Deficits in cognitive control correlate with depression and rumination.

Joormann et al. make some observations on 'sticky thoughts.' I've edited their abstract a bit:

Cognitive inflexibility may play an important role in rumination, a risk factor for the onset and maintenance of depressive episodes. In the study reported here, we assessed participants’ ability to either reverse or maintain in working memory the order of three emotional (positive or negative) or three neutral words. Differences (or sorting costs) between response latencies in backward trials, on which participants were asked to reverse the order of the words, and forward trials, on which participants were asked to remember the words in the order in which they were presented, were calculated. [A recognition probe was used to index sorting costs (i.e., differences between response latencies on the forward and the backward trials. The probe word consisting of one of the three words was presented until the subject responded. Participants were instructed to press a key (“1,” “2,” or “3”) to indicate as quickly and as accurately as possible whether the probe was the first, second, or third word (counting forward or backward, as appropriate) in the set they had been instructed to remember.] Compared with control participants, depressed participants had higher sorting costs, particularly when presented with negative words. It is important to note that rumination predicted sorting costs for negative words but not for positive or neutral words in the depressed group. These findings indicate that depression and rumination are associated with deficits in cognitive control.

Our economic history

I want to point you to this article by Robert Reich in the Sunday New York Times, which is one the best description of our current economic mess that I have seen. Here is just a fragment of a great graphic summary the article provides (click to enlarge):

Neuroeconomics and the current financial crisis.

Cell press does a really remarkable job of assembling and pointing out important article in seminal areas of research.  I'm wanting in this post to point you to their Neuroscience Newsletter (that anyone can subscribe to) whose current issue emphasizes Neuroeconomics,  It has open access links to important articles. 

Our brains beat with the music...

From Nozaradan et al.:

Feeling the beat and meter is fundamental to the experience of music. However, how these periodicities are represented in the brain remains largely unknown. Here, we test whether this function emerges from the entrainment of neurons resonating to the beat and meter. We recorded the electroencephalogram while participants listened to a musical beat and imagined a binary or a ternary meter on this beat (i.e., a march or a waltz). We found that the beat elicits a sustained periodic EEG response tuned to the beat frequency. Most importantly, we found that meter imagery elicits an additional frequency tuned to the corresponding metric interpretation of this beat. These results provide compelling evidence that neural entrainment to beat and meter can be captured directly in the electroencephalogram. More generally, our results suggest that music constitutes a unique context to explore entrainment phenomena in dynamic cognitive processing at the level of neural networks.

The genetics of cognition

Trends in Cognitive Science has published a special issue on the genetics of cognition that is open access through September.

Twin, family and adoption studies have demonstrated that there is a substantial heritable component to all cognitive functions. The articles in this special issue summarize what is currently known about the genetic underpinnings of these functions and their disorders. At the same time, they highlight just how much there is yet to be discovered in this rapidly advancing field.

Robbins and Kousta provide an overview for the issue.
Review topics include:

-Genetics and criminal responsibility
-Genetics of human episodic memory: dealing with complexity
-The genetics of cognitive ability and cognitive ageing in healthy older people
-Dissecting the genetic architecture of human personality
-Genetics of emotion
-Genetics of autism spectrum disorders
-Understanding risk for psychopathology through imaging gene–environment interactions
-The genetics of cognitive impairment in schizophrenia: a phenomic perspective
-The contribution of imaging genetics to the development of predictive markers for  addictions

Women on the make are better at spotting gay men

These observations by Rule et al. sort of make sense, if you're a woman looking for a potential father of your children, you don't want to waste time dating gay men....

People can accurately infer others’ traits and group memberships across several domains. We examined heterosexual women’s accuracy in judging male sexual orientation across the fertility cycle (Study 1) and found that women’s accuracy was significantly greater the nearer they were to peak ovulation. In contrast, women’s accuracy was not related to their fertility when they judged the sexual orientations of other women (Study 2). Increased sexual interest brought about by the increased likelihood of conception near ovulation may therefore influence women’s sensitivity to male sexual orientation. To test this hypothesis, we manipulated women’s interest in mating using an unobtrusive priming task (Study 3). Women primed with romantic thoughts showed significantly greater accuracy in their categorizations of male sexual orientation (but not female sexual orientation) compared with women who were not primed. The accuracy of judgments of male sexual orientation therefore appears to be influenced by both natural variations in female perceivers’ fertility and experimentally manipulated cognitive frames.

Ironic effects of dietary supplements

Chiou et al. suggest that illusory invulnerability created by taking dietary supplements licenses health-risk behaviors. Their abstract (slightly edited):

The use of dietary supplements and the health status of individuals have an asymmetrical relationship: The growing market for dietary supplements appears not to be associated with an improvement in public health. Building on the notion of licensing, or the tendency for positive choices to license subsequent self-indulgent choices, we argue that because dietary supplements are perceived as conferring health advantages, use of such supplements may create an illusory sense of invulnerability that disinhibits unhealthy behaviors. In two experiments, participants who took placebo pills that they believed were dietary supplements, compared with participants who were told the pills were a placebo, exhibited the licensing effect across multiple forms of health-related behavior: In a first experiment they expressed less desire to engage in exercise and more desire to engage in hedonic activities, and expressed greater preference for a buffet over an organic meal. In a second experiment they walked less to benefit their health. A mediational analysis indicated that perceived invulnerability was an underlying mechanism for these effects. Thus, a license associated with the use of dietary supplements may operate within cycles of behaviors that alternately protect and endanger health.

Microbes run the world

In my continuing scan of edge.org's annual question, I come across this essay by Stewart Brand, that continues the thread started last week on on how 'we' (humans) are mostly 'they' (microbes). Some clips:

Microbes make up 80 percent of all biomass, says Carl Woese. In one fifth of a teaspoon of seawater there's a million bacteria (and 10 million viruses), Craig Venter says, adding, "If you don't like bacteria, you're on the wrong planet. This is the planet of the bacteria." That means most of the planet's living metabolism is microbial. When James Lovelock was trying to figure out where the gases come from that make the Earth's atmosphere such an artifact of life (the Gaia Hypothesis), it was microbiologist Lynn Margulis who had the answer for him. Microbes run our atmosphere. They also run much of our body. The human microbiome in our gut, mouth, skin, and elsewhere, harbors 3,000 kinds of bacteria with 3 million distinct genes. (Our own cells struggle by on only 18,000 genes or so.) New research is showing that our microbes-on-board drive our immune systems and important portions of our digestion.

Microbial evolution, which has been going on for over 3.6 billion years, is profoundly different from what we think of as standard Darwinian evolution, where genes have to pass down generations to work slowly through the selection filter. Bacteria swap genes promiscuously within generations. They have three different mechanisms for this "horizontal gene transfer" among wildly different kinds of bacteria, and thus they evolve constantly and rapidly. Since they pass on the opportunistically acquired genes to their offspring, what they do on an hourly basis looks suspiciously Lamarckian — the inheritance of acquired characteristics.

Such routinely transgenic microbes show that there's nothing new, special, or dangerous about engineered GM crops. Field biologists are realizing that the the biosphere is looking like what some are calling a pangenome, an interconnected network of continuously circulated genes that is a superset of all the genes in all the strains of a species that form. Bioengineers in the new field of synthetic biology are working directly with the conveniently fungible genes of microbes.

This biotech century will be microbe enhanced and maybe microbe inspired. "Social Darwinism" turned out to be a bankrupt idea. The term "cultural evolution" never meant much, because the fluidity of memes and influences in society bears no relation to the turgid conservatism of standard Darwinian evolution. But "social microbialism" might mean something as we continue to explore the fluidity of traits and vast ingenuity of mechanisms among microbes — quorum sensing, biofilms, metabolic bucket brigades, "lifestyle genes," and the like.

G-Male

I just had to pass on this dead-on (and scary) parody of Google that my daughter pointed out to me.

Just looking at the American flag can make you a Republican?

Oh-my-gawd, now do we not only have a potential president Rick Perry who will rule by faith over reason, and doesn't believe in science, evolution, or climate change, we have a drift of the populace towards the republican base of his support by subtle nudges of the sort documented by Carter et al. Simple exposure to the American flag leads to a shift towards Republican beliefs:

There is scant evidence that incidental cues in the environment significantly alter people’s political judgments and behavior in a durable way. We report that a brief exposure to the American flag led to a shift toward Republican beliefs, attitudes, and voting behavior among both Republican and Democratic participants, despite their overwhelming belief that exposure to the flag would not influence their behavior. In Experiment 1, which was conducted online during the 2008 U.S. presidential election, a single exposure to an American flag resulted in a significant increase in participants’ Republican voting intentions, voting behavior, political beliefs, and implicit and explicit attitudes, with some effects lasting 8 months after the exposure to the prime. In Experiment 2, we replicated the findings more than a year into the current Democratic presidential term. These results constitute the first evidence that nonconscious priming effects from exposure to a national flag can bias the citizenry toward one political party and can have considerable durability.

Fat mice live longer with resveratrol.

Nicholas Wade points to a study by de Cabo, Sinclar, and colleages that studies the effect of a drug, SRT-1720, that has extends the lifespan of mice on a low calorie diet, but at much lower (less toxic) concentrations than resveratrol. Benefits of the drug are much easier to demonstrate in mice under physiological stress like obesity than in normal mice. The studied found that obese animals taking the drug lived 44 percent longer, on average, than control obese animals. From Wade's comments:

The sirtuins help bring about the 30 percent extension of life span enjoyed by mice and rats that are kept on very low-calorie diets. Since few people can keep to such an unappetizing diet, researchers hoped that doses of resveratrol might secure a painless path to significantly greater health and longevity...But large doses of resveratrol are required to show any effect, so chemical mimics like SRT-1720 were developed to activate sirtuin at much lower doses...Sirtuins have proved to be highly interesting proteins, but the goal of extending life span was set back last year when extensive trials of resveratrol showed it did not prolong mice’s lives, although it seemed to do them no harm. Another blow came in 2009, when biologists at Pfizer reported that SRT-1720 and other resveratrol mimics did not activate sirtuins and did not have any beneficial effects in fat mice...The report by Dr. de Cabo and his colleagues may do much to rescue SRT-1720 from this shadow. They found that SRT-1720 offered substantial benefits to the fat mice, with no signs of toxicity. Unlike the Pfizer study, which was short term, they followed large groups of mice for over three years.

Here is the article abstract:

Sirt1 is an NAD+-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and specific gene knockdowns we show SRT1720 affects mitochondrial respiration in a Sirt1- and PGC-1α-dependent manner. These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals.

Estimates of social influence - the "unfriending problem"

In the latest issue (Aug 26) of Science Magazine Barbara Jasny does a nice summary of recent work by Noel and Nyhan:

Studies of social influences on behavior have led to the idea that a range of characteristics from loneliness to obesity might be contagious. A significant problem for the field has been to distinguish effects due to similarities between people (homophily) from social influence. One strategy for doing this has been to look at changes that occur over time. However, such studies have been the subject of considerable debate, and Noel and Nyhan now add a cautionary note. Their analyses of a model used in past social contagion studies suggest that previous investigations have not fully controlled for the possibility that friendship formation and termination are dynamic processes, and friendships between people who are more similar may tend to be more stable over time. Or to put it in Facebook terms, friendships that are between people who are less similar may be less stable, and therefore may result in “unfriending.” Homophily might thus be having a larger effect than appreciated, and under certain conditions could account for most of the contagion effects observed. They conclude that this unfriending problem renders a determination of causality much more complicated in longitudinal social network data.

Synthesis of new brain cells and social dysfunction.

In rodent models of depression, antidepressant drugs are effective only if the hippocampus is able to generate new nerve cells (neurogenesis), suggesting an association between adult hippocampal neurogenesis and depression. Synder et al. have done the direct experiment of using a genetic trick to make mouse hippocampal cells sensitive to the antiviral drug valganciclovir, which inhibits cell proliferation. Valganciclovir treatment of the genetically altered mice almost completely abolished hippocampal neurogenesis. Their results support a direct role for adult neurogenesis in depressive illness. Here is their abstract:

Glucocorticoids are released in response to stressful experiences and serve many beneficial homeostatic functions. However, dysregulation of glucocorticoids is associated with cognitive impairments and depressive illness. In the hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis. Decreased neurogenesis has been implicated in the pathogenesis of anxiety and depression, but direct evidence for this role is lacking. Here we show that adult-born hippocampal neurons are required for normal expression of the endocrine and behavioural components of the stress response. Using either transgenic or radiation methods to inhibit adult neurogenesis specifically, we find that glucocorticoid levels are slower to recover after moderate stress and are less suppressed by dexamethasone in neurogenesis-deficient mice than intact mice, consistent with a role for the hippocampus in regulation of the hypothalamic–pituitary–adrenal (HPA) axis. Relative to controls, neurogenesis-deficient mice also showed increased food avoidance in a novel environment after acute stress, increased behavioural despair in the forced swim test, and decreased sucrose preference, a measure of anhedonia. These findings identify a small subset of neurons within the dentate gyrus that are critical for hippocampal negative control of the HPA axis and support a direct role for adult neurogenesis in depressive illness.

Brain excitation/inhibition balance and social dysfunction

Yates does a review of recent work by Deisseroth and colleagues, who have now shown that in mice, an elevation in the excitation/inhibition ratio in the medial prefrontal cortex (mPFC) impairs cellular information processing and leads to specific behavioral impairments. They made, and then genetically inserted, different forms of opsin molecules in different excitatory and inhibitory neuronal mPFC populations. By flashing the cortex with different wavelengths of light they could increase levels of either excitation or inhibition. Here is their abstract:

Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30–80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.

A unified bottleneck in our brains limits our attention

It has been a common assumption that different tasks requiring our attention, like making perception distinctions or making action choices are limited by brain areas most associated with those function. Tombu et al. now find a unified attentional bottleneck, including the inferior frontal junction, superior medial frontal cortex, and bilateral insula.

Human information processing is characterized by bottlenecks that constrain throughput. These bottlenecks limit both what we can perceive and what we can act on in multitask settings. Although perceptual and response limitations are often attributed to independent information processing bottlenecks, it has recently been suggested that a common attentional limitation may be responsible for both. To date, however, evidence supporting the existence of such a “unified” bottleneck has been mixed. Here, we tested the unified bottleneck hypothesis using time-resolved fMRI. The first experiment isolated brain regions involved in the response selection bottleneck that limits speeded dual-task performance. These same brain regions were not only engaged by a perceptual encoding task in a second experiment, their activity also tracked delays to a speeded decision-making task caused by concurrent perceptual encoding in a third experiment. We conclude that a unified attentional bottleneck, including the inferior frontal junction, superior medial frontal cortex, and bilateral insula, temporally limits operations as diverse as perceptual encoding and decision-making.

New views on cancer - 99% of the functioning genes in our bodies are not ‘ours’.

They are the genes of bacteria and fungi that have evolved with us in a symbiotic relationship. This fascinating factoid is from an article by George Johnson describing fundamental changes in the way researchers are viewing the cancer process, as the reigning model - that “Through a series of random mutations, genes that encourage cellular division are pushed into overdrive, while genes that normally send growth-restraining signals are taken offline” - is supplemented by a number of subtle variations:

..genes in this microbiome — [of bacteria and fungi] exchanging messages with genes inside human cells — may be involved with cancers of the colon, stomach, esophagus and other organs...The idea that people in different regions of the world have co-evolved with different microbial ecosystems may be a factor — along with diet, lifestyle and other environmental agents — in explaining why they are often subject to different cancers.

...Most DNA…was long considered junk … Only about 2 percent of the human genome carries the code for making enzymes and other proteins…These days “junk” DNA is referred to more respectfully as “noncoding” DNA, and researchers are finding clues that “pseudogenes” lurking within this dark region may play a role in cancer.

...With so much internal machinery, malignant tumors are now being compared to renegade organs sprouting inside the body…[they] contain healthy cells that have been conscripted into the cause. Cells called fibroblasts collaborate by secreting proteins the tumor needs to build its supportive scaffolding and expand into surrounding tissues. Immune system cells, maneuvered into behaving as if they were healing a wound, emit growth factors that embolden the tumor and stimulate angiogenesis, the generation of new blood vessels. Endothelial cells, which form the lining of the circulatory system, are also enlisted in the construction of the tumor’s own blood supply.

The article lists a number of further ideas, involving various classes of small or micro RNAs, here's a great sentence:

...other exotic players: lincRNA, (for large intervening noncoding), siRNA (small interfering), snoRNA (small nucleolar) and piRNA (Piwi-interacting (short for “P-element induced wimpy testis” (a peculiar term that threatens to pull this sentence into a regress of nested parenthetical explanations))).

Trying to live forever - Centenarians have plenty of bad habits

Here are two recent bits on aging:
O'Connor points to a study that

...focused on Ashkenazi Jews, a group that is more genetically homogenous than other populations, making it easier to identify genetic differences that contribute to life span. In the study, the researchers followed 477 Ashkenazi centenarians who were 95 or older and living independently. They asked them about their habits and the ways they lived when they were younger. Using data collected in the 1970s, the researchers compared the long-lived group with another group of 3,000 people in the general population who were born around the same time but who generally did not make it to age 95...They found that the people who lived to 95 and beyond did not seem to exhibit healthier lifestyles than those who died younger.

The article continues to discuss social, personality, and genetic factors influencing longevity. The take home message is that people with the genes for longevity live past age 95 with habits no different from most others, but the average person would probably have to follow a healthy lifestyle to live comfortably past 80.

And, here is a bit of sanity, from Gary Gutting, on trying to live forever. He emphasizes that correlations do not prove causes (lower HDL levels correlate with more heart attacks, but clinical studies show raising HDL (good) cholesterol with drugs does nothing to protect against heart attacks.) He argues against chasing after the latest dietary supplement whose relevance is implied from correlation studies ('It can't hurt, it might help'... which I'm guilty of), and simply following the humdrum standard advice we’ve heard all our lives about eating sensibly, exercising regularly, and having recommended medical tests and exams. Apart from that, "how we die is a crap-shoot, and, short of avoiding obvious risks such as smoking and poor diet, there’s little we can do to load the dice."

Neotony - how long does our pre-frontal cortex stay young?

When I first looked at the title "Extraordinary neoteny of synaptic spines in the human prefrontal cortex", I excitedly thought "Great, I'm going to learn that my 69 year old prefrontal cortex is still crafting and pruning synapses." Alas, by extraordinary, the authors mean that they have determined that the 2-3 fold decrease in the density of dendritic spines previously thought to be largely complete by the end of adolescence continues well into the third decade of life before stabilizing at the adult level.

The major mechanism for generating diversity of neuronal connections beyond their genetic determination is the activity-dependent stabilization and selective elimination of the initially overproduced synapses [Changeux JP, Danchin A (1976) Nature 264:705–712]. The largest number of supranumerary synapses has been recorded in the cerebral cortex of human and nonhuman primates. It is generally accepted that synaptic pruning in the cerebral cortex, including prefrontal areas, occurs at puberty and is completed during early adolescence [Huttenlocher PR, et al. (1979) Brain Res 163:195–205]. In the present study we analyzed synaptic spine density on the dendrites of layer IIIC cortico–cortical and layer V cortico–subcortical projecting pyramidal neurons in a large sample of human prefrontal cortices in subjects ranging in age from newborn to 91 y. We confirm that dendritic spine density in childhood exceeds adult values by two- to threefold and begins to decrease during puberty. However, we also obtained evidence that overproduction and developmental remodeling, including substantial elimination of synaptic spines, continues beyond adolescence and throughout the third decade of life before stabilizing at the adult level. Such an extraordinarily long phase of developmental reorganization of cortical neuronal circuitry has implications for understanding the effect of environmental impact on the development of human cognitive and emotional capacities as well as the late onset of human-specific neuropsychiatric disorders.

The dark side of emotion in decision making.

A mindblog reader emailed me pointing out this (before MindBlog started up) 2005 publication by Bechara and collaborators on the role of emotion in making decisions in risky situations (rather relevant to our current financial crisis, with investors rushing like lemmings to emotionally drive the market in huge up or down swings). Disabling normal emotional reactivity by either brain lesions or substance abuse leads people to make more advantageous decision in risky situation. (In a 2009 post I noted Bechara's more recent work on reward processing in different parts of the brain.

Can dysfunction in neural systems subserving emotion lead, under certain circumstances, to more advantageous decisions? To answer this question, we investigated how individuals with substance dependence (ISD), patients with stable focal lesions in brain regions related to emotion (lesion patients), and normal participants (normal controls) made 20 rounds of investment decisions. Like lesion patients, ISD made more advantageous decisions and ultimately earned more money from their investments than the normal controls. When normal controls either won or lost money on an investment round, they adopted a conservative strategy and became more reluctant to invest on the subsequent round, suggesting that they were more affected than lesion patients and ISD by the outcomes of decisions made in the previous rounds.

Why worry? It's good for you.

I've been meaning to point out an interesting piece by Robert Frank in the business section of the NYTimes, a subject mindblog has touched on in several posts. It's a bit of a gloss, but I pull out a few clips:

…people are particularly inept at predicting how changes in their life circumstances will affect their happiness. Even when the changes are huge — positive or negative — most people adapt much more quickly and completely than they expected…Paradoxically, our prediction errors often lead us to choices that are wisest in hindsight. In such cases, evolutionary biology often provides a clearer guide than cognitive psychology for thinking about why people behave as they do…the brain has evolved not to make us happy, but to motivate actions that help push our DNA into the next round. Much of the time, in fact, the brain accomplishes that by making us unhappy. Anxiety, hunger, fatigue, loneliness, thirst, anger and fear spur action to meet the competitive challenges we face…pleasure is an inherently fleeting emotion, one we experience while escaping from emotionally aversive states. In other words, pleasure is the carrot that provokes us to extricate ourselves from such states, but it almost always fades quickly…The human brain was formed by relentless competition in the natural world, so it should be no surprise that we adapt quickly to changes in circumstances.

Most people would love to have a job with interesting, capable colleagues, a high level of autonomy and ample opportunities for creative expression. But only a limited number of such jobs are available — and it’s our fretting that can motivate us to get them....Within limits, worry about success causes students to study harder to gain admission to better universities. It makes assistant professors work harder to earn tenure. It leads film makers to strive harder to create the perfect scene, and songwriters to dig deeper for the most pleasing melody. In every domain, people who work harder are more likely to succeed professionally, more likely to make a difference...The anxiety we feel about whether we’ll succeed is evolution’s way of motivating us.