The Doctor Weighs In

By Dov Michaeli MD, Ph.D

I vividly remember a conversation I had with a London cab driver just before the election that unseated John Major (Conservative party) and elected Tony Blair (Labor party). I asked him who he was going to vote for, fully expecting him to make a “rational” decision and vote his economic interests. But, to my astonishment, he was going to vote for the conservatives. Why? I asked in disbelief. The answer was shocking to me. I’ll paraphrase: “because we working class blokes should know our place. The Aristocrats have been running this country forever, and they have done a bloody good job at it. And every time labor got its hands on power they made a bloody mess”.

This episode was etched in my memory, so incredible and yet so profound it was. How to explain such reverence to social hierarchy? Is it a product of generations of social brainwashing? Shakespeare, himself not an aristocrat or even a minor noble, portayed with great disdain characters of low social standing who tried to reach beyond their class. But is it really just a function of culture? Did anything change in the USSR after the revolution, when all classes were abolished with the stroke of a pen (and a bullet, for added emphasis)? Definitely not. The peasant still “knew his place”, only the superior feudal, properly addressed as “gospodin”( sir, master) was replaced by a newly minted commissar, addressed as “tovarish” (comrade).

So if it’s not purely socio-cultural, what is it?

It’s all in your head

A wonderful paper was published in the latest issue of Neuron, the neurobiology magazine. It was authored by Caroline Zink, Ph.D., Andreas Meyer-Lindenberg, M.D., Ph.D., and colleagues of the NIMH Genes Cognition and Psychosis Program.

Prior studies have shown that social status strongly predicts health. Animals chronically stressed by their hierarchical position have high rates of cardiovascular and depression/anxiety-like syndromes. A classic study of British civil servants found that the lower one ranked, the higher the odds for developing cardiovascular disease and dying early. Lower social rank likely compromises health through psychological effects, such as by limiting control over one's life and interactions with others. However, in hierarchies that allow for more upward mobility, those at the top who stand to lose their positions can have higher risk for stress-related illness. Yet little is known about how the human brain translates such factors into health risk.

To find out, the NIMH researchers created an artificial social hierarchy in which 72 participants played an interactive computer game for money. They were assigned a status that they were told was based on their playing skill. In fact, the game outcomes were predetermined and the other "players" simulated by computer. While their brain activity was monitored by fMRI, participants intermittently saw pictures and scores of an inferior and a superior "player" they thought were simultaneously playing in other rooms.

Although they knew the perceived players' scores would not affect their own outcomes or reward -- and were instructed to ignore them -- participants' brain activity and behavior were highly influenced by their position in the implied hierarchy.

What did they find?

Key study findings included:

 The area that signals an event's importance, called the ventral striatum, responded to the prospect of a rise or fall in rank as much as it did to the monetary reward, confirming the high value accorded social status.

•  Just viewing a superior human "player," as opposed to a perceived inferior one or a computer, activated an area near the front of the brain that appears to size people up -- making interpersonal judgments and assessing social status. A circuit involving the mid-front part of the brain that processes the intentions and motives of others and emotion processing areas deep in the brain activated when the hierarchy became unstable, allowing for upward and downward mobility.
•  Performing better than the superior "player" activated areas higher and toward the front of the brain controlling action planning (prefrontal cortex), while performing worse than an inferior "player" activated areas lower in the brain associated with emotional pain and frustration (amygdala).
•  The more positive the mood experienced by participants while at the top of an unstable hierarchy, the stronger was activity in this emotional pain circuitry when they viewed an outcome that threatened to move them down in status. In other words, people who felt more joy when they won also felt more pain when they lost.

Surprise?

These findings are actually not very surprising. Anybody who ever observed monkeys and apes in their natural habitat could easily pick out the alpha male and female, and the submissive behavior of the rest of rest of the clan. But a more detailed observation reveals subtle gradations in social standing among the “lower class” members. Each member of the clan ”knew his or her place”, and acted accordingly. Furthermore, violations of the boundaries of social standing were promptly punished. Is it surprising then that a specific area in the brain, called the striatum, is dedicated to assessing one’s place in a group? Furthermore, it is located right behind the prefrontal cortex, the area that is making rational decisions based on the inputs that reach it from all areas of the brain. The proximity of the striatum to the prefrontal cortex reduces the time for a message to reach the decision-making circuits--a biological testament to the importance ascribed to social animals “knowing their place” in their society.

The experiment showing that in unstable hierarchies people at the top are just as anxious and stressed as people at the bottom is truly revealing. What is the societal equivalent to “unstable hierarchies”? Democracy, of course. Today you are on top, but your position there is constantly challenged, and eventually you have to give up your exalted position. Anybody who observed our presidents at the beginning of their term, and at the end, couldn’t fail but notice how much they aged. Even a clueless president like George W has aged noticeably.

What is truly remarkable in this study is the documentation of the existence of the ‘social brain’. It has long been hypothesized that areas in the brain are specializing in directing social interactions like emulation, attunement, empathy and altruism. This study provides unequivocal neuro-anatomical proof.

By Dov Michaeli MD, Ph.D

The April 14 online edition of the Proceedings of the National Academy of Sciences carried an intriguing article titled “ Endogenous steroids and financial risk taking on a London trading floor”. Both authors, J.M. Coates and J. Herbert are from the Dept. of Physiology, Development and Neuroscience at Cambridge University . But J.M.C. is also from the School of business at Cambridge , and his main research interests are summarized by him thusly: “ I have been sampling endogenous steroids from traders on a trading floor in the City to determine the role of both testosterone and cortisol in their decision making and in their performance. I compliment this field work with behavioral experiments set in the lab and in artificial asset markets”

Raging hormones and bubbles

The rationale for this field of research is both compelling and fascinating. As stated by J.M.C  “ the waves of irrational exuberance and pessimism that destabilize the financial markets ,may be driven by naturally produced steroid hormones. With receptors in almost every nucleated cell in the body, steroids such as testosterone and cortisol affect the moods we experience, the memories we store and recall, and the behavior we display in competitive and risk-taking situations”.

This is absolutely fascinating because for the first time we find a serious attempt to explain economic phenomena on the basis of human physiology.

What they found

The investigators took saliva samples from 17 male traders on a London stock trading floor twice daily over the course of eight days. They monitored the traders' levels of testosterone, the hormone most often associated with aggression and sexual behavior, and cortisol, the so-called stress hormone.

They tracked those levels against the amount of money that a trader made or lost, and against the variation in the market. What they found was that when the traders made more money, they had elevated levels of testosterone. When the markets were particularly variable, they had elevated levels of cortisol.

Aha, you might aver; how do you know what is cause and what is effect? Isn’t it just as possible that traders had their testosterone levels go up as a consequence of making money?

Good thought, but…

A further analysis showed that traders who started their days with elevated testosterone made more money than those who didn't. One trader went on a six-day winning streak, making twice as much money each day as the previous one. Over that period, his testosterone levels rose steadily, some 74 per cent! This guy must have been a raging bull by the end of the week. Just think of the rollicking weekend he must have had.

So should stock traders join the ranks of sports figures and take testosterone as a performance enhancer?

Not quite. There is a point of diminishing returns; too much testosterone leads to too much aggression and reckless decision making. In some it may even lead to criminal behavior.

Cortisol, anxiety and risk management

Cortisol is one of the stress hormones. It rises when stress levels are up, which is stating the obvious. But what is less apparent is its role in limiting risk. Let’s go back to the savannah for a minute. You spot a lion striding toward you. Being the testosterone macho that you are you’d be perfectly willing to take the beast on. One guy, Samson, actually did it and lived to tell the tale, so why can’t you? Fortunately, your eyes send the brain another message: don’t kid yourself, this is dangerous! The order goes out to the adrenal glands and a flood of cortisol is released into the circulation, raising your anxiety level and making you have some second thoughts: after all, this is a tale from the bible, and you know how believable those are; besides, this guy Samson- did anybody see him kill the lion? Maybe he was just using it as a line to get Delilah to do what Philistine girls do better than the Israelite ones do? So you hedge your bets and climb up the closest tree. In other words, cortisol made you manage your risks more rationally.

Indeed, when the markets stopped going in one direction and started fluctuating, as markets always do, cortisol levels went up and trading became more restrained.

Of course there is a downside to cortisol as well, especially when exposure to it is chronic.

The downside of cortisol

A few days ago we reported on a Kaiser Permanente study that showed increased risk of dementia in males over 40 who had an increased central obesity, or abdominal girth that is 35 inches in women and 40 inches in men. Even men with a normal BMI had a 2 fold increase in risk if their abdominal fat was excessive. Now, if you think that you are in great shape because your BMI is within the normal limits, and you proudly display your six-pack abs to anybody who would care to look, think again . Experts now think that subcutaneous fat -- the flabby variety under the skin in areas like the buttocks, legs and arms -- while unfashionable, is fairly benign. Researchers at the Washington University School of Medicine in St. Louis demonstrated that when they removed an average of 22 pounds of subcutaneous fat via liposuction from 15 overweight women, they found no change in the women's cholesterol levels, triglycerides, insulin sensitivity or other health risks. We are talking here about visceral fat, or fat that underlines your awsome abs, lining your intestines and other internal organs. This fat in excess can be deadly. It is associated with the diseases of metabolic syndrome, but also with gall bladder disease, sleep apnea, numerous cancers, and dementia. So even if you are not flabby (you cannot pinch your skin and subcutaneous fat), but your belly is sticking out – you probably have excess visceral fat.

A major factor in determining this deadly distribution of fat is cortisol. This is probably why people under chronic stress are more prone to all the diseases we just mentioned.

But wait, there is more. Cortisol also causes increased risk of arthritis. It also leads to shrinkage of the prefrontal cortex and hippocampus, brain regions associated with decision making and factual memory, meanwhile it contributes to growth in the amygdala, a region associated with emotional memory and anxiety. Not good stuff.

The good news

Cortisol levels can be controlled by reducing stress levels. And visceral fat is the first to go when someone loses weight in general. Aerobic exercise, like walking or running, is particularly effective. Doing sit-ups, abdominal crunches and pilates can strengthen your abdominal muscles, and help hold your stomach in, but they won't target visceral fat specifically.

Some final thoughts on stock trading

Here are some questions that beg for a study.

· Are women better traders because they are less prone to wild speculation?

· Are stock traders more prone to heart disease and diabetes? Or more critically for their clients, are they likelier to become demented?

· Should clients insist on a broker’s full disclosure of his health record?

Or may be the answer is a lot simpler: get a woman broker.

By Dov Michaeli MD, Ph.D

I recently came across a news item about a tearless onion developed by scientists in New Zealand . I, for one, shed many tears over the chopping board, and all because of a substance called the lachrymatory factor. Now, using molecular engineering techniques, the Kiwi scientists silenced the gene that codes for this factor, and voilá – a tearless onion.

This got me thinking: this kind of crying is really all reflex, a direct reaction to irritation. It is the same type of reflex that causes our eyes to well up when we are poked in the eye. Another type of tears is the so-called basal tearing, which bathes our eyes every time we blink. Now, these two types of tearing are common to many animals, and their function is straightforward: Housekeeping, or more specifically, preservation of the integrity of the outer structures of the eye.

What about crying?

Believe it or not – this is unique to us humans. Not even our closest relatives, the chimpanzees, are capable of shedding emotional tears. Yes, animals can howl in pain or in anguish; my dog yawls and howls to high heaven whenever I leave the house without getting his approval; but he doesn’t shed tears. And contrary to popular belief, crocodiles don’t shed tears; but real men do. So how did it come about?

There must have been a “mistake”

The fact that chimps cannot shed emotional tears means that a mutation occurred after our genus Homo split off the evolutionary branch  common to us and the chimps, namely less than 30 million years ago. Obviously, we don’t know exactly when that occurred. For instance, if we knew whether Lucy the Australopithecus could cry we could narrow it down to 300,000 years ago. She most likely had tear ducts like ours, but so do the chimps and the dogs. At some point in our human history a mutation occurred that connected our tear glands to the limbic system, which is responsible for feelings and expression of deep emotions. This system contains such organs as the amygdala, which are the seat of intense emotions as anger and pain. Who hasn’t experienced the connection between these emotions and tears? Or the hippocampus, the seat of memories; Have your eyes ever welled up when old memories floated up from a deep, long forgotten sad life story? The reward centers are part of the limbic system as well; just watch the glistening eyes of proud parents when their child graduates from college.

All this crying is totally involuntary. The autonomic nerves cause the mentalis muscle, the one in the chin, to quiver. They cause the lump in your throat, and the corners of the lips to depress (by activating the depressor anguli oris muscle). It is almost impossible to voluntarily control these actions.

What’s the use?

If we accept the premise that this mutation, like all other mutations are random events, why did it persist? What advantage did it bestow on the newly crying-capable humans?

Crying is the first mode of communication of babies. I always marvel at the capacity of parents to “read” their baby’s cry. Some are cries of hunger. Others are cries of fatigue. Yet others are cries of pain. And the ever discriminating parental ear can tell one from the other.

We can expand on this concept. Crying is not restricted to baby- parent communication. We adults communicate in a variety of ways: body language, speech, song, dance, laughter, and yes—crying.

The reason for this rich palette of communication modes is that it has an important survival value. Being vulnerable creatures in the savannah our only hope for survival was through cooperation. Not only could we better defend ourselves better against faster and more powerful predators, but we could even turn the table on them and make them our dinner.

Te key to cooperation is socialization, and one of the traits that characterize our capacity to socialize is empathy, the capacity to feel what the other person feels. Have you ever experienced sadness when talking to a person who had just experienced a terrible loss? Or looking at Picasso's heartrending painting of "The Tragedy"? Or joy when your friend is beaming with happiness? This is your empathy in action.

Empathy is not purely a psychological phenomenon; it has a neurological basis. There are special neurons in the brain that mirror the emotional state of the other person. These neurons, called appropriately enough mirror neurons, are extra large and most numerous in the human brain. They are distributed through many areas in the brain, all having to do with emotions. The amygdala have them, and so do the reward centers.  So that when my reward centers fire when I tell you about my fantastic trip the mirror neurons in your reward centers would fire as well, I hope.

And back to crying; when a person dear to us is crying, it “breaks our heart”, and we feel like crying as well. This is a form of bonding; those misty eyes and the outpouring of salt water are part of the glue that kept us together since we got off the trees and made our first uncertain steps in the hostile savannah.

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.

By Dov Michaeli MD, Ph.D

“Methought I heard a voice cry ‘Sleep no more!

Macbeth does murder sleep’—the innocent sleep,

… The death of each day’s life, sore labor’s bath,

Balm of hurt minds, great nature’s second course,

Chief nourisher in life’s feast”

Macbeth, William Shakespeare, 1600 AD.

Four hundred years later UC Berkeley scientists used brain imaging techniques to explain Lady Macbeth’s sleep-deprived brain descent into the darkness of insanity. They studied 26 young adults, half of whom were kept awake for 35 hours straight and the other half were allowed a normal night’s sleep in that same time period. Their brain was then studied using fMRI imaging. This technique shows the blood flow to different areas of the brain, and by extension, their state of activation.

What did they find?

The amygdala is the area in the brain that deals with unpleasant (or aversive) emotions, and puts the body on alert to protect itself. For instance, feelings of fear or rage are processed there. In the sleep-deprived subjects this area “lit up”, showing a high activation state.

On the other hand, the prefrontal area is responsible for tamping down those feeling, of adding some rationality into the mix; in a word, the outcome of its intervention is what we call ‘judgment’. In the sleep-deprived subjects the level of activation of the prefrontal cortex was significantly reduced.

Subjects who had gotten a full night of sleep showed normal brain activity.

This is not surprising to anybody who has experienced sleep deprivation, and that’s essentially all of us. Who hasn’t experienced the easy irritability, or alternatively the giddiness, that come after a sleepless night? Or the compulsive and nervous eating? Or the feeling that your “resistance is down” and that you are prone to a viral cold? These feelings are not “all in you head”. Sleep deprivation has been shown to affect emotional well-being, to alter metabolic control, and to adversely affect the part of the immune response (called innate immunity) that protects us from bacterial and viral infections.

There may be more to it

If the capacity to tamp down negative thinking is impaired, it opens up the possibility of a connection to psychiatric disorders like depression and anxiety. If you think of it, both of these disorders are a reflection of inappropriate or exaggerated negative response to a stressful event. Such events need not be dramatic, they could be quite trivial. A not-so-good grade at school, perceived slight from a friend, a critical remark by a coworker—all these can precipitate depression or anxiety. And the brain mechanism is identical to that of sleep deprivation: an imbalance between the negative messages flowing from the amygdala, and the moderating and rationalizing effect of the prefrontal cortex.

America the sleepless

How much sleep do we need? It varies with age and overall health. Most adults require 7- 8 hours a night. Older people may need 5-6 hours. Teenagers may require an hour or so more. Now consider the following:

· The National Sleep Foundation poll found that in 1998 35% of adult Americans got at least 8 hours of sleep a night. In 2005 this figure dropped to 26%.

· About 40% of Americans get less than 7 hours of sleep.

· 75% reported having some sleep disorder one or two nights a week.

These are sobering statistics. I can’t help but wonder if our chronic sleep deprivation is not a contributing factor to our elevated level of societal rancor, increased violence, our deteriorating civility, and our increased rate of diagnosed psychiatric disorders such as chronic depression, anxiety and sociopathic behavior.

Sleep has become synonymous with sloth in our “on the go” society. It would take more than academic studies to change this culture. We need nothing less than a paradigm shift in our outlook on life.

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

A few weeks ago (May 9, 2007) we posted a comment on Gina Kolata’s article in the New York Times (May 8, 2007) The article basically laid the blame for the obesity epidemic afflicting us at our genes. Kolata reviewed work suggesting that genes are involved in obesity, with the implication that a fight to lose and maintain a lower weight is not only excruciating, it is practically futile.

That simply didn’t sound right. At least 10 genes have been discovered thus far that are involved in obesity and diabetes; more are bound to be discovered. We also know that the US population is fast approaching the 50% mark of overweight (BMI 25-29.99) or obese (BMI > 30). These genes presumably are not recent mutations. Why is it then, that only relatively recently did these genes express themselves to cause the outbreak of obesity? I think the answer is quite obvious: we have here a classic case of genetic/ environmental interaction. The genes have been there all along; they haven’t changed. The new elements that caused such a massive upward shift in BMI are the invention of the car, television, computers, all leading to a sedentary life style. Couple this with profound changes in our dietary and eating habits, resulting in a significant increase in caloric intake, and you’ve got an inescapable outcome: weight gain.

Don’t go shopping for food when you are hungry

I don’t know who first pronounced this maxim, but I am sure many of us rediscovered it many times, independently. What we actually discovered is that hunger is such a powerful physiological drive that no rational, moderating influence can keep it in check.

The hunger drive

Our gut reaction, so to speak, to hunger is primarily hormonal. Fat cells secrete a hormone, leptin (leptos means thin, in Greek), that travels to the brain, and signals a message of satiety; the more leptin, the less hunger. Another hormone, called ghrelin is secreted from the stomach when it is empty, and its signal to the brain is hunger; the more ghrelin, the more hunger. This description is obviously a vast oversimplification, but the basic mechanism is clear: our sense of hunger or satiety is a balance between hormones with opposing influences on the center in the brain that controls feeding. This area, called the hypothalamus has neuronal connections to two other important areas: the amygdala, and the nucleus accumbens. Activation of the amygdala, when the hypothalamus senses hunger, causes a sense of alarm, sometimes accompanied by aggressiveness, easy irritability and other hard-edged feelings. On the other hand, a sense of satiety and fullness activates the nucleus accumbens, which is the seat of all the warm and fuzzy feelings, like reward and pleasure. The neurotransmitter that mediates this sense of pleasure is dopamine.

The cocaine connection

It turns out that dopamine is also secreted in the nucleus accumbens in response to cocaine, amphetamines and other recreational drugs. In fact, the response of the cells that carry the dopamine receptors to the sudden rise in dopamine concentration is to reduce the number of receptors, so as to keep the stimulus within manageable bounds, so to speak. This phenomenon is called receptor downregulation. To keep the pleasurable sensation at its previous level one needs to take even more cocaine, which in turn causes even more downregulation. You can readily see the neurobiological downward spiral that we call addiction.

Lo and behold, the same pattern is seen in brain scans during binge eating: Surfeit of dopamine, activation of the nucleus accumbens, and downregulation of dopamine receptors.

The brain’s “adult supervision”

Of course, being civilized creatures we could not let ourselves be governed by such “primitive” drives as pleasure and reward on the one hand, or anxiety, aggression and rage on the other. Indeed, evolution endowed us with a highly developed area in the brain called the prefrontal cortex. This is the seat of judgment and rational decision-making. It weighs the messages arriving from the reward and anxiety centers and renders judgments that find their expression in what we call behavior.

However, this Solomonic wisdom does not always prevail. When exceptionally strong messages arrive from one center, they overwhelm the messages from the other, and the judgment of the prefrontal cortex becomes skewed, or completely overwhelmed by the flood of the incoming powerful signals. Each one of us, after along period of fasting, must have felt an overwhelming desire to binge-eat. Only when we are finally disgustingly stuffed, do we ask ourselves: what am I doing? In neurobiological terms, the storm of signals from the amygdala (hunger to the point of anxiety) and the nucleus accumbens (“how sweet it is”, and the hell with the diet!) subsided, and the ever stern, judgmental prefrontal cortex reasserts itself (“have you no shame?”).

So, is it genes or addiction?

I believe that the addiction model is a more plausible explanation of the overeating epidemic that is afflicting us now. It also explains the extreme difficulty in “kicking the habit”, losing weight and maintaining it over a long period of time. As any recovered drug addict will tell you: one never really kicks the habit; it is a constant battle, and one is always on the brink.

The encouraging aspect of this grim picture is that addiction is susceptible to therapeutic intervention. There are drugs that can blunt the addictive urge. For instance, the drug naloxone reverses the effects of morphine. Interestingly, naloxone also blunts the hunger drive and reverses binge-eating.

Dov Michaeli, MD, Ph.D

If you enjoyed reading this, you may also want to read:

• Obesity:  The devil made me do it
• Genes and food -- good and genes

Genes

In 1993 scientists reported on a Dutch family, 14 members of whom were sociopaths, involved in aggressive crimes such as bullying, physical violence, rape, and arson. They all had in common a mutation in a gene that makes an enzyme called MAOA. The function of this enzyme is break down neurotransmitters such as serotonin and noradrenaline (or norepinephrine, a chemical first cousin of adrenaline). The ready conclusion was: defective enzyme caused elevated level of serotonin and noradrenaline, resulting in overactive brain circuits that serve aggressive behavior.

Case closed? Not so fast…

In a wonderful summary of the topic in Newsweek magazine ( April 30, 2007 ) one of my favorite writers on the subject, Sharon Begley) describes a 2002 study in New Zealand of 442 men who were followed since their birth. Indeed, men with low MAOA were more likely to engage in persistent fighting, bullying, cruelty and violent crime. But not all of them; only men who had been neglected or abused as children fit the bill. Men who grew up in a normal environment exhibited none of the violent traits.

Neuroanatomy

In previous postings we waxed scientific about the amygdala, two almond-shaped structures deep inside the brain, that are the seat of primitive emotions such as rage and fear; these constitute the emotional basis of the fight or flight reaction, which is mediated by noradrenaline. These waves of seemingly overwhelming emotions are checked and inhibited by another, more modern structure in the brain: the prefrontal cortex. This structure is the seat of judgment, planning, abstract thinking. It inhibits inappropriate or impulsive behavior, and is engaged in constant self-monitoring (could it be the anatomical seat of the Freudian super ego?). So in typical Ying/Yang fashion, the outcome of our behavior must then be the product of the amygdala and prefrontal interaction. Remember the then famous case of Kip Kinkel, a 15 year old who in 1998 killed his parents and two dozen schoolmates in Springfield , Oregon ? His brain scan showed a completely silent prefrontal lobe; he had nothing to check and balance his raging anger emanating from his amygdala.

Is this it? Not quite…

Hormones

Women love to point out, without much evidence I might add, that men’s aggressive behavior can be traced to their testosterone-addled brain. Only partly true. The level of testosterone is within normal limits between 20% and 200% of the mean; that’s a huge range of normal. However, if the level of testosterone exceeds 400% of the mean, then indeed women are right—men with these levels are more prone to violence. In fact, testosterone is an equal opportunity hormone; in a species of hyenas (I forget which) the first newborn in a litter, be it male or female, will eat the rest of the brood within days of birth. It turns out that this vicious sibling has inordinately high levels of testosterone in its brain, much higher then the other hapless siblings.

But to assume that we are simple automatons, following helplessly the script written by our genes, brain circuits and hormones, would deny a self evident fact—we don’t behave automatically, we do have a certain degree of free will.

Psychology

The interaction of biology and the life one leads turns out to be of paramount importance in shaping the criminal mind. The most important characteristic of the behavior of mass killers is paranoia. They have the sense that the whole world is against them, that everybody but themselves is responsible for their troubles, that the world is unfair. They are usually depressed and socially isolated.

This kind of personality, you might say, could be the product of brain circuitry gone awry. But here is a fascinating finding from animal and human studies: behavior can change brain circuitry and function-- an outstanding example of nature/nurture interaction. So what are the non-biological roots of violent behavior? We finally arrive at the inevitable:

Society and culture

It is the social environment that allows, indeed encourages, psychopathic criminal behavior. Many societies have members with genes gone awry, with malfunctioning brain circuits, with males suffering from raging hormones, with children raised in violent homes. But, sad to say, we have the dubious distinction of being the champions of gun violence in the civilized world. In 2004 there were 29,645 deaths due to gun violence in the US , or 10.08 per 100,000. For comparison, France had 4.93, Belgium 3.67,and Spain 0.75 per 100,000.

In 5 years of war in Iraq about 3200 of our soldiers got killed. Yet, we tend to see the situation in Iraq as intolerable but we dismiss  the carnage in our own streets with a helpless shrug: "It’s the culture… "

We mentioned the case of Kip Kinkel. Yes, his prefrontal lobe did not do its job. But here is rest of the story: a psychotherapist actually suggested that his dad buy him a gun so they could have something to do together.

As Pogo said: we have met the enemy, and it is us.

Dov Michaeli MD, Ph.D

A recent paper in the Journal Nature, Damage to the Prefrontal Cortex Increases Utilitarian Moral Judgments  (Nature, advance online publication 21 March 2007),  has provided strong evidence that we are indeed moral animals, and that certain aspects of our moral behavior are hardwired in our brain. The institutions involved in this research (U. Iowa Dept. of Neurology, Harvard U. Dept. of Psychology, and the Brain and Creativity Institute at the U. Southern California) reflect the multi-disciplinary approach required for such a study.

Where in the brain is Morality?

Our brain is organized in layers, somewhat like an onion. The deepest layer, like the brain stem and the structures around it, is the most ancient, or primitive, from an evolutionary point of view. These structures control vegetative functions, like heart rate, breathing, gastrointestinal motility, etc. These functions are essential for life, and are shared by organisms from the most primitive to the most complex.

Next in evolution came another layer of behavioral complexity: diverse functions such as thirst, hunger, sexual attraction, fight-or-flight responses to danger, responses to day-light cycles, short and long term memories. These functions are mediated by structures deep inside the brain called the midbrain.  The midbrain contains structures, such as the amygdala (fight of flight, rage, aggression), the hypothalamus (hunger), the nucleus accumbens (reward, pleasure) and the hippocampus (memory). These functions are not voluntary; they are found in mice and humans alike.

A more recent layer of the brain tissue, called prefrontal cortex, was added when monkeys started to evolve. In this layer resides the ability to function as a social animal, for instance traits like empathy and moral judgment. The last and outermost layer, added relatively recently, is called the frontal cortex.  It is most developed in humans. Messages from the brainstem, midbrain and prefrontal cortex feed into this area (situated right behind the eyes), where they are all integrated, weighed, judged, contemplated—and then translated into action.

What did the Nature paper find?

It has been suspected for about 10 years that an area within the prefrontal cortex, called the ventromedial prefrontal cortex or VMFC, is required for emotions and moral judgments. When subjects in a brain imaging study were presented with a scenario requiring moral judgments, the area that lit up was the VMFC. What kind of situations were they? Highly aversive ones; for instance, sacrificing one person in order to save several other. The anguish of such decisions is captured in Sophie’s Choice, or in King Solomon’s famous trial of the two women.

The vast majority of people will recoil from making a “utilitarian” calculation of killing one person so as to save others. Indeed, in this experiment over 80% refused this option. But in a group of 6 patients who had some kind of pathology in their VMFC, such as an aneurysm or a tumor, the judgment was completely utilitarian—kill the few to save the many. No hesitation, no compunction. In fact, Antonio Damasio, one of the authors of present study, published a study in 1999 of two patients who have had a defect in their VMFC since infancy ( Nature Neuroscience vol. 2, pp. 1032 - 1037 (1999). As adults, the two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities.  They showed insensitivity to future consequences of decisions, defective autonomic responses to punishment contingencies and failure to respond to behavioral interventions. The authors concluded: “Thus early-onset prefrontal damage resulted in a syndrome resembling psychopathy.”

What does it all mean?

The implications of these studies are enormous. For instance:

• We may finally get a handle on extreme psychopathic behavior, such as serial killing, serial raping, extreme levels of domestic violence.
• Our legal system will have to, sooner or later, come to grips with criminal behavior engendered by structural defects in the brain. Evidence of brain imaging (fMRI), is already being introduced in court, and juries are becoming receptive to the evidence.
• On a more hopeful note, but probably less imminent, we may learn one day how to intervene and enhance individuals' moral judgments. Wouldn’t that be a welcome development of this "1984 science?"

 Moral philosophers have dismissed evolutionary biologists and neuroscientists forays into the realm of ethical and moral judgment. They are now having second thoughts, and the more intellectually open and curious among them (a more developed frontal cortex?) are listening attentively. Can the days when vexing issues such as religion and faith in a higher being find a biological explanation be far off? Is conflict resolution between individuals and nations amenable to biological treatment? Science is what we make it to be. If we put it to good use it can promise humanity.

Dov Michaeli MD, Ph.D

I am at the Family Violence Prevention Fund’s National Conference on Health and Domestic Violence.  One of the panels that I attended examined the impact of child maltreatment on brain development.

David McCollum, MD, President of the Academy on Violence and Abuse, reviewed the medical literature on brain changes that occur after child abuse … and I am not talking about brain injury due to being hit on the head, rather I am talking about structural and functional changes in the brain that occur as a result of being exposed to the terror of family violence

Dr. McCollum briefly reviewed the biology of human brain maturation. Infants are born with an over  abundance of nerve cells, called neurons, and connections between nerve cells, called synapses. As the child gets older, there is a significant “pruning” of neurons as well as synapses.

Another process that occurs as the child’s brain matures is that the neurons become myelinated, a process that makes neuron-to-neuron transmission more efficient.

Myelination is inhibited when there are high levels of brain glucocorticoids, one class of hormone that is elevated during stress. There is no question -- being abused as a child or growing up in a home where your mother is abused is stressful…and, for many children, it is stressful over prolonged periods of time.

When the brains of children exposed to abuse are looked at anatomically, using imaging techniques, it turns out that there is a reduction in size of a number of key brain structures, including the amygdala, the hippocampus (mainly on the left side), and the cerebellar vermis. There is also a reduction in the size of the corpus callosum, the area that allows the two sides of the brain to communicate with each other. There is also an increase in the size of the putamen and the lateral ventricles (the cavities in the brain that contain cerebral spinal fluid). According to Dr. McCollum, many of these changes are explained by the inhibiting effect of glucocorticoids on myelination of neurons.

The areas of the brain impacted by glucocorticoid excess are components of the limbic system and related connections. The limbic system is involved in response to perceived danger.  It is also involved in our emotional response. The limbic system evolved to protect us from the dangers of the wild, and most likely played a role in our surviving attacks by predators. These stressful events were likely less common and less persistent than what is experienced by children trying to survive in a violent home.

Other chemical changes have been attributed to chronic stress, include overproduction of dopamine, a substance that, in excess, causes reduced attention, increased vigilance, impaired ability to learn new material, and increasing paranoid and psychotic behavior.

Serotonin levels are decreased as a result of stress. Suicidal behavior, depression, and aggression have been shown to result from low serotonin levels. Substance P, a neuropeptide that participates in pain response and inflammation, has been found at higher levels in the spinal fluid of abused, compared with non-abused individuals.

All of these findings have potentially profound implications for healthcare professionals. No longer can we say that family violence is not a health care issue. When your brain structure and function changes, for the worst, as a result of exposure to violence, I would say without a doubt that it is a healthcare issue of the highest magnitude.

We don’t yet know if these changes can be reduced with treatment. But our new understanding of the neurobiology of abuse is sure to lead to new therapies, some of which may be pharmacological and some of which may be behavioral. Hopefully, these new findings will also lead to more aggressive and more effective efforts identify kids at risk and to help families learn to live violence-free.

Finally, it is my profound wish that studies such as these will stimulate research into new ways to prevent violence in the first place. Primary prevention research in the field of family violence is woefully underfunded. It is time to get our priorities straight -- our kids brains are at risk.

If you would like to read more about this fascinating and important topic, take a look at Dr. McCollum's article on "Child Maltreatment and Brain Development" published in Minnesota Medicine in March 2006.

Pat Salber, MD

This is the title of an op-ed in the New York Times (Monday, February 12, 2007 ) by Lynn Chu, a New York lawyer, and John Yoo, a deputy assistant attorney general from 2001 to 2003, currently a law professor at UC Berkeley and a visiting scholar at the American Enterprise Institute.

For a moment I was excited by this title, because for quite a while I have been pondering the biological mechanisms underlying aggressive vs. non-aggressive (pacific?) behavior. Of course, you wouldn’t expect to find the answer in an article authored by two lawyers--and I didn’t. But it was not a total disappointment; the article was full of mischaracterizations (calling all Democrats Pacifists) and just plain verbal bullying.

Which again got me to think- what make aggressive people tick?

The answer, my friend, is written in the brain.

Our negative feelings of aggression, fear, hatred, revenge, all originate from deep inside the brain, in structures called the amygdala. This is not to say that these feelings are inherently bad—if they were, evolution would have selected them out of animals. The fight or flight reaction, so essential to an animal’s survival, originates in the amygdala. So does rage, important when your herd or tribe are under attack. These are ‘primitive’ reactions, in an evolutionary sense, since they are common to lower animals, and reside in the more ancient parts of our brain.

About 300,000 years ago, our ancestors became Homo sapiens (literally, thinking man). This new species was distinguished from other ape-men (Australopithecus) in the rapid development of a ‘new’ lobe in the brain- the prefrontal cortex. This area receives messages from all over the brain, processes them, suppresses some, allows others to be expressed; in other words—it makes judgments! How human, or, dare I say, civilized?

Was this prefrontal lobe just a device to make us high browed intellectuals? Probably not. It definitely had a survival advantage when our ancestors had to cooperate while hunting, or go hungry if they didn’t. Just as important, they had to make nice to the women of the tribe—or they’d end their lives without offspring.

So what makes people behave aggressively?

My own theory is that either their amygdala are overactive, or their prefrontal cortex is a bit lax in controlling the stream of negativity flowing in.

I first thought about this when I watched Bill O’Reilly (of “Culture Wars” fame) on TV debating Paul Krugman, a Princeton economist and a New York Times columnist. So there was O’Reilly, big, blustering, making totally unsubstantiated statements, and using the volume of his voice to ‘persuade’. Seated next to him was this diminutive man, affable, speaking in facts and figures, keeping his voice low, being polite to a fault. Perfect, I thought, amygdala vs. prefrontal brain match! Indeed, this ‘debate’ almost did not end up with words; the amygdala man was physically threatening the prefrontal man with physical harm, in plain view for the whole country to see.

You would think that evolution would have bred out people with unrestrained amygdala. Alas, evolution is just too slow a process to for us to enjoy it. But if we as a species survive another 1000 generations, our offspring will probably look back at us as semi-formed humans, a way station to a fully human species. Shouldn’t we leave a time capsule to tell them that we also had Einsteins, and Beethovens, and Martin Luther Kings, not just O’Reillys and Rush Limbaughs?

Dov Michaeli, MD, PhD

A research group working at the National Institute of Mental Health has published a paper (February 8, 2007 issue of the “Journal of Clinical Investigations (JCI)”) that contributes important genetic information about the normal functioning of our brains, and also raises interesting possibilities regarding the malfunction that results in schizophrenia.

How do we exercise judgment?

One of the hallmarks of being human is the capacity to exercise judgment. Like all animals, we are given to ‘primitive’ feelings of fear, rage, anger, and also pleasure and reward. The negative feelings arise from the amygdala. These are small groups of nerves, or nuclei, deep inside the brain, located beneath the cortex (the outer layer of the brain) and above the brainstem. The positive feelings of pleasure and reward originate from an adjacent nucleus, the nucleus accumbens,  one of the basal ganglia (which also plays a major role in addiction).

The behavior of lower animals is governed by these nuclei. For instance, the “fight or flight reaction” that occurs when animals are confronted with a dangerous situation originates in the amygdala. It is automatic—and this is important as there usually is not enough the time to filter information and make a rational judgment in an emergent situation.

Thankfully, we “higher beings” have the capacity to exercise some judgment. Next to the amygdala and the nucleus accumbens is another group of neurons called the striatum. This part of the brain gets its name because it has the appearance of layered bands of gray matter. The striatum has projections to the basal ganglia and to the prefrontal cortex.

Now, things are really getting interesting. The prefrontal cortex is the site where all those ‘primitive’ stimuli are being vetted, controlled and modulated, in other words—judgments are made. This prefrontal cortex (also called prefrontal lobe) is located in front of our brain, right behind the forehead. This is a relatively ‘modern’ addition to the brain, and humans have the most generous sized prefrontal cortex of all animals.

What the NIMH scientists have found is that a certain variant of a gene called DARPP -32 optimizes the functioning of the connection between the striatum and the prefrontal cortex. It is found in 75% of people. This is a major finding, because it gives us the genetic basis for exercising judgment. Furthurmore, the fact that such a large majority of people possess this variant means that it is probably the most effective variant of DARPP, which is why it was selected for by the evolutionary process of natural selection.

What does all this have to do schizophrenia?

It turns out that exactly the same DARPP-32 variant that occurs in most normally functioning brains has been found to be also common in people with schizophrenia. The evolutionary implication of this fact is that by selecting the most advantageous DARPP variant to optimize the connection between the striatum and the prefrontal cortex , natural selection also selected for schizophrenia. Nothing is perfect in life.

But there is another, more clinical, implication. It suggests that the striatum itself is not the seat of the schizophrenia abnormality, since schizophrenics possess DARPP-32, the gene that optimizes its function.

The authors of the JCI article speculate that the schizophrenia defect then must lie in the prefrontal cortex, the area that filters and controls all those stimuli coming from the striatum. It is possible that everyone could have an underlying propensity to have hallucinations, but normally functioning prefrontal lobes suppress them. (Indeed, in sleep, when the prefrontal lobe is 'asleep' as well, we may have dreams that sometimes have an hallucinatory character). Not so for people with schizophrenia--there is no 'censor' there to check those 'unnatural voices', as the bard would say, rising from the depths of their brain to haunt them.

 Is this speculation rational? Absolutely. Is it right? Hard to say. Biology has a way of confounding us every time we think we have found “the answer.” Only time will tell.

Dov Michaeli, MD, PhD