that persists or recurs over long or indefinite periods, such as might accompany a bone fracture in the hand. Although the two feel the same (painful), they have different biological functions and different evolutionary origins. Acute pain causes you to instantly remove your hand from the stove to prevent further tissue damage. Chronic pain motivates you to keep your fractured hand immobilized to prevent reinjury while it heals.
I began to wonder: If learned paralysis could explain immobilized phantoms, perhaps CRPS-II is a form of “learned pain.” Imagine a patient with a fractured hand. Imagine how, during his long convalescence, pain shoots through his hand every time he moves it. His brain is seeing a constant “if A then B” pattern of events, where A is movement and B is pain. Thus the synapses between the various neurons that represent these two events are strengthened daily—for months on end. Eventually the very attempt to move the hand elicits excruciating pain. This pain may even spread to the arm, causing it to freeze up. In some such cases, the arm not only develops paralysis but actually becomes swollen and inflamed, and in the case of Sudek’s atrophy the bone may even start atrophying. All of this can be seen as a strange manifestation of mind-body interactions gone horribly awry.
At the “Decade of the Brain” symposium that I organized at the University of California, San Diego, in October 1996, I suggested that the mirror box might help alleviate learned pain in the same way that it affects phantom pain. The patient could try moving her limbs in synchrony while looking in the mirror, creating the illusion that the afflicted arm is moving freely, with no pain being evoked. Watching this repeatedly may lead to an “unlearning” of learned pain. A few years later the mirror box was tested by two research groups and found to be effective in treating CRPS-II in a majority of patients. Both studies were conducted double-blind using placebo controls. To be honest I was quite surprised. Since that time, two other double-blind randomized studies have confirmed the striking effectiveness of the procedure. (There is a variant of CRPS-II seen in 15 percent of stroke victims, and the mirror is effective in them as well.)
I’ll mention one last observation on phantom limbs that is even more remarkable than the cases mentioned so far. I used the conventional mirror box but added a novel twist. I had the patient, Chuck, looking at the reflection of his intact limb so as to optically resurrect the phantom as before. But this time, instead of asking him to move his arm, I asked him to hold it steady while I put a minifying (image-shrinking) concave lens between his line of sight and the mirror reflection. From Chuck’s point of view, his phantom now appeared to be about one-half or one-third its “real” size.
Chuck looked surprised and said, “It’s amazing, Doctor. My phantom not only looks small but feels small as well. And guess what—the pain has shrunk too! Down to about one-fourth the intensity it was before.”
This raises the intriguing question of whether even real pain in a real arm evoked with a pinprick would also be diminished by optically shrinking the pin and the arm. In several of the experiments I just described, we saw just how potent a factor vision (or its lack) can be in influencing phantom pain and motor paralysis. If this sort of optically mediated anesthesia could be shown to work on an intact hand, it would be another astonishing example of mind-body interaction.
IT IS FAIR to say that these discoveries—together with the pioneering animal studies of Mike Merzenich and John Kaas and some ingenious clinical work by Leonardo Cohen and Paul Bach y Rita—ushered in a whole new era in neurology, and in neurorehabilitation especially. They led to a radical shift in the way we think about the brain. The old view, which prevailed through the 1980s, was that the brain consists of many specialized modules that are hardwired from birth to perform specific jobs. (The box-and-arrow diagrams of brain connectivity in anatomy textbooks have fostered this highly misleading picture in the minds of generations of medical students. Even today, some textbooks continue to represent this “pre-Copernican” view.)
But starting in the 1990s, this static view of the brain was steadily supplanted by a much more dynamic picture. The brain’s so-called modules don’t do their jobs in isolation; there is a great deal of back-and-forth interaction between them, far more than previously suspected. Changes in the operation of one module—say, from damage, or from maturation, or from learning and life experience—can lead to significant changes in the operations of many other modules to which it is connected. To a surprising extent, one module can even take over the functions of another. Far from being wired up according to rigid, prenatal genetic blueprints, the brain’s wiring is highly malleable—and not just in infants and young children, but throughout every adult lifetime. As we have seen, even the basic “touch” map in the brain can be modified over relatively large distances, and a phantom can be “amputated” with a mirror. We can now say with confidence that the brain is an extraordinarily plastic biological system that is in a state of dynamic equilibrium with the external world. Even its basic connections are being constantly updated in response to changing sensory demands. And if you take mirror neurons into account, then we can infer that your brain is also in synch with other brains—analogous to a global Internet of Facebook pals constantly modifying and enriching each other.
As remarkable as this paradigm shift was, and leaving aside its vast clinical importance, you may be wondering at this point what these tales of phantom limbs and plastic brains have to do with human uniqueness. Is lifelong plasticity a distinctly human trait? In fact, it is not. Don’t lower primates get phantom limbs? Yes, they do. Don’t their cortical limb and face representations remap following amputation? Definitely. So what does plasticity tell us about our uniqueness?
The answer is that lifelong plasticity (not just genes) is one of the central players in the evolution of human uniqueness. Through natural selection our brains evolved the ability to exploit learning and culture to drive our mental phase transitions. We might as well call ourselves
INCIDENTALLY, EVEN THOUGH I was never able to directly study Mikhey—the patient I met as a medical student who laughed when she should have yelped in pain—I never stopped pondering her case. Mikhey’s laughter raises an interesting question: Why does anybody laugh at anything? Laughter—and its cognitive companion, humor—is a universal trait present in all cultures. Some apes are known to “laugh” when tickled, but I doubt if they would laugh upon seeing a portly ape slip on a banana peel and fall on his arse. Jane Goodall certainly has never reported anything about chimpanzees performing pantomime skits for each other a la the Three Stooges or the Keystone Kops. Why and how humor evolved in us is a mystery, but Mikhey’s predicament gave me a clue.
Any joke or humorous incident has the following form. You narrate a story step-by-step, leading your listener along a garden path of expectation, and then you introduce an unexpected twist, a punch line, the comprehension of which requires a complete reinterpretation of the preceding events. But that’s not enough: No scientist whose theoretical edifice is demolished by a single ugly fact entailing a complete overhaul is likely to find it amusing. (Believe me, I’ve tried!) Deflation of expectation is necessary but not sufficient. The extra key ingredient is that the new interpretation must be inconsequential. Let me illustrate. The dean of the medical school starts walking along a path, but before reaching his destination he slips on a banana peel and falls. If his skull is fractured and blood starts gushing out, you rush to his aid and call the ambulance. You don’t laugh. But if he gets up unhurt, wiping the banana off his expensive trousers, you break out into a fit of laughter. It’s called slapstick. The key difference is that in the first case, there is a true alarm requiring urgent attention. In the second case it’s a
