Flipping switches in the brain with light.

The Aug. 14 science section of the NYTimes (PDF here) notes a technique which I mentioned in a previous post: making brain cells susceptible to light activation by inserting a light sensitive ion channel in their membranes.

A first step is establishing that it is possible to tweak a brain circuit by remote control and observe the corresponding behavioral changes in freely moving lab animals. On a recent Sunday at Stanford, Dr. Deisseroth and Feng Zhang, a graduate student, hovered over a dark brown mouse placed inside a white plastic tub. Through standard gene-manipulating tricks, the rodent had been engineered to produce channelrhodopsin only in one particular kind of neuron found throughout the brain, to no apparent ill effect....Mr. Zhang had implanted a tiny metal tube into the right side of the mouse’s partly shaved head...Now he carefully threaded a translucent fiber-optic cable not much wider than a thick human hair into that tube, positioned over the area of the cerebral cortex that controls movement...(then).. adjusted a key on a nearby laser controller box, and the fiber-optic cable glowed with blue light. The mouse started skittering in a left-hand spin, like a dog chasing its tail....“Turn it off, and then you can see him stand up,” Dr. Deisseroth continued. “And now turn it back on, and you can see it’s circling.”..Because the brain lacks pain receptors, the mouse felt no discomfort from the fiber optic, the scientists said, although it looked a tad confused. Scientists have long known that using electrodes to gently zap one side of a mouse’s motor cortex will make it turn the opposite way. What is new here is that for the first time, researchers can perturb specific neuron types using light.....

Legend: Light stimulation every 200 milliseconds generates electrical activity, right, in an area of the brain associated with depression.

At Stanford, Dr. Deisseroth’s group has identified part of a brain circuit, in the hippocampus, that is underactive in rats, with some symptoms resembling depression. The neural circuit’s activity — and the animals’ — perked up after antidepressant treatment, in findings reported last week in the journal Science. Now the team is examining whether they can lift the rats’ low-energy behavior by using channelrhodopsin to rev up the sluggish neural zone...

The Stanford group has sent DNA copies of the “on” and “off” light-switch genes to more than 175 researchers eager to try them in all stripes of electrically excitable cells, from insulin-releasing pancreas cells to heart cells.

Imaging Depression

Thomas Insel writes a perspectives article in the Aug. 10 issue of Science (PDF here) on efforts to specify brain areas that show abnormal activity during depression. A clip from his article:

Neuroimaging studies of humans with major depressive disorder have largely pointed to prefrontal sites, especially implicating an area in the midline subgenual anterior cingulate cortex, often denoted as area 25 (see the figure. Not only does this region appear abnormal on structural and functional scans, but also it is enriched with the serotonin transporter, a target for many antidepressant drugs. Individuals inheriting a risk allele within the promoter of the serotonin transporter gene have reduced volume of area 25 and reduced functional coupling of this region to the amygdala, a subcortical region implicated in the regulation of emotion. An initial study of treatment-resistant depressed patients reports that deep brain stimulation adjacent to area 25 relieves the symptoms of major depressive disorder.

Male sexual behavior circuits in female brains...

A fascinating bit of work by Kimchi and Dulac shows that female mice missing a gene involved in pheromone detection show the same sexual behaviour as males. Their abstract:

In mice, pheromone detection is mediated by the vomeronasal organ and the main olfactory epithelium. Male mice that are deficient for Trpc2, an ion channel specifically expressed in VNO neurons and essential for VNO sensory transduction, are impaired in sex discrimination and male–male aggression. We report here that Trpc2-/- female mice show a reduction in female-specific behaviour, including maternal aggression and lactating behaviour. Strikingly, mutant females display unique characteristics of male sexual and courtship behaviours such as mounting, pelvic thrust, solicitation, anogenital olfactory investigation, and emission of complex ultrasonic vocalizations towards male and female conspecific mice. The same behavioural phenotype is observed after VNO surgical removal in adult animals, and is not accompanied by disruption of the oestrous cycle and sex hormone levels. These findings suggest that VNO-mediated pheromone inputs act in wild-type females to repress male behaviour and activate female behaviours. Moreover, they imply that functional neuronal circuits underlying male-specific behaviours exist in the normal female mouse brain.

There is some controversy over whether this result is unique to inbred laboratory mouse strains, so Dulac is now breeding wild mice with the Trpc2-mutant mice, to experiment with a 'wilder' version.

Happiness Tips

I enjoyed watching an interview of Tal Ben-Shahar on the John Stewart Daily News shows several days ago, discussing his new book "Happier." He has integrated threads of the positive psychology movement initiated largely by Martin Seligman (see my post on Seligman) to offer the most popular undergraduate course at Harvard. Although I usually have a gag reaction at most of the self-help stuff I see, I thought I would pass on some of the sane happiness tips from his website. And, a quick search at YouTube gets you his promotional video, also shown below.

* 1. Give yourself permission to be human. When we accept emotions — such as fear, sadness, or anxiety — as natural, we are more likely to overcome them. Rejecting our emotions, positive or negative, leads to frustration and unhappiness.

* 2. Happiness lies at the intersection between pleasure and meaning. Whether at work or at home, the goal is to engage in activities that are both personally significant and enjoyable. When this is not feasible, make sure you have happiness boosters, moments throughout the week that provide you with both pleasure and meaning.

* 3. Keep in mind that happiness is mostly dependent on our state of mind, not on our status or the state of our bank account. Barring extreme circumstances, our level of well being is determined by what we choose to focus on (the full or the empty part of the glass) and by our interpretation of external events. For example, do we view failure as catastrophic, or do we see it as a learning opportunity?

* 4. Simplify! We are, generally, too busy, trying to squeeze in more and more activities into less and less time. Quantity influences quality, and we compromise on our happiness by trying to do too much.

* 5. Remember the mind-body connection. What we do — or don't do — with our bodies influences our mind. Regular exercise, adequate sleep, and healthy eating habits lead to both physical and mental health.

* 6. Express gratitude, whenever possible. We too often take our lives for granted. Learn to appreciate and savor the wonderful things in life, from people to food, from nature to a smile.

Genetic changes that influence memory

Mery et al. show that a natural genetic polymorphism influences short versus long term memory in fruit flies. You can extract the basic message from their abstract, passing over the molecular details if that's not your gig:

Knowing which genes contribute to natural variation in learning and memory would help us understand how differences in these cognitive traits evolve among populations and species. We show that a natural polymorphism at the foraging (for) locus, which encodes a cGMP-dependent protein kinase (PKG), affects associative olfactory learning in Drosophila melanogaster. In an assay that tests the ability to associate an odor with mechanical shock, flies homozygous for one natural allelic variant of this gene (forR) showed better short-term but poorer long-term memory than flies homozygous for another natural allele (fors). The fors allele is characterized by reduced PKG activity. We showed that forR-like levels of both short-term learning and long-term memory can be induced in fors flies by selectively increasing the level of PKG in the mushroom bodies, which are centers of olfactory learning in the fly brain. Thus, the natural polymorphism at for may mediate an evolutionary tradeoff between short- and long-term memory. The respective strengths of learning performance of the two genotypes seem coadapted with their effects on foraging behavior: forR flies move more between food patches and so could particularly benefit from fast learning, whereas fors flies are more sedentary, which should favor good long-term memory.

Followup on male promiscuity...

Gina Kolata follows up here original article which I mentioned earlier, getting responses concerning means, medians, averages, etc.:

The Median, the Math and the Sex

By GINA KOLATA

David Gale, eminent emeritus mathematics professor at the University of California, Berkeley, member of the National Academy of Sciences, household name in certain rarefied circles, wanted to sound off about sex surveys. Over and over again, he said, they report results that logic dictates can’t be right. The total number of sex partners for men, he said, must equal the total number for women.

So when I said I’d write about that for The New York Times, he was delighted. Do you think I’ll get a response, he asked?

Little did he know. The moment the article hit The Times’s Web site last weekend, the e-mail messages flew and a discussion ensued that might be bewildering to the nonmathematician.

Gotcha, readers said: Data in one of the surveys cited, they said, reported the median numbers of sexual partners — and Dr. Gale’s argument, they said, only holds for the average number of partners.

Some were polite. Andrew Odlyzko, a mathematician at the University of Minnesota, wrote, “David Gale’s argument is unimpeachable” but there is this problem of medians.

Others were blunt: “Theorem: Professor Gale never went to prom. Proof: His High School Prom Theorem fatally assumes that everyone has a partner for every dance and no one ever sits out. The alternative is he has confused medians (at issue in the article) with means (averages, not middle-points in data), a rather elementary mistake for an emeritus professor of mathematics at Berkeley.”

The problem, Dr. Gale says, is that people leapt to conclusions. He had looked at the actual data from the survey citing medians and found that it could not possibly be correct. Of course he knew the difference between a median and a mean.

He wrote an explanation to send out to his numerous correspondents. But the e-mail messages kept coming.

A few correspondents, at least, were gracious. James Smith, an economist at the RAND Corporation, replied: “Yes, my point was only that of a nerd,” he wrote. “I have no doubt that the puzzle you pointed out is indeed true and cannot be explained away by medians and means.”

For the unconvinced, Dr. Gale’s response:

What I did was to get a copy of the C.D.C. report and use the data in its tables. The C.D.C. groups people into four groups and gives percentage of men and women in each group


From these figures you can estimate the total partners claimed by each sex. I got between 40 percent and 75 percent more male than female partners depending on how you guess the average on each interval. Thus, the raw data is inconsistent (so it doesn’t matter whether you take averages or medians or any other statistic).

I hope this clarifies.

Dan Koshland on scientific discovery - his Cha-Cha-Cha theory

Early in my professional career, I had a long discussion with Dan Koshland on a bus ride back from a scientific meeting. This conversation and our subsequent exchanges had a strong influence on me. Koshland was the editor of Science Magazine for many years, and we are all sad at his passing. Here is one of his perspectives articles from the magazine, on the nature of scientific discovery, titled "The Cha-Cha-Cha Theory of Scientific Discovery."

Scientific discoveries are the steps--some small, some big--on the staircase called progress, which has led to a better life for the citizens of the world. Each scientific discovery is made possible by the arrangement of neurons in the brain of one individual and as such is idiosyncratic. In looking back on centuries of scientific discoveries, however, a pattern emerges which suggests that they fall into three categories--Charge, Challenge, and Chance--that combine into a "Cha-Cha-Cha" Theory of Scientific Discovery. (Nonscientific discoveries can be categorized similarly.)

"Charge" discoveries solve problems that are quite obvious--cure heart disease, understand the movement of stars in the sky--but in which the way to solve the problem is not so clear. In these, the scientist is called on, as Nobel laureate Albert Szent-Györgyi put it, "to see what everyone else has seen and think what no one else has thought before." Thus, the movement of stars in the sky and the fall of an apple from a tree were apparent to everyone, but Isaac Newton came up with the concept of gravity to explain it all in one great theory.

"Challenge" discoveries are a response to an accumulation of facts or concepts that are unexplained by or incongruous with scientific theories of the time. The discoverer perceives that a new concept or a new theory is required to pull all the phenomena into one coherent whole. Sometimes the discoverer sees the anomalies and also provides the solution. Sometimes many people perceive the anomalies, but they wait for the discoverer to provide a new concept. Those individuals, whom we might call "uncoverers," contribute greatly to science, but it is the individual who proposes the idea explaining all of the anomalies who deserves to be called a discoverer.

"Chance" discoveries are those that are often called serendipitous and which Louis Pasteur felt favored "the prepared mind." In this category are the instances of a chance event that the ready mind recognizes as important and then explains to other scientists. This category not only would include Pasteur's discovery of optical activity (D and L isomers), but also W. C. Roentgen's x-rays and Roy Plunkett's Teflon. These scientists saw what no one else had seen or reported and were able to realize its importance.

There are well-known examples in each one of the Cha-Cha-Cha categories (see the figure). Two conclusions are immediately apparent. The first is that the original contribution of the discoverer can be applied at different points in the solution of a problem. In the Charge category, originality lies in the devising of a solution, not in the perception of the problem. In the Challenge category, the originality is in perceiving the anomalies and their importance and devising a new concept that explains them. In the Chance category, the original contribution is the perception of the importance of the accident and articulating the phenomenon on which it throws light.


Second, most important discoveries are usually not solved in one "Eureka" moment, as movie scripts sometimes suggest. True, there are moments in which a scientist has been mulling over various facts and problems and suddenly puts them all together, but most major discoveries require scientists to make not one but a number of original discoveries and to persist in pursuing them until a discovery is complete. Thus, to solidify his theory of gravity, Newton developed calculus and laws of physics that he described in his Principia. In a modern example, Michael Brown and Joseph Goldstein not only studied the metabolism of cholesterol but also discovered the role of lipoprotein receptors and the movement of key proteins from the outside to the interior of cells. Great discoveries are frequently covered in textbooks with a single word or phrase, but the concepts actually become solidified as scientific understanding by a series of discoveries.

It is also pertinent to define "the prepared mind" that is required for all of these innovations. Such a mind must be curious and knowledgeable. Curious refers to the fact that the individual is interested in phenomena and is constantly seeking to understand and explain them. Knowledgeable means that the individual has a background of facts and theories as a fertile incubator into which the new facts can fall.

The Cha-Cha-Cha Theory pertains to small everyday findings by scientists as well as the big discoveries that appear in history books. When, for example, a researcher discovers a new chemical isolated from a plant, there is so much understood today that the "charge" to that scientist is to find the formula and structure of the compound. There are now many ways to find the structure of an unknown chemical. Along the way there may be anomalous results that present challenges to the scientist and unexpected findings that must be interpreted by the prepared mind. So each of these represent real discoveries, not as big as a theory of gravity, but important just the same.

Finally, scientific discoveries are not that different from nonscientific discoveries. In the earliest days, there was an obvious "charge" for a set of rules to guide conduct in the close environment of a village that led to social customs and religious guidelines such as the Ten Commandments. As more complex societies emerged, the idea of a democratic vote probably resulted from a "charge" that saw the importance of getting consensus. The Magna Carta and the Bill of Rights came out of "challenges" to an entrenched social system. So when Einstein said that scientific thinking and general thinking were not that different, he probably meant that the patterns of thought of those with "prepared minds" in government and law operated by some of the same general principles as science, even though the methods of science and law are very different.

Someday we may understand the arrangement of neurons in the brain enough to understand how originality can arise. A wild guess would be that the brain of a discoverer has a greater tendency than the average individual to relate facts from highly separate compartments of the brain to each other. As a step to making that Herculean problem tractable, we can at least follow the traditions of scientific reductionism and use the Charge, Challenge, and Chance categories to make the interpretation of brain imaging experiments easier to analyze.

Monkeys prefer silence...

The fact that monkeys prefer silence suggests that humans' music responses may reflect evolutionary selection for cognitive processes linked to emotion and motivation. Here is the brief review from the Random Samples section of the Aug. 3 issue of Science:

Cognitive scientists Joshua McDermott of the Massachusetts Institute of Technology in Cambridge and Marc Hauser of Harvard University put tamarins and marmosets in an apparatus with two chambers, each rigged to play music whenever an animal entered. In one experiment, the musical choices were a flute lullaby (65.26 beats per minute) and Alec Empire's electronic techno hit "Nobody Gets Out Alive" (369.23 beats per minute). The monkeys spent an average of about two-thirds of their time on the lullaby side, showing that they prefer slower tempos. But when given the choice of silence, lullabies, or a Mozart concerto, they spent most of their time avoiding music altogether. A similar experiment with eight humans showed a distinct preference for music--especially lullabies--over silence, the authors report in the September issue of Cognition.

"The observations suggest that only humans have a natural, or innate, inclination to engage with music," says Isabelle Peretz of the University of Montreal in Canada, who has concluded from studies of people with amusia (tone deafness) that humans have special brain pathways for music (Science, 1 June 2001, p. 1636). McDermott and Hauser--who earlier found that monkeys have no preference between harmonious and dissonant music--suggest that humans' music responses may reflect a "unique evolutionary history of selection" for cognitive processes linked to emotion and motivation.

Most popular consciousness papers for July 2007

From the Eprint archive of the Assoc. for the Scientific Study of Consciousness:

1. Windt, Jennifer Michelle and Metzinger, Thomas (2006) The philosophy of
dreaming and self-consciousness: What happens to the experiential subject
during the dream state? In: The new science of dreaming (1505 downloads from
18 countries). http://eprints.assc.caltech.edu/200/
2. Rosen, Alan and Rosen, David B. (2006) The Design of a
Sensation-generating Mechanism in the Brain: A first step towards a
quantitative definition of consciousness. In: Consciousness and Cognition
(1030 downloads from 20 countries). http://eprints.assc.caltech.edu/195/
3. Sagiv, Noam and Ward, Jamie (2006) Crossmodal interactions: lessons from
synesthesia. In: Visual Perception, Part 2 (873 downloads from 17
countries). http://eprints.assc.caltech.edu/224/
4. Koriat, A. (2006) Metacognition and Consciousness. In: Cambridge handbook
of consciousness. CUP (801 downloads from 17 countries).
http://eprints.assc.caltech.edu/175/
5. Robbins, Stephen E (2006) Bergson and the holographic theory of mind.
Phenomenology and the Cognitive Sciences, 5. pp. 365-394 (762 downloads from
14 countries). http://eprints.assc.caltech.edu/206

Notice that many of this year's conference presentations and related
material can now be found in the archive - for example, this year's William
James Prize winner Sid Kouder's paper: Kouider, Sid and Dehaene, Stanislas
and Jobert, Antoinette and Le Bihan, Denis (2007) Cerebral Bases of
Subliminal and Supraliminal Priming during Reading. Cerebral Cortex, 17 (9).
pp. 2019-2029. ( http://eprints.assc.caltech.edu/321)

Sugar more rewarding than cocaine...

From Lenoir et al.:

Background: Refined sugars (e.g., sucrose, fructose) were absent in the diet of most people until very recently in human history. Today overconsumption of diets rich in sugars contributes together with other factors to drive the current obesity epidemic. Overconsumption of sugar-dense foods or beverages is initially motivated by the pleasure of sweet taste and is often compared to drug addiction. Though there are many biological commonalities between sweetened diets and drugs of abuse, the addictive potential of the former relative to the latter is currently unknown.

Principal finding: ...when rats were allowed to choose mutually-exclusively between water sweetened with saccharin–an intense calorie-free sweetener–and intravenous cocaine–a highly addictive and harmful substance–the large majority of animals (94%) preferred the sweet taste of saccharin. The preference for saccharin was not attributable to its unnatural ability to induce sweetness without calories because the same preference was also observed with sucrose, a natural sugar. Finally, the preference for saccharin was not surmountable by increasing doses of cocaine and was observed despite either cocaine intoxication, sensitization or intake escalation–the latter being a hallmark of drug addiction.

Thus, they demonstrate (at least in rats) that:

...intense sweetness can surpass cocaine reward, even in drug-sensitized and -addicted individuals.

And speculate:

...that the addictive potential of intense sweetness results from an inborn hypersensitivity to sweet tastants. In most mammals, including rats and humans, sweet receptors evolved in ancestral environments poor in sugars and are thus not adapted to high concentrations of sweet tastants. The supranormal stimulation of these receptors by sugar-rich diets, such as those now widely available in modern societies, would generate a supranormal reward signal in the brain, with the potential to override self-control mechanisms and thus to lead to addiction.

New descriptions of our inner lives - part two

I came across a reaction to my original posting on this topic which is worth some discussion, because I think it oversimplifies the views of 'reductionists.' The original posting (which has received more views than any other posting on this blog) began with this brief introduction to some quotes from an article on the Neuro-philosophers Paul and Patricia Churchland:

I rarely mention my internal experience and sensations on this blog - first, because I have viewed readers as "wanting the beef," objective stuff on how minds work. Second and more important, because my experience of noting the flow of my brain products as emotion laced chunks of sensing/cognition/action - knowing the names of the neurotransmitters and hormones acting during desire, arousal, calming, or affiliation - strikes me as a process which would feel quite alien to most people. Still, if we are materialists who believe that someday we will understand how the brain-body generates our consciousness and sense of a self, we will be able to think in terms like the following (a quote taken from Larissa MacFarquhar's profile of Paul and Patricia Churchland in the Feb. 12 New Yorker Magazine):

to which one comment was:

Alien, yes. But it is also largely devoid of meaningful self-exploration as well. Science at it's worst takes itself too seriously. New discoveries are considered automatically as an advance in understanding. A dialogue about the known facts of internal experience contains about as much meaning in moment to moment experience as reciting the letters in a bowl of alphabet soup!

This is surprising to hear from a professional psychologist. It is not meaningful to simply be able to note whether one is angry, sad, loving, or is the grip of an obsession (or image brain correlates of those processes)? - which is what I am saying with "noting the flow of my brain products as emotion laced chunks of sensing/cognition/action." Consider an obsessive compulsive disorder such as constantly washing one's hands. Cognitive therapy training to 'notice a part of me that is not working' and not follow its direction has been useful for some in treatments of this syndrome. The technique of mindfulness meditation which simply notes thoughts and emotions as they arise can have the practical consequence of permitting more choice in whether they are expressed in actions.

A further comment was:

The so-called "objective" human sciences reduces people to parts and pieces so small that we can't recognize commonality or identify our own experiences within the narrow concepts in the models espoused. Science has somehow become primarily inductive. The deep understanding of theoretical deduction seems to have fallen into disfavor. Could it be because it is so easy to pick apart the substance of theoretical systems? I suspect so. The more reductionistic the model, the less likely it can be criticized.

I don't think that 'reductionists' like myself or the Churchlands think that focusing on different specific parts and mechanisms gets a complete description of the 'whole.' We don't deny the relevance of phenomenology of the whole system, of emergent properties, holism, etc. We simply think that it helps to know something about the parts!

The relevant arguments are quite venerable. In the ancient Buddhist text "The Question of King Milinda" the Greek King Menander (Milinda), an heir to Alexander the Great and military commander of what is now Afghanistan, questioned the local Buddhist sage. The sage asked the king to "explain to me what a chariot is.... Is the axle the chariot? Are the wheels, or the frame, or the yoke, or the reins the chariot? If not, then is the chariot all these parts?, is the chariot anything else than these?" (I take this rendering from Mark Epstein's book "Going on Being.")

The point is that 'chariot' (like 'awareness' or 'consciousness') is obviously more than a mere word, but it exists only in relationship to its parts. It doesn't help a lot to get snarled up in debates about induction versus deduction.

Neural Antecedents of Financial Decisions (and other choices)

A mini-review (PDF here) is offered by Knutson and Bossaerts on neural antecedents of financial decisions. It is one of a series of in the August 1 issue of the Journal of Neuroscience devoted to the neural basis of choice and decision making. Their abstract:

To explain investing decisions, financial theorists invoke two opposing metrics: expected reward and risk. Recent advances in the spatial and temporal resolution of brain imaging techniques enable investigators to visualize changes in neural activation before financial decisions. Research using these methods indicates that although the ventral striatum plays a role in representation of expected reward, the insula may play a more prominent role in the representation of expected risk. Accumulating evidence also suggests that antecedent neural activation in these regions can be used to predict upcoming financial decisions. These findings have implications for predicting choices and for building a physiologically constrained theory of decision-making.

An overview (The Neural Basis of Choice and Decision Making) of the other mini-reviews in this series is given in an introduction by Balleine, which I reproduce here:

Decision making refers to the ability of humans and other animals to choose between competing courses of action based on the relative value of their consequences. This capacity is, therefore, fundamentally integrative, melding the complex cognitive processes through which causal relations between actions and consequences are encoded, retrieved, and maintained in working memory with the motivational processes that determine the value, or utility, of actions or sequences of actions. As readers of this journal will be well aware, research in decision making has expanded in a variety of directions in recent years, but most notably into neuroscience. There are many reasons for this development, some merely technical, such as the increased use of functional magnetic resonance imaging (fMRI) in humans, but others that are more obviously innovative and that mark a change in the dominant approach to investigating the neural bases of the complex capacities of animals. There appears to be a developing consensus that the long tradition of studying these capacities by examining analogous processes in simple model systems has become an old tradition; that, rather than using a simple neural or behavioral preparation, methodologies better suited to examining functional, as opposed to structural, problems will provide a more secure basis for rapid progress. Indeed, much of the success of recent research in decision making has come from recognizing that the interaction of the cognitive, motivational, and behavioral processes engaged during the course of specific decisions cannot be reified to a single specialized circuit, cell type, or intracellular process and are best understood at a systems level.

As a consequence, the neuroscience of decision making is a very broad enterprise and crosses many traditional boundaries between research disciplines, species, and brain regions. This breadth is immediately apparent from a cursory survey of the range of interests of the authors of the following Mini-Reviews. There are, however, clear areas of overlap, and these have been exploited to explore what we see as emerging themes in decision-making research. In this series, these include descriptions of studies integrating computational and neuroeconomic approaches to investigate subjective decision variables, financial decisions, and the executive and evaluative functions of prefrontal cortex [particularly the role of orbitofrontal cortex (OFC) in establishing a common currency of value], together with reviews of recent research examining the functions of discrete corticostriatal networks and their integrated dopaminergic afferents in the acquisition and control of goal-directed and habitual instrumental actions.

Although the individual papers review themes that are, themselves, complex areas of issue around which substantial research efforts are currently organizing, they are each presented within a larger context and so, together, provide a general overview of this developing area. For example, in their description of the application of computational approaches to decision making, Doya and Corrado (2007) review both the development of computational models capable of capturing the dynamics of individual choice and specific cases in which the internal variables of these models have provided the basis for extracting the correlates of subjective choice from the electrophysiological data of primates. In this case, it is the dynamic integration of the computational, neural, and behavioral data that has provided insight into the subjective variables controlling choice. Similarly, Knutson and Bossaerts (2007) describe the emerging neurofinance approach to decision making but also examine the specific application of models of decision making under risk and the behavioral tasks that have been developed to examine financial decision processes in human subjects together with their neural correlates using fMRI.

Lee et al. (2007) review research on the involvement of prefrontal cortex in decision making in primates and, in the light of the connectivity of subdivisions of this region and of formal theories of decision making, propose that the lateral, medial, and ventral subregions may have the more specialized task of deriving predictions regarding the future value of reward on the basis of states, actions, and local predictive cues, respectively. Interestingly, Murray et al. (2007) come to similar conclusions with regard to the role of OFC in decision making based on a review of the comparative literature. They point particularly to its role in deriving reward value from predictive cues as well as to evidence suggesting that the OFC may play a specialized role by allowing animals to compare values across distinct event categories.

Finally, it is interesting to note convergence in the proposed functions of corticostriatal circuits and their midbrain dopaminergic afferents in decision making that has emerged in recent research. Although the involvement of the basal ganglia in motor learning, particularly in sensorimotor association, has long been recognized, recent evidence, reviewed by Balleine et al. (2007), suggests that they also play a critical role in the acquisition of actions instrumental to gaining access to reward (i.e., in goal-directed actions). Importantly, studies using rodent, nonhuman primate, and human subjects have found evidence of heterogeneity of neural function not previously anticipated, particularly in the striatum. Furthermore, there is evidence of a corresponding heterogeneity in neurodegenerative disorders, in neuronal plasticity, and in the involvement of dopaminergic processes across striatal subregions. The suggestion that the burst-firing pattern of midbrain dopamine neurons serves as an error signal for the prediction of reward has generated close collaboration between researchers using computational and neurophysiological approaches to study dopamine function. More recently, alterations in dopamine signaling have been reported to lead to regional changes in plasticity in the corticostriatal pathway together with changes in the excitability of the striatal output neurons. Indeed, as reviewed by Wickens et al. (2007), rapid alterations in dopamine transmission are related to substantial changes in the coordinated activity of neuronal ensembles in discrete corticostriatal circuits in a manner that could lead to the emergence of distinct patterns of behavioral abnormality. Clearly, the involvement of dopamine in striatal function, and in decision making generally, is rich and varied and is something that we are only beginning to understand.

Beethoven Piano/Violin sonata - a rehearsal

Daphne and I are working up the 3rd Beethoven Violin - Piano sonata, and made this video at my Twin Valley home to help us note dynamic problems and fumbled passages more clearly.

Our evolving human nature as primary cause of the industrial age?

It has been commonly assumed that technology and institutional changes were much more important than changes in basic human nature in triggering the sudden escape from subsistence poverty towards personal wealth and production that occurred at the end of the 18th century. The Aug. 7 issue of the NYTimes has a review of the work of Gregory Clark, who argues that the Industrial Revolution occurred because of a change in the nature of the human population. Through analysis of ancient wills, Clark found that:

Generation after generation, the rich had more surviving children than the poor... there must have been constant downward social mobility as the poor failed to reproduce themselves and the progeny of the rich took over their occupations...The modern population of the English is largely descended from the economic upper classes of the Middle Ages...As the progeny of the rich pervaded all levels of society...the behaviors that made for wealth could have spread with them...several aspects of what might now be called middle-class values changed significantly from the days of hunter gatherer societies to 1800. Work hours increased, literacy and numeracy rose, and the level of interpersonal violence dropped....Another significant change in behavior, Dr. Clark argues, was an increase in people’s preference for saving over instant consumption, which he sees reflected in the steady decline in interest rates from 1200 to 1800.

I knew I had read, and written, about this sort of idea. After thrashing about looking for it, I was embarrassed to simply find it in my Biology of Mind book, in the chapter on Hominid Mind:

Students of animal behavior use the term "phenotypic cloning" to describe the process by which parents can so firmly impress behaviors on their offspring that the behaviors (phenotypes) seem to be inherited. (In spite of what we like to think, we all act remarkably like our parents as we grow older.) A core point is the argument that differences in behavioral styles between one family line and another provide a context for natural selection. The behaviors that work best are passed on because of differential reproductive success, and less adaptive behaviors are lost from the "phenotypic pool" analogous to the gene pool of genetics. This mechanism acts also at the level of cultures of humans and animals, and in this context it is termed group selection. Over longer periods of time, genetic changes in individuals that facilitate the adaptive behaviors adopted by a group might then be selected for. This is the Baldwin effect mentioned in the section "Co-evolution of Humans and Their Tools" and is a scenario offered by some evolutionary psychologists.

A main point of this post is to pass on the elegant graphic in the NYTimes article, which summarizes Clark's ideas:

The male promiscuity myth

Perhaps the most common evidence offered in support of males and females having evolved different sexual psychologies is from numerous surveys that show, across cultures, that men report having many more sexual partners than women. This is argued to reflect a basic underlying genetic fact: the best investment for a male to generate the maximum number of offspring with his genes is to impregnate as many females as possible. A woman has to invest much more in her offspring and is better served by selected fewer male partners who are more likely to provide support for her and her children.

Gina Kolata, in the Aug. 12 N.Y. Times, reports an interesting slant on this story. Simple math shows that the numbers don't add up... she quotes David Gale of U.C. Berkeley:

Surveys and studies to the contrary notwithstanding, the conclusion that men have substantially more sex partners than women is not and cannot be true for purely logical reasons...By way of dramatization, we change the context slightly and will prove what will be called the High School Prom Theorem. We suppose that on the day after the prom, each girl is asked to give the number of boys she danced with. These numbers are then added up giving a number G. The same information is then obtained from the boys, giving a number B...Theorem: G=B...Proof: Both G and B are equal to C, the number of couples who danced together at the prom. Q.E.D.

Sex researchers know that this is correct. Men and women in a population must have roughly equal number of partners. So why do men report many more than women? They exaggerate? They go to prostitutes who don't appear in the survey? (The latter would not explain the huge difference in reporting.) The most likely explanation:

...the survey data themselves may be part of the problem. If asked, a man, believing that he should have a lot of partners, may feel compelled to exaggerate, and a woman, believing that she should have few partners, may minimize her past...In this way the false conclusions people draw from these surveys may have a sort of self-fulfilling prophecy.

Oscar, the cat of doom

I'm a cat person, so was attracted to this crazy story in the July 26 issue of the New England Journal of Medicine: "A day in the life of Oscar the cat." It describes the cat's daily rounds in a New England rest home.

Since he was adopted by staff members as a kitten, Oscar the Cat has had an uncanny ability to predict when residents are about to die. Thus far, he has presided over the deaths of more than 25 residents on the third floor of Steere House Nursing and Rehabilitation Center in Providence, Rhode Island. His mere presence at the bedside is viewed by physicians and nursing home staff as an almost absolute indicator of impending death, allowing staff members to adequately notify families. Oscar has also provided companionship to those who would otherwise have died alone. For his work, he is highly regarded by the physicians and staff at Steere House and by the families of the residents whom he serves.

A new compendium on mind and brain

The Dana Press (see www.dana.org) has published a volume of articles on mind and brain from The Scientific American, edited by Floyd Bloom (check out the table of contents on the Dana website). It contains a number of interesting articles that I am surprised that I missed at the time. (By the way, the Dana website is a good source of information on recent research on mind and brain, and has special sections devoted to kids and to seniors.)

Yet another anti-aging approach?

Yan et al. have shown that getting rid of a protein involved in adrenaline's control of heart rate reduces heart rate increase during stress and allows mice to live longer and have healthier hearts. Here is their abstract:

Mammalian models of longevity are related primarily to caloric restriction and alterations in metabolism. We examined mice in which type 5 adenylyl cyclase (AC5) is knocked out (AC5 KO) and which are resistant to cardiac stress and have increased median lifespan of ∼30%. AC5 KO mice are protected from reduced bone density and susceptibility to fractures of aging. Old AC5 KO mice are also protected from aging-induced cardiomyopathy, e.g., hypertrophy, apoptosis, fibrosis, and reduced cardiac function. Using a proteomic-based approach, we demonstrate a significant activation of the Raf/MEK/ERK signaling pathway and upregulation of cell protective molecules, including superoxide dismutase. Fibroblasts isolated from AC5 KO mice exhibited ERK-dependent resistance to oxidative stress. These results suggest that AC is a fundamentally important mechanism regulating lifespan and stress resistance.

Flash Earth

A bit outside our normal subject area, but a visually amazing compendium and demonstration of how publicly available geographic and atmospheric data can be organized and presented...It made me a bit queasy to zoom from the whole earth view to my Twin Valley home in Middleton Wisconsin.

Conscious awareness not required for planning and execution of actions

Damage to parts of the visual cortex can cause blindsight or agnosia, in which conscious awareness of an object is absent but subject can still make accurate judgements about it. Binsted et al al offer an interesting demonstration that this phenomenon is is part of the normal functioning of the visual system. They used the masking paradigm shown in the figure below to abolish conscious perception of an object, and found that subjects could point to that object as easily as to one that was perceived. Here is their abstract, followed by the central figure.

After lesions to primary visual cortex, patients lack conscious awareness of visual stimuli. Interestingly, however, some retain the ability to make accurate judgments about the visual world (i.e., so-called blindsight). Similarly, damage to inferior occipitotemporal regions of cortex (e.g., lateral occipital cortex) can result in an inability to perceive object properties while retaining the ability to act on them (i.e., visual form agnosia). In the present work, we demonstrate that the ability to interact with objects in the absence of conscious awareness is not isolated to those with restricted neuropathologic conditions. Specifically, neurologically intact individuals are able to program and execute goal-directed reaching movements to a target object without awareness of extrinsic target properties; they accurately tune the dynamics of their movement and modulate it online without conscious access to features of the goal object. Thus, the planning and execution of actions are not dependent on conscious awareness of the environment, suggesting that the phenomenon of blindsight (and agnosia) reflect normal conditions of the visual system.

Fig. 1. Display sequence for experiment. Participants initially observed a fixation cross and home position. After a variable foreperiod (1–3 s), an array of circles appeared; one circle was identified as the target by 4 red cue circles. In all cases the participant was asked to point to the middle of the target as quickly and accurately as possible. (a) Unconscious condition. The red cue circles remained present after removal of the array. This results in object substitution masking (4, 14), where participants have no conscious access to target properties (e.g., size). (b) Conscious condition. The red cue circles were removed concurrently with the array. In this condition, participants could consciously report the target properties.