Wednesday, August 17, 2022

Alcohol, neuronal plasticity, and mitochondrial trafficking

Hernandez and Kaun provide a nice description of work by Knabbe et al. with summary graphics. Here is the start of their text:
Consumption of alcohol creates a sense of euphoria, reduces inhibition, and increases sociability and impulsivity. The age at which alcohol is first experienced is a key factor contributing to the likelihood to misuse alcohol. However, the impacts of the first experience of alcohol on the molecules in the brain at these key developmental stages are not well understood. Knabbe et al. endeavored to address the neuromolecular alterations resulting from acute alcohol by combining hippocampal proteomics with somatosensory and motor cortex protein, dendrite, axon, and mitochondrial analysis in adolescent mice. Evidence from this array of preparations led to the hypothesis that alcohol disrupted mitochondrial trafficking, and using Drosophila they demonstrated a functional role for mitochondrial trafficking in cue-induced alcohol preference.
The cross-assay and cross-species approach outlined in Knabbe et al. proved to be an effective way of discovering how alcohol hijacks brain mechanisms. Animals from flies to humans maintain functionally consistent neurotransmitter systems, neural circuit mechanisms, and molecular pathways underlying reward.
And here is the abstract from Knabbe et al.:
Alcohol intoxication at early ages is a risk factor for the development of addictive behavior. To uncover neuronal molecular correlates of acute ethanol intoxication, we used stable-isotope-labeled mice combined with quantitative mass spectrometry to screen more than 2,000 hippocampal proteins, of which 72 changed synaptic abundance up to twofold after ethanol exposure. Among those were mitochondrial proteins and proteins important for neuronal morphology, including MAP6 and ankyrin-G. Based on these candidate proteins, we found acute and lasting molecular, cellular, and behavioral changes following a single intoxication in alcohol-naïve mice. Immunofluorescence analysis revealed a shortening of axon initial segments. Longitudinal two-photon in vivo imaging showed increased synaptic dynamics and mitochondrial trafficking in axons. Knockdown of mitochondrial trafficking in dopaminergic neurons abolished conditioned alcohol preference in Drosophila flies. This study introduces mitochondrial trafficking as a process implicated in reward learning and highlights the potential of high-resolution proteomics to identify cellular mechanisms relevant for addictive behavior.

Monday, August 15, 2022

A systematic review of microdosing - research on low dose psychedelics

I pass on the link to this review by Polito and Liknaitzky. Their abstract:
The use of low doses of psychedelic substances (microdosing) is attracting increasing interest. This systematic review summarises all empirical microdosing research to date, including a set of infrequently cited studies that took place prior to prohibition. Specifically, we reviewed 44 studies published between 1955 and 2021, and summarised reported effects across six categories: mood and mental health; wellbeing and attitude; cognition and creativity; personality; changes in conscious state; and neurobiology and physiology. Studies showed a wide range in risk of bias, depending on design, age, and other study characteristics. Laboratory studies found changes in pain perception, time perception, conscious state, and neurophysiology. Self-report studies found changes in cognitive processing and mental health. We review data related to expectation and placebo effects, but argue that claims that microdosing effects are largely due to expectancy are premature and possibly wrong. In addition, we attempt to clarify definitional inconsistencies in the microdosing literature by providing suggested dose ranges across different substances. Finally, we provide specific design suggestions to facilitate more rigorous future research.

Wednesday, August 10, 2022

Music training enhances auditory and linguistic processing.

From Neves et al.:  

Highlights

• Systematic review and meta-analysis of neurobehavioral effects of music training. 
• We ask whether music training shapes auditory-perceptual and linguistic skills. 
• Multivariate meta-analytic models are combined with narrative synthesis. 
• Music training has a positive effect on auditory and linguistic processing. 
• Our work informs research on plasticity, transfer, and music-based interventions.
Abstract
It is often claimed that music training improves auditory and linguistic skills. Results of individual studies are mixed, however, and most evidence is correlational, precluding inferences of causation. Here, we evaluated data from 62 longitudinal studies that examined whether music training programs affect behavioral and brain measures of auditory and linguistic processing (N = 3928). For the behavioral data, a multivariate meta-analysis revealed a small positive effect of music training on both auditory and linguistic measures, regardless of the type of assignment (random vs. non-random), training (instrumental vs. non-instrumental), and control group (active vs. passive). The trim-and-fill method provided suggestive evidence of publication bias, but meta-regression methods (PET-PEESE) did not. For the brain data, a narrative synthesis also documented benefits of music training, namely for measures of auditory processing and for measures of speech and prosody processing. Thus, the available literature provides evidence that music training produces small neurobehavioral enhancements in auditory and linguistic processing, although future studies are needed to confirm that such enhancements are not due to publication bias.

Monday, August 08, 2022

Old hearts learn new tricks

Nusinovich's summary in Science Magazine of work by Lerchenmüller et al.:
Aging-related diseases such as heart failure and other cardiovascular disorders are the leading causes of death in many countries, and they are becoming increasingly common worldwide as the number of older people increases. The ability of the heart to produce new cardiomyocytes decreases with age, which makes it more difficult to repair damage and increases the risk of heart failure. However, a study by Lerchenmüller et al. suggests that exercise may offer some help in this regard even if started late in life. The authors had previously reported that voluntary exercise can stimulate the generation of cardiomyocytes in young adult mouse hearts, and now they have also observed this phenomenon in aged animals.
Here is the results statement of the article:
Cardiomyogenesis was observed at a significantly higher frequency in exercised compared with sedentary aged hearts on the basis of the detection of mononucleated/diploid 15N-thymidine–labeled cardiomyocytes. No mononucleated/diploid 15N-thymidine–labeled cardiomyocyte was detected in sedentary aged mice. The annual rate of mononucleated/diploid 15N-thymidine–labeled cardiomyocytes in aged exercised mice was 2.3% per year. This compares with our previously reported annual rate of 7.5% in young exercised mice and 1.63% in young sedentary mice. Transcriptional profiling of young and aged exercised murine hearts and their sedentary controls revealed that exercise induces pathways related to circadian rhythm, irrespective of age. One known oscillating transcript, however, that was exclusively upregulated in aged exercised hearts, was isoform 1.4 of regulator of calcineurin, whose regulation and functional role were explored further.

Friday, August 05, 2022

Dissecting and improving motor skill acquisition in older adults

 From the introduction of Elvira et al. (open source):

We designed a study intended to identify (i) the main factors leading to differences in motor skill acquisition with aging and (ii) the effect of applying noninvasive brain stimulation during motor training. Comparing different components of motor skill acquisition in young and older adults, constituting the extremes of performance in this study, we found that the improvement of the sequence-tapping task is maximized by the early consolidation of the spatial properties of the sequence in memory (i.e., sequence order), leading to a reduced error of execution, and by the optimization of its temporal features (i.e., chunking). We found the consolidation of spatiotemporal features to occur early in training in young adults, suggesting the emergence of motor chunks to be a direct consequence of committing the sequence elements to memory. This process, seemingly less efficient in older adults, could be partially restored using atDCS by enabling the early consolidation of spatial features, allowing them to prioritize the increase of their speed of execution, ultimately leading to an earlier consolidation of motor chunks. This separate consolidation of spatial and temporal features seen in older adults suggests that the emergence of temporal patterns, commonly identified as motor chunks at a behavioral level, stem from the optimization of the execution of the motor sequence resulting from practice, which can occur only after the sequence order has been stored in memory.
Here is their abstract:
Practicing a previously unknown motor sequence often leads to the consolidation of motor chunks, which enable its accurate execution at increasing speeds. Recent imaging studies suggest the function of these structures to be more related to the encoding, storage, and retrieval of sequences rather than their sole execution. We found that optimal motor skill acquisition prioritizes the storage of the spatial features of the sequence in memory over its rapid execution early in training, as proposed by Hikosaka in 1999. This process, seemingly diminished in older adults, was partially restored by anodal transcranial direct current stimulation over the motor cortex, as shown by a sharp improvement in accuracy and an earlier yet gradual emergence of motor chunks. These results suggest that the emergence of motor chunks is preceded by the storage of the sequence in memory but is not its direct consequence; rather, these structures depend on, and result from, motor practice.

Wednesday, August 03, 2022

Motor learning without movement

Fascinating work from Kim et al. on the influence of the prediction errors that are essential in calibrating actions of our predictive minds:

Significance

Our brains control aspects of our movements without conscious awareness, allowing many of us to effortlessly pick up a glass of water or wave hello. Here, we demonstrate that this implicit motor system can learn to refine movements that we plan but ultimately decide not to perform. Participants planned to reach to a target but sometimes withheld these reaches while an animation simulated missing the target. Afterward, participants unknowingly reached opposite the direction of the apparent mistake, indicating that the implicit motor system had learned from the animated error. These findings indicate that movement is not strictly necessary for motor adaptation, and we can learn to update our actions without physically performing them.
Abstract
Prediction errors guide many forms of learning, providing teaching signals that help us improve our performance. Implicit motor adaptation, for instance, is thought to be driven by sensory prediction errors (SPEs), which occur when the expected and observed consequences of a movement differ. Traditionally, SPE computation is thought to require movement execution. However, recent work suggesting that the brain can generate sensory predictions based on motor imagery or planning alone calls this assumption into question. Here, by measuring implicit motor adaptation during a visuomotor task, we tested whether motor planning and well-timed sensory feedback are sufficient for adaptation. Human participants were cued to reach to a target and were, on a subset of trials, rapidly cued to withhold these movements. Errors displayed both on trials with and without movements induced single-trial adaptation. Learning following trials without movements persisted even when movement trials had never been paired with errors and when the direction of movement and sensory feedback trajectories were decoupled. These observations indicate that the brain can compute errors that drive implicit adaptation without generating overt movements, leading to the adaptation of motor commands that are not overtly produced.

Monday, August 01, 2022

Brain changes, or the absence thereof, associated with mindfulness training.

Richard Davidson and his collaborators (open source, with useful graphics) inject a note of sanity into evaluating widely reported claims of brain changes induced by mindfulness meditation techniques. They note in their introduction:
Findings from a few small studies have permeated popular media with the notion that a few weeks of training in mindfulness-based stress reduction (MBSR) can lead to measurable changes in brain structure and have been cited over 3200 times, combined. However, there is a lack of replication (conceptual or direct) or confirmatory analysis of these findings in a fully randomized trial. Moreover, a recent meta-analysis found that the proportion of high-quality publications in this domain have not improved over time, although there are a growing number of high-quality studies being conducted.
Their abstract:
Studies purporting to show changes in brain structure following the popular, 8-week mindfulness-based stress reduction (MBSR) course are widely referenced despite major methodological limitations. Here, we present findings from a large, combined dataset of two, three-arm randomized controlled trials with active and waitlist (WL) control groups. Meditation-naïve participants (n = 218) completed structural magnetic resonance imaging scans during two visits: baseline and postintervention period. After baseline, participants were randomly assigned to WL (n = 70), an 8-week MBSR program (n = 75), or a validated, matched active control (n = 73). We assessed changes in gray matter volume, gray matter density, and cortical thickness. In the largest and most rigorously controlled study to date, we failed to replicate prior findings and found no evidence that MBSR produced neuroplastic changes compared to either control group, either at the whole-brain level or in regions of interest drawn from prior MBSR studies.

Friday, July 29, 2022

Wolf attacks predict far-right voting

Under MindBlog's category of "random curious stuff" I couldn't resist passing on the following bit of quirky political analysis from von Hohenberg and Hager:
Does the return of large carnivores affect voting behavior? We study this question through the lens of wolf attacks on livestock. Sustained environmental conservation has allowed the wolf (Canis lupus) to make an impressive and unforeseen comeback across Central Europe in recent years. While lauded by conservationists, local residents often see the wolf as a threat to economic livelihoods, particularly those of farmers. As populists appear to exploit such sentiments, the wolf’s reemergence is a plausible source for far-right voting behavior. To test this hypothesis, we collect fine-grained spatial data on wolf attacks and construct a municipality-level panel in Germany. Using difference-in-differences models, we find that wolf attacks are accompanied by a significant rise in far-right voting behavior, while the Green party, if anything, suffers electoral losses. We buttress this finding using local-level survey data, which confirms a link between wolf attacks and negative sentiment toward environmental protection. To explore potential mechanisms, we analyze Twitter posts, election manifestos, and Facebook ads to show that far-right politicians frame the wolf as a threat to economic livelihoods.

Wednesday, July 27, 2022

Emotional contagion and prosocial behavior

Keysers et al. do an open source review of studies on emotional contagion and prosocial behavior in rodents, whose brain regions necessary for emotional contagion closely resemble those associated with human empathy:
Rats and mice show robust emotional contagion by aligning their fear and pain to that of others.
Brain regions necessary for emotional contagion in rodents closely resemble those associated with human empathy; understanding the biology of emotional contagion in rodents can thus shed light on the evolutionary origin and mechanisms of human empathy.
Cingulate area 24 in rats and mice contains emotional mirror neurons that map the emotions of others onto the witnesses’ own emotions.
Emotional contagion prepares animals to deal with threats by using others as sentinels; the fact that rodents approach individuals in distress facilitates such contagion.
In some conditions, rats and mice learn to prefer actions that benefit others, with notable individual differences. This effect depends on structures that overlap with those of emotional contagion.

Monday, July 25, 2022

Efficiently irrational: deciphering the riddle of human choice

Highlights of an open source article from Paul Glimcher:
A central question for decision-making scholars is: why are humans and animals so predictably inconsistent in their choices? In the language of economics, why are they irrational?
Data suggest that this reflects an optimal trade-off between the precision with which the brain represents the values of choices and the biological costs of that precision. Increasing representational precision may improve choice consistency, but the metabolic cost of increased precision is significant.
Given the cost of precision, the brain might use efficient value-encoding mechanisms that maximize informational content. Mathematical analyses suggest that a mechanism called divisive normalization approximates maximal efficiency per action potential in decision systems.
Behavioral studies appear to validate this claim. Inconsistencies produced by decision-makers can be well modeled as the byproduct of efficient divisive normalization mechanisms that maximize information while minimizing metabolic costs.

Friday, July 22, 2022

The End of the World is Just the Beginning

The title of this post repeats the title of Peter Zeihan's latest book, which I've just finished reading and found utterly fascinating and entertaining, in a gallows humor sort of way. During my awakening this morning my mind was generating words attempting to cook Zeihan's basic message down into a few sentences... Here they are:
In the new world that we are now entering America is one of the few countries that can both feed itself and make all the widgets that it needs. Together with its partners in the NAFTA alliance it is geographically and demographically secure, able to turn inwards and still maintain much of its population and lifestyle. Almost all other countries must either export or import energy, food, materials, or manufactured products. Free trade transport routes that have permitted this are crumbling as America continues its withdrawal from guaranteeing a world order formed to oppose a former Soviet Union that fell in 1990. As the level of global trade diminishes, most countries outside the North American group must reduce their population levels and living standards.
I was pointed to this book by listening to a Sam Harris "Makeing Sense" podcast titled titled "The End of Global Order," an interview with Peter Zeihand and Ian Bremmer. Zeihan integrates geopolitical and demographic perspectives to make a compelling case that that past few decades have been the best it will ever be in our lifetime, because our world is breaking apart. For the past seventy-five years we have been living a a perfect moment made possible by post World War II American fostering:
“an environment of global security so that any partner could go anywhere, anytime, interface with anyone, in any economic manner, participate in any supply chain and access any material input—all without needing a military escort. This butter side of the Americans’ guns-and-butter deal created what we today recognize as free trade. Globalization.”
But,
“Thirty years on from the Cold War’s end, the Americans have gone home. No one else has the military capacity to support global security, and from that, global trade. The American-led Order is giving way to Disorder. Global aging didn’t stop once we reached that perfect moment of growth...The global worker and consumer base is aging into mass retirement. In our rush to urbanize, no replacement generation was ever born...“The 2020s will see a collapse of consumption and production and investment and trade almost everywhere. Globalization will shatter into pieces. Some regional. Some national. Some smaller. It will be costly. It will make life slower. And above all, worse.”
Zeihan shows that the America and its partners in the NAFTA accord, Canada and Mexico, enjoy a "Geography of Success" and demographics that will render it vastly better off than the rest of the world.
Perhaps the oddest thing of our soon-to-be present is that while the Americans revel in their petty, internal squabbles, they will barely notice that elsewhere the world is ending!!! Lights will flicker and go dark. Famine’s leathery claws will dig deep and hold tight. Access to the inputs—financial and material and labor—that define the modern world will cease existing in sufficient quantity to make modernity possible. The story will be different everywhere, but the overarching theme will be unmistakable: the last seventy-five years long will be remembered as a golden age, and one that didn’t last nearly long enough at that.
In the introduction of his book, from which the above quotes are taken, Zeihan states that the book's real focus..
...is to map out what everything looks like on the other side of this change in condition. What are the new parameters of the possible? In a world deglobalized, what are the new Geographies of Success?
The book's introduction and epilogue are useful summaries, and you should check out the very instructive graphics provided on Zeihan's website.

Wednesday, July 20, 2022

Widespread ripples synchronize human cortical activity during sleep, waking, and memory recall

I pass on the summaries of work by Dickey et al.:  

Significance

Different elements of a memory, or any mental event, are encoded in locations distributed across the cortex. A prominent hypothesis proposes that widespread networks are integrated with bursts of synchronized high-frequency oscillations called “ripples,” but evidence is limited. Here, using recordings inside the human brain, we show that ripples occur simultaneously in multiple lobes in both cortical hemispheres and the hippocampus, generally during sleep and waking, and especially during memory recall. Ripples phase-lock local cell firing and phase-synchronize with little decay between locations separated by up to 25 cm, enabling long-distance integration. Indeed, corippling sites have increased correlation of very-high-frequency activity which reflects cell firing. Thus, ripples may help bind information across the cortex in memory and other mental events.
Abstract
Declarative memory encoding, consolidation, and retrieval require the integration of elements encoded in widespread cortical locations. The mechanism whereby such “binding” of different components of mental events into unified representations occurs is unknown. The “binding-by-synchrony” theory proposes that distributed encoding areas are bound by synchronous oscillations enabling enhanced communication. However, evidence for such oscillations is sparse. Brief high-frequency oscillations (“ripples”) occur in the hippocampus and cortex and help organize memory recall and consolidation. Here, using intracranial recordings in humans, we report that these ∼70-ms-duration, 90-Hz ripples often couple (within ±500 ms), co-occur (≥ 25-ms overlap), and, crucially, phase-lock (have consistent phase lags) between widely distributed focal cortical locations during both sleep and waking, even between hemispheres. Cortical ripple co-occurrence is facilitated through activation across multiple sites, and phase locking increases with more cortical sites corippling. Ripples in all cortical areas co-occur with hippocampal ripples but do not phase-lock with them, further suggesting that cortico-cortical synchrony is mediated by cortico-cortical connections. Ripple phase lags vary across sleep nights, consistent with participation in different networks. During waking, we show that hippocampo-cortical and cortico-cortical coripples increase preceding successful delayed memory recall, when binding between the cue and response is essential. Ripples increase and phase-modulate unit firing, and coripples increase high-frequency correlations between areas, suggesting synchronized unit spiking facilitating information exchange. co-occurrence, phase synchrony, and high-frequency correlation are maintained with little decrement over very long distances (25 cm). Hippocampo-cortico-cortical coripples appear to possess the essential properties necessary to support binding by synchrony during memory retrieval and perhaps generally in cognition.

Monday, July 18, 2022

Restoring the aged brain with cerebrospinal fluid.

The transfer of blood plasma from young animals to old animals, has been shown to reverse aging changes in the brain, and now Iram et al. show in mice that infusions of young CSF cerebrospinal fluid (CSF) into the brains of aged animals promote oligodendrogenesis and improve memory function, and that fibroblast growth factor 17 (FGF17) is a key molecule that mediates these effects.
Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds. We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.

Friday, July 15, 2022

How the organization of generalized knowledge promotes memory.

From Wing et al.: Significance
What we remember is shaped by what we already know. For example, remembering the angelfish from a recent aquarium visit is easier for those who already know what angelfish are and know things about them. In addition to facilitating memory retrieval of specific items, prior knowledge also supports memory by providing an overarching organizational structure for new information. Here, we show how expert knowledge leads birdwatchers to organize birds based on conceptual features, in contrast to novices who organize birds based on perceptual features. In turn, experts’ organizational structure supports memory by reducing interference typically caused by high overlap among items, even when to-be-remembered birds were unfamiliar species. These findings demonstrate how the organization of generalized knowledge promotes memory.
Abstract
The influence of prior knowledge on memory is ubiquitous, making the specific mechanisms of this relationship difficult to disentangle. Here, we show that expert knowledge produces a fundamental shift in the way that interitem similarity (i.e., the perceived resemblance between items in a set) biases episodic recognition. Within a group of expert birdwatchers and matched controls, we characterized the psychological similarity space for a set of well-known local species and a set of less familiar, nonlocal species. In experts, interitem similarity was influenced most strongly by taxonomic features, whereas in controls, similarity judgments reflected bird color. In controls, perceived episodic oldness during a recognition memory task increased along with measures of global similarity between items, consistent with classic models of episodic recognition. Surprisingly, for experts, high global similarity did not drive oldness signals. Instead, for local birds memory tracked the availability of species-level name knowledge, whereas for nonlocal birds, it was mediated by the organization of generalized conceptual space. These findings demonstrate that episodic memory in experts can benefit from detailed subcategory knowledge, or, lacking that, from the overall relational structure of concepts. Expertise reshapes psychological similarity space, helping to resolve mnemonic separation challenges arising from high interitem overlap. Thus, even in the absence of knowledge about item-specific details or labels, the presence of generalized knowledge appears to support episodic recognition in domains of expertise by altering the typical relationship between psychological similarity and memory.

Wednesday, July 13, 2022

fNIRS - Functional near Iinfrared spectroscopy as a monitor of brain activity

Functional magnetic resonance imaging, or fMRI, requires that a subject remain still for an extended period within the confines of a large, noisy magnet available only at a dedicated facility. Sakai does an accessible review of recent work on functional near-infrared spectroscopy, or fNIRS, which affords a view into the brain based on blood oxygenation without the need for a big, immobile scanner. This optical imaging technique detects changes in how hemoglobin absorbs near-infrared light—usually wavelengths between 750 and 1,200 nanometers. Like fMRI, fNIRS provides an indirect measure of localized brain activity. It has now advanced from relatively simple measures of blood-oxygen changes to a sophisticated method of recording real-time brain responses associated with a wide variety of activities and cognitive tasks. fNIRS offers much better temporal resolution than fMRI, but light scattering limits fNIRS signals to the outer two centimeters of the brain, with a spatial resolution of about two to three centimeters—lower than fMRI but higher than EEG. The portability of fNIRS systems is allowing researchers to scrutinize the brain activity of subjects who are on the move, and observe brain changes associated with language recovery after a stroke.

Friday, July 08, 2022

Stress in older adults accelerates immune system aging.

Seo does a summary article that points to the work of Klopak et al. The Klopak et al. abstract:  

Significance

As the world’s population of older adults increases, understanding disparities in age-related health is essential. Age-related changes in the immune system play a critical role in age-related morbidity and mortality. This study assesses associations between social stress and immunophenotypes as immune age phenotype markers for the first time in a national sample of older US adults. This study helps clarify mechanisms involved in accelerated development of the immune age phenotype, including socioeconomic and lifestyle factors and cytomegalovirus infection and reactivation. This study also identifies important points of intervention that may be useful in addressing inequalities in aging.
Abstract
Exposure to stress is a risk factor for poor health and accelerated aging. Immune aging, including declines in naïve and increases in terminally differentiated T cells, plays a role in immune health and tissue specific aging, and may contribute to elevated risk for poor health among those who experience high psychosocial stress. Past data have been limited in estimating the contribution of life stress to the development of accelerated immune aging and investigating mediators such as lifestyle and cytomegalovirus (CMV) infection. This study utilizes a national sample of 5,744 US adults over age 50 to assess the relationship of social stress (viz., everyday discrimination, stressful life events, lifetime discrimination, life trauma, and chronic stress) with flow cytometric estimates of immune aging, including naïve and terminally differentiated T cell percentages and the ratio of CD4+ to CD8+ cells. Experiencing life trauma and chronic stress was related to a lower percentage of CD4+ naïve cells. Discrimination and chronic stress were each associated with a greater percentage of terminally differentiated CD4+ cells. Stressful life events, high lifetime discrimination, and life trauma were related to a lower percentage of CD8+ naïve cells. Stressful life events, high lifetime discrimination, and chronic stress were associated with a higher percentage of terminally differentiated CD8+ cells. High lifetime discrimination and chronic stress were related to a lower CD4+:CD8+ ratio. Lifestyle factors and CMV seropositivity partially reduced these effects. Results identify psychosocial stress as a contributor to accelerating immune aging by decreasing naïve and increasing terminally differentiated T cells.

Wednesday, July 06, 2022

How stress focuses brain integration

From Wang et al.(open source, with good graphics):
Despite the prevalence of stress, how brains reconfigure their multilevel, hierarchical functional organization in response to acute stress remains unclear. We examined changes in brain networks after social stress using whole-brain resting-state functional MRI (fMRI) by extending our recently published nested-spectral partition method, which quantified the functional balance between network segregation and integration. Acute stress was found to shift the brain into a more integrated and less segregated state, especially in frontal-temporal regions. Stress also stabilized brain states by reducing the variability of dynamic transition between segregated and integrated states. Transition frequency was associated with the change of cortisol, and transition variability was correlated with cognitive control. Our results show that brain networks tend to be more integrated and less variable after acute stress, possibly to enable efficient coping.

Monday, July 04, 2022

Truly Humbled....

I came across this David Brooks piece while scanning the Atlantic Magazine App on my iPad this morning, and then found on checking my email that a friend had already sent the article link to me. Here it is, a brief read:
Truly Humbled to Be the Author of This Article - How to flaunt your modesty online, in three easy steps
“I was humbled to be awarded an honorary degree by the London School of Economics earlier this week. Thank you so much for this prestigious honour!” — Tweet from Christine Lagarde, president of the European Central Bank
Whenever I feel particularly humble, I tweet about myself. I have never earned an honorary degree from the London School of Economics, but if I ever did, I’d certainly tweet the hell out of it. I’d want to let the world know how humbled the experience had made me. I’d tweet my humility, Instagram my humility, and maybe even TikTok it if I could find dance moves humble enough to make my point.
In the meantime, I’m humbled by Lagarde’s tweet. I have spent years studying the fine art of humility display, and I am humbled by her masterful show of it. If you’ve spent any time on social media, and especially if you’re around the high-status world of the achievatrons, you are probably familiar with the basic rules of the form. The first rule is that you must never tweet about any event that could actually lead to humility. Never tweet: “I’m humbled that I went to a party, and nobody noticed me.” Never tweet: “I’m humbled that I got fired for incompetence.”
The whole point of humility display is to signal that you are humbled by your own magnificent accomplishments. We can all be humbled by an awesome mountain or the infinitude of the night sky, but to be humbled by being in the presence of yourself—that is a sign of truly great humility.
The second rule is that you must always use the word humbled when the word proud would actually be more accurate. For example: “Humbled to be make the 100 Under 100 list in Arbitrary Lists Magazine,” “Truly Humbled to be keynote speaker at TedXEastHampton,” “Humbled that Cameron Diaz is giving me a ride to Bradley Cooper’s surprise birthday party. Just thought I’d mention it.” The key to humility display is to use self-effacement as a tool to maximize your self-promotion.
The third rule is that you must never use a pronoun. I don’t mean to carp, but I think Christine Lagarde erred when she began her tweet “I am humbled …” If you’re a truly important person, you don’t have time for pronouns in your tweets, emails, or texts, so you’ll want to truncate all your communications. You’ll want to start your tweets with “Humbled to be …” or “Honored to be …” This sends the message that you have only a few seconds to dash off this tweet, because you’ve got Melinda Gates on hold.
The great thing about humility tweets is that you’re not trying to show that you are better than anybody else. You are showing that you are a regular, normal person, despite the fact that your life is so much more fabulous than those of the people around you. You are showing the world that you haven’t let your immense achievements go to your head! You’ve remained completely egalitarian—you just happen to be a better egalitarian than most people (and you are humbled by that fact). It’s easy to be humble when you’re most people. But just think about how amazing it is to be humble when you’re as impressive as you!
The art of humility display goes back centuries. The first recorded humility tweet was written thousands of years ago by a Greek woman named Helen: “Humbled that Achilles and Agamemnon would go to all that trouble!” The tradition continued in biblical times with Jesus of Nazareth: “Humbled to be the Messiah. Couldn’t have done it without Dad.” And one can find high-water moments of humility display throughout the centuries that followed, for example, from the great British general the Duke of Wellington: “Wow. A beef dish. Truly humbled.”
But the advent of social media has heralded a golden age of humility display. In 2012, the late screenwriter Harris Wittels wrote a book called Humblebrag: The Art of False Modesty, in which he compiled hundreds of actual tweets by people who are masters of this craft of one-downsmanship.
Here’s the television producer Judalina Neira: “I have a meeting with a Coppola tomorrow and I have absolutely no idea how I got it or what it’s about.” Here’s the male model Jake Pavelka: “Swimsuit photo shoots are like a shot in the arm. Glad when there over!” Here’s the musician Kris Allen: “I love how people get freaked out when I don’t fly 1st class. On a 45 min flight? Seriously? Not worth it.” Here’s Pete Wentz from the band Fall Out Boy: “Pumping gas in front of the paparazzi makes me way nervous.”
The key point is that none of these people is actually an A-list celebrity. But through their own creative tweeting, they have humbled themselves all the way up to superstardom! With a series of daring feints, they have hinted that their lives are so stratospheric as to leave Brad Pitt gaping and applauding.
It’s true that the world is full of narcissists—people so full of themselves they think about their own talents more than my own. But in the decade since Wittels compiled his book, we have entered an even greater age of humility. Back then, people danced around the fact that they were humblebragging. Now the humility is explicit, assertive, direct, and unafraid. We blaze forth so much humility that it’s practically blinding. Humility is the new pride.

Friday, July 01, 2022

Reduction of stress and inflammatory responses by transcutaneous cervical vagal nerve stimulation

I want to point to an article by Caron that reviews work investigating therapeutic effects of stimulating our vagus nerve, two large nerve fiber bundles that run down both sides of our neck from the brain stem to our internal organs to regulate our parasympathetic 'calming' nervous system (as distinguished from the 'arousing' sympathetic part of our autonomic nervous system.) In the work by Bremmer et al. (open source) cited by Caron I was struck by the simplicity and accessibility of the simple technique used to stimulate the neck vagus nerves and suppress inflammatory and stress responses.

 


Figure 3. Diagram showing placement of tcVNS device on the neck to target the vagus nerve as it travels through the carotid sheath.

For technically inclined readers like myself, I pass on the following details of the vagal stimulation:
Both active tcVNS and sham stimuli were administered using hand-held devices that target the cervical portion of the vagus nerve from the skin (GammaCore, ElectroCore, Basking Ridge, New Jersey). Stimulation was applied using collar, stainless steel electrodes with a conductive electrode gel placed on the left side of the neck over the carotid sheath as determined by palpation of the carotid artery (Figure 3). Active tcVNS devices produced an alternating voltage signal consisting of five 5kHz sine bursts (1 ms of five sine waves with pulse width of 40 ms) repeating at a rate of 25 Hz envelopes. The frequency of 25 Hz was chosen based on prior studies showing optimization of effects on autonomic function and other measures at this frequency...The sham devices produce an alternating biphasic voltage signal consisting of 0.2 Hz square pulses (pulse width of 5 s) eliciting a mild sensation...Both active and sham devices delivered two minutes of stimulation. The stimulation intensity (amplitude of the voltage wavefront) was adjustable using a roll switch that ranged from 0 to 5 a.u. (arbitrary units) with a corresponding peak output ranging from 0 to 30V for active tcVNS, and from 0 to 14 V for the sham device. During each application, the amplitude of the voltage waveform was increased to the maximum the subject could tolerate, without pain. The stimulation continued at the selected intensity...The rationale behind the frequency difference between active (5kHz) and sham (0.2Hz) device waveforms is based on the fact that high frequency voltage signals (such as the active stimulus, 5kHz) pass through the skin with minimal power dissipation due to the low skin-electrode impedance at kHz frequencies. In contrast, lower frequency signals (such as the sham stimulus, 0.2Hz) are mainly attenuated at the skin-electrode interface due to the high impedance (Rosell et al., 1988). Accordingly, the active device operating at higher frequencies can deliver substantial energy to the vagus nerve to facilitate stimulation, while the voltage levels appearing at the vagus would be expected to be orders of magnitude lower for the sham device and thus stimulation is unlikely. Nevertheless, since the sham device does deliver relatively high voltage levels directly to the skin, it activates skin nociceptors, causing a similar feeling to a pinch. This sensation is considered to be necessary for blinding of the participants, particularly longitudinal protocols such as in this manuscript.