The embodied cognition of your love life.

MindBlog has done a number of posts on how physical changes in our bodies can influence social cognition (Holding a warm versus an iced cup of coffee makes you more friendly). In yet another example of embodied cognition, Forest et al. note an interesting relationship between physical instability and perceived social relationship stability.

What influences how people feel about and behave toward their romantic partners? Extending beyond features of the partners, relationship experiences, and social context, the current research examines whether benign, relationship-irrelevant factors—such as one’s somatic experiences—can influence relationship perceptions and interpersonal behavior. Drawing on the embodiment literature, we propose that experiencing physical instability can undermine perceptions of relationship stability. Participants who experienced physical instability by sitting at a wobbly workstation rather than a stable workstation (Study 1), standing on one foot rather than two (Study 2), or sitting on an inflatable seat cushion rather than a rigid one (Study 3) perceived their romantic relationships to be less likely to last. Results were consistent with risk-regulation theory: Perceptions of relational instability were associated with reporting lower relationship quality (Studies 1–3) and expressing less affection toward the partner (Studies 2 and 3). These findings indicate that benign physical experiences can influence perceptions of relationship stability, exerting downstream effects on consequential relationship processes.

Kinda Neat! - a Soft Jumping Robot

Using a multi-material 3D printer for manufacturing allowed Wyss Institute researchers (Bartlett et al.) to fabricate the jumping robot in one uninterrupted job, seamlessly transitioning from rigid core components to a soft exterior in a single print session. It's first ever robot to be 3D printed with layers of material gradients, making it extremely durable and giving the jumping robot a long lifespan of use, and could lead to a new class of functionally-graded soft robots.

 

Why don't the poor rise up?

Thomas Edsall offers interesting comments on the seeming intractability of rising inequality in our society, and I pass on a few clips, continuing the MindBlog topic thread that has been contrasting the brains and behaviors of advantaged and disadvantaged segments of our society (cf. here).

Why are today’s working poor so quiescent?...First, although incomes have declined, the cost of many goods – televisions, computers, air-conditioners, household appliances, cellphones – has fallen, leaving the bottom quintile less deprived than simple income figures might reflect. Second, people nowadays marry and have children later in life than in the past, postponing some financial demands to better earning years. Third, some economists contend that commonly used inflation measures result in excessively high estimates of the real-world cost of goods for consumers, thus making living conditions less dire than they might otherwise be.

But there is another reason that there has not been broad public insurrection...Society has drastically changed since the high-water mark of the 1930s and 1960s when collective movements captured the public imagination. Now, there is an inexorable pressure on individuals to, in effect, fly solo. There is very little social support for class-based protest – what used to be called solidarity...Collective social action...has been supplanted by a different kind of revolt...the top priorities of the specific movements associated with individualization – “the feminist movement, lesbian-gay-bisexual-transgender movements, the black power movement, the disability rights movement, and, most recently, the fat-acceptance movement” – do not lend themselves to broad economic demands on behalf of the less well off.

Edsall offers summaries worth reading, of the arguments in several recent books on the individualization of society over the past 50 years.

Political ideology, self control, and belief in free will.

MindBlog has a thread of posts noting psychological studies on those who endorse traditional values and the status quo (conservatives) versus those who endorse egalitarian ideals and progressive change (liberals). Clarkson et al. add a further interesting instalment to such studies, using the usual gaggle of ~150 college undergraduates the first two of their three studies, and ~150 subjects chosen by Amazon's Mechanical Turk for the third.:

Significance

Surprisingly little is known about the self-control consequences of individuals’ political ideologies, given the centrality of political ideology to people’s self-identity and the vitality of self-control to human functioning. This research addresses this unexplored gap by offering insight into the processes (freewill beliefs) and factors (the value of freewill for effective self-control) that lead both conservatives and liberals to demonstrate greater self-control. In doing so, these findings provide a platform by which to broaden our understanding of the underlying mechanisms impacting self-control as well as an alternative perspective for interpreting previously documented differences between conservatives and liberals (e.g., intelligence, academic success).

Abstract

Evidence from three studies reveals a critical difference in self-control as a function of political ideology. Specifically, greater endorsement of political conservatism (versus liberalism) was associated with greater attention regulation and task persistence. Moreover, this relationship is shown to stem from varying beliefs in freewill; specifically, the association between political ideology and self-control is mediated by differences in the extent to which belief in freewill is endorsed, is independent of task performance or motivation, and is reversed when freewill is perceived to impede (rather than enhance) self-control. Collectively, these findings offer insight into the self-control consequences of political ideology by detailing conditions under which conservatives and liberals are better suited to engage in self-control and outlining the role of freewill beliefs in determining these conditions.

Caffeine as an antidote to depression caused by stress.

Kaster et al. do work that suggests adenosine A2A receptor (A2AR) antagonists might be therapeutic agents for relieving stress induced depression.:

Epidemiological studies show that individuals exposed to repeated stress, a major trigger of depression, increase their caffeine intake, which correlates inversely with the incidence of depression. However, the mechanism underlying this protective effect is unknown. We used an animal model of chronic unpredictable stress (CUS) to show that caffeine prevents the maladaptive changes caused by CUS in a manner mimicked by the selective blockade of adenosine A2A receptors (A2AR). CUS enhanced A2AR in synapses, and the selective elimination of neuronal A2AR abrogated CUS modifications. Moreover, A2AR blockade also afforded a therapeutic benefit, paving the way to consider A2AR blockers as a strategy to manage the negative impact of chronic stress on mood and memory.

Groups are better lie detectors than individuals.

From Klein and Epley:

Significance

Detecting lies is difficult. Accuracy rates in experiments are only slightly greater than chance, even among trained professionals. Costly programs aimed at training individual lie detectors have mostly been ineffective. Here we test a different strategy: asking individuals to detect lies as a group. We find a consistent group advantage for detecting small “white” lies as well as intentional high-stakes lies. This group advantage does not come through the statistical aggregation of individual opinions (a “wisdom-of-crowds” effect), but instead through the process of group discussion. Groups were not simply maximizing the small amounts of accuracy contained among individual members but were instead creating a unique type of accuracy altogether.

Abstract

Groups of individuals can sometimes make more accurate judgments than the average individual could make alone. We tested whether this group advantage extends to lie detection, an exceptionally challenging judgment with accuracy rates rarely exceeding chance. In four experiments, we find that groups are consistently more accurate than individuals in distinguishing truths from lies, an effect that comes primarily from an increased ability to correctly identify when a person is lying. These experiments demonstrate that the group advantage in lie detection comes through the process of group discussion, and is not a product of aggregating individual opinions (a “wisdom-of-crowds” effect) or of altering response biases (such as reducing the “truth bias”). Interventions to improve lie detection typically focus on improving individual judgment, a costly and generally ineffective endeavor. Our findings suggest a cheap and simple synergistic approach of enabling group discussion before rendering a judgment.

The science of 'Inside-Out"'

Sure enough - after last Monday's post pointing to Anthony Lane's review of 'Inside-Out' and noting how accurately the movie's depiction of goings-on inside an 11-year old girl's head corresponded to current neuroscience accounts of how our brains work - today's New York Times has an op-ed piece by psychologists Dacher Keltner and Paul Ekman, who in fact were scientific advisors to writer and director Pete Docter. They grumble a bit that Docter decided that the story could only handle five or six internal actors (Anger, Disgust, Fear, Sadness and Joy)rather than the more full array currently being studied by researchers like Keltner and others. (I've debated taking myself to the theater to watch the whole movie surrounded by a bunch of 8-13 year olds, and discover, short of doing that, that simply entering Inside Out in the YouTube search window gets you to brief video clips from different parts of the movie depicting its core animations of memory, the control room, etc.) A few clips from the Keltner and Ekman Op-Ed:

...the movie’s portrayal of sadness successfully dramatizes two central insights from the science of emotion. First, emotions organize — rather than disrupt — rational thinking. Traditionally, in the history of Western thought, the prevailing view has been that emotions are enemies of rationality and disruptive of cooperative social relations...But the truth is that emotions guide our perceptions of the world, our memories of the past and even our moral judgments of right and wrong, most typically in ways that enable effective responses to the current situation...Second, emotions organize — rather than disrupt — our social lives. Studies have found, for example, that emotions structure (not just color) such disparate social interactions as attachment between parents and children, sibling conflicts, flirtations between young courters and negotiations between rivals...Other studies find that it is anger (more so than a sense of political identity) that moves social collectives to protest and remedy injustice. Research that one of us has conducted has found that expressions of embarrassment trigger others to forgive when we’ve acted in ways that momentarily violate social norms.

The Higher Life - A mindfulness guru for the tech set.

A brief post to point to an engaging article in The New Yorker by Lizzie Widdicombe that describes the efforts of Andy Puddicombe and others to bring meditation and mindfulness techniques to digital burnouts, expanding the definition of success beyond money and power to include well-being, wonder, wisdom, giving...etc.

The smell of happiness.

Here's an interesting bit. de Groot et al. obtained armpit sweat from 12 young Caucasian heterosexual men in three consecutive sessions (with fear-inducing, happiness-inducing, or neutral film clips), separated by a week's interval. 36 female Caucasian undergraduates served as "receivers" of the odor stimuli. Exposure to sweat from happy senders elicited a happier facial expression than did sweat from fearful or neutral senders; further, sweat from happy senders elicited a more global processing style relative to sweat from fearful senders. Here is their abstract:

It is well known that feelings of happiness transfer between individuals through mimicry induced by vision and hearing. The evidence is inconclusive, however, as to whether happiness can be communicated through the sense of smell via chemosignals. As chemosignals are a known medium for transferring negative emotions from a sender to a receiver, we examined whether chemosignals are also involved in the transmission of positive emotions. Positive emotions are important for overall well-being and yet relatively neglected in research on chemosignaling, arguably because of the stronger survival benefits linked with negative emotions. We observed that exposure to body odor collected from senders of chemosignals in a happy state induced a facial expression and perceptual-processing style indicative of happiness in the receivers of those signals. Our findings suggest that not only negative affect but also a positive state (happiness) can be transferred by means of odors.

Cat videos are good for your health.

Why are there more than 2 million cat videos on YouTube with an average of 12,000 views per clip? Myrick surveyed ~ 7,000 internet users to find that in general people felt less anxious, annoyed or sad after watching the clips, with an emotional payoff that was stronger than feeling of guilt over procrastinating. And, it certainly is cheaper than paying a shrink! Here is the abstract, which gives you an idea of the waffling nature of the text:

Anecdotes abound about the frequent use of the Internet to view cat-related media. Yet, research has yet to seriously address this popular culture phenomenon rooted largely in social media platforms. It is possible that viewing of online cat media improves mood, but this activity may also foster negative outcomes linked to using the Internet for procrastination. The present survey of Internet users (N = 6795) explored the correlates of viewing “Internet cats,” motivations for consuming this media, and its potential effects on users. It also tested a conceptual model predicting enjoyment as a function of the relationships between procrastination, guilt, and happiness. Results reveal significant relationships between viewing and personality types and demonstrate conceptual nuances related to the emotional benefits of watching Internet cats.

I can't resist throwing in a cat video as a bonus:

 

Anti-ageing pill pushed as a bona fide drug.

Amazing. Now we are going to start treating normal aging as a disease? Maybe not as crazy as it sounds. Some clips from a review by Hayden:

Current treatments for diseases related to ageing “just exchange one disease for another”, says physician Nir Barzilai of the Albert Einstein College of Medicine in New York. That is because people treated for one age-related disease often go on to die from another relatively soon thereafter. “What we want to show is that if we delay ageing, that’s the best way to delay disease.”

Barzilai and other researchers plan to test that notion in a clinical trial called Targeting Aging with Metformin, or TAME. They will give the drug metformin to thousands of people who already have one or two of three conditions — cancer, heart disease or cognitive impairment — or are at risk of them. People with type 2 diabetes cannot be enrolled because metformin is already used to treat that disease. The participants will then be monitored to see whether the medication forestalls the illnesses they do not already have, as well as diabetes and death.

On 24 June, researchers will try to convince FDA officials that if the trial succeeds, they will have proved that a drug can delay ageing. That would set a precedent that ageing is a disorder that can be treated with medicines, and perhaps spur progress and funding for ageing research.

The TAME test is for metformin, which suppresses glucose production by the liver and increases sensitivity to insulin. The drug has been used for more than 60 years and is safe and prolongs healthy life and lifespan in worms and in some mouse strains. Data also suggest that it could delay heart disease, cancer, cognitive decline and death in people with diabetes. Plans call for the trial to enrol 3,000 people aged 70–80 years at roughly 15 centres around the United States. The trial will take 5–7 years and cost US$50 million, Barzilai estimates, although it does not yet have funding.

The power of positivity.

Ramirez et al. make the fascinating observation that depressive-like stress responses in mice can be acutely suppressed through artificial reactivation of a small population of neurons that had previously been activated by a positive experience - these cells apparently being the physical substrate, or engram, of the positive memory. This suggests a fundamental explanation for why eliciting the recall of pleasant memories can sometimes be an effective psychotherapeutic technique for relieving stress, lack of motivation, or anhedonia in humans.

Stress is considered a potent environmental risk factor for many behavioural abnormalities, including anxiety and mood disorders. Animal models can exhibit limited but quantifiable behavioural impairments resulting from chronic stress, including deficits in motivation, abnormal responses to behavioural challenges, and anhedonia. The hippocampus is thought to negatively regulate the stress response and to mediate various cognitive and mnemonic aspects of stress-induced impairments, although the neuronal underpinnings sufficient to support behavioural improvements are largely unknown. Here we acutely rescue stress-induced depression-related behaviours in mice by optogenetically reactivating dentate gyrus cells that were previously active during a positive experience. A brain-wide histological investigation, coupled with pharmacological and projection-specific optogenetic blockade experiments, identified glutamatergic activity in the hippocampus–amygdala–nucleus-accumbens pathway as a candidate circuit supporting the acute rescue. Finally, chronically reactivating hippocampal cells associated with a positive memory resulted in the rescue of stress-induced behavioural impairments and neurogenesis at time points beyond the light stimulation. Together, our data suggest that activating positive memories artificially is sufficient to suppress depression-like behaviours and point to dentate gyrus engram cells as potential therapeutic nodes for intervening with maladaptive behavioural states.

Inside Out

I can't resist passing on a few selected clips from Anthony Lane's review of the new Pixar Movie, "Inside Out." Pixar writer and director Pete Docter, in describing the actor's inside a child's head, has produced an an engaging depiction of of many of the ideas I try to get across (much more obtusely and ponderously) in my MindStuff: Guide for the curious user written ten years ago.

The new Pixar film, “Inside Out,” is about the life of Riley. She is an only child...who, aged eleven, moves with her parents ... from Minnesota to San Francisco. Not much happens...The bulk of the movie takes place out of sight, within the confines of Riley’s mind, where primary feelings affect her every move. There are five in all: Joy (Amy Poehler), who is butter-yellow and fuzzy at the edges; Anger (Lewis Black), who looks like SpongeBob soaked in blood; Fear (Bill Hader), a writhing dweeb with a bow tie; Disgust (Mindy Kaling), who has frosted green hair and lashes; and Sadness (Phyllis Smith), a bespectacled blob of blue. Now and then, they contend for supremacy, but mostly they join forces and react to the world beyond. They behold it through Riley’s eyes, from a spiffy control center, like Kirk, Spock, and the gang on the bridge of the Enterprise...Dreams are produced in—where else?—a dream factory, with soundstages and camera crews. It closes down when she wakes. Experiences are delivered to the control room as if they were bowling balls, colored according to their mood; some are stored away, others dropped into a pit of forgetfulness, where they darken and crumble like spent coals, and a few are enthroned as core memories. And that, we are told, is how a personality is made.

So brisk is the defining of all this...that we barely pause to consider the assumptions behind it. Pixar...has no time for old-school habits, like lodging the emotions in the heart...They are located squarely in the brain, presumably displacing Reason, whom we never meet, but whom I picture as French, bald, and wearing an English suit. ... Neurologists and therapists will examine the movie and pronounce themselves largely satisfied. ... I sensed..., that I was following the transcription, by very clever adults, of their own theorizing—literate, frantic, and endlessly chewed over—on the subject of human development, rather than the story of a growing girl.

...the biggest laughs, without exception, come when we exit Riley’s head and take a quick vacation to the crania—and the mania—of others. During an argument at dinner, for instance, her father’s emotions are miles away; all of them are watching a hockey game. And, as the closing credits approach, Docter, realizing that he has a pack of wild gags that have been kept leashed for too long, releases the lot in a flurry. We peek inside the mind of a dog, a cat, a prepubescent boy (“Girl! Girl!” the alarms sing out), and, best of all, the cool chick with eyeshadow at Riley’s school, voiced by Rashida Jones. ...You start to wonder what a grownup sequel to “Inside Out” would look like, with a host of new feelings barging into central command and wrenching the controls away from Joy. Would Lust be spoken by Rupert Everett, or would it sound more like Chico Marx, working his way through a chorus line? How about Love of Money, or black-browed Mortal Terror? There are places, I guess, where even Pixar cannot go.

Neuroanatomical correlates of the income-achievement gap.

The difference in academic achievement between students from higher- and lower-income backgrounds is substantial and growing. A group of collaborators from M.I.T., Harvard, and Columbia has examined the neuroanatomical correlates of the income-achievement gap by comparing the structure of the cerebral cortex (which supports perception, language, and thought) in public-school students who do (lower income) and do not (higher income) receive free or reduced-price lunch, and by relating this neuroanatomy to performance on standardized tests of academic skills. For further discussion of effects of poverty on young brains see the article by Ostrander in The New Yorker.

In the United States, the difference in academic achievement between higher- and lower-income students (i.e., the income-achievement gap) is substantial and growing. In the research reported here, we investigated neuroanatomical correlates of this gap in adolescents (N = 58) in whom academic achievement was measured by statewide standardized testing. Cortical gray-matter volume was significantly greater in students from higher-income backgrounds (n = 35) than in students from lower-income backgrounds (n = 23), but cortical white-matter volume and total cortical surface area did not differ significantly between groups. Cortical thickness in all lobes of the brain was greater in students from higher-income than lower-income backgrounds. Greater cortical thickness, particularly in temporal and occipital lobes, was associated with better test performance. These results represent the first evidence that cortical thickness in higher- and lower-income students differs across broad swaths of the brain and that cortical thickness is related to scores on academic-achievement tests.

Cortical-thickness differences between income groups. The brain images in (a) show regions where cortical thickness was significantly greater in the higher-income (HI) group than in the lower-income (LI) group.

Facebook internal research shows its algorithms enhance political polarization.

From the commentary by Lazer:

Bakshy et al. examine... whether Facebook's curation of news feeds prevents the intersection of conflicting points of view. That is, does a “filter bubble” emerge from this algorithmic curation process, so that individuals only see posts that they agree with? Such an algorithmic sorting has the potential to be unhealthy for our democracy, fostering polarization and undermining the construction of a vision of the common good...Their answer, after parsing the Facebook pages of ∼10 million U.S. individuals with self-declared ideologies, is that the curation does ideologically filter what we see.

It is laudable that Facebook supported this research and has invested in the public good of general scientific knowledge. Indeed, the information age hegemons should proactively support research on the ethical implications of the systems that they build. Facebook deserves great credit for building a talented research group and for conducting this research in a public way.

Here is the Bakshy et al. abstract:

Exposure to news, opinion, and civic information increasingly occurs through social media. How do these online networks influence exposure to perspectives that cut across ideological lines? Using deidentified data, we examined how 10.1 million U.S. Facebook users interact with socially shared news. We directly measured ideological homophily in friend networks and examined the extent to which heterogeneous friends could potentially expose individuals to cross-cutting content. We then quantified the extent to which individuals encounter comparatively more or less diverse content while interacting via Facebook’s algorithmically ranked News Feed and further studied users’ choices to click through to ideologically discordant content. Compared with algorithmic ranking, individuals’ choices played a stronger role in limiting exposure to cross-cutting content.

Acetaminophen - over the counter relief from both pain and emotions...

I've sometimes wondered why I feel a bit flat (anhedonic) after taking acetaminophen (Tylenol). Durso et al. show that it blunts sensitivity to both negative and positive stimuli.

Acetaminophen, an effective and popular over-the-counter pain reliever (e.g., the active ingredient in Tylenol), has recently been shown to blunt individuals’ reactivity to a range of negative stimuli in addition to physical pain. Because accumulating research has shown that individuals’ reactivity to both negative and positive stimuli can be influenced by a single factor (an idea known as differential susceptibility), we conducted two experiments testing whether acetaminophen blunted individuals’ evaluations of and emotional reactions to both negative and positive images from the International Affective Picture System. Participants who took acetaminophen evaluated unpleasant stimuli less negatively and pleasant stimuli less positively, compared with participants who took a placebo. Participants in the acetaminophen condition also rated both negative and positive stimuli as less emotionally arousing than did participants in the placebo condition (Studies 1 and 2), whereas nonevaluative ratings (extent of color saturation in each image; Study 2) were not affected by drug condition. These findings suggest that acetaminophen has a general blunting effect on individuals’ evaluative and emotional processing, irrespective of negative or positive valence.

How is creativity helped by being just a little bit crazy?

Park et al. examine individuals with schizotypal personality disorder, which is characterized by need for social isolation, anxiety in social situations, odd behavior and thinking, and often unconventional beliefs, but does not engage the false beliefs, unclear or confused thinking, and auditory hallucinations characteristic of schizophrenia. They suggest that the greater levels of creative behavior found in such individuals correlates with deactivation of specific cortical areas, in agreement with 'less is more' models for creativity.

Empirical studies indicate a link between creativity and schizotypal personality traits, where individuals who score highly on schizotypy measures also display greater levels of creative behaviour. However, the exact nature of this relationship is not yet clear, with only a few studies examining this association using neuroimaging methods. In the present study, the neural substrates of creative thinking were assessed with a drawing task paradigm in healthy individuals using fMRI. These regions were then statistically correlated with the participants’ level of schizotypy as measured by the Oxford–Liverpool Inventory of Feelings and Experiences (O-LIFE), which is a questionnaire consisting of four dimensions. Neural activations associated with the creativity task were observed in bilateral inferior temporal gyri, left insula, left parietal lobule, right angular gyrus, as well as regions in the prefrontal cortex. This widespread pattern of activation suggests that creative thinking utilises multiple neurocognitive networks, with creative production being the result of collaboration between these regions. Furthermore, the correlational analyses found the Unusual Experiences factor of the O-LIFE to be the most common dimension associated with these areas, followed by the Impulsive Nonconformity dimension. These correlations were negative, indicating that individuals who scored the highest in these factors displayed the least amount of activation when performing the creative task. This is in line with the idea that ‘less is more’ for creativity, where the deactivation of specific cortical areas may facilitate creativity. Thus, these findings contribute to the evidence of a common neural basis between creativity and schizotypy.

A new class of anti-aging drugs that selectively kill senescent cells.

From  Brian Ray in the Editor's Choice section of the June 5 issue of Science, another approach to life-extension drugs (and, to possibly curb your enthusiasm about the desirability of such anti-aging efforts, also have a look at "What Happens When We All Live to 100?" in The Atlantic Magazine). :

As organisms age, they accumulate cells that can no longer proliferate. Such cells— termed “senescent”—persist and appear to promote aging by producing and secreting a variety of proteins. Zhu et al. tested whether drugs that inhibit cellular signaling pathways that make senescent cells resistant to stress and cell death could deplete senescent cells in mice. A combination of two drugs that inhibit such pathways selectively killed senescent cells in vitro, improved heart and vascular function in aging mice, and improved symptoms in a mouse model of accelerated aging. Although pinpointing the relevant targets of these drugs is difficult, the studies indicate that selectively targeting senescent cells with small molecules may be feasible.

The Zhu et al. technical abstract:

The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and the burden of age-related chronic diseases. Here, we describe the rationale for identification and validation of a new class of drugs termed senolytics, which selectively kill senescent cells. By transcript analysis, we discovered increased expression of pro-survival networks in senescent cells, consistent with their established resistance to apoptosis. Using siRNA to silence expression of key nodes of this network, including ephrins (EFNB1 or 3), PI3Kδ, p21, BCL-xL, or plasminogen-activated inhibitor-2, killed senescent cells, but not proliferating or quiescent, differentiated cells. Drugs targeting these same factors selectively killed senescent cells. Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells and mouse BM-MSCs. The combination of dasatinib and quercetin was effective in eliminating senescent MEFs. In vivo, this combination reduced senescent cell burden in chronologically aged, radiation-exposed, and progeroid Ercc1^−/Δ mice. In old mice, cardiac function and carotid vascular reactivity were improved 5 days after a single dose. Following irradiation of one limb in mice, a single dose led to improved exercise capacity for at least 7 months following drug treatment. Periodic drug administration extended healthspan in Ercc1^−/Δ mice, delaying age-related symptoms and pathology, osteoporosis, and loss of intervertebral disk proteoglycans. These results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.

Ocytocin reverses amphetamine-induced deficits in social bonding.

As a followup to yesterday's post on a positive effects of amphetamine on the cognition of aging adults, I thought it would be interesting to point out a dark side of amphetamine by noting the paper by Young et al. showing reversal of amphetamine-induced social impairments by oxytocin treatment. (In addicts who fail to develop or maintain intimate relationships amphetamine appears to hijack the brain's social reward circuitry. Clinical trials in humans are indicating a clear potential for oxytocin as a treatment for addiction.) They use the prairie vole male pair bonding model.

Drug addiction has devastating consequences on social behaviors and can lead to the impairment of social bonding. Accumulating evidence indicates that alterations in oxytocin (OT) and dopamine (DA) neurotransmission within brain reward circuitry may be involved. We investigated this possibility, as well as the therapeutic potential of OT for drug-induced social deficits, using the prairie vole (Microtus ochrogaster)—a socially monogamous rodent that forms enduring pair bonds between adult mates. We demonstrate that repeated exposure to the commonly abused psychostimulant amphetamine (AMPH) inhibits the formation of partner preferences (an index of pair bonding) in female prairie voles. AMPH exposure also altered OT and DA neurotransmission in regions that mediate partner preference formation: it decreased OT and DA D2 receptor immunoreactivity in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc), respectively, and increased NAcc DA levels. Administration of OT directly into the mPFC of AMPH-exposed voles restored partner preferences, and altered NAcc DA levels, and this effect was dependent on OT receptor activation. Together, these data suggest that repeated AMPH exposure impairs pair bonding through an OT-mediated mechanism, and that OT and DA systems within brain reward circuitry may interact to mediate the complex relationship between drug abuse and social bonding. Further, these results provide empirical support for the idea that the central OT system may represent an important target for the treatment of social deficits in addiction.

A bit of amphetamine turns older brains into younger brains.

Fascinating. Garrett et al. show that raising dopamine levels with amphetamine (sold as the prescription drug Adderall, for ADHD), increases the brain wave variability that enhances working memory, so that seniors perform as well as younger people on the n-back working memory test. (Common prescription doses of 5-30 mg act as a cognitive enhancer.

Higher doses can be aphrodisiac, euphoriant, addictive, and have many bad side effects.) I pass on both their statement of significance and abstract. Also, a figure that tempts me to try to get an adderall prescription and do a self experiment.

Significance

Younger, better performing adults typically show greater brain signal variability than older, poorer performers, but the mechanisms underlying this observation remain elusive. We attempt to restore deficient functional-MRI–based blood oxygen level-dependent (BOLD) signal variability (SDBOLD) levels in older adults by boosting dopamine via d-amphetamine (AMPH). Notably, older adults met or exceeded young adult SDBOLD levels under AMPH. AMPH-driven changes in SDSDBOLD also predicted AMPH-driven changes in reaction time speed and variability on a working memory task, but depended greatly on age and drug administration order. These findings (i) suggest that dopamine may account for adult age differences in brain signal variability and (ii) highlight the importance of considering practice effects and state dependencies when evaluating the neurochemical basis of age- and cognition-related brain dynamics. 

Abstract

Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI–based blood oxygen level-dependent (BOLD) signal variability (SDBOLD) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SDBOLD levels in the presence of AMPH. Drug session order greatly moderated change–change relations between AMPH-driven SDBOLD and reaction time means (RTmean) and SDs (RTSD). Older adults who received AMPH in the first session tended to improve in RTmean and RTSD when SDBOLD was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SDBOLD decreased (for RTmean) or no effect at all (for RTSD). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.

Figure. Increased BOLD variability and improved cognitive performance under AMPH. Multivariate partial least-squares model of relation between SDBOLD, Age Group, AMPH, and Task Condition. Higher brain scores reflect higher BOLD signal variability. Error bars represent bootstrapped 95% confidence intervals (1,000× with replacement). Brain images are plotted in neurological orientation (left is Left). AMPH, amphetamine; BSR, bootstrap ratio.