More exercise correlates with younger body cells.

Reynolds points to work by Loprinzi et al. showing physicaly active people have longer telomeres at the end of their chromosomes' DNA strands than sedentary people. (A telomere is a region of repetitive nucleotide sequences at each end of a chromatid, which protects the end of the chromosome from deterioration from from fusion with neighboring chromosomes. It's length is a measure of a cell's biological age because it naturally shortens and frays with age.) Here is their abstract, complete with three (unnecessary) abbreviations, LTL (leukocyte telomere length), PA (physical activity) and MBB (movement based behaviors), that you will have to keep in your short term memory for a few seconds: 

INTRODUCTION: Short leukocyte telomere length (LTL) has become a hallmark characteristic of aging. Some, but not all, evidence suggests that physical activity (PA) may play an important role in attenuating age-related diseases and may provide a protective effect for telomeres. The purpose of this study was to examine the association between PA and LTL in a national sample of US adults from the National Health and Nutrition Examination Survey.  

METHODS: National Health and Nutrition Examination Survey data from 1999 to 2002 (n = 6503; 20-84 yr) were used. Four self-report questions related to movement-based behaviors (MBB) were assessed. The four MBB included whether individuals participated in moderate-intensity PA, vigorous-intensity PA, walking/cycling for transportation, and muscle-strengthening activities. An MBB index variable was created by summing the number of MBB an individual engaged in (range, 0-4).  

RESULTS: A clear dose-response relation was observed between MBB and LTL; across the LTL tertiles, respectively, the mean numbers of MBB were 1.18, 1.44, and 1.54 (Ptrend less than 0.001). After adjustments (including age) and compared with those engaging in 0 MBB, those engaging in 1, 2, 3, and 4 MBB, respectively, had a 3% (P = 0.84), 24% (P = 0.02), 29% (P = 0.04), and 52% (P = 0.004) reduced odds of being in the lowest (vs highest) tertile of LTL; MBB was not associated with being in the middle (vs highest) tertile of LTL.  

CONCLUSIONS: Greater engagement in MBB was associated with reduced odds of being in the lowest LTL tertile.

Low-power people are more trusting in social exchange.

Schilke et al. make observations suggestion that low-power individuals want high-power people they interact with to be trustworthy, and act according to that desire:

How does lacking vs. possessing power in a social exchange affect people’s trust in their exchange partner? An answer to this question has broad implications for a number of exchange settings in which dependence plays an important role. Here, we report on a series of experiments in which we manipulated participants’ power position in terms of structural dependence and observed their trust perceptions and behaviors. Over a variety of different experimental paradigms and measures, we find that more powerful actors place less trust in others than less powerful actors do. Our results contradict predictions by rational actor models, which assume that low-power individuals are able to anticipate that a more powerful exchange partner will place little value on the relationship with them, thus tends to behave opportunistically, and consequently cannot be trusted. Conversely, our results support predictions by motivated cognition theory, which posits that low-power individuals want their exchange partner to be trustworthy and then act according to that desire. Mediation analyses show that, consistent with the motivated cognition account, having low power increases individuals’ hope and, in turn, their perceptions of their exchange partners’ benevolence, which ultimately leads them to trust.

How much sleep do we really need?

A study by Yetish et al. casts fascinating light on the widespread idea that a large fraction of us in modern industrial societies are sleep-deprived, going to bed later than is "natural" and sleeping less than our bodies need. They monitored the sleep patterns of three hunter-gatherer cultures in Bolivia, Tanzania, and South Africa. Here is their summary:

Highlights

•Preindustrial societies in Tanzania, Namibia, and Bolivia show similar sleep parameters
•They do not sleep more than “modern” humans, with average durations of 5.7–7.1 hr
•They go to sleep several hours after sunset and typically awaken before sunrise
•Temperature appears to be a major regulator of human sleep duration and timing

Summary 

How did humans sleep before the modern era? Because the tools to measure sleep under natural conditions were developed long after the invention of the electric devices suspected of delaying and reducing sleep, we investigated sleep in three preindustrial societies. We find that all three show similar sleep organization, suggesting that they express core human sleep patterns, most likely characteristic of pre-modern era Homo sapiens. Sleep periods, the times from onset to offset, averaged 6.9–8.5 hr, with sleep durations of 5.7–7.1 hr, amounts near the low end of those industrial societies. There was a difference of nearly 1 hr between summer and winter sleep. Daily variation in sleep duration was strongly linked to time of onset, rather than offset. None of these groups began sleep near sunset, onset occurring, on average, 3.3 hr after sunset. Awakening was usually before sunrise. The sleep period consistently occurred during the nighttime period of falling environmental temperature, was not interrupted by extended periods of waking, and terminated, with vasoconstriction, near the nadir of daily ambient temperature. The daily cycle of temperature change, largely eliminated from modern sleep environments, may be a potent natural regulator of sleep. Light exposure was maximal in the morning and greatly decreased at noon, indicating that all three groups seek shade at midday and that light activation of the suprachiasmatic nucleus is maximal in the morning. Napping occurred on fewer than 7% of days in winter and fewer than 22% of days in summer. Mimicking aspects of the natural environment might be effective in treating certain modern sleep disorders.

Chilling down our religiousity and intolerance with some magnets?

A group of collaborators has used transcranial magnetic stimulation to dial down activity in the area of the posterior medial frontal cortex (pMFC)that evaluates threats and plans responses. A group of subjects who had undergone this procedure expressed less bias against immigrants and also less belief in God than a group that received a sham TMS treatment.

People cleave to ideological convictions with greater intensity in the aftermath of threat. The posterior medial frontal cortex (pMFC) plays a key role in both detecting discrepancies between desired and current conditions and adjusting subsequent behavior to resolve such conflicts. Building on prior literature examining the role of the pMFC in shifts in relatively low-level decision processes, we demonstrate that the pMFC mediates adjustments in adherence to political and religious ideologies. We presented participants with a reminder of death and a critique of their in-group ostensibly written by a member of an out-group, then experimentally decreased both avowed belief in God and out-group derogation by downregulating pMFC activity via transcranial magnetic stimulation. The results provide the first evidence that group prejudice and religious belief are susceptible to targeted neuromodulation, and point to a shared cognitive mechanism underlying concrete and abstract decision processes. We discuss the implications of these findings for further research characterizing the cognitive and affective mechanisms at play.

The hippocampus is essential for recall but not for recognition.

From Patai et al:

Which specific memory functions are dependent on the hippocampus is still debated. The availability of a large cohort of patients who had sustained relatively selective hippocampal damage early in life enabled us to determine which type of mnemonic deficit showed a correlation with extent of hippocampal injury. We assessed our patient cohort on a test that provides measures of recognition and recall that are equated for difficulty and found that the patients' performance on the recall tests correlated significantly with their hippocampal volumes, whereas their performance on the equally difficult recognition tests did not and, indeed, was largely unaffected regardless of extent of hippocampal atrophy. The results provide new evidence in favor of the view that the hippocampus is essential for recall but not for recognition.

Brain activity associated with predicting rewards to others.

Lockwood et al. make the interesting observation that a subregion of the anterior cingulate cortex shows specialization for processing others' versus one's own rewards.

Empathy—the capacity to understand and resonate with the experiences of others—can depend on the ability to predict when others are likely to receive rewards. However, although a plethora of research has examined the neural basis of predictions about the likelihood of receiving rewards ourselves, very little is known about the mechanisms that underpin variability in vicarious reward prediction. Human neuroimaging and nonhuman primate studies suggest that a subregion of the anterior cingulate cortex in the gyrus (ACCg) is engaged when others receive rewards. Does the ACCg show specialization for processing predictions about others' rewards and not one's own and does this specialization vary with empathic abilities? We examined hemodynamic responses in the human brain time-locked to cues that were predictive of a high or low probability of a reward either for the subject themselves or another person. We found that the ACCg robustly signaled the likelihood of a reward being delivered to another. In addition, ACCg response significantly covaried with trait emotion contagion, a necessary foundation for empathizing with other individuals. In individuals high in emotion contagion, the ACCg was specialized for processing others' rewards exclusively, but for those low in emotion contagion, this region also responded to information about the subject's own rewards. Our results are the first to show that the ACCg signals probabilistic predictions about rewards for other people and that the substantial individual variability in the degree to which the ACCg is specialized for processing others' rewards is related to trait empathy.

Drugs or therapy for depression?

I want to pass on a few clips from a piece by Friedman, summarizing work by Mayberg and collaborators at Emory University, who looked for brain activity that might predict whether a depressed patient would respond better to psychotherapy or antidepressant medication:

Using PET scans, she randomized a group of depressed patients to either 12 weeks of treatment with the S.S.R.I. antidepressant Lexapro or to cognitive behavior therapy, which teaches patients to correct their negative and distorted thinking.

Over all, about 40 percent of the depressed subjects responded to either treatment. But Dr. Mayberg found striking brain differences between patients who did well with Lexapro compared with cognitive behavior therapy, and vice versa. Patients who had low activity in a brain region called the anterior insula measured before treatment responded quite well to C.B.T. but poorly to Lexapro; conversely, those with high activity in this region had an excellent response to Lexapro, but did poorly with C.B.T.

We know that the insula is centrally involved in the capacity for emotional self-awareness, cognitive control and decision making, all of which are impaired by depression. Perhaps cognitive behavior therapy has a more powerful effect than an antidepressant in patients with an underactive insula because it teaches patients to control their emotionally disturbing thoughts in a way that an antidepressant cannot.

These neurobiological differences may also have important implications for treatment, because for most forms of depression, there is little evidence to support one form of treatment over another...Currently, doctors typically prescribe antidepressants on a trial-and-error basis, selecting or adding one antidepressant after another when a patient fails to respond to the first treatment. Rarely does a clinician switch to an empirically proven psychotherapy like cognitive behavior therapy after a patient fails to respond to medication, although these data suggest this might be just the right strategy. One day soon, we may be able to quickly scan a patient with an M.R.I. or PET, check the brain activity “fingerprint” and select an antidepressant or psychotherapy accordingly.

Is the nonspecific nature of talk therapy — feeling understood and cared for by another human being — responsible for its therapeutic effect? Or will specific types of therapy — like C.B.T. or interpersonal or psychodynamic therapy — show distinctly different clinical and neurobiological effects for various psychiatric disorders?...Right now we don’t have a clue, in part because of the current research funding priorities of the National Institute of Mental Health, which strongly favors brain science over psychosocial treatments. But these are important questions, and we owe it to our patients to try to answer them.

Hoopla over a bit of rat brain…a complete brain simulation?

A vastly expensive and heavily marketed international collaborative "Blue Brain Project (BBP)" has now reported its first digital reconstruction of a slice of rat somatosensory cortex, the most complete simulation of a piece of excitable brain matter to date (still, a speck of tissue compared to the human brain, which is two million times larger).  I, along with a chorus of critics, can not see how a static depiction and reconstruction of a cortical column (~30,000 neurons, ~40 million synapses) is anything but a waste of money. The biological reality is that those neurons and synapses are not just sitting there, with static components cranking away like the innards of a computer. The wiring is plastic, constantly changing as axons, dendrites, and synapses both grow and retract, changing the number and kind of their connections over which information flows.

Koch and Buice make the generous point that all this might not matter if one could devise the biological equivalent of Alan Turing's Imitation game, seeing if an observer could tell whether output they observe for a given input is being generated by the simulation or by electrical recording from living tissue. Here are some interesting clips from their article in Cell.

...the current BBP model stops with the continuous and deterministic Hodgkin-Huxley currents...And therein lies an important lesson. If the real and the synthetic can’t be distinguished at the level of firing rate activity (even though it is uncontroversial that spiking is caused by the concerted action of tens of thousands of ionic channel proteins), the molecular level of granularity would appear to be irrelevant to explain electrical activity. Teasing out which mechanisms contribute to any specific phenomena is essential to what is meant by understanding.

Markram et al. claim that their results point to the minimal datasets required to model cortex. However, we are not aware of any rigorous argument in the present triptych of manuscripts, specifying the relevant level of granularity. For instance, are active dendrites, such as those of the tall, layer 5 pyramidal cells, essential? Could they be removed without any noticeable effect? Why not replace the continuous, macroscopic, and deterministic HH equations with stochastic Markov models of thousands of tiny channel conductances? Indeed, why not consider quantum mechanical levels of descriptions? Presumably, the latter two avenues have not been chosen because of their computational burden and the intuition that they are unlikely to be relevant. The Imitation Game offers a principled way of addressing these important questions: only add a mechanism if its impact on a specific set of measurables can be assessed by a trained observer.

Consider the problem of numerical weather prediction and climate modeling, tasks whose physico-chemical and computational complexity is comparable to whole-brain modeling. Planet-wide simulations that cover timescales from hours to decades require a deep understanding of how physical systems interact across multiple scales and careful choices about the scale at which different phenomena are modeled. This has led to an impressive increase in predictive power since 1950, when the first such computer calculations were performed. Of course, a key difference between weather prediction and whole-brain simulation is that the former has a very specific and quantifiable scientific question (to wit: “is it going to rain tomorrow?”). The BBP has created an impressive initial scaffold that will facilitate asking these kinds of questions for brains.

Meditation madness

Adam Grant does a NYTimes Op-Ed piece that mirrors some of my own sentiments about the current meditation craze. There would seem to be almost nothing that practicing meditation doesn't enhance (ingrown toenails?) I'm fascinated by what studies on meditation have told us about how the mind works, and MindBlog has done many posts on the topic (click the meditation link under 'selected blog categories' in the right column.) I and many others personally find it very useful in maintaining a calm and focused mind.  But.... it is not a universal panacea, and many of its effects can be accomplished, as Grant points out, by other means. (By the way, a Wisconsin colleague of mine who has assisted in a number of the meditation studies conducted by Richard Davidson and collaborators at the University of Wisconsin feels that people who engage meditation regimes display more depressive behaviors after a period of time.) Some clips from Grant's screed:

...Every benefit of the practice can be gained through other activities...This is the conclusion from an analysis of 47 trials of meditation programs, published last year in JAMA Internal Medicine: “We found no evidence that meditation programs were better than any active treatment (i.e., drugs, exercise and other behavioral therapies).”

O.K., so meditation is just one of many ways to fight stress. But there’s another major benefit of meditating: It makes you mindful. After meditating, people are more likely to focus their attention in the present. But as the neuroscientist Richard Davidson and the psychologist Alfred Kaszniak recently lamented, “There are still very few methodologically rigorous studies that demonstrate the efficacy of mindfulness-based interventions in either the treatment of specific diseases or in the promotion of well-being.”

And guess what? You don’t need to meditate to achieve mindfulness either...you can become more mindful by thinking in conditionals instead of absolutes...Change “is” to “could be,” and you become more mindful. The same is true when you look for an answer rather than the answer.

(I would also point out that 'mindfulness' can frequently be generated by switching in your thoughts from a first to a third person perspective.) Finally:

...in some situations, meditation may be harmful: Willoughby Britton, a Brown University Medical School professor, has discovered numerous cases of traumatic meditation experiences that intensify anxiety, reduce focus and drive, and leave people feeling incapacitated.

A brain switch that can make the familiar seem new?

We all face the issue how to refresh and renew our energy and perspective after our brains have adapted, habituated, or densensitized to an ongoing interest or activity that lost its novelty. As I engage my long term interests in piano performance and studying how our minds work, I wish I could throw a "reset" switch in my brain that would let me approach the material as if it were new again. Ho et al. appear to have found such a switch, in the perirhinal cortex of rats, that regulates whether images are perceived as familiar or novel:

Perirhinal cortex (PER) has a well established role in the familiarity-based recognition of individual items and objects. For example, animals and humans with perirhinal damage are unable to distinguish familiar from novel objects in recognition memory tasks. In the normal brain, perirhinal neurons respond to novelty and familiarity by increasing or decreasing firing rates. Recent work also implicates oscillatory activity in the low-beta and low-gamma frequency bands in sensory detection, perception, and recognition. Using optogenetic methods in a spontaneous object exploration (SOR) task, we altered recognition memory performance in rats. In the SOR task, normal rats preferentially explore novel images over familiar ones. We modulated exploratory behavior in this task by optically stimulating channelrhodopsin-expressing perirhinal neurons at various frequencies while rats looked at novel or familiar 2D images. Stimulation at 30–40 Hz during looking caused rats to treat a familiar image as if it were novel by increasing time looking at the image. Stimulation at 30–40 Hz was not effective in increasing exploration of novel images. Stimulation at 10–15 Hz caused animals to treat a novel image as familiar by decreasing time looking at the image, but did not affect looking times for images that were already familiar. We conclude that optical stimulation of PER at different frequencies can alter visual recognition memory bidirectionally.

Unfortunately, given that rather fancy optogenetic methods were used to vary oscillatory activity in the perirhinal cortex, no human applications of this work are imminent.

Sir Reginald's Marvellous Organ

Under the "random curious stuff" category noted in MindBlog's title, above, I can't resist passing on this naughty video sent by a friend...apologies to sensitive readers who only want the brain stuff.

Great apes can look ahead in time

Yet another supposed distinction between human and animal minds has bit the dust. The prevailing dogma (expressed in my talk "The Beast Within") has been that animals don't anticipate the future. Now Kano and Hirata show that chimpanzees remember a movie they viewed a day earlier, because when the movie is shown again their eyes move to a part of the screen where an action is about to happen that is relevant to the storyline.

Highlights

•We developed a novel eye-tracking task to examine great apes’ memory skills
•Apes watched the same videos twice across 2 days, with a 24-hr delay
•Apes made anticipatory looks based on where-what information on the second day
•Apes thus encoded ongoing events into long-term memory by single experiences

Summary

Everyday life poses a continuous challenge for individuals to encode ongoing events, retrieve past events, and predict impending events. Attention and eye movements reflect such online cognitive and memory processes, especially through “anticipatory looks”. Previous studies have demonstrated the ability of nonhuman animals to retrieve detailed information about single events that happened in the distant past. However, no study has tested whether nonhuman animals employ online memory processes, in which they encode ongoing movie-like events into long-term storage during single viewing experiences. Here, we developed a novel eye-tracking task to examine great apes’ anticipatory looks to the events that they had encountered one time 24 hr earlier. Half-minute movie clips depicted novel and potentially alarming situations to the participant apes (six bonobos, six chimpanzees). In the experiment 1 clip, an aggressive ape-like character came out from one of two identical doors. While viewing the same movie again, apes anticipatorily looked at the door where the character would show up. In the experiment 2 clip, the human actor grabbed one of two objects and attacked the character with it. While viewing the same movie again but with object-location switched, apes anticipatorily looked at the object that the human would use, rather than the former location of the object. Our results thus show that great apes, just by watching the events once, encoded particular information (location and content) into long-term memory and later retrieved that information at a particular time in anticipation of the impending events.

Rhodopsin curing blindness?

In a previous life (1962-1998) my laboratory studied how the rhodopsin visual pigment in our eyes changes light into a nerve signal. Thus it excites me when I see major advances in understanding our vision and curing visual diseases. I want to pass on a nice graphic offered by Van Gelder and Kaur to illustrate recent work of Cehajic-Kapetanovic et al. (open access) showing that introduction of the visual pigment rhodopsin by viral gene therapy into the inner retina nerve cells of retinas whose rods and cones have degenerated can restore light sensitivity and can restore vision-like physiology and behavior to mice blind from outer retinal degeneration:

(click figure to enlarge)   Gene therapy rescue of vision in retinal degeneration. (A) In the healthy retina, light penetrates from inner to outer retina to reach the cones and rods, which transduce signals through horizontal, bipolar, amacrine, and ultimately retinal ganglion cells to the brain. (B) In outer retinal degenerative diseases, loss of photoreceptors renders the retina insensitive to light. (C) Gene therapy with AAV2/2 virus expressing human rhodopsin (hRod) under the control of the CAG promoter results in expression of the photopigment in many surviving cells of the inner retina, and results in restoration of light responses recognized by the brain. (D) More selective expression of rhodopsin in a subset of bipolar cells is achieved by use of a virus in which expression is driven by the grm6 promoter. This version appeared to restore the most natural visual function to blind mice.

Can epigenetics explain homosexuality?

Michael Balter notes work presented by Vilain's UCLA laboratory at this year's American Society of Human Genetics meeting. His abstract, followed by some clips of his text:

(added note: an alert reader, see comment below, just added this critique of the following work from The Atlantic)

A new study suggests that epigenetic effects—chemical modifications of the human genome that alter gene activity without changing the DNA sequence—may sometimes influence sexual orientation. Researchers studied methylation, the attachment of a methyl group to specific regions of DNA, in 37 pairs of male identical twins who were discordant—meaning that one was gay and the other straight—and 10 pairs who were both gay. Their search yielded five genome regions where the methylation pattern appears very closely linked to sexual orientation. A model that predicted sexual orientation based on these patterns was almost 70% accurate within this group—although that predictive ability does not necessarily apply to the general population.

Researchers thought they were hot on the trail of “gay genes” in 1993, when a team led by geneticist Dean Hamer of the National Cancer Institute reported that one or more genes for homosexuality had to reside on Xq28, a large region on the X chromosome...but some teams were unable to replicate the findings and the actual genes have not been found...Twin studies suggested, moreover, that gene sequences can't be the full explanation. For example, the identical twin of a gay man, despite having the same genome, only has a 20% to 50% chance of being gay himself.

That's why some have suggested that epigenetics—instead of or in addition to traditional genetics—might be involved. During development, chromosomes are subject to chemical changes that don't affect the nucleotide sequence but can turn genes on or off; the best known example is methylation, in which a methyl group is attached to specific DNA regions. Such “epi-marks” can remain in place for a lifetime, but most are erased when eggs and sperm are produced, so that a fetus starts with a blank slate. Recent studies, however, have shown that some marks are passed on to the next generation.

In a 2012 paper, Rice and his colleagues suggested that such unerased epi-marks might cause homosexuality when they are passed on from father to daughter or from mother to son...Such ideas inspired Tuck Ngun, a postdoc in Vilain's lab, to study the methylation patterns at 140,000 regions in the DNA of 37 pairs of male identical twins who were discordant—meaning that one was gay and the other straight—and 10 pairs who were both gay...the team identified five regions in the genome where the methylation pattern appears very closely linked to sexual orientation...Just why identical twins sometimes end up with different methylation patterns isn't clear. If Rice's hypothesis is right, their mothers' epi-marks might have been erased in one son, but not the other; or perhaps neither inherited any marks but one of them picked them up in the womb...In an earlier review, Ngun and Vilain cited evidence that methylation may be determined by subtle differences in the environment each fetus experiences during gestation, such as their exact locations within the womb and how much of the maternal blood supply each receives.

Musical expertise changes the brain's functional connectivity during audiovisual integration

Music notation reading encapsulates auditory, visual, and motor information in a highly organized manner and therefore provides a useful model for studying multisensory phenomena. Paraskevopoulos et al. show that large-scale functional brain networks underpinning audiovisual integration are organized differently in musicians and nonmusicians. They examine brain responses to congruent (sound played corresponding to musical notation) and incongruent (sound played different from notation) stimuli.

Multisensory integration engages distributed cortical areas and is thought to emerge from their dynamic interplay. Nevertheless, large-scale cortical networks underpinning audiovisual perception have remained undiscovered. The present study uses magnetoencephalography and a methodological approach to perform whole-brain connectivity analysis and reveals, for the first time to our knowledge, the cortical network related to multisensory perception. The long-term training-related reorganization of this network was investigated by comparing musicians to nonmusicians. Results indicate that nonmusicians rely on processing visual clues for the integration of audiovisual information, whereas musicians use a denser cortical network that relies mostly on the corresponding auditory information. These data provide strong evidence that cortical connectivity is reorganized due to expertise in a relevant cognitive domain, indicating training-related neuroplasticity.

Figure - Paradigm of an audiovisual congruent and incongruent trial. (A) A congruent trial. (B) An incongruent trial. The line “time” represents the duration of the presentation of the auditory and visual part of the stimulus. The last picture of each trial represents the intertrial stimulus in which subjects had to answer if the trial was congruent or incongruent.

Figure - Cortical network underpinning audiovisual integration. (Upper) Statistical parametric maps of the significant networks for the congruent > incongruent comparison. Networks presented are significant at P less than 0.001, FDR corrected. The color scale indicates t values. (Lower) Node strength of the significant networks for each comparison. Strength is represented by node size.

Runner's high? Thank your internal marijuana...

From Fuss et al.:

Exercise is rewarding, and long-distance runners have described a runner’s high as a sudden pleasant feeling of euphoria, anxiolysis, sedation, and analgesia. A popular belief has been that endogenous endorphins mediate these beneficial effects. However, running exercise increases blood levels of both β-endorphin (an opioid) and anandamide (an endocannabinoid). Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running. We show that anxiolysis depends on intact cannabinoid receptor 1 (CB1) receptors on forebrain GABAergic neurons and pain reduction on activation of peripheral CB1 and CB2 receptors. We thus demonstrate that the endocannabinoid system is crucial for two main aspects of a runner's high. Sedation, in contrast, was not influenced by cannabinoid or opioid receptor blockage, and euphoria cannot be studied in mouse models.

A Gee Whiz! moment. Activating neurons with ultrasound.

Optogenetics, making nerve cells sensitive to light by a genetic manipulation, has the limitation that light doesn't penetrate living tissue very well, and so must be delivered by a invasive thin fiber optic stimulation. Frank and Gorman offer a video clip describing work of Ibsen et al., who show a nerve cell can be genetically altered to become sensitive to activation by non-invasive ultrasound, an approach they described as "sonogenetics." The video (I could do without the rock music sound track) shows a worm's movement changing direction as a nerve cell is stimulated by ultrasound.

1/f brain noise increases with aging.

From Gazzaley and collaborators, a description of what in going on in our aging brains:

Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15–53 years) and scalp EEG data from healthy younger (20–30 years) and older (60–70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <−1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging.

Methionine, an amino acid, enhances recovery from cocaine addiction.

Wright et al. use a mouse model to show that the common amino acid methionine - which can serve as a methyl group donor for the DNA methylation that regulates neural functions associated with learning, memory, and synaptic plasticity - can reduce addictive like behaviors such as drug seeking, and block a cocaine-induced marker of neuronal activation after reinstatement in the nucleus accumbens and the medial prefrontal cortex, two brain regions responsible for drug seeking and relapse. Here is the technical abstract:

Epigenetic mechanisms, such as histone modifications, regulate responsiveness to drugs of abuse, such as cocaine, but relatively little is known about the regulation of addictive-like behaviors by DNA methylation. To investigate the influence of DNA methylation on the locomotor-activating effects of cocaine and on drug-seeking behavior, rats receiving methyl supplementation via chronic L-methionine (MET) underwent either a sensitization regimen of intermittent cocaine injections or intravenous self-administration of cocaine, followed by cue-induced and drug-primed reinstatement. MET blocked sensitization to the locomotor-activating effects of cocaine and attenuated drug-primed reinstatement, with no effect on cue-induced reinstatement or sucrose self-administration and reinstatement. Furthermore, upregulation of DNA methyltransferase 3a and 3b and global DNA hypomethylation were observed in the nucleus accumbens core (NAc), but not in the medial prefrontal cortex (mPFC), of cocaine-pretreated rats. Glutamatergic projections from the mPFC to the NAc are critically involved in the regulation of cocaine-primed reinstatement, and activation of both brain regions is seen in human addicts when reexposed to the drug. When compared with vehicle-pretreated rats, the immediate early gene c-Fos (a marker of neuronal activation) was upregulated in the NAc and mPFC of cocaine-pretreated rats after cocaine-primed reinstatement, and chronic MET treatment blocked its induction in both regions. Cocaine-induced c-Fos expression in the NAc was associated with reduced methylation at CpG dinucleotides in the c-Fos gene promoter, effects reversed by MET treatment. Overall, these data suggest that drug-seeking behaviors are, in part, attributable to a DNA methylation-dependent process, likely occurring at specific gene loci (e.g., c-Fos) in the reward pathway.

Memory aging and brain maintenance

An open access article by Nyberg et al. notes

The association of intact memory functioning in old age with maintenance and preservation of a functionally young and healthy brain may seem obvious. However, up to the present the focus has largely been on possible forms of compensatory brain responses. This is so, even though it remains unclear whether memory performance in old age can benefit from altered patterns of brain activation, with almost as many studies showing positive as negative relationships.

Their abstract suggests the relevance of "brain maintenance":

Episodic memory and working memory decline with advancing age. Nevertheless, large-scale population-based studies document well-preserved memory functioning in some older individuals. The influential ‘reserve’ notion holds that individual differences in brain characteristics or in the manner people process tasks allow some individuals to cope better than others with brain pathology and hence show preserved memory performance. Here, we discuss a complementary concept, that of brain maintenance (or relative lack of brain pathology), and argue that it constitutes the primary determinant of successful memory aging. We discuss evidence for brain maintenance at different levels: cellular, neurochemical, gray- and white-matter integrity, and systems-level activation patterns. Various genetic and lifestyle factors support brain maintenance in aging and interventions may be designed to promote maintenance of brain structure and function in late life.

The figures are worth a look, for they illustrate how a fraction of older individuals have brains that, at different levels of brain organization, are similar to younger brains in their relative lack of brain pathology. They say very little about the "lifestyle factors" or "interventions" that might promote brain maintenance.

The wealthy are different from you and me...

The abstract from an article titled "The distributional preferences of an elite" by Fisman et al.:

We studied the distributional preferences of an elite cadre of Yale Law School students, a group that will assume positions of power in U.S. society. Our experimental design allows us to test whether redistributive decisions are consistent with utility maximization and to decompose underlying preferences into two qualitatively different tradeoffs: fair-mindedness versus self-interest, and equality versus efficiency. Yale Law School subjects are more consistent than subjects drawn from the American Life Panel, a diverse sample of Americans. Relative to the American Life Panel, Yale Law School subjects are also less fair-minded and substantially more efficiency-focused. We further show that our measure of equality-efficiency tradeoffs predicts Yale Law School students’ career choices: Equality-minded subjects are more likely to be employed at nonprofit organizations.

Watching sleep deprivation cause a decline in prefrontal control of emotion.

From Simon et al.:

Sleep deprivation has been shown recently to alter emotional processing possibly associated with reduced frontal regulation. Such impairments can ultimately fail adaptive attempts to regulate emotional processing (also known as cognitive control of emotion), although this hypothesis has not been examined directly. Therefore, we explored the influence of sleep deprivation on the human brain using two different cognitive–emotional tasks, recorded using fMRI and EEG. Both tasks involved irrelevant emotional and neutral distractors presented during a competing cognitive challenge, thus creating a continuous demand for regulating emotional processing. Results reveal that, although participants showed enhanced limbic and electrophysiological reactions to emotional distractors regardless of their sleep state, they were specifically unable to ignore neutral distracting information after sleep deprivation. As a consequence, sleep deprivation resulted in similar processing of neutral and negative distractors, thus disabling accurate emotional discrimination. As expected, these findings were further associated with a decrease in prefrontal connectivity patterns in both EEG and fMRI signals, reflecting a profound decline in cognitive control of emotion. Notably, such a decline was associated with lower REM sleep amounts, supporting a role for REM sleep in overnight emotional processing. Altogether, our findings suggest that losing sleep alters emotional reactivity by lowering the threshold for emotional activation, leading to a maladaptive loss of emotional neutrality.

Ig Nobel Prizes for 2015

This year’s Ig Nobel Prizes, awarded in an annual ceremony in Harvard University’s Sanders Theater:

Chemistry prize - for inventing a chemical recipe to partially un-boil an egg.

Physics prize - for testing the biological principle that nearly all mammals empty their bladders in about 21 seconds (bigger bladders gush faster on emptying).

Literature prize - for discovering that the word "huh?" (or its equivalent) seems to exist in every human language — and for not being quite sure why.

Economics prize - to the Bangkok, Thailand, Metropolitan Police, for offering to pay policemen extra cash if the policemen refuse to take bribes.

Medicine prize - for experiments to study the biomedical benefits or biomedical consequences of intense kissing (and other intimate, interpersonal activities).

Mathematics prize - for trying to use mathematical techniques to determine whether and how Moulay Ismael the Bloodthirsty, the Sharifian Emperor of Morocco, managed, during the years from 1697 through 1727, to father 888 children.

Biology prize - for observing that when you attach a weighted stick to the rear end of a chicken, the chicken then walks in a manner similar to that in which dinosaurs are thought to have walked.

Diagnostic Medicine prize - for determining that acute appendicitis can be accurately diagnosed by the amount of pain evident when the patient is driven over speed bumps.

Physiology and Entomology prize - Awarded jointly to two individuals: Justin Schmidt [USA, CANADA], for painstakingly creating the Schmidt Sting Pain Index, which rates the relative pain people feel when stung by various insects; and to Michael L. Smith [USA, UK, THE NETHERLANDS], for carefully arranging for honey bees to sting him repeatedly on 25 different locations on his body, to learn which locations are the least painful (the skull, middle toe tip, and upper arm). and which are the most painful (the nostril, upper lip, and penis shaft).

For a full description of recipients and journal references, see this link.

Brain system for mental orientation in space, time, and person.

Peer and collaborators show that mental orientation in space, time, and person produces a sequential posterior–anterior pattern of activity in each participant’s brain.

Processing of spatial, temporal, and social relations relies on mental cognitive maps, on which the behaving self is oriented relative to different places, events, and people. Using high-resolution functional MRI scanning in individual subjects, we show that mental orientation in space, time, and person produces a sequential posterior–anterior pattern of activity in each participant’s brain. These activations are adjacent and partially overlapping, highlighting the relation between mental orientation in these domains. Furthermore, the activity is highly overlapping with the brain’s default-mode network, a system involved in self-referential processing. These findings may shed new light on fundamental cognitive processing of space, time, and person and alter our understanding of disorientation phenomena in neuropsychiatric disorders such as Alzheimer’s disease.

Midsagittal cortical activity during orientation in space, time, and person. (A) Domain-specific activity in a representative subject, identified by contrasting activity between each orientation domain and the other two domains. The precuneus region is active in all three orientation domains, and the medial prefrontal cortex only in person and time orientation. Dashed black lines represent the limit of the scanned region in this subject. (B) Precuneus activity in four subjects, demonstrating a highly consistent posterior–anterior organization (white dashed line); all other subjects showed the same activity pattern (Fig. S1). (C) Group average (n = 16) of event-related activity in independent experimental runs demonstrates the specificity of each cluster to one orientation domain. Lines represent activity in response to space (blue), time (green), and person (red) conditions. Error bars represent SEM between subjects. (D) Group average of beta plots from volume-of-interest GLM analysis, showing highly significant domain-specific activity. Error bars represent SEM between subjects. P, person; S, space; T, time.

More exercise correlates with younger body cells.

Reynolds points to work by Loprinzi et al. showing physically active people have longer telomeres at the end of their chromosomes' DNA strands than sedentary people. (A telomere is a region of repetitive nucleotide sequences at each end of a chromatid, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. It's length is a measure of a cell's biological age because it naturally shortens and frays with age.) Here is their abstract, complete with three (unnecessary) abbreviations, LTL (leukocyte telomere length), PA (physical activity) and MBB (Movement based behaviors), that you will have to keep in your short term memory for a few seconds:

INTRODUCTION: Short leukocyte telomere length (LTL) has become a hallmark characteristic of aging. Some, but not all, evidence suggests that physical activity (PA) may play an important role in attenuating age-related diseases and may provide a protective effect for telomeres. The purpose of this study was to examine the association between PA and LTL in a national sample of US adults from the National Health and Nutrition Examination Survey.

METHODS: National Health and Nutrition Examination Survey data from 1999 to 2002 (n = 6503; 20-84 yr) were used. Four self-report questions related to movement-based behaviors (MBB) were assessed. The four MBB included whether individuals participated in moderate-intensity PA, vigorous-intensity PA, walking/cycling for transportation, and muscle-strengthening activities. An MBB index variable was created by summing the number of MBB an individual engaged in (range, 0-4).

RESULTS: A clear dose-response relation was observed between MBB and LTL; across the LTL tertiles, respectively, the mean numbers of MBB were 1.18, 1.44, and 1.54 (Ptrend less than 0.001). After adjustments (including age) and compared with those engaging in 0 MBB, those engaging in 1, 2, 3, and 4 MBB, respectively, had a 3% (P = 0.84), 24% (P = 0.02), 29% (P = 0.04), and 52% (P = 0.004) reduced odds of being in the lowest (vs highest) tertile of LTL; MBB was not associated with being in the middle (vs highest) tertile of LTL.

CONCLUSIONS: Greater engagement in MBB was associated with reduced odds of being in the lowest LTL tertile.

Does exercise change your brain?

After yesterday's post suggesting no effects of common dietary supplements on cognitive changes with aging, I thought I would note work regarding exercise and brain health. mentioned by Reynolds, in particular a study by Burzynska et al. that monitored the daily activities of non-athletes:

...the most physically active elderly volunteers, according to their activity tracker data, had better oxygenation and healthier patterns of brain activity than the more sedentary volunteers — especially in parts of the brain, including the hippocampus, that are known to be involved in improved memory and cognition, and in connecting different brain areas to one another. Earlier brain scan experiments by Dr. Burzynska and her colleagues had established that similar brain activity in elderly people is associated with higher scores on cognitive tests.

Again, there is the caveat that a correlation does not prove a cause.

Can dietary supplements fight cognitive decline?

Maybe not...It is known that people who eat diets rich in fish and antioxidants have better brain health, but this association does not prove cause and effect. Rabin points to a recent massive NIH study of ~3,500 subjects that finds no cognitive effects of dietary supplementation wtih long-chain polyunsaturated fatty acids (LCPUFAs) (1 g) and/or lutein (10 mg)/zeaxanthin (2 mg) (tested vs placebo in a factorial design). All participants were also given varying combinations of vitamins C, E, beta carotene, and zinc. Participants,recruited by retinal specialists in 82 US academic and community medical centers as being at risk for developing late age-related macular degeneration, underwent cognitive tests every two years during the 5-year study. The bottom line: "A total of 89% (3741/4203) of the Age-Related Eye Disease Study 2 participants consented to the ancillary cognitive function study and 93.6% (3501/3741) underwent cognitive function testing. The mean (SD) age of the participants was 72.7 (7.7) years and 57.5% were women. There were no statistically significant differences in change of scores for participants randomized to receive supplements vs those who were not."

Humanity as a Competitive Advantage

Some clips from a review by Tony Schwartz, of Geoff Colvin's new book “Humans Are Underrated: What High Achievers Know That Brilliant Machines Never Will.”

…computers are rapidly getting better – often far better — than humans are in dozens of areas…analyzing legal cases, providing financial advice, diagnosing illnesses, driving cars and even fighting wars, with battlefield robots and drones. “Affective” computing makes it possible for these machines to understand human emotions and measure levels of stress, often better than we can ourselves.

From Oxford Economics, a research firm: skills employers said they would need more of in the next five to 10 years were not so much analytic and technical ones as they were “relationship building, teaming, co-creativity, brainstorming, cultural sensitivity and ability to manage diverse employees – the skills… of “social interaction.”…organizations will build competitive advantage through qualities such as empathy, care, attunement, self-awareness and even generosity….The more valued, appreciated, cared for and taken care of we feel, the more secure and trusting we become, the less preoccupied by fear, and the more likely we are to generate our highest value.

…leaders in the workplace must become not just chief executive officers, but also chief energy officers, because their energy – and emotions – are so contagious, for better or for worse.

Is "gaydar" a myth?

Cox et al. contest work by Rule et al. that I mentioned in a previous post and suggest that the idea of "gaydar" is a myth. (Use gaydar as a search term in the search box in the left column for other posts on this topic.)

In the present work, we investigate the pop cultural idea that people have a sixth sense, called “gaydar,” to detect who is gay. We propose that “gaydar” is an alternate label for using stereotypes to infer orientation (e.g., inferring that fashionable men are gay). Another account, however, argues that people possess a facial perception process that enables them to identify sexual orientation from facial structure (Rule et al., 2008). We report five experiments testing these accounts. Participants made gay-or-straight judgments about fictional targets that were constructed using experimentally-manipulated stereotypic cues and real gay/straight people’s face cues. These studies revealed that orientation is not visible from the face—purportedly “face- based” gaydar arises from a third-variable confound. People do, however, readily infer orientation from stereotypic attributes (e.g., fashion, career). Furthermore, the folk concept of gaydar serves as a legitimizing myth: Compared to a control group, people stereotyped more when led to believe in gaydar, whereas people stereotyped less when told gaydar is an alternate label for stereotyping. Discussion focuses on the implications of the gaydar myth and why, contrary to some prior claims, stereotyping is highly unlikely to result in accurate judgments about orientation.

Consolidating motor skills in our sleep.

It is well known that sleep, in ourselves and in other animals, helps in consolidating learned motor tasks. (When I am learning difficult passage in a new piano piece I’m preparing for performance, during initial stages of waking I observe my mind playing through the notes.) Ramanathan et al. examine the neurophysiological basis for this by recording from single motor cells in the rat brain to examine the replay of synchronous neural activity during sleep that mediates large-scale neural plasticity and stabilizes kinematics during early motor learning:

Sleep has been shown to help in consolidating learned motor tasks. In other words, sleep can induce “offline” gains in a new motor skill even in the absence of further training. However, how sleep induces this change has not been clearly identified. One hypothesis is that consolidation of memories during sleep occurs by “reactivation” of neurons engaged during learning. In this study, we tested this hypothesis by recording populations of neurons in the motor cortex of rats while they learned a new motor skill and during sleep both before and after the training session. We found that subsets of task-relevant neurons formed highly synchronized ensembles during learning. Interestingly, these same neural ensembles were reactivated during subsequent sleep blocks, and the degree of reactivation was correlated with several metrics of motor memory consolidation. Specifically, after sleep, the speed at which animals performed the task while maintaining accuracy was increased, and the activity of the neuronal assembles were more tightly bound to motor action. Further analyses showed that reactivation events occurred episodically and in conjunction with spindle-oscillations—common bursts of brain activity seen during sleep. This observation is consistent with previous findings in humans that spindle-oscillations correlate with consolidation of learned tasks. Our study thus provides insight into the neuronal network mechanism supporting consolidation of motor memory during sleep and may lead to novel interventions that can enhance skill learning in both healthy and injured nervous systems.

More bad things about sleep debt.

This post is to point to two recent articles on pathologies induced by sleep debt. He et al. show that sleep restriction impairs blood-brain barrier function:

The blood–brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice.

And, Weljie et al. find cross-species molecular markers of sleep debt:

Reduced sleep duration is a hallmark of modern-day society and is increasingly associated with medical conditions, such as diabetes, obesity, metabolic syndrome, and cardiovascular disease. Here we present data from a rat model and human clinical study of chronic sleep restriction, both revealing that two metabolites in blood, oxalic acid and diacylglycerol 36:3, are quantitatively depleted under sleep-restricted conditions and restored after recovery sleep. Our findings also reveal a significant overall shift in lipid metabolism, with higher levels of phospholipids in both species and evidence of a systemic oxidative environment. This work provides a potential link between the known pathologies of reduced sleep duration and metabolic dysfunction.

Our nervous systems are lazy.

Selinger et al. show that the subconscious nervous processes that regulate our movement are constantly adapting to minimize the energy required for movement in a given situation. To show this, they had subjects wear robotic exoskeletons that could increase or decrease resistance to the knees, to change the difficulty of swinging the legs during walking. Within minutes, gate was adjusted to be energetically more optimal.

Highlights

•People readily adapt established gait patterns to minimize energy use 

•People converge on new energetic optima within minutes, even for small cost savings 

•Updated predictions about energetically optimal gaits allow re-convergence within seconds 

•Energetic cost is not just an outcome of movement, but also continuously shapes it

Summary

People prefer to move in ways that minimize their energetic cost. For example, people tend to walk at a speed that minimizes energy use per unit distance and, for that speed, they select a step frequency that makes walking less costly. Although aspects of this preference appear to be established over both evolutionary and developmental timescales, it remains unclear whether people can also optimize energetic cost in real time. Here we show that during walking, people readily adapt established motor programs to minimize energy use. To accomplish this, we used robotic exoskeletons to shift people’s energetically optimal step frequency to frequencies higher and lower than normally preferred. In response, we found that subjects adapted their step frequency to converge on the new energetic optima within minutes and in response to relatively small savings in cost (less than 5%). When transiently perturbed from their new optimal gait, subjects relied on an updated prediction to rapidly re-converge within seconds. Our collective findings indicate that energetic cost is not just an outcome of movement, but also plays a central role in continuously shaping it.

The social mysteries of the superior temporal sulcus

Michael Beauchamp does a summary of work by Deen et al. (open access), who use functional magnetic resonance imaging (fMRI) to show a regular anterior–posterior organization in the STS for different social tasks such as theory of mind, biological motion, faces, voices and language. Here is the summary graphic:

Organization of social perception and cognition within the superior temporal sulcus (STS). Results of Deen et al. are shown on an inflated cortical surface model of the left and right hemisphere. Filled circles show the location of the peak activation, averaged across subjects, for each contrast. Colored regions show the extent of the activation for each contrast (multiple colored regions for some contrasts). 

A final musical/social at Twin Valley - some Rachmaninoff

A personal posting: On Sunday Sept. 13, Len and I hosted our last musical/social at the 1860 stone school house we have lived in for 25 years (I have been doing affairs like these since 1971-72). The following Wednesday, the Steinway B left for our Fort Lauderdale condo. The school house will be offered for sale in the spring of 2016, as we contract our Madison WI footprint to a condo near the university campus. Good friend Roy Wesley did video recordings of the concert, using a simple camera whose automatic volume control for audio damped out dynamic volume changes. I've posted these on YouTube, commentary and glitches included, just to have a record for myself and a few friends. I thought I would pass on the concert program, some pictures, an embedded video of the final Rachmaninoff  pieces, and URLS of the others, to MindBlog readers.

Program 

Chopin Nocturne in C# minor No. 18 (post.), Trois Ecossaises Op. 72 (post.) No. 3 

J. Brahms Capriccio Op 76. No 2; Waltzes, Op. 39 Nos.1, 12, 13, 14, 15. 

C. Debussy - Preludes Livre I - Danseuse de Delphes, Minstrels , Les Collines d’Anacapri 

F. Poulenc - Valse, Improvisation No. 14, Nocturne No. 2 

S.  Rachmaninoff Morceaux de fantasie (Fantasy pieces) Op. 3, No. 1, Elegie; No. 4, Polichinelle

Here is a video of the Rachmaninoff:

And URLs:
J. Brahms Capriccio Op 76. No 2; Waltzes, Op. 39 Nos.1, 12, 13, 14, 15
C. Debussy - Preludes Livre I - Danseuse de Delphes, Minstrels , Les Collines d’Anacapri 
F. Poulenc - Valse, Improvisation No. 14, Nocturne No. 2 

Hormones and clothing choices.

Here is an interesting and curious bit from Eisenbruch et al.:

Recent evidence supports the idea that women use red clothing as a courtship tactic, and results from one study further suggested that women were more likely to wear red on days of high fertility in their menstrual cycles. Subsequent studies provided mixed support for the cycle-phase effect, although all such studies relied on counting methods of cycle-phase estimation and used between-subjects designs. By comparison, in the study reported here, we employed frequent hormone sampling to more accurately assess ovulatory timing and used a within-subjects design. We found that women were more likely to wear red during the fertile window than on other cycle days. Furthermore, within-subjects fluctuations in the ratio of estradiol to progesterone statistically mediated the within-subjects shifts in red-clothing choices. Our results appear to represent the first direct demonstration of specific hormone measurements predicting observable changes in women’s courtship-related behaviors. We also demonstrate the advantages of hormonal determination of ovulatory timing for tests of cycle-phase shifts in psychology or behavior.

Heritable risk of developing anxiety correlates with brain metabolism, not structure.

A group of Univ. of Wisconsin collaborators adds another installment to their series of articles on anxiety in a primate model for humans.

Significance

According to the World Health Organization, anxiety and depressive disorders are a leading source of disability, affecting hundreds of millions of people. Children can inherit an extremely anxious temperament, which is a prominent risk factor for the later development of anxiety, depression, and comorbid substance abuse. This study uses high-resolution functional and structural imaging in our well-established developmental nonhuman primate model to identify the heritable neural substrate that underlies extreme childhood anxious temperament. Using a large multigenerational family pedigree, genetic correlation analyses revealed a tripartite neural circuit where metabolism likely shares a genetic substrate with early-life dispositional anxiety. Interestingly, we found that brain function—not structure—is the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology.

Abstract

Understanding the heritability of neural systems linked to psychopathology is not sufficient to implicate them as intergenerational neural mediators. By closely examining how individual differences in neural phenotypes and psychopathology cosegregate as they fall through the family tree, we can identify the brain systems that underlie the parent-to-child transmission of psychopathology. Although research has identified genes and neural circuits that contribute to the risk of developing anxiety and depression, the specific neural systems that mediate the inborn risk for these debilitating disorders remain unknown. In a sample of 592 young rhesus monkeys that are part of an extended multigenerational pedigree, we demonstrate that metabolism within a tripartite prefrontal-limbic-midbrain circuit mediates some of the inborn risk for developing anxiety and depression. Importantly, although brain volume is highly heritable early in life, it is brain metabolism—not brain structure—that is the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology.

Inventing new words - iconic sounds are used.

Perlman and collaborators find that students inventing new words use certain types of vocalizations with certain words. For example, made-up words for “up” have a rising pitch, words for “down” have a falling pitch. “Slow” has a long duration and a low pitch, whereas “fast” has a short duration and high pitch. And “smooth” has a high degree of harmonicity, whereas “rough” has a high degree of the opposite quality—noise. This suggests that vocal communication systems can originate from spontaneously created iconic characteristics of sound, just as gestural communication systems can originate from spontaneously created iconic gestures. The chart shows the data describing characteristics of words invented for 18 contrasting ideas: up, down, big, small, good, bad, fast, slow, far, near, few, many, long, short, rough, smooth, attractive, and ugly.

The plots show the acoustic characteristics of each of the 18 meanings. The five variables are represented on the x-axis: D, duration; H, harmonics to noise ratio; I, intensity; P, pitch; C, pitch change. All values are normalized (z-scored) for each of the five measures. The red line shows the median and the blue box spans the first and third quartiles. The up and down arrows indicate variables that differed reliably between antonymic meanings. For example, vocalizations for bad differed from those for good by having a lower harmonics to noise ratio and pitch. The variables marked with arrows were the basis for the iconic template of each meaning.

Brain correlates of learning character traits versus rewards.

Hsu and Jenkins summarize work of Hackel et al. showing where our brains learn about traits versus rewards.

In a functional magnetic resonance imaging (fMRI) study..., Hackel et al use an innovative combination of ideas and tools from social psychology, economics and cognitive neuroscience, they offer neural evidence that associative learning processes are involved in making inferences about traits. Specifically, the authors conducted a study in which participants interacted repeatedly with eight different partners: four purported human participants and four slot machines. On each trial, participants chose to interact with one of two human (or slot machine) counterparts. The chosen counterpart, who had been endowed with a certain number of points on that trial, then shared some proportion of those points with the participant. Critically, targets varied orthogonally in terms of the average magnitude of their starting endowment (reward) and the average proportion of the endowment that was shared with the participant (generosity), enabling the authors to dissociate signals associated with trait learning from those associated with reward processing.

Consistent with the idea that trait learning engages associative learning processes, BOLD (blood oxygen level-dependent) responses of the ventral striatum during an initial training phase were predicted by an associative learning model that captures both reward and trait information. Moreover, two pieces of evidence support the idea that participants were able to make use of this trait information in a manner described by psychological theories of trait attribution. First, in a test phase in which participants knew each potential partner's starting endowment, participants chose interaction partners on the basis of those partners' past levels of generosity, and the extent to which they did so was associated with activity in the ventromedial prefrontal cortex (see figure). In addition, participants exhibited a tendency to generalize these generosity attributions, preferring the more generous targets when asked to pick a collaborator for a new, cooperative task-a hallmark of trait attribution.

Figure: Learning about traits versus rewards.  In an fMRI study, participants interacted with partners who varied in reward (the absolute amount of money shared with the participant) and generosity (the proportion shared). Activity in the ventromedial prefrontal cortex (vmPFC) was associated with preferring more generous targets, even when those targets shared less money in absolute terms.

Thinking too much - Self generated thought as the engine of neuroticism.

Perkins et al. offer an opinion piece in which they propose that the cost and benefits of neuroticism are surface manifestations of a tendency to engage in negatively hued self generated thought. I pass on their abstract and text from one of their figures:

•Existing neuroticism models cannot explain its link to both unhappiness and creativity. 

•Self-generated thought (SGT) facilitates creativity but can cause unhappiness. 

•Threat-related regions of medial prefrontal cortex (mPFC) generate blue-tinted SGT. 

•High neuroticism may reflect proneness to SGT arising from mPFC hyperactivity. 

Neuroticism is a dimension of personality that captures trait individual differences in the tendency to experience negative thoughts and feelings. Established theories explain neuroticism in terms of threat sensitivity, but have limited heuristic value since they cannot account for features of neuroticism that are unrelated to threat, such as creativity and negative psychological states experienced in benign, threat-free environments. We address this issue by proposing that neuroticism stems from trait individual differences in activity in brain circuits that govern the nature of self-generated thought (SGT). We argue our theory explains not only the association of neuroticism with threat sensitivity but also the prominence within the neurotic mind of representations of information that are unrelated to the way the world is right now, such as creativity and nonsituational ‘angst’.

A figure legend from the text (graphics did not have resolution adequate to display here):

Neuroticism, self-generated thought (SGT) and perceptions of threat intensity. (A) If an individual with ventromedial prefrontal cortex (vmPFC)/basolateral nuclei of the amygdala (BLA) that is twice as reactive as that of the average person switches from anxiety to panic when a spider encroaches within 4 m (an early switcher), then an average person will switch from anxiety to panic only when that same spider encroaches within 2 m (an ‘average switcher’). Conversely, a person with vmPFC/BLA that is half as reactive as that of the average person will switch from anxiety to panic only when that same spider encroaches within 1 m (a ‘late switcher’). The same psychological state (panic) is achieved in each individual, but the physical distance to threat that elicits it is different. (The graphic showed approaching spider.)(B) A model of how neuroticism is driven by individual differences in susceptibility to negatively hued SGT. Individuals who happen to have greater spontaneous activity in regions of mPFC associated with threat perception, experience frequent, spontaneous activation of threat-related amygdala circuits in situations that are wholly nonthreatening. (The graphic was picture of flowers.) In individuals who also happen to have a highly reactive vmPFC/BLA, these activations are likely to be sufficiently intense to be debilitating; therefore, such individuals present as being highly neurotic.

Savoring happy memories - value representations in the striatum

Speer et al. observe responses in the corticostriatal circuits that respond to monetary reward when positive autobiographical memories are recalled. These response "may be adaptive for regulating positive emotion and promoting better well-being."

Highlights 

•The act of recalling positive life events enhances emotion and has tangible value
•Corticostriatal fMRI signals index emotion evoked by recalling positive life events
•Striatal activity relates to positive mood enhancing effects of reminiscing
•Striatal responses to positive memories may relate to individual resilience 

Summary 

Reminders of happy memories can bring back pleasant feelings tied to the original experience, suggesting an intrinsic value in reminiscing about the positive past. However, the neural circuitry underlying the rewarding aspects of autobiographical memory is poorly understood. Using fMRI, we observed enhanced activity during the recall of positive relative to neutral autobiographical memories in corticostriatal circuits that also responded to monetary reward. Enhanced activity in the striatum and medial prefrontal cortex was associated with increases in positive emotion during recall, and striatal engagement further correlated with individual measures of resiliency. Striatal response to the recall of positive memories was greater in individuals whose mood improved after the task. Notably, participants were willing to sacrifice a more tangible reward, money, in order to reminisce about positive past experiences. Our findings suggest that recalling positive autobiographical memories is intrinsically valuable, which may be adaptive for regulating positive emotion and promoting better well-being.

Convergent evolution of numerosity detection in bird and primate brains.

From Ditz and Nieder:

Birds are known for their advanced numerical competence, although a six-layered neocortex that is thought to enable primates with the highest levels of cognition is lacking in birds. We recorded neuronal activity from an endbrain association area termed nidopallium caudolaterale (NCL) in crows that discriminated the number of items in displays. NCL neurons were tuned to preferred numerosities. Neuronal discharges were relevant for the crows’ correct performance. Both the neuronal and the behavioral tuning functions were best described on a logarithmic number line, just as predicted by the psychophysical Weber–Fecher Law. The behavioral and neuronal numerosity representations in the crow reflect surprisingly well those found in the primate association cortex. This finding suggests that distantly related vertebrates with independently developed endbrains adopted similar neuronal solutions to process quantity - convergent evolution of a superior solution to a common computational problem.

A classification of cognitive mechanisms in meditation practice.

Dahl, Lutz, and Davidson offer an interesting classification system for different styles of meditation. Here is a paste up from their abstract and introduction:

Scientific research highlights the central role of specific psychological processes, in particular those related to the self, in various forms of human suffering and flourishing. This view is shared by Buddhism and other contemplative and humanistic traditions, which have developed meditation practices to regulate these processes. Building on a previous paper in this journal, we propose a novel classification system that categorizes specific styles of meditation into attentional, constructive, and deconstructive families based on their primary cognitive mechanisms. According to this model, the primary cognitive mechanisms in these three families are: (i) attention regulation and meta-awareness; (ii) perspective taking and reappraisal; and (iii) self-inquiry, respectively. To illustrate the role of these processes in different forms of meditation, we discuss how experiential fusion, maladaptive self-schema, and cognitive reification are differentially targeted by these processes in the context of Buddhist meditation, integrating the perspectives of other contemplative, philosophical, and clinical perspectives when relevant. The mechanisms and targets we propose are drawn from cognitive science and clinical psychology. Although these psychological processes are theoretically complex, as are the meditation practices that target them, we propose this novel framework as a first step in identifying specific cognitive mechanisms to aid in the scientific study of different families of meditation and the impact of these practices on well-being.

This article appears to be open source, and well worth reading for those interested in meditation. (I can send full text to motivated readers who have difficulty securing the full text.) I thought I would pass on just one edited clip from the section on the constructive family of meditation practices:

One of the most widely studied practices in the constructive family is the cultivation of compassion. Compassion training is held to alter core self-related processes, initiating a shift from self-oriented cognitive, affective, and behavioral patterns to patterns that are oriented toward the well-being of others...Research into the neural correlates of empathy has found that similar regions, including the insula, the anterior and mid-cingulate cortices, and the supplementary motor area, are activated across various forms of empathy...By way of contrast, compassion is linked to regions associated with reward, positive affect, and feelings of affection, such as the ventral striatum and medial orbitofrontal cortex...Studies of compassion training have also found increased activation in regions associated with executive function, including the dorsolateral prefrontal cortex and the anterior cingulate cortex...these preliminary findings suggest that cultivating compassion strengthens multiple networks, each of which may affect distinct psychological processes and thereby contribute to well-being in different ways.

Empathy and compassion also affect the peripheral biology of the human body. Perceiving stress in another individual has been linked to elevated cortisol levels, a relation that is more robust in those with high trait empathy, whereas compassion has been linked to lower levels of cortisol reactivity. Preliminary studies of compassion training have found associations between the amount of time spent engaging in compassion training and inflammatory biomarkers, with more compassion training leading to decreased levels of both C-reactive protein and interleukin 6. These findings suggest that the mind can be trained to orient itself toward the well-being of others and that this shift from self- to other-orientation impacts both the brain and the peripheral biology of the body and, in particular, the way the body responds to environmental stressors. Further research is required to elucidate the precise mechanisms through which these states affect the body, and also to investigate how changes in peripheral biology reciprocally impact psychological processes and the relationship between these processes and well-being.

Brain imaging can predict six-year outcomes in children’s numerical abilities.

Interesting work from Evans et al.:

Significance Statement

Children show substantial individual differences in math abilities and ease of math learning. Early numerical abilities provide the foundation for future academic and professional success in an increasingly technological society. Understanding the early identification of poor math skills has therefore taken on great significance. This work provides important new insights into brain structure and connectivity measures that can predict longitudinal growth of children's math skills over a 6 year period, and may eventually aid in the early identification of children who might benefit from targeted interventions.

Abstract

Early numerical proficiency lays the foundation for acquiring quantitative skills essential in today's technological society. Identification of cognitive and brain markers associated with long-term growth of children's basic numerical computation abilities is therefore of utmost importance. Previous attempts to relate brain structure and function to numerical competency have focused on behavioral measures from a single time point. Thus, little is known about the brain predictors of individual differences in growth trajectories of numerical abilities. Using a longitudinal design, with multimodal imaging and machine-learning algorithms, we investigated whether brain structure and intrinsic connectivity in early childhood are predictive of 6 year outcomes in numerical abilities spanning childhood and adolescence. Gray matter volume at age 8 in distributed brain regions, including the ventrotemporal occipital cortex (VTOC), the posterior parietal cortex, and the prefrontal cortex, predicted longitudinal gains in numerical, but not reading, abilities. Remarkably, intrinsic connectivity analysis revealed that the strength of functional coupling among these regions also predicted gains in numerical abilities, providing novel evidence for a network of brain regions that works in concert to promote numerical skill acquisition. VTOC connectivity with posterior parietal, anterior temporal, and dorsolateral prefrontal cortices emerged as the most extensive network predicting individual gains in numerical abilities. Crucially, behavioral measures of mathematics, IQ, working memory, and reading did not predict children's gains in numerical abilities. Our study identifies, for the first time, functional circuits in the human brain that scaffold the development of numerical skills, and highlights potential biomarkers for identifying children at risk for learning difficulties.

Bioethics - Doing more harm than good?

Steven Pinker recently ignited a small firestorm with his piece in the Boston Globe arguing that bioethical issues that slow down research have a massive human cost. "Even a one-year delay in implementing an effective treatment could spell death, suffering, or disability for millions of people." Below are some clips from his piece, and rebuttals to Pinker's points can be found in this Nature article:

Biomedical research, then, promises vast increases in life, health, and flourishing. Just imagine how much happier you would be if a prematurely deceased loved one were alive, or a debilitated one were vigorous — and multiply that good by several billion, in perpetuity. Given this potential bonanza, the primary moral goal for today’s bioethics can be summarized in a single sentence.

Get out of the way.

A truly ethical bioethics should not bog down research in red tape, moratoria, or threats of prosecution based on nebulous but sweeping principles such as “dignity,” “sacredness,” or “social justice.” Nor should it thwart research that has likely benefits now or in the near future by sowing panic about speculative harms in the distant future. These include perverse analogies with nuclear weapons and Nazi atrocities, science-fiction dystopias like “Brave New World’’ and “Gattaca,’’ and freak-show scenarios like armies of cloned Hitlers, people selling their eyeballs on eBay, or warehouses of zombies to supply people with spare organs. Of course, individuals must be protected from identifiable harm, but we already have ample safeguards for the safety and informed consent of patients and research subjects.

Biomedical research in particular is defiantly unpredictable. The silver-bullet cancer cures of yesterday’s newsmagazine covers, like interferon and angiogenesis inhibitors, disappointed the breathless expectations, as have elixirs such as antioxidants, Vioxx, and hormone replacement therapy. Nineteen years after Dolly the sheep was cloned, we are nowhere near seeing parents implanting genes for musical, athletic, or intellectual talent in their unborn children.

In the other direction, treatments that were decried in their time as paving the road to hell, including vaccination, transfusions, anesthesia, artificial insemination, organ transplants, and in-vitro fertilization, have become unexceptional boons to human well-being.

Biomedical advances will always be incremental and hard-won, and foreseeable harms can be dealt with as they arise. The human body is staggeringly complex, vulnerable to entropy, shaped by evolution for youthful vigor at the expense of longevity, and governed by intricate feedback loops which ensure that any intervention will be compensated for by other parts of the system. Biomedical research will always be closer to Sisyphus than a runaway train — and the last thing we need is a lobby of so-called ethicists helping to push the rock down the hill.

Oxytocin - more sophisticated views of its functions

Helen Shen offers a review of studies on oxytocin, the “hug hormone,” which influences maternal behavior and social attachment in various species. She notes research showing that oxytocin acts on inhibitory interneurons in a way that quiets background chatter within neuronal circuits, and thus may help social interaction and recognition is by enhancing the brain's response to socially relevant sights, sounds or other stimuli. MindBlog has done posts on experiments showing that oxytocin, delivered through an intranasal spray, can promote various aspects of social behavior in healthy adults. People who inhale oxytocin before playing an investment game are more willing to entrust their money to a stranger than are placebo-treated players. A dose of the hormone increases the amount of time people spend gazing at the eye region of faces, and improves their ability to infer the emotional state of others from subtle expressions. Shen’s review also summarizes efforts to test oxytocin’s usefulness in treating psychiatric disorders such as autism.

Birth of the moralizing gods.

Lizzie Wade offers two interesting summaries of work on the evolution of religion that suggest that as societies grew bigger, so did their gods. She describes the efforts of Anders Petersen, who is asking religious studies scholars to contribute his "Database of Religious History" project by answering a series of questions about the ancient religions in which each of them specialize. This kind of survey can help in testing a “big gods” hypothesis: "Did moralizing gods, community-wide rituals, and supernatural punishment emerge before or after societies became politically complex? Has any large-scale society succeeded without prosocial religion? And what does “moralizing” really mean in different cultures and at different times?" Wade's second article describes work of Ara Norenzayan and others suggesting that judgemental deities were the key to obtaining the cooperation needed to build and sustain large and complex ancient societies..."once big gods and big societies existed, the moralizing gods helped religions as dissimilar as Islam and Mormonism spread by making groups of the faithful more cooperative, and therefore more successful."

The benefits of reading to children.

Two items...First, from Montag et al.:

Young children learn language from the speech they hear. Previous work suggests that greater statistical diversity of words and of linguistic contexts is associated with better language outcomes. One potential source of lexical diversity is the text of picture books that caregivers read aloud to children. Many parents begin reading to their children shortly after birth, so this is potentially an important source of linguistic input for many children. We constructed a corpus of 100 children’s picture books and compared word type and token counts in that sample and a matched sample of child-directed speech. Overall, the picture books contained more unique word types than the child-directed speech. Further, individual picture books generally contained more unique word types than length-matched, child-directed conversations. The text of picture books may be an important source of vocabulary for young children, and these findings suggest a mechanism that underlies the language benefits associated with reading to children.

And, Hutton et al. note that children with greater home reading exposure exhibit higher activation of left-sided brain regions involved with semantic processing (extraction of meaning).

Self-policing by psychologists - many prominent experiments fail replication tests

Benedict Carey offers context, summary, and reactions to the recent Science article reporting work of a consortium of 270 scientists on five continents led by psychologist Brian Nosek at the University of Virginia. (Other commentaries on this work are offered by Bohannon and by The Guardian.) The bottom line is that only 36 percent of the findings from almost 100 studies in the top three psychology journals held up when the original experiments were rigorously redone. This work was an 'inside job,' with psychologists doing the replication attempts communicating with cooperative original researchers. Carey describes a culture change that is taking hold in the psychological research community, towards greater transparency, data sharing, and preregistration of studies with journals that spells out hypotheses and how they are going to be tested. "Doing this upfront is a powerful check against moving the goal posts on a study — that is, analyzing the data and working backward, reverse-engineering the “hypothesis” to fit those findings."

(addendum 9/1/2015:  another useful commentary, "Psychology is Not in Crisis")