By Melanie Thernstrom | The New York Times | May 14, 2006
Who hasn’t wished she could watch her brain at work and make changes to it, the way a painter steps back from a painting, studies it and decides to make the sky a different hue? If only we could spell-check our brain like a text, or reprogram it like a computer to eliminate glitches like pain, depression and learning disabilities. Would we one day become completely transparent to ourselves, and — fully conscious of consciousness — consciously create ourselves as we like?
The glitch I’d like to program out of my brain is chronic pain. For the past 10 years, I have been suffering from an arthritic condition that causes chronic pain in my neck that radiates into the right side of my face and right shoulder and arm. Sometimes I picture the pain — soggy, moldy, dark or perhaps ashy, like those alarming pictures of smokers’ lungs. Wherever the pain is located, it must look awful by now, after a decade of dominating my brain. I’d like to replace my forehead with a Plexiglas window, set up a camera and film my brain and (since this is my brain, I’m the director) redirect it. Cut. Those areas that are generating pain — cool it. Those areas that are supposed to be alleviating pain — hello? I need you! Down-regulate pain-perception circuitry, as scientists say. Up-regulate pain-modulation circuitry. Now.
Recently, I had a glimpse of what that reprogramming would look like. I was lying on my back in a large white plastic f.M.R.I. machine that uses ingenious new software, peering up through 3-D goggles at a small screen. I was experiencing a clinical demonstration of a new technology — real-time functional neuroimaging — used in a Stanford University study, now in its second phase, that allows subjects to see their own brain activity while feeling pain and to try to change that brain activity to control their pain.
Over six sessions, volunteers are being asked to try to increase and decrease their pain while watching the activation of a part of their brain involved in pain perception and modulation. This real-time imaging lets them assess how well they are succeeding. Dr. Sean Mackey, the study’s senior investigator and the director of the Neuroimaging and Pain Lab at Stanford, explained that the results of the study’s first phase, which were recently published in the prestigious Proceedings of the National Academy of Sciences, showed that while looking at the brain, subjects can learn to control its activation in a way that regulates their pain. While this may be likened to biofeedback, traditional biofeedback provides indirect measures of brain activity through information about heart rate, skin temperature and other autonomic functions, or even EEG waves. Mackey’s approach allows subjects to interact with the brain itself.
“It is the mind-body problem — right there on the screen,” one of Mackey’s collaborators, Christopher deCharms, a neurophysiologist and a principal investigator of the study, told me later. “We are doing something that people have wanted to do for thousands of years. Descartes said, ‘I think, therefore I am.’ Now we’re watching that process as it unfolds.”
Suddenly, the machine made a deep rattling sound, and an image flickered before me: my brain. I am looking at my own brain, as it thinks my own thoughts, including these thoughts.
How does it work? I want to ask. Just as people were once puzzled by Freud’s talking cure (how does describing problems solve them?), the Stanford study makes us wonder: How can one part of our brain control another by looking at it? Who is the “me” controlling my brain, then? It seems to deepen the mind-body problem, widening the old Cartesian divide by splitting the self into subject and agent.
But most of all I want to know: Will I be able to learn it?
For most of history, the idea of watching the mind at work was as fantastical as documenting a ghost. You could break into the haunted house — slice the brain open — but all you would find would be the house itself, the brain’s architecture, not its invisible occupant. Photographing it with X-rays resulted only in pictures of the shell of the house, the skull. The invention of the CT scan and magnetic resonance imaging (M.R.I.) were great advances because they reveal tissue as well as bones — the wallpaper as well as the walls — but the ghost still didn’t show up. Consciousness remained elusive.
A newer form of M.R.I., functional magnetic resonance imaging (f.M.R.I.), used with increasingly sophisticated software, is accomplishing this, taking “movies” of brain activity. Researchers are able to watch the brain work, as the films show parts of the brain becoming active under various stimuli by detecting areas of increased blood flow connected with the faster firing of nerve cells. These films are difficult to read; researchers puzzle over the new images like Columbus staring at the gray shoreline, thinking, India? Most of the brain is uncharted, the nature of the terrain unclear. But the voyage has been made; the technology exists. Pain — a complex perception occupying the elusive space spanning sensation, emotion and cognition — is a particularly promising area of imaging research because, researchers say, it has the potential to make great progress in a short time.
Perhaps more than any other aspect of human existence, persistent pain is experienced as something we cannot control but desperately wish we could. Acute pain serves the evolutionary function of warning us of tissue damage, but chronic pain does nothing except undo us. Pain is the primary complaint that sends people to the doctor. Of the 50-odd million sufferers in the United States, half cannot get adequate relief from their chronic pain. Many do not even have a diagnosis.
Unlike acute pain, chronic pain is now thought to be a disease of the central nervous system that may or may not correlate with any tissue damage but involves an errant reprogramming in the brain and spinal cord. The brain can generate terrible pain in a wound that is long healed, in a body that is numb and paralyzed or — in the case of phantom-limb pain — in a limb that no longer even exists.
Although there have been many theories about how pain works in the brain, it is only through neuroimaging that the process has actually been observed. It is now clear that there is no single pain center in the brain. Rather, pain is a complex, adaptive network involving 5 to 10 areas of the brain transmitting information back and forth.
This network has two pain systems: pain perception and pain modulation, which involve both overlapping and distinct brain structures. The pain-modulatory system constantly interacts with the pain-perception system, inhibiting its activity. Much chronic pain is thought to involve either an overactive pain-perception circuit or an underactive pain-modulation circuit.
Like everyone who suffers from chronic pain, I find it hard to believe that I have a pain-modulation circuit. The aspect of my pain I feel most certain about is that it is not voluntary: I cannot modulate it. And this belief is reinforced every single day that I suffer from pain, which is every day. Yet I know that pain is not a fact, like a broken bone; it’s a perception, like hunger, about a physical state (“an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage,” as the International Association for the Study of Pain defines it). And it’s a mercurial perception; under certain circumstances the pain-modulatory system works like a spell and the brain completely blocks out pain.
Soldiers, athletes, martyrs and pilgrims engage in battles, athletic feats or acts of devotion without being distracted by the pain of injuries. When the teenage surfer Bethany Hamilton’s arm was bitten off by a shark, she felt pressure, but “I didn’t feel any pain — I’m really lucky, because if I felt pain, things might not have gone as well,” she said (articulating one reason the modulatory system evolved: if she had thrashed about in pain, she would have bled until she drowned).
In addition to being activated by stress, the pain-modulatory system is triggered by belief. The brain will shut down pain if it believes it has been given pain relief, even when it hasn’t (the placebo effect), and it will augment pain if it believes you are being hurt, even if you aren’t (the nocebo effect). The brain’s modulatory system relies on endogenous endorphins, its own opiatelike substances. The nature of a placebo has long been a source of speculation and debate, but neuroimaging studies have shown the way a placebo actually helps to activate the pain-modulatory system.
In a recently published study led by Dr. Jon-Kar Zubieta at the University of Michigan Medical School, the brains of 14 men were imaged after a stinging saltwater solution was injected into their jaws. They were then each given a placebo and told that it would positively relieve their pain. The men immediately felt better — and the screen showed how. Parts of the brain that release endogenous opiates lighted up. In other words, fake opiates caused the brain to dispense real ones. Like some New Age dictum, philosophy becomes chemistry; believing becomes reality; the mind unites with the body.
Other studies have shown that opiates and other medications rely on a placebo to achieve part of their effect. When subjects are covertly given strong opiates like morphine, they don’t work nearly as well as they do if the subjects are told they are being given a powerful pain reliever. Even real medications require some of the brain’s own bounty.
Conversely, thinking about pain creates pain. In studies at Oxford University, Irene Tracey has shown that asking subjects to think about their chronic pain, for example, increases activation in their pain-perception circuits. Distraction, on the other hand, is a great analgesic; when Tracey’s volunteers were asked to engage in a complicated counting task while being subjected to a painful heat stimulus, she could watch the pain-perception matrix decrease while cognitive parts of the brain involved in counting lighted up. At McGill University, Catherine Bushnell has shown that simply listening to tones while being subjected to a heat stimulus decreased activity in the pain-perception circuit. +++
“There is an interesting irony to pain,” comments Christopher deCharms, who worked with Mackey designing and carrying out the Stanford study. We were talking in his office at Omneuron, a Menlo Park medical-technology company he founded three years ago to develop clinical applications of neuroimaging. “Everyone is born with a system designed to turn off pain. There isn’t an obvious mechanism to turn off other diseases like Parkinson’s. With pain, the system is there, but we don’t have control over the dial.”
The goal of the Stanford technique is to teach people to control their dials — to activate their modulatory systems without requiring the extreme stress of fleeing from a shark or the deception of a placebo. The hope of neuroimaging therapy (as deCharms calls the Stanford technique) is that repeated practice will strengthen and eventually change the ineffective modulatory system to eliminate chronic pain, the way long-term physical therapy can change muscular weakness. The scan would thus be more than a research tool:the scan itself would be the treatment, and the subject his or her own researcher.
Only once do I recall having a glimmer of my own pain-modulatory system at work: a hidden power that emerged, dispensed with pain and then returned to some forgotten fold in my brain, where I have never been able to locate it again. The event did not take place on a battlefield or a marathon course or in a temple; it was in a basement of the Stanford University medical center three years ago. At the time, Mackey had designed an earlier study that did not use imaging technology but focused on how suggestion alters pain perception. Although I was not formally enrolled in the study, I asked if I could undergo a clinical demonstration. My experience illustrated the power of suggestion in an unexpected fashion.
A metal probe attached to the underbelly of my arm heated up and cooled down at set intervals. I was told that although the heat probe would feel uncomfortable, my skin would not be burned. During one exposure, I was instructed to think of the pain as positively as possible, during another to think of it as negatively. After each sequence, I was asked to rate my pain on a 0-to-10 scale, with 10 being the worst pain I could imagine.
Although I discovered that I could make the pain fluctuate depending on whether I was imagining that I was sunbathing or was the victim of an inquisition, I still rated all the pain as low — ranging from a 1 to a 3. If 10 was being slowly burned alive, I felt I should at least be begging for mercy to justify a rating of 5. So I insisted that Mackey turn up the dial so I could get a real response. But even during the moments when I was actively trying to imagine the pain as negatively as possible, it remained in a mental box of “not even burned,” which kept it from really hurting: hurting, that is, the way a burn would.
As it turned out, I got a second-degree burn that later darkened into a square mark. Mackey was more than a little dismayed as we watched the reddening skin pucker, but I was thrilled. Naturally the protocol had been carefully designed not to injure anyone, yet in my case that protection had failed because of the very phenomenon it was designed to study: expectation — the effect of the mind on pain or placebo.
I had recently spent several weeks observing Mackey in the university’s pain clinic, where he is associate director. I was so convinced that Mackey — then a tall sandy-haired 39-year-old with a deep interest in technology (he got a Ph.D. in electrical engineering before he went to medical school) and an air of radiant integrity — would not burn me that my brain had not perceived the stimulus as a threat and generated pain. I admired him, I trusted him, I was positive that he wouldn’t hurt me. And, ipso facto, he hadn’t.
Mackey’s genius as a practitioner, I thought, lay partly in his ability to similarly inspire patients. “When I started working with pain patients, I realized how much of the treatment involved trying to reverse learned helplessness,” he said — to rally them out of the despair ingrained from years of unremitting pain and cajole their minds to chip in its own analgesic to their therapies. “The purpose of this study is to show patients their mind matters,” Mackey said.
The mark of the burn is barely visible now, but for a couple of years afterward, at times when my chronic pain was making me miserable, the sight of it would both encourage and reproach me. Here is the ultimate proof that my mind can control pain, I would think, yet I didn’t know how to make it wake up and do so. I could take the edge off the pain by conjuring positive images, but the effects didn’t last, and I never again had the remarkable placebo response that masked a second-degree burn. In fact, a mild burn from spilling tea on my hand one day brought tears to my eyes.
When the real-time neuroimaging study began, I couldn’t wait to try it.