Inflam-aging

Leucht and collaborators show that injured bones do not heal as well with age because of the increases in chronic inflammation that occur with aging.

Significance

As we age, our capacity for tissue repair and regeneration in response to injury declines. Accordingly, bone repair is delayed and impaired in older patients. At the cornerstone of bone healing is the skeletal stem/progenitor cell (SSPC), whose function and number diminishes with age. However, the mechanisms driving this decline remain unclear. Here, we identify age-associated inflammation (“inflamm-aging”) as the main culprit of SSPC dysfunction and provide support for a central role of NF-κB as a mediator of inflamm-aging. Our results show that modification of the inflammatory environment may be a translational approach to functionally rejuvenate the aged SSPC, thereby improving the regenerative capacity of the aged skeleton.

Abstract

Aging is associated with impaired tissue regeneration. Stem cell number and function have been identified as potential culprits. We first demonstrate a direct correlation between stem cell number and time to bone fracture union in a human patient cohort. We then devised an animal model recapitulating this age-associated decline in bone healing and identified increased cellular senescence caused by a systemic and local proinflammatory environment as the major contributor to the decline in skeletal stem/progenitor cell (SSPC) number and function. Decoupling age-associated systemic inflammation from chronological aging by using transgenic Nfkb1KO mice, we determined that the elevated inflammatory environment, and not chronological age, was responsible for the decrease in SSPC number and function. By using a pharmacological approach inhibiting NF-κB activation, we demonstrate a functional rejuvenation of aged SSPCs with decreased senescence, increased SSPC number, and increased osteogenic function. Unbiased, whole-genome RNA sequencing confirmed the reversal of the aging phenotype. Finally, in an ectopic model of bone healing, we demonstrate a functional restoration of regenerative potential in aged SSPCs. These data identify aging-associated inflammation as the cause of SSPC dysfunction and provide mechanistic insights into its reversal.

Affect theory and the new age of anxiety.

Hua Hsu, in the March 25, 2019, issue of The New Yorker, does a fascinating presentation of the work and ideas of Lauren Berlant, whose writing is an example of new field of literary criticism, termed "affect theory", that focuses on nonlinguistic feelings and emotions. Here are a few clips from the article:

In October, 2011, the literary scholar and cultural theorist Lauren Berlant published “Cruel Optimism,” a meditation on our attachment to dreams that we know are destined to be dashed...We like to imagine that our life follows some kind of trajectory, like the plot of a novel, and that by recognizing its arc we might, in turn, become its author. But often what we feel instead is a sense of precariousness—a gut-level suspicion that hard work, thrift, and following the rules won’t give us control over the story, much less guarantee a happy ending. For all that, we keep on hoping, and that persuades us to keep on living...The persistence of the American Dream, Berlant suggests, amounts to a cruel optimism, a condition “when something you desire is actually an obstacle to your own flourishing.”

...our Sisyphean pursuit of the good life has high stakes, and its amalgam of fantasy and futility is something that we process as experience before we rationalize it in thought. These feelings, Berlant says, are the “body’s response to the world, something you’re always catching up to.”...We dream of swimming toward a beautiful horizon, but in truth, Berlant evocatively observed, we are constantly “dogpaddling around a space whose contours remain obscure.” What stories do we tell ourselves in order to stay afloat?

“The Hundreds” (Duke), Berlant’s latest book, co-written with Kathleen Stewart, an anthropologist at the University of Texas at Austin, grows out of ... short writing exercises. Each entry is an experiment in “following out the impact of things” in a hundred words, or a multiple of a hundred words...The result is a strange and captivating book.

In Berlant and Stewart’s hands, affect theory provides a way of understanding the sensations and resignations of the present, the normalized exhaustion that comes with life in the new economy. It is a way of framing uniquely modern questions: Where did the seeming surplus of emotionality that we see on the Internet come from, and what might it become? What new political feelings were being produced by the rudderless drift of life in the gig economy? What if millennials were unintelligible to their parents simply because they have resigned themselves to precariousness as life’s defining feature?

Berlant’s work can feel strangely and kindly optimistic...Maybe relinquishing or recalibrating our fantasies of the good life doesn’t lead to absolute darkness. It can simply be a matter of coming to grips with different possibilities of communion, figuring out who benefits from our collective weariness...But attentiveness to affect encourages us to imagine ourselves beyond the present: even if feelings of exhaustion, indifference, or disillusionment may have been naturalized, that doesn’t mean they’re natural...

“No one wants to be a bad or compromised kind of force in the world, but the latter is just inevitable,” Berlant once wrote in a short essay on her personal credos. “The question is how to develop ways to accentuate those contradictions, to interrupt their banality and to move them somewhere.” We can build worlds out of these small ambitions. We continue to write, even if it occasionally feels as though we were spinning our wheels, and we continue to live, even if it means giving up the certainty that our story is going to end the way we want it to. Writing on her blog a few years ago, Berlant issued what she described as her collective’s secret motto: “We refuse to be worn out.”

More green space in childhood, fewer psychiatric disorders in adulthood.

From Engemann et al.:

Urban residence is associated with a higher risk of some psychiatric disorders, but the underlying drivers remain unknown. There is increasing evidence that the level of exposure to natural environments impacts mental health, but few large-scale epidemiological studies have assessed the general existence and importance of such associations. Here, we investigate the prospective association between green space and mental health in the Danish population. Green space presence was assessed at the individual level using high-resolution satellite data to calculate the normalized difference vegetation index within a 210 × 210 m square around each person’s place of residence (∼1 million people) from birth to the age of 10. We show that high levels of green space presence during childhood are associated with lower risk of a wide spectrum of psychiatric disorders later in life. Risk for subsequent mental illness for those who lived with the lowest level of green space during childhood was up to 55% higher across various disorders compared with those who lived with the highest level of green space. The association remained even after adjusting for urbanization, socioeconomic factors, parental history of mental illness, and parental age. Stronger association of cumulative green space presence during childhood compared with single-year green space presence suggests that presence throughout childhood is important. Our results show that green space during childhood is associated with better mental health, supporting efforts to better integrate natural environments into urban planning and childhood life.

Neural signal diversity is increased by psychedelics

From Carhart-Harris and collaborators:

What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity.

Knowing your own heart - distinguishing interoceptive accuracy and awareness

Garfinkel et al. categorize three different aspects of the internal bodily sensing (interoception) that informs our interactions with the external world, focusing on heartbeats - whose frequency and intensity vary with the degree of our emotional arousal (calm, anticipating, fearful, excited, etc.).

Highlights

• Interoception refers to the signalling and perception of internal bodily sensations.

• We validate a three dimensional construct of interoception.

• This comprises: interoceptive accuracy, sensibility and awareness (metacognition).

• These interoceptive dimensions represent dissociable interoceptive processes.

• Interoceptive accuracy serves as the core (central) construct.

Abstract

Interoception refers to the sensing of internal bodily changes. Interoception interacts with cognition and emotion, making measurement of individual differences in interoceptive ability broadly relevant to neuropsychology. However, inconsistency in how interoception is defined and quantified led to a three-dimensional model. Here, we provide empirical support for dissociation between dimensions of: (1) interoceptive accuracy (performance on objective behavioural tests of heartbeat detection), (2) interoceptive sensibility (self-evaluated assessment of subjective interoception, gauged using interviews/questionnaires) and (3) interoceptive awareness (metacognitive awareness of interoceptive accuracy, e.g. confidence-accuracy correspondence). In a normative sample (N = 80), all three dimensions were distinct and dissociable. Interoceptive accuracy was only partly predicted by interoceptive awareness and interoceptive sensibility. Significant correspondence between dimensions emerged only within the sub-group of individuals with greatest interoceptive accuracy. These findings set the context for defining how the relative balance of accuracy, sensibility and awareness dimensions explain cognitive, emotional and clinical associations of interoceptive ability.

Lethal mass partisanship

I think everyone should read this lucid piece by Thomas Edsall, which describes the emerging consensus on the stark biological and evolved psychological roots of the contempt. moral disgust, and aggression that individual members of right and left wing political groups are now directing toward members of the opposing camp, playing out a primitive tribal in-group/out-group dynamic that has ancient evolutionary roots in primate and other social animal behaviors. We seem to be tearing down the fragile political and legal structures, erected by framers of the US constitution, that allowed this country to at least briefly transcend the warring tribes scenario that has prevailed through most of human history.

Some clips of points that I found fascinating:

As partisan hostility deepens, there is one group that might ordinarily be expected to help pull the electorate out of this morass — the most knowledgeable and sophisticated voters... In “Understanding Partisan Cue Receptivity,” Bert N. Bakker and Yphtach Lelkes...find...the most active voters — those notably “high in cognitive resources” — are the most willing to accept policy positions endorsed by their party, and they are doing so not out of principle, but to affirm their identity as a Democrat or Republican. They are expressing “the desire to reach conclusions that are consistent with a valued identity.”

Ironically, reflective citizens, who are sometimes seen as ideal citizens, might be the subset of strong partisan identifiers most likely to fall in line with the party. Since higher levels of cognitive resources and partisan social identity are associated with higher levels of political activism, the effect may be self-reinforcing, wherein political elites polarize the strongly identified and cognitively reflective, who then elect more polarized elites. The democratic dilemma may not be whether low information citizens can learn what they need to know, but whether high information citizens can set aside their partisan predispositions.

And, some quotes from Steven Pinker:

Certainly there is a tribal flavor to political polarization. Men’s testosterone rises or falls on election night, depending on whether their side wins, just as it does on Super Bowl Sunday...the coalitions clustering at the poles are not tribes in the classical anthropological sense. Today’s left- and right-wingers for the most part aren’t inventing myths of shared blood and common ancestry, or binding together in ritual ordeals, or blending in appearance with a common uniform...I think we’re seeing a somewhat different psychological phenomenon: dynamically sorting ourselves into coalitions defined by moralistic condemnation of designated enemies.

From John Hibbing, a political scientist at the University of Nebraska,

...the central political issues of the day revolve around in-group versus out-group, the definition of the in-group, and the unity and security of the in-group...the problem today is that there are so few cross-cutting cleavages. There is only one cleavage and it is the most evolutionarily primal cleavage of them all...people became tribal because the fundamental substantive issues today are about tribe. We are a group-based species.

From Cosmides and Tooby at UC Santa Barbara,

The set of evolved programs that enable and drive warfare and politics strongly overlap with the set of evolved programs that drive human morality. The mapping of these evolved programs and their embedded circuit logic is only in its infancy, and we have only sketched out some of the known or predicted features of our coalitional and moral psychologies. However, progress in this enterprise holds out the possibility of gradually throwing light on some of the darkest areas of human life...everybody benefits from participating in groups of alliances and factions on different scales, and people also benefit by fractionating solidarity in such a way that those on the far side of the boundary seem undesirable, worth spurning, contemptible, deplorable.

And, the most sobering note from NYU psychologist Jonathan Haidt:

I am expecting that America’s political dysfunction and anger will worsen, and will continue to worsen even after Donald Trump leaves the White House....The reasons for my pessimism are that 1) social media gets ever more effective at drowning us in outrage; 2) overall trust in institutions continues to decline, which makes it seem ever more urgent that “our” side take total control; 3) the younger generations have not seen effective political institutions or norms during their lives, and also seem less adept at handling political disagreements; and 4) the norms of campus regarding call-out culture seem to be spreading quickly into business and many other institutions.

MRI can detect the content of decisions 11 seconds before they are made.

Goldhill points to and summarizes work of Koening-Rober and Pearson. Their abstract:

Is it possible to predict the freely chosen content of voluntary imagery from prior neural signals? Here we show that the content and strength of future voluntary imagery can be decoded from activity patterns in visual and frontal areas well before participants engage in voluntary imagery. Participants freely chose which of two images to imagine. Using functional magnetic resonance (fMRI) and multi-voxel pattern analysis, we decoded imagery content as far as 11 seconds before the voluntary decision, in visual, frontal and subcortical areas. Decoding in visual areas in addition to perception-imagery generalization suggested that predictive patterns correspond to visual representations. Importantly, activity patterns in the primary visual cortex (V1) from before the decision, predicted future imagery vividness. Our results suggest that the contents and strength of mental imagery are influenced by sensory-like neural representations that emerge spontaneously before volition.

Why science needs philosophy

I have always been in awe of the clarity and precision of the thinking of one of my Univ. of Wisconsin colleagues, philosopher Elliott Sober. He is one of the coauthors of a fascinating article on the uses science has for the tools of philosophers (for example, to clean up their fuzzy thinking.) The article might be a bit intense for many readers, but I recommend reading through it. Just a few clips:

...philosophy’s contribution can take at least four forms: the clarification of scientific concepts, the critical assessment of scientific assumptions or methods, the formulation of new concepts and theories, and the fostering of dialogue between different sciences, as well as between science and society.

An example of conceptual clarification:

The definition of stem cells is a prime example. Philosophy has a long tradition of investigating properties, and the tools in use in this tradition have recently been applied to describe “stemness,” the property that defines stem cells. One of us has shown that four different kinds of properties exist under the guise of stemness in current scientific knowledge (1). Depending on the type of tissue, stemness can be a categorical property (an intrinsic property of the stem cell, independent of its environment), a dispositional property (an intrinsic property of the stem cell that is controlled by the microenvironment), a relational property (an extrinsic property that can be conferred to non–stem cells by the microenvironment), or a systemic property (a property that is maintained and controlled at the level of the entire cell population).

Spinning drops!

Here is a really neat, gee whiz kind of study:

To make the water droplets spin, researchers first had to make sure they didn’t wet the surface they fell on—otherwise, they’d just splash. The researchers did this by coating alumina plates with a fluorinated nonstick coating, similar to those found in nonstick cooking pans. Next, they masked some regions of the surface and shone ultraviolet (UV) light on the entire plate. The regions exposed to the UV became highly “wettable,” meaning water touching those regions spread out immediately rather than bouncing back up. The team created several designs of the wettable regions, including one with spiral arms radiating out from a center, much like a pinwheel.

As the droplet bounds up from the patterned surface, the portions encountering the wettable spirals stick to the surface, whereas the parts of the droplet in contact with the water-repelling surface rebound immediately. This creates a set of unbalanced forces, pulling on the droplet more in some parts than in others, twisting it.

Psychological underpinnings of politics

I want to point to a number of commentaries on psychological determinants of political behavior that have been languishing in my queue of potential posts...

How brain science could determine the election. A review of differences between liberals and conservatives in brain processes - with a strong genetic component - that regulate risk tolerance, openness to novelty, fearfulness, etc.

Why Trump will win a second term. Amy Chozick discusses Trump's uncanny grasp, deriving from his experience as a reality show host, of how to keep people's attention by creating an unscripted drama that fills living rooms everywhere, providing entertainment value in the chaos.

The end of the two-party system. David Brooks describes the dissolution of political parties into warring clans competing for declining resources.

Our Culture of Contempt.  Arthur Brooks notes that the problem in America today is not incivility or intolerance, it is contempt for those with opposing views. This is based on motive attribution asymmetry, which leads one side to consider itself driven by benevolence while thinking the other side is motivated by evil and hatred.

Is there such a thing as an authoritarian voter?  Molly Worthen review work studying the psychological traits of voters who are attracted to authoritarian personalities. 

Why is it so hard for democracy to deal with inequality? The Brahmins vs the Merchants

I want to pass on an article that I wish I had made the subject of a longer post when it first appeared.

Thomas Edsall, in "Why is it so hard for democracy to deal with inequality" points to a Power Point presentation by Thomas Piketty, "Brahmin Left vs Merchant Right," that notes a straightforward answer:

Traditional parties of the left no longer represent the working and lower middle classes...the domination of the Democratic Party here (and of socialist parties in France) by voters without college or university degrees came to an end over the period from 1948 to 2017. Both parties are now led by highly educated voters whose interests are markedly different from those in the working class...The result, Piketty argues, is a political system that pits two top-down coalitions against each other...high-education elites vote for the left, while high-income/high-wealth elites for the right, i.e., intellectual elite (Brahmin Left) vs business elite (Merchant Right).

Social threat learning transfers to our decision making.

Lindström et al. (open source) demonstrate that threat associations acquired both by social observation (e.g., through video) and by instruction (e.g., through spoken language) strongly transfer to decision making. This transfer leads to maladaptive decisions when socially acquired associations are outdated rather than valid. The full text describes the three different experimental paradigms noted in the abstract below:

Significance

In today’s world, indirect exposure to threatening situations is more common than ever, as illustrated by footage of terror and disaster in social media. How do such social threat learning experiences shape our decisions? We found that learning about threats from both observation and verbal information strongly influenced decision making. As with learning from our own experience, this influence could be either adaptive or maladaptive depending on whether the social information provided accurate expectations about the environment. Our findings can help explain both adaptive and pathological behaviors resulting from the indirect exposure to threatening events.

Abstract

In today’s world, mass-media and online social networks present us with unprecedented exposure to second-hand, vicarious experiences and thereby the chance of forming associations between previously innocuous events (e.g., being in a subway station) and aversive outcomes (e.g., footage or verbal reports from a violent terrorist attack) without direct experience. Such social threat, or fear, learning can have dramatic consequences, as manifested in acute stress symptoms and maladaptive fears. However, most research has so far focused on socially acquired threat responses that are expressed as increased arousal rather than active behavior. In three experiments (n = 120), we examined the effect of indirect experiences on behaviors by establishing a link between social threat learning and instrumental decision making. We contrasted learning from direct experience (i.e., Pavlovian conditioning) (experiment 1) against two common forms of social threat learning—social observation (experiment 2) and verbal instruction (experiment 3)—and how this learning transferred to subsequent instrumental decision making using behavioral experiments and computational modeling. We found that both types of social threat learning transfer to decision making in a strong and surprisingly inflexible manner. Notably, computational modeling indicated that the transfer of observational and instructed threat learning involved different computational mechanisms. Our results demonstrate the strong influence of others’ expressions of fear on one’s own decisions and have important implications for understanding both healthy and pathological human behaviors resulting from the indirect exposure to threatening events.

How sleep aids recovery from infection, may protect brain from Alzheimer's disease

Dimitrov et al. show how a good night's sleep accelerates recovering from an infection. Glue like proteins (integrins) used by immune system T cells to attach to virus particles and mark them for destruction are produced at greater levels during sleep. In the awake state, signaling molecules like adrenaline are produced at greater levels and inhibit integrin production, reducing the ability of T cells to attach to invading microbes. Here is their technical abstract:

Efficient T cell responses require the firm adhesion of T cells to their targets, e.g., virus-infected cells, which depends on T cell receptor (TCR)–mediated activation of β2-integrins. Gαs-coupled receptor agonists are known to have immunosuppressive effects, but their impact on TCR-mediated integrin activation is unknown. Using multimers of peptide major histocompatibility complex molecules (pMHC) and of ICAM-1—the ligand of β2-integrins—we show that the Gαs-coupled receptor agonists isoproterenol, epinephrine, norepinephrine, prostaglandin (PG) E2, PGD2, and adenosine strongly inhibit integrin activation on human CMV- and EBV-specific CD8+ T cells in a dose-dependent manner. In contrast, sleep, a natural condition of low levels of Gαs-coupled receptor agonists, up-regulates integrin activation compared with nocturnal wakefulness, a mechanism possibly underlying some of the immune-supportive effects of sleep. The findings are also relevant for several pathologies associated with increased levels of Gαs-coupled receptor agonists (e.g., tumor growth, malaria, hypoxia, stress, and sleep disturbances).

Also, Holth et al. show that sleep appears to have a direct protective effect on a key protein that drives AD pathology. They provide direct evidence that disrupting sleep, or stimulating excitatory neurons in brain nuclei that control wakefulness and arousal, promotes the release and spread of damaging tau aggregates across the brains of mice, and that sleep deprivation leads to increased extracellular Aβ and tau in people.

The sleep-wake cycle regulates interstitial fluid (ISF) and cerebrospinal fluid (CSF) levels of β-amyloid (Aβ) that accumulates in Alzheimer’s disease (AD). Furthermore, chronic sleep deprivation (SD) increases Aβ plaques. However, tau, not Aβ, accumulation appears to drive AD neurodegeneration. We tested whether ISF/CSF tau and tau seeding and spreading were influenced by the sleep-wake cycle and SD. Mouse ISF tau was increased ~90% during normal wakefulness versus sleep and ~100% during SD. Human CSF tau also increased more than 50% during SD. In a tau seeding-and-spreading model, chronic SD increased tau pathology spreading. Chemogenetically driven wakefulness in mice also significantly increased both ISF Aβ and tau. Thus, the sleep-wake cycle regulates ISF tau, and SD increases ISF and CSF tau as well as tau pathology spreading.

How many push-ups can you do? Predicting heart health...

Gretchen Reynolds points to work showing that men who could get through 40 or more push-ups had 96 percent less risk of heart problems in the next 10 years than those who quit at 10 or fewer.

Abstract

Importance - Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Robust evidence indicates an association of increased physical fitness with a lower risk of CVD events and improved longevity; however, few have studied simple, low-cost measures of functional status.

Objective - To evaluate the association between push-up capacity and subsequent CVD event incidence in a cohort of active adult men.

Design, Setting, and Participants - Retrospective longitudinal cohort study conducted between January 1, 2000, and December 31, 2010, in 1 outpatient clinics in Indiana of male firefighters aged 18 years or older. Baseline and periodic physical examinations, including tests of push-up capacity and exercise tolerance, were performed between February 2, 2000, and November 12, 2007. Participants were stratified into 5 groups based on number of push-ups completed and were followed up for 10 years. Final statistical analyses were completed on August 11, 2018.

Main Outcomes and Measures - Cardiovascular disease–related outcomes through 2010 included incident diagnoses of coronary artery disease and other major CVD events. Incidence rate ratios (IRRs) were computed, and logistic regression models were used to model the time to each outcome from baseline, adjusting for age and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared). Kaplan-Meier estimates for cumulative risk were computed for the push-up categories.

Results - A total of 1562 participants underwent baseline examination, and 1104 with available push-up data were included in the final analyses. Mean (SD) age of the cohort at baseline was 39.6 (9.2) years, and mean (SD) BMI was 28.7 (4.3). During the 10-year follow up, 37 CVD-related outcomes (8601 person-years) were reported in participants with available push-up data. Significant negative associations were found between increasing push-up capacity and CVD events. Participants able to complete more than 40 push-ups were associated with a significantly lower risk of incident CVD event risk compared with those completing fewer than 10 push-ups (IRR, 0.04; 95% CI, 0.01-0.36).

Conclusions and Relevance - The findings suggest that higher baseline push-up capacity is associated with a lower incidence of CVD events. Although larger studies in more diverse cohorts are needed, push-up capacity may be a simple, no-cost measure to estimate functional status.

Control of OCD behavior by amygdala to prefrontal input.

Sun et al. find a brain circuit in mice regulating OCD behavior that in humans might be susceptible to non drug manipulations such as transcranial magnetic stimulation.

Significance

The pathophysiology underlying obsessive-compulsive disorder (OCD) remains unclear, leading to major challenges in the treatment of OCD patients. Here, we defined a projection from the basolateral amygdala glutamate neurons to the medial prefrontal cortex glutamate and GABA neurons and described the putative importance of this circuit in manifesting the checking symptoms of OCD in mice. In addition, the above major findings were further verified in an fMRI mouse study. These findings raise the possibility of developing optimal treatments for OCD that involve the use of nondrug approaches, such as transcranial magnetic stimulation, that target the converging pathways.

Abstract

Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world’s population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLA^Glu) project onto both medial prefrontal cortex glutamate (mPFC^Glu) and GABA (mPFC^GABA) neurons that locally innervate mPFC^Glu neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLA^Glu inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA–mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLA^Glu→mPFC^GABA→Glu circuit that controls the checking symptoms of OCD.

Long term trends in politics - Trump is not an outlier

A sobering analysis from Jordan et al.:

Significance

Donald Trump and a small group of emerging leaders around the world have been labeled as outliers in the ways that they think and communicate with others. Are they really anomalies, or do they fit into larger political trends? This study adds to existing scholarship by analyzing two important psychological dimensions, analytic thinking and confidence, in 12 large corpora of political texts representing political leaders of various levels in both the United States and other countries as well as 4 corpora of cultural texts. Rather than being anomalous, linguistic analyses find that, over the last century, there have been consistent declines in analytic thinking and rises in confidence in the ways that political leaders communicate with the public.

Abstract

From many perspectives, the election of Donald Trump was seen as a departure from long-standing political norms. An analysis of Trump’s word use in the presidential debates and speeches indicated that he was exceptionally informal but at the same time, spoke with a sense of certainty. Indeed, he is lower in analytic thinking and higher in confidence than almost any previous American president. Closer analyses of linguistic trends of presidential language indicate that Trump’s language is consistent with long-term linear trends, demonstrating that he is not as much an outlier as he initially seems. Across multiple corpora from the American presidents, non-US leaders, and legislative bodies spanning decades, there has been a general decline in analytic thinking and a rise in confidence in most political contexts, with the largest and most consistent changes found in the American presidency. The results suggest that certain aspects of the language style of Donald Trump and other recent leaders reflect long-evolving political trends. Implications of the changing nature of popular elections and the role of media are discussed.

Even 10 minutes of low intensity physical activity enhances executive function in older adults

Petrella et al. (open source) find that executive function in older adults is boosted almost immediately by low intensity exercise as brief as 10 minutes. When a group of 17 older adults with average age of 73 engaged moderate, heavy and very heavy levels of brief exercise, the authors found that the magnitude of the post-exercise executive function benefit did not vary that much with intensity. They evaluated executive function with a pre- and post-exercise antisaccade task. Antisaccades require that an individual look (i.e., saccade) mirror-symmetrical to a visual stimulus and result in longer reaction times, increased directional errors, and less accurate and more variable endpoints than their prosaccade (i.e., saccade to a target’s veridical location) counterparts. Here is the detailed abstract:

Highlights

•Antisaccades assess executive function.

•Older adults show decreased antisaccade reaction times following exercise.

•The executive benefit is observed across moderate to very-heavy exercise intensities.

•Older adults demonstrate subtle executive-related aerobic exercise effects.

Abstract

Ten minutes of aerobic or resistance training can ‘boost’ executive function in older adults. Here, we examined whether the magnitude of the exercise benefit is influenced by exercise intensity. Older adults (N = 17: mean age = 73 years) completed a volitional test to exhaustion (VO2peak) via treadmill to determine participant-specific moderate (80% of lactate threshold (LT)), heavy (15% of the difference between LT and VO2peak) and very-heavy (50% of the difference between LT and VO2peak) exercise intensities. Subsequently, in separate sessions all participants completed 10-min constant load single-bouts of exercise at each intensity. Pre- and post-exercise executive function were examined via the antisaccade task. Antisaccades require a saccade mirror-symmetrical to a target and extensive evidence has shown that antisaccades are supported via frontoparietal networks that demonstrate task-dependent changes following single-bout and chronic exercise. We also included a non-executive task (saccade to veridical target location; i.e., prosaccade) to determine whether a putative post-exercise benefit is specific to executive-related oculomotor control. Results showed that VO2 and psychological ratings of perceived exertion concurrently increased with increasing exercise intensity. As well, antisaccade reaction times showed a 24 ms (i.e., 8%) reduction from pre- to post-exercise assessments (p less than .001), whereas prosaccade values did not (p = .19). Most notably, the post-exercise change in antisaccade RTs did not reliably vary with exercise intensity. Further, for each exercise intensity participants’ cardiorespiratory fitness level was unrelated to the magnitude of the post-exercise executive benefit (ps greater than .13). Accordingly, an exercise duration as brief as 10-min provides a selective benefit to executive function in older adults across the continuum of moderate to very-heavy intensities.

Our emotional reward from music is modulated by dopamine.

Ferreri et al. present evidence that enhancing or inhibiting dopamine signaling using levodopa or risperidone modulates the pleasure experienced while listening to music:

Significance

In everyday life humans regularly seek participation in highly complex and pleasurable experiences such as music listening, singing, or playing, that do not seem to have any specific survival advantage. The question addressed here is to what extent dopaminergic transmission plays a direct role in the reward experience (both motivational and hedonic) induced by music. We report that pharmacological manipulation of dopamine modulates musical responses in both positive and negative directions, thus showing that dopamine causally mediates musical reward experience.

Abstract

Understanding how the brain translates a structured sequence of sounds, such as music, into a pleasant and rewarding experience is a fascinating question which may be crucial to better understand the processing of abstract rewards in humans. Previous neuroimaging findings point to a challenging role of the dopaminergic system in music-evoked pleasure. However, there is a lack of direct evidence showing that dopamine function is causally related to the pleasure we experience from music. We addressed this problem through a double blind within-subject pharmacological design in which we directly manipulated dopaminergic synaptic availability while healthy participants (n = 27) were engaged in music listening. We orally administrated to each participant a dopamine precursor (levodopa), a dopamine antagonist (risperidone), and a placebo (lactose) in three different sessions. We demonstrate that levodopa and risperidone led to opposite effects in measures of musical pleasure and motivation: while the dopamine precursor levodopa, compared with placebo, increased the hedonic experience and music-related motivational responses, risperidone led to a reduction of both. This study shows a causal role of dopamine in musical pleasure and indicates that dopaminergic transmission might play different or additive roles than the ones postulated in affective processing so far, particularly in abstract cognitive activities.

From a review piece by Goupil and Aucouturier in the same PNAS issue:

This result is the latest development in an already remarkable series of studies by the groups of Robert Zatorre and Antoni Rodriguez-Fornells on the implication of the reward system in musical emotions. In their seminal 2001 study, Blood and Zatorre used the PET imaging technique to show that episodes of peak emotional responses to music (or musical “chills”) were associated with increased blood flow in the ventral striatum, the amygdala, and other brain regions associated with emotion and reward. In a 2011 follow-up study, Salimpoor et al. then relied on [11C]raclopride PET—a technique that allows estimating dopamine release in cerebral tissue—to show that peak emotional arousal during music listening is associated with the simultaneous release of dopamine in the bilateral dorsal and ventral striatum. With the increasing spatial resolution of fMRI techniques, in 2013 the same team was able to narrow in on a specific dopaminoceptive subregion of the ventral striatum, the nucleus accumbens (NAcc). Specifically, they found that NAcc activity during music listening is associated with how much money participants are subsequently willing to pay for the songs that they found pleasurable. In a final salvo to establish not only the correlational but also the causal implication of dopamine in musical pleasure, the authors have turned to directly manipulating dopaminergic signaling in the striatum, first by applying excitatory and inhibitory transcranial magnetic stimulation over their participants’ left dorsolateral prefrontal cortex, a region known to modulate striatal function, and finally, in the current study, by administrating pharmaceutical agents able to alter dopamine synaptic availability, both of which influenced perceived pleasure, physiological measures of arousal, and the monetary value assigned to music in the predicted direction.

The finding that music constitutes a privileged stimulus able to activate phylogenetically ancient systems involved in valuation and motivation may very well be interpreted as an indication that the human brain contains an adaptive neural specialization for processing music as a rewarding stimulus. As such, one might wonder whether the crucial question for future research is not so much whether music is rewarding, but rather why.

Mindfulness + acceptance training - randomized controlled trial shows prosocial effects, less loneliness

From Lindsay et al.:

Significance

Loneliness (i.e., feeling alone) and social isolation (i.e., being alone) are among the most robust known risk factors for poor health and accelerated mortality. Yet mitigating these social risk factors is challenging, as few interventions have been effective for both reducing loneliness and increasing social contact. Mindfulness interventions, which train skills in monitoring present-moment experiences with an orientation of acceptance, have shown promise for improving social-relationship processes. This study demonstrates the efficacy of a 2-wk smartphone-based mindfulness training for reducing loneliness and increasing social contact in daily life. Importantly, this study shows that developing an orientation of acceptance toward present-moment experiences is a critical mechanism for mitigating these social risk factors.

Abstract

Loneliness and social isolation are a growing public health concern, yet there are few evidence-based interventions for mitigating these social risk factors. Accumulating evidence suggests that mindfulness interventions can improve social-relationship processes. However, the active ingredients of mindfulness training underlying these improvements are unclear. Developing mindfulness-specific skills—namely, (i) monitoring present-moment experiences with (ii) an orientation of acceptance—may change the way people perceive and relate toward others. We predicted that developing openness and acceptance toward present experiences is critical for reducing loneliness and increasing social contact and that removing acceptance-skills training from a mindfulness intervention would eliminate these benefits. In this dismantling trial, 153 community adults were randomly assigned to a 14-lesson smartphone-based intervention: (i) training in both monitoring and acceptance (Monitor+Accept), (ii) training in monitoring only (Monitor Only), or (iii) active control training. For 3 d before and after the intervention, ambulatory assessments were used to measure loneliness and social contact in daily life. Consistent with predictions, Monitor+Accept training reduced daily-life loneliness by 22% (d = 0.44, P = 0.0001) and increased social contact by two more interactions each day (d = 0.47, P = 0.001) and one more person each day (d = 0.39, P = 0.004), compared with both Monitor Only and control trainings. These findings describe a behavioral therapeutic target for improving social-relationship functioning; by fostering equanimity with feelings of loneliness and social disconnect, acceptance-skills training may allow loneliness to dissipate and encourage greater engagement with others in daily life.

A ketamine inspired nasal spray for depression.

I pass on this New Atlas article link on a nasal spray based on ketamine (the party drug PCP or 'angel dust') that is likely to receive FDA approval soon. From the article (which has a link to a series on that site called Psychedelic medicine 101, describing formerly taboo substances now being found useful, cf. Michael Pollan's recent book "Changing your Mind"):

Originally developed decades ago as a novel anesthetic, ketamine has been undergoing a renaissance in recent years... Of course in the world of Big Pharma there is no money to be made investing in clinical trials for a decades-old drug past its patent. So in comes esketamine, a chemical cousin of ketamine with many similar pharmacological actions. Esketamine is roughly twice as strong as ketamine, eliminated by the body faster, and allegedly presents less negative dissociative symptoms when compared to its relative. For the most part, esketamine acts on the brain in similar ways to ketamine, except it doesn't influence a few key neurological receptors.

Johnson & Johnson has been developing an esketamine-based nasal spray to treat depression for several years. The treatment's development process has been undeniably rocky with two major clinical trials failing to prove the drug is more effective than placebo and some experts questioning its ultimate efficacy.

Ahead of a final FDA decision, expected by early March, an independent advisory committee was recently established to offer a recommendation on the treatment's efficacy. After evaluating a multitude of research submitted by the pharmaceutical company, the committee overwhelmingly voted 14-to-2 in favor of recommending the treatment.