these hypotheses in a randomized controlled study that primed participants to either mindfully respond or naturally react to alcohol cues during fMRI and administered text reminders and measurements of alcohol consumption during 4 wk postscan. We found that participants with greater network controllability moderated alcohol consumption. Mindful regulation of alcohol cues, compared to one’s own natural reactions, reduced craving, but craving did not differ from the baseline group. Mindful regulation of alcohol cues, compared to the natural reactions of the baseline group, involved more-effortful control of neural dynamics across cognitive control and attention subnetworks. This effort persisted in the natural reactions of the mindful group compared to the baseline group. More-effortful neural states had shorter timescales than less effortful states, offering an explanation for how mindful attention promotes being present.

COVID-19 and brain aging

Over the Christmas and New Year's holidays I was hit first by a mild Covid infection that lasted only a few days (I've had all 5 vaccinations and immediately took Paxlovid on testing positive) and then five days later had a slightly longer Paxlovid-rebound infection. A transient brain fog seems to have cleared by now. This personal experience makes me especially attentive to articles like Welberg's note on Covid-19 and brain aging, which suggests that brain changes associated with Covid infection are most likely due to neuroinflammation resulting from the infection, not from the virus itself. Here is the abstract:

Severe COVID-19 has been associated with cognitive impairment and changes in the frontal cortex. In a study published in Nature Aging, Mavrikaki, Lee et al. performed RNA sequencing on frontal cortex samples from 21 individuals with severe COVID-19, 22 age- and sex-matched uninfected controls, and 9 uninfected people who had received intensive care or ventilator treatment. The authors found almost 7,000 differentially expressed genes (DEGs) in the patient samples compared to controls. Upregulated DEGs were enriched for genes involved in immune-related pathways, and downregulated DEGs were enriched for genes involved in synaptic activity, cognition and memory — a profile of transcriptional changes that resembles those previously observed in aging brains. Direct comparisons between frontal cortex samples from young and old individuals confirmed this overlap. Application of tumor necrosis factor, interferon-β or interferon-γ to cultured human primary neurons induced transcriptional changes similar to those seen in patients with severe COVID-19. As no SARS-CoV-2 RNA was detected in the patient samples, these data suggest that the transcriptomic changes in frontal cortex of patients with severe COVID-19 were due to neuroinflammatory processes rather than a direct effect of the virus.

Materialism meets transcendence

I want to pass on the URL to a PBS series by Alan Lightman that I plan to start watching as soon as I can, based on the following description and review in Science Magazine:

In part 1, “The Stars & The Osprey,” Lightman undergoes functional magnetic resonance imaging and interviews neuroscientist Robert Desimone about how much neuroimaging can tell us about Lightman’s transcendental experience. He ultimately finds this approach unsatisfying and introduces viewers to the debate between mechanists, who believe that the laws of physics, chemistry, and biology are sufficient to explain life, and vitalists, who believe that living creatures are imbued with an additional spiritual quality not explainable by science.

Here, he interviews biologist and Nobel laureate Jack Szostak and the Dalai Lama as proponents of these two camps, respectively. Although the Dalai Lama expresses enthusiasm for scientific investigation, most scientists will likely resonate with Szostak’s declaration that “It’s not just atoms and molecules, it’s the organization…it’s no less wonderful or beautiful because we understand that there is a natural origin for [life].”

Part 2, “The Big & The Small,” begins with the familiar “powers of 10” view of the Universe, moving from the subatomic to the galactic. Lightman then queries what such explorations have to do with consciousness, conversing with BINA48, an extraordinary humanoid robot programmed by artificial intelligence with >100 hours of a real woman’s memories. Here, he speculates that BINAs of the future may achieve consciousness. He then probes this issue over Zoom with the Dalai Lama, whom viewers observe watching a movie of BINA48 conversing with the woman from whom BINA48 was programmed; this multilayered interaction is simultaneously disconcerting, comical, and wondrous. After additional interviews with a bioethicist, a rabbi, and others, Lightman ultimately concludes that we may be just atoms and molecules, but, in the words of Emily Dickinson, “The brain is wider than the sky.”

In part 3, “Homo Techno,” Lightman contemplates our inner world of perception, consciousness, and self-awareness. He meets Erik Sorto, who lost all movement from the neck down after being shot in the back. With electrodes implanted into his posterior parietal cortex and 2 years of training, Sorto learned to control the movement of a robotic arm by thought. This is an extraordinary achievement, and Lightman posits that it is an example of the beginning of our transition from Homo sapiens into Homo techno, part-human, part-machine entities that reflect the modification of human evolution by technological means. From an actual evolutionary biology standpoint, this is nonsensical, and it is unclear that Lightman even means to propose such an idea, but this section’s loose language will rankle some viewers.

At another point in the series’ final episode, Lightman finds himself dizzy from talk of neurons and galaxies and takes refuge in closely examining a single square inch of earth. His biophilia is obviously meaningful to him, and it would have been stimulating had the episode included interviews with an evolutionary biologist or naturalist, who might have helped to better articulate this facet of the human experience. The series closes, appropriately, with philosophical musings about the need for each of us to find meaning for ourselves.

A small problem at the outset is the inherent impossibility of conveying transcendence through description—the degree to which viewers relate to Lightman’s moment of enlightenment will depend on their own experiences and inclinations. Additionally, Lightman’s screen persona leaves something to be desired. There are, however, few people better qualified to explore these issues, and as the series progresses, his humanity shines through, bringing a welcome lightness to some potentially ponderous material.

Despite its focus on phenomena currently unexplainable by science, Searching is full of the joy and passion that can be found in the doing of science and succeeds in conveying how deeply meaningful science is to its practitioners. It is well worth your time and is especially recommended to families with kids curious about life and our world.