Nocebo pain facilitation occurs at spinal cord level.

I have had the impression that placebo and nocebo effects were the province of higher cortical brain machinations, the power of suggestion tweaking our subjective experience to feeling more or less pain than in the absence of an intervention. Geuter and Büchel now make the interesting observation this power of suggestion relays right down into the spinal cord, to alter its pain signalling pathways:

Nocebo hyperalgesia is an increase in subjective pain perception after a patient or subject underwent an inert treatment without any active ingredient. For example, verbal suggestion of increased pain can enhance both pain experience and responses in pain-related cortical brain areas. However, changes in cortical pain responses may be secondary to earlier amplification of incoming pain signals within the spinal cord. To test for a potential early enhancement of pain signals in the dorsal horn of the spinal cord, we combined a nocebo heat pain paradigm with spinal functional magnetic resonance imaging in healthy volunteers. We found that local application of an inert nocebo cream on the forearm increased pain ratings compared with a control cream, and also reduced pain thresholds on the nocebo-treated skin patch. On the neurobiological level, pain stimulation induced a strong activation in the spinal cord at the level of the stimulated dermatomes C5/C6. Comparing pain stimulation under nocebo to a control pain stimulation of the same physical intensity revealed enhanced pain-related activity in the ipsilateral dorsal horn of the spinal cord. Importantly, the activation of the main effect of pain and the nocebo effect spatially overlapped. The current study thus provides direct evidence for a pain-facilitating mechanism in the human spinal cord before cortical processing, which can be activated by cognitive manipulations such as nocebo treatments.

The Innovation of Loneliness

This is a wonderful succinct video that has gone viral, and I would encourage MindBlog readers to have a look at it. I can't imagine a more effective presentation of how connectivity can destroy real community.

"Life Enhancement"

A colleague sends me material he finds on longevity, life enhancement, etc. and I thought I would pass on two links on trendy compounds du jour, galantamine and theanine. The magazine on this site offers articles on various compounds suspected to be beneficial and actually lists supporting scientific references. This is a contrast with many sites that hawk some proprietary expensive mixture of amino acids or whatever, with no documentation or journal citations pointing to original research.

Meditation factoids - enhancement of “good” genes expression, smoking reduction

Herbert Benson (of "relaxation response" fame) and collaborators have offered a study suggesting that meditation or relaxation down regulates expression of genes involved in inflammation and HPA stress axis (fight or flight) responses. Beneficial changes in genes regulating mitochondrial energy metabolism and insulin production were also noted. Here is their technical abstract:

The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.

The second item: Posner and collaborators find that brief meditation training induces smoking reduction

More than 5 million deaths a year are attributable to tobacco smoking, but attempts to help people either quit or reduce their smoking often fail, perhaps in part because the intention to quit activates brain networks related to craving. We recruited participants interested in general stress reduction and randomly assigned them to meditation training or a relaxation training control. Among smokers, 2 wk of meditation training (5 h in total) produced a significant reduction in smoking of 60%; no reduction was found in the relaxation control. Resting-state brain scans showed increased activity for the meditation group in the anterior cingulate and prefrontal cortex, brain areas related to self-control. These results suggest that brief meditation training improves self-control capacity and reduces smoking.

More on the Neuro-Utopians

A recent article by Benjamin Fong. "Bursting the neuro-utopian bubble" was so widely reported that I have delayed mention of it. In that article he takes on the hubris of some proponents of Obama's "Brain Activity Map Project" that I have mentioned previously. In response to extensive feedback, Fong has issued a clarification of the core of his argument which is worth excerpting here:

One way to present my view would thus be to say that I would like to see a more comprehensive view of scientific inquiry that tames its more “religious” elements, which have gravitated to a particular position that accords the study of the brain a primary importance, and the investigation of psychosocial factors a definitively secondary one...I believe that the $100 million going to the Brain Initiative shows where our priorities lie. We are still far from rectifying a gross imbalance in funding and focus, one that has stemmed, in my view, from an ardent desire for an increasing instrumental control over the world and ourselves.

I attempted to consider two conceptions of scientific inquiry, one of which (science as agent of technological mastery) has come to dominate the other (science as critical examination of our current practices). Drawing on the tradition of critical social theory, I called one “instrumental” and the other “communicative.” My point in distinguishing these two forces was not to give preference to the subordinate party but to argue for the necessity of maintaining a healthy tension between them, especially when it comes to the problem of mental health. I thus heartily agree with many responders that we need both...my concern in the piece was not with “abuses” of science but with the very desire itself and what it unconsciously represses. One does not have to be a psychoanalyst to know that our desires often make us do things of which we are not aware.

In short, it was not my primary intention to argue against the advances of neuroscience, but simply to convey a philosophical wonder about the fact that the idea of changing human physiology — transforming the human being itself — is, at least in some circles, both more “scientific” and more “realistic” than changing human society.

Song of our warming planet

A colleague in the chaos seminar group here at the Univ. of Wisconsin sent around this video translating global warming data into a musical piece. I wanted to pass it on to you, because I find it very effective....

A Song of Our Warming Planet from Ensia on Vimeo.

The Beethoven mouse - a key to auditory transduction

I have to pass on this great montage cover and its legend from the journal Neuron. The article referenced described a gene mutation that leads to progressive hearing loss.

The Beethoven mouse, like its namesake the classical music composer Ludwig von Beethoven, suffers progressive hearing loss and eventual profound deafness. In this issue, Pan et al. examined sensory transduction in inner ear hair cells of Beethoven mice, which carry a point mutation in Transmembrane channel-like 1 gene (Tmc1). They report reduced calcium permeability and reduced single-channel conductance in Beethoven hair cells relative to hair cells that expressed wild type Tmc1. The Beethoven data demonstrate that TMC1 is a component of the hair cell transduction channel. The authors found that a closely related homolog, TMC2, also functions as a component of the transduction channel. The image shows Ludwig von Beethoven as portrayed by Joseph Stieler (1820). A cross-section of the ear, including external ear, middle, and inner ear, appears below. Within the inner ear is the spiral-shaped cochlea. The inset below shows the sensory organ, or organ of Corti. At the bottom right is a scanning electron micrograph of a hair bundle from an inner hair cell, which was the main focus of the Pan et al. study. Cover montage by Emily Mills.

Early experience shapes the amygdala’s sensitivity to race.

Here is a fascinating finding. Not surprising, I suppose, but Telzer et al. show that orphan human infants raised with exposure to only same-race faces (European or Asian) have heightened amygdala responses to out-group faces than those raised with exposure to same- and other-race faces. Later age of adoption is associated with greater biases to race.

In the current study, we investigated how complete infant deprivation to out-group race impacts behavioral and neural sensitivity to race. Although monkey models have successfully achieved complete face deprivation in early life, this is typically impossible in human studies. We overcame this barrier by examining youths with exclusively homogenous racial experience in early postnatal development. These were youths raised in orphanage care in either East Asia or Eastern Europe as infants and later adopted by American families. The use of international adoption bolsters confidence of infant exposure to race (e.g., to solely Asian faces or European faces). Participants completed an emotional matching task during functional MRI. Our findings show that deprivation to other-race faces in infancy disrupts recognition of emotion and results in heightened amygdala response to out-group faces. Greater early deprivation (i.e., later age of adoption) is associated with greater biases to race. These data demonstrate how early social deprivation to race shapes amygdala function later in life and provides support that early postnatal development may represent a sensitive period for race perception.

Looking at the Posit Science brain renewal training program.

I recently did a post pointing to Patricia Marx's article on brain exercises meant to counter aging. The authors went through the training regime of Mike Merzenich's company "Posit Science." I just got the Kindle version of his new book (pub. date July 27, 2013) "Soft Wired - How the new science of brain plasticity can change your life." I got impatient with the excellent presentation of background material in parts I-III of the book that I am familiar with and noted that at the end of each chapter a URL pointed to a bibliography of original articles supporting its statements. On reaching part IV of the book, "The Brain in Retreat," after a brief scan of the text, I ditched reading the book and went straight to the richly annotated gold mine of references. Below, for example, are some slightly edited clips from the references for Chapter 19 "Losing Ground, Just By Having a Birthday!
How, more exactly, do mental and physical performance abilities change as we grow older?"...probably more than you wanted to know about how our brains and bodies lose it with aging.

I soon found that the references are a work in progress. Detailed literature citations disappear at chapter 22 then reappear with chapter 25, and then trying to pull up references for chapters 32-37 gets a "bad link" message. Both the book and the references detail hassles with getting patents on brain training exercises, forming first one, and then a second company. I would have been happy to be spared this information and would like to have seen some justification why patents and private profits were appropriate for research publicly funded by foundations and the government.

I was frustrated by Part V, "Strengthening, correction, and rejuvenation through brain training" because it was mainly a string of homilies on good living, an advertisement for Posit Science, and an account of Merzenich's personal regimes. What about actually explaing a few of the exercises??? The references did give the meat of studies testing the efficacy of various attention, memory, and language exercises.

I'm currently looking at some of the free exercises, and may get back to you if I decide to cough up the subscription fee for the whole set and really get into it.

Here then are samples from the Merzenich Ch. 19 references:

-Several hundred studies have documented changes in processing speed associated with aging. There are many measured brain process “speeds;” they ALL slow down. See Salthouse TA (2000) Aging and measures of processing speed.  Biol Psychol 45:35

-There is one interesting exception: The strength of fast inhibitory processes normally weaken, to the extent that the modulatory response characteristics of neurons in the cortex support faster successive-signal responding (because post-excitatory inhibition is weaker). This change confers no behavioral advantage because the responding in such an inhibition-impaired brain is so noisy that information that comes from signal processing with such degradation declines dramatically. See de Villers-Sidani et al (2010) Recovery of functional and structural age-related changes in the primary auditory cortex with operant training. PNAS 107:13900.

-The extensions of time required to identify successively presented inputs are, on the average, substantially longer in older populations…I identify the MIT professor Jim DiCarlo as making the most convincing arguments that the richer exploration of stimuli via repeated eye movements—more strongly expressed in young vs older individual—is a key to accurate recognition. For example, see DiCarlo JJ et al (2012)  How does the brain solve visual object recognition? Neuron 73:415.

-We commonly record correlated changes in representational accuracy and speed in variously impaired (including aging) brains…The less accurate the brain’s neurological representation of what it sees or hears or feels, the longer it takes to “get the answer right,” i.e., to resolve what it is being seen or heard or felt.

-The degradation of our ability to suppress distractors of either external or internal origin with age has been repeatedly documented in behavioral and brain imaging studies; and the susceptibility to distractors has been shown to directly contribute to forgetfulness in older and otherwise-impaired individuals.  See, as an introduction to this rapidly growing literature, Gazzaley A, D’Esposito M (2007) Top-down modulation and normal aging.  Ann NY Acad Sci 1097:67.

-Many studies have shown that the strength of modulation of brain activity by attention is weaker in most neurologically and psychiatrically impaired populations. That modulation is largely controlled by the release of the neuromodulator acetylcholine. On the statistical average, acetylcholine-based modulation progressively weakens as the decades pass by.  For an introduction to this literature, see, for example, Pekkonen E et al (2005) Cholinergic modulation of preattentive auditory processing in aging. Neuroimage 27:387

The list goes on: references on contraction of useful field of vision, changes in driving abilities with aging, hearing loss, less vestibular control, less 'executive control'

-For documentation of the multifaceted decline into a more egocentric older life, see, for example, Orth U et al (2010) Tracking the trajectory of shame, guilt and pride across the life span. J Per Soc Psychol 99:1061; or McFarland C et al (1992) Biased recollections in older adults: The role of implicit theories of aging. J Pers Soc Psychol 62:837.

How the brain shifts between purpose and habit.

Gremel et al. do a nice explication of the brain's upstairs/downstairs story, illustrating with direct electrical recordings how the mouse brain switches between different action strategies (goal-directed and habitual). Goal directed action recruits the frontal cortex while habitual action correlates more with activity in a deeper subcortical structure, the striatum. More indirect imaging data show the story is almost surely same for us. It is the upstairs stuff that is more susceptible to aging, and most of us find it more of an effort to do novel versus habitual actions as we age.

Shifting between goal-directed and habitual actions allows for efficient and flexible decision making. Here we demonstrate a novel, within-subject instrumental lever-pressing paradigm, in which mice shift between goal-directed and habitual actions. We identify a role for orbitofrontal cortex (OFC) in actions following outcome revaluation, and confirm that dorsal medial (DMS) and lateral striatum (DLS) mediate different action strategies. Simultaneous in vivo recordings of OFC, DMS and DLS neuronal ensembles during shifting reveal that the same neurons display different activities depending on whether presses are goal-directed or habitual, with DMS and OFC becoming more and DLS less engaged during goal-directed actions. Importantly, the magnitude of neural activity changes in OFC following changes in outcome value positively correlates with the level of goal-directed behavior. Chemogenetic inhibition of OFC disrupts goal-directed actions, whereas optogenetic activation of OFC specifically increases goal-directed pressing. These results also reveal a role for OFC in action revaluation, which has implications for understanding compulsive behavior.

A brain correlate of near death hallucinations and visions?

Borjigin et al. make some fascinating observations on brain activity that occurs during the moments of cardiac arrest when brain glucose levels have dropped precipitously. Activity associated with information processing briefly increases 8-fold, a burst even after 'clinical death.' Maybe this is why some patients can recall conversation happening in the operating room.

The brain is assumed to be hypoactive during cardiac arrest. However, the neurophysiological state of the brain immediately following cardiac arrest has not been systematically investigated. In this study, we performed continuous electroencephalography in rats undergoing experimental cardiac arrest and analyzed changes in power density, coherence, directed connectivity, and cross-frequency coupling. We identified a transient surge of synchronous gamma oscillations that occurred within the first 30 s after cardiac arrest and preceded isoelectric electroencephalogram. Gamma oscillations during cardiac arrest were global and highly coherent; moreover, this frequency band exhibited a striking increase in anterior–posterior-directed connectivity and tight phase-coupling to both theta and alpha waves. High-frequency neurophysiological activity in the near-death state exceeded levels found during the conscious waking state. These data demonstrate that the mammalian brain can, albeit paradoxically, generate neural correlates of heightened conscious processing at near-death.

War of science and the humanities redux: Ross Douthat on The Scientism of Steven Pinker

I enjoyed a very well written article by Steven Pinker in the New Republic titled "Science is not your enemy", which argued that an increasing melding of science and the humanities should not be seen at a threat to, but rather as an expansion of, humanistic studies - enhanced by science's quest for intelligibility of the world and a quest for objectivity about its workings. Ross Douthat writes a critique that nails more clearly than I would have the insidious naturalistic fallacy that still lurks in Pinker's prose, the conflating of "is" with "ought to be". He notes that Pinker offers a

...defensible-if-tendentious account of how the progress of science has undercut the world-pictures bequeathed to us by tradition, intuition and religion. Now an innocent reader might assume that the crack-up of these world pictures, with their tight link between cosmic design and human purposes, might make moral consensus more difficult to realistically achieve. After all, if our universe’s testable laws and empirical realities have no experimentally-verifiable connection to human ends and values, then one would expect rival ideas of the good to have difficulty engaging with one another fruitfully, escaping from the pull of relativism or nihilism, and/or grounding their appeals in anything stronger than aesthetic preference.

But then cites the following passage from Pinker to point out that isn't where Pinker is going:

In other words, the worldview that guides the moral and spiritual values of an educated person today is the worldview given to us by science. Though the scientific facts do not by themselves dictate values, they certainly hem in the possibilities. By stripping ecclesiastical authority of its credibility on factual matters, they cast doubt on its claims to certitude in matters of morality. … The facts of science, by exposing the absence of purpose in the laws governing the universe, force us to take responsibility for the welfare of ourselves, our species, and our planet. For the same reason, they undercut any moral or political system based on mystical forces, quests, destinies, dialectics, struggles, or messianic ages. And in combination with a few unexceptionable convictions— that all of us value our own welfare and that we are social beings who impinge on each other and can negotiate codes of conduct—the scientific facts militate toward a defensible morality, namely adhering to principles that maximize the flourishing of humans and other sentient beings. This humanism, which is inextricable from a scientific understanding of the world, is becoming the de facto morality of modern democracies, international organizations, and liberalizing religions, and its unfulfilled promises define the moral imperatives we face today.

Douthat:

This is an impressively swift march from allowing, grudgingly, that scientific discoveries do not “dictate” values to asserting that they “militate” very strongly in favor of … why, of Steven Pinker’s very own moral worldview! You see, because we do not try witches, we must be utilitarians! Because we know the universe has no purpose, we must imbue it with the purposes of a (non-species-ist) liberal cosmopolitanism! Because of science, we know that modern civilization has no dialectic or destiny … so we must pursue its “unfulfilled promises” and accept its “moral imperatives” instead!

Douthat suggest Pinker is promulgating the Whig interpretation of history (from Wikipedia: Whig history ... is the approach to historiography which presents the past as an inevitable progression towards ever greater liberty and enlightenment, culminating in modern forms of liberal democracy and constitutional monarchy. In general, Whig historians emphasize the rise of constitutional government, personal freedoms and scientific progress. The term is often applied generally (and pejoratively) to histories that present the past as the inexorable march of progress toward enlightenment.)

Like Sam Harris, who wrote an entire book claiming that “science” somehow vindicates his preferred form of philosophical utilitarianism (when what he really meant was that if you assume utilitarian goals, science can help you pursue them), Pinker seems to have trouble imagining any reasoning person disagreeing about either the moral necessity of “maximizing human flourishing” or the content of what “flourishing” actually means — even though recent history furnishes plenty of examples and a decent imagination can furnish many more. Like his whiggish antecedents, he mistakes a real-but-complicated historical relationship between science and humanism for a necessary intellectual line in which the latter vindicates the former, or at least militates strongly in its favor. 

That's the nub of it. What authority does science have to define what "maximizing human flourishing" means?

Factoids on exercise and learning - the kind of exercise is important

In my scans of journals' tables of contents for potential MindBlog posts I keep an eye out for articles on exercise, probably the most life enhancing activity one can engage in. A large number of studies document enhancement of learning and memory in animals and people who exercise, and more structure is added to this effect by the study of Schmidt-Kassow et al., that shows that light to moderate physical activity while listening to equivalent nouns in German (familiar language) and Polish (the unfamiliar language) enhances the memorization of the unfamiliar words. Recall two days later was better for this group than for a group sitting quietly before the word presentations or another group that exercised just before the word presentations. Here is their abstract:

Acute physical activity has been repeatedly shown to improve various cognitive functions. However, there have been no investigations comparing the effects of exercise during verbal encoding versus exercise prior to encoding on long-term memory performance. In this current psychoneuroendocrinological study we aim to test whether light to moderate ergometric bicycling during vocabulary encoding enhances subsequent recall compared to encoding during physical rest and encoding after being physically active. Furthermore, we examined the kinetics of brain-derived neurotrophic factor (BDNF) in serum which has been previously shown to correlate with learning performance. We also controlled for the BDNF val66met polymorphism. We found better vocabulary test performance for subjects that were physically active during the encoding phase compared to sedentary subjects. Post-hoc tests revealed that this effect was particularly present in initially low performers. BDNF in serum and BDNF genotype failed to account for the current result. Our data indicates that light to moderate simultaneous physical activity during encoding, but not prior to encoding, is beneficial for subsequent recall of new items.

Another study finds a different result for more strenuous exercise during reading for which retention was tested. Exercise decreased retention tested immediately after exercise but after two days retention was the same for exercise and non-exercise groups. Perhaps the low level of physiological arousal in the first study primed the brain for the intake of new information while more vigorous exercise overstimulated and monopolized more of the brain's attentional resources. (This second study had only 11 subjects in the test group, versus 105 used for the first study.)

Do you have a tidy or messy desk?

Vohs et al. have done an interesting experiment that suggests that physical order enhances healthy choices, generosity, and conventionality, while disorder correlates with greater creativity. I don't go with their "novel hypothesis" description, but the results describe my partner and myself rather well (I'm the tidy one). The abstract:

Order and disorder are prevalent in both nature and culture, which suggests that each environ confers advantages for different outcomes. Three experiments tested the novel hypotheses that orderly environments lead people toward tradition and convention, whereas disorderly environments encourage breaking with tradition and convention—and that both settings can alter preferences, choice, and behavior. A first experiment showed that relative to participants in a disorderly room, participants in an orderly room chose healthier snacks and donated more money. A second experiment showed that participants in a disorderly room were more creative than participants in an orderly room. A final experiment showed a predicted crossover effect: Participants in an orderly room preferred an option labeled as classic, but those in a disorderly room preferred an option labeled as new. Whereas prior research on physical settings has shown that orderly settings encourage better behavior than disorderly ones, the current research tells a nuanced story of how different environments suit different outcomes.

Clips from the text:

Being in a clean room seemed to encourage people to do what was expected of them. Compared with participants in the messy room, they donated more of their own money to charity and were more likely to choose the apple over the candy bar....Being in a messy room led to something that firms, industries, and societies want more of: Creativity...Orderly environments promote convention and healthy choices, which could improve life by helping people follow social norms and boosting well-being. Disorderly environments stimulated creativity, which has widespread importance for culture, business, and the arts.

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.