Monday, March 26, 2007

'Thinking about thinking' shown in Rats...

A simple experiment can be used to demonstrate 'thinking about thinking', or metacognition in humans, monkeys, and bottlenose dolphins. In dealing with uncertain situations, we more likely to decline a visual, auditory or memory discrimination task that can involve reward or punishment if we are uncertain of the discrimination (more/less, same/different) being requested. Thus we are testing possible future outcomes. This behavior has not been seen in pigeons and rats.

In a recent issue of Current Biology Foote and Crystal now:
demonstrate for the first time that rats are capable of metacognition—i.e., they know when they do not know the answer in a duration-discrimination test. Before taking the duration test, rats were given the opportunity to decline the test. On other trials, they were not given the option to decline the test. Accurate performance on the duration test yielded a large reward, whereas inaccurate performance resulted in no reward. Declining a test yielded a small but guaranteed reward. If rats possess knowledge regarding whether they know the answer to the test, they would be expected to decline most frequently on difficult tests and show lowest accuracy on difficult tests that cannot be declined. Our data provide evidence for both predictions and suggest that a nonprimate has knowledge of its own cognitive state.
PDE of article HERE.

Why antipsychotics lose their effectiveness...

Antipsychotics often lose efficacy in patients despite chronic continuous treatment. Why this occurs is not known. It is known, however, that withdrawal from chronic antipsychotic treatment induces behavioral dopaminergic supersensitivity in animals. Samaha et al. show in experiments with a rat model system using clinically relevant does of haloperidol and olanzapine that loss of antipsychotic efficacy is linked to an increase in dopamine D2 receptor number and sensitivity. This data suggests that dopamine supersensitivity overcomes the behavioral and neurochemical effects of antipsychotics while they are still in use.

Sunday, March 25, 2007

Karate Chimp

As a followup to my 3/22/07 post on primate origins of morality, I thought I would pass on two entertaining videos of the chimp repertoire. The Karate Chimp is just for fun, the spearing chimp in the accompanying post is a new discovery.

KARATE CHIMP

Spearing Chimp

Chimps fashion sharp pointed spears they use to stab prey (in this case a Bush Baby. The actual thrusting of the spear was not caught on camera. The chimp then proceeds to break the tree open in order to get to the bush baby that it had speared inside. It's been heavily reported.

Exploiting the moral impulse

Daniel Gilbert writes a nice OpEd piece in today's NY Times, titled "Compassionalte Commercialism" (He is the psychology professor at Harvard whose book "Stumbling on Happiness" I abstracted in a series of posts 6/29/2006.)
In an advertising campaign that began last week, Nissan left 20,000 sets of keys in bars, stadiums, concert halls and other public venues. Each key ring has a tag that says: “If found, please do not return. My next generation Nissan Altima has Intelligent Key with push-button ignition, and I no longer need these.”

This campaign is clever, but not particularly original.

It was 1997, and the man who was crouched on the sidewalk at 68th and Broadway in New York City was one of the most pathetic souls I’d ever seen. His limbs were twisted in what appeared to be arthritic agony and tears were streaming down his face. “Please,” he whimpered. “Please, somebody help me.”

Most passers-by did what they were named for, but my wife and I stopped. The man looked up. “Please,” he sobbed. “I just want to go home.” My hand needed no guidance from my brain as it reached into my wallet and extracted $10. “Thank you,” he said as I handed him the money. “Thank you so much.” My wife and I mumbled some embarrassed words and walked on.

We hadn’t gone a block when she tugged my sleeve. “Maybe we should have gotten him into a cab,” she said. “He could barely stand up. He might need help. We should go back to see.” My wife is the patron saint of lost kittens and there is no arguing, so we went back to see. And what we saw was our horribly crippled friend walking briskly and happily up 68th Street, opening the door to a late-model car, getting in and driving away after what was apparently a short day of theatrical work.

I know two things now that I didn’t know then.

First, I now know that my hand did what human hands were designed to do. Research suggests that we are hard-wired with a strong and intuitive moral impulse — an urge to help others that is every bit as basic as the selfish urges that get all the press. Infants as young as 18 months will spontaneously comfort those who appear distressed and help those who are having difficulty retrieving or balancing objects. Chimpanzees will do the same, though not so reliably, which has led scientists to speculate about the precise point in our evolutionary history at which we became the “hypercooperative” species that out-nices the rest.

The second thing I know now that I didn’t know then is that this was the most damaging crime I had ever experienced. Like most residents of large cities, I’d been a victim before — of burglary once, of vandalism several times. But this was different. The burglars and vandals had taken advantage of my forgetfulness (“Why didn’t I double lock the door?”) and taught me to be better.

But the actor on 68th Street had taken advantage of my helpfulness and taught me to be worse. The hand that had automatically reached for my wallet had been slapped, and once slapped was twice shy. I’ve never again given money to a stranger without scrutinizing him for the signs that distinguish suffering from its imitation. And because I don’t know what those signs are, I typically just walk by.

Now corporate America has taken a lesson from the guild of shameless grifters. Nissan’s plan to leave those 20,000 sets of keys in public venues is every bit as crafty as the fraudulent performance that a decade ago left me with holes in both my pocketbook and soul. There is no selfish reason to bend down and pick up a key ring, but Nissan knows that we will bend without thinking because the impulse to help is bred into our marrow. Our best instinct will be awakened by a key ring and then punished by a commercial. Like rubes throughout the ages, we will be lured by a false cry of distress and quickly cured of our innocence and compassion.

We are used to commercial tricks that play on our fears. The official-looking letter marked “Verification Audit” is actually a magazine subscription renewal form; the credit card company’s ominous call to “discuss your account” is actually an attempt to sell new services.

Should we now get used to commercial tricks that play on our humanity? How would we feel about a device planted in trash bins that screams “I’m stuck!” until the lid is opened, at which point it continues, “Stuck in a dead end job, that is — and if you are too, then let us show you how to make millions in real estate with no money down”? Is it O.K. to send a thousand doleful puppies into the streets with tags that say: “Thanks for checking. And speaking of checking, our bank charges no monthly fees”?

What happens to us when greed masquerades as need, when cries for help become casting calls for chumps, when our most noble actions make us patsies? “You put an idea out there and seed it,” said the president of the advertising agency that came up with Nissan’s key ring ploy. “And people carry it for you.” Indeed they do. The idea being seeded and carried in this case is that the world cries wolf, that our moral impulse betrays us and that smart people should keep on walking.


Friday, March 23, 2007

Brain movies...

Great images, even if the verbal narrative is a bit vacuous. The time lapse photos of neurons growing in cell culture are nice, as they fade into a cartoon version....

New brain cell synthesis supports new memories? It isn't that simple.

Several laboratories have performed experiments suggesting that our ability to store new memories might be related to the generation of new nerve cells in the hippocampus, which is essential to forming episodic memories. Now Kandel's laboratory now offers the contrary finding that reducing new nerve cell synthesis can enhance working memory. Their abstract:
To explore the function of adult hippocampal neurogenesis, we ablated cell proliferation by using two independent and complementary methods: (i) a focal hippocampal irradiation and (ii) an inducible and reversible genetic elimination of neural progenitor cells. Previous studies using these methods found a weakening of contextual fear conditioning but no change in spatial reference memory, suggesting a supportive role for neurogenesis in some, but not all, hippocampal-dependent memory tasks. In the present study, we examined hippocampal-dependent and -independent working memory using different radial maze tasks. Surprisingly, ablating neurogenesis caused an improvement of hippocampal-dependent working memory when repetitive information was presented in a single day. These findings suggest that adult-born cells in the dentate gyrus have different, and in some cases, opposite roles in distinct types of memory.
Their full paper (PDF download HERE) has a nice illustration of the techniques used.

Reduce social recognition in mice by reducing amygdala oxytocin receptors.

From Choleris et al. :
Social recognition constitutes the basis of social life. In male mice and rats, social recognition is known to be governed by the neuropeptide oxytocin (OT) through its action on OT receptors (OTRs) in the medial amygdala. In female rats and mice, which have sociosexual behaviors controlling substantial investment in reproduction, an important role for OT in sociosexual behaviors has also been shown. However, the site in the female brain for OT action on social recognition is still unknown. Here we used a customized, controlled release system of biodegradable polymeric microparticles to deliver, in the medial amygdala of female mice, "locked nucleic acid" antisense (AS) oligonucleotides with sequences specific for the mRNA of the OTR gene. We found that single bilateral intraamygdala injections of OTR AS locked nucleic acid oligonucleotides several days before behavioral testing reduced social recognition. Thus, we showed that gene expression for OTR specifically in the amygdala is required for normal social recognition in female mice. Importantly, during the same experiment, we performed a detailed ethological analysis of mouse behavior revealing that OTR AS-treated mice underwent an initial increase in ambivalent risk-assessment behavior. Other behaviors were not affected, thus revealing specific roles for amygdala OTR in female social recognition potentially mediated by anxiety in a social context. Understanding the functional genomics of OT and OTR in social recognition should help elucidate the neurobiological bases of human disorders of social behavior (e.g., autism).
The whole article can be downloaded HERE.

Thursday, March 22, 2007

Take a whiff of Oxytocin and become a better mind-reader!

Domes et al. show that a single oxytocin dose from a nasal inhaler (Syntocinon spray, Novartis, Basel, Switzerland) improves the ability of 21-30 year old men to infer the mental state of others from social cues triggered by small muscle movements in the eye region. Here is a PDF of the article. Previous work has shown that oxytocin, in addition to its familiar roles in labor and lactation, reduces responses to social stress and increases trust in social interactions.

Reduce anxiety behavior by making more of a forebrain glucocorticoid receptor.

A paper from Rozeboom et al. whose abstract I reproduce here:
Although numerous stress-related molecules have been implicated in vulnerability to psychiatric illness, especially major depression and anxiety disorders, the role of the brain mineralocorticoid receptor (MR) in stress, depression, and affective function is not well defined. MR is a steroid hormone receptor that detects circulating glucocorticoids with high affinity and has been primarily implicated in controlling their basal level and circadian rhythm. To specifically address the role of MR in hypothalamic-pituitary-adrenal axis activity and anxiety-related behaviors, we generated transgenic mice with increased levels of MR in the forebrain (MRov mice) by using the forebrain-specific calcium/calmodulin-dependent protein kinase II {alpha} promoter to direct expression of MR cDNA. A mild but chronic elevation in forebrain MR results in decreased anxiety-like behavior in both male and female transgenic mice. Female MRov mice also exhibit a moderate suppression of the corticosterone response to restraint stress. Increased forebrain MR expression alters the expression of two genes associated with stress and anxiety, leading to a decrease in the hippocampal glucocorticoid receptor (GR) and an increase in serotonin receptor 5HT-1a, consistent with the decreased anxiety phenotype. These data suggest that the functions of forebrain MR may overlap with GR in hypothalamic-pituitary-adrenal axis regulation, but they dissociate significantly from GR in the modulation of affective responses, with GR overexpression increasing anxiety-like behavior and MR overexpression dampening it. These findings point to the importance of the MR:GR ratio in the control of emotional reactivity.
The whole paper, with an introduction that gives more context, can be downloaded HERE.

Wednesday, March 21, 2007

Motion aftereffect demonstration

I'm passing this on, a rather powerful (practically hallucinatory) demonstration. Look at the center of the moving lines for 20 seconds and then at a picture on the wall. DO NOT TRY THIS IF YOU HAVE PHOTOSENSITIVE EPILEPSY!

Primate beginnings of morality

Nicholas Wade, in the NY Times science section, presents a nice summary of the views of Franz de Waal, Marc Hauser, and other regarding moral behaviors in primates that are antecedent, and similar, to our own. Here is the PDF of the article, and I show the illustrations by Edel Rodriguez based on source material from Frans de Waal and legends below.

Chimpanzees have a sense of social structure and rules of behavior, most of which involve the hierarchy of a group, in which some animals rank higher than others. Social living demands a number of qualities that may be precursors of morality.


Frans de Waal argues that the building blocks of human morality can be seen in the behavior of nonhuman primates like himpanzees. Mutual grooming, for example, shows a sense of fairness or reciprocity.



Chimpanzees engage in both reconciliation and peacemaking. Male chimpanzees routinely reconcile after fights, which protects their group’s social fabric. And Dr. de Waal has described female chimpanzees removing stones from the hands of males about to fight.


The ability to understand the plight of others — empathy — is clearly an essential part of any moral system. Chimpanzees exhibit a variety of behaviors that suggest they have the capacity for empathy, such as helping a frightened young chimp down from a tree.

More on "gay" male fruit flies...

Ed Kravitz is an amazing guy who has made numerous major shifts in his research approach. I was a postdoctoral student with him in the 1960's in the Neurobiology Dept. at Harvard Med. Then we were working on the lobster nervous system and its GABA and glutamate neurotransmitters. Now the Kravitz laboratory is studying the genetics of aggressive and sexual behavior in Drosophila fruit flies. From his recent PNAS abstract:
legend: Drosophila courtship dance
The reproductive and defensive behaviors that are initiated in response to specific sensory cues can provide insight into how choices are made between different social behaviors. We manipulated both the activity and sex of a subset of neurons and found significant changes in male social behavior. Results from aggression assays indicate that the neuromodulator octopamine (OCT) is necessary for Drosophila males to coordinate sensory cue information presented by a second male and respond with the appropriate behavior: aggression rather than courtship. In competitive male courtship assays, males with no OCT or with low OCT levels do not adapt to changing sensory cues and court both males and females. We identified a small subset of neurons in the suboesophageal ganglion region of the adult male brain that coexpress OCT and male forms of the neural sex determination factor, Fruitless (FruM).


A single FruM-positive OCT neuron sends extensive bilateral arborizations to the suboesophageal ganglion [Su oes g in the image, click on image to enlarge], the lateral accessory lobe, and possibly the posterior antennal lobe, suggesting a mechanism for integrating multiple sensory modalities. Furthermore, eliminating the expression of FruM by transformer expression in OCT/tyramine neurons changes the aggression versus courtship response behavior. These results provide insight into how complex social behaviors are coordinated in the nervous system and suggest a role for neuromodulators in the functioning of male-specific circuitry relating to behavioral choice.

Tuesday, March 20, 2007

Heroes and Happiness


Here is a posting and an audio clip on the topic of happiness that you might find interesting. It includes material from Daniel Gilbert at Harvard, whose book "Stumbling Towards Happiness" I abstracted in earlier blog postings. There is a bit of rap music at the start of the audio, before the spoken text begins.

Most laughing has little to do with humor...

A nice piece by John Tierney (PDF download here) in the NY Times points out that
It’s an instinctual survival tool for social animals, not an intellectual response to wit. It’s not about getting the joke. It’s about getting along.
I recommend that you also have a look at an engaging article by Panksepp and Burgdorf: ‘‘Laughing’’ rats and the evolutionary antecedents of human joy? (PDF download here)

Temporal Lobe Seizures and God

Here are two engaging video clips from Ramachandran, who has also done fascinating work on the phantom limb syndrome and synesthesia.

Part I

Part II

Monday, March 19, 2007

Getting brain wiring correct during development...

During development optic nerve axons connect to cells in the lateral geniculate part of the thalamus, which then sends its axons on to the visual cortex. Inputs from the two eyes need to be sorted out from each other. Carla Shatz's laboratory in the Neurobiology Dept. at Harvard Med. reports very elegant experiments showing how how correct connections between retina and thalamus are reinforced.

Their summary:

The brain is comprised of an immense number of connections between neurons, and clever strategies are required to achieve the correct wiring during development. One common strategy uses neural activity itself as feedback to instruct individual connections (synapses) through synaptic learning rules that delineate which patterns of activity strengthen the synapse and which weaken it. Throughout life, such activity-dependent synaptic changes are likely driven by experience and are thought to underlie learning and memory, but during early stages of development, they are often driven by activity spontaneously generated within the brain. Here, we study connections in the visual pathway between the retina and lateral geniculate nucleus (LGN), which—to develop correctly—require spontaneous “retinal waves” before the eye is responsive to light. By replaying the retinal wave activity as it appears at single LGN synapses, we observe a novel learning rule that describes a relatively simple computation for the developing synapse in the context of retinal wave activity. We then demonstrate how this learning rule is matched to properties of the retinal waves in order to robustly drive the synaptic refinement that occurs in the visual system.
More specifically:
Retinogeniculate synapses have a novel learning rule that depends on the latencies between pre- and postsynaptic bursts on the order of one second: coincident bursts produce long-lasting synaptic enhancement, whereas non-overlapping bursts produce mild synaptic weakening. It is consistent with “Hebbian” development thought to exist at this synapse, and we demonstrate computationally that such a rule can robustly use retinal waves to drive eye segregation and retinotopic refinement. Thus, by measuring plasticity induced by natural activity patterns, synaptic learning rules can be linked directly to their larger role in instructing the patterning of neural connectivity.

How Lotto makes sense...

I've always thought of Lotto games as regressive taxation, and have been totally unable to understand why people would play them instead of socking the money away in a savings account. Benedict Carey has written a nice piece in the March 11 New York Times showing how I have completely missed the point.
...lottery tickets are not an investment but a disposable consumer purchase, which changes the equation radically. Like a throwaway lifestyle magazine, lottery tickets engage transforming fantasies: a wine cellar, a pool, a vision of tropical blues and white sand. The difference is that the ticket can deliver.

And as long as the fantasy is possible, even a negligible probability of winning becomes paradoxically reinforcing...One is willing to pay hard cash that it be so real, so objective, that it is actually calculable — by someone, even if not oneself.

Because it is pure luck, the lottery is easy to grasp and allows for plenty of perfectly loopy — and very enjoyable — number superstitions. Your birthday digits never won you a dime? Try your marriage date; your favorite psalm verse; the day your bullying father-in-law died.... psychologists have found that ticket holders are very reluctant to trade their tickets for others, precisely because they have an illusion of control from having picked magical numbers.

This sense of power infuses the waiting period with purpose. And the hope of a huge payoff, however remote, is itself a source of pleasure. In brain-imaging studies of drug users, as well as healthy adults placing bets, neuroscientists have found that the prospect of a reward activates the same circuits in the brain that the payoffs themselves do.

Friday, March 16, 2007

The End Of The 'Natural'

This stimulating essay by Andy Clark I pass on in its entirety:
I am optimistic that the human race will continue to find ways of enhancing its own modes of thought, reason, and feeling. As flexible adaptive agents we are wide open to a surprising variety of transformative bodily and mental tricks and ploys, ranging from the use of software, sports regimes and meditational practice, to drug therapies, gene therapies, and direct brain-machine interfaces.

I am optimistic that, stimulated by this explosion of transformative opportunities, we will soon come to regard our selves as constantly negotiable collection of resources, easily able to straddle and criss-cross the boundaries between biology and artifact. In this hybrid vision of our own humanity I see increased potentials not just for repair but for empowerment, expansion, recreation, and growth. For some, this very same hybrid vision may raise specters of coercion, monstering and subjugation. For clearly, not all change is for the better, and hybridization (however naturally it may come to us) is neutral rather than an intrinsic good. But there is cause for (cautious) optimism.

First, there is nothing new about human enhancement. Ever since the dawn of language and self-conscious thought, the human species has been engaged in a unique 'natural experiment' in progressive niche construction. We engineer our own learning environments so as to create artificial developmental cocoons that impact our acquired capacities of thought and reason. Those enhanced minds then design new cognitive niches that train new generations of minds, and so on, in an empowering spiral of co-evolving complexity. The result is that, as Herbert Simon is reputed to have said, 'most human intelligence is artificial intelligence anyway'. New and emerging technologies of human cognitive enhancement are just one more step along this ancient path.

Second, the biological brain is itself populated by a vast number of hidden 'zombie processes' that underpin the skills and capacities upon which successful behavior depends. There are, for example, a plethora of such unconscious processes involved in activities from grasping an object all the way to the flashes of insight that characterize much daily skilful problem-solving. Technology and drug based enhancements add, to that standard mix, still more processes whose basic operating principles are not available for conscious inspection and control. The patient using a brain-computer interface to control a wheelchair will not typically know just how it all works, or be able to reconfigure the interface or software at will. But in this respect too, the new equipment is simply on a par with much of the old.

Finally, empirical science is at last beginning systematically to address the sources and wellsprings of human happiness and human flourishing, and the findings of these studies must themselves be taken as important data points for the design and marketing of (putative) technologies of enhancement.

In sum, I am optimistic that we will soon see the end of those over-used, and mostly ad hoc, appeals to the 'natural'...

Origins of Religious Violence

An essay by Ledford in the News section of the March 8 issue of Nature points out an interesting study on bad behavior that follows reading religious texts. A group of religious Mormon students in Utah and a group from the Free University in Amsterdam (in which only 50% believed in God and 27% in the Bible) read a passage from the Old Testament in which God commanded a tribe to "take arms against their brothers and chasten them before the Lord". Control groups did not read the passage, and then all participated in an exercise to measure aggression.
...whether the students were based in the Netherlands or the United States, and believed in God or not — the trend was the same: those who were told that God had sanctioned the violence against the Israelite were more likely to act aggressively in the subsequent exercise.
This simple experiment:
...does suggest that selective exposure to violent passages in a scriptural canon can promote aggression....That response probably reflects a long-standing finding in psychology that people respond more aggressively to a depiction of violence that they feel is justified.
What about:
...a radical solution to theologically inspired violence — cut the violent passages out of the scripture....It's a wildly controversial idea that ought not to be...because spiritual leaders effectively do that on a regular basis. "A lot of churches have a series of passages that they read during the year," says Avalos. "And usually they don't choose the passages involving genocide."