“There you are!” I turned to see Lindsay approaching rapidly, with two people tailing her. I resisted the sudden urge to run. “This is Shirley Fecteau,” she said, pointing to her dark-haired colleague. “She’s another post-doc. And this is Lin, our lab assistant.” I photographed their name tags with my iPhone because I have trouble with names and that seemed like the best way to keep track of who was who. They looked at me a bit strangely and herded me toward a room at the far end of the hall. We all took seats, and they looked at me expectantly.
“Alvaro is on his way,” Lindsay said. I thought I had snuck into the office quietly, but her words made me realize that the receptionist must have called ahead.
Never before had I been accorded such respect and deference in a medical office, treatment I imagined was usually reserved for famous surgeons visiting from afar. I was wondering what I’d done to merit such an honour, and then Lin mentioned my book. Not only was I the first autistic adult to join their study, I was the first autistic person any of them had met who had written a book about the experience.
The researchers were young, and most of their work to date had been with autistic kids and young adults. They hadn’t met many successful older autistic adults, and in the spring of 2008, my book was pretty novel. Consequently, I wondered if they were waiting for me to say or do something. I thought of the sixties soul singer Archie Bell up onstage, shouting, “We don’t only sing, but we dance just as good as we want!”* Unfortunately, I didn’t sing, and I sure couldn’t dance.
Years before, my grandmother had taught me to ask people about themselves when I didn’t have anything else to say, and it generally worked. I asked Shirley, who spoke with a strong accent, where she was from. It turned out she was French Canadian. I already knew Lindsay had studied at UCSD, and I learned that Shirley had come to Alvaro’s lab from Quebec. Scientists seemed to travel great distances to work with him, and I asked Lindsay and Shirley why that might be.
It turned out that there were not very many people doing research into noninvasive brain stimulation, and Alvaro was a leader in the field. In the years to come I would meet visitors from many other countries in the halls of the TMS lab.
All of them had unique areas of interest. Shirley’s interest was brain stimulation, and it just happened that the current study was on autism. But she was also interested in using TMS to treat addiction and in working on what she called “military applications of brain stimulation”—whatever that might mean. Lindsay, on the other hand, had come to the lab specifically to study autism and TMS together. Lin, the assistant, was a student at a local university and was gathering experience before deciding what to do in grad school.
Just then, Alvaro appeared in the doorway. “Welcome to the centre,” he said, smiling and holding out his hand. “Please join me, and let’s have a look around.” Walking a short distance down the hall, he motioned us into a room that was larger than the office we’d just been in, with a big comfortable-looking chair and a bunch of medical electronics.
“This is a TMS machine,” he said as he patted a large box with MAGSTIM printed in block letters on its side. Then he picked up a heavy insulated cord with a plastic figure eight at the end about the size of my hand. “This is the coil,” he said.
He proceeded to show me other equipment in the lab, which included brain-wave-monitoring gear, otherwise known as an EEG system, another smaller TMS machine, several more oddly shaped coils—“They have different stimulation patterns,” he explained—a monitoring camera, and two computers. The only sign that this was a medical office was the soap dispenser and medical wastebasket by the sink.
It took a moment for me to take it all in, but then I started asking questions. They told me the TMS equipment was used in many studies, and it was also being used to treat patients in the hospital for depression and stroke and for other experimental procedures. Alvaro’s centre was exploring autism, Fragile X, depression, Alzheimer’s, and a host of other maladies. The place was really hopping.
“Alvaro is not just a researcher. He’s also a practising neurologist,” Lindsay said with some pride. “He does rounds in the hospital and sees patients here in the clinic. He has a particular focus on TMS, but he treats people with all sorts of neurological problems.” There were several other neurologists in his clinic too, along with research scientists. The lab was even more impressive than what I’d envisioned—spotless and efficient and bustling with motivated people.
It was all a bit intimidating, but at the same time I felt privileged to be part of their efforts, even if I was only a glorified guinea pig. But unlike a guinea pig, I did have to willingly agree to be involved and sign my life away, after a fashion. I also had to be tested—to make sure I was “fit for study.” All that happened on my next visit, two weeks later.
Lindsay met me in the Beth Israel lobby and led me into an examination room in Alvaro’s Berenson-Allen Center. She took out a big folder containing what looked like an inch-thick stack of papers. “This is what’s called an informed-consent form,” she told me as I picked up the first of several multipage documents. It’s my nature to actually read that kind of paperwork and even ask questions. Later, Lindsay would say I asked more questions than any research subject she’d ever encountered, but she said it with a smile so I figured it was okay.
After a quick read through the stack of papers I got the gist of what they said:
We (the folks at the hospital) are going to do certain experiments on you.
They may make you better, or they may not.
You understand the possible risks and agree that it’s okay to proceed.
It was a little ominous, when I thought about it. Maybe that was why they had taken five pages to say what they could have said in three sentences—to ensure their inscrutability to the average person. But mostly I felt a little disappointed. The scientists had talked about “remediating the deficits of autism.” That had had me imagining life-altering changes, but there was nothing at all promised in those pages.
“We’re going to do at least six stimulations,” Lindsay explained, “and we’ll have you do tests on the computer before and after the TMS so we can measure the effect.”
“At least six?” That sounded a little open-ended, but she was quick to clarify what she meant. “There’s a possibility of error doing these stimulations. If something doesn’t work out, we might have to redo it.” I wondered what she’d meant by “error,” but I guessed it made sense. This was, after all, research.
“Has Alvaro ever done something like this before?” I asked.
“This is a brand-new study,” she explained, “but he’s based it on his previous TMS work in other areas of the brain, and on animal models.” Hearing that I might be Subject One was a little scary, but it was also exciting.
When I arrived at the TMS lab in March 2008, I was told there were already five other volunteers for the study. Two had beaten me to the hospital and signed their consent papers, but no one had actually started the stimulations. In the next few weeks three more people would join this first Harvard–Beth Israel TMS autism study, which would run through the summer. None of us knew one another, with one exception.
Michael Wilcox was a little older than I was, and very smart. He was a former financial analyst who had gotten fed up with corporate life and retired to a farm in the Berkshires. Then, at about age sixty, he learned he was autistic. We’d met when he read about my first book and realized I was local. He emailed me to ask where he could find it, but it wasn’t yet on sale. “You may be able to buy a review copy on eBay,” I’d replied, and that’s what he did. After reading the book, he invited me to lunch, beginning a tradition of periodically shared food and conversation that continues to this day. We both joined our local Asperger’s support group and took an immediate liking to each other. A few weeks earlier—after the dinner with Lindsay and Alvaro—I had told the group I’d decided to try TMS, and he said, “I think I’ll talk to them too.”
A
week later he told me he’d done just that and shared how impressed he was with Lindsay and Alvaro and their ideas. He’s just as excited about this as I am, I realized. Michael and I had agreed to do our sessions at different times, and we resolved to avoid talking to each other as it was happening, because we didn’t want to affect the results.
It didn’t completely turn out that way, but we did our best.
The description of the research in the consent papers threw some cold water on my eagerness. According to the forms, they were going to test our ability to recognize common objects. And they were going to measure prosody—the rhythm, stress, and range of my voice as I expressed emotion—to determine whether TMS changed those things.
It wasn’t the most thrilling proposal, but I told myself they had to take small steps before the big leaps. I did wonder if they thought TMS would do a lot more than the forms suggested, and later on I asked Lindsay if my suspicion had been true, and what her real goal was. “I want to win the Nobel Prize for my discoveries in autism!” Her enthusiasm made me smile, and I hope that comes true.
The potential risks outlined in the waiver didn’t seem too scary, and the forms explained that “previous studies have shown that effects of TMS lasted half as long as the time of stimulation.” That meant a half-hour stimulation would only affect me for fifteen minutes.
Although the briefness of the experiment’s effect seemed somehow reassuring, it also worried me. Where was the lasting benefit? At my next opportunity, I asked Alvaro what good TMS could do if its impact was so short-lived. “We believe its effects are cumulative,” he explained. “We think TMS opens up paths in the mind, and when you use them, you make them wider. We also believe continued stimulation strengthens them. Think of sledding down a hill when you were a kid. When the snow was fresh, you could make a path anywhere. But after a while the paths get worn in, and all you can do is follow one or two routes down the hill. We think TMS can open new paths and help tread them down so you can keep them open. Some of the people in our depression programme are seeing benefits lasting six weeks to two months.” Their TMS depression programme was very close to getting FDA approval, and they were excited by that prospect.
“We’ve done TMS for depression for a few years in Spain, and they do it in Canada and elsewhere in Europe. It’s not permanent, but it lasts a long time. It’s a good alternative to daily medication for the people it helps.”
“How similar are the depression and autism therapies?” I asked. Penicillin will treat an infection in your ear or your toe and all you have to do is swallow a pill. I wondered if TMS worked the same way—going wherever it was needed.
“They’re not similar at all,” Lindsay told me. “Remember, TMS only reaches a tiny part of the brain. It’s not like a medicine that diffuses throughout the body. The areas that are stimulated to treat depression are totally different from the parts we’re stimulating in the autism study.”
Hearing her made me realize that my penicillin analogy was wrong because it referred to a pill. TMS might better be compared to an antibiotic ointment—you could put it on your cheek or on your leg, and it would treat infection in either place. But putting it on one spot wouldn’t do anything for an infection somewhere else.
“That’s a better way to look at it,” Lindsay agreed when I suggested the comparison. I’m very lucky she was patient as I tried to turn complex questions of neuroscience into simple analogies a bumpkin like me could understand. Then I wondered if the study we were about to begin would lead to an FDA-approved treatment. “We’ve got a long way to go for that,” she told me. “First we’d have to demonstrate a real benefit in this study. Then we’d have to do several follow-up studies to refine a treatment. Then we’d need to do a bigger trial with lots more people. This is just a small study with a few subjects. Getting from the lab to an FDA-approved treatment is a very slow process.”
As it turned out, TMS would be approved by the FDA for depression while we were doing the TMS autism study. There was considerable rejoicing in the lab when that happened and they realized their research had finally paid off. Today, Alvaro’s lab has an outpatient clinic that’s using TMS to treat a steady stream of patients. His reputation is so good that patients travel hundreds of miles for their treatments.
Their talk of success with depression was reassuring. Even so, other people’s reactions sometimes got me worried. One day I told someone about TMS, and he said it sounded like another term for ECT, the electro-shock therapy of medical horror movies.
“I don’t think that’s true,” I had replied hesitantly, but I didn’t know enough to really explain the difference. Later, Lindsay helped me understand. “ECT works by putting so much energy into the brain that it induces a seizure, a massive reset if you will. ECT is also very diffuse, whereas TMS is tightly focused. Even today, ECT is a violent process, enough so that it’s done under anaesthesia. TMS is none of those things, and its effects are a lot gentler. The two technologies both deliver energy to the brain, but the energy TMS puts in the brain is a tiny fraction of what’s used in ECT and it’s aimed right where we want it, not scattered everywhere.”
When I read about ECT—and looked at the energy levels involved—I realized that ECT was probably “burning out” some of the delicate wiring in the brain, which was scary to contemplate. From the beginning, ECT had a reputation for wiping away pieces of patients’ minds. TMS and ECT were both electrical therapies, but one was at the level of an AA battery in your pocket flashlight, while the other was like the high-tension wires coming out of the generator station at Hoover Dam.
That really put the two techniques in perspective, and a little later Alvaro reinforced what Lindsay had said. “We’ve done everything we can to ensure this is safe. There’s always a neurologist on duty when we do TMS, and no one has ever had a seizure from it in this lab. The energy levels we use for TMS today are minuscule compared to what doctors used for ECT and a fraction of what they used for direct stimulation treatments twenty years ago. We are doing depressive stimulation, which is inherently safer than excitatory TMS. It’s always safer to turn something down than to turn it up.”
The difference, as they explained it, was that depressive stimulation meant producing a slowing down or weakening of brain activity in a particular area, whereas excitatory TMS meant speeding up activity in the target part of the brain. But if all they performed on us were depressive stimulations, how could they actually improve anything? Musicians turn it up to make rock and roll better and race car drivers go ever faster. Turning things down seemed like a road to nowhere, but Alvaro had the answer.
“The brain has a huge network of wiring called the corpus callosum that keeps the two sides of your brain connected and in balance. One way to think about that in the context of TMS would be to imagine a teeter-totter. We can raise a side by lifting it up. But we can also raise that side by pushing the other side down. We think TMS works the same way, and it’s why we can use depressive TMS to lift or lower. By pushing one side down, we think the corresponding area on the opposite side will rise. That’s safer than lifting directly, and that’s what we are doing here.” And as an additional salve for my concerns, Lindsay added, “The institutional review board goes over every detail of proposed research, and they are very cautious about what they approve.”
The review board was part of an eerily titled organization called the Human Subjects Protection Office. That name alone would make anyone uneasy, but I chose to trust the scientists. I knew of course that there were risks; with this sort of research there’s always a leap of faith required, from both the researchers and the subjects. That’s how science moves forward. And who better to do the leaping than those who feel they might benefit most from the results—those whom researchers call the “affected population”?
Looking back, I was about the furthest from “informed” that one could be, in spite of what the doctors had told me and all my outside reading. None of us knew where the results might lead, and there
was no way to know if TMS would even make me better. To complicate things further, I realized I couldn’t have even defined what “better” meant, had someone at the hospital asked me. It was almost a shot in the dark. But if it did help, I was getting in on the ground floor and I would be a decade ahead of everyone else who might eventually benefit from the treatment. I took a deep breath and signed on the dotted line.
* This passage comes from the hit song “Tighten Up,” written by Archie Bell and Billy Buttier. The song was a big hit in 1968 for Archie Bell and the Drells of Houston. Several of the bands I toured with played the song in the seventies.
The History of Brain Stimulation
I MAY HAVE BEEN AWED into submission by my visit, but I still retained the smallest trace of scepticism, even as I was deciding to trust my brains to this team of smart researchers who might be planning something really great, or possibly something a lot worse than a painful shot.
I also retained a measure of what some would call arrogant confidence when it came to the electronics. After all, with all the work I’d done with transformers, inductors, and electromagnetic pulses, I figured I might well know more about how TMS delivered energy than they did. That was the one area where they didn’t have all the answers when I visited the lab. I had asked if their devices used tubes or thyristors, and no one knew. I asked what the peak voltages were, and they weren’t sure of that either, though they knew they were high. By that time, they had wowed me with so much that they did know, and with their level of intellect, that I was desperate to find even one area where my own knowledge might be enough to stand alongside theirs.
If there was such a place, it would be the electrical engineering side of TMS. I readily conceded that I had absolutely no idea where to deliver a stimulation, or in what quantity. All I knew were the general parameters. Too little energy and nothing would happen. Too much and those tiny brain wires would go up in a flash. Watch the ears when you try it, I told myself. Little white tendrils emanating from the holes would be a warning, for sure. Smoke was always a reliable indicator of electronic circuit overload.
Switched On Page 6