Castration delays aging

I pass on this nugget by Beverly Purnell in the Editor's Choice section of this week's Science Magazine noting an interesting paper by Sugrue et al. First her summary, then the abstract of the Sugrue et al. paper.  

The summary:

As we age, our genetic material changes, not only through DNA mutation but also by epigenetic modification. Indeed, chronological age can be estimated based on analysis of DNA methylation. Male and female mammals display different average life spans, and a role for sex hormones is expected in this effect. Sugrue et al. established an epigenetic clock in sheep by examining methylated DNA in samples from blood and ears. They show that castration extends an animal's life span and feminizes the epigenome at specific androgen-regulated loci during aging.

The Abstract:

In mammals, females generally live longer than males. Nevertheless, the mechanisms underpinning sex-dependent longevity are currently unclear. Epigenetic clocks are powerful biological biomarkers capable of precisely estimating chronological age and identifying novel factors influencing the aging rate using only DNA methylation data. In this study, we developed the first epigenetic clock for domesticated sheep (Ovis aries), which can predict chronological age with a median absolute error of 5.1 months. We have discovered that castrated male sheep have a decelerated aging rate compared to intact males, mediated at least in part by the removal of androgens. Furthermore, we identified several androgen-sensitive CpG dinucleotides that become progressively hypomethylated with age in intact males, but remain stable in castrated males and females. Comparable sex-specific methylation differences in MKLN1 also exist in bat skin and a range of mouse tissues that have high androgen receptor expression, indicating that it may drive androgen-dependent hypomethylation in divergent mammalian species. In characterizing these sites, we identify biologically plausible mechanisms explaining how androgens drive male-accelerated aging.

What is our brain's spontaneous activity for?

Continuing in MindBlog's recent thread on the predictive brain (see here and here), I pass on highlights of an opinion piece by Pezzulo et al., who suggest that all that background brain noise has a very specific purpose - figuring out what to expect next:

Spontaneous brain dynamics are manifestations of top-down dynamics of generative models detached from action–perception cycles.

Generative models constantly produce top-down dynamics, but we call them expectations and attention during task engagement and spontaneous activity at rest.

Spontaneous brain dynamics during resting periods optimize generative models for future interactions by maximizing the entropy of explanations in the absence of specific data and reducing model complexity.

Low-frequency brain fluctuations during spontaneous activity reflect transitions between generic priors consisting of low-dimensional representations and connectivity patterns of the most frequent behavioral states.

High-frequency fluctuations during spontaneous activity in the hippocampus and other regions may support generative replay and model learning.

Brains at rest generate dynamical activity that is highly structured in space and time. We suggest that spontaneous activity, as in rest or dreaming, underlies top-down dynamics of generative models. During active tasks, generative models provide top-down predictive signals for perception, cognition, and action. When the brain is at rest and stimuli are weak or absent, top-down dynamics optimize the generative models for future interactions by maximizing the entropy of explanations and minimizing model complexity. Spontaneous fluctuations of correlated activity within and across brain regions may reflect transitions between ‘generic priors’ of the generative model: low dimensional latent variables and connectivity patterns of the most common perceptual, motor, cognitive, and interoceptive states. Even at rest, brains are proactive and predictive.

The connections between two brain regions that are required for consciousness are regulated by dopamine.

Important work from Spindler et al.:  

Significance

Understanding the neural bases of consciousness is of basic scientific and clinical importance. Human neuroimaging has established that a network of interconnected brain regions known as the default mode network disintegrates in anesthesia and after brain damage that causes disorders of consciousness. However, the neurochemical underpinnings of this network change remain largely unknown. Motivated by preclinical animal work and clinical observations, we found that across pharmacological (sedation) and pathological (disorders of consciousness) consciousness perturbation, the dopaminergic source nucleus, the ventral tegmental area, disconnects from the main nodes of the default mode network. As the severity of this dopaminergic disconnection was associated with default mode network disintegration, we propose that dopaminergic modulation may be a central mechanism for consciousness maintenance.

Abstract

Clinical research into consciousness has long focused on cortical macroscopic networks and their disruption in pathological or pharmacological consciousness perturbation. Despite demonstrating diagnostic utility in disorders of consciousness (DoC) and monitoring anesthetic depth, these cortico-centric approaches have been unable to characterize which neurochemical systems may underpin consciousness alterations. Instead, preclinical experiments have long implicated the dopaminergic ventral tegmental area (VTA) in the brainstem. Despite dopaminergic agonist efficacy in DoC patients equally pointing to dopamine, the VTA has not been studied in human perturbed consciousness. To bridge this translational gap between preclinical subcortical and clinical cortico-centric perspectives, we assessed functional connectivity changes of a histologically characterized VTA using functional MRI recordings of pharmacologically (propofol sedation) and pathologically perturbed consciousness (DoC patients). Both cohorts demonstrated VTA disconnection from the precuneus and posterior cingulate (PCu/PCC), a main default mode network node widely implicated in consciousness. Strikingly, the stronger VTA–PCu/PCC connectivity was, the more the PCu/PCC functional connectome resembled its awake configuration, suggesting a possible neuromodulatory relationship. VTA-PCu/PCC connectivity increased toward healthy control levels only in DoC patients who behaviorally improved at follow-up assessment. To test whether VTA–PCu/PCC connectivity can be affected by a dopaminergic agonist, we demonstrated in a separate set of traumatic brain injury patients without DoC that methylphenidate significantly increased this connectivity. Together, our results characterize an in vivo dopaminergic connectivity deficit common to reversible and chronic consciousness perturbation. This noninvasive assessment of the dopaminergic system bridges preclinical and clinical work, associating dopaminergic VTA function with macroscopic network alterations, thereby elucidating a critical aspect of brainstem–cortical interplay for consciousness.

How the insiders win - Philanthropy, advocacy, and profit.

From Bertrand et al., a study showing how U.S. Federal rulemaking based on considering "independent viewpoints" is corrupted:

Information is central to designing effective policy, and policymakers often rely on competing interests to separate useful from biased information. We show how this logic of virtuous competition can break down, using a new and comprehensive dataset on U.S. federal regulatory rulemaking for 2003–2016. For-profit corporations and nonprofit entities are active in the rulemaking process and are arguably expected to provide independent viewpoints. Policymakers, however, may not be fully aware of the financial ties between some firms and nonprofits – grants that are legal and tax-exempt, but hard to trace. We document three patterns which suggest that these grants may distort policy. First, we show that, shortly after a firm donates to a nonprofit, that nonprofit is more likely to comment on rules on which the firm has also commented. Second, when a firm comments on a rule, the comments by nonprofits that recently received grants from the firm’s foundation are systematically closer in content to the firm’s own comments, relative to comments submitted by other nonprofits. Third, the final rule’s discussion by a regulator is more similar to the firm’s comments on that rule when the firm’s recent grantees also commented on it.

Electromagnetic radiation in the wireless signal range increases wakefulness in mice

Liu et al. (open source) find that electromagnetic radiation (EMR) in the wireless signal range used by our cell phones, laptops, and Wi-Fi routers can increase wakefulness in mice, but only if the signal is pulsed and at much higher levels than are present in our homes.  

Significance

The steady increase of electromagnetic radiation (EMR) in the environment, particularly the wireless signal, causes serious public concern over its potential negative impact on health. However, it is challenging to examine such impact on human subjects due to associated complex issues. In this study, we establish an experimental system for the investigation of EMR impact on mice. Using this system, we uncovered a causal relationship between 2.4-GHz EMR modulated by 100-Hz square pulses and increased wakefulness in mice. This result identifies sleep alteration as a potential consequence of exposure to excessive wireless signals.

Abstract

Electromagnetic radiation (EMR) in the environment has increased sharply in recent decades. The effect of environmental EMR on living organisms remains poorly characterized. Here, we report the impact of wireless-range EMR on the sleep architecture of mouse. Prolonged exposure to 2.4-GHz EMR modulated by 100-Hz square pulses at a nonthermal output level results in markedly increased time of wakefulness in mice. These mice display corresponding decreased time of nonrapid eye movement (NREM) and rapid eye movement (REM). In contrast, prolonged exposure to unmodulated 2.4-GHz EMR at the same time-averaged output level has little impact on mouse sleep. These observations identify alteration of sleep architecture in mice as a specific physiological response to prolonged wireless-range EMR exposure.

The final two paragraphs of the paper make clear that the effects on mouse sleep require much higher power densities for the 2.4-GHz EMR signals than are emitted by smartphones, laptops, or Wi-Fi routers.

....the average power density at close proximity is about 0.037 W/m2 for a smartphone, 0.013 W/m2 for a laptop, and 0.13 W/m2 near the Wi-Fi router (1). These values are considerably lower than the time- and whole-body–averaged general public exposure limit of 10 W/m2 or occupational exposure limit of 50 W/m2 for 2–300 GHz suggested by International Commission on Non-Ionizing Radiation Protection (43). In our experiments, the measured spatial averaged power density for Conti8W is 36.80 ± 0.92 W/m2. Pulse64W is expected to have the same power density. Importantly, the effective EMR dose for inducing a biological response in mice is likely to be different from that in humans. Therefore, the relatively high EMR dose of the Pulse64W regimen that causes increased wakefulness in mice could be markedly reduced in humans. An epidemiological survey among those who work under either very high or very low doses of wireless radiation may reveal some clues.

In this study, 2.4-GHz EMR is modulated by 100-Hz square pulses, which have sharp edges and thus might have some unanticipated impact on neural activity in the brain. Additional experiments should be performed to examine whether other modulation functions such as sinusoidal modulation can induce similar increase of wakefulness in mice. In addition, other modulation frequencies such as 10 and 1,000 Hz should be investigated to answer the question of whether increased wakefulness is specific to certain modulation frequencies. Finally, both the intensity and the frequency of the carrier EMR (2.4 GHz in this study) should be scrutinized.

Seeing others react to threats triggers our own internal threat responses.

From Haaker et al. (open source): 

Significance

Social transmission of threat information by observation is effective in humans and other animals. However, it is unknown if such observation of others’ reacting to threats can retrieve memories that have been previously learned through direct, firsthand aversive experiences. Here, we show concordantly in humans and rats that observing a conspecific’s reactions to a threat is sufficient to recover associative memories of direct, firsthand aversive experiences, measured as conditioned threat responses (physiological responses and defensive behavior) in the observer. The reinstatement of threat responses by observation of others is specific to the context that is observed as being dangerous. Our findings provide cross-species evidence that observation of others’ threat reactions can recover associative memories of direct, firsthand aversive experiences.

Abstract

Information about dangers can spread effectively by observation of others’ threat responses. Yet, it is unclear if such observational threat information interacts with associative memories that are shaped by the individual’s direct, firsthand experiences. Here, we show in humans and rats that the mere observation of a conspecific’s threat reactions reinstates previously learned and extinguished threat responses in the observer. In two experiments, human participants displayed elevated physiological responses to threat-conditioned cues after observational reinstatement in a context-specific manner. The elevation of physiological responses (arousal) was further specific to the context that was observed as dangerous. An analogous experiment in rats provided converging results by demonstrating reinstatement of defensive behavior after observing another rat’s threat reactions. Taken together, our findings provide cross-species evidence that observation of others’ threat reactions can recover associations previously shaped by direct, firsthand aversive experiences. Our study offers a perspective on how retrieval of threat memories draws from associative mechanisms that might underlie both observations of others’ and firsthand experiences.

Historical language records reveal societal depression and anxiety in past two decades higher than during 20th century.

Fascinating work from Bollen et al. (open source):  

Significance

Can entire societies become more or less depressed over time? Here, we look for the historical traces of cognitive distortions, thinking patterns that are strongly associated with internalizing disorders such as depression and anxiety, in millions of books published over the course of the last two centuries in English, Spanish, and German. We find a pronounced “hockey stick” pattern: Over the past two decades the textual analogs of cognitive distortions surged well above historical levels, including those of World War I and II, after declining or stabilizing for most of the 20th century. Our results point to the possibility that recent socioeconomic changes, new technology, and social media are associated with a surge of cognitive distortions.

Abstract

Individuals with depression are prone to maladaptive patterns of thinking, known as cognitive distortions, whereby they think about themselves, the world, and the future in overly negative and inaccurate ways. These distortions are associated with marked changes in an individual’s mood, behavior, and language. We hypothesize that societies can undergo similar changes in their collective psychology that are reflected in historical records of language use. Here, we investigate the prevalence of textual markers of cognitive distortions in over 14 million books for the past 125 y and observe a surge of their prevalence since the 1980s, to levels exceeding those of the Great Depression and both World Wars. This pattern does not seem to be driven by changes in word meaning, publishing and writing standards, or the Google Books sample. Our results suggest a recent societal shift toward language associated with cognitive distortions and internalizing disorders.

Our gut microbiome pattern reflects healthy aging and survival

Interesting analysis by Wilmanski et al.:

The gut microbiome has important effects on human health, yet its importance in human ageing remains unclear. In the present study, we demonstrate that, starting in mid-to-late adulthood, gut microbiomes become increasingly unique to individuals with age. We leverage three independent cohorts comprising over 9,000 individuals and find that compositional uniqueness is strongly associated with microbially produced amino acid derivatives circulating in the bloodstream. In older age (over ~80 years), healthy individuals show continued microbial drift towards a unique compositional state, whereas this drift is absent in less healthy individuals. The identified microbiome pattern of healthy ageing is characterized by a depletion of core genera found across most humans, primarily Bacteroides. Retaining a high Bacteroides dominance into older age, or having a low gut microbiome uniqueness measure, predicts decreased survival in a 4-year follow-up. Our analysis identifies increasing compositional uniqueness of the gut microbiome as a component of healthy ageing, which is characterized by distinct microbial metabolic outputs in the blood.

How our brain cortex changes in the transition from childhood to adolescence.

This open source article from Dong et al. has some excellent summary graphics:  

Significance

Here, we describe age-dependent shifts in the macroscale organization of cortex in childhood and adolescence. The characterization of functional connectivity patterns in children revealed an overarching organizational framework anchored within the unimodal cortex, between somatosensory/motor and visual regions. Conversely, in adolescents, we observed a transition into an adult-like gradient, situating the default network at the opposite end of a spectrum from primary somatosensory/motor regions. This spatial framework emerged gradually with age, reaching a sharp inflection point at the transition from childhood to adolescence. These data reveal a developmental change from a functional motif first dominated by the distinction between sensory and motor systems and then balanced through interactions with later-maturing aspects of association cortex that support more abstract cognitive functions.

Abstract

The transition from childhood to adolescence is marked by pronounced shifts in brain structure and function that coincide with the development of physical, cognitive, and social abilities. Prior work in adult populations has characterized the topographical organization of the cortex, revealing macroscale functional gradients that extend from unimodal (somatosensory/motor and visual) regions through the cortical association areas that underpin complex cognition in humans. However, the presence of these core functional gradients across development as well as their maturational course have yet to be established. Here, leveraging 378 resting-state functional MRI scans from 190 healthy individuals aged 6 to 17 y old, we demonstrate that the transition from childhood to adolescence is reflected in the gradual maturation of gradient patterns across the cortical sheet. In children, the overarching organizational gradient is anchored within the unimodal cortex, between somatosensory/motor and visual territories. Conversely, in adolescence, the principal gradient of connectivity transitions into an adult-like spatial framework, with the default network at the opposite end of a spectrum from primary sensory and motor regions. The observed gradient transitions are gradually refined with age, reaching a sharp inflection point in 13 and 14 y olds. Functional maturation was nonuniformly distributed across cortical networks. Unimodal networks reached their mature positions early in development, while association regions, in particular the medial prefrontal cortex, reached a later peak during adolescence. These data reveal age-dependent changes in the macroscale organization of the cortex and suggest the scheduled maturation of functional gradient patterns may be critically important for understanding how cognitive and behavioral capabilities are refined across development.

Graphic depictions of an integrative model of mind

To hopefully enhance the chance that you will pay attention to the creative and seminal thinking in the open source Laukkonen and Slagter review article whose abstract I passed on in my July 21 post,  I now pass on their striking concluding statement and then  two graphics whose legends summarize the main ideas presented. I think this work offers a plausible and appealing integration of neuroscience and meditative traditions.  

We have taken on the daunting task of providing a theory for understanding the effects of meditation within the predictive processing framework. Contemplative science is a young field and predictive processing is a new theory, although both have roots going much farther back. All theories are subject to change, but perhaps particularly so for such new domains of enquiry. Nevertheless, we think the conditions are suitable for a more overarching theory that may also thwart further siloing and fragmentation of scientific research, as has been commonplace among the mind-sciences. A strength of our framework is its simplicity: Being in the here and now reduces predictive processing. And yet, this basic idea can explain how each meditation technique uniquely deconstructs the minds tendency to project the past onto the present, how certain insights may arise, the nature of hierarchical self-processing, and the plasticity of the human mind. There is scope here, we think, to eventually reveal what makes a meditator an expert, why meditation has such broad clinical effects, and how we might begin mitigating some of the negative consequences of meditation. Last but not least, our framework seems to bring ancient Eastern and modern scientific ideas closer together, showing how the notion of conditioned experience in Buddhism aligns with the notion of the experience-dependent predictive brain.

Fig. 1. Here we use the Pythagoras Tree to provide an intuitive illustration of how organisms represent the world with increasing counterfactual depth or abstraction. The tree is constructed using squares that are scaled down by the square root of 2 divided by 2 and placed such that the corners of the squares meet and form a triangle between them, recursively. Analogously, the brain constructs experience from temporally precise and unimodal models of present-moment sensory representations and input (e.g., pixels on a screen), into ever more abstract, transmodal, and temporally deep models (e.g., a theory paper). Meditation brings one increasingly into the present moment, thus reducing the tendency to conceptualize away from the here and now, akin to observing the pixels rather than the words. This reduction of conceptualization ought to also have profound effects on the sense of self, which also relies on abstract model building, and ultimately is said to reveal an underlying seemingly “unconditioned” state of consciousness as such (like the white background underlying the pixels).

 

Fig. 2. In this schematic we illustrate two aspects of the many-to-(n)one model. The first and most foundational proposal is that meditation gradually flattens the predictive hierarchy or ‘prunes the counterfactual tree’, by bringing the meditator into the here and now, illustrated in the left figure. Thus, meditative depth is defined by the extent that the organism is not constructing temporally thick predictions. In the right figure, we dissect the predictive hierarchy into three broad levels. We propose that thinking (and therefore the narrative self [NS]) sits at the top of the predictive hierarchy (Carhart-Harris and Friston, 2010, 2019). Sensing and perceiving and therefore the embodied experiencing self [ES] sits below it (Gallagher, 2000; Seth, 2013). Finally, a basal form of self-hood characterized by the subject-object [S/O] duality sits at the earliest level. FA brings the practitioner out of the narrative self and into a more experiencing and embodied mode of being. Then, through dereification from present moment experience (including bodily sensations) OM brings the practitioner more into a state where contents of experience are treated equally, and one is able to experience non-judgmentally (sensing without appraisal), but even in very advanced states, a subject-object duality remains. During OM, certain epistemic discoveries or insights about the nature and behavior of generative models may occur. Finally, through ND practices the subject-object distinction may fall away and the background or “groundless ground” of all experience—awareness itself—can be uncovered. Another way to characterize this process is as follows: FA employs regular (conditional) attention to an object of sensing, OM employs bare (unconditional) attention, and ND practice employs reflexive awareness that permits the non-dual witnessing of the subject-object dichotomy and finally pure or non-dual awareness by releasing attention altogether.

 

 

Stable individual differences in infants’ responses to violations of intuitive physics

Interesting observations by Perez and Feigenson:

Infants look longer at impossible or unlikely events than at possible events. While these responses to expectancy violations have been critical for understanding early cognition, interpreting them is challenging because infants’ responses are highly variable. This variability has been treated as an unavoidable nuisance inherent to infant research. Here we asked whether the variability contains signal in addition to noise: namely, whether some infants show consistently stronger responses to expectancy violations than others. Infants watched two unrelated physical events 6 mo apart; these events culminated in either an impossible or an expected outcome. We found that infants who exhibited the strongest looking response to an impossible event at 11 mo also exhibited the strongest response to an entirely different impossible event at 17 mo. Furthermore, violation-of-expectation responses in infancy predicted children’s explanation-based curiosity at 3 y old. In contrast, there was no longitudinal relation between infants’ responses to events with expected outcomes at 11 and 17 mo, nor any link with later curiosity; hence, infants’ responses do not merely reflect individual differences in attention but are specific to expectancy violations. Some children are better than others at detecting prediction errors—a trait that may be linked to later cognitive abilities.

A place in the brain for the sense of ‘self’

Fascinating observations from Parvizi et al, whose findings provide a causal link between the right anterior and dorsal posteromedial cortex (PMC) and the sense of self and provide unique clues about the pathophysiology of self-dissociation in neuropsychiatric conditions. Their abstract:

The posteromedial cortex (PMC) is known to be a core node of the default mode network. Given its anatomical location and blood supply pattern, the effects of targeted disruption of this part of the brain are largely unknown. Here, we report a rare case of a patient (S19_137) with confirmed seizures originating within the PMC. Intracranial recordings confirmed the onset of seizures in the right dorsal posterior cingulate cortex, adjacent to the marginal sulcus, likely corresponding to Brodmann area 31. Upon the onset of seizures, the patient reported a reproducible sense of self-dissociation—a condition he described as a distorted awareness of the position of his body in space and feeling as if he had temporarily become an outside observer to his own thoughts, his “me” having become a separate entity that was listening to different parts of his brain speak to each other. Importantly, 50-Hz electrical stimulation of the seizure zone and a homotopical region within the contralateral PMC induced a subjectively similar state, reproducibly. We supplement our clinical findings with the definition of the patient’s network anatomy at sites of interest using cortico-cortical–evoked potentials, experimental and resting-state electrophysiological connectivity, and individual-level functional imaging. This rare case of patient S19_137 highlights the potential causal importance of the PMC for integrating self-referential information and provides clues for future mechanistic studies of self-dissociation in neuropsychiatric populations.

From many to (n)one: Meditation and the plasticity of the predictive mind

I had a chat with my former University of Wisconsin colleague Richard Davidson during my visit to Madison, WI last week, and he pointed me to an excellent open source review article by Laukkonen and Slagter, From many to (n)one: Meditation and the plasticity of the predictive mind. They offer an integrated predictive processing account of three main styles of meditation. I just finished reading through their lucid account and plan to carefully re-read it several times. I pass on the summary points and abstract: 

Highlights

• Predictive processing provides a novel theoretical window on meditation. 

• Deconstructive meditations progressively reduce temporally deep processing. 

• Insight experiences arise during meditation due to Bayesian model reduction 

• Meditation deconstructs self models by reducing abstract processing. 

• Non-dual awareness or pure consciousness is the ‘here and now’.

Abstract

How profoundly can humans change their own minds? In this paper we offer a unifying account of deconstructive meditation under the predictive processing view. We start from simple axioms. First, the brain makes predictions based on past experience, both phylogenetic and ontogenetic. Second, deconstructive meditation brings one closer to the here and now by disengaging anticipatory processes. We propose that practicing meditation therefore gradually reduces counterfactual temporally deep cognition, until all conceptual processing falls away, unveiling a state of pure awareness. Our account also places three main styles of meditation (focused attention, open monitoring, and non-dual) on a single continuum, where each technique relinquishes increasingly engrained habits of prediction, including the predicted self. This deconstruction can also permit certain insights by making the above processes available to introspection. Our framework is consistent with the state of empirical and (neuro)phenomenological evidence and illuminates the top-down plasticity of the predictive mind. Experimental rigor, neurophenomenology, and no-report paradigms are needed to further understanding of how meditation affects predictive processing and the self.

Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo

Interesting results from Shao et al.: 

 Highlights

• Psilocybin ameliorates stress-related behavioral deficit in mice 

• Psilocybin increases spine density and spine size in frontal cortical pyramidal cells 

• Psilocybin-evoked structural remodeling is persistent for at least 1 month 

• The dendritic rewiring is accompanied by elevated excitatory neurotransmission

Summary

Psilocybin is a serotonergic psychedelic with untapped therapeutic potential. There are hints that the use of psychedelics can produce neural adaptations, although the extent and timescale of the impact in a mammalian brain are unknown. In this study, we used chronic two-photon microscopy to image longitudinally the apical dendritic spines of layer 5 pyramidal neurons in the mouse medial frontal cortex. We found that a single dose of psilocybin led to ∼10% increases in spine size and density, driven by an elevated spine formation rate. The structural remodeling occurred quickly within 24 h and was persistent 1 month later. Psilocybin also ameliorated stress-related behavioral deficit and elevated excitatory neurotransmission. Overall, the results demonstrate that psilocybin-evoked synaptic rewiring in the cortex is fast and enduring, potentially providing a structural trace for long-term integration of experiences and lasting beneficial actions.

Graphical Abstract:

Albert Einstein Quotes

I am sending on some juicy Albert Einstein quotes posted by one of the members of the Madison Wisconsin book group that I still belong to...

 

“I didn't arrive at my understanding of the fundamental laws of the universe through my rational mind.”

 

“Concerning matter, we have been all wrong. What we have called matter is energy, whose vibration has been so lowered as to be perceptible to the senses. Matter is spirit reduced to point of visibility. There is no matter.”

 

"Time and space are not conditions in which we live, but modes by which we think. Physical concepts are free creations of the human mind, and are not, however it may seem, determined by the external world."

 

“Time does not exist – we invented it. Time is what the clock says. The distinction between the past, present and future is only a stubbornly persistent illusion.”

 

“I think 99 times and find nothing. I stop thinking, swim in silence, and the truth comes to me."

 

"The intellect has little to do on the road to discovery. There comes a leap in consciousness, call it intuition or what you will, the solution comes to you and you don’t know how or why.”

 

"A human being experiences himself, his thoughts and feelings as something separated from the rest, a kind of optical delusion of consciousness. This delusion is a kind of prison for us, restricting us to our personal desires and to affection for a few persons nearest to us. Our task must be to free ourselves from this prison by widening our circle of compassion to embrace all living creatures and the whole of nature in its beauty."

 

"Our separation from each other is an optical illusion."

 

“When something vibrates, the electrons of the entire universe resonate with it. Everything is connected. The greatest tragedy of human existence is the illusion of separateness.”

 

“Reality is merely an illusion, albeit a very persistent one.”

 

“We are souls dressed up in sacred biochemical garments and our bodies are the instruments through which our souls play their music.”

 

“When you examine the lives of the most influential people who have ever walked among us, you discover one thread that winds through them all. They have been aligned first with their spiritual nature and only then with their physical selves.”

 

“The true value of a human being can be found in the degree to which he has attained liberation from the self.”

 

“The ancients knew something, which we seem to have forgotten.”

 

“The more I learn of physics, the more I am drawn to metaphysics.”

 

“One thing I have learned in a long life: that all our science, measured against reality, is primitive and childlike. We still do not know one thousandth of one percent of what nature has revealed to us. It is entirely possible that behind the perception of our senses, worlds are hidden of which we are unaware.”

 

“I’m not an atheist. The problem involved is too vast for our limited minds. We are in the position of a little child entering a huge library filled with books in many languages. The child knows someone must have written those books.”

 

"The common idea that I am an atheist is based on a big mistake. Anyone who interprets my scientific theories this way, did not understand them."

 

"Everything is determined, every beginning and ending, by forces over which we have no control. It is determined for the insect, as well as for the star. Human beings, vegetables, or cosmic dust, we all dance to a mysterious tune, intoned in the distance by an invisible piper."

 

“The religion of the future will be a cosmic religion. It will transcend a personal God and avoid dogma and theology.”

 

“Energy cannot be created or destroyed, it can only be changed from one form to another.”

 

“Everything is energy and that is all there is to it. Match the frequency of the reality you want and you can not help but get that reality. It can be no other way. This is not philosophy. This is physics.”

 

"I am happy because I want nothing from anyone. I do not care about money. Decorations, titles or distinctions mean nothing to me. I do not crave praise. I claim credit for nothing. A happy man is too satisfied with the present to dwell too much on the future."

 

Evolutionary models of financial markets.

Levin and Lo's introduction of a PNAS special issue on evolutionary models of financial markets is an interesting read. A few clips:

The brilliant evolutionary insights of Darwin and others have revolutionized our understanding of the world. Darwin was impressed by the “tangled bank” of elaborate forms that emerged from the undirected processes of evolution to produce the complexity of the biological world. Through continuous innovation coupled with the deceptively simple filter known as natural selection, the characteristics of species and their interactions change in response to changing environments. However, evolution is not limited only to the biological world. Wherever the evolutionary forces of reproduction, variation, and selection exist—as they do in financial markets—evolutionary consequences will follow. There are of course major differences as well between the nature of the evolutionary process in ecological and economic contexts, largely influenced by the relative importance of top-down control, and the degree to which predictive models and long-term planning can be invoked. These are, however, differences of degree.

There are profound similarities between financial systems and the biosphere. Both are complex adaptive systems in which individual agents act to enhance their own interests and objectives, leading to self-organization and emergent features. In viewing global financial markets as comprising a complex-adaptive biological system, researchers in this area intend to develop more effective models to understand these systems. This is not only of theoretical interest, but also has the practical aim to promote economic growth while maintaining financial stability, with the ultimate goal of allocating resources more efficiently through better financial methods.

Evolution is about short-term, relative optimality with respect to other participants in the system. In the biosphere, natural selection acts to improve reproductive success relative to the benchmark of other genomes, within and across species. Evolutionary change can thus be thought of in terms of differential fitness: that is, small differences in reproductive rates between individuals over time leading to large differences in populations. Even the very mechanisms of evolution—including those that generate new variation—are subject to constant modification. In the financial world, the evolutionary forces of mutation, recombination, reproduction, and selection often work on financial institutions and market participants through direct competition, finance “red in tooth and claw.” Financial concepts and strategies thus reproduce themselves through cultural transmission and adoption based on their success in the marketplace. These strategies undergo variation through financial innovation, analogous to mutation or genetic recombination in a biological system, but take place at the level of information and abstract thought in financial contexts. It is “survival of the richest.”

The evolutionary lens provides a natural way to introduce biological concepts into financial and economic analysis. As the evolutionary biologist Theodosius Dobzhansky said, “Nothing in biology makes sense except in the light of evolution” (5). The same may hold for the financial world. Phenomena that have been difficult to analyze within a traditional economic framework, such as growth, size, scale, self-organization, the lifecycle of products and industries, bull/bear market cycles, and the rate of variation or innovation within a system, are all subject to evolutionary forces, whether they take place in the Petri dish or on the trading floor. Biological experiments thus may be able to directly inform economic insights, and market behavior may be able to shed light on evolutionary mysteries in the biological world.

The A.I. Revolution, Trillionaires and the Future of Political Power.

I want to point to a fascinating Ezra Klein podcast - you can read the transcript here - that is an interview with Sam Altman, the C.E.O. of OpenAI, which is one of the biggest and most interesting of the companies trying to create general purpose artificial intelligence. His recent essay titled "Moore's Law for Everything" has received wide comment, and it's topics are the focus of the interview. Klein notes: "what caught my eye about this essay, “Moore’s Law for Everything,” is Altman’s effort to try and imagine the political consequences of true artificial intelligence and the policies that could decide whether it ushers in utopia or dystopia." I'm going to pass on only clips from Klein's general introductions to give you a taste of the direction of the arguments, and urge you to read both the transcript of the podcast and Altman's essay.

“The technological progress we make in the next 100 years will be far larger than all we’ve made since we first controlled fire and invented the wheel...This revolution will generate enough wealth for everyone to have what they need, if we as a society manage it responsibly.”...Altman's argument is this: Since the 1970s, computers have gotten exponentially better even as they’re gotten cheaper, a phenomenon known as Moore’s Law. Altman believes that A.I. could get us closer to Moore’s Law for everything: it could make everything better even as it makes it cheaper. Housing, health care, education, you name it.

A.I. will create phenomenal wealth, but it will do so by driving the price of a lot of labor to basically zero. That is how everything gets cheaper. It’s also how a lot of people lose their jobs...To make that world a good world for people, to make that a utopia rather than a dystopia, it requires really radical policy change to make sure the wealth A.I. creates is distributed broadly. But if we can do that, he says, well, then we can improve the standard of living for people more than we ever have before in less time. So Altman’s got some proposals here for how we can do that. They’re largely proposals to tax wealth and land. And I push on them here.

This is a conversation, then, about the political economy of the next technological age. Some of it is speculative, of course, but some of it isn’t. That shift of power and wealth is already underway. Altman is proposing an answer: a move toward taxing land and wealth, and distributing it to all. We talk about that idea, but also the political economy behind it: Are the people gaining all this power and wealth really going to offer themselves up for more taxation? Or will they fight it tooth-and-nail?

We also discuss who is funding the A.I. revolution, the business models these systems will use (and the dangers of those business models), how A.I. would change the geopolitical balance of power, whether we should allow trillionaires, why the political debate over A.I. is stuck, why a pro-technology progressivism would also need to be committed to a radical politics of equality, what global governance of A.I. could look like, whether I’m just “energy flowing through a neural network,” and much more.

(You can also listen to the whole conversation by following “The Ezra Klein Show” on Apple, Spotify, Google or wherever you get your podcasts.)

Watching a brain encode present, past, and future….

We all exist as an ongoing simulation of past, present, and future in our brains, with the hallucination we take to be reality being perturbed only when our brains’ expectations are not met. Dotson and Yartsev do experiments in flying bats (of a sort not permitted in humans) that record from the hippocampus showing patterns of neuron activity of the sort needed to support this process. They find that this activity not only encodes the bat’s present location but also signals its positions in the past and future. The technology involved in doing the brain implants that record and wirelessly transmit the neuronal activity, as well as the sophisticated data analysis, is truly awesome (One has to download a massive technical supplement, much too large to include in the article, to get the details.) Here I pass on only the editor’s summary and the abstract for the article:  

Representing space in past and future

As an organism moves through space, its brain has to remember its most recent location and anticipate its future position, not just its current place in the world. Earlier studies reported so-called retrospective and prospective place coding in rats while they were running along linear tracks. However, it would be advantageous to study an animal that rapidly moves through three-dimensional space with high precision. Dotson and Yartsev recorded from flying bats to investigate whether place cell activity in hippocampus area CA1 represents local (current) or nonlocal positions. They discovered that the hippocampus not only encodes the bat's present location but also signals its positions in the past and future.

Abstract

Navigation occurs through a continuum of space and time. The hippocampus is known to encode the immediate position of moving animals. However, active navigation, especially at high speeds, may require representing navigational information beyond the present moment. Using wireless electrophysiological recordings in freely flying bats, we demonstrate that neural activity in area CA1 predominantly encodes nonlocal spatial information up to meters away from the bat’s present position. This spatiotemporal representation extends both forward and backward in time, with an emphasis on future locations, and is found during both random exploration and goal-directed navigation. The representation of position thus extends along a continuum, with each moment containing information about past, present, and future, and may provide a key mechanism for navigating along self-selected and remembered paths.

Sullivan on what has happened to the belief system of the American elites.

In a strident essay Andrew Sullivan pushes back against his critics who troll him as being a far rightist. He deflects the critique by charging that the belief system of the Democratic progressive American elites has moved much farther to the left than the Republicans have moved to the right. Some clips:

Take a big step back. Observe what has happened in our discourse since around 2015...What is it? It is, I’d argue, the sudden, rapid, stunning shift in the belief system of the American elites. It has sent the whole society into a profound cultural dislocation. It is, in essence, an ongoing moral panic against the specter of “white supremacy,” which is now bizarrely regarded as an accurate description of the largest, freest, most successful multiracial democracy in human history...The elites, increasingly sequestered within one political party and one media monoculture, educated by colleges and private schools that have become hermetically sealed against any non-left dissent, have had a “social justice reckoning” these past few years.

..the core point of that movement, its essential point, is that liberalism is no longer enough. Not just not enough, but itself a means to perpetuate “white supremacy,” designed to oppress, harm and terrorize minorities and women, and in dire need of dismantling. That’s a huge deal. And it explains a lot.

The reason “critical race theory” is a decent approximation for this new orthodoxy is that it was precisely this exasperation with liberalism’s seeming inability to end racial inequality in a generation that prompted Derrick Bell et al. to come up with the term in the first place, and Kimberlé Crenshaw to subsequently universalize it beyond race to every other possible dimension of human identity (“intersectionality”)...A specter of invisible and unfalsifiable “systems” and “structures” and “internal biases” arrived to hover over the world. Some of this critique was specific and helpful: the legacy of redlining, the depth of the wealth gap. But much was tendentious post-modern theorizing.

The movement is much broader than race — as anyone who is dealing with matters of sex and gender will tell you. The best moniker I’ve read to describe this mishmash of postmodern thought and therapy culture ascendant among liberal white elites is Wesley Yang’s coinage: “the successor ideology.”...to describe a hegemony that is saturated with “anti-Blackness,” misogyny, and transphobia, in a miasma of social “cis-heteronormative patriarchal white supremacy.” And the term “successor ideology” works because it centers the fact that this ideology wishes, first and foremost, to repeal and succeed a liberal society and democracy...Liberalism leaves you alone. The successor ideology will never let go of you. Liberalism is only concerned with your actions. The successor ideology is concerned with your mind, your psyche, and the deepest recesses of your soul. Liberalism will let you do your job, and let you keep your politics private. S.I. will force you into a struggle session as a condition for employment.

A plank of successor ideology, for example, is that the only and exclusive reason for racial inequality is “white supremacy.” Culture, economics, poverty, criminality, family structure: all are irrelevant, unless seen as mere emanations of white control. Even discussing these complicated factors is racist...The proponents of the successor ideology are] not trying to be malicious, but they are trying to basically annihilate a lot of the foundational processes that we depend upon and then remake them anew. You operate from the starting point that all the previous ideologies, methods, and processes are untrustworthy, because they produced this outcome previously, so we’ve got to remake all of them. Precisely. This is a revolution against liberalism commanded from above.

Due process? If you’re a male on campus, gone. Privacy? Stripped away — by anonymous rape accusations, exposure of private emails, violence against people’s private homes, screaming at folks in restaurants, sordid exposés of sexual encounters, eagerly published by woke mags. Non-violence? Exceptions are available if you want to “punch a fascist.” Free speech? Only if you don’t mind being fired and ostracized as a righteous consequence. Free association? You’ve got to be kidding. Religious freedom? Illegitimate bigotry. Equality? Only group equity counts now, and individuals of the wrong identity can and must be discriminated against. Color-blindness? Another word for racism. Mercy? Not for oppressors. Intent? Irrelevant. Objectivity? A racist lie. Science? A manifestation of white supremacy. Biological sex? Replaced by socially constructed gender so that women have penises and men have periods. The rule of law? Not for migrants or looters. Borders? Racist. Viewpoint diversity? A form of violence against the oppressed.

...check out Kevin Drum’s analysis of asymmetric polarization these past few decades. He shows relentlessly that over the past few decades, it’s Democrats who have veered most decisively to the extremes on policy on cultural issues since the 1990s. Not Republicans. Democrats.On immigration, Republicans have moved around five points to the right; the Democrats 35 points to the left. On abortion, Republicans who advocate a total ban have increased their numbers a couple of points since 1994; Democrats who favor legality in every instance has risen 20 points. On guns, the GOP has moved ten points right; Dems 20 points left.

It is also no accident that, as Drum notes and as David Shor has shown: “white academic theories of racism — and probably the whole woke movement in general —have turned off many moderate Black and Hispanic voters.” This is why even a huge economic boom may not be enough to keep the Democrats in power next year.

Does that mean we should support an increasingly nihilist cult on the right among the GOP? Of course not. Does it mean we should ignore its increasingly menacing contempt for electoral integrity and a stable democracy? Absolutely not. But one reason to fight for liberalism against the successor ideology is that its extremes are quite obviously fomenting and facilitating and inspiring ever-rising fanaticism in response. I fear the successor ideology’s Kulturkampf is already making the 2022 midterms a landslide for a cultish, unmoored GOP. In fighting S.I., we are also fighting Trump.

But I am not making a tactical argument here. I’m making a deeper moral argument. We can and must still fight and argue for what we believe in: a liberal democracy in a liberal society. This fight will not end if we just ignore it or allow ourselves to be intimidated by it, or join the tribal pile-ons. And I will not apologize for confronting this, however unpopular it might make me, just as I won’t apologize for confronting the poison and nihilism on the right. And if you really want to be on “the right side of liberalism,” you will join me.

Coffee is good for you, mostly....

I am dysfunctional on waking every morning until I have had a strong cup of coffee, a personal experience that makes me want to pass on Jane Brody's nice review of studies showing that drinking coffee reduces risk of all kinds of ailments, including Parkinson’s disease, melanoma, prostate cancer, even suicide.

...in numerous studies conducted throughout the world, consuming four or five eight-ounce cups of coffee (or about 400 milligrams of caffeine) a day has been associated with reduced death rates.

But,

..coffee doesn't warrant a totally clean bill of health...The most common ill effect associated with caffeinated coffee is sleep disturbance...People vary widely in how rapidly they metabolize caffeine, enabling some to sleep soundly after drinking caffeinated coffee at dinner while others have trouble sleeping if they have coffee at lunch. But even if you can fall asleep readily after an evening coffee, it may disrupt your ability to get adequate deep sleep, Mr. Pollan states in his forthcoming book, “This Is Your Mind on Plants.”

Caffeine is one of more than a thousand chemicals in coffee, not all of which are beneficial. Among others with positive effects are polyphenols and antioxidants. Polyphenols can inhibit the growth of cancer cells and lower the risk of Type 2 diabetes; antioxidants, which have anti-inflammatory effects, can counter both heart disease and cancer, the nation’s leading killers.