Imperceptible current applied to our scalp enhances general intelligence.

Here is yet another of the increasing number of articles examining the effects of very weak electrical stimulation of our frontal scalp with surface electrodes. I've done a number of posts on this topic, the most recent citing concerns over do it yourself kits now available to anyone. Santarnecchi et al. address the frequency-specific effect of stimulation with the main physiological brain rhythms by comparing performance during four tACS (transcranial alternating current stimulation) conditions — 5 Hz (θ band), 10 Hz (α band), 20 Hz (β band), and 40 Hz (γ band) — and a placebo, sham stimulation. Their summary:

-Online prefrontal γ-tACS selectively accelerated logical reasoning.

-Effects were frequency and task specific

-This contrasts with views of gamma-band activity as a byproduct of neuronal activity

-Gamma-band activity plays a functional role in fluid-intelligence-based reasoning

Everyday problem solving requires the ability to go beyond experience by efficiently encoding and manipulating new information, i.e., fluid intelligence (Gf). Performance in tasks involving Gf, such as logical and abstract reasoning, has been shown to rely on distributed neural networks, with a crucial role played by prefrontal regions. Synchronization of neuronal activity in the gamma band is a ubiquitous phenomenon within the brain; however, no evidence of its causal involvement in cognition exists to date. Here, we show an enhancement of Gf ability in a cognitive task induced by exogenous rhythmic stimulation within the gamma band. Imperceptible alternating current delivered through the scalp over the left middle frontal gyrus resulted in a frequency-specific shortening of the time required to find the correct solution in a visuospatial abstract reasoning task classically employed to measure Gf abilities (i.e., Raven’s matrices). Crucially, gamma-band stimulation (γ-tACS) selectively enhanced performance only on more complex trials involving conditional/logical reasoning. The present finding supports a direct involvement of gamma oscillatory activity in the mechanisms underlying higher-order human cognition.

Left Middle Frontal Gyrus

Evidence that the Lunar cycle influences human sleep.

I have kept a log for many years that has convinced me that I have roughly monthly oscillations in motivation and libido, but I've not come across convincing evidence for roughly lunar or monthly cycles in men in literature searches. So, I perk up on seeing the examination by Cajochen et al. of sleep behavior under highly controlled conditions of a circadian laboratory study protocol without time cues. They find that subjective and objective measures of sleep vary according to lunar periodicity (~29.5 days). Subjects in the study were seventeen healthy young volunteers (nine women and eight men; age range, 20–31 years; mean, 25.0 ± 3.6 years [SD]) and 16 healthy older volunteers (eight women and eight men; age range, 57–74 years; mean, 65.0 ± 5.5 years) Here is their abstract:

Endogenous rhythms of circalunar periodicity (∼29.5 days) and their underlying molecular and genetic basis have been demonstrated in a number of marine species. In contrast, there is a great deal of folklore but no consistent association of moon cycles with human physiology and behavior. Here we show that subjective and objective measures of sleep vary according to lunar phase and thus may reflect circalunar rhythmicity in humans. To exclude confounders such as increased light at night or the potential bias in perception regarding a lunar influence on sleep, we retrospectively analyzed sleep structure, electroencephalographic activity during non-rapid-eye-movement (NREM) sleep, and secretion of the hormones melatonin and cortisol found under stringently controlled laboratory conditions in a cross-sectional setting. At no point during and after the study were volunteers or investigators aware of the a posteriori analysis relative to lunar phase. We found that around full moon, electroencephalogram (EEG) delta activity during NREM sleep, an indicator of deep sleep, decreased by 30%, time to fall asleep increased by 5 min, and EEG-assessed total sleep duration was reduced by 20 min. These changes were associated with a decrease in subjective sleep quality and diminished endogenous melatonin levels. This is the first reliable evidence that a lunar rhythm can modulate sleep structure in humans when measured under the highly controlled conditions of a circadian laboratory study protocol without time cues.

 

Personal control enhances treatment effectiveness.

An interesting fragment, relating to the powerful vs helplessness theme of a recent post, subjects faced with alternative pain control drugs (both actually placebos) reported better pain relief if they chose the drug rather than having it chosen for them. From Geers et al.:

In modern health care, individuals frequently exercise choice over health treatment alternatives. A growing body of research suggests that when individuals choose between treatment options, treatment effectiveness can increase, although little experimental evidence exists clarifying this effect. Four studies were conducted to test the hypothesis that exercising choice over treatment alternatives enhances outcomes by providing greater personal control. Consistent with this possibility, in Study 1 individuals who chronically desired control reported less pain from a laboratory pain task when they were able to select between placebo analgesic treatments. Study 2 replicated this finding with an auditory discomfort paradigm. In Study 3, the desire for control was experimentally induced, and participants with high desire for control benefited more from a placebo treatment when they were able to choose their treatment. Study 4 revealed that the benefit of choice on treatment efficacy was partially mediated by thoughts of personal control. This research suggests that when individuals desire control, choice over treatment alternatives improves treatment effectiveness by enhancing personal control.

Think your radiologist gets it right? The invisible gorilla strikes again.

A well known video shows the famous experiment of missing a gorilla walking through a basketball game when you have been instructed to count the number of times the ball is being passed during playing. (I can not refer you to a free viewing of this video, since the academic who originated it, Dan Simons, has copyrighted it, and aggressively pursues those who might wish to watch it without paying him for a DVD that contain it.) Anyway, an extension of his basic experiment gives you reason to feel even less confident about the expertise of high priced radiologists examining your X-rays. This from Drew et al.:

Researchers have shown that people often miss the occurrence of an unexpected yet salient event if they are engaged in a different task, a phenomenon known as inattentional blindness. However, demonstrations of inattentional blindness have typically involved naive observers engaged in an unfamiliar task. What about expert searchers who have spent years honing their ability to detect small abnormalities in specific types of images? We asked 24 radiologists to perform a familiar lung-nodule detection task. A gorilla, 48 times the size of the average nodule, was inserted in the last case that was presented. Eighty-three percent of the radiologists did not see the gorilla. Eye tracking revealed that the majority of those who missed the gorilla looked directly at its location. Thus, even expert searchers, operating in their domain of expertise, are vulnerable to inattentional blindness.

Degree of Musical Expertise Modulates Higher Order Brain Functioning

A piece like this one by Oechslin et al. gives me some hope that my piano playing and sight reading compensate for my aversion to spending any significant amount of time on anti-aging brain exercise regimes of the sort described in a recent post. Hopefully, if I keep up my piano playing as I age, I will be going ga-ga later rather than sooner. The abstract:

Using functional magnetic resonance imaging, we show for the first time that levels of musical expertise stepwise modulate higher order brain functioning. This suggests that degree of training intensity drives such cerebral plasticity. Participants (non-musicians, amateurs, and expert musicians) listened to a comprehensive set of specifically composed string quartets with hierarchically manipulated endings. In particular, we implemented 2 irregularities at musical closure that differed in salience but were both within the tonality of the piece (in-key). Behavioral sensitivity scores (d′) of both transgressions perfectly separated participants according to their level of musical expertise. By contrasting brain responses to harmonic transgressions against regular endings, functional brain imaging data showed compelling evidence for stepwise modulation of brain responses by both violation strength and expertise level in a fronto-temporal network hosting universal functions of working memory and attention. Additional independent testing evidenced an advantage in visual working memory for the professionals, which could be predicted by musical training intensity. The here introduced findings of brain plasticity demonstrate the progressive impact of musical training on cognitive brain functions that may manifest well beyond the field of music processing.

Be young in perception and behavior! Put yourself in a virtual child’s body!

Banakou et al. show that if we use some simple tricks to project ourselves into a 4-year old's body, we overestimate object sizes and more readily associate ourselves with child-like attributes:

An illusory sensation of ownership over a surrogate limb or whole body can be induced through specific forms of multisensory stimulation, such as synchronous visuotactile tapping on the hidden real and visible rubber hand in the rubber hand illusion. Such methods have been used to induce ownership over a manikin and a virtual body that substitute the real body, as seen from first-person perspective, through a head-mounted display. However, the perceptual and behavioral consequences of such transformed body ownership have hardly been explored. In the first experiment, immersive virtual reality was used to embody 30 adults as a 4-y-old child (condition C), and as an adult body scaled to the same height as the child (condition A), experienced from the first-person perspective, and with virtual and real body movements synchronized. The result was a strong body-ownership illusion equally for C and A. Moreover there was an overestimation of the sizes of objects compared with a nonembodied baseline, which was significantly greater for C compared with A. An implicit association test showed that C resulted in significantly faster reaction times for the classification of self with child-like compared with adult-like attributes. A second experiment with an additional 16 participants extinguished the ownership illusion by using visuomotor asynchrony, with all else equal. The size-estimation and implicit association test differences between C and A were also extinguished. We conclude that there are perceptual and probably behavioral correlates of body-ownership illusions that occur as a function of the type of body in which embodiment occurs.

Experimental setup. The body of the participant was substituted by a sex-matched virtual body, viewed from first-person perspective, onto which body and head movements were mapped in real time. The body could also be seen as reflected in a virtual mirror as shown. The body each participant viewed depended on the condition C (for child) or A (for adult) to which each one was assigned. (A) A female participant in a child’s body. (B) A female participant in a scaled-down adult’s body. (C) Participants’ body movements were tracked by 34 Optitrack markers.

The bad kind of stress - perceived helplessness

Velasquez-Manoff does a nice discussion of a topic that has been recurrent in MindBlog, understanding the kind of stress that is really bad for us. Not the stress that goes with daily personal and professional aggravations, but the long term stress that derives from feeling helpless to control our lives. Numerous studies, the best known being a long term study of British civil servants, have shown that being higher in a social hierarchy correlates with having better health. The sense of control:

...tends to decline as one descends the socioeconomic ladder, with potentially grave consequences. Those on the bottom are more than three times as likely to die prematurely as those at the top. They’re also more likely to suffer from depression, heart disease and diabetes. Perhaps most devastating, the stress of poverty early in life can have consequences that last into adulthood.

The article quotes Robert Sapolsky at Stanford, whose classic book "Why Zebras Don't Get Ulcers" is still a must read, as saying:

Early-life stress and the scar tissue that it leaves, with every passing bit of aging, gets harder and harder to reverse...You’re never out of luck in terms of interventions, but the longer you wait, the more work you’ve got on your hands.

Bruce McEwen and others talk about

...the “biological embedding” of social status. Your parents’ social standing and your stress level during early life change how your brain and body work, affecting your vulnerability to degenerative disease decades later. They may even alter your vulnerability to infection. In one study, scientists at Carnegie Mellon exposed volunteers to a common cold virus. Those who’d grown up poorer (measured by parental homeownership) not only resisted the virus less effectively, but also suffered more severe cold symptoms.

Another clip:

Animal studies help dispel doubts that we’re really seeing sickly and anxiety-prone individuals filter to the bottom of the socioeconomic heap. In primate experiments females of low standing are more likely to develop heart disease compared with their counterparts of higher standing. When eating junk food, they more rapidly progress toward heart disease. The lower a macaque is in her troop, the higher her genes involved in inflammation are cranked. High-ranking males even heal faster than their lower-ranking counterparts. Behavioral tendencies change as well. Low-ranking males are more likely to choose cocaine over food than higher-ranking individuals.

Finally:

...while Americans generally gained longevity during the late 20th century, those gains have gone disproportionately to the better-off. Those without a high school education haven’t experienced much improvement in life span since the middle of the 20th century. Poorly educated whites have lost a few years of longevity in recent decades.

A National Research Council report, meanwhile, found that Americans were generally sicker and had shorter life spans than people in 16 other wealthy nations. We rank No. 1 for diabetes in adults over age 20, and No. 2 for deaths from coronary artery disease and lung disease. The Japanese smoke more than Americans, but outlive us — as do the French and Germans, who drink more. The dismal ranking is surprising given that America spends nearly twice as much per capita on health care as the next biggest spender.

Different kinds of happiness - different immune system consequences.

Happiness is usually classified into two main flavors: hedonic and eudaimonic. Hedonic refers mainly to self gratification and eudaimonic to a sense of meaning and purpose beyond that. In a study involving 80 healthy adult subjects, Fredrickson et al. used a questionnaire to asses levels of hedonic and eudaimonic happiness (questions such as 'over the last week, how often did you feel happy or satisfied? (hedonic); or, 'how often in the last week did you feel your life has a sense of purpose, meaning or direction?' (eudaimonic). They also looked at expression of genes associated with immune system responses. The fascinating result was that hedonic happiness correlated with higher expression of genes typically activated by extended periods of stress, activity that increases inflammation and decreases antiviral responses. Higher Eudaimonic happiness correlated with lower activation levels of these genes and strengthened immune function.

Both kinds of happiness make us "feel good." The central point is that our genome may be "more sensitive to qualitative variations in well-being than are our conscious affective experiences." Here is their abstract:

To identify molecular mechanisms underlying the prospective health advantages associated with psychological well-being, we analyzed leukocyte basal gene expression profiles in 80 healthy adults who were assessed for hedonic and eudaimonic well-being, as well as potentially confounded negative psychological and behavioral factors. Hedonic and eudaimonic well-being showed similar affective correlates but highly divergent transcriptome profiles. Peripheral blood mononuclear cells from people with high levels of hedonic well-being showed up-regulated expression of a stress-related conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes and decreased expression of genes involved in antibody synthesis and type I IFN response. In contrast, high levels of eudaimonic well-being were associated with CTRA down-regulation. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity in structuring the observed differences in gene expression associated with eudaimonic well-being (reduced NF-κB and AP-1 signaling and increased IRF and STAT signaling). Transcript origin analysis identified monocytes, plasmacytoid dendritic cells, and B lymphocytes as primary cellular mediators of these dynamics. The finding that hedonic and eudaimonic well-being engage distinct gene regulatory programs despite their similar effects on total well-being and depressive symptoms implies that the human genome may be more sensitive to qualitative variations in well-being than are our conscious affective experiences.

Workouts at the brain gym.

Patricia Marx writes an engaging article in The New Yorker, "Mentally Fit," that describes her foray into various regimes for building cognitive and emotional muscle, to stave off the declines in memory and attention capacity that come with aging, and are accelerated by vascular dementia and Alzheimer's pathology.

Staving off dotage is not cheap. According to a recent report issued by SharBrains, the amount spent on brain fitness in 2012 was more than a billion dollars, and by 2020, it is estimated, that figure will exceed six billion dollars. Most of the merchandise is some kind of software (note: which have been the subject of several MindBlog posts). …. to name just a few: Cogmed, Lumosity, Brain Games, Jungle Memory, Cognifit, MindSparke, MyBrainSolution, Brain Spa, brainTivity, Brainiversity, Brain Metrix, Mind Quiz, Your Brain Coach, Brain Exercise with Dr. Kawashima, Nintendo's Brain Age, MindHabits, NeuroNation, Happyneuron. There seem to be enough products to give each of your synapses its very own person-training program.

The cost of these programs ranges from zero to $1,500. The author chose BrainHQ, a platform offered by Posit Science, a San Francisco company co-founded by respected neuroscientist Michael Merzenich. It's exercises center around making your eyes and attention more childlike and sparky, countering the decay that makes the peripheral vision of a sixty-year-old three-quarters as panoramic as that of a twenty-year-old. After training for an hour a day over six weeks, scores in an array of different exercises were higher across the board. Merznich is probably correct in stating that the observed stronger, faster, more accurate and reliable brain performance after training comes from synaptic remodeling in the brain, a change that he says can persist for a year or more, but that does slips back past the neurological position that you were at when you began the training. (Motivated readers can email me to obtain a PDF of the article.)

Loneliness promotes inflammation in our bodies

Jaremka et al provide further data on how our social status reaches down to the most intimate details of our personal chemistry, with their present study providing details of how loneliness during stress turns on our inflammatory pathways, thus putting us at greater risk for health problems. Here's the abstract:

Although evidence suggests that loneliness may increase risk for health problems, the mechanisms responsible are not well understood. Immune dysregulation is one potential pathway: Elevated proinflammatory cytokines such as interleukin-6 (IL-6) increase risk for health problems. In the first study (N = 134), lonelier healthy adults exposed to acute stress exhibited greater synthesis of tumor necrosis factor-alpha (TNF-α) and IL-6 by peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS) than their less lonely counterparts. Similarly, in the second study (N = 144), lonelier posttreatment breast-cancer survivors exposed to acute stress exhibited greater synthesis of IL-6 and interleukin-1 beta (IL-1β) by LPS-stimulated PBMCs than their counterparts who felt more socially connected. However, loneliness was unrelated to TNF-α in the second study, although the result was in the expected direction. Thus, two different populations demonstrated that lonelier participants had more stimulated cytokine production in response to stress than less lonely participants, which reflects a proinflammatory phenotype. These data provide a glimpse into the pathways through which loneliness may affect health.

Markers of our aging

I thought I would point to this interesting piece in the New York Times about the search for some simple objective assay of our biological age, as distinct from our chronological age. We all know people who seems much older or younger than their actual age. Things like skin wrinkles or blood pressure are not a very useful indicator, because they can be confounded by factors unrelated to aging. Reliable biomarkers of aging could:

...tell us a lot about our current and future health. Tracking these indexes before and after starting a new diet or exercise program, for instance, might show you whether it was actually pushing off your decline and fall. Aging-rate tests could help scientists evaluate possible anti-aging compounds in humans without prohibitively long studies.

One study of older women age 65-69 found that 13 factors correlate with healthy aging, including the eye’s ability to pick out very lightly shaded images on white backgrounds, and the number of rapid step-ups on a low platform that subjects could complete in 10 seconds. A more promising approach is finding that a number of chemical tags on our DNA - epigenetic markers, which I have mentioned in previous posts - correlate with our biological age in a way that yields a signature of aging that is not changed by disease or ethnic background.

If this continuing research pans out, aging-rate tests may someday be standard in annual physicals, and tracking the results over time would offer unprecedented insights on health risks. But such tests also may well raise fractious privacy and social equity issues.

Insurers might demand that customers take them in order to set premiums for life and health care policies. The tests may also reveal how factors like exposure to environmental toxins and the stress of job loss accelerate aging, and by how much — fodder for lawsuits.

Some of us will be relatively short-lived, fast-aging “less fortunate,” and others will be long-lived, slow-aging “more fortunates,” predicted John K. Davis, a philosophy professor at California State University, Fullerton. And age discrimination will gain an entirely new meaning.

Unconscious activation of our brains' inhibitory controls.

Hepler and Albarracin have done the interesting experiment of exposing participants in an experiment to subliminally presented inaction (calm) and action (move) words, and then ascertaining that participants were unaware of these primers. They subsequently presented the participants with a Go/No-Go task (press a button if you see an "X", don't press it if you see a "Y") and also measured the P3 component of the event-related brain potential known to index inhibitory control. The subliminally presented inaction (calm) and action (move) words increased inhibitory neural activity whereas the latter set decreased it, relative to a control set of neutral words. Here is the author's summary:

-Event-related potentials were recorded during two go/no-go task with subliminal primes

-Subliminal primes related to general concepts of action, inaction, or were controls.

-Inaction/action primes strengthened/weakened inhibitory control mechanisms (ICMs).

-The primes had never been consciously associated with task responses or goals.

-This is the first demonstration that ICMs can operate completely unconsciously.

Although robust evidence indicates that action initiation can occur unconsciously and unintentionally, the literature on action inhibition suggests that inhibition requires both conscious thought and intentionality. In prior research demonstrating automatic inhibition in response to unconsciously processed stimuli, the unconscious stimuli had previously been consciously associated with an inhibitory response within the context of the experiment, and participants had consciously formed a goal to activate inhibition processes when presented with the stimuli (because task instructions required participants to engage in inhibition when the stimuli occurred). Therefore, prior work suggests that some amount of conscious thought and intentionality are required for inhibitory control. In the present research, we recorded event-related potentials during two go/no-go experiments in which participants were subliminally primed with general action/inaction concepts that had never been consciously associated with task-specific responses. We provide the first demonstration that inhibitory control processes can be modulated completely unconsciously and unintentionally.

Why does time speed up for older people?

I've come across two recent articles recently on how our experience of time is our own invention - "mind time" - that can be faster or slower than clock or calendar time. I find myself incredulous at how fast time seems to pass now compared with my recollection of when I was a 30 or 40-something and felt large periods of leisure in the midst of what was a much more complex (and productive) life than my current retired life (at 71 years of age). In general older people are more likely than younger to report that the last decade has passed quickly. The Friedman piece has a great quote from William James, who argued that the apparent speed of time's passage was a result of adult's experiencing fewer memorable events:

“Each passing year converts some of this experience into automatic routine which we hardly note at all, the days and the weeks smooth themselves out in recollection to contentless units, and the years grow hollow and collapse.”

From Friedman:

Why, then, do older people look back at long stretches of their lives and feel it’s a race to the finish? Here’s a possible answer: think about what it’s like when you learn something for the first time — for example how, when you are young, you learn to ride a bike or navigate your way home from school. It takes time to learn new tasks and to encode them in your memory. And when you are learning about the world for the first time, you are forming a fairly steady stream of new memories of events, places and people.

When, as an adult, you look back at your childhood experiences, they appear to unfold in slow motion probably because the sheer number of them gives you the impression that they must have taken forever to acquire… Most adults do not explore and learn about the world the way they did when they were young; adult life lacks the constant discovery and endless novelty of childhood.

Studies have shown that the greater the cognitive demands of a task, the longer its duration is perceived to be…Is it possible that learning new things might slow down our internal sense of time?…It’s simple: if you want time to slow down, become a student again. Learn something that requires sustained effort; do something novel…Take a new route to work; vacation at an unknown spot. And take your sweet time about it.

The second piece, by Maria Popova article points to Hammond's recent book "Time Warped: Unlocking the Mysteries of Time Perception" and offers a synopsis through multiple quotes, including descriptions of how fear slows down subjective time.

…when people with arachnophobia were asked to look at spiders — the very object of their intense fear — for 45 seconds and they overestimated the elapsed time. The same pattern was observed in novice skydivers, who estimated the duration of their peers’ falls as short, whereas their own, from the same altitude, were deemed longer.

...and the Holiday Paradox

…the contradictory feeling that a good holiday whizzes by, yet feels long when you look back.” (An “American translation” might term it the Vacation Paradox.) Her explanation of its underlying mechanisms is reminiscent of legendary psychologist Daniel Kahneman’s theory of the clash between the “experiencing self” and the “remembering self”….We constantly use both prospective and retrospective estimation to gauge time’s passing. Usually they are in equilibrium, but notable experiences disturb that equilibrium, sometimes dramatically. This is also the reason we never get used to it, and never will. We will continue to perceive time in two ways and continue to be struck by its strangeness every time we go on holiday.

...the difference in the number of novel experiences at different ages:

…we are most likely to vividly remember experiences we had between the ages of 15 and 25. What the social sciences might simply call “nostalgia” psychologists have termed the “reminiscence bump”…The key to the reminiscence bump is novelty. The reason we remember our youth so well is that it is a period where we have more new experiences than in our thirties or forties. It’s a time for firsts — first sexual relationships, first jobs, first travel without parents, first experience of living away from home, the first time we get much real choice over the way we spend our days. Novelty has such a strong impact on memory that even within the bump we remember more from the start of each new experience.

A mechanism of why novelty seeking individuals are more vulnerable to social defeat stress.

Duclot and Kabbaj offer an interesting result that suggests at least part of the reason for why individuals more likely to seek novelty (whether humans or mice) are also more vulnerable to social defeat stress. They do not demonstrate the stress induced increase in levels of a brain growth factor (brain derived neurotrophic factor, or BNDF), that is observed in low novelty seeking individuals. BDNF regulation after stress has been suggested as an important mediator of vulnerability and resilience. Higher BDNF levels in the hippocampus - which can be caused by classic antidepressants - promote resilience to a chronic mild stress. Here is the abstract, with technical details:

Some personality traits, including novelty seeking, are good predictors of vulnerability to stress-related mood disorders in both humans and rodents. While high-novelty-seeking rats [high responders (HRs)] are vulnerable to the induction of depressive-like symptoms by social defeat stress, low-novelty-seeking rats [low responders (LRs)] are not. Here, we show that such individual differences are critically regulated by hippocampal BDNF. While LR animals exhibited an increase in BDNF levels following social defeat, HR individuals did not. This difference in hippocampal BDNF expression promoted the vulnerability of HR and the resilience of LR rats. Indeed, preventing activation of BDNF signaling by infusing the BDNF scavenger TrkB-Fc into the dentate gyrus of the hippocampus of LR rats led to social defeat-induced social avoidance, whereas its activation in HR rats by the TrkB agonist 7,8-dihydroxyflavone promoted social approach. Along with the changes in BDNF expression following defeat, we report in LR animals a downregulation of the inactive BDNF receptor TrkB.T1, associated with an activation of CREB through Akt-mediated signaling, but not MSK1-mediated signaling. In HR animals, none of these molecules were affected by social defeat. Importantly, the BDNF upregulation involved an epigenetically controlled transcription of bdnf exon VI, associated with a coherent regulation of relevant epigenetic factors. Altogether, our data support the importance of hippocampal BDNF regulation in response to stressful events. Moreover, we identify a specific and adaptive regulation of bdnf exon VI in the hippocampus as a critical regulator of stress resilience, and strengthen the importance of epigenetic factors in mediating stress-induced adaptive and maladaptive responses in different individuals.

Positive feedback loop between social connections, positive emotions, and vagal tone.

Kok et al. suggest that positive emotions, positive social connections, and physical health reinforce one another in a positive feedback loop.They use cardiac vagal tone as an objective proxy for physical health. Indexed at rest as variability in heart rate associated with respiratory patterns, vagal tone reflects the functioning of the vagus nerve, which is the 10th cranial nerve and a core component of the parasympathetic nervous system, which regulates heart rate in response to signals of safety and interest. Low vagal tone has been linked to high inflammation, greater risk for myocardial infarction, and lower odds of survival after heart failure.

Their positive feedback loop suggestion sounds good - and is consonant with many recent studies correlating positive emotions, physical health, and longevity - but they do tend to confuse cause and correlation, and do not have appropriate control groups. A 'waiting list control group' really doesn't hack it. A control group should at least have some sort of experimenter engagement with subjects that is as similar as possible to the control group except without the exercises for self-generated positive emotions. Still, the results do show convincing correlations between vagal tone, positive emotions, and social connections in a group that receives training and practices loving kindness meditation for 61 days. Here is the abstract:

The mechanisms underlying the association between positive emotions and physical health remain a mystery. We hypothesize that an upward-spiral dynamic continually reinforces the tie between positive emotions and physical health and that this spiral is mediated by people’s perceptions of their positive social connections. We tested this overarching hypothesis in a longitudinal field experiment in which participants were randomly assigned to an intervention group that self-generated positive emotions via loving-kindness meditation or to a waiting-list control group. Participants in the intervention group increased in positive emotions relative to those in the control group, an effect moderated by baseline vagal tone, a proxy index of physical health. Increased positive emotions, in turn, produced increases in vagal tone, an effect mediated by increased perceptions of social connections. This experimental evidence identifies one mechanism—perceptions of social connections—through which positive emotions build physical health, indexed as vagal tone. Results suggest that positive emotions, positive social connections, and physical health influence one another in a self-sustaining upward-spiral dynamic.

http://pss.sagepub.com/content/24/7/1123.abstract http://pss.sagepub.com.ezproxy.library.wisc.edu/content/24/7/1123.full

Sebastian - The Maestro

Deric and 16 month old grandson Sebastian improvising.

An ancestral logic of politics?

Another evolutionary psychology speculation: If individual dispositions about modern political conflicts are partly generated by evolved mechanisms designed for evolutionarily recurrent conditions, then men with greater upper-body strength should be more likely to adopt political positions that increase their share of resources, whereas men with lesser upper-body strength should be more likely to adopt positions that relinquish resources demanded by other individuals. Peterson et al. test this speculation:

Over human evolutionary history, upper-body strength has been a major component of fighting ability. Evolutionary models of animal conflict predict that actors with greater fighting ability will more actively attempt to acquire or defend resources than less formidable contestants will. Here, we applied these models to political decision making about redistribution of income and wealth among modern humans. In studies conducted in Argentina, Denmark, and the United States, men with greater upper-body strength more strongly endorsed the self-beneficial position: Among men of lower socioeconomic status (SES), strength predicted increased support for redistribution; among men of higher SES, strength predicted increased opposition to redistribution. Because personal upper-body strength is irrelevant to payoffs from economic policies in modern mass democracies, the continuing role of strength suggests that modern political decision making is shaped by an evolved psychology designed for small-scale groups.

Pathways through which loneliness affects health.

From Jaremka et al., some technical data on how stress correlates with activation of inflammatory chemistry in our bodies - chemistry started up by our immune system as if it were responding to infections or disease:

Although evidence suggests that loneliness may increase risk for health problems, the mechanisms responsible are not well understood. Immune dysregulation is one potential pathway: Elevated proinflammatory cytokines such as interleukin-6 (IL-6) increase risk for health problems. In our first study (N = 134), lonelier healthy adults exposed to acute stress exhibited greater synthesis of tumor necrosis factor-alpha (TNF-α) and IL-6 by peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS) than their less lonely counterparts. Similarly, in the second study (N = 144), lonelier posttreatment breast-cancer survivors exposed to acute stress exhibited greater synthesis of IL-6 and interleukin-1 beta (IL-1β) by LPS-stimulated PBMCs than their counterparts who felt more socially connected. However, loneliness was unrelated to TNF-α in Study 2, although the result was in the expected direction. Thus, two different populations demonstrated that lonelier participants had more stimulated cytokine production in response to stress than less lonely participants, which reflects a proinflammatory phenotype. These data provide a glimpse into the pathways through which loneliness may affect health.

How exercise calms anxiety.

In my scans of journals' tables of contents I missed this interesting piece by Schoenfeld et al., which is pointed to by a summary in the New York Times "Well" section. Running is known to stimulate the production of more dendritic spines, the primary sites of excitatory synapses, on excitatory neurons throughout the hippocampal circuitry known to be involved in emotion processing. In spite of producing more excitable nerve tissue, exercise also calms anxiety (in mice and in humans). Schoenfeld suggest that this is because another effect of exercise is to increase the levels of proteins that process the inhibitory neurotransmitter GABA in local inhibitory nerve cells. Their results suggest that running improves anxiety regulation by engaging local inhibitory mechanisms in the ventral hippocampus. (By the way, GABA is a popular dietary supplement for supposedly calming social anxiety.) Here is their more technical abstract:

Physical exercise is known to reduce anxiety. The ventral hippocampus has been linked to anxiety regulation but the effects of running on this subregion of the hippocampus have been incompletely explored. Here, we investigated the effects of cold water stress on the hippocampus of sedentary and runner mice and found that while stress increases expression of the protein products of the immediate early genes c-fos and arc in new and mature granule neurons in sedentary mice, it has no such effect in runners. We further showed that running enhances local inhibitory mechanisms in the hippocampus, including increases in stress-induced activation of hippocampal interneurons, expression of vesicular GABA transporter (vGAT), and extracellular GABA release during cold water swim stress. Finally, blocking GABAA receptors in the ventral hippocampus, but not the dorsal hippocampus, with the antagonist bicuculline, reverses the anxiolytic effect of running. Together, these results suggest that running improves anxiety regulation by engaging local inhibitory mechanisms in the ventral hippocampus.

Quality of early parent input predicts child vocabulary 3 years later

Here is a fascinating result from Cartmill et al.:

Children vary greatly in the number of words they know when they enter school, a major factor influencing subsequent school and workplace success. This variability is partially explained by the differential quantity of parental speech to preschoolers. However, the contexts in which young learners hear new words are also likely to vary in referential transparency; that is, in how clearly word meaning can be inferred from the immediate extralinguistic context, an aspect of input quality. To examine this aspect, we asked 218 adult participants to guess 50 parents’ words from (muted) videos of their interactions with their 14- to 18-mo-old children. We found systematic differences in how easily individual parents’ words could be identified purely from this socio-visual context. Differences in this kind of input quality correlated with the size of the children’s vocabulary 3 y later, even after controlling for differences in input quantity. Although input quantity differed as a function of socioeconomic status, input quality (as here measured) did not, suggesting that the quality of nonverbal cues to word meaning that parents offer to their children is an individual matter, widely distributed across the population of parents.

A defense of evolutionary psychology.

For those of you who follow the debate over the legitimacy of the evolutionary psychology perspective, I recommend a look at this contribution by Jerry Coyne, which features Steven Pinker responding to a critique originating from a panel at the Convergence 2013 conference (described here). whose main point was summarized by P.Z. Myers as:

Developmental plasticity is all. The fundamental premises of evo psych are false.

The response:

This paragraph disturbed me for two reasons. First, the notion that “the fundamental premises of evo psych are false” seems deeply misguided. After all, those premises boil down to this statement: some behaviors of modern humans reflect their evolutionary history. That is palpably uncontroversial, since many of our behaviors are clearly a product of evolution, including eating, avoiding dangers, and the pursuit of sex.  And since our bodies reflect their evolutionary history, often in nonadaptive ways (e.g., wisdom teeth, bad backs, the coat of hair we produce as a transitory feature in fetuses), why not our brains, which are, after all, just bits of morphology whose structure affects our behaviors?

Second, “developmental plasticity” does not stand as a dichotomous alternative to “evolved features.” Our developmental plasticity is to a large extent the product of evolution: our ability to learn language, our tendency to defer to authorities when we’re children, our learned socialization—those are all features almost certainly instilled into our brains by natural selection as a way to promote behavioral flexibility in that most flexible of mammals.

These points are followed by a list of rejoinders made by Pinker to points in the panel discussion

The obesity paradox - fat people may live longer!

Virginia Hughes writes about accumulating data on obesity and longevity that many researchers wish would just go away, after all the effort that has been put into documenting the health risks that go with obesity. At issue, for example, is a meta-analysis, lead by Katherine Flegal, of 97 studies including 2.88 million people that reported people deemed 'overweight' by international standards to be 6% less likely to die than were those of 'normal' weight over the same time period. There has been furious debate over this result because the epidemiology involved is complex, and eliminating confounding factors is difficult. However,

....many researchers accept Flegal's results and see them as just the latest report illustrating what is known as the obesity paradox. Being overweight increases a person's risk of diabetes, heart disease, cancer and many other chronic illnesses. But these studies suggest that for some people — particularly those who are middle-aged or older, or already sick — a bit of extra weight is not particularly harmful, and may even be helpful. (Being so overweight as to be classed obese, however, is almost always associated with poor health outcomes.)  Click on graphic to enlarge:

...the most contentious part of the debate is not about the science per se, but how to talk about it. Public-health experts, including Willett, have spent decades emphasizing the risks of carrying excess weight. Studies such as Flegal's are dangerous, Willett says, because they could confuse the public and doctors, and undermine public policies to curb rising obesity rates. “There is going to be some percentage of physicians who will not counsel an overweight patient because of this,” he says. Worse, he says, these findings can be hijacked by powerful special-interest groups, such as the soft-drink and food lobbies, to influence policy-makers.

But many scientists say that they are uncomfortable with the idea of hiding or dismissing data — especially findings that have been replicated in many studies — for the sake of a simpler message. “One study may not necessarily tell you the truth, but a bulk of studies saying the same thing and being consistent, that really is reinforcing,” says Samuel Klein, a physician and obesity expert at Washington University in St Louis, Missouri. “We need to follow the data just like the yellow brick road, to the truth.”

The gospel according to me...

I want to pass on a few clips from the stimulating essay by Critchley and Webster in "The Stone" forum of the New York Times:

…many citizens in rich Western democracies have merely switched one notion of God for another — abandoning their singular, omnipotent (Christian or Judaic or whatever) deity reigning over all humankind and replacing it with a weak but all-pervasive idea of spirituality tied to a personal ethic of authenticity and a liturgy of inwardness. The latter does not make the exorbitant moral demands of traditional religions, which impose bad conscience, guilt, sin, sexual inhibition and the rest.

In the gospel of authenticity, well-being has become the primary goal of human life….The stroke of genius in the ideology of authenticity is that it doesn’t really require a belief in anything, and certainly not a belief in anything that might transcend the serene and contented living of one’s authentic life and baseline well-being. In this, one can claim to be beyond dogma.

This is the phenomenon that one might call, with an appreciative nod to Nietzsche, passive nihilism….In a seemingly meaningless, inauthentic world awash in nonstop media reports of war, violence and inequality, we close our eyes and turn ourselves into islands. We may even say a little prayer to an obscure but benign Eastern goddess and feel some weak spiritual energy connecting everything as we listen to some tastefully selected ambient music. Authenticity, needing no reference to anything outside itself, is an evacuation of history. The power of now.

Work is no longer a series of obligations to be fulfilled for the sake of sustenance: it is the expression of one’s authentic self…But here’s the rub: if one believes that there is an intimate connection between one’s authentic self and glittering success at work, then the experience of failure and forced unemployment is accepted as one’s own fault…A naïve belief in authenticity eventually gives way to a deep cynicism. A conviction in personal success that must always hold failure at bay becomes a corrupt stubbornness that insists on success at any cost. Cynicism, in this mode, is not the expression of a critical stance toward authenticity but is rather the runoff of this failure of belief.

Nothing seems more American than this forced choice between cynicism and naïve belief. Or rather, as Herman Melville put it in his 1857 novel “The Confidence Man,” it seems the choice is between being a fool (having to believe what one says) or being a knave (saying things one does not believe). For Melville, who was writing on the cusp of modern capitalism, the search for authenticity is a white whale.

Order your DIY brain stimulation kit to improve your cognition?

Nature Magazine has an interesting editorial on dealing with the fact that transcranial direct-current stimulation (tDCS) kits (costing ~ $200) are likely to soon get into the hands, and onto the heads, of many more people. A few clips:

The recent surge in interest in tDCS piggybacks on an increasing number of academic studies of its potential to boost cognitive ability, which themselves build on decades-old work using electrical stimulation of the brain to treat ailments such as depression (see Nature 472, 156–159; 2011).

In an opinion piece published earlier this month, Nicholas Fitz and Peter Reiner of the National Core for Neuroethics at the University of British Columbia in Vancouver, Canada, argue that scientists and regulators can no longer ignore the amateurish meddling with tDCS (N. Fitz and P. Reiner J. Med. Ethics http://doi.org/mv8; 2013). “The challenge for the field,” they write, “is to develop policy that thoughtfully deals with the issues stemming from people using tDCS devices at home.”

Such home use of experimental laboratory kit puts neuroethicists, and journals such as Nature, in a bind. To draw attention to it could promote and accelerate its use, and so increase the risk of a mishap. To ignore it leaves the risks unexplored. The scale of at-home tDCS use is unclear at present. It might fizzle out. Or, as scientific interest in the power of electrical stimulation of the brain grows, it might appeal to more enthusiasts, just as the fascination and potential of synthetic biology has spawned a parallel DIY community known as biohackers. The scientific interest is certainly there.

Last month, researchers at the University of Oxford, UK, published a study suggesting that random electrical stimulation of the brain could improve mathematical abilities (A. Snowball et al.Curr. Biol. 23, 987–992; 2013). And there is no lack of exposure. Drawn by the ease of access and the killer copy, science journalists are queuing up to try tDCS for themselves and to write about the effects.

Fitz and Reiner are not the first to raise concerns over the DIY tDCS community. Brain researchers flagged the problem last year, as part of a discussion on the broader ethics of using non-invasive brain-stimulation (R. Cohen Kadosh et al. Curr. Biol. 22, R108–R111; 2012). The researchers even raised the prospect of the ultimate in pushy parents: those who would use the technology on their children to try to boost their cognitive function. And back in 2011, scientists working on tDCS told Nature that they were concerned for the safety of those who tried it at home.

It is easier to raise these questions than to answer them. Fitz and Reiner have some sensible suggestions, ranging from greater reporting of the possible long-term risks of tDCS to mimicking the open communication and education strategy with which the life-sciences field has started to engage biohackers. The first step is to acknowledge the issue to get a sense of how widespread the demand for home electrical self-improvement really is. The next few months will tell us more.

Want to see the metadata on yourself (like the NSA already has)??

Intrigued by two recent articles by Lapidos and Chen, I've taken myself to the MIT media program called "Immersion". "... it only works with Gmail and you have to reveal your password...but, unlike Google, or the NSA, the project also offers an instant deletion option: Remove your name, and it erases your metadata.”  I couldn't resist. I forward all of my older email accounts (University of Wisconsin, etc.) to gmail, so it gives a good picture of my email contacts.  Below I show the graphic of my modest contact network, with names deleted.  And, of course, I've now erased the data and withdrawn the access permissions.  While doing this, I was astounded to see the list of widgets (I was completely unaware of) that have access to all my google data.  I started to delete a few, but gave up after awhile.  I assume the NSA has a vastly more complete picture, which is not being deleted!   And - whistling in the dark - I hope that nothing I do could possibly be of interest to security snoops.  

How our brain cortex receives information about the world

This post is for that subset of MindBlog readers interested in details of brain wiring. Constantinople and Bruno have upset a basic dogma taught to budding neuroscientists (like myself, in the 1960s) - that (from the Science editor's summary):

...there is a “canonical microcircuit” in the neo cortex, in which information is transformed as excitation spreads serially along connections from thalamus, to cortical layer 4, then to layers 2/3, to layers 5/6, and finally to other brain regions. Each cortical layer is thought to transform sensory signals to extract behaviorally relevant information. Now, from Constantinople and Bruno...In vivo whole-cell recordings revealed that sensory stimuli activate neurons in deep cortical layers simultaneously to those in layer 4 and that a large number of thalamic neurons converge onto deep pyramidal neurons, possibly allowing sensory information to completely bypass upper layers. Temporary blockade of layer 4 revealed that synaptic input to deep cortical layers derived entirely from the thalamus and not at all from upper cortical layers. This thalamically derived synaptic input reliably drove pyramidal neurons in layer 5 to discharge action potentials in the living animal. These deep layer neurons project to numerous higher-order brain regions and could directly mediate behavior.

Here is a summary graphic from the paper:

(A) In the conventional serial model, sensory information is transformed as excitation spreads from thalamus to L4 to L2/3 to L5/6 along the densest axonal pathways (green). (B) In the bistratified model, thalamus copies sensory information to both an upper stratum (L4 and L2/3) and a lower stratum (L5/6), which differ in coding properties and downstream target

s.

Eye widening in fear - sensory and social benefits

An interesting bit from Lee et al. Their abstract:

Facial expressions may have originated from a primitive sensory regulatory function that was then co-opted and further shaped for the purposes of social utility. In the research reported here, we tested such a hypothesis by investigating the functional origins of fear expressions for both the expresser and the observer. We first found that fear-based eye widening enhanced target discrimination in the available visual periphery of the expresser by 9.4%. We then found that fear-based eye widening enhanced observers’ discrimination of expressers’ gaze direction and facilitated observers’ responses when locating eccentric targets. We present evidence that this benefit was driven by neither the perceived emotion nor attention but, rather, by an enhanced physical signal originating from greater exposure of the iris and sclera. These results highlight the coevolution of sensory and social regulatory functions of emotional expressions by showing that eye widening serves to enhance processing of important environmental events in the visual fields of both expresser and observer.

Inflammation links ageing to the brain.

Gabuzda et al. do a nice review of work by Zhang et al., that suggests that manipulation of hypothalamus regulation, and especially levels of the hormone GnRH (gonadotropin-releasing hormone) might abrogate some effects of ageing.  I want to pass on several clips from their summary:

One of the least-understood aspects of ageing is its coordinated and stereotyped progression in all organ systems. Although researchers have long suspected that the brain orchestrates systemic ageing, compelling evidence of this in mammals has been lacking. Furthermore, we have had no clear understanding of how ageing is affected by inflammation, which is a hallmark of age-related diseases such as diabetes, cardiovascular disease, arthritis and Alzheimer's disease. Zhang et al. help to make this connection by documenting the integration of inflammatory responses with systemic control of ageing by the hypothalamus — a part of the brain that controls growth, reproduction and metabolism.

FIGURE - Zhang et al. report that inflammation leads to activation of the signalling molecule NF-κB in the hypothalamus of the brain, and suggest that this contributes to the control of systemic ageing. They show that NF-κB activation in hypothalamic cells called microglia results in production of TNF-α, which, in turn, stimulates NF-κB activity in nearby neurons. This signalling results in epigenetic repression of the gene that encodes gonadotropin-releasing hormone (GnRH), leading to reduced GnRH release from the neurons, which is associated with multiple physiological changes related to ageing, including bone loss, skin atrophy, muscle weakness and memory loss. This pathway might also mediate the effects of a variety of environmental and physiological stressors.

'Inflammageing' describes the close relationship between low-grade chronic inflammation and ageing that has been linked to a wide spectrum of age-related disorders in various organs, including the brain6. Healthy ageing and longevity could relate, in part, to reduced levels of inflammation or strong protective mechanisms that guard against adverse effects of chronic inflammation. Conversely, genetic and environmental factors that promote inflammation or disrupt the mechanisms involved in reducing inflammation seem to confer increased susceptibility to 'accelerated ageing' and age-related disorders such as insulin resistance, metabolic disorders and cardiovascular disease7. Accelerated ageing typically involves multiple organ systems, although the effects in some organs might not be seen as clinical symptoms.

In addition to the classical activity of GnRH in regulating the release of sex steroids involved in development and reproduction (oestrogens and progesterone in females and androgens in males), the hormone might also mediate other functions12. Notably, Zhang et al. found that when mice were administered GnRH, it abrogated ageing effects and increased the production of new neurons in the hypothalamus and hippocampus (a part of the brain that regulates memory). By contrast, sex steroids did not have these anti-ageing effects. A decrease in gonadal sex steroids is a well-established marker of ageing, but many other hormonal changes occur as well; and some of these age-regulated hormones (such as dehydroepiandrosterone) also regulate inflammation and other immune responses. Thus, interplay between the hormonal and immune systems occurs at multiple levels.

How might hypothalamic regulation of ageing have evolved? Chronic inflammation arises from many kinds of insult, from acute infection to genomic instability. The concept that the hypothalamus can sense inflammation through immune pathways is a new one; just as the hypothalamus responds to nutrient status, its response to inflammation may enable the organism to rapidly adapt to physiological perturbations. Turning down the hypothalamic release of modulators such as GnRH to prevent reproduction and reduce growth may be evolutionarily advantageous during acute infection, injury or deprivation. Although this would have been adaptive for our shorter-lived ancestors, it may accelerate ageing in older individuals and have become apparent now that we live longer. This idea also raises the intriguing possibility that hypothalamic regulation could be therapeutically manipulated to have broad effects on the ageing process and age-related pathology.

A spiritual home for atheists.

For many of us secular humanists, agnostics, or atheists, life after our alienation from conventional religious congregations that offer prayers to an anthropomorphic god (or gods) ends up feeling a bit rye-crispy. We lose also the sense of belonging and community that was part of the experience of being in a church congregation. Thus I was struck by this article about a former Pentecostal minister who has started in Baton Rouge, LA., to offer atheist services with impassioned sermons, singing and light swaying, exhortations to service, etc., everything but God! Jerry DeWitt, who was raised as a pentecostal and served 25 years as a minister, now offers an emotional counterpoint to more academic atheist exponents like Richard Dawkins and Christopher Hitchens. While other non-deistic spiritual congregations now exist, especially in many larger urban areas ( usually with some mix or mysticism, new age rituals, or religious-scientific components) I doubt that many of them get quite as close to reproducing the gut-wrenching intensity of DeWitt’s pentecostal service minus God!

Linking brain imaging to our subjective experience - focused attention versus mind-wandering

An interesting study from Garrison et al at Yale:

Recent advances in brain imaging have improved the measure of neural processes related to perceptual, cognitive and affective functions, yet the relation between brain activity and subjective experience remains poorly characterized. In part, it is a challenge to obtain reliable accounts of participant's experience in such studies. Here we addressed this limitation by utilizing experienced meditators who are expert in introspection. We tested a novel method to link objective and subjective data, using real-time fMRI (rt-fMRI) to provide participants with feedback of their own brain activity during an ongoing task. We provided real-time feedback during a focused attention task from the posterior cingulate cortex, a hub of the default mode network shown to be activated during mind-wandering and deactivated during meditation. In a first experiment, both meditators and non-meditators reported significant correspondence between the feedback graph and their subjective experience of focused attention and mind-wandering. When instructed to volitionally decrease the feedback graph, meditators, but not non-meditators, showed significant deactivation of the posterior cingulate cortex. We were able to replicate these results in a separate group of meditators using a novel step-wise rt-fMRI discovery protocol in which participants were not provided with prior knowledge of the expected relationship between their experience and the feedback graph (i.e., focused attention versus mind-wandering). These findings support the feasibility of using rt-fMRI to link objective measures of brain activity with reports of ongoing subjective experience in cognitive neuroscience research, and demonstrate the generalization of expertise in introspective awareness to novel contexts.

Enhanced emotion regulation persists after meditation training.

Desbordes and collaborators have looked at the effects of training in both mindful attention meditation and compassion meditation in two groups of subject with no previous experience meditating enrolled in 8-week training courses in both. 12 participants from each group reacted to images of people in situations with positive, negative, or neutral emotional content during fMRI measurements made during three weeks before or at three weeks after the training sessions. From the review in The Harvard Gazette:

In the mindful attention group, the after-training brain scans showed a decrease in activation in the right amygdala in response to all images, supporting the hypothesis that meditation can improve emotional stability and response to stress. In the compassion meditation group, right amygdala activity also decreased in response to positive or neutral images. But among those who reported practicing compassion meditation most frequently outside of the training sessions, right amygdala activity tended to increase in response to negative images, all of which depicted some form of human suffering. No significant changes were seen in the control group or in the left amygdala of any study participants.

The Harm-Made Mind

Here is a fascinating bit from Daniel Wegner and his collaborators. (I cite Wegner extensively in my "I-Illusion" web-lecture in introductory lectures sections of the left had column of this web page.)

People often think that something must have a mind to be part of a moral interaction. However, the present research suggests that minds do not create morality but that morality creates minds. In four experiments, we found that observing intentional harm to an unconscious entity—a vegetative patient, a robot, or a corpse—leads to augmented attribution of mind to that entity. A fifth experiment reconciled these results with extant research on dehumanization by showing that observing the victimization of conscious entities leads to reduced attribution of mind to those entities. Taken together, these experiments suggest that the effects of victimization vary according to victims’ preexisting mental status and that people often make an intuitive cognitive error when unconscious entities are placed in harm’s way. People assume that if apparent moral harm occurs, then there must be someone there to experience that harm—a harm-made mind. These findings have implications for political policies concerning right-to-life issues.

Are you married? Did you meet on-line or off-line?

Interesting bit from Cacioppo et al.

Marital discord is costly to children, families, and communities. The advent of the Internet, social networking, and on-line dating has affected how people meet future spouses, but little is known about the prevalence or outcomes of these marriages or the demographics of those involved. We addressed these questions in a nationally representative sample of 19,131 respondents who married between 2005 and 2012. Results indicate that more than one-third of marriages in America now begin on-line. In addition, marriages that began on-line, when compared with those that began through traditional off-line venues, were slightly less likely to result in a marital break-up (separation or divorce) and were associated with slightly higher marital satisfaction among those respondents who remained married. Demographic differences were identified between respondents who met their spouse through on-line vs. traditional off-line venues, but the findings for marital break-up and marital satisfaction remained significant after statistically controlling for these differences. These data suggest that the Internet may be altering the dynamics and outcomes of marriage itself.

Brain science backlash, throwing out the baby with the bathwater.

A recent NYTimes Op-Ed piece by David Brooks' ("Beyond the Brain") references the recent book "“Brainwashed: The Seductive Appeal of Mindless Neuroscience.” a book that appropriately notes some of the limitations of zealous over interpretation of brain imaging data but also includes some facile straw man arguments. Brooks kind of loses it in his comment:

It is probably impossible to look at a map of brain activity and predict or even understand the emotions, reactions, hopes and desires of the mind...there appears to be no dispersed pattern of activation that we can look at and say, “That person is experiencing hatred."

These sentiments are simply wrong, and I thought, rather than rambling on myself, I would point interested readers to two cogent commentaries on the recent anti-brain science surge, one in The New Yorker blog posted by Gary Marcus, the other in The Neurocritic blog.

Paternal stress changes stress axis in offspring

A study from Bale and colleagues shows that stress on preadolescent and adult male mice induces an epigenetic mark in their sperm that reprogramms their offspring's hypothalamic-pituitary-adrenal (HPA) axis, the brain regions that governs responses to stress. Offspring from paternal stress groups displayed significantly blunted levels of the stress hormone corticosterone -- in humans, it's cortisol -- in response to stress. It is curious that both male and female offspring had abnormally low reactivity to stress. Perhaps this reduced physiological stress response may reflect some adaptive evolutionary benefit passed on to offspring to ensure survival in what is expected to be a more stressful environment.

Neuropsychiatric disease frequently presents with an underlying hyporeactivity or hyperreactivity of the HPA stress axis, suggesting an exceptional vulnerability of this circuitry to external perturbations. Parental lifetime exposures to environmental challenges are associated with increased offspring neuropsychiatric disease risk, and likely contribute to stress dysregulation. While maternal influences have been extensively examined, much less is known regarding the specific role of paternal factors. To investigate the potential mechanisms by which paternal stress may contribute to offspring hypothalamic–pituitary–adrenal (HPA) axis dysregulation, we exposed mice to 6 weeks of chronic stress before breeding. As epidemiological studies support variation in paternal germ cell susceptibility to reprogramming across the lifespan, male stress exposure occurred either throughout puberty or in adulthood. Remarkably, offspring of sires from both paternal stress groups displayed significantly reduced HPA stress axis responsivity. Gene set enrichment analyses in offspring stress regulating brain regions, the paraventricular nucleus (PVN) and the bed nucleus of stria terminalis, revealed global pattern changes in transcription suggestive of epigenetic reprogramming and consistent with altered offspring stress responsivity, including increased expression of glucocorticoid-responsive genes in the PVN. In examining potential epigenetic mechanisms of germ cell transmission, we found robust changes in sperm microRNA (miR) content, where nine specific miRs were significantly increased in both paternal stress groups. Overall, these results demonstrate that paternal experience across the lifespan can induce germ cell epigenetic reprogramming and impact offspring HPA stress axis regulation, and may therefore offer novel insight into factors influencing neuropsychiatric disease risk.

Paper is not dead...

Sorry to spam you, but particularly after yesterday's post about smartphone apps I thought this was hysterical.

More on smartphone brain training apps.

This post is just a quickie pointer to update the series of posts I have done on smart phone or PC apps that give your brain a workout.  It reviews several current products.  I try each new iteration for a bit,  but then fade because I am phobic about "competing" with myself or anyone else and also get concerned that my scores are not improving fast enough.  I didn't grow up in a video game playing world, and they feel too much like hard work - I like things that feel easy with the skills I have,  like learning a new piano score. 

Neuroimaging our self esteem - be happy!

There are more papers coming out on brain correlates of whatever aspect of our behaviors you care to name than anyone could possibly keep up with. I have the ‘my eyes glaze over’ experience in just scanning tables of contents of the relevant journals. Occasionally an item pops out that grabs my attention, such as this one (open access) on imaging brain correlates of self esteem. The drums continue to beat (see this book review) on how important a positive self image and an "Up" attitude are for health and longevity. Maybe someone will develop some kind of magnetic zapper that we can shoot ourselves up with whenever whenever we are feeling like a piece of …... 

Although neuroimaging studies strongly implicate the medial prefrontal cortex (ventral and dorsal), cingulate gyrus (anterior and posterior), precuneus and temporoparietal cortex in mediating self-referential processing (SRP), little is known about the neural bases mediating individual differences in valenced SRP, that is, processes intrinsic to self-esteem. This study investigated the neural correlates of experimentally engendered valenced SRP via the Visual–Verbal Self-Other Referential Processing Task in 20 women with fMRI. Participants viewed pictures of themselves or unknown other women during separate trials while covertly rehearsing ‘I am’ or ‘She is’, followed by reading valenced trait adjectives, thus variably associating the self/other with positivity/negativity. Response within dorsal and ventral medial prefrontal cortex, cingulate cortex and left temporoparietal cortex varied with individual differences in both pre-task rated self-descriptiveness of the words, as well as task-induced affective responses. Results are discussed as they relate to a social cognitive and affective neuroscience view of self-esteem.

.... stimulus presentations were blocked in terms of the conditions Reference (Self vs Other, i.e. photographs) and Valence (words), creating four trial types: self-negative (S-N), self-positive (S-P), other-negative (O-N) and other-positive (O-P). Participants were not instructed that they ‘should try to press the buttons as fast as possible’ as is often done in social cognition experiments. In contrast, participants were instructed only to press the buttons ‘so that we can assess afterwards whether you are paying attention to and completing the task’. This passive orientation was intended to focus attention towards introspection and interoception with participants reminded repeatedly of the importance of ‘paying close attention to how you are feeling throughout the different parts of the task’.

Young blood makes younger hearts (and brains) - also, aging resistant brains

I've previously mentioned work showing that providing young blood to an older brain can be beneficial, and now want to note work by Loffredo et al. that shows that exposure to a young circulation reverses age-related cardiac hypertrophy, which is a prominent feature of age-related diatolic heart failure. The TGFβ family member GDF11 appears to be the crucial circulating factor that declines with age; restoring GDF11 to youthful levels reverses age-related cardiac hypertrophy. 

Also, relevant to aging, I might note a longitudinal study by Pudas et al. comparing MRI data from elderly people most successful in preserving episodic memory and ability on paired association tasks with measurements on average contemporaries. The results suggest that successful cognitive aging is associated with preservation of the responsiveness of the hippocampus and prefrontal cortex.

Heart rate variability, ANS aging - a new device from "Phyode" - therapeutic agent or scam??

I want to put in this post a comment by reader "Andre" on my June 11 post ("Changes as an autonomic nervous system ages 11 years - The "Wild Divine" is a bit less wild.", along with my response.

Last week I backed a Kickstarter project from Phyode called the W/Me (http://goo.gl/en1Ea), a smartwatch that uses HRV and "ANS Age" as its primary markers for assessing the user's "mental state". I couldn't find a research precedent for using ANS aging for this purpose until your post came up in a Google search. Do you think Phyode's methodology is valid?

My response on looking at the website:

This is a very slick presentation, and looks like a potentially interesting product...If it were not for the fact that its development appears to be limited to Android products (i.e. no iPhone App)[NOTE! 10/22/13 - comment below says I'm wrong, it is for iPhone, not Android, my bad..] I would probably try it out when it is sold (There are, by the way several iPhone apps that do heart rate, HRV, etc.).....BUT, there are no pointers to basic scientific references on heart rate variability, ANS age, how it can be therapeutically altered in a beneficial way, or how his device would be used to do that. The FAQ section at the end of the web page with what look like links to such items as "What is HRV?" don't link to anything!! The Phyode "Full bio and links" doesn't yield anything significant! I would be interested in seeing something a bit more substantial from the people in the flashy video presentations (all appear to be 20-somethings, by the way). I don't want to play the complete nasty guy here, because a lot of effort went into the slick videos and description, and they look plausible, but what assures us that the fund raising "Back this project" (minimum donation $1.00) is not a scam? Does the Kickstarter cloud funding site that hosts this webpage have any quality controls or review criteria?? The "report this site to Kickstarter" link takes you to a page that requires you to join or be member of Kickstarter, and I'm not inclined to take that much time on this....

Carrying human (and mouse) babies reduces their crying and heart rate.

Esposito et al. present some really nice observations. They demonstrate for the first time that the infant calming response to maternal carrying is a coordinated set of central, motor, and cardiac regulations and is a conserved component of mammalian mother-infant interactions. You should watch the video.


-Maternal carrying reduces crying, body movement, and heart rate of infants
-In mice, a similar set of calming responses is observed during carrying
 -Mouse calming response requires proprioception and somatosensation
 -The calming responses in infants function to increase maternal carrying efficacy

Here we show a novel set of infant cooperative responses during maternal carrying. Infants under 6 months of age carried by a walking mother immediately stopped voluntary movement and crying and exhibited a rapid heart rate decrease, compared with holding by a sitting mother. Furthermore, we identified strikingly similar responses in mouse pups as defined by immobility and diminished ultrasonic vocalizations and heart rate. Using pharmacologic and genetic interventions in mouse pups, we identified the upstream and downstream neural systems regulating the calming response. Somatosensory and proprioceptive input signaling are required for induction, and parasympathetic and cerebellar functions mediate cardiac and motor output, respectively. The loss of the calming response hindered maternal rescue of the pups, suggesting a functional significance for the identified calming response.

Our memory can be selectively rewritten during its reconsolidation.

Chan and LaPaglia make an interesting observation in humans that had previously only been reported in animal studies. We can mess with an existing declarative memory of an event after that memory has been reactivated, if during its reconsolidation we are presented with changes that target and change some details of the original memory. Reactivated memories are vulnerable only to interference that specifically targets the existing memories. This work provides yet another example of how eye witness testimony of the sort used in legal proceedings can become unreliable.

During the past decade, a large body of research has shown that memory traces can become labile upon retrieval and must be restabilized. Critically, interrupting this reconsolidation process can abolish a previously stable memory. Although a large number of studies have demonstrated this reconsolidation associated amnesia in nonhuman animals, the evidence for its occurrence in humans is far less compelling, especially with regard to declarative memory. In fact, reactivating a declarative memory often makes it more robust and less susceptible to subsequent disruptions. Here we show that existing declarative memories can be selectively impaired by using a noninvasive retrieval–relearning technique. In six experiments, we show that this reconsolidation-associated amnesia can be achieved 48 h after formation of the original memory, but only if relearning occurred soon after retrieval. Furthermore, the amnesic effect persists for at least 24 h, cannot be attributed solely to source confusion and is attainable only when relearning targets specific existing memories for impairment. These results demonstrate that human declarative memory can be selectively rewritten during reconsolidation.

Antonin Scalia Does Not Believe in Molecular Biology

Thanks to my son Jon for pointing this out to me.

Private behaviors from public records...

The exposure of the PRISM surveillance system by Edward Snowden gave me a sort of "So what else is new?" reaction... I thought we knew this unfortunate stuff was happening, particularly in view of numerous academic articles in the vein of the following from Kosinski et al.:

We show that easily accessible digital records of behavior, Facebook Likes, can be used to automatically and accurately predict a range of highly sensitive personal attributes including: sexual orientation, ethnicity, religious and political views, personality traits, intelligence, happiness, use of addictive substances, parental separation, age, and gender. The analysis presented is based on a dataset of over 58,000 volunteers who provided their Facebook Likes, detailed demographic profiles, and the results of several psychometric tests. The proposed model uses dimensionality reduction for preprocessing the Likes data, which are then entered into logistic/linear regression to predict individual psychodemographic profiles from Likes. The model correctly discriminates between homosexual and heterosexual men in 88% of cases, African Americans and Caucasian Americans in 95% of cases, and between Democrat and Republican in 85% of cases. For the personality trait “Openness,” prediction accuracy is close to the test–retest accuracy of a standard personality test. We give examples of associations between attributes and Likes and discuss implications for online personalization and privacy.

Changes as an autonomic nervous system ages 11 years - The "Wild Divine" is a bit less wild.

Just after I retired from being a Univ. of Wisconsin department chair in 2001 I bought a set of finger sensors that fit on one's three middle fingers to report skin conductance and heartbeat to a PC or MAC via an A/D converter. These were part of a package with several CDs that installed a new age game on the computer that lead you through a rich environment of classical greek temples and waterfalls, attended by soothing music, that presented tasks in which you dinked with your own heart rate variability and sympathetic (arousing)/parasympathetic (calming) balance, going alternatively through periods of calm and arousal. I thought it was a hoot, and took the time to go through the "Journey to Wild Divine: passage" and "Journey to Wild Divine: Wisdom Quest."

Some of the current incarnations of these programs have moved to web browsers. Over the years a number of heavy weight new age gurus have signed on with their wares - Deepak Chopra, Dean Ornish, and Andrew Weil (Weil was in my Harvard graduating class...I'm tempted, but I won't burden you with my jaded opinion of this class of entrepreneurs, particularly Mr. Chopra.)

The main point of this post is note my experience on pulling out the finger sensors after 11 years trying the same exercises in their new presentation. What's the difference when this 71 year old tries the same manipulations of calm and arousal that the 60 year old played with with 11 years earlier? In a nutshell, I have less command over heart rate variability, which is lower, as the swings between calm and arousal have less amplitude.

And indeed, this fits with the literature on changes in the autonomic nervous system that occur on aging. If you simply do a google search for "autonomic nervous system and aging" numerous references appear that document how healthy aging is associated with lowered heart rate variability, elevated basal sympathetic nervous activity, and reduction of overall autonomic reactivity of sympathetic and parasympathetic nervous systems. Here is a very recent review, from which I pass on one figure:

Schematic of proposed features associated with the imbalance in the autonomic nervous system during aging. During aging there is a shift in the balance of the autonomic nervous system (ANS) towards the sympathetic nervous system (SNS). This may be influenced by circulating or local brain levels of angiotensin (Ang) II and leptin. The lower activity of the parasympathetic nervous system (PSNS) is proposed to result at least in part from an age-related decline in Angiotensin-(1–7). Lower Angiotensin-(1–7) and higher Ang II or leptin in the brain medulla would predispose to a decline in baroreceptor reflex sensitivity (BRS) for control of heart rate and heart rate variability (HRV), both of which are associated with aging. Moreover, impairments in BRS and HRV can contribute to target organ damage, including metabolic dysfunction, with or without an increase in blood pressure. 

If you're inclined, like Mr. Dylan Thomas, to not "go gently into that good night" you can find numerous sources (example here) on slowing these aging changes, usually by some sort of physical movement or stimulation.

Preventing Alzheimer’s associated brain cell atrophy with B vitamin treatment.

I pass this on because it seems like a very striking result. Douaud et al. find that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) causes a 7-fold decrease in cerebral atrophy of nerve cell areas most vulnerable to the Alzheimer's process over a 2-year period in a group of elderly subjects with increased dementia risk. (For comparison, Centrum Silver 50+ has Folic Acid 0.4 mg, Vitamin B6 3 mg, and Vitamin B12 0.025 mg.) The supplements decrease plasma levels of one of the bad players in the Alzheimer's story, homocysteine. (Homocysteine is a homologue of the amino acid cysteine,and can be recycled into methionine or converted into cysteine with the aid of B-vitamins.) Here's the abstract:

Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer’s disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, we go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.

Here is one figure from the paper:

B-vitamin treatment significantly reduces regional loss of gray matter. (A) Brain regions in blue demonstrate where B-vitamin treatment significantly reduces GM loss over the 2-y period. All blue areas correspond to regions of significant loss in placebo and known to be vulnerable in AD. (B) Percentage of GM loss for the 156 participants over the 2-y period, averaged across those brain regions that showed significant effect of B vitamins: placebo group (red triangles) had an average loss of 3.7% (±3.7), whereas the B-vitamin group (green circles) showed a loss of 0.5% (±2.9).