The Doctor Weighs In

By Dov Michaeli MD, Ph.D

A few days ago my good friend Michael Millenson steered me to a video on a website called Ted.com (www.ted.com/talks/view/id/229). What I saw there was so profound and so exhilarating that I had to replay it several times. It was nothing short of an epiphany.

The view from within

"Neuroanatomist Jill Bolte Taylor had an opportunity few brain scientists would wish for: One morning, she realized she was having a massive stroke. As it happened – as she felt her brain functions slip
away one by one, speech, movement, understanding -- she studied and
remembered every moment. This is a powerful story about how our brains define us and connect us to the world and to one another".

To put things in context. In Biology we study cells, organs, and organisms. We study in detail their molecular makeup, their anatomy and their behavior. But there is one drawback: we are on the outside, trying to decipher the inside workings. We cannot physically get into a cell and observe its workings. So we do the second best, and use all kinds of tools and signs that suggest what is going on inside. We assume that these signs indeed reflect the inside reality. For instance, a cells recoils in response to a noxious stimulus. We can see under the microscope the scaffolding of a cell (a) organizing itself into cable-like structures(b), shortening on the one hand, elongating on the other, and the cell moves. We can inhibit the organizing of the scaffolding and abort the movement. So we ascribe the movement to the action of the molecular scaffolding—an eminently reasonable assumption.

But an assumption nonetheless. For instance, have we ruled out beyond a reasonable doubt that the chemical we used to inhibit the activity of the scaffolding hasn’t affected a yet undiscovered system, which could be the real driver of the cell’s response to the stimulus? We cannot get into the cell and directly observe the scaffold molecules tugging on the membrane; we stain the molecules that make up the scaffold so we can observe them, we measure their length and thickness before, during and after the movement, we inhibit their activity by adding inhibitory molecules or drugs. Based on all these observations we conclude that they are all consistent with the scaffold being responsible for cell movement. If it looks like a duck, walks like a duck, quacks like a duck—it must be a duck.

The pitfalls of observing from the outside

The danger is that these kind of observations basically amount to connecting the dots. And in the vast majority of cases, the picture we paint stands the test of accumulating evidence. But as we know from bitter experience, one can have a set of observations (the “dots”), and connect them in more than one way, many times in ways that serve an agenda rather than the truth. For a while there flourished a sociological specialty of “deconstructing” the sociology of science. These were non-scientists who looked at science from the outside, by interviews, observations of behaviors, interpretations of statements, "deconstruction" of writings—and then coming to conclusions about the workings of the scientific enterprise. Their theories were so laughable, so off the mark as to be outrageous, sometimes tinged with malice. I know it—I was on the inside,  they were on the outside looking in, through distorting lens as it were.

What does all this have to do with nirvana?

When we study the brain, we are basically outsiders looking in; we make reasonable assumptions, we arrive at reasonable conclusions. But we don’t directly experience the phenomena we are studying. That’s why I was so struck by Jill Bolte Taylor’s account of her left-sided stroke. Her left hemisphere slowly shut down while her right hemisphere continued to function more or less normally (the connections between the right and left hemispheres, called corpus callosum, were disrupted). Now, from countless observations and experiments we know that the left hemisphere is the seat of analytical thought, of memory, of language, of all our “executive” functions. The right hemisphere is the seat of our position in space, creativity, of art and music and the sense of wonder. But is that all? Dr. bolte Taylor's detailed account of the experience tells us that we were missing a deeper function of the right brain.

What she experienced was that unlike the left hemisphere, where boundaries of objects are sharply demarcated, the boundaries of things as perceived by the right hemisphere are fuzzy, they tend to merge with their surroundings. Objects appear misshapen, having indistinct boundaries. She felt that she is literally merging with the environment, becoming one with the universe. And in Buddhist writings, that’s the essence of what they call nirvana.

I know, I know, sounds like more “new age”-speak. Or just a malfunctioning brain akin to an LSD trip. But mind you, this is not your next door “flower child” speaking—this is a hard-nosed Harvard-trained neurobiologist chronicling her experience. This is a scientist observing from the inside!

The possibilities are endless

If true, then we can begin to understand the mechanism of meditation. We can possibly understand better the creative process, the deeper meaning of art, and music, and poetry. And maybe, just maybe, we could learn to become one with our environment, our world, and our fellow human beings.

By Dov Michaeli MD, Ph.D

Who hasn’t complained about loss of memory? With increasing frequency, I forget where I left my glasses, what’s her name? Where did I meet him? And for the hundredth time, what’s the name of this bird?

No, it is not incipient Alzheimer’s. I still write blogs, although that’s no proof of a sound mind. I manage a large drug development project, read the newspapers daily and am up on the latest political twist. So what’s going on?

Beware received wisdom

When I went to medical school (UCSF) I was struck by a paper I read claiming that 50% of what we were taught would be either obsolete, or plain wrong, within 5 years; amazing, but true, and not very reassuring to both physician and patient. One of the things I was taught with great certitude was that with age we progressively lose neurons, which make up the gray matter in the brain. True enough even today. It was then a no brainer to conclude that this loss of neurons is responsible for the creeping loss of cognitive function in the elderly. This tidbit of “information” turns out to be part of the 50% that is obsolete, and maybe even wrong.

The nerve cell

A neuron, like any other cell, has a “body”, enclosed by a membrane. It contains a nucleus, where DNA resides, mitochondria, the power plants that provide energy for the functions a neuron performs, and cytoplasm, where proteins are shuttled about and enzymes perform what they are supposed to. But then there is something unique to neurons: they have long projections, some of them inches long (which is enormous in the context of microscopically small cells). These long projections, called axons, serve two purposes: they serve as conduits for a traffic of neurotransmitters and other substances on their way out of the neuron. And, through tiny projections coming off their surface, called dendrites (small branches, in Latin), they make contact with other neurons around them. This is how information, in the form of electrical impulses, is passed around the brain along precisely demarcated circuits and over very long distances. The neuronal cell bodies, where the nucleus and the DNA reside, are the “brain” of the cell; they have a gray hue under the microscope—hence “gray matter”. The axons, on the other hand, are considered conduits only, very much like water or sewer pipes—no “brain” at all. They have a white hue, and are called the “white matter”.

Organization of the brain

The human brain can be divided into major functional regions, each responsible for different kinds of “applications,” such as memory, sensory input and processing, executive function or even one's own internal musing. The functional regions of the brain are linked by a network of white matter conduits. These communication channels help the brain coordinate and share information from the brain's different regions. White matter is the tissue through which messages pass from different regions of the brain.

Scientists have known that white matter degrades with age, but they did not understand how that decline contributes to the degradation of the large-scale systems that govern cognition.

So what’s new?

New research, published December 6, 2007, in the journal Neuron, begins to reveal how simply growing old can affect the higher-level brain systems that govern cognition. The research was conducted by Randy buckner’s group at the Harvard Medical School and the Howard Hughes Medical Institute. As Jessica Andrews-Hanna, a graduate student in Buckner's lab and the lead author of the study stated:
“The crosstalk between the different parts of the brain is like a conference call; we were eavesdropping on this crosstalk and we looked at how activity in one region of the brain correlates with another.”
Buckner, Andrews-Hanna, and their colleagues looked at crosstalk in the brains of 93 people aged 18 to 93, divided roughly into a young adult group (18-34 years old) and an old adult group (60-93 years old). The older participants were given a battery of tests to measure their cognitive abilities—including memory, executive function and processing speed. Each person was studied using functional magnetic resonance imaging (fMRI) exams to measure activity in different parts of the brain. fMRI can precisely map enhanced blood flow in specific regions of the brain. Increased blood flow reflects greater activity in regions of the brain that are utilized during mental tasks.
For the task used in the Neuron study, subjects were presented words and were asked to decide whether each word represented a living (e.g., dog) or nonliving (e.g., house) object. Such a task requires the participants to meaningfully process the words.
Buckner's group explored whether aging in the older group caused a loss of correlation between the regions of the brain that — at least in young adults — engage in robust neural crosstalk.
They focused on the links within two critical networks, one responsible for processing information from the outside world and one, known as the default network, which is more internal and kicks in when we muse to ourselves. For example, the default network is presumed to depend on two regions of the brain linked by long-range white matter pathways. The new study revealed a dramatic difference in these regions between young and old subjects. “We found that in young adults, the front of the brain was pretty well in sync with the back of the brain,” said Andrews-Hanna. “In older adults this was not the case. The regions became out of sync and they were less correlated with each other.” Interestingly, the older adults with normal, high correlations performed better on cognitive tests.
According to the authors, it is inferred that in a young, healthy brain, signals are readily transmitted by white-matter conduits. As we age, those conduits are compromised. Depending on the networks at play, the result may be impaired memory, reasoning or other important cognitive functions. Buckner and Andrews-Hanna emphasized that other changes in the aging brain may contribute to cognitive decline. For example, cells' ability to express chemical neurotransmitters may also be compromised.

My take

1. Extremely important work. The dogma that “dropped neurons” is solely responsible for the cognitive deficits of normal aging simply did not make sense. First, the billions of neurons in the brain have plenty of capacity to make up for losses; we have a tremendous reserve. Second, the brain has the capacity to reroute specific information through alternative circuits if the original ones are compromised in any way. This is what underlies the phenomenon called “brain plasticity”, which is the basis for rehabilitation of stroke victims, or the educational strategies for dyslectic children.

2. This finding, like any in science, raises new questions. What is the nature of the disruption in the default network? Is it reduced number of axons due to neuronal death? Is it a functional defect in the conductive properties of the axons? Is the dysfunction generalized or restricted to specific pathways? What is the root cause of the changes? How can they be avoided?

What can we do about it now?

No doubt you have encountered claims of “brain rejuvenation”. Just work on your daily crossword puzzle, learn a new language, solve sudoku puzzles, stand on your head. The trouble with all these is that they work—but very specifically. If you do your daily crossword puzzles or sudoku you’d be good at them, but you will still forget names and misplace your car keys.

So far, the most convincing global change in the aging brain is reduced blood supply. Blood vessels either get occluded (atherosclerosis) or degenerate because of death of tissue they had supplied. Not surprisingly, the only strategy that proved effective in maintaining the overall integrity of cognitive function is, you guessed it, increase blood supply through aerobic exercise.

So throw away your sudoku puzzle or crossword puzzle and go out for a brisk walk or run. And don’t forget the keys to the house.

Dov Michaeli MD, Ph.D is in the biotech industry.

By Dov Michaeli MD, Ph.D

On November 11 I read an Op Ed article in the New York Times titled “This is Your Brain on Politics”. Being interested in neurobiology, and an addict of all things political, I homed in like a laser beam: is this the holy grail of neuroscience? Are we capable of deciphering our innermost thoughts (in this case, political thoughts) using brain imaging techniques?

The article was written by three neuroscientists: Marco Iacoboni, Joshua Freedman and Jonas Kaplan of the University of California, Los Angeles, Semel Institute for Neuroscience; a communications professor, Kathleen Hall Jamieson of the Annenberg Public Policy Center at the University of Pennsylvania; and Tom Freedman, Bill Knapp and Kathryn Fitzgerald of FKF Applied Research.

The experiment

The authors used functional magnetic resonance imaging (fMRI) to scan the subjects' brains while they viewed images of political candidates. This imaging technique can be used to measure changes in oxygenated blood and hence to infer changes in metabolic activity in different parts of the brain. Some parts of the brain reliably alter their activity under certain conditions, and scientists have used this fact, along with information drawn from other techniques in both humans and animals, to document which brain area is associated with which cognitive function. For example, greater activity in the insula is often reported when people experience disgust, whereas more activity in the amygdala is reported when people are anxious.

While in the scanner, the subjects viewed political pictures through a pair of special goggles; first a series of still photos of each candidate was presented in random order, then video excerpts from speeches. Then they were shown the set of still photos again. On the before and after questionnaires, subjects were asked to rate the candidates on the kind of 0-10 thermometer scale frequently used in polling, ranging from “very unfavorable” to “very favorable.”

The results

Here are some excerpts from the findings:

1. Voters sense both peril and promise in party brands. When we showed subjects the words “Democrat,” “Republican” and “independent,” they exhibited high levels of activity in the part of the brain called the amygdala, indicating anxiety. The two areas in the brain associated with anxiety and disgust — the amygdala and the insula — were especially active when men viewed “Republican.” But all three labels also elicited some activity in the brain area associated with reward, the ventral striatum, as well as other regions related to desire and feeling connected. There was only one exception: men showed little response, positive or negative, when viewing “independent.”

2. Emotions about Hillary Clinton are mixed. Voters who rated Mrs. Clinton unfavorably on their questionnaire appeared not entirely comfortable with their assessment. When viewing images of her, these voters exhibited significant activity in the anterior cingulate cortex, an emotional center of the brain that is aroused when a person feels compelled to act in two different ways but must choose one. It looked as if they were battling unacknowledged impulses to like Mrs. Clinton.

Subjects who rated her more favorably, in contrast, showed very little activity in this brain area when they viewed pictures of her.

This phenomenon, not found for any other candidate, suggests that Mrs. Clinton may be able to gather support from some swing voters who oppose her if she manages to soften their negative responses to her. But she may be vulnerable to attacks that seek to reinforce those negative associations.

7. John Edwards has promise — and a problem. When looking at pictures of Mr. Edwards, subjects who had rated him low on the thermometer scale showed activity in the insula, an area associated with disgust and other negative feelings. This suggests that swing voters’ negative emotions toward Mr. Edwards can be quite powerful .

Oh, Yeah?

Take John Edward’s “problem”, for example. Is the fact that the insula showed higher activity dooms his campaign? increased activity in any brain area is rarely exclusive to any one function. That insula activity did not necessarily mean the subjects were disgusted. Insula activity has also been associated with drug craving, the taste of chocolate, pain and the quality of orgasm (!). Not necessarily such bad news after all.

This is not “junk Science”; it is purely junk

The authors wouldn’t dare publish such an article anywhere else but on an Op-Ed page; a peer-reviewed journal would send a rejection notice by return mail.

Here is a response of Brandon Keim in Wired science magazine:

“As science, it was a joke. As political theory, it was shallow. As an op-ed, it should have been thrown out at first glance. Uninformed opinion is tolerable in an editorial, but not when it purports to be validated by bad science .”

And the response of 14 heavy-weight neuroscientists:

“The results reported in the article were apparently not peer-reviewed, nor was sufficient detail provided to evaluate the conclusions.

As cognitive neuroscientists, we are very excited about the potential use of brain imaging techniques to better understand the psychology of political decisions. But we are distressed by the publication of research in the press that has not undergone peer review, and that uses flawed reasoning to draw unfounded conclusions about topics as important as the presidential election .”

Why shame on the NYT?

After all, you might think, why not open a window of expression to all scientific observations, valid or not? We do publish rubbish like “intelligence design”, or “creationist theory” side by side with “evolutionary theory”. As chief Justice Brandeis famously said: sunshine is the best disinfectant. But as Nature magazine stated: “What is troubling about the NYT is that the results described in the op-ed are apparently the claims of a commercial product posing as a scientific study. This is only partially transparent. Three of the authors list their affiliation with FKF Applied Research, a company based in Washington DC that is notorious for using similar brain-scan analysis to conclude which TV adverts (pardon the Britishism) aired during a major sporting event were most effective. In its own words, the company is a "business intelligence firm selling fMRI brain scan-based research to Fortune 500 companies".

More troubling for a mainstream newspaper that prides itself on its balanced reporting is the absence of declarations from three other authors. Rightly listed as affiliated to a neuroscience institute at the University of California, Los Angeles, one is also a co-founder of FKF Applied Research and all three, according to a previous publication, have benefited from funding from the company.”

Any harm done?

Yes, and yes. First, harm was done to the reputation of Science as a self-monitoring and self-correcting mechanism, whose only fealty is to the Truth. It gives credibility to political hacks in Congress and other branches of the government who claim that global warming is a figment of statistical models conjured up by “UN scientists”, that Evolution is “only a theory” propagated by atheist-scientists, that the medical harm of tobacco smoking is not supported by credible evidence, and so on and so on. In a day when the assault on science has not reached such a magnitude since the days of the medieval church—we don’t need to provide more weapons for their armamentarium.

And second: The “Twinkies Defense”, used in supervisor Dan White’s defense of his murder of S.F. mayor John Moscone and supervisor Harvey Milk, was a harbinger of things to come. This junk science was presented to the court by a psychologist-“scientist”. Brain imaging “evidence” is now being presented in court by hired gun-“neuroscientists”. Genetic information is being twisted beyond recognition in the service of racists and other malevolent rabble.

This is why an article such as this one is not just an innocent romp through neuroscience and politics, maybe even with a faint sense of humor. It is harmful, and shame on the NYT for publishing it.

Dov Michaeli MD, Ph.D is in the biotech industry

By Dov Michaeli MD, Ph.D

An article in the Sept. 17 2007 issue of Time magazine tweaked my interest. In it the author, John Cloud, argues that the recent crop of Republican homosexual legislators deserves our understanding of their weakness, rather the opprobrium of hypocrisy. To quote Cloud, he is offering “a moistly liberal request: Can we have a moment of pity for moralizers who fall?”

His argument runs as follows:

“Hypocrisy is among the most universal and well-studied of psychological phenomena, and the research suggests that Craig, Haggard and the others may be guilty not so much of moral hypocrisy as moral weakness. The distinction may sound trivial at first, but as a society, we tend to forgive the weak and shun the hypocritical.

Assume for a moment that Craig and Haggard actually believed what they said--that homosexuality is sin. They spent most of their lives fighting for the conservative cause. But in Craig's case, the Idaho Statesman has published allegations that there were at least three other slipups involving men, beginning in 1967. What if, like the radio host who gets fat but commits to losing weight, the moralizers were trying through their "pro-family" endeavors to expiate their lustful sins? You may think they are wrong about homosexuality (I do), but that doesn't make them hypocrites.”

With all due respect, this argument is not “moistily lliberal”, it is down right wrong on scientific and moral grounds.

What did  Larry (wide stance) Craig actually say? Here is one quote: “It is important for us to stand up now and protect traditional marriage, which is under attack by a few unelected judges and litigious activists”. Here is a man who married a woman and for decades fought against equality for gays.

So that we are not accused of picking on one unfortunate soul, remember Mark Foley?

Here is what he said: “For those pedophiles and predators across this country that have harmed or are considering harming a child, let me tell you that you are on notice… Your days in the shadows are over.” How prophetic, and how poetically just. This is the stuff Greek tragedies are made of.

Is it classical hubris, or is it hypocrisy?

The classical Greeks did not have Freud to kick around. They attributed human failings to hubris, a cardinal sin in the eyes of the Olympian gods. And the retribution that followed was swift and merciless. No moistily liberal excuses for them.

Two thousand years later, Shakespeare took a more nuanced approach to human failing. The hubris of the proud and vain King Lear had to be paid for, and dearly. But the process of suffering cleansed him of his hubris and opened his heart to love. His tragic death broke the hearts of millions.

Enter Freud, about 300 years later. His original psychoanalytic theories have been largely discredited, but the psychobabble residue they have left behind is still with us. Hence the “psychological” and moral sleight of hand a la Cloud: these people are not hypocritical at all, they are just weak.

Neurobiology refutes this argument

A recent review in Science (“Social Decision-Making: Insights from Game Theory and Neuroscience”) makes the point that social decision-making is controlled by a complex network of centers in the brain. The middle area of the prefrontal cortex (MPFC) and the area just below it (the orbitofrontal cortex, or OFC) constitute the “executive center”, making final judgments that balance inputs from the anterior and posterior cingulate cortex (ACC and PCC) which are the reward areas, and from the amygdala and the insula (AMY and INS), which process the more primitive urges, such as fright, aggression, hatred, rage, etc (Dr. Freud, is this the anatomical locus of your concept of the “subconscious”?).

What is important about this new research is showing the part of emotions in the overall mix of inputs into our decision-making. And this brings us to a potential explanation for what is called “cognitive dissonance”. What is meant by that is the nagging, and sometimes profound discomfort we feel when our behaviors don’t align with our beliefs. Our prefrontal cortex will keep nagging us, disturbing our peace of mind, interfere with our sleep, afflict us with unpleasant dreams—until we bring our behavior into alignment with our beliefs, which in reality are the products of the judgments made in the prefrontal cortex.

I accept that if you say one thing and then do another, the cognitive dissonance you will suffer is a result of your weakness. But when you do one thing and then say another—this is no weakness, this is willful hypocrisy. Larry Craig did not become a homosexual last month or last year. He was probably gay before he was a senator. Science tells us that he probably was born a homosexual. Mark Foley didn’t discover children when he first saw a congressional intern. They were most likely the objects of his desire decades ago.

Which leads me to the most “unmoistily liberal” conclusion: these people are hypocritical. The excuse of weakness or “the devil made me do it” doesn’t wash: Your prefrontal cortex warned you time and again that your behavior is reprehensible; you chose to ignore it. You did one thing and then chose to say or do something antithetical, in order to advance your political career. If the consequences began and ended with you alone—nobody cares. But your decision-making had social consequences. Your words, votes, actions— they inflicted grave harm on innocent people who have done you no wrong.

Dov Michaeli MD, Ph.D is in biotech and brooks no B.S.

I was really amused by Dr. Pat Salber’s latest posting on hapless guys gone shopping.  Was this a subtle literary allusion to Damon Runion’s “On guys and dolls”? His ‘guys’ are pretty much the same: a bunch of pathetic, testosterone-exuding losers. Even more amusing was the storm of plaintive protests from our guy readers, who claimed that this was a stereotype that was divorced from modern reality.

Seriously, how did stereotypes come to be accepted? If they did not have some roots in reality, Darwinian theory predicts that they would not survive the selective force of public acceptance. If you think that the “dumb blonde” or the “stupid jock” stereotypes have no basis in reality—think again.

Evolutionary Psychology.

Broadly speaking, this field is attempting to explain human behavior in evolutionary terms, or more specifically, in terms of survival advantage. The field is fraught with problems, the major one being that its analysis is by and large retrospective. What I mean by that is that the investigator describes a certain human behavior, and then in effect says “but of course, it makes a lot of evolutionary sense”, many times without a shred of empirical evidence, all the fruit of armchair “thought experiments”. An example: in 2001 a book was published by MIT Press (can it get more prestigious than that?) titled “A Natural History of Rape: Biological bases of Sexual Coercion”. In it the authors, Craig Palmer and Randy Thornhill, argue that rape should be expected because it increases the number of the rapist’s offspring; voilá, survival advantage—Q.E.D. Both authors are respected university researchers, but I submit that such a conclusion ignores overwhelming neurobiological evidence suggesting that far from doing what comes naturally, our rapist guy is actually deficient in his decision making power and his “executive functioning”—traits that reside in the prefrontal cortex of the brain.

Well, maybe not a very scientific “science”, but you’ve got to admit that it’s a lot of fun.

Seriously now.

One of my favorite evolutionary psychologists is Dr. Satoshi Kanawaza of the London School of economics, a truly creative researcher and thinker. To give you an idea why I like to read his papers, here is a selection of a few of them:

1. Kanazawa, Satoshi. 2007. "Beautiful Parents Have More Daughters: A Further Implication of the Generalized Trivers-Willard Hypothesis (gTWH)", Journal of Theoretical Biology. 244: 133-140

2. Takahashi, Chisato, Toshio Yamagishi, Shigehito Tanida, Toko Kiyonari, and Satoshi Kanazawa. 2006. "Attractiveness and Cooperation in Social Exchange", Evolutionary Psychology. 4: 315-329.

3. Kanazawa, Satoshi. 2006. "Why the Less Intelligent May Enjoy Television More than the More Intelligent", Journal of Cultural and Evolutionary Psychology. 4: 27-36.

4. Kanazawa, Satoshi. 2006."Violent Men Have More Sons: Further Evidence for the Generalized Trivers-Willard Hypothesis(gTWH)" Journal of Theoretical Biology. 239: 450-459

5.Kanazawa, Satoshi and Deanna L. Novak. 2005. "Human Sexual Dimorphism in Size May Be Triggered by Environmental Cues." Journal of Biosocial Science. 37: 657-665. What ‘size’ is he referring to?

6. Kanazawa, Satoshi. 2005. "Big and Tall Parents Have More Sons: Further Generalizations of the Trivers-Willard Hypothesis." Journal of Theoretical Biology. 235: 583-590

7. Kanazawa, Satoshi and Griet Vandermassen. 2005. "Engineers Have More Sons, Nurses Have More Daughters: An Evolutionary Psychological Extension of Baron-Cohen's Extreme Male Brain Theory of Autism and Its Empirical Implications

8. Yamagishi, Toshio, Shigehito Tanida, Rie Mashima, Eri Shimoma, and Satoshi Kanazawa. 2003. "You Can Judge a Book by Its Cover: Evidence that Cheaters May Look Different from Cooperators." Evolution and Human Behavior. 24: 290-301

9. Kanazawa, Satoshi and Rebecca L. Frerichs. 2001. "Why Single Men Might Abhor Foreign Cultures." Social Biology. 48: 321-328.

And so on, and so on.

If we apply some rudimentary logic to the titles, we would have to conclude that  big and tall men (paper 6) are violent  (paper 4) and they are also ugly, because if they were attractive they would have had more daughters (paper 1).

Since I had the fortune of having one son and one daughter I am in limbo (recently abolished by the Catholic Church, after several centuries of existence): I should be short, non-violent, and ugly. My wife wholeheartedly concurs. Saving grace, I don’t like to watch TV, which at least makes me intelligent (paper 3).

Back to the dumb blonde

A recent paper by Kanazawa and Jody L. Kovar of Indiana University of Pennsylvania ( "Why Beautiful People Are More Intelligent." Intelligence. 32: 227-243,2004.) illustrates the “thought experiments” used in many such publications. The authors suggest that:

1. Blondes are perceived in most cultures as more attractive,

2. Men prefer great looks over awesome intelligence (to wit, the irrefutable “evidence” that “gentlemen prefer blondes”).

It would then make perfect evolutionary and economic sense for blondes to invest their energy and talents in snagging an attractive, high earning man, rather than invest in their own education. All their daughters (paper 1) will be intelligent, attractive and… blonde.

Hence the stereotype. These gals are not dumb, they just didn’t go to school; they actually made a smart economic decision. Who would argue with such logic? Certainly not a dumb blonde.

In terms of my own situation, I am a total evolutionary failure. And you, Pat, are just too smart for your own evolutionary good.

Dov Michaeli MD, Ph.D

Having a stroke changes your life in many dramatic ways. People, who were previously mobile and independent, often find themselves unable to do many of the things they did prior to the stroke. With one side of the body paralyzed, simple tasks, such as opening a can of food or making a bed, can present daunting challenges to stroke survivors.

The results of a new study, published earlier this month in the Journal of the American Medical Association, offers some hope that some lost motor (movement) function can be reversed. The study is named EXCITE (which stands for Extremity Constraint Induced Therapy Evaluation)…and the results are, well, EXCITE-ing.

Steven Wolf, a PhD, physical therapist was the lead researcher on the study. The study had a strong clinical design, known as a multi-site, randomized, single-blind clinical trial. Patients who were left with a limited disability of their hand 3 to 9 months after a stroke were recruited from seven different clinical centers. They were randomly assigned to be in one of two intervention groups. One group received a treatment called “constraint-induced movement therapy (or CIMT). The other group of stroke patients received “usual care.” The patients, of course, knew what kind of therapy they received, but the evaluators of their clinical response did not.

Constraint-induced movement therapy (or CIMT) improved functional outcomes

CIMT, in this study, consisted of two major components. Participants received up to 6 hours per day of physical therapy per day for two weeks. The physical therapy emphasized repetitive motion of the affected arm. They were also asked to wear a safety mitt on their good hand that prevented the use of that hand for at least 90% of waking hours daily for 14 days. The group receiving “usual care” ranged from no treatment at all to the use of orthotics, or different types of occupational and/or physical therapy.

Individuals treated with CIMT has significantly improved functional use of the affected hand and reduced disability compared to people who only received “usual care.” Further, the benefits were maintained for at least 12 months -- the duration of the study.

In an editorial accompanying the research article, neurologists Andreas Luft, MD and Daniel Hanley, MD, note that “early mechanistic work suggests that constraint-induced therapy modifies brain circuitry, particularly motor and premotor cortices in the affected hemisphere, to produce its benefit. Further studies, using sophisticated brain imaging techniques, need to be done in order to confirm if structural brain changes underlie the functional improvement.

Ready for prime time?

A number of questions still remain about the generalizability of the results of this study:

• Will individuals with more severe paralysis, say a dense hemiparesis (or complete paralysis of one-half of the body) have the same benefit?
• Is it safe in people with larger neurologic deficits? Would they fall more if a good limb is immobilized? Would they have more post-stroke injuries?
• How long after a stroke can CIMT be initiated and still produce benefits? People in this study were 3 to 6 months post stroke. Can CIMT produce functional improvements in people who have been paralyzed for 1 year, 2 years, or more after stroke?
• Is the improvement sustainable beyond the initial post-treatment period? Improvements lasted for up to a year in this study. Will these improvements last for 5 years? 10 years?

Despite these remaining questions – which will undoubtedly be subjected to study in the near future – the results of this study are indeed, EXCITE-in. For the first time, in a well-designed study, an aggressive intervention -- 2 weeks of CIMT -- has been shown to significantly improve functional outcomes in stroke patients compared to the usual array of interventions we have employed so far. This study produces more than a few rays of hope in the area of post-stroke rehabilitation.

Dov Michaeli, MD, PhD explores the impact of aerobic exercise on brain function.

Aerobic exercise and the brain

Now, I want to turn our attention to the brain. Don't worry, I will come back and tell you how this all relates to the titillating findings I wrote about in my last post on the relationship between resveratrol and endurance. But first let's examine the results of a study of the impact of aerobic exercise on brain function.

We know from prior studies that aerobic exercise has beneficial effects on brain function in older adults. For example, compared to elderly people who are sedentary, seniors who engage in regular aerobic exercise demonstrate the following:

• They are more nimble at being able to switch between mental tasks
• Their working memory improves significantly, and
• They can better screen out distractions

In a recent study, reported in the November 2006 issue of the Journal of Gerontology, Dr. Arthur Kramer and his research colleagues delve deeper into the relationship between aerobic exercise and improved brain activity. They used sophisticated brain imaging techniques to demonstrate that these improvements in brain function have an anatomical basis.

They showed that new neurons were formed as a result of aerobic physical activity. This phenomenon is called neurogenesis. Until quite recently, the idea that new neurons could be formed in adults was considered heretical. The researchers noted that exercise-related neurogenesis was especially prone to occur in the frontal lobes of the brain. These are the areas of the brain that are responsible for cognitive functions, such as thinking, working memory, attention.

Furthermore, they showed they showed a large increase in the “white matter” in the brains of exercising seniors. The white matter contains the connections between the neurons (which constitute the “gray matter” of the brain). A particularly important area of white matter is an area called the corpus callosum. The corpus callosum connects the two hemispheres of the brain, right and left. Increased volume of this area explains the observation that exercise increases the integration and coordination of the right and left brains and, thus, increases cognitive efficiency.

Whose brains benefit from aerobic exercise?

The Kramer study included 59 adults, ages 60 to 79. Half of this group exercised (a brisk walk at about 3 miles per hour) 3 hours a week, the other half performed non-aerobic exercises like stretching and toning. Only the aerobic exercisers showed brain benefit.

Since we know that cognitive functions begin a slow decline from about age 40, it may be that adults 40 and elders are the prime beneficiaries of aerobic exercise when it comes to improved brain function.   However, we cannot say definitively that younger people's brains do not benefit from aerobic exercise as that simply not been studied yet.

Resveratrol, aerobics, and the brain: bringing it all together .

As I discussed in my last post, we know that resveratrol does a number of good things with respect to cellular energy metabolism:

• It improves the efficiency of oxygen utilization in cellular organelles called mitochondria
• The improved efficiency of oxygen utilization in mitochondria leads to enhanced ATP production (ATP is the prime energy storage unit for cells)
• Enhanced ATP production facilitates increased physical endurance, at least in mice.

Aerobic exercise, on the other hand, leads to an increased number of cells and therefore, an increased number of mitochondria that produce ATP.  The endpoint is the same as resveratrol.  There is an increased amount of energy, stored as ATP, to fuel various cellular functions.  Thus, enhanced physical endurance and increased brain power.

The problem is, from a practical point of view, very large amounts of red wine must be consumed in order to consume enough resveratrol it to do any good. So, if you think you can drink your way to everlasting happy/healthy life--fuggedaboudit.   You would need to drink hundreds of glasses of red wine every day to consume the required amount of resveratrol. Most likely, rather than live forever with great endurance and expanded brain power,  you’d die of cirrhosis and alcohol-related mental problems.

Let's  consider now what aerobic exercise can do for us. We have now compelling evidence that it is good not only for the body but also for the mind (unlike exessive amounts of red wine). It increases the volume of muscle tissue, the efficiency of mitochondria and their number per cell. Likewise, it increases the number of neurons in the frontal lobes (as well as in the areas of the brain that control motor functions), and it increases the number and efficiency of mitochondria in those neurons.

Here is another  fact: many neurodegenerative diseases, like Alzheimer's disease and Parkinson's disease, are associated with mitochondrial loss of function. Could aerobic exercise slow down the progression of such diseases? We don't know the answer to this question yet, but it is an intriguing possibility.

What is the bottom line with respect to improved mitochondrial energy production?: The best way to develop high functioning mitochondrial energy production is via regular AEROBIC EXERCISE!  It may not be as palatable as drinking lots of red wine, but it is pretty safe, it can be fun, and it improve, not pollutes brain power.

Your weight is ultimately in your head by Dov Michaeli, MD, PhD After spending twenty years in the rarified atmosphere of academic research and teaching medical school, followed by a long stint in the biotechnology industry, I decided to revisit a subject I used to teach: energy metabolism. Wow! This was a culture “shock and awe”. Twenty years ago we used to teach our budding doctors the simple fact that if there are more calories in the diet than are burned by physical activity, the excess energy is stored as fat. We understood in great detail, the metabolic pathways by which food is used to provide energy and the excess converted to fat. When it came to overeating, the message we gave our students, and they in turn gave to their patients, was the equivalent of “just say no”.

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