Anti-aging drugs - Clarification on Resveratrol and SIRT1 activators

Resveratrol, the natural compound in red wine, and other small molecules are allosteric activators of SIRT1, an enzyme with roles in many biological processes (including DNA repair, metabolism, programmed cell death, and inflammation) that affect human life span. Studies have shown that Sirtuin activators like resveratrol can extend the lifespan of yeast, worms, and flies. From an editor's summary of work by Hubbard et al in the latest issue of Science:

Intense attention has focused on the SIRT1 deacetylase as a possible target for anti-aging drugs. But unexpected complications in assays of SIRT1 activity have made it unclear whether compounds thought to be sirtuin-activating compounds (STACs) are really direct regulators of the enzyme. Further exploration of these effects by Hubbard et al. revealed that interaction of SIRT1 with certain substrates allows activation of SIRT1 by STACs and identified critical amino acids in SIRT1 required for these effects. Mouse myoblasts reconstituted with SIRT1 mutated at this amino acid lost their responsiveness to STACs.

The Hubbard et al abstract:

A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1α and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu230, located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs.

The mental cost of cognitive enhancement.

There has been quite a bit of interest lately in the prospect of enhancing various brain operations by the use of trans-cranial electrical stimulation (TES). Iuculano and Kadosh make the fascinating observation that enhancing one activity with TES can compromise another:

Noninvasive brain stimulation provides a potential tool for affecting brain functions in the typical and atypical brain and offers in several cases an alternative to pharmaceutical intervention. Some studies have suggested that transcranial electrical stimulation (TES), a form of noninvasive brain stimulation, can also be used to enhance cognitive performance. Critically, research so far has primarily focused on optimizing protocols for effective stimulation, or assessing potential physical side effects of TES while neglecting the possibility of cognitive side effects. We assessed this possibility by targeting the high-level cognitive abilities of learning and automaticity in the mathematical domain. Notably, learning and automaticity represent critical abilities for potential cognitive enhancement in typical and atypical populations. Over 6 d, healthy human adults underwent cognitive training on a new numerical notation while receiving TES to the posterior parietal cortex or the dorsolateral prefrontal cortex. Stimulation to the the posterior parietal cortex facilitated numerical learning, whereas automaticity for the learned material was impaired. In contrast, stimulation to the dorsolateral prefrontal cortex impaired the learning process, whereas automaticity for the learned material was enhanced. The observed double dissociation indicates that cognitive enhancement through TES can occur at the expense of other cognitive functions. These findings have important implications for the future use of enhancement technologies for neurointervention and performance improvement in healthy populations.

And you thought you knew the data on wealth inequality?

I found this a jaw-dropping clarification of wealth inequality in the U.S.

Can the Catholic Church evolve?

Maureen Dowd discusses gay author Colin Toibin’s “The Testament of Mary,” a one-woman show with Fiona Shaw previewing later this month on Broadway, and I pass on this fascinating clip on Toibin’s thoughts about the Church and homosexuality (I was fascinated to learn about Benedict's “Gorgeous Georg”, who he takes with him into retirement.):

Benedict may have given up his flashy red loafers, downgrading to brown ones made for him in Mexico, but he is taking “Gorgeous Georg,” as the younger German is known, to live in his new home, a monastery in the Vatican. Some cardinals are worried about the arrangement of having Gänswein serve two pontiffs, by day as prefect of the new pope’s household and at night as secretary to the emeritus pope.

“An 85-year-old man having such a beautiful companion with him morning and night to talk to and walk with,” Toibin said. “It’s like the end of a novel. It’s what all of us want for ourselves, straight or gay. It’s better than sex.”

I ask him whether he thinks the church will evolve under a new pope.

“Everyone is hoping for some change,” he said. “If you could see nuns making sermons. Clerical celibacy has to be abolished and soon. And we must quickly begin the process of allowing women into the priesthood.

“They need to think very carefully about not recognizing that gay people, like all other people, are made in God’s image. It’s just possible that they have more gay priests than they know. I think most gay priests are very good people in the priesthood for very good reasons, and actually faithful to the vows of celibacy. On the issue of gays, Benedict made things even worse.”

As Cardinal Ratzinger, Benedict called homosexuality a “more or less strong tendency ordered towards an intrinsic moral evil.” As pope, he reiterated the church view that homosexuals were “objectively disordered” and that men who had such tendencies could not be allowed into seminaries. He called gay marriage a threat to “the future of humanity itself.”

Toibin says that the church must have tolerance, and that its leaders have lost any sense of how their sanctimonious denunciations clash with their scandals and imagery, causing nothing but pain.

“I remember being at the Vatican at Easter 1994,” he recalled, “and watching all the cardinals and bishops, wonderfully powerful old men with great chins, sitting nobly with a long row of extraordinarily beautiful young seminarians standing behind, shading them with different colored sun umbrellas, some of which were pink."

“It was remarkable that none of them seemed to know what it looked like, and I watched it thinking, somebody must tell them.”

Neural mechanisms of stress vulnerability and resilience.

Two interesting papers in the Journal of Neuroscience  deal with what is happening to nerve cells in mouse brains as they either do or don't recover from stress. Lehmann et al. demonstrate that glucocorticoid-dependent declines in neurogenesis drive changes in mood after social defeat and that glucocorticoids secreted during enrichment promote hippocampal neurogenesis and restore normal behavior after defeat, suggesting that treatments promoting neurogenesis can enhance stress resilience. Gourley et al. looked at the elimination of dendritic spines in the hippocampus caused by chronic stress exposure, and show that resilience, or recovery from stress, correlates with spine proliferation.

In praise of the unexamined, unlived life?

I was sufficiently interested by two reviews of a new book by British psychoanalyst Adam Phillips (“Missing Out: In Praise of the Unlived Life”), one in the NYTimes (Sheila Heti), one in The New Yorker (Joan Acocella), that I downloaded a Kindle version to look over. I totally regret having spent the 11 bucks. There are two main messages noted by reviewers, one is the dressing up of homily common to many self help books. From Acocella:

Instead of feeling that we should have a better life, he says, we should just live, as gratifyingly as possible, the life we have.  Otherwise, we are setting ourselves up for bitterness.  What makes us think that we could have been a contender?  Yet, in the dark of night, we do think this, and grieve that it wasn’t possible.  “And what was not possible all too easily becomes the story of our lives,” Phillips writes.  “Out lived lives might become a protracted mourning for, or an endless trauma about, the lives we were unable to live.”

OK, fair enough. It can be an error to spend our  time thinking on what we might have been or want to be or ought to be or be doing, rather than just living  and being who we are, getting on with it.  Just doing things. The rub is that Phillips is completely unwilling to write simple sentences with simple ideas. He generates complex elliptical sentences designed more to illustrate his erudition and mental pyrotechnics than to inform, lost in a world of abstraction.

I completely lost it with his second chapter "On Not Getting It," where he essentially argues that we are better off not understanding ourselves, or others. His correct contention that we can never really understand ourselves or others is beside the point. Our illusions of understanding ourselves and others are a feature evolved by our social brains that has proven its utility in enhancing and passing on the genes of groups of humans who share common illusions. And, we sure have gotten a lot of mileage out of trying to understand. Otherwise we wouldn't be attempting to read psychoanalytic babble like Philips' or write things like MindBlogs.

Is the insula necessary for our feelings? If not, where are they?

I have been fairly uncritical in passing on simplifications like “The insula is the sensory cortex for our internal visceral feelings” and so was grateful to see, in Damasio’s recent review article “The nature of feelings: evolutionary and neurobiological origins” a critique of this idea:

Feelings and the insula. Interoceptive information mapped in the brainstem is projected rostrally to the subcortical basal forebrain and to the cortical telencephalon, where it is remapped in the insula and somatosensory cortices SI and SII.

Contemporary neuroscience has identified the insula as the main cortical target for signals from the interoceptive system, and functional neuroimaging studies consistently implicate the human insula in both interoceptive and emotional feelings.

Recently, it has been proposed that the insula is not merely involved in human feelings but is their sole platform and, by extension, the critical provider of human awareness. Several findings suggest that this hypothesis is problematic. First, given that several topographically organized nuclei of the upper brainstem, which are obligatory relay stations for most signals conveyed from the body to the insula, can produce elaborate representations of multiple parameters of body states, these regions should not be excluded a priori as platforms for feelings. Second, children born without cerebral cortex exhibit behaviours compatible with feeling states. Third, bilateral insular damage does not abolish all feelings. Specifically, complete bilateral destruction of the insula as a result of herpes simplex encephalitis does not abolish either body or emotional feelings, including pain, pleasure, itch, tickle, happiness, sadness, apprehension, irritation, caring and compassion, in addition to hunger, thirst, and bladder and colon distension. In fact, feelings seem to dominate the mental landscape of patients with bilateral insular damage. Immediate comfort appears to be their main concern, fairly unbridled by cognitive constraints.

These observations do not support a view of the insula as a necessary substrate for feeling states. Thus, the generation of feelings must also rely on the brainstem and possibly on the SI and SII somatosensory cortices of the parietal lobe, which are spared in some patients that lack the insular cortices but remain fully capable of feeling. Indeed, damage to the posterior half of the upper brainstem is associated with coma or vegetative state — two conditions in which feelings and sentience are abolished.

After reviewing data on how feelings persist after lesions to other cortical regions suggested central to feelings, Damasio suggests that subcortical regions such as the upper brainstem and hypothalamus are most central in the generation of feelings, and that this has resounding evolutionary implications:

...the fundamental elements of body state mapping, sentience and feelings imbued with valence are likely to be far older than our species, and probably even older than the advent of cerebral cortices. There is good reason to believe that the primate brain inherited the neural instruments for feeling from its ancestors and elaborated upon them.

Watching our auditory brain, like a radio, switch hearing frequency channels.

From Da Costa et al.:

Cocktail parties, busy streets, and other noisy environments pose a difficult challenge to the auditory system: how to focus attention on selected sounds while ignoring others? Neurons of primary auditory cortex, many of which are sharply tuned to sound frequency, could help solve this problem by filtering selected sound information based on frequency-content. To investigate whether this occurs, we used high-resolution fMRI at 7 tesla to map the fine-scale frequency-tuning (1.5 mm isotropic resolution) of primary auditory areas A1 and R in six human participants. Then, in a selective attention experiment, participants heard low (250 Hz)- and high (4000 Hz)-frequency streams of tones presented at the same time (dual-stream) and were instructed to focus attention onto one stream versus the other, switching back and forth every 30 s. Attention to low-frequency tones enhanced neural responses within low-frequency-tuned voxels relative to high, and when attention switched the pattern quickly reversed. Thus, like a radio, human primary auditory cortex is able to tune into attended frequency channels and can switch channels on demand.

Amygdala damage can make us more generous

From van Honk et al.:

Contemporary economic models hold that instrumental and impulsive behaviors underlie human social decision making. The amygdala is assumed to be involved in social-economic behavior, but its role in human behavior is poorly understood. Rodent research suggests that the basolateral amygdala (BLA) subserves instrumental behaviors and regulates the central-medial amygdala, which subserves impulsive behaviors. The human amygdala, however, typically is investigated as a single unit. If these rodent data could be translated to humans, selective dysfunction of the human BLA might constrain instrumental social-economic decisions and result in more impulsive social-economic choice behavior. Here we show that humans with selective BLA damage and a functional central-medial amygdala invest nearly 100% more money in unfamiliar others in a trust game than do healthy controls. We furthermore show that this generosity is not caused by risk-taking deviations in nonsocial contexts. Moreover, these BLA-damaged subjects do not expect higher returns or perceive people as more trustworthy, implying that their generous investments are not instrumental in nature. These findings suggest that the human BLA is essential for instrumental behaviors in social-economic interactions.

Here is the anatomical location of the human lesions:

MR images (coronal view) of the three subjects with Urbach–Wiethe disease (UWD), with their year of birth and red crosshairs indicating the calcified brain damage...the lesions of the three patients are located in the BLA...the functional method shows activation during emotion matching in the superficial amygdala (SFA) and CMA, but not in the BLA.

How our viscera influence our brain and behavior

I want to pass on this fascinating and useful open source review by Critchley and Harrison in the journal Neuron. Having just had the flu, I found their presentation of visceral regulation of sickness behaviors very relevant! The article is worthwhile especially for the summary figures showing functional and anatomical pathways. (I resist the urge to paste them into this post, you can look at them by clicking on the link above. Here is their abstract:

Mental processes and their neural substrates are intimately linked to the homeostatic control of internal bodily state. There are a set of distinct interoceptive pathways that directly and indirectly influence brain functions. The anatomical organization of these pathways and the psychological/behavioral expressions of their influence appear along discrete, evolutionarily conserved dimensions that are tractable to a mechanistic understanding. Here, we review the role of these pathways as sources of biases to perception, cognition, emotion, and behavior and arguably the dynamic basis to the concept of self.

And, two clips from the text:

The internal state of the body motivates our desire to walk in the shade on a warm summer’s day and inhibits the desire to eat or socialize when feeling off-color. Communication from the viscera to brain is continuous and pervasive, yet we rarely give it a second thought. Visceral fluctuations and reactions accessible to introspective appraisal represent only the visible tip of the iceberg.

A comprehensive understanding of the integration of internal bodily signals in health is ultimately required for effective management of physical and psychological symptoms in illness. Such a goal can only be achieved through coordinated experimental approaches and perhaps a move away from treating physiological changes as irrelevant confounds in neuropsychological experiments. Together, these observations make “us realize more deeply than ever how much of our mental life is knit up in our corporeal frame” (James, 1890).

How ambient light might influence our mood.

The visual pigment melanopsin in the intrinsically photosensitive retinal ganglion cells (ipRGCs) of our inner retinas (two cells layers away from our rods and cones) detect ambient light and send this information to brain areas that regulate circadian rhythms and mood. LaGates et al. have now found that inappropriately timed light exposure that does not alter normal sleep architecture and circadian rhythmicity of body temperature and general activity still can cause impaired learning and depression-like behaviors in mice. In mice genetically altered to remove ipRGC cells, the depressive-like behaviors and learning deficits are not observed. If similar mechanisms operate in us humans, this suggests a potential mechanism by which abnormal ambient light schedules — caused by shift work or simply switching on an artificial light — might influence mood and learning. Here is their abstract:

The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep–wake cycles to the correct temporal niche. Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits. Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules. Whether irregular light schedules directly affect mood and cognitive functions in the context of normal sleep and circadian rhythms remains unclear. Here we show, using an aberrant light cycle that neither changes the amount and architecture of sleep nor causes changes in the circadian timing system, that light directly regulates mood-related behaviours and cognitive functions in mice. Animals exposed to the aberrant light cycle maintain daily corticosterone rhythms, but the overall levels of corticosterone are increased. Despite normal circadian and sleep structures, these animals show increased depression-like behaviours and impaired hippocampal long-term potentiation and learning. Administration of the antidepressant drugs fluoxetine or desipramine restores learning in mice exposed to the aberrant light cycle, suggesting that the mood deficit precedes the learning impairments. To determine the retinal circuits underlying this impairment of mood and learning, we examined the behavioural consequences of this light cycle in animals that lack intrinsically photosensitive retinal ganglion cells. In these animals, the aberrant light cycle does not impair mood and learning, despite the presence of the conventional retinal ganglion cells and the ability of these animals to detect light for image formation. These findings demonstrate the ability of light to influence cognitive and mood functions directly through intrinsically photosensitive retinal ganglion cells.

The lament of the historian…

My colleague William Cronon at the University of Wisconsin was President of the American Historical Association for 2012,  and I want to pass on a clip from the AHA Presidential Address he delivered in Jan. 2013.  Among his concerns about the future of historical studies as a discipline is the digital revolution and internet that are transforming literally everything about the way historians work and how people read:

One of my deepest fears about this brave new digital world has to do with reading itself...It seems to me that the book-length monograph on which our discipline has long relied is very much at risk as texts migrate from paper to screens. It is not just that libraries are reducing purchases, that university presses are facing cutbacks, or that declining print runs and rising per-unit costs are pricing many specialized monographs beyond the reach of ordinary buyers. My deeper fear comes from watching my own students, many of whom no longer read books for pleasure. If they have any prior experience doing research, almost all of it is online. If a piece of information cannot be Googled, it effectively does not exist for them. More than a few of my students have never actually been inside the stacks of a library. To the extent that good writing is predicated on frequent skilled reading, the ability of such students to recognize and construct grammatical sentences and paragraphs—let alone graceful or elegant ones—is plummeting.

In a manically multitasking world where even e-mail takes too long to read, where texts and tweets and Facebook postings have become dominant forms of communication, reading itself is more at risk than many of us realize. Or, to be more precise, long-form reading is at risk: the ability to concentrate and sustain one's attention on arguments and narratives for many hours and many thousands of words. I have come to think of this as the Anna Karenina problem: will students twenty years from now be able to read novels like Tolstoy's that are among the greatest works of world literature but that require dozens of hours to be meaningfully experienced? And if a novel as potent as Anna lies beyond reach, what does that imply for complex historical monographs that are in many ways even more challenging in the demands they make on readers?

What is the future of history?...there is one answer that is arguably the most basic of all, and that is, simply: storytelling. We need to remember the roots of our discipline and be sure to keep telling stories that matter as much to our students and to the public as they do to us. Although the shape and form of our stories will surely change to meet the expectations of this digital age, the human need for storytelling is not likely ever to go away. It is far too basic to the way people make sense of their lives—and among the most important stories they tell are those that seek to understand the past. Hang on to this truth, and there is no reason to fear that history will be any less important to the human future than it has been to the human past.

In an uncertain world, fairness finishes first.

I usually get hopelessly lost in accounts of variations of the ultimatum game used to model human behavior and its evolutionary rationale or origins. This experiment by Rand et al. seems relatively clear and crisp:

Classical economic models assume that people are fully rational and selfish, while experiments often point to different conclusions. A canonical example is the Ultimatum Game: one player proposes a division of a sum of money between herself and a second player, who either accepts or rejects. Based on rational self-interest, responders should accept any nonzero offer and proposers should offer the smallest possible amount. Traditional, deterministic models of evolutionary game theory agree: in the one-shot anonymous Ultimatum Game, natural selection favors low offers and demands. Experiments instead show a preference for fairness: often responders reject low offers and proposers make higher offers than needed to avoid rejection. Here we show that using stochastic evolutionary game theory, where agents make mistakes when judging the payoffs and strategies of others, natural selection favors fairness. Across a range of parameters, the average strategy matches the observed behavior: proposers offer between 30% and 50%, and responders demand between 25% and 40%. Rejecting low offers increases relative payoff in pairwise competition between two strategies and is favored when selection is sufficiently weak. Offering more than you demand increases payoff when many strategies are present simultaneously and is favored when mutation is sufficiently high. We also perform a behavioral experiment and find empirical support for these theoretical findings: uncertainty about the success of others is associated with higher demands and offers; and inconsistency in the behavior of others is associated with higher offers but not predictive of demands. In an uncertain world, fairness finishes first.

Big brains decrease fertility.

More intelligent mammals, such as humans, whales, and dolphins, have decreased fertility. One ideas has been that the energetic cost of increased brain power has been meet by decreasing the size of the gut and decreasing reproductive function. Kotrschal et al. have tested this idea by selecting for brain size in guppies and obtaining populations of fish whose brains were larger or smaller than normal and differed from one another by about 10%. The cost of the increased brain power was a decrease in the size of the gut and a decrease in reproductive function. Here is their abstract:

The large variation in brain size that exists in the animal kingdom has been suggested to have evolved through the balance between selective advantages of greater cognitive ability and the prohibitively high energy demands of a larger brain (the “expensive-tissue hypothesis”). Despite over a century of research on the evolution of brain size, empirical support for the trade-off between cognitive ability and energetic costs is based exclusively on correlative evidence, and the theory remains controversial. Here we provide experimental evidence for costs and benefits of increased brain size. We used artificial selection for large and small brain size relative to body size in a live-bearing fish, the guppy (Poecilia reticulata), and found that relative brain size evolved rapidly in response to divergent selection in both sexes. Large-brained females outperformed small-brained females in a numerical learning assay designed to test cognitive ability. Moreover, large-brained lines, especially males, developed smaller guts, as predicted by the expensive-tissue hypothesis, and produced fewer offspring. We propose that the evolution of brain size is mediated by a functional trade-off between increased cognitive ability and reproductive performance and discuss the implications of these findings for vertebrate brain evolution.

How mindfulness meditation works in the brain - a model

Kerr et al make some interesting speculations. Their article contains some useful summary graphics.

Using a common set of mindfulness exercises, mindfulness based stress reduction (MBSR) and mindfulness based cognitive therapy (MBCT) have been shown to reduce distress in chronic pain and decrease risk of depression relapse. These standardized mindfulness (ST-Mindfulness) practices predominantly require attending to breath and body sensations. Here, we offer a novel view of ST-Mindfulness's somatic focus as a form of training for optimizing attentional modulation of 7–14 Hz alpha rhythms that play a key role in filtering inputs to primary sensory neocortex and organizing the flow of sensory information in the brain. In support of the framework, we describe our previous finding that ST-Mindfulness enhanced attentional regulation of alpha in primary somatosensory cortex (SI). The framework allows us to make several predictions. In chronic pain, we predict somatic attention in ST-Mindfulness “de-biases” alpha in SI, freeing up pain-focused attentional resources. In depression relapse, we predict ST-Mindfulness's somatic attention competes with internally focused rumination, as internally focused cognitive processes (including working memory) rely on alpha filtering of sensory input. Our computational model predicts ST-Mindfulness enhances top-down modulation of alpha by facilitating precise alterations in timing and efficacy of SI thalamocortical inputs. We conclude by considering how the framework aligns with Buddhist teachings that mindfulness starts with “mindfulness of the body.” Translating this theory into neurophysiology, we hypothesize that with its somatic focus, mindfulness' top-down alpha rhythm modulation in SI enhances gain control which, in turn, sensitizes practitioners to better detect and regulate when the mind wanders from its somatic focus. This enhanced regulation of somatic mind-wandering may be an important early stage of mindfulness training that leads to enhanced cognitive regulation and metacognition.

Interdependent behavior facilitated by independent behavior?

Hamedani et al. , who end up suggesting that it may be necessary to invoke independent behaviors in order to successfully motivate interdependence, start their article with a Quote:

"Each time I look at that flag, I’m reminded that our destiny is stitched together like those 50 stars and those 13 stripes . . . And if we hold fast to that truth, in this moment of trial, there is no challenge too great." "—U.S. president Barack Obama, State of the Union address, January 24, 2012 "

They then outline the context for their study on factors that influence the kinds of interdependent behavior needed to face problems common to all people, such as the environmental crisis. They:

...compared European Americans, who have been exposed primarily to mainstream cultural contexts that promote and value independence, with East Asian Americans, who have been exposed both to these contexts and also to cultural contexts that promote and value interdependence. Asian Americans are considered bicultural because they are exposed not only to mainstream American contexts that foster independent behavior (e.g., in schools and workplaces), but also to East Asian contexts that foster interdependent behavior (e.g., in families and communities)...This European American/Asian American cultural contrast allowed us to examine whether independence necessarily functions as a barrier to interdependent awareness and action. Comparing two American groups who are similar in their exposure to independence but different in their exposure to interdependence enabled us to test the theory that interdependence may undermine motivation because of a lack of exposure to cultural contexts that promote and value it as a normatively “good” style of behavior.1 Specifically, we tested the hypothesis that invoking interdependent behavior, compared with invoking independent behavior, would undermine motivation for European Americans but not for bicultural Asian Americans.

Here is their abstract:

Today’s most pressing social challenges require people to recognize their shared fate and work together—to think and act interdependently. In the three studies reported here, we found that appeals for increased interdependence may undermine the very motivation they seek to inspire. We examined the hypothesis that invoking interdependent action undermines motivation for chronically independent European Americans but not for bicultural Asian Americans who are both chronically independent and chronically interdependent. Two studies demonstrated that priming interdependent rather than independent action undermined European Americans’ motivation to perform challenging mental and physical tasks. A third study showed that framing an appeal for environmental sustainability in terms of interdependent rather than independent action led to decreased motivation and resource allocation among European Americans. Motivation was not undermined for Asian Americans, which reveals how behavior is divergently shaped, in the land of the free, by foundational sociocultural schemas of independence and interdependence. This research has the novel implication that it may be necessary to invoke independent behaviors in order to successfully motivate interdependence.

Red Brain, Blue Brain

Darren Schreiber and collaborators add yet another article to what is a growing literature on the differing sensitivities to threat of liberals and conservatives. Their open access article shows brain imaging and behavioral correlates. It seems likely not only that having a particular brain would influence our political views, but also that having a particular political view would influence and change our brains. The causal arrow seems likely to run in both directions—which would make sense in light of what we know about the plasticity of the brain.

Liberals and conservatives exhibit different cognitive styles and converging lines of evidence suggest that biology influences differences in their political attitudes and beliefs. In particular, a recent study of young adults suggests that liberals and conservatives have significantly different brain structure, with liberals showing increased gray matter volume in the anterior cingulate cortex, and conservatives showing increased gray matter volume in the in the amygdala. Here, we explore differences in brain function in liberals and conservatives by matching publicly-available voter records to 82 subjects who performed a risk-taking task during functional imaging. Although the risk-taking behavior of Democrats (liberals) and Republicans (conservatives) did not differ, their brain activity did. Democrats showed significantly greater activity in the left insula, while Republicans showed significantly greater activity in the right amygdala. In fact, a two parameter model of partisanship based on amygdala and insula activations yields a better fitting model of partisanship than a well-established model based on parental socialization of party identification long thought to be one of the core findings of political science. These results suggest that liberals and conservatives engage different cognitive processes when they think about risk, and they support recent evidence that conservatives show greater sensitivity to threatening stimuli.

Chimps play fair in the ultimatum game.

These interesting observations by Proctor, de Waal et al. using a new experimental design that resolves conflicting data in studies by other authors suggest that our human sense of fairness has an early origin in primate behavior.

Is the sense of fairness uniquely human? Human reactions to reward division are often studied by means of the ultimatum game, in which both partners need to agree on a distribution for both to receive rewards. Humans typically offer generous portions of the reward to their partner, a tendency our close primate relatives have thus far failed to show in experiments. Here we tested chimpanzees (Pan troglodytes) and human children on a modified ultimatum game. One individual chose between two tokens that, with their partner’s cooperation, could be exchanged for rewards. One token offered equal rewards to both players, whereas the other token favored the chooser. Both apes and children responded like humans typically do. If their partner’s cooperation was required, they split the rewards equally. However, with passive partners—a situation akin to the so-called dictator game—they preferred the selfish option. Thus, humans and chimpanzees show similar preferences regarding reward division, suggesting a long evolutionary history to the human sense of fairness.

How we listen to music...

Adam Gopnik has a very nice essay in The New Yorker on the mysteries of sound and the quest for 3-D recording. I was struck by his description of how the way we listen to music has changed. (I sometimes think with nostalgia about growing up in a 1950's household where "Hi Fidelity" was taken very seriously, trying as closely as possible to re-create the experience in the concert hall. Good old analog vinyl records played on mechanically sophisticated turntables with fancy diamond needles tracking the grooves, state of the art amplifiers, and speakers.... And now I have the best quality wireless speaker one can get, but it still must depend entirely on the compressed audio computer file formats such as .mp3 or.aiff, that throw away the richness I used to know.) His comments on how the music listening of his teen-age kids has changed, they:

...have an entirely different way of listening. They ignore the glowing-tube amp and classy articulate speakers in our living room; they bounce instead to tinny earbuds, and often spend hours listening to Taylor Swift or Radiohead on the still more tinny speakers of their computers. Sound quality seems secondary to some other thing they take from music...they have a more limited conception of larger forms, of the... of the symphony's three or four parts, of the swell and structure of a cantata. It isn't a question of classical tastes against pop; it's a question of small forms heard in motion against large form heard with solemn intent. "Sgt. Pepper: baffles them as much as Beethoven's Ninth. They snatch at music as we snatched at movies, filling our heads with plural images.

Gopnik's article presents fascinating interviews with current music researchers, from engineers like Edgar Choueiri to brain scientists such as Zatorre and Levitin at McGill University in Montreal. (MindBlog has several posts on their work.)

Internal threats to our bodies trigger different fear system from external threats.

A large volume of work has documented the amygdala's role in fear, and now Feinstein et al. present a surprising finding that carbon dioxide inhalation evokes fear and panic in three patients with bilateral amygdala damage (who feel no fear from external threats). These results indicate that the amygdala is not required for fear triggered internally rather than by external threats.  Here is the abstract:

Decades of research have highlighted the amygdala's influential role in fear. We found that inhalation of 35% CO₂ evoked not only fear, but also panic attacks, in three rare patients with bilateral amygdala damage. These results indicate that the amygdala is not required for fear and panic, and make an important distinction between fear triggered by external threats from the environment versus fear triggered internally by CO₂.

Why do these 'fearless' patients feel fear when CO₂ levels in their blood are increased? The authors suggest:

...that all of these other stimuli were exteroceptive in nature, mainly processed through visual and auditory pathways that project to the amygdala. In contrast, CO₂ acts internally at acid-activated chemoreceptors and causes an array of physiological changes. Thus, CO₂ might engage interoceptive afferent sensory pathways that project to the brainstem, diencephalon and insular cortex. In addition, many brain areas outside the amygdala possess CO2 and pH-sensitive chemoreceptors, including acid-sensing ion channels. Thus, CO₂ may directly activate extra-amygdalar brain structures that underlie fear and panic, which may help to explain the apparent discrepancy between these findings and previous work in mice. In either case, our results indicate that, in humans, the internal threat signaled by CO₂ is detected and interpreted as fear and panic despite the absence of an intact amygdala.