Transcranial Magnetic Stimulation

Ravi Rajakumar, Rat-Trap (detail), 2000. Courtesy of the artist.

Just remember what a stir it made when the Stethoscope was introduced. Soon we shall have reached the point where every barber will use it and, when shaving you, will ask: Would you like to be stethoscoped, Sir? Then someone else will invent an instrument for listening to the beats of the brain. That will make a tremendous stir until, in fifty years, every barber can do it. Then in a barbershop, when one has had a haircut and a shave and has been stethoscoped (for by then it will be very common) the barber will ask: Perhaps you would also like me to listen to your brain beats?

—Søren Kierkegaard, 1846

In December of 2001, in a small, paper-crowded office on the third floor of the Beth Israel Deaconess Medical Center, in Boston, Alvaro Pascual-Leone, an associate professor of neurology at Harvard University, showed me a video in which a colleague used a small paddle made of coiled wires to stop a man from speaking. The man, who appeared to be in his mid-sixties, was seated in a chair in a hospital laboratory. Poised above the left side of his head, just above the temple, was a circular device that looked like a thin rubber donut attached to wires. A voice from offscreen instructed the man to read a series of words off of a piece of paper, and he began. For several seconds, the man spoke normally. Then, again offscreen, a technician pressed a button, and there was a sharp electric crack. Suddenly, the man went mute. His tongue protruded from his mouth, his face contorted, and he could be seen struggling to get words out. No matter how hard he tried, though, he was silent, save for a few dim grunting noises. When the device was finally shut off, after several seconds, the man looked up with a bemused expression on his face, as if to say, “Well, that was odd.”

The technology the researcher had used to perform this experiment, and in which Pascual-Leone is a leading expert, is called Transcranial Magnetic Stimulation. It is among the less well-known neurological tools to have emerged from the neuroscientific revolution, developed as it was on the periphery of that movement, in a physiology lab in Sheffield, England. TMS works according to the centuries-old principle of electromagnetic induction, in which an alternating magnetic field is used to produce an electrical current in a conductor—in this case, in the neurons of the human cortex. TMS was invented in 1985, but it is only recently, in the past five years or so, that its applications have advanced to the point that it has come to garner some real attention in both the scientific and the general press. It was that attention that had drawn me to Pascual-Leone. But, more important, it was that attention that had drawn him to me, for although Pascual-Leone is among the more prominent researchers of TMS, he is also concerned about it as a potential source or symbol of abuse.

“Let’s say you have these guys in these airplanes trying to detect enemy fighter pilots,” he said. He was referring to a study that showed that TMS, by directly interfering with an area in one hemisphere of the brain, could improve vision in the related eye, on the opposite side of the body. “So if you have one guy on the right side and one guy on the left side with a TMS machine on the parietal lobe improving attention to their side of space, that would be super! They’d kill much more. But is this an OK thing to test? Is it an OK thing to apply?”

He proposed another scenario: “You have all this work on false memories. You have all the work on making up stories. And so you can easily envision experiments aimed at trying to find out—it may not work, but still—trying to find out if you could block a certain area of a circuit and make people unable to lie. Is that the kind of experiment that would be appropriate?”

And another: “Can you target the drive for sex in your son, so when he goes out on a date with his girlfriend he won’t embarrass you?”

Pascual-Leone had chosen to make me the recipient of these scenarios because I had a commission from a national magazine to write about TMS and neurotechnology, and I was therefore well placed to coax any theoretical questions about the applications of TMS into the public sphere. But I had become intrigued by TMS for other reasons. First, it was beginning to show great potential as a research tool. Brain research has traditionally been done on subjects with damage to a specific area of the brain; the trouble is there aren’t enough brain-damaged patients to go around, and the lesion in the patient’s brain might be too big, surpassing the area of interest, or there might be more than one lesion. Most frustrating, by the time the researchers get to them, the subjects’ brains have almost always had time to reorganize in response to the damage, rendering any results inaccurate. TMS has the ability to create “virtual lesions”—temporarily dead areas—and can therefore create “virtual patients” for the purposes of wide-scale testing of normal subjects.

The second reason I was interested in TMS was more personal. I wanted Pascual-Leone to zap me with the thing. I wanted to be a subject. During our meeting I made this request.

“Can I be zapped?” I said.

“No, I’m afraid not.”

“Please? Can’t you apply speech arrest?” Speech arrest was what the video he had shown me earlier exhibited, and it is TMS’s most dramatic effect.

“No. I can just show you videos. I really don’t think we should trivialize this technique. With speech arrest there’s a lot of useful utility in understanding language. But it’s not show-and-tell.”

“I know that,” I said. “But I want to be zapped.”

In 1964, in a bullfighting ring in Cordova, Spain, the psychologist Jose Delgado confronted a bull in whose brain he had implanted an electrode with a receiver. Holding a red cape in one hand and a remote control in the other, Delgado goaded the bull to charge. It did, but when it was only a few feet away from goring him, Delgado pressed a button. The bull stopped suddenly in its tracks. Delgado had, through electrical control, stifled the innate aggressiveness of the bull.

He was clearly pleased. In Physical Control of the Mind: Toward a Psychocivilized Society, the creepily titled book Delgado published five years later—and toward which Pascual-Leone directed me as a primer on the threats that neurotechnology posed—he argued that electrical stimulation of the brain could and should be used to influence behavior in human beings. The concept of free will, he wrote, is a fallacy—the mind cannot conquer the body because it is the body. And the body is hardwired. “The role of the will,” Delgado wrote, “is mainly to trigger previously established mechanisms” (his italics). It is foolish, therefore, to combat social ills by political, sociological, religious, or psychological means when all behavior is the result of intracerebral function.

Delgado’s experiment and opinions are remembered only dimly by those outside of the psychological sciences, but they have helped to fuel forty years of dystopian neurological fantasies. Increasingly, popular discussions about the future of neurotechnology have also taken on a particularly Delgadoian tenor. And possibly for good reason. Recently, the Defense Advanced Research Project Agency (DARPA), the research and development arm of the Department of Defense, granted the Brain Stimulation Laboratory at the Medical University of South Carolina, a leading site for TMS research, a $2 million contract (title: “Creating a Man-portable Transcranial Magnetic Stimulation System to Improve War-fighter Performance”) to develop a TMS helmet for sleep-deprived soldiers in the field.

There is also the possibility that TMS will produce super-geniuses. Allan Snyder, the director of Australia’s Centre for the Mind, has focused TMS on a portion of the brain known as Miller’s area in an initial attempt to turn normal subjects into temporary savants—able to count, draw, or remember with autistic precision. His theory is that each of us possesses latent abilities and that a systematic realignment of our brain’s focus may draw those abilities to the surface.

But as I pursued my proposed article on TMS and raised, as per Pascual-Leone’s recommendation, the specter of Delgado, I was assured that, so far as TMS was concerned, this was all highly speculative.

Eric Wasserman, of the National Institute of Neurological Disorders and Stroke: “To do a Jose Delgado you need to stick electrodes down into deeper areas of the brain. If you think about certain areas of the cortex like the area for generating speech, the area for perceiving visual input, and the area for limb movement, they’re all areas that have very strong hardwired inputs and outputs. They’re organized in very focal and structured ways that vary little from individual to individual.” You can stimulate areas such as these fairly easily, Wasserman told me, but to modify something like lying—well, “lying is complex and probably distributed. In order to lie you have to have motivation and you have to make all kinds of calculations about what the consequences of lying or not lying are going to be and you have to recruit judgment and do all kinds of things.” Even if one could identify the circuitry for a function as complex as lying, in other words—which science is unable to do—the complexity would still prohibit any attempt to stifle it.

What’s more, Wasserman said, the brain’s inherent plasticity allows it to adjust to external attempts at control or modification. “If you learn that two plus two equals four, your brain has been modified. There’s absolutely no doubt about that. You can forget that two plus two equals four but your brain was still modified. It’s not an Etch-A-Sketch that you can turn over and shake. It’s very easy to modify the brain behaviorally. And it is quite possible that by using something like TMS if you were able to get the paradigm right, you could modify connections. And that would be permanently modifying the brain. . . . However, behavior is such a powerful modifier of synapses that you probably just have to walk into the other room and everything would get reset.”

Even the reach of TMS is limited—by the basic laws of physics. The magnetic field created by a TMS device degrades exponentially, and so, unless it is prohibitively immense, it is only, as Wasserman pointed out, able to reach into the cortical layer of the brain. “It’s been suggested that sex offenders might be stimulated so that they’re no longer a danger to society,” Oxford experimental psychologist Vincent Walsh told me. “But the areas that are all of interest for things like this—the hypothalamus, the amygdala, or the orbitofrontal cortex—are all either too deep or too ventral to get at with TMS anyway. You’re really looking at a very restricted area of theoretical implication.”

Lastly, TMS works by a mechanism too simple to do much harm. The working theory of TMS is that it introduces noise into the area it’s “stimulating,” as electromagnetic interference introduces noise into a radio broadcast. Neurons typically fire many hundreds of times per second, and they fire in a heterogeneous, complex manner. TMS, it seems, synchronizes the firing of a group of brain cells so that no coherent or useful processing can occur. So, if the TMS device were set to pulse at, say, fifteen times per second, the affected neurons would be made to fire at the same rate—as though, instead of dancing a ballet, they were marching in time. This method is able to produce a few dramatic effects—the “speech arrest” that I saw on video, for example—but it is both clunky and unsubtle. And its effect, for the reasons Wasserman explained, would likely always be temporary.

“Have you used TMS on yourself?” I asked Wasserman.

“Oh yeah. Extensively.”

“That doesn’t worry you?”

“My wife made me stop. She noticed I was coming home with magic marker on my head all the time.”

“I heard the same thing from Dr. Pascual-Leone about his wife.”

“Actually,” Wasserman said, “he has a lot more hair than I do. But his wife heard that my wife said stop. And my wife is a neuropsychologist, so his wife told him that he couldn’t do it anymore, either.”

In this way and others I was assured again and again: no Delgado by way of TMS. No mind control. No social danger. Pascual-Leone had been brainstorming aloud; or he had been attempting innocently to pique the curiosity of a visiting journalist; or, as one of his colleagues fondly suggested, he was simply more willing to indulge theoretical scenarios than most scientists. And yet Delgado’s bull stuck with me. Because if for most ordinary people, with their ordinary conceptions of human will and human personality, the bull is terrifying—indicative of an incursion upon human dignity—for me he was indicative of hope. What I couldn’t tell anybody is that I wanted to be zapped because I wanted to be the bull.

Ten years ago, I had just begun college at a school in eastern Massachusetts, and I was having a terrible time of it. I had been dropped off by my parents in late August, and almost immediately I was hit with a wave of anxiety. I have always been unusually sensitive to change, and so initially I attributed the sensation to homesickness, academic pressure, lack of privacy (one of my roommates was an Indian immigrant with a seemingly endless supply of foul-smelling pickled beets)—and I therefore assumed it would quickly subside. But it persisted, and the effects were crippling: I was constantly on the verge of tears. I could not concentrate in class. I had little appetite. I was missing out, I thought, on the sex and narcotics that freshman orientation offers to all of America’s young students.

Several weeks later, my worried parents, who had been fielding a number of tearful collect calls, came to visit, and we went for a stroll in downtown Boston to talk. It was there that I had what I remember to this day as one of the most crippling panic attacks of my life. It is possible that the surroundings were what sparked it, for we had just passed the city’s gruesomely effective Holocaust Memorial—six glass smokestacks on which numbers representing all six million victims of the Final Solution are etched, and through which an ersatz smoke rises all day as a reminder of their immolation. Or it’s possible that my mother sparked it, for the attack coincided with her informing me that I was suffering from the effects of Generalized Anxiety Disorder (my mother is a psychotherapist), and this diagnosis, spoken out loud, scared the hell out of me, proof as it seemed to be at the time that I was irretrievably, because clinically, insane. Whatever the cause, however, the moment marks the precise point in my life at which I first decided to take medication. And I have been on and off of psycho-pharmaceuticals ever since.

I take medication because anxiety—and its Incredible-Hulk companion, panic—is the single most painful human psychological experience I have ever encountered. It is, I’m sure, a hell of a lot easier to tolerate than many forms of depression, which often includes anxiety. But still, it is, at the risk of building a monument in adjectives, brutal, demoralizing, spiteful, and paralyzing. “No Grand Inquisitor has in readiness such terrible tortures as has anxiety,” wrote Kierkegaard, “and no spy knows how to attack more artfully the man he suspects, choosing the instant when he is weakest.”

Physiologically, anxiety is the condition of heightened vigilance. It is like fear, in that the brain gears the body up to react to a perceived threat—releasing adrenaline into the system, increasing blood pressure and heart rate, activating the sweat glands, redirecting blood flow to the limbs in preparation for escape. But it is unlike fear in that there is no object, nothing from which one can escape. With anxiety, the threat is diffuse and unidentifiable, and it should come as no surprise that what occurs in the brain during states of anxiety is very much linked to our primitive neurological centers—deeper, reptilian structures such as the almond-shaped amygdalae, which help us to respond to threatening stimuli. In anxiety, the amygdalae take precedence over the evolutionarily more sophisticated areas of the brain, most notably the frontal lobes, which are responsible for our so-called executive functions. In short, there is a breakdown in the balance between rationality and emotion, and this dichotomy is only slightly complicated by the role that cognition can come to play in the experience. For the frontal lobes soon begin to see threats everywhere, and the ensuing feedback only sets the amygdalae further ablaze with activity. Phenomenologically speaking, the result is like being constantly in the state that horses are in when they are trapped in a barn that has been set on fire. One’s only, desperate thought is of escape.

But escape from what? One friend has described to me a job interview in which the entire time that she was answering questions she felt as if the bells of Notre Dame were pealing between her ears. She didn’t get the job. This is anxiety in response to a relatively anxiety-provoking situation. But anxiety also comes when all is calm and unthreatening. There is nothing to confront or to fear, and yet the bells peal and continue to peal. I used to work at a prominent magazine, and I have, to my fiancée, described several months of my existence there—months during which I was treated well and surrounded by intelligent, kind, compassionate people, months during which there was nothing amiss with my social life or with my physical health or that of my loved ones—as not unlike having to sit calmly and function normally while acid ate at my flesh. This I think of as the essence of chronic anxiety. At its best it is a slow, cold ache in the sternum and the feeling, despite whatever proof there is to the contrary, that you have somehow irrevocably damaged your life. At its worst, it is an intolerable torture.

So, then: I hate my anxiety. Consequently, I love my medication, for it has proven its ability to alleviate this horrific state. The way it has done so is not by enhancing my mood, as the common term for the drugs suggests, but by regulating it. Pills bring me not to the condition of bliss, but to the condition of rationality. Which is to say, the anxiety does not disappear but becomes manageable again. The pedestrian stimuli that once made me start with panic—the noise of birds, car horns, actual pedestrians—become what they truly are, simple noises. Situations of novelty become once again a cause for excitement and not alarm. And the thoughts of catastrophe and imminent disaster become once again susceptible to my faculties of ratiocination, such as they are.

But there are problems with medication. For one, there is the dreadful wait for efficacy. “Three to four weeks,” is the line one is invariably handed along with a prescription, and the promise always seems a yawning gulf of infinite horror. Then there are the side effects. For me these have been relatively benign. The first pills I ever took made me sweat profusely under a single underarm, my left, so that I wasted many hours trying to hide monstrous pit stains from bosses, friends, coworkers, and girlfriends, and many more poised awkwardly beneath restroom hand dryers. Some of my antimedication friends find this pleasantly ironic—what better way to induce chronic anxiety, after all, than to induce chronic left-underarm sweating?—but to me the sweating illustrates a much more profound trouble with medication. Namely, doctors have far more easily been able to enumerate the side effects of the drugs I have been on than they have been able to explain what mechanisms cause those side effects, or, for that matter, what mechanisms result in the calm that the pills elicit. We have come some way from the time when trepanation or a blast from a water tank was used to treat mental illness—there now exists a cornucopia of relatively innocuous pills that can be drawn on to quell symptoms. But the benefits yielded by pharmaceuticals do not necessarily suggest an advanced state of knowledge about the mechanisms toward which they apply, or even the mechanisms by which those benefits work.

To take the most common form of medication: selective serotonin reuptake inhibitors—otherwise known as SSRIs, the pills for anxiety and depression that are prescribed to millions and that I am currently on—block the reabsorption of the brain chemical serotonin (among others) from the synapse between neurons. This has led to the popular belief that serotonin is at the crux of the depressive condition and that it is the chemical link to happiness. Which is of course wildly simplistic, but also basically false. People who are depressed do not have low serotonin levels. Rather, what seems to be the case is that their neurochemical system is somehow imbalanced, and, as serotonin levels are increased, the brain is led back toward equilibrium. SSRIs seem not so much to increase any magic-bullet chemical in the brain as they seem to reconfigure the sensitivity and the specialization of brain cells.

Or, to put it another way, pills cause something to go on up there but no one knows exactly what. In the aggregate, of course, this is not necessarily a significant problem. I would personally consume any foreign substance that didn’t melt my skin if I could be assured it would quiet my anxiety. But the lack of basic scientific understanding does tend to stoke a blunt anxiety. When one is mucking about with one’s own brain, after all, one prefers a modicum of precision.

So, because I am in the end a very rational person, I keep going off the pills. Two years ago, for example, I was completely medication free. I had gone off of them because I was feeling well, and it seemed as though I was no longer in need of pills to reduce my anxiety. I had learned some cognitive tools to keep myself even, and, aware of studies that show cognitive therapy (on the principle described by Wasserman of the self-shifting brain) to induce the same neurological changes as medication, I considered myself ready to go it alone. Then the panic returned. Going back on the same medication I had been on proved to be ineffective, however, and so I spent the next year and a half beset by an almost daily sense of failure. Self-recrimination and self-hatred are the characteristics of my particular anxiety, and I have grown adept at them. Again, as I had before, I spent many of my days fending off tears, and many hours uselessly attempting to get to the source of my despair. (This is both the boon and the horror of workaday insanity: one knows full well that one is thinking insanely.) Still, I was intent upon going it alone, attacking my fears and my panic head on. Then, several months ago, I had had enough. I found another psychiatrist and got on a new medication. This one has seemed to quiet my anxiety—not once and for all, undoubtedly, but once again. And I will stay on this medication for as long as it works, or until, along with my doctors, I have found a reasonable way to manage my anxiety without them. If I have to I will stay on medication my entire life. I will do so because the prospect of my anxiety flaring up again is so devastating not only to myself but to the people that I love that it is something I cannot abide. In fear one lashes out, and those lashes do damage.

Which brings us back to TMS. A high-end TMS device produces a magnetic field in the shape of a reverse cone, the tip of which is only millimeters across. That field can be directed at any focal point of the brain’s cerebral cortex. Right now, because the tip of that cone is most readily able to produce a “virtual lesion,” researchers wishing to enhance the brain’s cognitive abilities typically use it in a manner known as “paradoxical facilitation.” In essence, they knock out an area of the brain in the expectation that a distant but connected area will compensate with more vigorous activity. Though indirect, it is beginning to show some dramatic results. So is a more direct approach. In 1995, researchers for the first time used the device to stimulate the prefrontal cortex—a region of the brain that lies just behind the forehead and is implicated in mood disorders—and they found that TMS can serve as a sort of electromagnetic antidepressant, helping to improve the prefrontal cortex’s activity and its communication with deeper, more profoundly mood-regulating regions of the brain. Since then, TMS has been used to treat, with varying effects, Parkinson’s disease, Tourette’s syndrome, obsessive-compulsive disorder, epilepsy, and schizophrenia. Right now, depression is the largest target; a nationwide clinical trial is currently underway that will make TMS the first non-pharmaceutical treatment to gain FDA approval since electroshock therapy. Anxiety has been less focused on, but it is, I think, just a matter of time.

So on that day in Pascual-Leone’s office, I demanded to be zapped, to see this new technology in its infancy—to test a new drug. And I used all the cajoling I could muster, all of my borrowed authority as a freelance from a leading national magazine, all of my charm, to insist. Until, for all that he wanted to discuss bioethical implications, he relented.

Pascual-Leone led me into a laboratory where two men were working. They looked like graduate students. One was visiting from England to learn the ropes in the TMS laboratory. They sat among tangled wires and computer equipment. We talked a little about TMS and they related how they had used the device frequently on one another. They seemed, in fact, to be quite cavalier about it—they even told me about the time, early in the development of the technology, a TMS coil had shot out of its rubber sheath and embedded itself in a wall. They thought this was very funny. We laughed.

One of the grad students set up the device. To induce speech arrest, TMS machines are set to pulse rapidly, but according to ethical regulations—in rare cases, rapid TMS can cause seizures, and so its application must be officially sanctioned by the hospital’s Internal Review Board—Pascual-Leone could only set the machine to fire in single pulses. It was a disappointment, but one to which I was willing to acquiesce. No prepping was necessary. The magnetic pulse goes directly through hair and bone, and so requires no conductive material as an intermediary. Pascual-Leone told me he was going to zap my motor strip, an area of the brain in which the tissue easily corresponds to different nerves in the body. He was going, he said, to locate the area for my left hand.

It was, to them, a mundane procedure, something they had done a thousand times before. And the device, it was clear, was to them just that: a device, one that required electricity and wire and rubber. And yet, to me, standing there, the paddle poised above my head, it was a glimpse, however minor, into the birth of a potential hope. Let them do what they would with my will. Let them make me into their bull.

At first, nothing happened. Was my brain broken? Was my skull too thick? Pascual-Leone moved the paddle across my head, trying to find the correct spot. Then, finally, there it was: My finger twitched, my middle finger. Briefly, but it twitched upward, as though someone had taken temporary control of my desire to move. It moved. I smiled in awe at this minor miracle. And someone turned off the device.

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