Prozac reverses maturation of some brain cells

Here is some intriguing work from Kobayashi et al. showing that fluoxetine (Prozac) indices a dematuration of hippocampus dentate gyrus cells that reinstates synaptic plasticity that is reduced with development, thereby potentially causing beneficial effects on the adult brain. (These cells are key in learning and memory processes). Their results suggest that the state of neuronal maturation, including aberrant maturation, might be controlled or corrected in adults, a unique approach to treating neuronal dysfunctions associated with neurodevelopmental disorders. Some clips from the abstract:

Serotonergic antidepressant drugs have been commonly used to treat mood and anxiety disorders, and increasing evidence suggests potential use of these drugs beyond current antidepressant therapeutics. Facilitation of adult neurogenesis in the hippocampal dentate gyrus has been suggested to be a candidate mechanism of action of antidepressant drugs, but this mechanism may be only one of the broad effects of antidepressants. Here we show a distinct unique action of the serotonergic antidepressant fluoxetine in transforming the phenotype of mature dentate granule cells. Chronic treatments of adult mice with fluoxetine strongly reduced expression of the mature granule cell marker calbindin. The fluoxetine treatment induced active somatic membrane properties resembling immature granule cells and markedly reduced synaptic facilitation that characterizes the mature dentate-to-CA3 signal transmission. These changes cannot be explained simply by an increase in newly generated immature neurons, but best characterized as “dematuration” of mature granule cells...Our results suggest that serotonergic antidepressants can reverse the established state of neuronal maturation in the adult hippocampus...Such reversal of neuronal maturation could affect proper functioning of the mature hippocampal circuit, but may also cause some beneficial effects by reinstating neuronal functions that are lost during development.

Six Famous Geniuses You Didn't Know Were Perverts

Another random curious piece. 

MindBlog in Austin Texas

Having just returned from Istanbul last Friday, I travel again - this time with my partner Len Walker to Austin Texas to attend the 50th reunion of Austin High School Alumni. I will be vacationing here through next week.   Being in Austin requires adapting the digestive system to gargantuan servings of TexMex dishes. 

Aging brains are less able to recover from the effects of stress

It is well documented that aging reduces the effectiveness of our prefrontal cortex in mediating cognitive processing and decision making, including working memory and flexible use of mental strategies. Bloss, McEwen et al. have now conducted studies that suggest that one reason for this decline may be that aging reduces the ability of prefrontal cortex to recover from stress-induced damage. Their abstract:

Neuronal networks in the prefrontal cortex mediate the highest levels of cognitive processing and decision making, and the capacity to perform these functions is among the cognitive features most vulnerable to aging. Despite much research, the neurobiological basis of age-related compromised prefrontal function remains elusive. Many investigators have hypothesized that exposure to stress may accelerate cognitive aging, though few studies have directly tested this hypothesis and even fewer have investigated a neuronal basis for such effects. It is known that in young animals, stress causes morphological remodeling of prefrontal pyramidal neurons that is reversible. The present studies sought to determine whether age influences the reversibility of stress-induced morphological plasticity in rat prefrontal neurons. We hypothesized that neocortical structural resilience is compromised in normal aging. To directly test this hypothesis we used a well characterized chronic restraint stress paradigm, with an additional group allowed to recover from the stress paradigm, in 3-, 12-, and 20-month-old male rats. In young animals, stress induced reductions of apical dendritic length and branch number, which were reversed with recovery; in contrast, middle-aged and aged rats failed to show reversible morphological remodeling when subjected to the same stress and recovery paradigm. The data presented here provide evidence that aging is accompanied by selective impairments in long-term neocortical morphological plasticity.

Michelangelo as brain anatomist

Check out this Andrew Sullivan post.

Overimitation of adults by kids is a cultural universal.

Most studies showing overimitation of adults by children during learning have been conducted on middle- to upper-class kids of Western-educated parents. Nielsen and Tomaselli studied (from Telis's review)

...a culture with a distinctly different parenting style: the Bushmen of the Kalahari Desert. Whereas a Western parent might teach a youngster to use a bow and arrow by standing behind her and guiding her motions, a parent from the indigenous African Bushmen culture would allow the child to come along for a hunt and learn by observation and through trial and error. Nielsen hypothesized that a child taught in this hands-off manner would have less reason to overimitate adults and would do so less often.

The Nielsen and Tomaselli abstract:

Children are surrounded by objects that they must learn to use. One of the most efficient ways children do this is by imitation. Recent work has shown that, in contrast to nonhuman primates, human children focus more on reproducing the specific actions used than on achieving actual outcomes when learning by imitating. From 18 months of age, children will routinely copy even arbitrary and unnecessary actions. This puzzling behavior is called overimitation. By documenting similarities exhibited by children from a large, industrialized city and children from remote Bushman communities in southern Africa, we provide here the first indication that overimitation may be a universal human trait. We also show that overimitation is unaffected by the age of the child, differences in the testing environment, or familiarity with the demonstrating adult. Furthermore, we argue that, although seemingly maladaptive, overimitation reflects an evolutionary adaptation that is fundamental to the development and transmission of human culture.

The Telis review has an interesting video of overimitation in a Bushmen child.

Prehistoric makeover

From the 21 May Science Magazine "Random Samples" section:

Care to feel closer to your extinct relatives? The Smithsonian Institution's MEanderthal app for iPhones and Android devices melds your mug shot with features of Homo neanderthalensis, modern humans' closest kin—or, if you prefer, the more distant H. heidelbergensis or H. floresiensis. In the first case, expect to gain a big nose and a puffier face, says Robert Costello, an outreach manager with the Smithsonian. Neandertals needed large sinus cavities to cope with the colder climate in Europe and Asia 28,000 to 200,000 years ago.

The cognitive niche

Steven Pinker offers (full text, open access) one of several fascinating paper in a special PNAS supplement issue: In the light of evolution IV: The human condition. All of the papers are open access. Pinker's title is "The cognitive niche: Coevolution of intelligence, sociality, and language." The abstract:

Although Darwin insisted that human intelligence could be fully explained by the theory of evolution, the codiscoverer of natural selection, Alfred Russel Wallace, claimed that abstract intelligence was of no use to ancestral humans and could only be explained by intelligent design. Wallace's apparent paradox can be dissolved with two hypotheses about human cognition. One is that intelligence is an adaptation to a knowledge-using, socially interdependent lifestyle, the “cognitive niche.” This embraces the ability to overcome the evolutionary fixed defenses of plants and animals by applications of reasoning, including weapons, traps, coordinated driving of game, and detoxification of plants. Such reasoning exploits intuitive theories about different aspects of the world, such as objects, forces, paths, places, states, substances, and other people's beliefs and desires. The theory explains many zoologically unusual traits in Homo sapiens, including our complex toolkit, wide range of habitats and diets, extended childhoods and long lives, hypersociality, complex mating, division into cultures, and language (which multiplies the benefit of knowledge because know-how is useful not only for its practical benefits but as a trade good with others, enhancing the evolution of cooperation). The second hypothesis is that humans possess an ability of metaphorical abstraction, which allows them to coopt faculties that originally evolved for physical problem-solving and social coordination, apply them to abstract subject matter, and combine them productively. These abilities can help explain the emergence of abstract cognition without supernatural or exotic evolutionary forces and are in principle testable by analyses of statistical signs of selection in the human genome.

Contra doomsayers, a bright future beckons?

Matt Ridley has a new book out, "The Rational Optimist", reviewed by John Tierney.  (Ridley is a very bright polymath, I recall he did a much better job than I did some ~15 years ago,  as a fellow contributor of several chapters of a standard introductory biology text book - a hack writing for pay gig).  Ridley argues in his grand theory that it was the invention of the exchange of one object for another,  rather than increasingly big brains or cooperation and reciprocity, that started the explosive growth of civilization. 

Adam potentially now had access to objects he did not know how to make or find; and so did Oz,” Dr. Ridley writes. People traded goods, services and, most important, knowledge, creating a collective intelligence: “Ten individuals could know between them ten things, while each understanding one.”

Rulers like to take credit for the advances during their reigns, and scientists like to see their theories as the source of technological progress. But Dr. Ridley argues that they’ve both got it backward: traders’ wealth builds empires, and entrepreneurial tinkerers are more likely to inspire scientists than vice versa. From Stone Age seashells to the steam engine to the personal computer, innovation has mostly been a bottom-up process.
“Forget wars, religions, famines and poems for the moment,” Dr. Ridley writes. “This is history’s greatest theme: the metastasis of exchange, specialization and the invention it has called forth, the ‘creation’ of time.”

Progress this century could be impeded by politics, wars, plagues or climate change, but Dr. Ridley argues that, as usual, the “apocaholics” are overstating the risks and underestimating innovative responses....with new hubs of innovation emerging elsewhere, and with ideas spreading faster than ever on the Internet, Dr. Ridley expects bottom-up innovators to prevail. His prediction for the rest of the century: “Prosperity spreads, technology progresses, poverty declines, disease retreats, fecundity falls, happiness increases, violence atrophies, freedom grows, knowledge flourishes, the environment improves and wilderness expands.”

Mindblog as dutiful tourist

I'm heading back to Wisconsin from Istanbul tomorrow, and have just taken time to post the obligatory vacation shots. Being a foodie, I've been especially attentive to treats of the sort shown below, a local cheap restaurant to which my student guide Fatih took us after my piano and lecture gig.

A lecture and piano recital in Istanbul

As this post appears I will just be landing in Istanbul to attend "Cognitive VII", an international cognitive neuroscience meeting being held here May 18-20. The organizers asked me to give both a piano recital and a talk at the May 19 session, which features several talks on art, music, and the brain. I've elected to play a number of pieces, most of which I have previously posted on YouTube. The Chopin Prelude Op. 28 no. 17 shown just below I posted this past weekend.

F. Chopin - Nocturne Op. 27 no. 2
F. Chopin - Prelude Op. 28, no. 17
E. Grieg - Lyric Pieces Op. 43, no. 5 Erotic Piece
E. Grieg - Lyric Pieces Op. 47, no. 5 Melancholy
E. Grieg - Lyric Pieces Op. 54, no. 4, Notturno
C. Debussy - Reverie  (version I  and version II)
C. Debussy - Minuette from Suite Bergmanesque
C. Debussy - Valse Romantique

The talk following this performance is titled "Who wants to know - the nature of our subjective I." I have posted a web version of this talk on my website.

I will be on vacation in Istanbul after the meeting, and probably will suspend MindBlog posts for several weeks.

Here is the Chopin prelude:

The chemistry of commitment

Parker-Pope does an interesting article on a topic that has repeatedly appeared in this blog, the role of vasopressin in regulating affiliative behavior. Here she notes studies on correlations between a gene regulating vasopressin activity and commitment and marital stability. Studies on 552 sets of twins found:

...men who carried a variation in the gene were less likely to be married, and those who had wed were more likely to have had serious marital problems and unhappy wives. Among men who carried two copies of the gene variant, about a third had experienced a serious relationship crisis in the past year, double the number seen in the men who did not carry the variant.

Parker-Pope also notes experiments suggesting that women might have developed a kind of early warning system to alert them to relationship threats.

More on the science of morality - baby morals.

Sam Harris deals with the massive (mostly critical) response to the TED lecture which I pointed to in my March 30 post, in which he argues for a natural and scientific basis for morality.  And,  Paul Bloom discusses observations on very young human infants that provide very strong evidence for our having an innate primitive moral capacity that is refined by individual and group interactions starting in the first year after birth .

Nasal attraction

Olsson and Laska find an exception to the generalization that women sense chemicals better than men. Men are better at detecting the lily-of-the-valley flower smell of the compound bourgeonal. This same compound is a powerful chemical attractant for male sperm cells. Because the olfactory receptors on sperm cells are also expressed in the human nose, and selective pressure for keener receptors would act on men but not on women, it makes sense that men are more sensitive to the sperm attractant.

Recent studies have shown that sperm chemotaxis critically involves the human olfactory receptor OR1D2, which is activated by the aromatic aldehyde bourgeonal. Given that both natural and sexual selection may act upon the expression of receptors, we hypothesized that human males are more sensitive than human females for bourgeonal. Using a 3-alternative forced-choice test procedure, olfactory detection thresholds were determined for a total of 500 subjects, 250 males, and 250 females between 18 and 40 years of age. We found that male subjects detected bourgeonal at significantly lower concentrations (mean value: 13 ppb) compared with female subjects (mean value: 26 ppb), whereas no such gender difference in olfactory sensitivity was found with helional, a structural analog of bourgeonal, and with n-pentyl acetate, an aliphatic ester, which were tested in parallel. Males and females did not differ in their frequency of specific anosmia for any of the 3 odorants. The frequency distributions of olfactory detection thresholds were monomodal with all 3 odorants in both genders. Olfactory detection thresholds did not differ significantly between pre- and postovulatory females with any of the 3 odorants. To the best of our knowledge, this is the first study ever to find a human male superiority in olfactory sensitivity. Single nucleotide polymorphisms and/or copy number variations in genes coding for olfactory receptors may be the proximate cause for our finding, whereas a gender difference in the behavioral relevance of bourgeonal may be the ultimate cause.

Eipgenetics and cognitive aging

Aging-related cognitive decline begins for most of us when we are in our late 40s.  Deterioration is mosty pronounced the ability to recall facts and experiences (declarative memory) and has been associated with aberrant changes in gene expression in the brain's hippocampus and frontal lobe. Peleg et al. now find support for an emerging hypothesis that changes in the epigenetic modification of chromatin in the adult central nervous system drive cognitive decline. They show that restoring a reaction that places acetyl groups on the histone proteins that regulate gene expression reinstates the expression of learning-induced genes.

As the human life span increases, the number of people suffering from cognitive decline is rising dramatically. The mechanisms underlying age-associated memory impairment are, however, not understood. Here we show that memory disturbances in the aging brain of the mouse are associated with altered hippocampal chromatin plasticity. During learning, aged mice display a specific deregulation of histone H4 lysine 12 (H4K12) acetylation and fail to initiate a hippocampal gene expression program associated with memory consolidation. Restoration of physiological H4K12 acetylation reinstates the expression of learning-induced genes and leads to the recovery of cognitive abilities. Our data suggest that deregulated H4K12 acetylation may represent an early biomarker of an impaired genome-environment interaction in the aging mouse brain.

More on creativity and the brain

This past Saturday's NYTimes had an article featuring work by Rex Jung which was the subject of last Tuesday's post. A bit facile and simplistic, but I thought I would pass on some of the eye-catching graphics supplied by researchers:

Images from brain research conducted by the Mind Research Network. While intelligence and skill are associated with the fast and efficient firing of neurons in the brain, subjects who tested high in creativity had thinner white matter and connecting axons that slow nerve traffic. In these images, the green tracks show the white matter being analyzed. The yellow and red spots show where creativity corresponds with slower nerve traffic. The blue areas show where “openness to experience,” associated with creativity, corresponds with slower nerve traffic. (from Jung).

Left, before an insight, activity drops in the visual cortex; right, in the “aha! moment,” activity in the right temporal lobe spikes. (from Ohn Kounios, Drexel University)

Chimps have tools for sex

Here is a great item from Tierney in this past Tuesday's NYTimes Science section. With the use of about 20 different tools having been documented in different groups of chimpanzees, now a 'come hither' tool for a male trying to get a female to mate has been recorded.

The male will pluck a leaf, or a set of leaves, and sit so the female can see him. He spreads his legs so the female sees the erection, and he tears the leaf bit by bit down the midvein of the leaf (making a rasping noise), dropping the pieces as he detaches them. Sometimes he’ll do half a dozen leaves until she notices.,,,And then?...Presumably she sees the erection and puts two and two together, and if she’s interested, she’ll typically approach and present her back side, and then they’ll mate.

...you might see this chimp as the equivalent of a human (wearing pants, one hopes) trying to attract women by driving around with a car thumping out 120-decibel music... But it would be fairer to compare the clipped leaf with the most popular human sex tool...the vibrator, considered taboo a few decades ago, has become one of the most common household appliances in the United States....

William's syndrome: Disappearance of racism along with social fear.

Meyer-Lindenberg and collaborators report the interesting observation that racial stereotyping, but not gender stereotyping, disappears in children with Williams syndrome (who lack social fear):

Stereotypes — often implicit attributions to an individual based on group membership categories such as race, religion, age, gender, or nationality — are ubiquitous in human interactions. Even three-year old children clearly prefer their own ethnic group and discriminate against individuals of different ethnicities. While stereotypes may enable rapid behavioural decisions with incomplete information, such biases can lead to conflicts and discrimination, especially because stereotypes can be implicit and automatic, making an understanding of the origin of stereotypes an important scientific and socio-political topic. An important process invoked by out-groups is social fear. A unique opportunity to study the contribution of this mechanism to stereotypes is afforded by individuals with the microdeletion disorder Williams syndrome (WS), in which social fear is absent, leading to an unusually friendly, high approachability behaviour, including towards strangers. Here we show that children with WS lack racial stereotyping, though they retain gender stereotyping, compared to matched typically developing children. Our data indicate that mechanisms for the emergence of gender versus racial bias are neurogenetically dissociable. Specifically, because WS is associated with reduced social fear, our data support a role of social fear processing in the emergence of racial, but not gender, stereotyping.

Our brain as a cognitive miser - where decision costs are registered.

McGuire1 and Botvinick show that lateral prefrontal cortex (LPFC) is where the costs of cognitively demanding decisions are reflected. From their introduction:

...decision-makers balance a motive to maximize gains with a motive to minimize decision costs. The concept of decision costs helps explain such behavioral phenomena as effort-accuracy tradeoffs, reliance on fast and frugal heuristics, failure to consider all available alternatives, effort discounting, the use of stereotypes, and salutary effects of monetary incentives. Amplified decision costs might play a role in clinical depression and chronic fatigue syndrome. This idea is related to the view that decision-making consumes a limited resource, and, more generally, that humans act as cognitive misers.

Their abstract: (Experiment 1 elicited repeated self-reports of experienced decision costs, measured in terms of participants’ rated desire to avoid the task. Experiment 2 sought to confirm the relevance of LPFC to the evaluation of decision costs, with costs measured directly in terms of observed avoidance behavior.)

Human choice behavior takes account of internal decision costs: people show a tendency to avoid making decisions in ways that are computationally demanding and subjectively effortful. Here, we investigate neural processes underlying the registration of decision costs. We report two functional MRI experiments that implicate lateral prefrontal cortex (LPFC) in this function. In Experiment 1, LPFC activity correlated positively with a self-report measure of costs as this measure varied over blocks of simple decisions. In Experiment 2, LPFC activity also correlated with individual differences in effort-based choice, taking on higher levels in subjects with a strong tendency to avoid cognitively demanding decisions. These relationships persisted even when effects of reaction time and error were partialled out, linking LPFC activity to subjectively experienced costs and not merely to response accuracy or time on task. In contrast to LPFC, dorsomedial frontal cortex—an area widely implicated in performance monitoring—showed no relationship to decision costs independent of overt performance. Previous work has implicated LPFC in executive control. Our results thus imply that costs may be registered based on the degree to which control mechanisms are recruited during decision-making.

Slowing down the brain may enhance creativity.

Geddes points to work by Jung et al. that suggest an inverse correlation in human subjects between brain connectivity, reflected by the amount of the cortical myelin that sheathes nerve tracts (see the illustrations here), and creativity, assayed by a "composite creativity index."  If  less myelin corresponds to slower communication between regions of the brain, this could suggest that slowing down our brains makes them more creative:

That creativity and psychopathology are somehow linked remains a popular but controversial idea in neuroscience research. Brain regions implicated in both psychosis-proneness and creative cognition include frontal projection zones and association fibers. In normal subjects, we have previously demonstrated that a composite measure of divergent thinking (DT) ability exhibited significant inverse relationships in frontal lobe areas with both cortical thickness and metabolite concentration of N-acetyl-aspartate (NAA). These findings support the idea that creativity may reside upon a continuum with psychopathology. Here we examine whether white matter integrity, assessed by Fractional Anisotropy (FA), is related to two measures of creativity (Divergent Thinking and Openness to Experience). Based on previous findings, we hypothesize inverse correlations within fronto-striatal circuits. Seventy-two healthy, young adult (18–29 years) subjects were scanned on a 3 Tesla scanner with Diffusion Tensor Imaging. DT measures were scored by four raters (α = .81) using the Consensual Assessment Technique, from which a composite creativity index (CCI) was derived. We found that the CCI was significantly inversely related to FA within the left inferior frontal white matter (t = 5.36, p = .01), and Openness was inversely related to FA within the right inferior frontal white matter (t = 4.61, p = .04). These findings demonstrate an apparent overlap in specific white matter architecture underlying the normal variance of divergent thinking, openness, and psychotic-spectrum traits, consistent with the idea of a continuum.