Do we need an Apollo moon project for the brain?

I have collected a sampling of the many commentaries on the Brain Activity Map project to which Barack Obama alluded in his State of the Union address which is becoming a high profile 3-billion dollar endeavor. For a few examples, see the NYTimes, The Altantic, and Plos Blogs. I finally want to put in my two cents worth to say that such an effort is completely misguided. But first, clips from a Science article contributed by 'big science' luminaries who would profit from such a project.

...the mechanisms of perception, cognition, and action remain mysterious because they emerge from the real-time interactions of large sets of neurons in densely interconnected, widespread neural circuits. It is time for a large-scale effort in neuroscience to create and apply a new generation of tools to enable the functional mapping and control of neural activity in brains with cellular and millisecond resolution...This initiative, the Brain Activity Map (BAM), could put neuroscientists in a position to understand how the brain produces perception, action, memories, thoughts, and consciousness

The last phrase, in particular, is borderline delusional. As John Horgan points out, we don't even see the side of the barn yet. Apart from the fact that we don’t know what to include in a simulation and what to leave out, we already have conclusive evidence that a search for a road map of stable neural pathways that can represent brain functions is futile. Edited from Horgan:

...the brain is radically unlike and more complex than any existing computer. A typical brain contains 100 billion cells, and each cell is linked via synapses to as many as 100,000 others. Synapses are awash in neurotransmitters, hormones, modulatory peptide (small proteins), neural-growth factors and other chemicals that affect the transmission of signals, and synapses constantly form and dissolve, weaken and strengthen, in response to new experiences...not only do old brain cells die, new ones can form via neurogenesis...many genes are constantly turning on and off and thereby further altering operations of brain nerve cells...the brain may be processing information at many levels below and above that of individual neurons and synapses...each individual neuron, rather than resembling a transistor, maybe be more like a computer in its own right, engaging in complex information-processing.

I fear that these big, much-hyped initiatives will turn out to be as disappointing as the Decade of the Brain. Rather than boosting the status of neuroscience, they may harm its credibility.

A particularly telling story comes from my long time friend and colleague Tony Stretton at the University of Wisconsin, who studies the very simple nervous system of the parasitic nematode Ascaaris suum, that has only 298 neurons, for which a functional circuit from the morphological synapses, scored by electron microscopy, has been obtained. This is just the sort of information the Brain Activity Map project is trying to obtain for our brains. So, do we know how the Ascaris nervous system works? No, we're not even close, because Stretton has discovered that their are numerous peptides (as many as 250) that modulate the activity of neurons. Go figure how neurons in that complex modulatory soup work!! And multiply the problem by at least a billion for our brains.

To be fair, the vigorous discussion over the merits of a big push has led, as Markoff and Gorman describe in the NYTimes, to cast the enterprise as trying to better define the playing field, rather than assuming that we now know what it is.  

A next generation of antidepressants?

Russo and Charney do a brief write up on recent work of Nasca et al., who find that a common dietary supplement, L-acetylcarnitine, is a potential rapidly acting antidepressant:

Over the past 50 y, there have been few mechanistically distinct drugs for the treatment of major depressive disorders, despite the fact that nearly two-thirds of patients do not achieve full remission of symptoms on currently available antidepressants. In addition, even when adequate remission is achieved, patients require 2–4 wk of treatment before any significant effects, increasing the risk for complications, such as suicide. This delay in effectiveness has resulted in a major push to identify and develop novel therapeutics with more rapid effects. The recent identification of ketamine as a rapid antidepressant effective in treatment-resistant patients has been groundbreaking.

Nasca et al.  describe in PNAS a unique potential rapidly acting antidepressant, l-acetylcarnitine (LAC), which is a dietary supplement that acts by acetylating protein targets to control their function. LAC is reported to be well tolerated and can readily cross the blood-brain barrier. A recent study suggests it has promise in the treatment of Parkinson disease because of its neroprotective properties. Strikingly, LAC exhibits antidepressant efficacy within 2–3 d following intraperitoneal administration in rodents, compared with 2–3 wk with a standard antidepressant treatment, such as chlorimipramine. Although LAC is relatively nonspecific and can target many biological pathways, it is suggested by Nasca et al.  to promote rapid antidepressant responses by acetylation of histone proteins that control the transcription of BDNF and metabotropic glutamate 2 (mGlu2) receptors in the hippocampus (Hipp) and prefrontal cortex (PFC).

One of the more impressive aspects of this article is that Nasca et al. verify rapid antidepressant efficacy of LAC in both a genetic rat model of susceptibility [Flinders Sensitive Line (FSL)] and following chronic stress exposure, factors that are thought to be the primary cause of depression in humans. Although there is clearly far more work necessary to understand the mechanisms of antidepressant action of LAC in rodents, and the dose and relative safety profile for depression treatment in humans, these exciting results are a first step toward that goal.

What are philosophers good for?

Perhaps an appropriate post for April 1st...If you are looking for a good headache, take yourself to Gary Gutting's rehashing of the "can consciousness be explained in physical terms?" debate by dragging out the classic "Mary, the color blind scientist who knows all the physical facts about colors and their perception" and the "philosophical zombie, defined as physically identical to you or me but utterly lacking in internal subjective experience." Gutting solicits comments on his article, and in a subsequent article presents a selection of the responses. From Gutting's final paragraph:

...my conclusion is that neither the Mary nor the Zombie Argument makes a decisive case against physicalism...professional philosophers have uncovered a number of subtle and complex problems for both arguments. For anyone interested in pursuing the discussion further, I would recommend the Stanford Encyclopedia of Philosophy articles “Qualia: The Knowledge Argument” (by Martine Nida-Rümelin) and “Zombies” (by Robert Kirk).

I like Metzinger's stance that consciousness is epistemologically irreducible (see his book "The Ego Tunnel"). There is one reality, one kind of fact, but two kinds of knowledge: first-person knowledge and third-person knowledge, that never can be conflated. There is a long list of ideas on why consciousness evolved, what it is good for, doing goal hierarchies and long-terms plans, enhancement of social coordination, etc. I like Metzinger's description of consciousness as a as a new kind of virtual organ - unlike the permanent hardware of the liver, kidney, or heart it is always present. Virtual organs form for a certain time when needed (like desire, courage, anger, an immune response)..."they are a new computational strategy, that makes classes of facts globally available and allows attending, flexible reacting, within context." "Reality generation" allowed animals to represent explicitly the fact that something is actually the case, the world is present. (conscious color gives information about nutritional value, red berries among green leaves, empathy gives information about the emotional state of conspecifics).

For those of you who like this sort of stuff I point out "A darwinist lynch mob goes after a philosopher" by Leon Wieseltier in the March 11 New Republic, on some outraged reactions to Nagel's new book: "Mind and Cosmos: Why the Materialist Neo-Darwinian Conception of Nature Is Almost Certainly False."

Also,"Was Wittgenstein Right? by Paul Horwich:

Wittgenstein claims that there are no realms of phenomena whose study is the special business of a philosopher, and about which he or she should devise profound a priori theories and sophisticated supporting arguments. There are no startling discoveries to be made of facts, not open to the methods of science, yet accessible “from the armchair” through some blend of intuition, pure reason and conceptual analysis. Indeed the whole idea of a subject that could yield such results is based on confusion and wishful thinking.

To which Michael Lynch makes a rejoinder.

 I have to end by repeating another old chestnut:

Philosophy, n. A route of many roads leading from nowhere to nothing. -AMBROSE BIERCE, The Devil's Dictionary

Brain activity associated with the "Cocktail Party Effect."

Zion et al. do interesting experiments, with an array of sub-dural electrodes implanted in surgical epilepsy patients, to show what is happening as we attend to one of several simultaneously talking voices. From a commentary by Miller:

The data clearly show that both low-frequency phase (delta-theta, 1–7 Hz) and high gamma power (70–150 Hz) yield consistent trial-to-trial responses to speech. Other frequency bands do not, nor does low frequency power—adding weight to the argument that speech tracking is partly due to entrainment of endogenous rhythms. However, these effects are not equally distributed across cortical areas. The high-gamma tracking tends to be clustered in the superior temporal lobe and the low-frequency phase response is more widespread, including superior and anterior temporal regions and inferior parietal and frontal lobes. Across electrodes though, both the low-frequency phase and high-gamma power showed more consistent responses to the attended versus the ignored speech. Corroborating this observation, speech envelope acoustics could only be reconstructed from neural responses for the attended talker, not the unattended.

The Zion et al. abstract:

The ability to focus on and understand one talker in a noisy social environment is a critical social-cognitive capacity, whose underlying neuronal mechanisms are unclear. We investigated the manner in which speech streams are represented in brain activity and the way that selective attention governs the brain’s representation of speech using a “Cocktail Party” paradigm, coupled with direct recordings from the cortical surface in surgical epilepsy patients. We find that brain activity dynamically tracks speech streams using both low-frequency phase and high-frequency amplitude fluctuations and that optimal encoding likely combines the two. In and near low-level auditory cortices, attention “modulates” the representation by enhancing cortical tracking of attended speech streams, but ignored speech remains represented. In higher-order regions, the representation appears to become more “selective,” in that there is no detectable tracking of ignored speech. This selectivity itself seems to sharpen as a sentence unfolds.

The perils of perfectionism, and the world we are losing.

I want to mention one of the many items in my queue of articles for potential posts that I have neglected so far.  Vgeny Morozov does a precis of his new book “To Save Everything, Click Here: The Folly of Technological Solutionism.”

Silicon Valley’s technophilic gurus and futurists have embarked on a quest to develop the ultimate patch to the nasty bugs of humanity…Facebook’s former marketing director, enthused about a trendy app to “crowdsource absolutely every decision in your life.” Called Seesaw, the app lets you run instant polls of your friends and ask for advice on anything…Jean-Paul Sartre, the existentialist philosopher who celebrated the anguish of decision as a hallmark of responsibility, has no place in Silicon Valley.

All these efforts to ease the torments of existence might sound like paradise to Silicon Valley. But for the rest of us, they will be hell. They are driven by a pervasive and dangerous ideology that I call “solutionism”: an intellectual pathology that recognizes problems as problems based on just one criterion: whether they are “solvable” with a nice and clean technological solution at our disposal. Thus, forgetting and inconsistency become “problems” simply because we have the tools to get rid of them — and not because we’ve weighed all the philosophical pros and cons…Given Silicon Valley’s digital hammers, all problems start looking like nails, and all solutions like apps…Whenever technology companies complain that our broken world must be fixed, our initial impulse should be to ask: how do we know our world is broken in exactly the same way that Silicon Valley claims it is? What if the engineers are wrong and frustration, inconsistency, forgetting, perhaps even partisanship, are the very features that allow us to morph into the complex social actors that we are?

In the same apocalyptic spirit Edward Hoagland writes a lyrical elegy to the natural world we are losing:

Aesop, the fabulist and slave who, like Scheherazade, may have won his freedom by the magic of his tongue and who supposedly shared the Greek island of Samos with Pythagoras 2,500 years ago, nailed down our fellowship with other beasties of the animal kingdom. Yet we seem to have reached an apogee of separation since then. The problem is, we find ourselves quite ungovernable when operating solo, shredding our habitat, while hugging our dogs and cats as if for consolation and dieting on whole-food calories if we are affluent enough. Google Earth and genome games also lend us a fitful confidence that everything is under control.

It’s a steeplechase, hell-for-leather and exhilarating, for the highest stakes, but not knowing where we’re going. Call it progress or metastasizing, what we have done as a race, a species or a civilization is dumbfounding. Every inch of the planet is ours, we claim, and elements of clear improvement are intertwined with cancerous excess

…Aesopian metaphors were artesian if not prehistoric. The tortoise and the hare, the lion saved by the mouse, the monkey who would be king, the dog in the manger, the dog and his shadow, the country mouse and the city mouse, the wolf in sheep’s clothing, the raven and the crow, the heron and the fish, the peacock and the crane. From where will we draw replacement similes and language? Pop culture somersaults “bad” to mean good, “cool” to mean warm, and bustles and bodices segue into tank tops and cargo pants, as in a robust society they should. But will a natural keel remain, as we face multiflex, multiplex change? “Hogging” the spotlight, playing possum, resembling a deer in the headlights, being buffaloed or played like a fish: will the clarity of what is said hold? A “tiger,” a “turtle,” a “toad.” After the oceans have been vacuumed of protein and people are eating farmed tilapia and caked algae, will Aesop’s platform of markers remain?

Ambivalence and Body Movement

Schneider et al. make interesting observations about circulation correlations between our thoughts and body movements. We sway more from side to when we feel ambivalent about a choice or situation, and if we apply a swaying motion to our bodies, that makes us feel more ambivalent about a topic on which we are already uncertain.

Prior research exploring the relationship between evaluations and body movements has focused on one-sided evaluations. However, people regularly encounter objects or situations about which they simultaneously hold both positive and negative views, which results in the experience of ambivalence. Such experiences are often described in physical terms: For example, people say they are “wavering” between two sides of an issue or are “torn.” Building on this observation, we designed two studies to explore the relationship between the experience of ambivalence and side-to-side movement, or wavering. In a first study, we used a Wii Balance Board to measure movement and found that people who are experiencing ambivalence move from side to side more than people who are not experiencing ambivalence. In a second study, we induced body movement to explore the reverse relationship and found that when people are made to move from side to side, their experiences of ambivalence are enhanced.

If you use Google Reader to follow Deric's MindBlog, please read on....

This blog has ~2,500 RSS subscribers. As I write this, 2,240 subscribers are obtaining the feed via Feedfetcher, which is how Google grabs RSS or Atom feeds when users subscribe to them in Google Reader or iGoogle. Feedfetcher collects and periodically refreshes these user-initiated feeds.

Because it doesn't make the billions of dollars that Google requires for a service, Google has announced that it is shutting it down on July 1. If you want to continue getting MindBlog's RSS feed you will need to use an alternative reader. This Lifehacker post suggests five of the best alternatives - a few further suggestions are here. (I use my My Yahoo home page to obtain RSS feeds from blogs I follow.) Also, a note: There are more petitions floating around the web to keep Google Reader alive than it is possible to count.

(added note, comment from blog re3ader: "It should be noted that you don't need to use unreliable web services to aggregate rss/atom feeds. There are lots of excellent software programs to do so. By using actual software instead of a third party web service you have both insured access and offline access. I use rssowl, a program that runs on the big three OSes (http://www.rssowl.org/)." )

Are there trendy parts of the brain?

Behrens et al. do an interesting analysis, asking:

Are there really trendy parts of the brain? Or does each scientist falsely believe their own research area to be underrepresented in the top journals, and their friend's recent Nature paper to be the result of a passing fad? The maturity of functional brain imaging allows us to perform a rigorous test of this instinctual feeling. There have now been many thousands of imaging papers published across the journal spectrum. Are some brain regions really overrepresented in this literature? In addition, are papers reporting activation in some brain regions preferentially published in high-impact journals, whereas others are published in low-impact ones? To answer these questions, we examined 7342 functional contrasts published between 1985 and 2008 and documented in the BrainMap database.

Figure - (a) Distributions of activation frequency across the brain. Popular voxels are portrayed in red; unpopular ones in blue. (b) Frequency distribution of keywords describing experimental domains, paradigms, and functional contrasts. The size of each word is proportional to its frequency in the BrainMap database.

Journal impact factor strongly predicted activity in several different brain areas. With one exception in the primary visual cortex, we suspect these brain regions would largely confirm anecdotal hypotheses. For example, researchers who find activity in a prescribed part of the fusiform gyrus should be confident of having their article selected for publication in a high-impact journal, perhaps due to the role of the region in face processing. Other regions with proposed roles in emotional processing returned similarly stellar performances, including both the ventral and dorsal portions of the rostral medial prefrontal cortex, the anterior insular cortex, the anterior cingulate gyrus, and the amygdala. The recent interest in reward prediction errors might explain impactful peaks in the mid-brain and ventral striatum, areas that exhibited independent significant effects of impact factor, publication date, and their interaction: studies reporting activation in these regions are published in high-impact journals, and are increasing in number (as a proportion of all studies) over time.

A Cornucopia of Mind Blog sites.

Scientific American has announced that its daughter magazine Scientific American Mind has set up a Blogs site that lists a number of psychology, neuroscience, etc. blogs dealing with the Mind. Just starting to sample from the blogs listed is an overwhelming experience. Keeping up with blogs dealing with mind in the current blogosphere would be more than a full time job. My own list of "Other Mind Blogs" in the right hand column of this blog is several years old, and now doesn't include many excellent current efforts. I occasionally find this blog listed in "Top Psychology Blogs" on other sites.  We could all easily spend all our time "taking in each other's laundry," to become aggregators of aggregators of aggregators ad infinitum. This is why I don't look much at other Mind Blogs, but rather stick to looking through recent original research articles in the major journals. The efforts of each of us who labor away passing on some small fraction of the research world are appreciated by a sufficient number of readers to motivate us to continue.

Having said I don't look at other mind blogs,  I'll pass on this gem from "Brain Pickings" (click to enlarge and see text more clearly: "Friendship-The Silent Places-Where Speech Ends"

The brain basis of our superiority illusion.

One of the most robustly documented findings of psychology is the "optimism" bias, which leads us to put rose-colored glasses on past, future, and our own abilities. (Did you know that a spectacular 94% of college professors rate themselves to have teaching abilities that are above average?.) Equally well documented is the fact the people who have a fully realistic view of their abilities and their importance to groups tend to be depressed. It seems clear that most of us are completely unequipped to function without a vast array of positive delusions about our abilities, our futures, etc.

There is a large literature on this. Dan Dennett and McKay have written a treatise in Brain and Behavioral Science that examines possible evolutionary rationales for mistaken beliefs, bizarre delusions, instances of self-deception, etc., they conclude that only positive illusions meet their criteria for being adaptive. Johnson and his colleagues have produced an evolutionary model suggesting that overconfidence maximizes individual fitness and that populations tend to become overconfident as long as benefits from contested resources are sufficiently large compared with the cost of competition.

 Yamada et al. now look at resting state functional connectivity between brain regions whose activity correlates with the superiority illusion. Their abstract, and one figure from their paper:

The majority of individuals evaluate themselves as superior to average. This is a cognitive bias known as the “superiority illusion.” This illusion helps us to have hope for the future and is deep-rooted in the process of human evolution. In this study, we examined the default states of neural and molecular systems that generate this illusion, using resting-state functional MRI and PET. Resting-state functional connectivity between the frontal cortex and striatum regulated by inhibitory dopaminergic neurotransmission determines individual levels of the superiority illusion. Our findings help elucidate how this key aspect of the human mind is biologically determined, and identify potential molecular and neural targets for treatment for depressive realism.

Influence of striatal D2 availability on superiority illusion is mediated through dorsal anterior cingulate - striatal functional connectivity. Assuming an inverse relationship between D2 receptor availability and presynaptic dopamine release, dopamine likely acts on striatal D2 receptors to suppress functional connectivity between the dorsal striatum and dACC (2). This connectivity predicts individual differences in the superiority illusion  The indirect effect of striatal D2 receptor availability on the superiority illusion is significantly mediated through dACC-striatal functional connectivity . “+” indicates a positive relationship; “–,” a negative relationship.

Would Tarzan believe in God?

Some clips from Konika Banerjee and Paul Bloom:

Would someone raised without exposure to religious views nonetheless come to believe in the existence of God, an afterlife, and the intentional creation of humans and other animals? Many scholars would answer yes, proposing that universal cognitive biases generate religious ideas anew within each individual mind. Drawing on evidence from developmental psychology, we argue here that the answer is no: children lack spontaneous theistic views and the emergence of religion is crucially dependent on culture.

...if universal, early-emerging cognitive biases generate religious ideas, we would expect to see these ideas emerge spontaneously. This would be akin to the process of creolization, such as when deaf children who are exposed to non-linguistic communication systems create their own sign language. However, such cases are, as best we know, non-existent. There are many examples where children are quick to endorse religious beliefs, often surprising their atheist parents. But this is consistent with receptivity, not generativity, as these beliefs correspond to those endorsed within the social environment in which children are raised.

Findings from developmental psychology support the following theory of the emergence of religious belief: humans possess a suite of sophisticated cognitive adaptations for social life, which make accessible certain concepts that are associated with religion, including design, purpose, agency, and body–soul dualism. However, more is needed to generate fully-fledged, sustained, and conscious religious beliefs, including a belief in gods, in divine creation of natural entities, and in life after death. Such beliefs require cultural support.

Negativity bias and political ideology

I've just received a reviewer's copy of an upcoming article in Brain and Behavioral Science in the vein of several MindBlog posts mentioning work on the brains of conservatives versus liberals: "Differences in Negativity Bias Underlie Variations in Political Ideology" by J. R. Hibbing, K.B. Smith, and John R. Alford. I thought MindBlog readers might be interested in their abstract:

Disputes between those holding differing political views are ubiquitous, deep-seated, and often follow common, recognizable lines, with the supporters of tradition and stability, sometimes referred to as conservatives, doing battle with the supporters of innovation and reform, sometimes referred to as liberals. Understanding the correlates of these distinct political orientations is likely a prerequisite for managing political disputes, a source of social conflict often leading to frustration and even bloodshed. A rapidly growing body of empirical evidence documents a multitude of ways in which liberals and conservatives differ from each other in purviews of life with little direct connection to politics, from tastes in art to desire for closure and from disgust sensitivity to the tendency to pursue new information, but the central theme of these differences is a matter of debate. In this article, we argue that one organizing element of the many differences between liberals and conservatives is the nature of their physiological and psychological responses to features of the environment that are negative. Compared to liberals, conservatives tend to register greater physiological responses to such stimuli and also to devote more psychological resources to them. Operating from this point of departure, we suggest future approaches for refining understanding of the broad relationship between political views and response to the negative. We conclude with a discussion of normative implications, stressing that identifying differences across ideological groups is not tantamount to declaring one ideology superior to another.

Reversal of hearing decline with aging.

It is known that life-long musical experience partially offsets age-related neural timing delays. Such delays make it harder to process speech in noisy environments, and hearing aids don't help. (This is one reason I keep giving piano recitals). In a fascinating recent article, Anderson et al. show a partial reversal of these age-related neural timing delays can be partially reversed by cognitive auditory training. Edited from their text (in which the data show the indicated expectation were confirmed):

An auditory training group (n = 35) completed an adaptive computer-based auditory training program that combines bottom-up perceptual discrimination exercises with top-down cognitive demands. The second group (active control; n = 32) participated in a general educational stimulation program that was matched for time and computer use to that of the auditory training group. We recorded auditory brainstem responses to the speech syllable [da] presented in quiet and noise and assessed speech-in-noise perception, short-term memory, and speed of processing before and after 8 wk of training. We expected that auditory training would induce earlier brainstem peak latencies at posttest compared with pretest, and that the effects of noise on response timing would be reduced. Given previously demonstrated cognitive and perceptual gains from both short-term and long-term auditory training, we expected that auditory training would also improve speech-in-noise perception, short-term memory, and speed of processing.

The abstract:

Neural slowing is commonly noted in older adults, with consequences for sensory, motor, and cognitive domains. One of the deleterious effects of neural slowing is impairment of temporal resolution; older adults, therefore, have reduced ability to process the rapid events that characterize speech, especially in noisy environments. Although hearing aids provide increased audibility, they cannot compensate for deficits in auditory temporal processing. Auditory training may provide a strategy to address these deficits. To that end, we evaluated the effects of auditory-based cognitive training on the temporal precision of subcortical processing of speech in noise. After training, older adults exhibited faster neural timing and experienced gains in memory, speed of processing, and speech-in-noise perception, whereas a matched control group showed no changes. Training was also associated with decreased variability of brainstem response peaks, suggesting a decrease in temporal jitter in response to a speech signal. These results demonstrate that auditory-based cognitive training can partially restore age-related deficits in temporal processing in the brain; this plasticity in turn promotes better cognitive and perceptual skills.

By the way, on this topic, Miller has a recent interesting article on the brain basis of the "cocktail party effect', how we single out a single voice in a room full of conversations.

How to dress to say it is wrong to be gay!

I had to pass this on.....

FABULOUS! The Pope Emeritus, wearing a fabulous vintage chiffon-lined Dior gold lame gown
over a silk Vera Wang empire waist tulle cocktail dress,
accessorized with a three-foot House of Whoville hat
and the ruby slippers Judy Garland wore in the Wizard of Oz,
on his way to tell us it's wrong to be gay.

Stay plain and simple, Francis! Stay plain and simple!

Does cannabis use cause lower IQ?

Rogeberg offers a critique of a recent suggestion by Meyer et. al. of a neurotoxic effect of cannabis on developing brains that permanently lowers IQ, based on on a correlation between persistent cannabis use initiated in adolescence and a decline in IQ-scores between the ages of 13 and 38. The data come  the" Dunedin cohort," 1,037 individuals followed from birth (1972/1973) to age 38 y. An alternative confounding model can be based on time-varying effects of socioeconomic status on IQ.

Does cannabis use have substantial and permanent effects on neuropsychological functioning? Renewed and intense attention to the issue has followed recent research on the Dunedin cohort, which found a positive association between, on the one hand, adolescent-onset cannabis use and dependence and, on the other hand, a decline in IQ from childhood to adulthood [Meier et al. (2012) Proc Natl Acad Sci USA 109(40):E2657–E2664]. The association is given a causal interpretation by the authors, but existing research suggests an alternative confounding model based on time-varying effects of socioeconomic status on IQ. A simulation of the confounding model reproduces the reported associations from the Dunedin cohort, suggesting that the causal effects estimated in Meier et al. are likely to be overestimates, and that the true effect could be zero. Further analyses of the Dunedin cohort are proposed to distinguish between the competing interpretations. Although it would be too strong to say that the results have been discredited, the methodology is flawed and the causal inference drawn from the results premature.

Observing regulatory connections correlating with emotion control during transition to adolescence.

Interesting work from Gee et al. showing some brain changes that correlate with the inhibition of emotional reactivity that occurs during human adolescence:

Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. Although tracing studies have suggested changes in amygdala–cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala–prefrontal circuitry across the ages of 4–22 years using task-based functional magnetic resonance imaging. Results suggest positive amygdala–prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala–medial prefrontal cortex functional connectivity was significantly positive (greater than zero) among participants younger than 10 years, whereas functional connectivity was significantly negative (less than zero) among participants 10 years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections.

How do alligators get errections?

I couldn't resist passing on this Discoblog pointer to Kelly's article. Most birds, reptiles, and mammals have penises that become erect by filling with fluid, but the alligator penis does not change shape or stiffness before sex. Kelly suggests it is popped out of the cloaca by muscles evolved for this purpose:

The intromittent organs of most amniotes contain variable-volume hydrostatic skeletons that are stored in a flexible state and inflate with fluid before or during copulation. However, the penis in male crocodilians is notable because its shaft does not seem to change either its shape or bending stiffness as blood enters its vascular spaces before copulation. Here I report that crocodilians may have evolved a mechanism for penile shaft erection that does not require inflation and detumescence. Dissections of the cloaca in sexually mature male American alligators (Alligator mississippiensis) show that the cross section of the proximal shaft of the alligator penis contains dense collagenous tissues that do not significantly change shape when fluid is added to the central vascular space. The large amount of collagen in the wall and central space of the alligator penis stiffen the structure so it can be simply everted for copulation and rapidly retracted at its completion. Because no muscles insert directly onto the penis, eversion and retraction must be produced indirectly. My results suggest that the contraction of paired levator cloacae muscles around the anterior end of the cloaca rotates the penis out of the cloacal opening and strains the ligamentum rami that connect the base of the penis to the ischia. When the cloacal muscles relax, the elastic recoil of the ligamentum rami can return the penis to its original position inside the cloaca.

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.