Since its original description in the late ’70s, experts have held widely divergent views about the cause of fibromyalgia; some even doubt that it is a real condition. Recently, though, with the advent of fMRI scans, researchers have shown that patients with fibromyalgia have different responses to pain than the “normal” population. This discovery holds out “proof” that fibromyalgia is a definitive organic condition requiring specific treatment. That may be good news for people who suffer from the mysterious condition, but it’s great news for the pharmaceutical industry, which can march to the U.S. Food and Drug Administration and seek authorization for a drug to cure the now official disease. Which is exactly what Pfizer did in 2007, earning approval to treat fibromyalgia with Lyrica, already a blockbuster drug.

But hold on. Is that possible? Can an fMRI scan determine the presence or absence of disease? To date, no evidence convincingly shows that fMRI, designed to measure cerebral metabolism, is sufficient to diagnose a specific underlying disease. So what’s going on here?

Let’s begin with a closer look at fibromyalgia itself. Despite strong convictions on all sides, nobody knows whether fibromyalgia is a primary medical condition, part of a larger constellation of other ill-defined conditions, such as chronic fatigue or irritable bowel syndrome, or a label given to a variety of physical complaints that arise out of various mental states, such as anxiety and depression. There haven’t been any reproducible and clear-cut objective findings, such as blood and lab tests, X-rays or anatomical abnormalities on biopsy, to provide a satisfactory understanding of the disease. Even the 1990 American College of Rheumatology diagnostic criteria — widespread muscle pain of more than three months, unassociated with other known illnesses, and the presence of at least 11 tender points over 18 muscle groups — are nothing more than subjective patient descriptions.

By the way, I don’t mean to denigrate patients who experience pain associated with fibromyalgia. My concern is the notion that an fMRI can distinguish between psychological states and so-called “organic” processes that affect how we experience pain. And how patients and physicians respond to the uncertainty of fibromyalgia is often dependent on how they think about “real” vs. “imagined.” Popular mythology has it that if you have physical complaints that arise out of worry and anxiety, the symptoms aren’t as “real” as if they are caused by disease. But this distinction between “real” and “imagined” is both philosophically naive and unfair to patients with psychological conditions.

If you think an inert sugar pill (placebo) is a powerful analgesic, taking it can reduce your level of pain from, say, a dental procedure or wear-and-tear arthritis. Conversely, if you are given the same sugar pill and told it is a new untested drug and might make your pain worse, you might experience more pain (nocebo effect). Your imagined expectation of what the pill might do will affect both your pain perception and what changes will be seen on functional brain imaging. Nowhere in this schema is there any suggestion that changes in pain perception arising out of imagination aren’t real. Placebo-induced relief of pain is clinically identical to pain relief from standard analgesics such as morphine.

Now consider one of the central features of fibromyalgia — an increased number of areas sensitive to ordinary pressure. If you believe you have a condition that makes you more sensitive to painful stimuli, you may well experience more pain than those who believe they aren’t sensitive to painful stimuli. This difference in pain appreciation or description, and the attendant brain changes on fMRI, will not reflect any underlying disease; both will be the reflections of your own self-perception. Even such personality traits such as optimism or pessimism (half-empty vs. half-full), or one’s attitudes toward the medical establishment, can make critical differences.

With this basic principle in mind, let’s look at what fMRI studies are telling us about fibromyalgia. In 2002, Georgetown University researchers compared how 16 women with fibromyalgia and 16 pain-free control subjects responded to both painful and nonpainful stimuli (a small piston generating various amounts of pressure to a thumbnail bed). They found that control subjects required more than twice the amount of pressure to elicit the same degree of pain and fMRI activation as fibromyalgia patients.

The authors concluded: “These results, combined with other work done by our group and others, have convinced us that some pathologic process is making these patients more sensitive. For some reason, still unknown, there’s a neurobiological amplification of their pain signals.”

Perhaps that is true, but amplification of pain signals can also occur simply from imagining an increased pain, as seen with the nocebo effect. So can simple anxiety.

In a subsequent 2007 study, the researchers used the same pain-eliciting techniques but different functional brain scans to look for differences between fibromyalgia patients and controls. This time they found a single region of altered activity between fibromyalgia patients and control subjects — in the right thalamus. The severity of this difference correlated with the degree of fibromyalgia symptoms; the greater the difference, the worse the patient’s symptoms were likely to be. The authors speculate that the findings “are likely the result of neuronal dysfunction.”

But a closer look at this study suggests an alternative interpretation, one more consistent with the notion of how anticipation and expectation can alter brain function.

The researchers found fibromyalgia patients who believe their pain is the result of some external factor, such as a prior injury or exposure to toxic chemicals, experience a higher degree of altered activity on imaging studies. That belief also leads to a higher depression rating on the study questionnaire. The authors comment that attributing clinical symptoms to an external source, even in the absence of clear-cut evidence, is a characteristic feature of chronic pain patients who don’t respond well to treatment.

In short, the described functional imaging findings correlate with patient expectation and belief. What we can’t know is whether the beliefs cause the functional change or are the result of the alleged change. And, more important, there is nothing on the scan to point to whether this activity is or isn’t “normal.” Nevertheless, the authors conclude, “there is really something wrong going on in the brains of the patients with fibromyalgia.”

Of course there is a physiological explanation for the pain of fibromyalgia. Ultimately there is a physiological explanation for all experience, whether it be pain, love or the hallucinations of acute psychosis. The issue isn’t whether a condition is associated with “brain changes” on functional imaging, but whether such changes reflect a specific organic disease as opposed to a psychological state of mind.

And let’s not kid ourselves. Researchers at big pharmaceutical companies are fully aware of the subtleties of how fMRI is performed and what interpretations can be drawn from even questionable studies. They realize that studies on chronic pain are notoriously difficult to interpret and prone to faulty interpretations. They understand overall results can be skewed by underestimating or misassigning the placebo effect. But the stakes are enormous; finding medical literature to support a claim that will dramatically boost sales is like striking gold.

Once a condition has been “authenticated,” it’s only a matter of time before Big Pharma steps in with a treatment. Armed with such “objective” fMRI evidence that fibromyalgia is a bona fide condition, Pfizer undertook a series of clinical studies that showed that some patients with fibromyalgia did experience at least partial relief of symptoms with Lyrica. (On a scale of 1 to 10, the fibromyalgia patients achieved an average reduction in symptoms of 2, whereas the controls given placebo had a 1 point reduction.)

As the result of these studies, in 2007, the FDA approved the use of Lyrica for the treatment of fibromyalgia. (Since the approval in 2007, it has been estimated that worldwide sales of Lyrica have increased 30 percent, to well over $2 billion annually.) Without making specific claims about what fibromyalgia is or how Lyrica works, Pfizer, on its Web site, states that “recent research suggests that changes in the central nervous system may be responsible for the chronic pain that comes with fibromyalgia.” It adds that nerve damage may occur because of an infection or injury.

Suggesting that patients with fibromyalgia might have altered or damaged brain cells is based in part on fMRI studies. From there it’s a short commercial step to suggesting that there could be an underlying infection or injury to fibromyalgia, for which there is no convincing evidence to date.

What isn’t mentioned on the Pfizer’s fibromyalgia Web site is that Lyrica has been approved in Europe for the treatment of generalized anxiety. Lyrica was shown to be effective in providing relief of both emotional symptoms, such as depressive symptoms and panic, as well as physical symptoms, including headaches and muscle aches. Yes, another way of thinking about the benefit of Lyrica is that it helps relieve the muscle aches and pains associated with generalized anxiety and that these may be the same aches and pains as described by patients diagnosed with fibromyalgia. (Without objective lab studies, this distinction is impossible to make.)

Now, perhaps a counterargument could be made that the fMRI changes in fibromyalgia are different than those with generalized anxiety. But to make this argument, we would need to have clear-cut and reproducible findings specific to fibromyalgia, and we should know precisely what such specific regional differences mean, from what the brain is doing to how accurately these changes predict both behavior and what the person is experiencing. So far, we have none of the above.

The fMRI is a wonderful, rapidly evolving technology; much of the research is in its infancy and will undoubtedly change as both the machinery and our understanding of the techniques improve. Meanwhile, the follies of bad and excessive interpretations continue to be both well documented and generally overlooked in the popular press. Of these excesses, I can imagine none with more potential for harm than “objectifying” a clinical syndrome without good peer-reviewed additional data.

The primary tenet of medicine is to do no harm. Everyone involved in the study of controversial conditions such as fibromyalgia — physicians, researchers, pharmaceutical companies and the FDA — has a huge moral obligation to be sure that questionable conclusions aren’t foisted on the public as the final word, particularly without a clear understanding of whether such claims have their own adverse side effects. If beliefs change brain function, false beliefs in the mechanism of a condition can have real and lasting adverse effects.

If a patient believes that there is something “wrong with my brain,” the effects can be disastrous. Anyone who has been told of a possible abnormality on a lab test knows how hard it is to shake off that disturbing knowledge even when repeat studies turn out to be normal. If a single lab test result can generate persistent anxiety despite contrary evidence, imagine the degree of negative expectation generated in those with fibromyalgia when they watch the woman in the Pfizer TV ad claim “my fibromyalgia is real.” If negative expectation (the belief that you are more sensitive to pain than others because of a condition that has altered your pain perception) plays a significant role in the production of fibromyalgia symptoms, Pfizer runs the risk of creating or augmenting the very symptoms it is trying to treat. Talk about a vicious feedback loop!

Before jumping to conclusions about diseases and their causes, we need a more comprehensive and philosophical approach to how we integrate new technologies with basic understanding of human nature. We need to look at how thoughts, beliefs and expectations can generate or affect physical symptoms, and vice versa. And we need to abandon concepts like “real” and “all in your head” once and for all.

It’s astounding that a trait normally considered admirable — one usually sought out in choosing personal relationships, colleagues and associates — is now seen as synonymous with being emotional and partisan, as though being empathetic makes one less rational and reasonable. It’s understandable, given the deplorable nature of partisan politics, that conservative critics would come up with a unified denouncement of whomever Obama chooses. But why settle on an argument that flies in the very face of modern cognitive science and the understanding of how our brains function?

At the heart of the misunderstanding are erroneous assumptions that stripping empathy from decision-making will necessarily improve the quality of the decision, and that one has the ability to consciously control his or her feelings of empathy.

Anyone familiar with modern psychology is aware of the concept of emotional intelligence — that good decisions combine reason and awareness of one’s feelings. As many recent popular cognitive science books have pointed out, the vast majority of our thoughts originate outside of awareness. They stem from neural networks that silently combine our basic biological predispositions with past experience, both remembered and long-forgotten. Present at the very origin of our thoughts, and integral to the final shape of each of our decisions, are the various inherent biological traits that make each human unique.

For example, someone who’s prone to taking risks will have a different perspective on any risk-reward decision than someone who is inherently timid. These differences don’t begin as conscious choices; our biology guides our thoughts in these varying directions. Part of this difference is as basic as our DNA, such as a gene for dopamine-receptor activity being strongly correlated with risky behavior.

Studies on empathy reveal a similarly strong biological component. Even at a personal experiential level, we suspect that some people are naturally more empathetic than others. How much empathy can be achieved through parenting and proper education remains an open question. But such efforts are the hallmarks of how civilized people can overcome the barbarism of pure self-interest. The converse, trying to avoid feelings of empathy, hardly seems like a noble goal.

Until the recent criticism of Obama’s mention of what he seeks in a Supreme Court justice, I had never heard of or considered how empathy might impair judgment. After all, sound judgment is based upon considering all possible information that is available, rather than discarding observations or feelings that aren’t strictly “reason-based.” Furthermore, having a feeling doesn’t mean that you must act on it — unless you believe we have no element of free will, not even the veto power over biased thoughts.

The idea that we can cleanse our thoughts of allegedly negative influences arising out of empathy is profoundly misguided. Listen to the argument of Richard Epstein, a legal scholar and professor of law at the University of Chicago. “Empathy matters in running business, charities and churches,” he argues. “But judges perform different functions. They interpret laws and resolve disputes. Rather than targeting his favorite groups, Obama should follow the most time-honored image of justice: the blind goddess, Iustitia, carrying the scales of justice.” Only one who subscribes to the scientifically outdated notion that we can step back from our thoughts in order to judge them, and strip them of unconscious and emotion-laden influences, could come up with such a half-baked idea.

But to play devil’s advocate, what if one could eliminate empathy from decision-making? Exactly how would this improve our thinking on complex moral issues? Consider for a moment Harvard neuroscientist Joshua Greene‘s view of a famous moral philosophy dilemma:

“A runaway trolley is hurtling down the tracks toward five people who will be killed if it proceeds on its present course. You can save these five people by diverting the trolley onto a different set of tracks, one that has only one person on it, but if you do this that person will be killed. Is it morally permissible to turn the trolley and thus prevent five deaths at the cost of one? Most people say “Yes.’”

Now consider a second scenario. “Once again, the trolley is headed for five people. You are standing next to a large man on a footbridge spanning the tracks. The only way to save the five people is to push this man off the footbridge and into the path of the trolley. Is that morally permissible? Most people say “No.’”

Why the difference? Aren’t pulling the switch and pushing the man into the path of the trolley morally equal in terms of saving the maximal number of lives?

According to Greene, “our differing responses to these two dilemmas reflect the operations of at least two distinct psychological/neural systems.” One system “tends to think about both of these problems in utilitarian terms: better to save as many lives as possible.” This system depends on the dorsolateral prefrontal cortex, a part of the brain associated with “cognitive control” and reasoning — a region felt to be “more controlled, perhaps more reasoned, and relatively unemotional.”

But on fMRI, a second anatomically different neural system — the superior temporal sulcus, posterior cingulate and medial frontal gyrus — responds quite differently, generating a relatively strong, negative emotional response to pushing the man off the footbridge dilemma but not to pulling the switch.

Though not exactly a scientific term, this difficulty or revulsion in pushing the man off the footbridge is often referred to as the “ick factor,” a reflection that certain behavior is intrinsically disgusting or revolting, irrespective of whether it is reasonable. For most people, shoving a man to his death “feels like murder,” while pulling an impersonal lever constitutes a “rational decision.” Whether or not this cognitive dissonance is strictly reasonable is irrelevant; this is how humans think.

What Greene’s studies (duplicated by others) suggest is that brain systems involved with moral judgments must balance utilitarian concerns with deeply rooted emotional tendencies. Both modes of thinking arise out of unconscious brain mechanisms that jostle for priority outside of conscious control. It isn’t hard to imagine that one’s degree of personal empathy toward any situation will be a major factor in how these two systems eventually arrive at a decision. Indeed, fMRI studies show that feelings of empathy are activated in the same general regions as the emotional system that prevents you from pushing the man off the bridge.

From a strictly utilitarian perspective, pushing the man off the bridge is the correct decision. By empathizing with the man and deciding that pushing him is the wrong choice, you are condemning five people to death to save one. In those rare real-life circumstances where the moral decision gets down to a black-and-white calculation, it might seem relatively easy to determine what’s best for society. But even here, the decision has wide-reaching implications not apparent in this simple calculation. If we consistently push one man off a bridge to save five innocent people, we will have an entirely different culture from one that balks at the notion of pure utilitarianism at the cost of any innocent lives. Imagine a society in which you knew that you could, at any moment, be sacrificed for a “greater good.”

But few complex decisions have an obvious, easily calculated solution. We cannot know with certainty that a war is just, embryos have “souls,” or whether an unconscious patient wishes to be kept alive. In such situations, we must look to our feelings. All good legal opinions arise out of a balance between deeply rooted moral feelings and conscious deliberations.

Not surprisingly, one group has consistently been shown to have a much higher percentage of willingness to push the man off the footbridge — those with injuries to the emotional decision-making brain centers. Italian researchers have shown that patients with “focal ventral medial prefrontal cortex lesions” were more willing than controls (volunteers with no evidence of any brain injury) to judge personal moral violations as acceptable behaviors, yet on impersonal judgments, they were comparable to controls. In short, they lacked the “ick” feeling that prevented the controls from making morally revolting choices.

Such prefrontal cortical injuries, if acquired early in life and before normal social skills develop, have been correlated with a variety of personality traits that are commonly bundled together under the labels of sociopath or psychopath — lying, stealing, violence, and lack of remorse after committing such violations.

Some cognitive scientists suspect this at least partially explains adult sociopathic behavior. The suggestion is that there is a subtle functional deficit in the circuitry for processing emotions key to making moral decisions. Kent Kiehl, a Yale psychologist investigating the biological roots of psychopathy, has demonstrated that criminals without a sense of remorse differed from criminals with a sense of guilt: The remorseless psychopaths had far less activity in those regions that automatically and quickly process moral emotions. Paul Eslinger, Penn State College of Medicine neurology professor, after uncovering similar results in a group of patients clinically diagnosed as sociopaths, suggests, “‘Snakes in suits’ may have specific neural deficits that preclude social emotional responses.”

Years ago, I had dinner with a highly respected California State Supreme Court Chief justice, an old friend of mine nearing the end of his career. After musing on some of his many difficult decisions, he turned to me and said, “Robert, I have always identified with the underdog and felt that society had an obligation to protect those without a voice. Do you think I was wrong?”

His question still haunts me with its humility and self-reflection. After all his years on the bench, he continued to re-evaluate how his feelings for others impacted his opinions. Indeed, it’s this wise approach to recognizing the limits of pure reason that we want in our justices, not folks with the blind and scientifically unjustifiable belief that they can keep emotions out of their decisions, or that empathy is somehow a dirty word. But then you need a heart to appreciate how empathy is the basis of good law.

Unfortunately, nearly a year has passed and nothing has changed. Last week, I turned to my local PBS station, KQED, and ran headlong into yet another program of medical self-promotion. Mark Hyman, M.D., a family physician, was talking about “brain fog” and “broken minds” and how such “conditions” could be cured or prevented by using “The UltraMind Solution” — a combination of books, DVDs and home questionnaires.

Before I could change the channel, I heard Dr. Hyman make the following comments: “The way we think about disease, mental illness, and our brain aging, actually has nothing, nothing to do with how our body actually works … The way we think about disease is all wrong … the name of the disease tells us nothing about the real reason or the causes of them. Diseases don’t exist.”

Surely this rather unconventional opinion should have caught the attention of those responsible for airing this program on public television. I find it hard to believe that this type of rhetoric can be seen as consistent with mainstream medical wisdom, even by those who are not well versed in science.

If Dr. Hyman is correct, then we should disregard present medical knowledge and research. And yet, to justify his pet theories, Dr. Hyman cherry-picks from the very medical literature that he thinks approaches disease from the wrong perspective. Take, for example, his opinion that “the most remarkable scientific finding of the last decade is that you can have an inflamed, sore and swollen brain.” And from his blog site: “New research proves that almost all brain problems are connected to or caused by inflammation.” Indeed, Dr. Hyman opines that “if you treat the inflammation, the symptoms go away.”

To support this fringe opinion, Dr. Hyman has used what I refer to as a cut-and-paste technique; he takes isolated observations out of context to generate a theory not proven or justified by the findings.

He begins by saying that Martha Herbert, M.D., neurologist at Harvard, “has found that kids with autism have swollen large brains on MRI.” But what Dr. Herbert has written on the National Autism Association Web site is that “children with autism tend to have heads that are larger than normal,” but when “you look at the brains of these children with large heads using an MRI scan, they usually look normal.” Her conclusion: “At the current time, we do not understand the relationship of the large brains to the autism in these children.”

Note to Dr. Hyman: Larger is a measurement of size and isn’t synonymous with swollen.

Equally puzzling is his line of reasoning in assigning inflammation a primary role in diseases as diverse as autism and Alzheimer’s. Dr. Hyman cites the observation of Johns Hopkins neuroscientist Dr. Diana Vargas that there is evidence for “inflammation in the spinal fluid and brains of autistic children.” But in her paper, Dr. Vargas points out that “there has been no direct evidence linking findings in the peripheral blood to immune activity in the brain of autistic patients; the most comprehensive postmortem study reported no inflammatory changes or glial reactions.” (Glial cells are the non-neuronal brain cells that, among other things, protect against pathogens and remove the debris of neurons that have died.) However, with new techniques, Dr. Vargas believes that she has demonstrated glial reactions in the brains of autism sufferers.

Finding such glial cell changes, if confirmed in other laboratories, wouldn’t be particularly surprising. Glial cells respond to all sorts of insults. Dr. Vargas has found similar findings in widely disparate disorders, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis — all diseases for which the underlying causes remain poorly understood, but are associated with destruction of neurons specific to that illness. Perhaps the glial reactions seen by Dr. Vargas are nothing more than a normal response to damaged or dead neurons.

An appropriate analogy would be a bacterial sore throat. The streptococcus organism causes the sore throat; what we see on examination of the throat is inflammation of the underlying tissues. But it wouldn’t make sense to say that the inflammation caused strep throat; rather it would be a response to the strep. In order to blame inflammation as the primary cause, one has to abandon the traditional disease model — the position that Dr. Hyman takes at the start of his program.

Note to Dr. Hyman: Association is not causation.

There is no need for a further line-by-line dissection of Dr. Hyman’s claims. His opinions are clearly controversial both in terms of content and logic, and it doesn’t take a medical degree to spot them. Nor does it take more than a few minutes on the Internet to uncover the discrepancies between Dr. Hyman’s comments and the actual research cited.

My first exposure to public television was in 1955, watching “Science in Action,” a program locally produced by the California Academy of Sciences. Through the years, I have felt that PBS has provided many of the best science programs on television. Science is a method of thought. It’s through good science programs that we learn how to think, including how to properly assess conflicting information. I would hate to see their airtime curtailed because of lack of funding.

But showing dubious science like Dr. Hyman’s “The UltraMind Solution” on pledge nights, as KQED has been doing in past weeks, is to demean viewers’ reasons for watching public television. Apparently PBS’s mission is to raise money by exploiting viewers’ gullibility at the expense of trustworthy programming. If so, it has achieved its goal — and undermined the central reason for having educational TV in the first place.

I suspect we all wonder what, if anything, Madoff feels when directly confronted by those he has utterly destroyed. He cooked the books and perpetually lied to his investors. He pulled off the ongoing deception with an utter insensitivity to others. If shown videos of interviews of his victims, would he wince, laugh or simply shrug dismissively and say, “There’s a sucker born every minute.” For me, a glimpse into Madoff’s brain can shed light on the origins of how we treat each other, and perhaps most important, why we treat each other so poorly.

If there’s any single attribute that separates Madoff from the average Wall Street thief, I’d suggest that it’s his extraordinary ability to read what others think and desire, and especially to know what will give them the greatest satisfaction. (In technical jargon, this ability to read another’s thoughts is referred to as Theory of Mind). 

From a neurological perspective, a prime candidate for how we learn how others think is the mirror neuron system. In turn, it’s been proposed that this ability to read the mind of another makes it possible for us to experience empathy toward others. We know what they’re thinking and feeling and this triggers a similar response in us.

Behavioral neurologist V.S Ramachandran has referred to mirror neurons as “empathy neurons” or “Dalai Lama neurons.” He believes this system, by allowing us to understand the intentions and desires of others, is the principal driving force behind “the great leap forward” in human evolution. As a result of such claims, the mirror neuron system has risen to the level of accepted folk psychology. According to U.C. Berkeley psychologist Alison Gopnik, “Mirror neurons have become the ‘left brain/right brain’ of the 21st century.”

But Madoff’s behavior raises serious questions about the relationship between mirror neurons and empathy — and represents a golden opportunity to study the as yet puzzling connection between them.

Over a decade ago, Italian neurophysiologist Giacomo Rizzolatti and his colleagues studied motor control in macaque monkeys by placing electrodes in the region of a monkey’s pre-motor cortex responsible for hand movements. To their surprise, they noticed that these neurons fired both when a monkey reached for an object and when the monkey observed someone else (other monkeys and researchers) reach for an object such as a peanut or bit of banana.

The resulting interpretation has been that you recognize the intentions of others by equating their action with what you would do under the same circumstances. These neurons mirror the activity of others and allow you to see the world “from the other person’s point of view.” Marco Iacoboni, collaborator with Rizzolatti and author of “Mirroring Others,” has written that this system is capable of automatically assigning intention to another.

(Although it’s not possible to directly isolate and detect mirror neurons in humans, functional studies — both fMRI and transcranial magnetic stimulation — strongly suggest that we possess a similar brain system, primarily in the inferior frontal and inferior parietal regions).

To have played his investors as flawlessly as he did for several decades, I’m tempted to say that Madoff knew his investors’ minds better than they did — presumably good evidence for a well-functioning mirror neuron system. But contrary to Ramachandran’s view that mirror neurons are synonymous with “empathy neurons,” Madoff gets a zero in the empathy department. Just watch Madoff on the news, disdainfully and without any outward appearance of contrition, remorse, guilt or embarrassment, push his way through a crowd of angry onlookers and reporters. Contrast this contempt and disregard for his accusers with his savvy, sophisticated understanding of what his neighbors might expect from him, and we get a sense of the disconnect between understanding the thoughts of others and genuinely sharing their feelings.

Consider this letter that Madoff posted in his apartment building:

Dear neighbors,

Please accept my profound apologies for the terrible inconvenience that I have caused over the past weeks. Ruth and I appreciate the support we have received.

Best regards,

Bernard Madoff

If Madoff’s mirror neuron system appears clinically intact, and mirror neurons are key to the development of empathy, what allowed him to muster the callous indifference to ruin so many friends and associates? The obvious candidate would be something awry in the emotional centers and empathy circuitry that allow each of us to feel another’s pain and suffering.

In general, there appear to be two distinctly different, albeit overlapping, types of empathy: intellectual empathy, or knowing what someone is feeling; and affective empathy, or experiencing the same feeling as the other person. For example, a life insurance salesman and his wife can attend a funeral of her co-worker. The salesman might understand the mourners are grieving, and yet the sight of their weeping doesn’t affect him emotionally; instead he might feel a bit giddy that the mourners would be easy marks for some term insurance policies. His wife, on the other hand, might become overwhelmed with real grief.

One of the best-studied examples of this disconnect between understanding the feelings of others and sharing their feelings is the patient “Elliott,” described by neurologist Antonio Damasio in his book “Descartes’ Error.” Following the removal of a benign brain tumor, Elliot underwent a dramatic personality change. Although his imaging studies showed bilateral damage to his prefrontal cortex, he scored above average on standard intelligence tests, including some designed to detect frontal lobe damage. He responded normally to standard tests of personality, and retained his ability to speak and reason about topics such as politics and economics.

What was strikingly different was his affect. Although he was able to intellectually recognize emotional content, he now was unable to feel these emotions. When shown pictures of gory accidents such as a decapitated car accident victim, or a child drowning, Elliot reported having no emotional response at the same time as he remembered previously having had strong emotional responses to similar photos. His ability to intellectually experience empathy was disconnected from any affective response.

Even the neural substrates of affective empathy aren’t neatly organized; they vary according to what emotion is being experienced. If you see a woman in danger and feel fearful for her, your amygdala — a limbic system structure critical to experiencing fear and trembling — will light up on fMRI. If you witness quarterback Joe Thiesmann’s leg being broken on Monday Night Football, the anterior mid-cingulate cortex and the anterior insula — two regions that process pain perception — will go into overdrive.

But do we really need to have prior similar experiences to empathize with others? This is the fundamental argument underlying the theory that the mirror neuron system, by providing the ability to read the thoughts and feelings of others, is essential for empathy.

In a January 2009 study, French neuroscientist Nicolas Danziger wanted to see whether a person could empathize with an unfamiliar emotional state. He studied a group of patients with congenital insensitivity to pain — a rare condition present at birth and related to genetic changes in sensory nerves. Such patients have never felt physical pain sensations and have no idea what pain feels like. Interested in seeing how these patients would respond to seeing others in pain, Danziger showed them photos of a person getting her finger caught in gardening shears and a video clip of Theismann’s leg being broken.

Surprisingly, some of the pain-insensitive patients responded on fMRI similarly to normal controls — their pain perception regions lit up. Others had the anticipated lack of response. The difference between the two groups correlated with the degree of empathy that was elicited on a standard empathy assessment questionnaire. The authors concluded that those patients who responded had the “empathy trait.”

If this study pans out and can be duplicated under a variety of similar circumstances, the inference is profound: Each of us is wired differently for feeling the pain and suffering of others, irrespective of our past personal experience.

So is empathy an inborn trait?

One piece of evidence comes from observations on the Autism Spectrum Disorder. Thought to have a strong genetic predisposition, patients with autism and Asperger’s syndrome commonly are unable to grasp what others are thinking and feeling. Listen to this mother of a toddler with Asperger’s syndrome describe his reactions to his 8-month old brother crying whenever he fell down, bumped his head or pinched a finger. “My son asked me the most puzzling questions such as ‘Why is that baby crying?’ ‘Why is he doing that?’ and, my favorite, ‘Can’t we take that noisy baby back to the store and get a new one?’” If genes play a significant role in the Autistic Spectrum patient’s lack of empathy, it stands to reason that there might be a similar genetic contribution to the experience of empathy in all of us.

Further support comes from studies on antisocial behavior, both in young children and in adult “psychopaths.” (I’m using the unfortunately biased term “psychopath” to denote folks with chronic antisocial behavior who lack remorse for their actions, as opposed to antisocial behavior in which remorse and guilt are present.)

Looking at 3,600 pairs of 7-year-old twins, the British Twins Early Development Study found antisocial behavior in 7-year-olds generally fell into two categories: those with normal degrees of empathy and those described as callous and lacking in empathy. The former group was felt to be primarily environmentally mediated (learned behavior), whereas those lacking in empathy demonstrated that their antisocial behavior (primarily bullying and conduct disorders) strongly ran in families. In a subsequent fMRI study, this non-empathic group was shown to have decreased activation of the amygdala in response to looking at fearful faces. In other words, those who lack proper emotional responses to negative stimuli are more likely to have genetic underpinnings to their disorder.

Perhaps the most compelling predictive data supporting the “bad seed” hypothesis is a 25-year study showing that, as early as the age of 3, there are temperamental and physiological difference between those who show psychopathic tendencies as adults and those who don’t. In the early ’70s, 1,800 3-year-olds were observed and rated on several psychological scales, including their degree of fearfulness and inhibition. Twenty-five years later they were reexamined. Those with the higher psychopathy rating scores were found to be significantly less fearful and inhibited and more glib, charming and manipulative.

The authors concluded that children with a low level of fearfulness may be more likely to develop antisocial personality as adults. I’m always leery about accepting purely questionnaire-based studies at face value, but being able to predict the bad seeds at age 3 is hard to entirely ignore.

Although it’s painfully obvious that we don’t know what makes Madoff tick, it is hard not to speculate. If there is such a thing as empathy deficiency, Madoff would be its poster child. Perhaps this was a trait that he shares with his mother, Sylvia Madoff, who was registered as a broker, but in the 1960s was forced to close shop as part of an agreement with the Securities and Exchange Commission not to further investigate her brokerage. (I know it’s impossible with our present state of knowledge to sort out nature from nurture, but the above studies on empathy certainly suggest the possibility of there being a primary biological contribution.)

Even if true, a genetic predisposition for lack of empathy cannot possibly excuse Madoff’s behavior. We all have genetic predispositions for various personality traits — it is our struggle against baser biologic urges that distinguishes us from the rest of the animal kingdom. Deferring to biology as explanation or excuse for a behavior is to abandon all notions of what it means to be human.

Madoff can’t repay his victims, but we can learn from him. That’s why he should be forced to participate in medical studies as part of his sentence. The best cognitive scientists, philosophers, geneticists and sociologists should be allowed to administer to him whatever non-invasive and ethically appropriate clinical studies they can dream up. See if any pattern emerges that is sufficiently reliable to qualify as predictive. Even if our present knowledge is insufficient to draw conclusions, Madoff would make a great set of data points. Perhaps one day he can give something back to society by teaching us about human empathy, and its limitations.

Add the growing number of kids playing soccer, hockey, lacrosse and extreme sports, and the concussion rate is staggering. But youth is about taking risks and proving oneself, not about trying to avoid life. Being KO’d or having your bell rung is a rite of passage, proof that you can take whatever is dished out. Parents be damned; let the games begin.

A timeout may in order, however. In the past few years, long-term studies suggest that seemingly uncomplicated concussions, like those sustained in high school sports, may put an athlete at increased risk for Alzheimer’s disease. Is this a real and well-established association, or just scare mongering?

A concussion — often referred to as a mild traumatic brain injury — is generally defined as a blow to the head followed by transient alterations in mental state ranging from confusion, disorientation and short-term memory defects to an actual loss of consciousness of less than 30 minutes in duration. Traditionally, concussion is divided into degrees of severity based on the duration of posttraumatic amnesia: the failure to accurately recall events that occur subsequent to the head injury. It’s generally accepted that a mild concussion results in less than 30 minutes of amnesia, a moderate concussion causes 30 minutes to 24 hours of amnesia, while with a severe concussion, the amnesia persists for greater than 24 hours.

Fortunately, the vast majority of minor concussions clinically resolve themselves within a short time, ranging from a few minutes to a few days to a week. Follow-up neuropsychological testing rarely demonstrates any residual cognitive problems in otherwise healthy young athletes. As a result, minor concussions have been considered self-limiting and without any significant long-term risk. Until now.

Perhaps the best place to begin is with a systematic review of the medical records of a group of 548 veterans who sustained a moderate or severe concussion during World War II. Over the subsequent 40 years, the incidence of Alzheimer’s disease in the moderate concussion group was twice the rate in those soldiers without a prior head injury. Those with a severe concussion had a risk four times that of the control group. The effect of minor concussion was not adequately assessed in this study.

In 2003, an editorial in the Journal of Neurology, Neurosurgery, and Psychiatry opined that, at least in males, the risk of Alzheimer’s in patients with mild traumatic brain injury was sufficient to advise head-injured patients of the risk of further injuries.

In 2005, scientists at the National Center for Catastrophic Sports Injury tested more than 2,500 retired professional football players. Those with three or more concussions were five times as likely to have cognitive declines classified as mild cognitive impairment, and three times as likely to have significant memory problems as retirees without a history of concussion. Although the researchers didn’t find a definite association between recurrent concussion and Alzheimer’s disease, keep in mind that the majority of patients with mild cognitive impairment eventually progress to full-blown Alzheimer’s. As tentative supporting evidence, the researchers observed an earlier onset of Alzheimer’s in the retirees than in the general American male population.

Again, these findings were seen in athletes with a minimum of three concussions; one or two concussions did not have any clearly increased risk of subsequent cognitive impairment.

How brain injuries might predispose someone to Alzheimer’s disease remains conjectural. It’s clear that significant forces are required for a concussion. An ongoing study at the University of North Carolina found that the impact magnitude of hits delivered by youth hockey players aged 13 to 15 was similar to that experienced by college football players. The average head impact among the youth hockey players was around 20 Gs, but some surpassed 100 Gs — the forces sustained by a car-crash dummy when a car traveling at 25 mph smashes into a brick wall.

Animal studies show that at a cellular level, brain injuries cause metabolic changes that range from the quickly reversible to the release of chemicals that are toxic to neurons. Some animal studies have shown that such toxic effects can include the production and deposition of beta amyloid plaques, a central feature of the pathology of Alzheimer’s disease.

One Alzheimer’s disease researcher, Daniel Laskowitz, an associate professor of medicine and the director of the Neurovascular Laboratories at Duke University Medical Center, suspects that this amyloid deposition can trigger an inflammatory response, which in turn leads to further neuronal injury and cell death. Such a process might explain the long lag time between the initial injury and the later-life development of dementia.

Another possibility is that mild traumatic brain injury causes some degree of neuronal loss that is tolerated in young people. This relative depletion of neurons, though, might leave one with less brain “reserve” in older age.

On the other hand, several excellent studies have failed to demonstrate an association between minor concussions and Alzheimer’s. After more than 20 years of research, there isn’t a true consensus of opinion. The problem, in large part, stems from the methodology of assessing head injuries.

To begin with, imagine the inherent difficulties of doing a good neurological examination during the middle of a close, hard-fought football game. By necessity, evaluations tend to be brief and rudimentary. Over the roar of the crowd, team trainers or physicians without adequate neurological training make complex mental health assessments. Even in the NFL, where all 32 teams use sophisticated neurocognitive testing to evaluate the severity of a concussion, the evaluations are considered imperfect. A further limitation is the hard reality that, by definition, an uncomplicated concussion manifests no specific objective neurological findings on brain scans.

A second problem is that self-reporting from athletes is notoriously unreliable: They lack awareness of the significant symptoms of a concussion and fear that reporting a head injury may sideline them. In a postseason survey, more than 50 percent of high school football players failed to report documented concussions; 70 percent of those who did report experiencing symptoms of a concussion denied any specific history of concussion on pre-participation exams.

Ultimately, good medical advice boils down to opinions based on the best available medical data. Evidence-based medicine is far superior to individual experience and gut feelings. But there is often a long lag time between suspicion and definitive proof.

Take the issue of cholesterol and coronary artery disease. Although it was known in the 1960s that elevated cholesterol was associated with coronary artery disease, it took another couple of decades to acquire hard data that elevated cholesterol contributes to coronary artery disease and that it is a modifiable risk factor. During this extended period between suspicion and proof, many physicians, out of a combination of doubt and inherent conservatism, downplayed or completely ignored the possibility that lowering an elevated cholesterol might also reduce the incidence of coronary artery disease. Retrospectively, it is hard to calculate how many lives were adversely affected.

To put this argument into a practical perspective, consider what happens to your brain in ordinary childhood. In a population-based study of 1.3 million children and adolescents attending school in Ontario, the cumulative incidence of concussion over their entire 12 years of primary and secondary schooling was less than 2 percent in males and less than 1 percent in females. By contrast, in a given football season, 10 percent of all college and 20 percent of high school players sustain a mild traumatic brain injury. The same incidence has been shown in high school soccer.

Of even greater significance is the fact that players who sustained one concussion in a season were three times as likely to sustain a second concussion in the same season as uninjured players. It’s a downward spiral: Concussions beget concussions. (Remember Roger Staubach?) If you play long enough, odds are high that you will sustain at least one concussion. In a study of soccer players, the 10-year incidence of sustaining at least one concussion was greater than 50 percent.

The American Academy of Neurology has issued fairly stringent guidelines for the management of sports-related head injuries. For the most severe concussion, it recommends that the player be withheld from sports for at least two weeks. If the athlete sustains a second concussion, he is withheld from sports until he is asymptomatic for at least a month or longer. But the guidelines are primarily concerned with immediate cognitive deficits that arise from the actual head injury; they are not designed to specifically address the possibility of long-term risks like Alzheimer’s disease.

Whether or not to play contact sports, especially after having sustained one or more concussions, isn’t an easy decision. There are no right answers. In the end, it boils down to athletes using their heads off the field to determine what using their heads on the field might cost them.