Brain Rules

What Humans Can Learn From Monkeys

noreply@blogger.com (John Medina) — Fri, 02 Dec 2011 03:07:00 +0000

We are exploring the sometimes creepy, always fascinating distance between genes and behaviors. In this entry, I wish to illustrate a dramatic example of how nature and nurture interact, not by examining humans, but by considering some genetic next-door neighbors: vervet monkeys. This is a great example of “Learn from your parents — it’s good for you!” without a human parent in sight.

Vervet monkeys have interesting predator vocalizations, and even something of a vocabulary. The animals appear to be born with this ability — there’s our nature. As we shall see, however, the application requires some practice — and that’s our nurture. This is easily seen in vervet monkey foraging behaviors, whether the animals are searching for food on the ground or in the trees.

Vervet monkeys have a vocalization for the warning “Run, you idiot, there’s a snake on the ground!”, for example. When an adult vocalizes this warning, the whole tribe runs into the trees, and everyone is safe. They have another word for “Run, you idiot, there’s a predatory bird in the air!” When an adult vocalizes this warning, the whole tribe dives to the ground, and everyone is safe one again.

Note that I italicized the word “adult” throughout the previous paragraph. That’s because when the tribe hears a youngster vocalize either the snake or bird warning, the tribe doesn’t do anything. The members wait until they hear an adult say it. Why do they pause? Because the little ones often get the vocabulary mixed up. They have not yet learned the correct application of their handy early warning system.

The adults aren’t trying to be obnoxious. They are trying to avoid a disaster. Imagine the tragedy if the whole tribe responded to a juvenile’s call to hit the dirt when the little guy saw a snake. The funny cartoon version has him saying sheepishly, “Oops. I meant, trees” — but the deadly real world version is “no more tribe.” Little vervets may be born with the ability to warn others, but they have not yet been instructed on its proper use. They will eventually learn the correct behavior by persistent interactions with older members of the tribe, but the instruction set is not innate. They may have been born with pre-loaded vocalizing software. That doesn’t mean they know how to use it.

A very similar situation between biological ability and social experience is observed with humans, examples of which we will explore in the next few entries. We may come into this world with some pretty sophisticated DNA, but like our primate cousins, that is no guarantee we know how to use it.

How do you get a baby to sleep through the night? We have no idea.

noreply@blogger.com (John Medina) — Sat, 05 Nov 2011 01:27:00 +0000

I am often asked why Brain Rules for Baby doesn't include advice on how to get your child to sleep through the night. The omission is deliberate, and my recent answer to one reader's question via e-mail explains the reasoning. I thought you would like to see the answer, too. Thanks for all of your interest in the book. It means a great deal.
-- John

Dear Reader;

You raise an important issue regarding sleep, one of the most critical in the early months of child-rearing. Unfortunately, I cannot give a response equal to its criticality.

If you are having problems with getting your child to sleep through the night, you have probably read everything you could on the issue. In that journey, you might have noticed there are many different opinions about how to get kids to sleep through the night - often by experts in the field. You might further have noticed that these well-established researchers and clinicians often appear to say contradictory things. The advice can almost be put into a continuum. On one end, there are researchers like Dr. Richard Ferber, interpreted as saying draconian things like “let your kid tough it out at night” (that’s hardly a fair characterization, by the way). On the other end is pediatrician William Sears and family who is interpreted as saying “respond to every demand at night” (also hardly a fair characterization). Here are the two references from these seasoned medical professionals, which make great comparative reading for the views they hold:

“Solve Your Childs’ Sleep Problems”,

Richard Ferber, 2006

and

“The Baby Sleep Book”

William Sears et al, 2005

Why the contradiction? BECAUSE NOBODY REALLY KNOWS HOW TO ADDRESS THE SLEEP ISSUE. There does not appear to be a one-size-fits-all answer, which is why any advice which claims to be THE ANSWER does not pass my “grump factor”, as a scientist. My standard response, therefore, is to appeal to the wisdom of the real expert, the parent – YOU – and say something like “Every brain is wired differently from every other brain. Go out and buy both of these books and expose yourself to the various recommendations. Then determine which strategies (or combinations of strategies) your child – based on your knowledge – is most likely to respond. Try these strategies in a systematic fashion, and progressively design new ones until you find the strategy that does work.”

I have an example of this flexible, deliberate approach in my own child-rearing experience.

It was almost seven months before my eldest child slept successfully through the night. What worked for me was to give him a “modified” Ferber protocol – a gentler version of his recommendation, which took almost a week to execute successfully (I literally took off time from work to do it, relieving my poor exhausted wife).

My youngest child also had trouble getting to sleep. But when I tried my “modified” Ferber strategy, it did not work for him. What did the trick was a modified “Sears” strategy. And it also took about a week to become successful too. Living proof for the fact there is no over-arching strategy that will work for every child.

I wish you well. Solving this riddle is one of the toughest tasks in the early years of child-rearing.

John Medina

Why is it So Hard to Get Kids To Do the Right Thing? (VIDEO)

noreply@blogger.com (John Medina) — Wed, 13 Jul 2011 17:19:00 +0000

If children are born with a sense of right and wrong, as brain science shows, why don't they just do the right thing?

Part of the reason it's tough is that the moment children observe bad behavior, they have learned it. Even if the bad behavior is punished, it remains easily accessible in the child's brain. Psychologist Albert Bandura was able to show this with help from a clown.

In the 1960s, Bandura showed preschoolers a film involving a Bobo doll, one of those inflatable plastic clowns weighted on the bottom. In the film, an adult named Susan kicks and punches the doll, then repeatedly clobbers it with a hammer. After the film, the preschoolers are taken into another room filled with toys, including (surprise) a Bobo doll and a toy hammer.

What do the children do? It depends. If they saw a version of the film where Susan was praised for her violent actions, they hit the doll with great frequency. If they saw a version where Susan got punished, they hit Bobo with less frequency. But if Bandura then strides into the room and says, "I will give you a reward if you can repeat what you saw Susan do," the children will pick up a hammer and start swinging at Bobo.

Whether the children saw the violence as rewarded or punished, they learned the behavior. Bandura calls this "observational learning," and his finding is an extraordinary weapon of mass instruction. Observational learning plays a powerful role in moral reasoning.

How does moral reasoning develop? Slowly. Harvard psychologist Kohlberg believed that moral reasoning depended upon general cognitive maturity--another way of saying that these things take time. He outlined a progressive process:

1. Avoiding punishment. Moral reasoning starts out at a fairly primitive level, focused mostly on avoiding punishment. Kohlberg calls this stage pre-conventional moral reasoning.

2. Considering consequences. As a child's mind develops, she begins to consider the social consequences of her behaviors and starts to modify them accordingly. Kohlberg terms this conventional moral reasoning.

3. Acting on principle. Eventually, the child begins to base her behavioral choices on well-thought-out, objective moral principles, not just on avoidance of punishment or peer acceptance. Kohlberg calls this coveted stage post-conventional moral reasoning. One could argue that the goal of any parent is to land here.

This willingness to make the right choices--and to withstand pressure to make the wrong ones, even when the possibility of detection and punishment is zero--is the goal of moral development. We parents use rules and discipline, of course, to get our children to this stage.

In my book "Brain Rules for Baby: How to Raise a Smart and Happy Child from Zero to 5," I discuss the research-tested strategies that parents can use to aid moral development. At the end of the book, I gather practical tips, including these two:

CAP your rules

Discipline FIRST

Need one more? Read "A Magic Trick for Getting Kids to Follow Rules."

Watch more parenting videos or learn more about your baby's brain at brainrules.net.

Custom-Made Neural Stem Cells

noreply@blogger.com (John Medina) — Tue, 10 May 2011 04:45:00 +0000

It is ironic that an attempt to do a molecular end-run around a politically hot topic could result in an important breakthrough in the treatment of neurological disease with potentially strong implications for the psychiatric community. Ironic maybe, but true.

In this column, we explore how the judicious use of neural stem cells (NSCs) has led to a research Holy Grail: the creation of research-ready, patient-specific neurons. This technology did not use the famously controversial embryonic stem cells. These custom-made NSCs were created from politically neutral adult tissues (fibroblasts), which were originally isolated from an affected patient. With no embryo in sight, scientists genetically reprogrammed fibroblasts into stem cells, which were then induced to develop into NSCs. This is an extraordinary finding with many topics to be discussed here:

• The potential research utility for patient-specific neurons

• An explanation of how stem cells can be made from adult tissues

• A striking set of results that involve one of the most commonly inherited and lethal childhood neurological disorders: spinal muscular atrophy (SMA)

Research utility for NSCs

Of what possible utility could molecular investigations of a motor disorder have for the mental health community? Before getting into the specifics of the breakthrough, it might be useful to address a real-world psychiatric need, using depression and SSRIs as an example, to see where these data fit.

When we consider the molecular mechanisms of SSRI interactions, it is easy to resort to commonly taught ideas about interactions that involve a single synapse. Nothing could be further from the truth. The most comprehensive neurological view of SSRI interactions must take into account the participation of thousands of individual neurons strung together in coordinated, complex neural networks.

And not just serotonergic neurons. These cells are in contact with many other central nervous denizens, from adjacent glial cells to the extracellular matrix into which the cells are embedded. What do these circuits actually look like in patients who are vulnerable to depression? Is their architecture all that different from patients who do not exhibit this vulnerability? If there are differences, could they eventually predict drug efficacy? Could these differences only be detected by constructing parts of the circuit from scratch, or could they be observed at the level of a single cell?

The first step in answering these questions involves growing a custom-made batch of serotonergic neurons derived only from the affected patients, and then asking relevant structure/function questions. From attempting to understand molecular mechanisms of disease to testing the efficacy of potential medications, such patient-specific test beds would have a powerful research utility. Until recently, the creation of such tailor-made neural substrates had been an impossible goal.

While it will certainly be quite some time before we can grow entire parkinsonian dopaminergic pathways in a dish, it is now possible to create individual patient-specific neurons in culture. The technology comes from that end-run I mentioned earlier, through the use of a certain type of stem cell. It is to these interesting cellular substrates that we now turn.

Inducible stem cells

To say that embryonic stem cell research has been subject to heated political debate is an understatement. The bugaboo has been the source materials from which the stem cells would be isolated—human embryos—many left over from embryos generated in in vitro fertilization laboratories.

In 2006, researchers found a way to create stem cells that bypassed the need for human embryos. The original technique involved the introduction of 4 specific gene products into mature mouse fibroblasts. Surprisingly, this cocktail was found to reprogram adult stem cells and reverse-engineer them into pluripotent stem cells. Like embryonic stem cells, the altered stem cells had the ability to differentiate into any cell type. Eventually, a protocol was developed that did the same thing in human tissues. The cells were called iPSCs, short for induced pluripotent stem cells.

This was quite a breakthrough. No longer would researchers need to harvest cells from extant human embryos to do stem cell research. Skin cells would do. Scientists were soon able to regenerate—and then correct—molecular dysfunction in a mouse model of sickle cell anemia using this technology.

Could any of this work apply to humans, specifically to human neural tissue? Another successful round of experiments (with amyotrophic lateral sclerosis neurons) prompted researchers to study motor disease, ie, SMA.

Of those hereditary neurological disorders capable of causing death in pediatric populations, SMA is easily the most common. The disease is unique to humans and associated with 2 genes, SMN1 and SMN2. For reasons that are not well understood, the absence of the survival motor neuron (SMN) protein results in an alteration of the function of spinal motor neurons. The primary feature is muscle weakness and atrophy. Death occurs at infancy in the most severe forms of the disease, with symptoms generally presenting several weeks after birth. There are many other, nonlethal forms of the disorder, however, with a wide spectrum of symptoms that range from trivial motor effects to catastrophic impairment.

Why this variation? Both genes express in unaffected individuals, but the biological heavy lifting belongs to the SMN1 gene. Because of structural constraints, the expression pattern of the SMN2 gene normally results in only 10% of its protein being processed as a full-length (and functional) polypeptide; 90% of its protein output is truncated (and nonfunctional). That is okay, as long as the SMN1 gene is intact. But when SMN1 is mutated and silent, the disease condition results. Assuming there is a damaged SMN1, the severity of SMA varies according to the number of other SMN2 copies the infant may carry. The more copies of SMN2 gene, the greater the population of functional protein. This interaction explains in part why there can be so much varia-tion in the clinical presentation.

The great mystery is why SMN protein loss results in motor cell alterations that lead to the disease state in the first place. The protein is known to be essential for normal messenger RNA processing and is expressed throughout the body. Yet its absence most severely affects spinal motor neurons.

The most exacting way to attack this “black box” would be to isolate the motor neuron populations from the patient, then compare these populations with unaffected controls and look for differences, of which there are many. These include responses to various medications. It is well known that the application of valproic acid (an anticonvulsant and/or mood stabilizer) or tobramycin(Drug information on tobramycin) (an aminoglycoside) to cultured cells, for example, leads to changes in the expression patterns of both full-length SMN protein and truncated forms. What is the molecular basis of this unusual interaction? And could such differences be used as a “molecular flashlight” to ferret out other secrets regarding the SMN protein? Creating custom-made neurons—one population from an affected individual, another from an unaffected control—would certainly give a test bed capable of answering this question.

The data

Studying these 2 populations is precisely what a group of investigators did. The researchers isolated fibroblasts from an affected child and also from the child’s healthy unaffected mother.

The next step was to generate custom-made neurons. Several steps would be required (Figure). First, using the iPSC protocols I mentioned, the researchers would attempt to create stem cells from both child and parent sources. If that worked, the researchers would then try to induce these patient-derived stem cells into motor neurons—ones that would carry the same biological mechanisms observed in both the diseased and the healthy populations. If successful, the researchers would have their custom-made test beds. They could begin characterization studies; reactions to valproic acid and tobramycin would make obvious first choices to try.

The first step worked. The researchers were able to generate custom-made stem cells from both child and parent. The researchers then tackled the hard part: manufacturing spinal motor neurons from these stem cell populations. They certainly generated promising cellular populations. But the iPSC technolo-gies are new enough that a visual inspection of the generated cells might be necessary—but certainly not sufficient—to show the presence of motor neurons.

There are ways to gain greater reassurance. One way to assay the success of the protocol is to look for bona fide molecular markers of developing spinal neurons. It is known, for example, that extant motor neurons express the protein SMI032 and choline acetyltransferase. Did these induced cells express such proteins? The answer turned out to be yes, both for the affected child and for the unaffected parent. Developing cells in these populations possess transcription factors such as HOXB4, ISLET1, HB9, and OLIG2 as well. Did the induced populations express these markers? They did indeed. While not completely conclusive, it appeared that the researchers had generated patient-specific motor neurons from known affected and unaffected sources.

The next characterization experiments also yielded fruit. They were able to find that the child and parent neurons reacted very differently to the normally stimulating effects of valproic acid and tobramycin. The child’s cells showed elevated levels of SMN protein, both of the truncated form and full-length version. In addition, SMN-containing nuclear structures were altered. No such elevation occurred in the unaffected maternal line of cells.

These differences were significant for 2 reasons. First, it gave the investigators a toehold in their attempts to characterize at a more intimate level the differences between affected and unaffected cells. Second, the differences were discovered as reactions to known medications. The hope is that similar approaches could be used to test the efficacy of various medications before committing to human trials.

Conclusions

These data, full of promising implications as they are, need to be treated with some caution. First, the experimental cells are pure populations derived from stem cells. This hardly reflects the physical in vivo situation. The cells and matrix components that normally surround such cells in nature, including skeletal muscle tissues and even other neurons, are not present in these studies.

Another objection concerns the fidelity of the conversion process itself. The differentiation pattern seen in various molecular markers hinted that the investigators generated real live spinal motor neurons; however, one cannot a priori say they have in every way created a motor neuron that precisely mimics the real-world situation. These cells may lack many subtle molecular processes—and a few extra, equally subtle interactions—that could easily escape detection, at least by current technologies. Because subtle differences can profoundly influence intracellular molecular interactions, especially when we think about reactions to medications, this is a true concern.

The most exciting aspect of these studies comes from what the future holds. A great deal of speculation has gone into thinking about how to tailor medications to individual patients. That certainly is a psychiatric issue . . . I need not talk to this audience about the variable effects of, say, fluoxetine(Drug information on fluoxetine) on clinical outcomes. We have visited this topic in past columns. The ability to create patient-specific cellular test beds may go a long way toward solving some of these problems. Indeed, clinics of the future might routinely screen to decide what medications their patients should receive—and in what concentrations.

There is much work to do. To date, none has been applied to neurological systems relevant to mental health professionals. Even given the cautions mentioned above, there is no reason why it couldn’t. That’s not bad for having to do with an end-run around a hostile, politically charged issue such as stem cell debates. Would that all ethical issues could be decided so cleanly, or with so much fruit.

This article first appeared in Psychiatric Times.

To Sirtuin With Love: Caloric Restrictions and the Genes of the Aging Brain

noreply@blogger.com (John Medina) — Thu, 07 Apr 2011 23:02:00 +0000

One of the most interesting research efforts of the past few years seems to have taken a page from the preoccupations of the self-help magazine world: the cognitive decline of the brains of aging baby boomers and the obese nature of their grandchildren. These topics have been united by the well-established finding that restricting caloric intake leads to an increased life span in almost every animal tested. Because eating habits are formed early in life, the prediction is that a sensible diet will increase a person’s life span.

Is that true? The link between caloric restriction and life span is certainly solid, although the jury is still out on many of the claims made in the general media. Serious scientists have been studying the molecular biology behind this link for a number of years. One particular group of sequences seems to stand in the gap between aging and food, that of the sirtuin family of genes (also called silent information regulator [SIR] genes). One member of the family, the SIR2 gene, has been studied in particular detail. This article discusses age-related cognitive decline, caloric intake restriction, and the role SIR2 plays in the process.

As the brain ages

It is the canonical experience of people older than 40 that senior moments become an increasingly familiar part of one’s thinking life. We forget names, we forget places, we forget where we put our car keys, and we wonder when—and why—our retrieval systems began to abandon us. Higher-order processing begins to change as well as memory, perhaps not as obviously, but apparently in a far more dramatic way. Although the types of cognitive decline clearly vary from one person to the next, no one escapes these behavioral changes completely or, perhaps, the panic that ensues for some individuals when they compare their previous talent with current abilities.

It is axiomatic that cognitive decline occurs because of physical changes that human brains undergo as they age. Yet demonstrating the specifics of the relationship has not always been easy. With the advent of more sophisticated technologies (and improvements in older technologies), that has begun to change. We now know that changes in the regulation of global gene expression patterns—mostly down-shifting—are observed in a broad swath of the CNS during aging. Gene products specifically involved in the physiological processing of inhibitory signals mediated by γ-aminobutyric acid) have shown particular vulnerability. These neuron-related changes are disproportionately large when compared with changes in other tissues (eg, kidney and muscle tissues show age-related up-regulation).

Alterations in gross neuroanatomical structure have also been observed for many years. Some of the most dramatic involve disruptions of the myelinated fibers that yoke disparate brain regions together to provide specific functions—particularly in the prefrontal cortex (PFC). The changes are generally not due to neuronal loss in the PFC, which is actually quite minimal in most aging brains, but to loss of functional connectivity. The accompanying disruptions of neural integration in these regions of the aging brain result in less organized activity than is found in the brains of youthful controls. Such alterations are thought to be associated with a measurable behavioral change in aging populations: disruption of executive function (a task involved in everything from impulse control to planning for the future). This is part of a general age-related decline in the brain’s higher-order functional abilities.

One of the challenges of studying cognitive decline in elderly populations is separating normal changes in cognition from abnormal pathological changes. Although these are not always easy to distinguish, examination of the aging hippocampus has provided valuable insights. The normal aging pattern of the hippocampus involves an inhibition of metabolic activities of the dentate gyrus and subiculum. That is not what you see in patients who have Alzheimer disease. At least initially, the inhibition primarily targets the entorhinal cortex. Neuronal death in these tissues, with a general volumetric shrinkage of the medial temporal lobe, has been shown to distinguish the disease state from typical aging processes.

It is also a matter of calories

Many of the data presented above appear to describe natural, typical processes. But are they inevitable? One of the first questions many people ask after going a few rounds with their senior moment brains is: can the decline be reversed? These are often the questions asked by people who want to increase their life span. The surprising answer to both questions, in a few cases described below, is yes.

One of the most remarkable discoveries in the field of life span alteration occurred in the past century and has to do with caloric restriction. (This does not mean caloric starvation; malnutrition does not provide the benefit and is a completely different issue.) A controlled decrease in the amount of calories consumed has changed the life span of a surprising variety of animals, including mammals. It truly does mean that if you eat less, you will live longer.

The benefits of caloric restriction have been shown to have brain-specific effects as well. Caloric restriction can alter the regulatory genetic down-shifting phenomenon discussed earlier. It has also been shown to change the age-related neuronal degradation in nonhuman primates. Most relevant to our story, caloric restriction can affect human cognitive functioning. In one remarkable study, a caloric restriction protocol that lasted 90 days dramatically improved the verbal memories of a healthy geriatric cohort. Caloric restriction has even been shown to inhibit amyloid-related plaque formation in transgenic mice models of Alzheimer disease.

A matter of genes

Such robust findings work like scaffolding for researchers interested in the molecular biology behind the aging process and have certainly piqued the interest of people wanting to extend their life spans. What is the molecular mechanism behind the life span–extending properties of feeling hungry all the time? One of the earliest fruits of these research efforts was the isolation and characterization of the SIR genes.

The SIR genes were first isolated and characterized in yeast. They are a highly conserved family of sequences found in animals as diverse as roundworms and humans. One intensely studied member of this family is the SIR2 gene (Figure).

The SIR2 gene product functions as an NAD+-dependent deacetylase. In the presence of NAD+, SIR2 removes acetyl groups from proteins. Histone proteins are a favorite target of SIR2. As you may recall from your undergraduate days, histones are groups of proteins around which DNA molecules wrap themselves, somewhat like popcorn wrapped around string. Histones are deeply involved in regulating gene expression. Adding or subtracting subgroups to histones can profoundly influence the expression patterns of the genes in contact with the molecules.

How does SIR2 fit into the caloric restriction story? It was shown years ago that if you introduce SIR2 into yeast in such a fashion that you overdrive its expression, you can increase the yeast’s life span (measured as the number of times a cell completes a round of replication). If you severely restrict the caloric intake of an unmanipulated yeast, you can do the same thing. If you look for levels of SIR2 protein, you find that starvation has elevated its activity. The association appears to be strong, both by correlation and by direct intervention. The link between SIR2 protein and caloric restriction was first found in insects and then in mammals.

Subsequent research has muddied the waters of this otherwise seemingly tight story, however. Other researchers failed to replicate the results of the initial findings. Questions about various technical aspects that provided the original findings have been raised as well. There appear to be differences between genetic backgrounds in the primary test vehicles, from yeast to mice. These issues have yet to be fully resolved.

Such controversies are the nature of a good research project that, while hardly finished, has reached a certain maturity. These controversies are not deal killers regarding the association between the aging process and what goes in your mouth. The devil, as they say, is in the details. The fact that these issues can be raised at all demonstrates the enormous strides that researchers are making regarding the association between aging and eating—two of the most socially important issues of our time. That the arguments can revolve around deciding how the subtraction of acetyl groups changes the cell cycle simply shows how intimate, and how sophisticated, the progress has become.

This article originally appeared in Psychiatric Times.

References

Andrews-Hanna JR, Snyder AZ, Vincent JL, et al. Disruption of large-scale brain systems in advanced aging. Neuron. 2007;56:924-935.

Bishop NA, Lu T, Yankner BA. Neural mechanisms of ageing and cognitive decline. Nature. 2010;464:529-535.

Haigis, MC, Guarente LP. Mammalian sirtuins—emerging roles in physiology, aging and calorie restriction. Genes Dev. 2006;20:2913-2921.

Welberg L. A long and lean life. Nat Rev Neurosci. 2007;8:494-495.

The Neurobiology of Conscious Intent

noreply@blogger.com (John Medina) — Fri, 04 Mar 2011 00:49:00 +0000

Perhaps the seminal component of any clinician’s behavioral repertoire is the ability to understand the conscious motivations and intentions of their clients. This article addresses the work of conscious motivations at the neuroanatomical level.

I seldom address the notion of consciousness—let alone motivations—in this column for a very good reason. Nobody really knows what they are or even if there is a “they.” The literature is confusing, but it hasn’t stopped researchers from speculating on possible neuroanatomical and biochemical substrates that undergird the phenomena. Without a broad consensus about what is being studied, there can be no neurons, let alone molecules, for active experimental consideration. After all these years, researchers have yet to isolate an area of the brain solely devoted to the experience of consciousness. There may be none.

Given the importance of these issues to the mental health professions, I revisit the concept of motivations from time to time—but only when the data are conservatively presented, with sober, modest conclusions. The findings described here originate from experiments that have attempted to determine how we voluntarily choose to perform a motor task (action planning). This work requires reviewing background information on association cortices and the neural substrates behind a decision to initiate voluntary action.

Association cortices

Functionally, the cortical regions of the brain and their myriad interlocking circuits can be divided into 3 modules. These consist of front-, back-, and middle-end domains.

• Front-end functional domains are sensory information processing centers. The brain receives input from the eyes, ears, and other sensory systems. It sends the input off to various places for further processing.

• Back-end functional domains involve motor control systems. These systems essentially respond to whatever command the sensory cortices give to it (eg, execute a decision to move).

• The middle-end suite involves nearly everything other than front-end and back-end functional domains. These association cortices generally entail higher processing features and are some of the least understood and the most mysterious parts of the brain.

One such cortex, located in the inferior posterior parietal cortex, is a sensorimotor association region that links sensory stimuli to motor movement. It may even be involved in sensory prediction, which calculates the consequences of a given action through the simultaneous evaluation of input from both sensory (front-end) and motor (back-end) functional domains.

Volitional motor movement

Many of the actions humans initiate on a day-to-day basis seem to depend on a kind of internal free will. This sequence of events (also known as volitional motor movement) gives humans a sense of control: we act because we want to act. That is why researchers use volitional motor movements in their research designs. Researchers interested in volitional behavior study neural prime movers behind decision making.

Exactly what does it mean to want to do something? We do not really know. The events that initiate movement occur in a fairly straightforward sequence (although it depends on the source of the signal). For example, a central processing area with directives for voluntary motor movements pass through a final staging area before the execution of an action. This region is the primary motor cortex.

Research on laboratory animals demonstrates that this cortex decides on a course of action that depends on the source of signals it receives before the execution of that action. One source originates in the premotor cortex. Signals in this area initiate movements in response to a specific external trigger, such as a visual cue.

The second source arises in the presupplementary motor area, which is stimulated when laboratory animals make the same movements mentioned above, but they do not originate from responses to an external source. The movement instead arises spontaneously; a thought is internally generated through intentional actions. There is an observed rapid rise in electrical signals that build up just before the brain executes these actions. This has led to the notion that the presupplementary motor area harbors some kind of readiness potential, a useful function in generating movement (Figure).

In terms of human behavior, complex human brains have many more research issues to solve than standard laboratory animal research can address. One potential confounder is conceptual. With research of this type, scientists often tell subjects to choose (or not to choose) from a variety of options. Is that voluntary? Hardly. This is like saying, “Okay, it’s time to have some voluntary volitional behavior now,” or like runners at a race who respond to the starting gun. Do volitional actions disappear in these experiments with human subjects? Are these subjects simply reacting to commands to respond, not to respond, or to respond however they want? To test volition, researchers should not control the input. Nevertheless the experimenter must, almost by definition.

Wilder Penfield revisited

Another complexity involves engineering. How does conscious intent to move an arm relate to the actual movement of the arm? This could be partially resolved with electrical stimulation mapping in which surgeons create a map of the brain on conscious patients to understand what tissues need to be avoided during certain manipulations (such as resection). No pain neurons exist in the brain. The patient, immobilized in a stereotactic frame, can be consciously interrogated while the surgery takes place. The surgeon applies a gentle electrical current to the open tissue, talks to the patient about what he or she is experiencing, and makes a map that discerns what areas to avoid during cutting. Working primarily with epileptic patients, the legendary Canadian physician Wilder Penfield first performed these techniques.¹

This technique has proved to be of great value in understanding volitional components of motor movement. It was discovered almost 2 decades ago that if one stimulates a specific area of the human presupplemental area, the patient will experience a conscious urge to move.² This gets around the runner’s starting gun problem mentioned previously. An external electrical stimulator supplies a specific quantity of electricity—and a desire to do something is suddenly generated!

As important and well-characterized as these data are, they hardly explain what causes the presupplemental area to generate the signal in subjects not undergoing surgery. Some research findings answer this question and have led to some intriguing results.^3,4

When the inferior posterior parietal cortex was stimulated, the patient experienced an urge to move specific body parts. Stimulating one area caused patients to want to move their arms. Another region, the lips. Another region, the chest. This is similar to what one observes in frontal lobes, except that you are nowhere near the frontal lobes. Recall that this is the associative cortex region (a sensorimotor associative area at that), quite distinct from anything observed in the well-characterized general motor areas of the frontal lobes. Was this simply a remote stimulation?

This result showed that the answer would be no. The parietal cortex urges were qualitatively different from those obtained by stimulating parts of the presupplementary cortex. It is well known that if the presupplementary cortex is stimulated at a low current, the urge to act is acquired. However, if the same region is stimulated at high current, actual movement occurs. That’s not what happened in the parietal cortex. The urge was stimulated at low intensities, but movement was never generated at higher ones. Instead, subjects felt that they had already performed some movement.

This is important. The desire to move did not result from subtle motor contractions that may have been generated by motor regions (an alternative idea that has been put forth as a rational explanation for the results in previous experiments). Parietal stimulation never produces muscle activity, regardless of the intensity. The stimulation of the premotor cortex itself produces large-limb movements in subjects, but never the desire to move the limbs. They usually remain unaware that movement has occurred when these regions are stimulated.

These results suggest the presence of 2 specific aspects of conscious intention (however one defines it). One might be the conscious correlation of preparatory motor commands in the presupplemental cortex region, as is clearly observed in laboratory studies of animals. The other might involve sensory prediction of the consequences of those commands, under the domain of the association cortex region. A portion of conscious intent seems to be a specific class of experiences housed within the parietal lobe.

Conclusions

It appears that the parietal lobe contributes to the conscious experience of intention, at least in regard to motor movement. These results cement 1 more brick onto the great construction project that seeks to define intention. But they hardly hint at the overall building.

Pushing the edge of our understanding into the murky world of association cortex only means that future experiments will be trickier to interpret. Electrical stimulation mapping, as good as it is, is necessarily a blunt instrument that stimulates thousands of neurons simultaneously. Not isolated modules, these regions connect to each other in complex, little-understood ways. That the regions produce different behaviors is an important finding but not a defining one.

How do the frontal and motor aspects of volitional experience differ from the parietal, sensory versions? What factors stimulate the parietal lobes in the first place? What about remote effects?

Questions such as these remain to be answered and are just a few of the many that researchers will face as they attempt to define intentional and conscious experiences.

This article originally appeared in the Psychiatric Times.

References

1. Penfield W, Erickson TC. Epilepsy and cerebral localization: a study of the mechanism, treatment and prevention of epileptic seizures (Review). South Med J. 1942;35:222.
2. Fried I, Katz A, McCarthy G, et al. Functional organization of human supplementary motor cortex studied by electrical stimulation. J Neurosci. 1991;11:3656-3666.
3. Haggard P. Human volition: towards a neuroscience of will. Nat Rev Neurosci. 2008;9:934-946.
4. Custers R, Aarts H. The unconscious will: how the pursuit of goals operates outside of conscious awareness. Science. 2010;329:47-50.

Discipline Advice: A Magic Trick for Getting Kids to Follow Rules

noreply@blogger.com (John Medina) — Mon, 21 Feb 2011 22:49:00 +0000

Let's say little Aaron has been punished for a moral infraction -- stealing a pencil from classmate Jimmy -- just before a test. The punishment was subtractive in nature -- Aaron would have no dessert that night. But Aaron was not just punished and left alone.

He was also given a magic follow-up sentence, one that makes any form of punishment more effective, long-lasting, and internalized.

Watch this video from brainrules.net to see an example (watch on YouTube):

Explanations given to Aaron ranged from "How could Jimmy possibly complete his test without his pencil?" to "Our family doesn't steal."

Here's what happens to Aaron's behavior when explanations are supplied consistently over the years:

When Aaron thinks about committing that same forbidden act in the future, he will remember the punishment. He becomes more physiologically aroused, generating uncomfortable feelings.

Aaron will make an internal attribution for this uneasiness. Examples might include: "I'd feel awful if Jimmy failed his test," "I wouldn't like it if he did that to me," "I am better than that," and so on. Your child's internal attribution originates from whatever rationale you supplied during the correction.

Now, knowing why he is uneasy -- and wanting to avoid the feeling -- Aaron is free to generalize the lesson to other situations. "I probably shouldn't steal erasers from Jimmy, either." "Maybe I shouldn't steal things, period."

Cue the applause of a million juvenile correction and law-enforcement professionals. Inductive parenting provides a fully adaptable, internalizable moral sensibility -- congruent with inborn instincts. (Aaron also was instructed to write a note of apology, which he did the next day.)

Kids who are punished without explanation do not go through these steps. Parke found that such children only externalize their perceptions, saying, "I will get spanked if I do this again." They were constantly on the lookout for an authority figure; it was the presence of an external credible threat that guided their behavior, not a reasoned response to an internal moral compass. Children who can't get to step two can't get to step three, and they are one step closer to Daniel, the boy who stabbed a classmate in the cheek with a pencil.

The bottom line: Parents who provide clear, consistent boundaries whose reasons for existence are always explained generally produce moral kids.

Note that I said "generally." Inductive discipline, powerful as it is, is not a one-size-fits-all strategy. The temperament of the child turns out to be a major factor. For toddlers possessed of a fearless and impulsive outlook on life, inductive discipline can be too weak. Kids with a more fearful temperament may react catastrophically to the sharp correctives their fearless siblings shrug off. They need to be handled much more gently.

All kids need rules, but every brain is wired differently, so you need to know your kid's emotional landscapes inside and out -- and adapt your discipline strategies accordingly.

Brain Rules in the News:
Forbes - Being There why it still pays to meet in the flesh
Our 365 - 6 Questions for John Medina
Radio New Zealand Interview with John Medina
Sound Medicine (NPR) Interview

Breast-Feeding Debate Closed? Brain Science Weighs In

noreply@blogger.com (John Medina) — Thu, 27 Jan 2011 20:38:00 +0000

I remember meeting up with an old friend who had just become a mother. Baby in tow, we entered a restaurant. She immediately insisted on sitting at a private booth, and after five minutes, I discovered why. Mom knew that her baby would soon be hungry. When he was, she discreetly unbuttoned her blouse, adjusted her bra, and began breast-feeding. The baby latched on for dear life.

Mom had to go through all kinds of contortions to hide this activity. "I've been thrown out of other places because I did this," she explained. Though shrouded in an oversize sweater, she was visibly nervous as the waiter took her order.

If America knew what breast milk can do for the brains of it youngest citizens, lactating mothers across the nation would be enshrined, not embarrassed. Though the topic is much debated, there's little controversy about it in the scientific community.

Breast milk is the nutritional equivalent of a magic bullet for a developing baby. It has important salts and even more important vitamins. Its immune-friendly properties prevent ear, respiratory and gastrointestinal infections.

And in a result that surprised just about everybody, studies around the world confirmed that breast-feeding, in short, makes babies smarter. Breast-fed babies in America score on average eight points higher than bottle-fed kids when given cognitive tests, an effect still observable nearly a decade after the breast-feeding has stopped. They get better grades, too, especially in reading and writing.

Why? We have some ideas (watch on YouTube):

The American Academy of Pediatrics recommends that all mothers breast-feed exclusively for the first six months of their babies' lives, continue breast-feeding as their kids start taking on solids, and wean them after a year.

If we as a country wanted a smarter population, we would insist on lactation rooms in every public establishment. A sign would hang from the door of these rooms: "Quiet, please. Brain development in progress."

Kids Lie Every 90 Minutes -- And That's a Good Thing (VIDEO)

noreply@blogger.com (John Medina) — Wed, 19 Jan 2011 22:28:00 +0000

Kids are bad at lying, at least at first. In the magical fairy dust of the childhood mind, kids initially have a hard time distinguishing reality from fancy, which you can see in their eagerness to engage in imaginative play.

They also perceive their parents to be essentially omniscient, a belief that won't be completely destroyed until the 20-kiloton blast of puberty. The fuse gets lit early, though, around 36 months, when kids begin to realize that parents can't always read their minds. To their delight (or horror), children discover they can give their parents false information without its being detected. Or, at least, they think they can. The child's realization that you can't always read his or her mind coincides with the flowering of something we call Theory of Mind skills.

What is Theory of Mind? This video explains:

This timeline suggested to researchers that children have an age-dependent relationship with certain types of moral reasoning, too. There's evidence that kids are born with certain moral instincts, but it takes a while to coax them into their mature form.

Babies Pick Up On More Than You'd Think

noreply@blogger.com (John Medina) — Wed, 15 Dec 2010 20:54:00 +0000

At first blush, babies seem mostly preoccupied with more mundane biological processes, like eating and pooping and spitting up all over your shirt. This fooled a lot of researchers into believing that babies weren't thinking about anything at all. Scientists coined the term "tabula rasa" -- blank slate -- to describe these "empty" creatures. They regarded infants as merely helpless helpings of cute, controllable, human potential.

Modern research reveals a radically different point of view. We now know that a baby's greatest biological preoccupation involves the organ atop their necks. Infants come preloaded with lots of software in their neural hard drives, most of it having to do with learning. Want some startling examples?

In 1979, University of Washington psychologist Andy Meltzoff stuck out his tongue at a baby that was just 42 minutes old, then sat back to see what happened. After some effort, the baby returned the favor, slowly rolling out his own tongue. Meltzoff stuck his tongue out again. The infant responded in kind. Meltzoff discovered that babies could imitate right from the start of their little lives (or, at least, 42 minutes from the start of their little lives).

That's an extraordinary finding. Imitation involves many sophisticated realizations for babies, from discovering that other people exist in the world to realizing that they have operating body parts, and the same ones as you. That's not a blank slate. That's an amazing, fully operational cognitive slate.

Capitalizing on this finding, Meltzoff designed a series of experiments revealing just how much babies are prewired to learn -- and how sensitive they are to outside influences in pursuit of that goal. Here's one of those experiments (Watch Deferred Imitation on YouTube):

Yes, infants come equipped with an amazing array of cognitive abilities -- and they are blessed with many intellectual gadgets capable of extending those abilities:

They understand that size stays constant even when distance changes the appearance of size.

They display velocity prediction.

They understand the principle of common fate: The reason the black lines on the basketball move when the ball bounces is because the lines are part of the basketball.

Infants can discriminate human faces from nonhuman faces at birth and seem to prefer them. From an evolutionary perspective, this latter behavior represents a powerful safety feature. We will be preoccupied with faces most of our lives.

How did babies acquire all of this knowledge before being exposed to the planet? Nobody knows, but they have it, and they put it to good use with astonishing speed and insight. Babies create hypotheses, test them, and then relentlessly appraise their findings with the vigor of a seasoned scientist. This means infants are extraordinarily delightful, surprisingly aggressive learners. They pick up everything.

Which is one reason you want to be careful about what kind of television shows your children watch. You may also want to take a look at the behaviors your kids see most often: yours.

More Resources
The Art of Childraising - interview with Guy Kawasaki
Brain Rules Videos - all the segments from the Brain Rules DVD
Brain Rules for Baby Videos - watch videos ranging from temper tantrums to TV viewing

The Business of Pleasure and Pain

noreply@blogger.com (John Medina) — Thu, 09 Dec 2010 17:46:00 +0000

The neuroanatomical linkage that emerges from a normal part of business experience—the reaction to success and also to failure (especially if that failure happens to someone else)—is the focus of this post. I am often asked to speak to groups of business executives, mostly to discuss a possible connection between neuroscience and business practices. These meetings are always challenging for me, because I don’t think brain science has much to do with the world of business. My own opinion is that the field of neuroscience is simply not mature enough to tell business executives how to manage their subordinates or how to lure customers into buying their products. “I have nothing real to say to you,” I usually start, “We don’t even understand how humans know how to put their socks on in the morning.”

There are usually some murmurs in the crowd at this point, but since I still have 45 to 60 minutes to burn, I continue, “My perspective isn’t hopeless, though. In fact, almost all of the brain’s neural circuitry can be easily explained—especially if you are looking at people’s interior motivations.” Then I continue with what turns into a Darwinian lecture: “People will do whatever they think will ultimately benefit them. And people will do whatever they can to avoid pain. Almost everything we know about how the brain generates behavior can be couched as combinatorial activations of these 2 broad sets of purpose-driven circuits—seeking pleasure, avoiding pain.”

The human brain as a mass of biological tissue is most clearly understood as a survival organ—the world’s most sophisticated. Given this performance envelope, a great deal of theoretical common ground exists between what we know about the brain and the needs of business. Even though not much of the brain has been mapped, my corporate audiences and I usually end up with lots to say to each other.

This post is all about mapping a specific parcel of this common ground between pleasure and pain and gives a suggestion for a specific investigative direction. We will explore how a subset of these circuits supports the social experience of pleasure and pain.

There is a powerful bridge between pleasure and pain and their social equivalents; indeed, to the brain, they are nearly identical. Recent findings confirm that the same reward circuits are activated during sex and also while delighting in someone else’s misfortune (schadenfreude).¹ Similarly, both physical pain and envy over another person’s success activate these circuits.

The biology of pleasure and pain

We start with a basic review of canonical circuits normally associated with pleasure and pain, and then discuss interesting data from a collaboration of scientists in Japan and the United Kingdom. Much of the brain’s pleasure circuitry has been studied through the lens of reward reception and the establishment of addictive behavior. Invariably, this involves the neurotransmitter dopamine and a number of neural circuits that have been isolated and characterized in surprising detail.

Three networks are briefly reviewed. The first circuit involves the interaction of dopamine in neurons within the ventral tegmental area, especially in response to external rewards (eg, sexual activity, drugs, food). Associated with these circuits, the second network comprises neurons embedded in the nucleus accumbens, within the ventral striatum. The nucleus accumbens has been shown to play a vital role in the learning of reward and the regulation of pleasurable states. The third circuit involves the ventromedial prefrontal cortex in association with the amygdala. These 3 networks are also vital parts of the dopaminergic system and are thought to mediate reward processing and the emotional responses involved in the experience of pleasure.

Association never means causation. If you could somehow temporarily deactivate the ventral striatum, would schadenfreude suddenly disappear?

The various circuits associated with mediating the experience of pain are collectively termed the “cortical pain network” (see Figure). This network consists of specific regions, mostly ventral to the pleasure centers; in turn, these are coupled with 2 subcortical structures. The specific regions are the somatosensory cortex, the dorsal anterior cingulate cortex (dACC), and the insula. The connecting subcortical regions are the periaqueductal gray and the thalamus.

Each region makes unique contributions in the perception of pain. For example, the somatosensory cortex is associated with the localization of the stimulus within the body. The dACC and, to a lesser extent, the insula are associated with the processing of more distressing aspects of pain.

These circuits undergird the twin Darwinian “motivations.” But can I really say that? After all, they have been mostly characterized as physical reactions to rewarding stimuli (such as drugs) or as physical reactions to aversive stimuli (such as an electrical shock). These networks have deep evolutionary roots, which means we share many of these same circuits with other mammals. However, none of this history involves a businessperson’s reaction to marketing strategies or mitigating highbrow office politics that are associated with management.

Does the creation and perception of social rewards and punishments activate the same regions as nucleus accumbens and the dACC? In the past few years, the surprising answer from research is a clear “yes.” Social rewards and punishments appear to hijack the same systems we use to mediate laboratory-based measurements of pleasure and pain. If you are being treated fairly, are feeling cooperative, or have been blessed with a good reputation, you feel so in part because of circuits activating the ventral striatum. This reward network is activated whenever you make a charitable contribution—even more than if you suddenly inherited a lot of money!

Similarly, specific circuits of the cortical pain network become activated whenever you experience social pain, such as grief over the loss of a loved one. The same circuits are activated if you feel you are being treated unfairly. The dACC and insula are recruited whenever you feel socially excluded. The more social pain you feel, the more activity is generated within the dACC.

The bottom line is that the brain appears to treat material physical stimuli and amorphous social perceptions in a manner more similar than previously thought.

The data

Researchers from Japan and the United Kingdom explored 2 specific types of social interactions in a 2-part study1 involving the above data. What they found has potentially high relevance to business practices. While it is beyond the scope of this column to go into specifics, we will say that in general, 19 volunteer participants were supplied with information concerning imaginary target persons. These persons were characterized by levels of possession and self-relevance. The participants underwent functional MRI, more social information was supplied, and the experiments commenced.

When the participants were told that the targets had superior possessions and self-relevance, they reported strong feelings of envy. Surprisingly, the areas of the brain associated with physical pain—particularly the dACC—showed a very strong signal in the people experiencing envy, even though no physical pain was being experienced. The effect appeared to be linear and cumulative. The more envy evinced, the stronger the dACC signal was observed.

For the second part of the study, researchers tested for schadenfreude, or delight in someone else’s misfortune. The participants were told that the “superior” targets had experienced something awful. What did their brains do? The areas associated with pleasure, particularly the ventral striatum, showed an immediate and powerful activation. This effect was also linear and cumulative. The more envy evoked in the first part of study, the greater the pleasure signals were observed in the second. For the first time, research demonstrated a lively and dramatic integration between the experiences of social pleasure and social pain.

Conclusions

There is a lot more work to be done before a clear picture emerges. For one thing, areas of the brain—such as the dACC and the ventral striatum—include a broad range of activities, not all of which fall under the rubric of pleasure and pain mitigation. Experiments will need to rely on the power of future technologies to identify the boundaries of actual neural networks involved. And, of course, association never means causation. If you could somehow temporarily deactivate the ventral striatum, would schadenfreude suddenly disappear? This research has yet to be done.

Still, the data in context with previous research undergird critical insight into the incredible evolutionary importance of social relationships to the human brain. Many researchers believe it was our dependence on relational activities that created the need for this big, unique brain of ours in the first place. As weak as our bodies are, it was more convenient for us to double our biomass by creating a cooperative ally than by creating a bigger body. This meant putting pressure on a relatively small number of neurons in the brain, rather than a large number of cells throughout the body.

Moreover, the brain is an efficient and evolutionary manager of its bioenergetic needs. It is not surprising that regions associated with the physical needs of pleasure and pain might be recruited for the more abstract social versions of the same thing. The gift this gives people interested in the biological roots of behavior is enormous: certain previously considered subjective experiences—such as envy—may not be as subjective as we once thought. If that’s the case, I will eventually owe my business audiences a big apology. Perhaps in a few years, brain scientists will have something to say to business people interested in improving their “bottom lines.”

Reference

1. Takahashi H, Kato M, Matsuura, et al. When your gain is my pain and your pain is my gain: neural correlates of envy and schadenfreude.Science.2009;323:937-939.

This post originally appeared in the November 2010 issue of the Psychiatric Times.

More Resources

This is your brain at work - John Medina featured in New York Post

Brain Rules for Presenters - slideshow on what all presenters need to know

John Medina Facebook - stay in the brain science loop

Brain Rules DVD - watch videos on exercise, stress, sleep, and more

'Parentese': Can Speaking To Your Baby This Way Make Her Smarter? (VIDEO)

noreply@blogger.com (John Medina) — Tue, 07 Dec 2010 06:09:00 +0000

For the longest time, we couldn't figure out the words coming from our nine-month-old son Josh.

Whenever he took a car ride, he would start saying the word "dah," repeating it over and over again as we strapped him into his car seat, "Dah dah dah, goo, dah dah, big-dah, big-dah." It often sounded like a child's version of an old Police song. We couldn't decode it and would just respond, a bit sheepishly, "Dah?" He would emphatically reply, "Dah." Sometimes our response made him happy. Sometimes it didn't do anything at all.

It wasn't until we were tooling down the interstate one fine, sunny day, moon-roof wide open to the clouds, that we finally figured it out.

Josh saw an airplane flying overhead and shouted excitedly, "Sky-dah! Sky-dah!" My wife suddenly understood. "I think he means airplane!" she said. She asked him, pointing to the sky, "Sky-dah?" Josh cheerily replied, "Sky-dah!" Just then a big noisy semi-truck passed us, and Josh pointed to it with concern. "Big-dah, Big-dah," he said. My wife pointed at the truck too, now shrinking in the distance. "Big-dah?" she asked, and he responded excitedly, "Big-dah!" Then "dah, dah, dah."

We got it. For whatever reason, "dah" had become Joshua's word for "vehicle." Later, Josh and I watched a ship cross Puget Sound. I pointed to the container vessel and guessed, "Water-dah?" He sat up, staring at me like I was from Mars. "Wet-dah," he declared, like a mildly impatient professor addressing a slow student.

Few interactions with children are as much fun as learning to speak their language. As they learn to speak ours, heaping tablespoons of words into their minds is one of the healthiest things parents can do for their brains.

Speak to your children as often as you can. It is one of the most well-established findings in all of the developmental literature -- which is why it is among those detailed in my new book, "Brain Rules for Baby: How to Raise a Smart and Happy Child From Zero to Five."

The linkage between words and smarts was discovered through some pretty invasive research. In one study, investigators descended upon a family's home every month for three years and jotted down every aspect of verbal communication parents gave their children. They measured size of vocabulary, diversity and growth rate of vocabulary, frequency of verbal interaction, and the emotional content of the speech. Just before the visits were finished, the researchers gave IQ tests. They did this with more than 40 families, then followed up years later.

Through exhaustive analysis of this amazingly tough work, two very clear findings emerged:

1) The variety and number of words matter.

The more parents talk to their children, even in the earliest moments of life, the better their kids' linguistic abilities become and the faster that improvement is achieved. The gold standard is 2,100 words per hour. The variety of the words spoken (nouns, verbs, and adjectives used, along with the length and complexity of phrases and sentences) is nearly as important as the number of words spoken. So is the amount of positive feedback.

You can reinforce language skills through interaction: looking at your infant; imitating his vocalizations, laughter and facial expressions; rewarding her language attempts with heightened attention.

Children whose parents talked positively, richly and regularly to them knew twice as many words as kids whose parents talked to them the least. When these kids entered the school system, their reading, spelling and writing abilities soared above those of children in less verbal households. Even though babies don't respond like adults, they are listening, and it is good for them.

2) Talking increases IQ.

Talking to children early in life raises their IQs, too, even after controlling for important variables such as income. By age three, kids who were talked to regularly by their parents (called the talkative group) had IQ scores 1.5 times higher than those kids whose parents talked to them the least (called the taciturn group). This increase in IQ is thought to be responsible for the talkative group's uptick in grades.

It takes a real live person to benefit your baby's brain, so get ready to exercise your vocal cords. Not the portable DVD players, not your television's surround sound, but your vocal cords.

What should you say and how should you say it? Find out in these videos (also on YouTube):

WATCH:

More Brain Rules Resources
- Brain Rules Multimedia on Exercise, Sleep, Stress, and more
- Brain Rules Sleep Slideshow Sleep well, think well
- Take the Parent Quiz What's the best way to handle a temper tantrum?
- Brain Rules for Baby Podcast John talks with Geoffrey Grosenbach about parenting
- Brain Rules for Baby Introduction Share the intro with a friend

How Much TV Should Kids Be Allowed To Watch?

noreply@blogger.com (John Medina) — Fri, 19 Nov 2010 21:58:00 +0000

The issue of kids' exposure to TV doesn't throw off as many sparks as it used to. There is general agreement that a child's exposure to television of any type should be limited. There is also general agreement that we are completely ignoring this advice. I remember as a kid waiting every Sunday night for Walt Disney's "Wonderful World of Color" to come on, and loving it. I also remember my parents turning off the television when it was over. We don't do that anymore.

Americans two years of age and older now spend an average of four hours and 49 minutes per day in front of the TV -- 20 percent more than 10 years ago. And we are getting this exposure at younger and younger ages, made all the more complex because of the wide variety of digital screen time now available. In 2003, 77 percent of kids under six watched television every day. And children younger than two got two hours and five minutes of "screen time" with TVs and computers per day.

What effect might this have on our children's brains? It's not good news.

For decades we have known of the connection between hostile peer interactions and the amount of kids' exposure to television. The linkage used to be controversial (maybe aggressive people watch more TV than others), but we now see that it's an issue of our deferred-imitation abilities, coupled with a loss of impulse control. One personal example: When I was in kindergarten, my best friend and I were watching "The Three Stooges," a 1950s TV show. The program involved lots of physical comedy, including people sticking their fingers in other people's eyes. When the show was over, my friend fashioned his little fingers into a V, then quickly poked me in both eyes. I couldn't see anything for the next hour and was soon whisked to the emergency room. Diagnosis: scratched corneas and a torn eye muscle.

Other examples come from studies that looked at bullying, attentions spans and the ability to focus, and secondhand exposure to TV. Watch this video to find out the results:

Disturbing stuff. Since the first studies on television, researchers have discovered that not everything about TV is negative. The effect depends upon the content of the TV show, the age of the child, and perhaps even the child's genetics. Before age two, TV is best avoided completely. That includes videos that claim to be baby brain-boosters. (More on that, and video games, in my new book, "Brain Rules for Baby: How to Raise a Smart, Happy Child from Zero to Five.")

After age five, the jury is out on this harsh verdict -- way out, in fact. Some television shows improve brain performance at this age. Not surprisingly, these shows tend to be the interactive types ("Dora the Explorer," good; "Barney and Friends," bad, according to certain studies). So, although the case is overwhelming that television exposure should be limited, TV cannot be painted with a monolithic brush.

Here are a few recommendations for TV viewing the data suggest:

Keep the TV off before the child turns two. I know this is tough to hear for parents who need a break. If you can't turn it off -- if you haven't created those social networks that can allow you a rest -- at least limit your child's exposure to TV. We live in the real world, after all, and an irritated, overextended parent can be just as harmful to a child's development as an annoying purple dinosaur.

After age two, help your children choose the shows (and other screen-based exposures) they will experience. Pay special attention to any media that allow intelligent interaction.

Watch the chosen TV show with your kids, interacting with the media, helping them to analyze and think critically about what they just experienced. And keep the TV out of the kids' room: Kids with their own TVs score an average of eight points lower on math and language-arts tests than those in households with TVs in the family room.

More parenting videos on brainrules.net detail key insights from the book, from how to deal with temper tantrums to the surprising way a "cookie test" can predict SAT scores.

How A Pair Of Cookies Can Help Predict Your Child's SAT Scores (VIDEO)

noreply@blogger.com (John Medina) — Tue, 09 Nov 2010 06:07:00 +0000

A healthy, well-adjusted preschooler sits down at a table in front of a giant, freshly baked chocolate chip cookie. It's not a kitchen table -- it's Walter Mischel's Stanford lab during the late 1960s. The smell is heavenly.

"You see this cookie?" Mischel says. "You can eat it right now if you want, but if you wait, you can have two of them. I have to go away for five minutes. If I return and you have not eaten anything, I will let you have both cookies. If you eat this one while I'm gone, the bargain is off and you don't get the second one. Do we have a deal?" The child nods. The researcher leaves. What does the child do?

Mischel has the most charming, funny films of children's reactions. They squirm in their seat. They turn their back to the cookie (or marshmallow or other assorted caloric confections, depending on the day). They sit on their hands. They close one eye, then both, then sneak a peek. We took a camera into a preschool to see what would happen for ourselves (watch The Cookie Test):

The children in Mischel's experiment are trying to get both cookies, but the going is tough. If the children are kindergartners, 72 percent cave in and gobble up the cookie. If they're in fourth grade, however, only 49 percent yield to the temptation. By sixth grade, the number is 38 percent, about half the rate of the preschoolers.

Welcome to the interesting world of impulse control. It is part of a suite of behaviors under the collective term "executive function." Executive function controls planning, foresight, problem solving, and goal setting. It engages many parts of the brain, including a short-term form of memory called working memory.

Mischel and his many colleagues discovered that a child's executive function is a critical component of intellectual prowess. We now know that it is actually a better predictor of academic success than I.Q. It's not a small difference, either: Mischel found that children who could delay gratification for 15 minutes scored 210 points higher on their SATs than children who lasted one minute.

A child's brain can be trained to enhance self-control and other aspects of executive function. But genes are undoubtedly involved. There seems to be an innate schedule of development, which explains why the cookie experiment shows a difference in scores between kindergartners and sixth graders. Some kids display the behaviors earlier, some later. Some struggle with it their entire lives. It's one more way every brain is wired differently. But children who are able to filter out distractions, the data show, do far better in school.

Learn more about why in my new book, "Brain Rules for Baby: How to Raise a Smart and Happy Child from Zero to Five." Watch more parenting videos at brainrules.net.

Authors@Google: John Medina Brain Rules for Baby

noreply@blogger.com (John Medina) — Fri, 05 Nov 2010 17:06:00 +0000

Watch John Medina's Authors@Google talk on Brain Rules for Baby: How to Raise a Smart and Happy Child from Zero to Five.

The #1 mistake parents make with praise (VIDEO)

noreply@blogger.com (John Medina) — Fri, 29 Oct 2010 15:15:00 +0000

Does your child give up easily? It could be because of a common parenting mistake.

Ethan's parents constantly told him how brainy he was. The wiry son of a highly educated professor in Seattle, Ethan was indeed smart. Every time he sailed through a test, his parents would say, "You're so smart! You can do anything, Ethan. We are so proud of you." Sounds nice. Sounds encouraging, right?

Wrong. Little Ethan quickly learned that any academic achievement that required no effort was the behavior that defined his gift. His parents, with the best of intentions, consistently tethered Ethan's accomplishments to some vague, innate characteristic. Researchers call this "appealing to fixed mindsets."

When Ethan hit junior high school, he ran into subjects that did require effort. He could no longer sail through; for the first time, he started making mistakes. Ethan had no idea what to do when he failed, except to conclude that he must not be smart anymore. He got discouraged, then depressed. Quite simply, Ethan quit trying, and his grades collapsed. Research shows that Ethan's unfortunate story is typical of kids regularly praised for some fixed characteristic.

Research shows a simple solution. Certainly, scientists don't know everything about the brain. But what we do know gives parents their best chance at raising smart, happy children. What should Ethan's parents have done?

Rather than praising him for being smart, they should have praised him for working hard. On the successful completion of a test, they should not have said, "I'm so proud of you. You're so smart." They should have said, "I'm so proud of you. You must have really studied hard." Big difference. This appeals to your child's controllable effort rather than to mysterious, unchangeable talent. It's called "growth mindset" praise.

More than 30 years of study show that children raised in growth-mindset homes consistently outscore their fixed-mindset peers in academic achievement. There's more detail about why in my new book, "Brain Rules for Baby: How to Raise a Smart and Happy Child from Zero to Five."

Children with a growth mindset tend to:
• Have a refreshing attitude toward failure. They do not ruminate over their mistakes.
• Perceive errors simply as problems to be solved. "I love a challenge," is one delightfully common statement.
• Spend more time on problems--and solve those problems more often, too. Kids regularly praised for effort solve 50% to 60% more hard math problems than kids praised for intelligence.

Because they believe mistakes occur from of lack of effort, not from a lack of ability, the kids know exactly how to remedy mistakes: simply apply more effort.

You can watch this in action in the following video, from brainrules.net:

More parenting videos detail key insights from the book, from how to deal with temper tantrums to the surprising "cookie test."

The Parent Quiz (VIDEO)

noreply@blogger.com (John Medina) — Tue, 19 Oct 2010 20:58:00 +0000

Parents need facts, not just advice, about raising their children. Too bad those facts are difficult to find in the ever-growing mountain of parenting books. And blogs. And message boards, and podcasts, and mothers-in-law, and every relative who's ever had a child. There's plenty of information out there. It's just hard for parents to tell what to believe.

That's why I wrote "Brain Rules for Baby: How to Raise a Smart and Happy Child from Zero to Five." It's based on science that most parents (unless they subscribe to scientific journals) don't get a chance to see. The great thing about science is that it takes no sides -- and no prisoners. Once you know which research to trust, the big picture emerges and myths fade away. To gain my trust, research must first have been published in the refereed literature and then successfully replicated.

Scientists certainly don't know everything about the brain. But what we do know gives parents their best chance at raising smart, happy children.

Surprises in "Brain Rules for Baby" include:

• Why men should do more household chores
• What you do when emotions run hot profoundly affects how your child turns out
• Why you shouldn't praise your kid's intelligence
• The amount of TV kids under two should watch
• The best predictor of academic performance

Know the answers? Test yourself in the video "The Parent Quiz." In the first half, you'll watch a dad, Michael, deal with the baby crying, the wife sighing, and the goldfish dying. In the second half, I give a "Who Wants to Be a Millionaire?"-style quiz:

More videos detail key insights from the book, from how to deal with temper tantrums to the benefits of breast-feeding.

Nature and nurture may be split 50-50. But there's a great deal parents can do with the influence they have.

More content:
Watch Part One "Parenting Fail?"
Watch Part Two "The Parent Quiz"
Brain Rules for Baby on Facebook
Happy baby - How to head off temper tantrums

Brain Rules for Baby - Book Tour

noreply@blogger.com (John Medina) — Fri, 24 Sep 2010 05:24:00 +0000

Brain Rules for Baby: How to Raise a Smart and Happy Child from Zero to Five is coming out in just two weeks. John Medina is hitting the road and speaking in Portland, NYC, Philadelphia, Chicago, Cleveland, Seattle, Denver, and San Francisco! View the book tour page or check out the schedule below.

Thursday, October 7 @7pm -- Portland

Portland State University Smith Memorial Student Union

1825 SW Broadway

Portland, OR 97201

Download PDF Invite

Facebook Invite

Tuesday, October 12 @7pm -- New York City

Riverdale Country School

5250 Fieldston Road

Bronx, NY 10471

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Wednesday, October 13 @1pm -- New York City

Barnes & Noble Upper East Side

150 East 86th Street (Lexington)

New York, NY 10028

(212) 369-2180

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Facebook Invite

Thursday, October 14 @7pm -- Philadelphia

Episcopal Academy

1785 Bishop White Drive

Newtown Square, PA 19073

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Saturday, October 16 @9am - noon -- New York City

NYC AEYC Conference

Food and Finance High School

525 West 50th Street

New York, NY 10019

Cost $50; Register (note: select "keynote speaker only" on the form)

Download PDF Invite

Facebook Invite

Download NYC Flyer (Oct 12, 13, 16 Events)

Tuesday, October 19 @7pm -- Seattle

Town Hall Seattle (Great Hall)

1119 8th Avenue (8th and Seneca)

Seattle, WA 98101

Cost $25 (includes copy of Brain Rules for Baby or Brain Rules) Buy tickets

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Friday, October 22 @6:30pm -- Seattle

Children's Trust Foundation

Fundraiser at The Edgewater Hotel

2411 Alaskan Way, Pier 67

Seattle, WA 98121

Cost $75 (all proceeds go to Children's Trust; book is included) Register

Monday, October 25 @7pm -- Chicago

Cornerstone Center

1111 N. Wells St.

Chicago, IL 60610

RSVP: Archie Jeter, 312.427.5399 or ajeter@chicagometroaeyc.org

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Tuesday, October 26 @7pm -- Cleveland

Joseph-Beth Booksellers

Legacy Village

24519 Cedar Road

Lyndhurst, OH 44124

(216) 691-7000

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Thursday, October 28 @4:30pm -- Denver

Gates Concert Hall at the Newman Center, University of Denver Campus

2344 East lliff Avenue at University Boulevard

Denver, CO 80208

There is no charge, however you are required to register.

Friday, October 29 1:30pm - 3:00pm -- Denver

Children's Museum of Denver

2121 Children's Museum Drive

Denver, CO 80211

(303) 43307444

Download PDF Invite

Facebook Invite

Book signing (come anytime between 1:30pm - 3:00pm). Bring the kids in costume for Trick or Treat Street!

Wednesday, November 3 @7pm -- San Francisco

Walt Disney Museum Theatre

104 Montgomery Street

San Francisco, CA 94129

Hosted by Bay Area Discovery Museum (BADM)

Download PDF Invite

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Thursday, November 4 @7pm -- Los Altos Hills (SF Bay Area)

Foothill College

12345 El Monte Road

Los Altos Hills, CA 94022

Hosted by Bay Area Discovery Museum (BADM)

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Facebook Invite

Q&A with John Medina

noreply@blogger.com (John Medina) — Tue, 07 Sep 2010 22:23:00 +0000

Q&A with John Medina, author of the forthcoming Brain Rules for Baby: How to Raise a Smart and Happy Child from Zero to Five (Oct 12).

Latest news: Fall 2010 Book Tour Schedule

How important is "nurture" in brain development?

The nature/nurture debate is summed up in this old joke: A third-grade boy comes home and hands his father his report card. His father looks at it and says, “How do you explain these D’s and F’s?” The boy looks up at him and says, “You tell me: Is it nature or nurture?”

There are some factors parents can’t control and some they can. There’s seed, and there’s soil. All the nurture in the world won’t change the fact that 50 percent of your child’s potential is genetic. Good news: As a parent, you can only do your best. That said, even as a professional geneticist, I am convinced we can exert far more influence over our kids’ behavior than is popularly imagined. It’s a very, very big task that takes a lot of work. The hardest job in the world. And also the most important.

Isn't brain power a matter of genetics?

For all of us, nature controls about 50 percent of our intellectual horsepower, and environment determines the rest. This means two things for parents: First, no matter how hard your child tries, there will be limits to what his brain can do. Second, that’s only half of the story. Aspects of your child’s intelligence will be deeply influenced by his environment, especially by what you do as parents.

What's the best thing a pregnant woman can do for her baby to be?

If I were to give a single sentence of advice based on what we know about in utero development during the first half of pregnancy, it would be this: The baby wants to be left alone.

At least at first. From the baby’s point of view, the best feature of life in the womb is its relative lack of stimulation. The uterus is dark, moist, warm, as sturdy as a bomb shelter, and much quieter than the outside world. And it needs to be. Once things get going, your little embryo’s pre-brain will pump out neurons at the astonishing rate of 500,000 cells a minute. That’s more than 8,000 cells per second, a pace it will sustain for weeks on end. This is readily observable three weeks after conception, and it continues until about the mid-point in your pregnancy. The kid has a great deal to accomplish in a very short time! A peaceful lack of interference from amateur parents is just what you’d expect the baby to need.

What are some things parents can do for their babies?

Here are a few things to do:

- Address the Four Grapes of Wrath new parents face: sleep loss, social isolation, unequal workload, and depression
- Talk to your baby a lot. This is as simple as saying, “It’s a beautiful day” when you look outside
and see the sun. Just talk. At infancy, do so in “parentese,” those clusters of exaggerated vowel
sounds at high frequencies. A rate of 2,100 words per hour is the gold standard.
- Focus on face time, not screen time. Babies love to gaze at human faces. Mom’s is best of all. TV
before age 2 is harmful to children.
- Praise effort, not IQ. Praise your child’s effort (“I’m proud of you. You really worked hard on that”) rather than innate ability (“You’re so smart!”).

Introduction - Brain Rules for Baby: How to Raise a Smart and Happy Child from Zero to Five

noreply@blogger.com (John Medina) — Tue, 20 Jul 2010 01:14:00 +0000

I'd like to share with you an excerpt from the introduction to my next book, Brain Rules for Baby: How to Raise a Smart and Happy Child from Zero to Five (October 12, 2010). Stay tuned for more information on the book and Fall book tour.

Every time I lectured to a group of parents-to-be about baby brain development, I made a mistake.

The parents, I thought, had come for a tasty helping of science about the brain in utero—a little neural crest biology here, a little axonal migration there. But in the Q&A session after each lecture, the questions were always the same. The first, delivered by a very pregnant woman one rainy night in Seattle, was “What can my baby learn while she is still in my womb?” Another woman asked, “What’s going to happen to my marriage after we bring our baby home?” A dad delivered the third question, with some authority: “How do I get my kid into Harvard?” An anxious mom asked the fourth question: “How can I make sure my little girl is going to be happy?” And the fifth belonged to a downright noble grandmother. “How do I make my grandchild good?” she asked. She had taken over parenting responsibilities from a drug-addicted daughter. She did not want the same thing to happen again.

No matter how many times I tried to steer the conversation toward the esoteric world of neural differentiation, parents asked variations on these same five questions—over and over again. Finally, I realized my mistake. I was giving parents Ivory Tower when they needed Ivory Soap. So, this book will not be concerned with the nature of gene regulation in the developing rhombencephalon. Brain Rules for Baby instead will be guided by the practical questions my audiences keep asking. “Brain Rules” are the name I give what we know for sure about how the early-childhood brain works. Each one is quarried from the much larger seams of behavioral psychology, cellular biology, and molecular biology. Each was selected for its ability to assist newly minted moms and dads in the daunting task of caring for a helpless little human.

I certainly understand the need for answers. Having a first child is like swallowing an intoxicating drink made of equal parts joy and terror, chased with a bucketful of transitions nobody ever tells you about. I know firsthand: I have two boys, both of whom came with bewildering questions, behavioral issues, and no instructions.

I soon learned that’s not all they came with. They possessed a gravitational pull that could wrest from me a ferocious love and a tenacious loyalty. They also were magnetic; I could not help staring at their perfect fingernails, clear eyes, dramatic shocks of hair. By the time my second child was born, I understood that it is possible to split up love ad infinitum and not decrease any single portion of it. With parenting, it is truly possible to multiply by dividing. My wife and I still marvel at how different our sons are from us, and yet how similar. Having kids is like mailing yourself a letter from the most delightful, meaningful future you can imagine.

My children also amplified the meaning of my work as a scientist. Watching a baby’s brain develop is like having a front-row seat to the Big Bang. It starts out as a single cell in the womb, quiet as a secret. Within a few weeks, it is pumping out nerve cells at the astonishing rate of 8,000 per second. Within a few months, it is on its way to becoming the world’s finest thinking machine. These mysteries fueled not only wonder and love but, as a rookie parent, I remember, anxiety and questions.

Too many myths

Parents need facts, not just advice, about raising their children. Unfortunately, those facts are difficult to find in the ever-growing mountain of parenting books. And blogs. And message boards, and podcasts, and mother-in-laws, and every relative who’s ever had a child. There’s plenty of information out there. It’s just hard for parents to tell what to believe.

The great thing about science is that it takes no sides—and no prisoners. Once you know which research to trust, the big picture emerges and myths fade away. To gain my trust, research must pass my “grumpfactor.” To make it into this book, studies must first have been published in the refereed literature and then successfully replicated. Some have been confirmed dozens of times. Where I make an exception for cutting-edge research, reliable but not yet fully vetted by the passage of time, I will note it.

To me, parenting is about brain development. That’s not surprising, given what I do for a living. I am a developmental molecular biologist, with strong interests in the genetics of psychiatric disorders. My research life has been spent mostly as a private consultant, a for-hire troubleshooter, to industries and public research institutions in need of a geneticist with mental-health expertise. I also founded the Talaris Institute, located in Seattle next to the University of Washington, whose original mission involved studying how infants process information at the molecular, cellular, and behavioral levels. That is how I came to talk to groups of parents from time to time, like on that rainy Seattle night.

Scientists certainly don’t know everything about the brain. But what we do know gives us our best chance at raising smart, happy children. And it is relevant whether you just discovered you are pregnant, already have a toddler, or find yourself needing to raise grandchildren. So it will be my pleasure in this book to answer the big questions parents have asked me—and debunk their big myths, too. Here are some of my favorites:

Myth: Playing Mozart to your womb will improve your baby’s future math scores.

Truth: Your baby will simply remember Mozart after birth—along with many other thingsshe hears, smells, and tastes in the womb. If you want her to do well in mathin her later years, the greatest thing you can do is to teach her impulse control in her early years.

Myth: Exposing your infant or toddler to language DVDs will boost his vocabulary.

Truth: Some DVDs can actually reduce a toddler’s vocabulary. It is true that thenumber and variety of words you use when talking to your baby boost both his vocabulary and his IQ. But the words have to come from you—a real, live human being.

Myth: To boost their brain power, children need French lessons by age 3 and a room piledwith “brain-friendly” toys and a library of educational DVDs.

Truth: The greatest pediatric brain-boosting technology in the world is probably a plain cardboard box, a fresh box of crayons, and two hours. The worst is probably your new flat-screen TV.

Myth: Telling your children they are smart will boost their confidence.

Truth: They’ll become less willing to work on challenging problems. If you want to get your baby into Harvard, praise her effort instead.

Myth: Children somehow find their own happiness.

Truth: The greatest predictor of happiness is having friends. How do you make and keep friends? By being good at deciphering nonverbal communication. Learning a musical instrument boosts this ability by 50 percent. Text messaging may destroy it.

Research like this is continually published in respected scientific journals. But unless you have a subscription to the Journal of Experimental Child Psychology, this rich procession of findings may pass you by. This book is meant to let you know what scientists know—without having a Ph.D. to understand it.

Memory Reconsolidation and What Albert Ellis Knew All Along

noreply@blogger.com (John Medina) — Mon, 17 May 2010 15:43:00 +0000

I can almost hear Albert Ellis saying “Amen” to the data I am about to share. To explain his reaction, I have to talk about war.

As a former military brat (my father was an Air Force “lifer”), I grew up hearing about large-scale military plans designed mostly to contain the formidable Soviet threat. Once that threat dissolved, those large-scale strategies had to undergo a radical revision—an amending process that is ongoing today. We are learning to confront smaller threats in countries whose formal militaries we can overthrow in weeks, sometimes days, but whose informal warriors can take years to defeat. It is sometimes called “asymmetric warfare”: the operations in Iraq and Afghanistan are prime examples.

Many things concern me about our military operations in those theaters, but one of them touches on a professional interest—the growing incidence of posttraumatic stress disorder (PTSD). There are 3 reasons that prick up my research instincts, all springing from this asymmetric warfare.

• First, there are no real “fronts” to many of these operations. As a result, soldiers who used to be able to sit comfortably in the rear (often called the “tail”) are now as exposed to the hazards of combat as those charged with fighting (often called the “tooth”). Consequently, the pool of soldiers who are potential candidates for PTSD has increased. This means the research cohort is getting larger and increasingly better defined.

• Second, soldiers are returning into these asymmetric environments multiple times for very long periods. This provides an opportunity to study the mental health effects of combat over a sustained period of years—valuable for countries such as Somalia and parts of Uganda, which have been in a continuous state of war for decades.

• Third, the number of women exposed to combat is increasing. Since there is growing evidence that men and women process stress very differently, these populations represent valuable research opportunities to ask and answer sex-based questions regarding the effects of combat on behavioral outcomes.

All of these issues present mental health challenges, enormous scientific opportunities, and a compelling reason to vastly increase funding for research into the long-term effects of disorders such as PTSD.

Into this breech comes a very interesting finding of potentially great value for the mental health community in general and the American military in particular. It involves new insights into how the brain copes with fearful stimuli in the midst of a cognitive process called “reconsolidation.” The finding suggests powerful noninvasive behavioral protocols that might have real applications in the modern battlefield, and in this column, we are going to discuss it. We’ll start with some background information (dusting off some old skinnerian nomenclature), talk about the cognitive neuroscience behind reconsolidation, then move directly to the data.

PAVLOV’S BELLS

It might take removing a few cobwebs for you to recall your Behaviorism 101 lectures, particularly regarding “classical conditioning.” The CliffsNotes version involves pairing some neutral stimulus with an unconditioned stimulus (UCS). This pairing ends up eliciting an unconditioned response (UCR). Through a series of repeated pairing experiences, the neutral stimulus is transformed into a conditioned stimulus (CS). The CS then evinces a conditioned response (CR), which is similar to the UCR.

Does that ring a bell? It might, if we add back Pavlov and his canonical experiments involving teaching a dog to salivate whenever the animal hears one. The sound of the bell is the neutral stimulus as the experiment begins, which fully exploits the fact that dogs naturally salivate in the presence of food—something you don’t have to teach them. Food is thus the UCS, and salivation is the UCR. In a series of learning trials, the bell and the food are paired together. Whenever the animal hears a bell, the dog is presented with food. After multiple exposures, the dog salivates just to the bell. The bell is now transformed into the CS, and the salivation in response is the CR.

CONSOLIDATION

Understanding the concept of “consolidation” is considerably harder. There are many different types of memories, and different categories follow different consolidating rules. We are capable of experiencing classical conditions—combat veterans learn to pair very quickly the presence of tiny wires in dirt with a panic response. But they are also capable of remembering that the Battle of Hastings occurred in 1066, and most still know how to ride a bike. Different brain mechanisms are used for each type of memory, categories that are called by different names. The history lesson is termed “declarative memory,” for example.

When declarative memories are first formed, the traces are fragile, labile, and at great risk for extinction. To make a memory more durable, it has to undergo a series of processing steps (consolidation). Eventually the memories will reach a state in which they are infinitely retrievable and not subject to amendment. But it takes a great deal of time to render them permanent.

There is mounting evidence that every time you retrieve a memory—even ones you have fully consolidated—you return that memory to its former fragile, labile state. It then has to undergo another round of consolidation to stabilize—via reconsolidation. At the point where it is still fragile, it is temporarily subject to amendment, even loss. (The window is about an hour.) Although the particulars remain controversial, there is growing evidence that this Pause button exists in both animals and humans. It is this hour-long pause in the consolidation stream that a group of researchers in the psych department at New York University (NYU) used to do the following experiments.¹

THE DATA

The idea for the NYU experiment1 was very simple: suppose a person learned a fear response in a classical condition paradigm, then was asked to recall the experience at a later time into memory. What if, during the hour the reconsolidation Pause button is in the On position, and the subject was treated to new, non-threatening, non–anxiety-inducing information?

The researchers decided to find out. They used human subjects, mild electrical shocks delivered to the wrist, and squares of different colors projected onto a video screen as their materials. The level of fear was assayed continuously using standard skin conductance measures. Participants’ memory behaviors were measured 10 minutes after exposure to certain stimuli, 6 hours after exposure, and 12 months after exposure.

The first manipulation was divided into 3 parts, which can be divided into the days in which the actual research took place.

Day 1

Subjects were presented with a video screen that displayed squares of 2 different colors, which, as you’ll see, becomes the CS. Whenever subjects saw 1 of the colors (which I’ll call the “hot” color), they got a shock to the wrist. After a few repeated pairings, whenever the subjects saw the hot-colored square, their fear responses jumped considerably. The subjects were then divided into 3 groups, whose experiences I will talk about in a minute.

Day 2

The next day, all groups underwent repeated exposure to the same 2 colored squares—this time without the electrical shocks. The attempt was to introduce an extinction experience process, to defang the effects of the hot color—and it worked. After a while, fear was reduced even for the hot color—and in all 3 groups. But what happened before this delightful fear reduction separated the subjects into their respective groups?

The first group simply went through the extinction process as described above, functioning as controls. The second group was reexposed to the hot color (just once) without receiving the shock 10 minutes before the extinction process began. This represents the “new” information. The third group was also reexposed to their hot color (just once, and also without the shock) 6 hours before the extinction process began. This represented the same “new” information.

Why the difference in the period between the second and third groups? The idea for the second group was to bring back a fearful memory—but with new information about it—within their Pause button reconsolidation window (that’s why the 10 minutes) before undergoing extinction. The hot color was supposed to shock them, but it didn’t (which is what was new). So the fearful memory was retrieved but was soon greeted with this new, delightful finding, which would be reinforced when they underwent the formal extinction process.

The idea for the third group was to bring back a memory after the Pause button reconsolidation window (thus the 6 hours) before it underwent extinction. They, too, got delightful news, but there was no reinforcement within the 1-hour window. They had to wait 6 hours to start the confirming extinction procedure.

Day 3

The last day—which was 24 hours after extinction—all groups underwent the same shock regimens done initially. This was an attempt to reestablish the fear response to the hot color. How did the 3 groups respond? (See Figure.)

The first group—the controls—recovered their fear responses spontaneously. When they saw the hot color, their skin conductance immediately showed “fear.” The extinction procedures they had undergone the previous day were essentially a waste of time.

The third group, the ones who had been presented with “good news” but had to wait 6 hours before it could be reinforced, might as well have gone home. They showed the same spontaneous recovery and the same resistance to extinction.

The real research gold is what happened to the second group—the ones who had gotten “Hey, its going to be alright” information 10 minutes before extinction reinforcement procedures began. They showed no fear response when they were reexposed to the hot color. Their fears had been blocked by the administration of updated information. Even when tested a year later, the fear-response memory was still blocked. The effect was long-lasting, powerful, and event-specific. Controls were performed to ensure against a generalized bleed-through effect (this was to ascertain that interfering with the reconsolidation of 1 memory trace did not influence the processing of a similar stimulus).

CONCLUSION

This is a remarkable achievement. The ability to block fearful memories was done by capturing a reconsolidation window, without any pharmacological agent, but with effects as long-lasting as any medication. Memories marinated in apprehension could be blocked simply by updating them with positive information within a specific period of time. By amending the experience before the consolidating stopwatch struck “60 minutes,” a new perception, quite resistant to change, was obtained.

The potential mental health applications of this work are extraordinary, both for civilian and military populations. It may be very possible to boost the power of introducing non–self-defeating thoughts by exploiting the reconsolidation window. This would allow one to rewrite—even efface—toxic emotional memories, which would represent a noninvasive way of helping a person control his or her psychological interiors. In the future, an entire therapy may evolve around just such timing issues. These data are just begging for application-oriented investigations to commence.

Hear that rustling? That’s the sound of Albert Ellis, from his grave, mumbling his “Amen,” and possibly, “You see? I told you so.”

This column appears in the May 2010 issue of Psychiatric Times.

Apple's 1984 Super Bowl Ad

noreply@blogger.com (John Medina) — Fri, 14 May 2010 16:32:00 +0000

When my mother got angry (which was rare), she went to the kitchen, washing LOUDLY any dishes she discovered in the sink. And if there were pots and pans, she deliberately would crash them together as she put them away. This noise served to announce to the entire household (if not the city block) her displeasure at something. To this day, whenever I hear loudly clanging pots and pans, I experience an emotionally competent stimulus—a fleeting sense of “You’re in trouble now!” My wife, whose mother never displayed anger in this fashion, does not associate anything emotional with the noise of pots and pans. It’s a uniquely stimulated, John-specific ECS.

Universally experienced stimuli come directly from our evolutionary heritage, so they hold the greatest potential for use in teaching and business. Not surprisingly, they follow strict Darwinian lines of threats and energy resources. Regardless of who you are, the brain pays a great deal of attention to these questions:

“Can I eat it? Will it eat me?”

“Can I mate with it? Will it mate with me?”

“Have I seen it before?”

Any of our ancestors who didn’t remember threatening experiences thoroughly or acquire food adequately would not live long enough to pass on his genes. The human brain has many dedicated systems exquisitely tuned to reproductive opportunity and to the perception of threat. We also are terrific pattern matchers, constantly assessing our environment for similarities, and we tend to remember things if we think we have seen them before.

One of the best TV spots ever made used all three principles in an ever-increasing spiral. Stephen Hayden produced the commercial, introducing the Apple computer in 1984. It won every major advertising award that year and set a standard for Super Bowl ads. The commercial opens onto a bluish auditorium filled with robot-like men all dressed alike. In a reference to the 1956 movie 1984, the men are staring at a screen where a giant male face is spouting off platitude fragments such as “information purification!” and “unification of thought!” The men in the audience are absorbing these messages like zombies. Then the camera shifts to a young woman in gym clothes, sledgehammer in hand, running full tilt toward the auditorium. She is wearing red shorts, the only primary color in the entire commercial. Sprinting down the center aisle, she throws her sledgehammer at the screen containing Big Brother. The screen explodes in a hail of sparks and blinding light. Plain letters flash on the screen: “On January 24th, Apple Computer will introduce Macintosh. And you’ll see why 1984 won’t be like 1984.”

All of the elements are at work here. Nothing could be more threatening to a country marinated in free speech than George Orwell’s 1984 totalitarian society. There is sex appeal, with the revealing gym shorts, but there is a twist. Mac is a female, so-o-o … IBM must be a male. In the female-empowering 1980s, a whopping statement on the battle of the sexes suddenly takes center stage. Pattern matching abounds as well. Many people have read 1984 or seen the movie. Moreover, people who were really into computers at the time made the connection to IBM, a company often called Big Blue for its suit-clad sales force.

What most people remember about that commercial is its emotional appeal rather than every detail. There is a reason for that. The brain remembers the emotional components of an experience better than any other aspect.

The Epigenetics of Stress

noreply@blogger.com (John Medina) — Thu, 08 Apr 2010 15:32:00 +0000

News: Brain Rules 2010 Workshops in Seattle, Denver, and Boise

Overly sensitive, aversive reactions to stress seem to run in families. The literature abounds with reports of relatives in these populations predisposed to depression, anxiety, and even suicide. Some family members present with glucocorticoid levels notched abnormally high, and in curiously deregulated concentrations. Behaviorally, they seem to exist at a permanent state of high alert.

Attempts to isolate the genetic underpinnings of this obvious hyperaroused stress sensitivity have met with mixed success. People carrying certain mutations in the serotonin transporter gene seem particularly vulnerable to the normal stresses and strains in life, although there have been difficulties in replicating all the findings. Plenty of people exist who are just as vulnerable to stress but who do not carry this mutation—or any other suspect genetic anomaly—that could explain the behavior.

It is now possible to characterize some of this seeming heritability—and accompanying statistical turbulence—without invoking heritability at all. This is the world of epigenetic transfer, the ability to pass on a trait without having to stop at a meiotic border. A recent study has demonstrated how a powerful environmental stressor can exert molecular effects that last over a long period. The mechanism is epigenetic. It is the first result to characterize a molecular mechanism, induced by early life stressors, that influences behaviors penetrating into adulthood.

To explain these findings, I will first talk about transplacental cortisol and its effects on the developing fetal brain. Then I will move to the data, which do not involve humans at all.

The starting observation

For years, we have known that stressed wombs tend to produce stressed babies. Most molecular explanations for this observation invoke the effects of transplacental glucocorticoids on fetal brain development. If mothers become too stressed (so the idea posits), too many stress hormones enter the womb, penetrate the fetal brain, and interfere with its proper development.

There is some empirical support for this notion. First, excess levels of maternal glucocorticoids have been shown to cross the placenta, targeting the fetal limbic system and causing it to develop much more slowly than in typical controls. This is thought to result in future behavioral dysfunction, particularly regarding reactions to external stressors. It specifically hampers the developing “braking system” of the hypothalamic-pituitary-adrenal (HPA) axis. (As you recall, the HPA axis is a series of biochemical reactions to threat that involve interactions between the hypothalamic, pituitary, and adrenal glands.)

Social states experienced in early life can directly affect later behavior. Until now, exactly what molecular mechanisms undergird such effects have remained a complete mystery.

This embryonic braking system is a coordinated series of responses that normally result in the inhibition of glucocorticoid production after some environmental stress has been successfully negotiated. Without this braking system, the fetal brain is wired to produce excess glucocorticoids in an increasingly unregulated fashion. The baby carries this deregulated system into adulthood. If the adult is female and becomes pregnant, her system, which is already flooded with cortisol, marinates her new baby with glucocorticoid. This once again creates a hyperaroused womb, complete with new fetal damage. The trait is thus passed along, not through the germ line but simply through womb exposure.

Although a great deal of work needs to be done to complete this admittedly depressing story, large parts have empirical support. This includes some intimate, biochemical details. Recently, a molecular mechanism has been uncovered that may explain this nongenetic inheritance. Although work has been done mostly in rats, there are broad implications for human behaviors. After a brief explanation of an epigenetic mechanism involving DNA methylation, it will be to these data that we turn next.

Early life stress

The work to be described involved inducing behavioral stress in a cohort of laboratory rodent pups, and then watching the effects of that stress on behavior as the rats matured. The standard protocol to induce developmental behavioral stress is to apply an infant-mother separation schedule early in postnatal life. Typically, the animal is separated from its mother 3 hours a day for the first 10 days of its life. The experience of early life stress (ELS) results in a lifelong elevation of glucocorticoid secretion and a disruption in normal stress responses (a permanent and heightened endocrine reaction to externally supplied stress). The animal becomes hyperaroused, presenting an abnormal regulation of the HPA axis. This arousal induces broad behaviors associated with mood and cognitive disorders.

A number of important hormones regulate the HPA axis, including 2 hypothalamic secretagogues—corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). When a stressful experience is encountered, signals arise that increase the synthesis and release of pituitary CRH and AVP. There is a rich history linking CRH and AVP to cognitive and affective disorders; their receptors are the targets of a number of psychopharmacological medications. AVP is also expressed in a specific subset of neurons within the hypothalamic paraventricular nucleus.

Understanding the molecular mechanisms behind the regulation of the HPA axis involves, in part, understanding how the AVP gene is regulated. Like all genes, AVP has a promoter region (which, as you recall from your undergraduate biochem class, functions as an on/off switch for the gene). A number of regulatory sequences surround this on/off switch, controlling its transcriptional activity. What happens to these sequences ultimately determines the role AVP plays in regulating stress responses (Figure).

One biochemical modification of the AVP promoter involves a process of methylation, the replacement of a hydrogen atom in certain nucleotide residues (generally cytosine residues) with a methyl group. This process is mediated by a class of enzymes termed “methyltransferases.” Many sites along the chromosomes are naturally methylated, but the process is in equilibrium, and many residues don’t stay that way. The amount of methylation on the regulatory region of a gene can control its transcriptional activity.

Methyltransferases are enzymes whose activities are also tightly controlled. One protein involved in regulating their activity is called MeCP2. This protein is specifically involved in recruiting proteins that will assist in the methylation of DNA. If MeCP2 activity is inhibited, the methylation of specific regions of DNA will also be inhibited, and the region is said to be hypomethylated. Because methylation affects a promoter’s ability to regulate the gene to which it is attached, one way to control gene activity is to control MeCP2 activity.

Results

With this background information in mind, we are ready to talk about the data. A typical ELS protocol was instituted immediately after the rats were born. Biochemical assessments began when the animals were 6 weeks old and continued for the next 10 months. A total of 4 findings emerged from these studies:

• ELS animals secreted abnormally high levels of stress hormone (specifically corticosterone) when compared with control groups. This excess persisted over the life of the experiment.

• ELS animals experienced a sustained rise in vasopressin expression (messenger RNA) in the hypothalamic paraventricular nucleus. That’s significant. This region of the hypothalamus is involved in regulating hormones associated with stress. Reassuringly, this elevation could be reversed with the application of an AVP receptor agonist.

• There was reduced methylation in a specific regulatory region for the AVP gene.

• The change in methylation was shown to be a result of the inactivation of MeCP2.

The behavioral changes in these mature animals were what you would expect in hyperaroused humans. They were less able to cope with stress in a wide variety of testing conditions, and they showed persistent memory impairments when compared with control groups.

Conclusions

These findings are quite stunning. For the first time, a molecular change associated with a persistent hyperaroused state in an adult animal was induced by behavioral neglect during the animal’s extreme youth. It is axiomatic from a counseling perspective that social states experienced in early life can directly affect later behavior. Until now, exactly what molecular mechanisms undergird such effects have remained a complete mystery. These data reveal strong epigenetic factors.

The normal caveats apply, of course. The experiments were done in laboratory animals, not humans—a red flag for anyone trying to apply animal-based behavioral results to human patients. Also, the stress was experienced after the pup was born, not during gestation. No measurements of transplacental glucocorticoid trafficking were made in these experiments. Nor was the post-ELS next generation examined. The behaviors induced in the offspring of these animals is an area of future research.

None of these objections hurt the findings, of course—just their interpretation. Their real value lies in what they portend for the future. Uncovering a mechanism induced in childhood that mediates a persistent behavioral experience in adults is a phenomenal achievement. Showing that these associations sometimes have epigenetic underpinnings is an added bonus. These results serve as flashlights, directing where scientists interested in human reactions should spend their next research dollars. Stress responses really do run in families. Showing that some reasons for this may be mostly environmental—with no DNA in sight—is the biggest plus of all.

This article appeared in the April 2010 issue of the Psychiatric Times.

The Genetics of Temperament

noreply@blogger.com (John Medina) — Tue, 16 Mar 2010 17:20:00 +0000

There are a lot of temperamental Jerome Kagan moments in my friend’s household—an observation that will require this entire column to explain. What exactly is a temperamental moment? And who exactly is Jerome Kagan?

Before we start, it might be useful to know that my friend’s household consists of a husband, a wife, and 2 little girls, aged 6 and 9. Their temperaments could not be more different. The 6-year-old is little Miss Sunshine—socially fearless, prone to risk taking, ebullient, confident. She will charge into a playroom full of strangers, initiate 2 conversations at once, quickly survey all the toys in the room, and then lock down on the dolls, playing with them for hours.

Her big sister behaves in exactly the opposite way. She seems fearful, tentative, cautiously tiptoeing into the same playroom after only reluctantly leaving her mother’s side. She will then find some safe corner and just sit there. It is a bit sad to watch; this older girl seems to show no interest in exploring, hardly speaks at all, and appears scared if somebody tries to talk to her. She is extremely averse to taking risks of any kind.

The younger daughter doesn’t have a shy bone in her body. The older daughter appears highly reactive, anxious, and afraid. Yet, they both come from the same family. What is the difference between these 2 kids?

Psych 101

A partial answer comes from the laboratory of legendary psychologist Jerome Kagan, in case you’ve forgotten your Psych 101. Many years ago, Kagan noticed that babies seemed to fall into a reactivity continuum. Some kids at one end of the spectrum behaved like my friend’s self-confident 6-year-old girl. At the other end resided kids who were like the self-doubting 9-year-old. And there were kids whose behaviors fell between the extremes.

Temperament provides the emotional and behavioral building blocks on which adult personalities are constructed.

Kagan was the first to posit that where a child sat on this continuum—a description of one dimension of their temperament—was in large part hardwired—or at least, observable shortly after birth and mightily resistant to change. These traits may even be genetic. Now that several longitudinal studies have matured and their research paybacks have long since been cashed, Kagan’s insights have been shown to be well-placed. Temperament is resistant to change, depending on how you define it, and there may even be a few genes that help explain the behaviors. Because it may have been a while since your last psych class, I thought you’d like an update.

We will begin by briefly reviewing the definition of the notion of temperament, spend some time discussing Kagan’s initial experiments, then move to a genetic system that shows great promise in helping to describe the DNA behind the behavior. Feel free to skip to the section, “The gene work,” if Kagan’s great body of research is part of your vocabulary.

A review of temperament

In the cognitive neurosciences, temperament is a multilayered concept. It is often defined as a person’s characteristic way of responding emotionally and behaviorally to external events. These responses are fairly fixed, innate, and observable soon after birth and may have genetic components. Personality is defined as not being so immutable. It is shaped primarily by the parental and cultural factors into which a child is born and raised.

Personality is influenced by temperament, the same way a house is influenced by its foundation. Many researchers believe temperament provides the emotional and behavioral building blocks on which adult personalities are constructed.

There is some real controversy about the edges of these definitions, of course—conflicts typical of the “nature/nurture” battlefields researchers have been fighting for decades. Jerome Kagan was really the first to sink some empirical teeth into an argument previously based on opinion. He screened 400 kids way back in 1979, doing experiments in places similar to the rooms in which the 6- and 9-year-olds mentioned above were playing. He found about 15% acted like the younger daughter (behaviorally ebullient, or low-reactive [LR]) and another 15% acted like the older daughter (behaviorally inhibited, or highly reactive [HR]). He measured a subset 5 years later and found things were remarkably stable. Only 3% of the children had actually changed categories.

Kagan next investigated 500 kids starting at 4 months of age, coding them using the same LR or HR behavioral algorithms as before. He retested these same kids at 4, 7, 11, and 15 years (the experiment is still ongoing, although Kagan has retired and bequeathed the work to another colleague). He found that HR babies were 4 times more likely to be behaviorally inhibited by age 4 (like my friend’s older daughter). By age 7, some form of anxiety had developed in half of these kids, compared with 10% of the control HRs (who made up about 20% of the population).

As HR kids navigated through school, Kagan noticed most were academically successful, even if they were a bucket of nerves. They got good grades and made lots of friends. They were less likely to experiment with drugs, to get pregnant, or to drive recklessly—perhaps because of an anxiety-driven need to acquire compensatory mechanisms to socialize properly. Kagan actually liked HR people and regularly employed them during his research career. “I always look for high reactives,” he told The New York Times in 2009. “They’re compulsive, they don’t make errors, they’re careful when they’re coding data.”

Kagan’s conclusion? Babies come into this world with an inborn temperament. About 20% are born with a predisposition to anxiety—a behavioral type that remains remarkably stable over time. Kagan calls this the long shadow of temperament.

There are, of course, confounders and nuances to these conclusions, familiar to anyone who does behavioral work for a living. Kagan and colleagues have shown that these findings are not necessarily deterministic. Not every brain state sparks the same behavior. Nor do they say everything there is to know about temperament. Kagan freely admits he is only studying 1 dimension of the phenomenon—the reaction to new things. At least 6 different dimension scales have been cited by researchers in the field at various times to describe this multidimensional idea, ranging from fearful distress to attention span/persistence to rhythmicity. (For the complete list, see the Figure.)

Most important, these studies make conclusions about tendencies, not destinies. Even when the trends are strong, the predictive power of Kagan’s work runs in 1 direction. The data do not forecast what these children will become as much as they predict what they will not become. HR infants will not grow up to be exuberant, outgoing, bubbly, or bold. The older daughter will never become the younger daughter.

Even with these caveats in mind, the data almost beg for genetic research. The fruit of one of these inquiries is described next.

The gene work

The discoveries suggesting genetic components to temperament started with that workhorse of the human behavioral lab—twin studies, monozygotes versus dizygotes versus siblings versus strangers. Clear findings emerged. Using infant temperamental inventories, the degree of resemblance (correlation) for identical twins was shown to be about 0.4. For fraternal twins and non-twin siblings, the resemblance score was between 0.15 and 0.18. In these studies, about 60% of kids who seemed very inhibited as youngsters grew up to be inhibited as adults. They were prone to the same strong fears and phobias shown previously and were the most anxious in the group. Ninety percent of the uninhibited group stayed uninhibited as a group when adults.

A 0.4 resemblance score is enough to start thinking about DNA. Not surprisingly, molecular biologists have gotten into the fray in the past few years. It has admittedly been tough going. The twin findings hardly represent a 100% determinative slam dunk, and that’s because of this work’s ancient foe—nature versus nurture. Discovering what percentage of nature and nurture exists within any human behavior is hard to do, plagues even the most robust research of this type, and is not accomplished in the gene I am about to describe. The word “partial influence” or “susceptibility” could—and should—be used for the following.

There is a gene that is considered by some researchers to play a large role in the ebullient risk takers at the far end of Kagan’s findings. It is sometimes called the risk-taking gene, dopamine receptor D_⁴ (DRD4). This protein is a member in good standing of the range of molecules capable of binding to dopamine and exerting its specific physiological effects.

There is a large number of variants (polymorphisms) in this gene. One that has received a great deal of attention is a variable number terminal repeat (VNTR) in exon 3. That last sentence is a bit dense and is described below.

As you know, DNA is made up of long strings of nucleotides, As, Gs, Ts, and Cs. A VNTR is simply a region on the chromosome that has been organized into a tandemly repeated sequence. A tandem repeat is a repeated sequence of nucleotides that are jammed together. They can be quite long. Because VNTRs are on a chromosome, they are inherited.

An exon refers to the structure of a gene as it lies on a chromosome. As you may recall, structural genes in eukaryotic cells are discontinuous. Genes are sprinkled with regions that code for protein (called exons) and regions that code for nothing (called introns). They can possess VNTRs. Exon 3 is simply the third exon from the starting sequence and possesses the VNTRs in question. Each VNTR is 48 base pairs in length.

DNA samples from many people have been isolated, and the DRD4 gene characterized. They are infested with 48–base pair VNTRs, which can be divided roughly into “short form” and “long form” versions of the repeat. The short form is considered to be under 6 repeats of the VNTR. The long form is anything over 6 tandemly repeated sequences.

The collision between the DRD4 polymorphisms and Kagan’s work occurred more than a decade ago when it was noticed that people who scored high for risk-taking behaviors possessed the long variant of the DRD4 gene. Those who did not, carried the short form. This association has been replicated several times.

Further studies with these polymorphisms seemed to show a parenting effect. Most kids who have an emotionally distant parent develop “externalizing behaviors,” heart-breaking attempts to get their parents to pay attention to them. Those behaviors vanish if the kid has a specific variant of the DRD4 gene. They seem Teflon-coated, stress-resistant, and show little probability of becoming emotionally insecure.

Of course, all these data are correlative—the causal work has yet to be done—which means there’s a lot more work to do. One central mystery is figuring out exactly how low- or high-reacting behaviors and risk-taking behaviors relate to each other. DRD4 does lots of things besides mediate temperament. The role of other genes has not yet been determined. Most behaviors of this complexity are the result of dozens of interacting gene sequences.

So, the work continues. It is always marvelous to see well-done behavioral research starting to be fleshed out in molecular terms—even if there is a long way to go. The information certainly seemed to soothe my friends when I told them about it. They, like all good parents, felt the behavioral differences in their little girls were entirely a result of their failings as parents. In fact, the daughters may have been guilty of nothing more than, for better or worse, choosing their parents the way they did.

This article appears in the March issue of the Psychiatric Times.

We do not see with our eyes. We see with our brains.

noreply@blogger.com (John Medina) — Thu, 18 Feb 2010 17:45:00 +0000

We do not see with our eyes. We see with our brains.

The evidence lies with a group of 54 wine aficionados. Stay with me here. To the untrained ear, the vocabularies that wine tasters use to describe wine may seem pretentious, more reminiscent of a psychologist describing a patient. (“Aggressive complexity, with just a subtle hint of shyness” is something I once heard at a wine-tasting soirée to which I was mistakenly invited—and from which, once picked off the floor rolling with laughter, I was hurriedly escorted out the door).

These words are taken very seriously by the professionals, however. A specific vocabulary exists for white wines and a specific vocabulary for red wines, and the two are never supposed to cross. Given how individually we each perceive any sense, I have often wondered how objective these tasters actually could be. So, apparently, did a group of brain researchers in Europe. They descended upon ground zero of the wine-tasting world, the University of Bordeaux, and asked: “What if we dropped odorless, tasteless red dye into white wines, then gave it to 54 wine-tasting professionals?” With only visual sense altered, how would the enologists now describe their wine? Would their delicate palates see through the ruse, or would their noses be fooled? The answer is “their noses would be fooled.” When the wine tasters encountered the altered whites, every one of them employed the vocabulary of the reds. The visual inputs seemed to trump their other highly trained senses.

Folks in the scientific community had a field day. Professional research papers were published with titles like “The Color of Odors” and “The Nose Smells What the Eye Sees.” That’s about as much frat boy behavior as prestigious brain journals tolerate, and you can almost see the wicked gleam in the researchers’ eyes. Data such as these point to the nuts and bolts of the Brain Rule: Vision trumps all other senses. Visual processing doesn’t just assist in the perception of our world. It dominates the perception of our world.