I settled in to consider what they were doing. I had to take my mind back to the 1980s, when I worked on power systems that delivered the kinds of pulses Alvaro’s people wanted to use for TMS. The pulses we created back then were used to fire laser tubes, or “other things” in classified weapons systems. Alvaro and Lindsay had talked about high-power pulses in their medical machines, but I’d worked with high-power pulses too. When I worked at Candela we powered lasers that shot light to the moon and vaporized crucibles of uranium in microseconds. When I’d worked at Isoreg I’d designed power conditioners to withstand nuclear blasts, and you can’t get much more high-powered than that. I had a good understanding of how electromagnetic energy worked, but twenty years had passed. Now I struggled to bring it all back.
Electricity and electromagnetism are two things you can never see. You just have to imagine them and observe their effects. We can bind two objects with a piece of rope, and it’s obvious what holds them together. Make one of those objects a piece of iron and the other a magnet and they will snap together tightly even though there’s nothing visibly holding them together. If the magnet is strong enough, you’ll break your back trying to pull them apart.
Tie a rope between two cars and you can pull one of them out of a mudhole or a snowbank. Use a wire “rope” to tie a generator to the power panel on a big building, and you can deliver light to a thousand people. Which carries more energy—the rope or the wire? Clearly, the wire has the edge.
I’ve always felt an affinity for powerful elemental forces. Electromagnetic induction is one of the things that makes modern society possible. It’s the principle by which electricity is generated in power plants all over the world, and it’s the principle behind electric motors in toys, trains, blenders, and washing machines. It makes Tasers tase and electric guitars sing.
The initial theory of electromagnetism was arguably the greatest achievement of Michael Faraday, a prolific self-taught British scientist of the early nineteenth century. In the fall of 1831 Faraday took a ring of soft iron and wrapped copper wire around it. He called that helix A. Then he wrapped another length of wire around the same ring and called that helix B. He wired helix B to a meter and hooked the wires from helix A to a battery.
You have to ask yourself what possessed Faraday to do such a thing when it had never been done before. What did he think would happen? Sometimes the most remarkable inventions spring from inexplicable flights of fancy.
Faraday would have said, “We have to start somewhere,” and that’s what he did. As soon as he touched the wires from helix A to the battery, the meter needle jumped. When he took the wires off, it jumped again, this time in the opposite direction. That was the first demonstration of electromagnetic induction—the process of turning electrical energy into magnetic energy. To an engineer, Faraday’s achievement was akin to inventing the paper clip, or maybe the wheel. It was an incredibly big deal.
And it hasn’t changed much in 160 years. If you were to hold Faraday’s helix up to a TMS coil in Alvaro’s lab, the similarity would be instantly apparent. And best of all, it still works the same way. That’s what I like about engineering. When you figure out a principle, you can always count on it. When I repeated Faraday’s experiments in my basement lab as a teenager, I felt my own thrill of discovery.
Faraday also learned that he could wrap wire around an iron core and induce electricity in a freestanding coil next to the wire-wrapped core. That proved that energy moved through space—it didn’t just travel through the iron bar. That property is what makes TMS possible today.
In TMS there is one coil of wire wrapped around the iron core, which is held against your head. The “receiving” coil—if you could call it that—is the invisible jumble of biological “wires” that connect the neurons of the brain beneath where the TMS coil is placed against the scalp. Scientists put pulses of electricity into the TMS coil, creating magnetic fields that induce electricity in the wires of the brain.
So the question we come to now is: Where does it go from there?
The principles of electromagnetism told me that the physical orientation of the wires in my brain would affect their sensitivity to TMS. Brain wires that go up and down might not receive a signal that would be strong on side-to-side wires, and vice versa. So which way did the wires in my head go? You can look at a computer circuit board and see which way its wires go. Brains aren’t so easily examined, and their wiring is immeasurably more complex. Every person is unique, but I figured there must be general patterns of brain wiring, just as our bodies are generally similar in other ways. I turned to the literature for an answer, but I could not find a consensus.
Some scientists—including Alvaro—believe that brain wiring runs in all directions, and they counted on that randomness to ensure that some energy would be delivered beneath the coil, no matter how it was placed on my head. Another researcher—Dr. Manny Casanova at the University of Louisville—had published an article suggesting that the cortex was dominated by structures called minicolumns, stacks of neurons that make up the brain’s outer layer. He seemed to believe that the minicolumns have a core of excitatory neurons surrounded by a sheath of inhibitory “horse-tail” neurons. The inhibitory neurons—by virtue of their structure—are more sensitive to the effects of a TMS coil laid on the scalp, when the pulses come slowly. Casanova suggests that greater sensitivity makes most TMS inhibitory in nature. He believes higher-frequency stimulation can reach through that inhibitory curtain to stimulate the excitatory neurons at the core of the minicolumns, and that explains the working of a different type of TMS. However, other scientists disagree with that notion; a positive answer will have to wait for advances in brain imaging technology.
One thing the researchers all agreed on was that some of the neuron wires were short while others were quite long—reaching right across the brain and even out into the body’s nervous system. So TMS might deliver energy to the front of my brain, but those long wires could carry it everywhere else, and who knew what that would mean. It was a lot to wrap my head around, and it showed how incredibly complex the brain is and how little we really know of its architecture. Even today, the threads that connect our billions of neurons together are only mapped in the broadest, most general sense. Details of the individual connections remain largely unknown.
The research papers I tried to read were full of technical terms that I had to look up and still didn’t always understand. The problem was that I didn’t know enough about the architecture of the brain to make much sense of them. Dr. Casanova had described wiring between the minicolumn structures as if it were clear as day, but when I looked at images of actual brain tissue from his article, the threads seemed to go every which way, and it was hard to call what I saw anything but random.
Then there was the question of autism. For years I had heard people say things like “Autistic brains are wired differently,” and I wondered how literally true that might be. Do the wires actually follow different pathways in brains like mine, and are there individual differences in up-and-down or side-to-side wiring? I learned that the limited research we’ve done with brain tissue hasn’t shown huge differences, but that might not be the whole story. There was a lot of talk about connections, and there seemed to be several schools of thought. Some researchers thought autistic people had too many connections, while others thought we had too few. One team of researchers—Nancy Minshew of the University of Pittsburgh and Marcel Adam Just of Carnegie Mellon University—proposed that we had both in a complex but fascinating theory. Just and Minshew had used brain scanners to map out some of the major connection pathways in the brain. They hypothesized that autistics have imbalances between the pathways, but interestingly, they thought the balance might change as we age. Our “different connectivity” might make for mental confusion, but it might also help some of us excel at reasoning tasks that use one concentrated area of the brain. Their ideas were extremely interesting, but I found it hard to make the leaps of reasoning to con
nect microscopic differences in brain structure with real, observable behaviours.
Dr. Casanova thought the minicolumn structures that make up the cortex are different in autistic people too, but his explanation of what that might mean was too technical for me to grasp. After overloading my brain with online reading, I wrote to him and asked a few questions, and to my surprise he responded right away.
Manny has been studying autism for about ten years. He started out in pathology, looking at brain tissue samples from people who had died. What he learned there led him into the lab and toward novel lines of research with living people. He’s been using TMS most of that time. He had his theories, but he didn’t know how it works with any more certainty than Alvaro, and the two of them don’t always seem to agree. What they did agree on was this: medical imaging—as good as it is—is not at the point where the effects of TMS can be observed at a cellular level in living people, and until that changes, we are left with observations of larger brain function and best hypotheses.
I asked Dave what he thought about my struggles to make sense of what I was reading, and he laughed and said, “I’m just a country radiologist! You probably know more about it than me, with all you’ve been reading.” Maybe so, but I was a long way from figuring it out.
The differences between the scientists’ theories just served to illustrate that while everyone agreed on how TMS energy is made, there are differing ideas of what happens when it gets into the brain. Did the TMS pulses overwhelm the signals that flowed on the interneuron circuits? Did TMS energy cause the neurons to shut down or become paralyzed by electrical overload? Or might it make them hyperactive? All those theories and more have been proposed, and I realized that there might well be more than one explanation. The brain has many different kinds of neurons and they might respond very differently to TMS signals. If my brief foray into brain science taught me one thing, it was how little we really understand about the brain’s inner processes.
That made the ideal location for the TMS coil a little uncertain, as I would soon discover. Alvaro and his team had proposed to change the way I think, but reason and cognition are two of the most amorphous and elusive things that go on inside the brain. Even with the latest imaging tools, we struggle to understand where thought resides and how it is processed. Alvaro had already told me they had several target areas in the current study. The reason they had that many was that it wasn’t clear which—if any—was the exact area they were looking for. It’s easy to determine where the nerve fibres from your eyes and ears enter the brain, and we know where the nerves for our hands and legs emerge. But where do we form a thought like “I love my puppy”? We don’t know for sure, but there are probably many areas involved in synthesizing that four-word emotion.
Magnetic resonance imaging (MRI) has been able to show us the inside of the brain for quite a while. The newest functional imaging tools can show us activity in the brain as we think and do tasks. But its resolution is limited. Faced with a brain that holds hundreds of millions of neurons in every cubic inch, even those state-of-the-art tools can’t tell us what’s going on except in the most superficial way.
We know how the brain is connected to our muscles and how that system works. But where did I get the idea to move my arm just now? How do we decide to talk, or blink an eye? Those are very different matters. We have very little knowledge of how abstract thoughts are formed and how and when they are translated into action. Yet abstract thought is one of the things that makes us human.
And I couldn’t help but take my line of inquiry a step further. If the brain contains the mind, does the mind contain the soul? Is there somewhere physical we can point to and say, “There is the essence of John”? If Alvaro and his team knew the answer to that, they sure didn’t share it with me.
That’s what makes TMS and similar experimentation such a leap of faith. We cannot truly understand the impact of any given stimulation until we try it. If things go well, all is great. But what if they don’t? Would we be able to reverse a bad effect? We had dreams and theory, but we didn’t have hard answers.
I had started reading about brain wiring in the hope of finding an understandable foundation for the experiments I’d volunteered to take part in. But all I got was more confusion, and I was left with the knowledge that I just had to trust Alvaro’s experience and instinct.
All we had were a TMS machine, some ideas, a few volunteers, and a lot of hope. For some reason, that still felt like enough.
Mapping My Brain
A WEEK AFTER I SIGNED the consent forms, it was time to begin. “We have to start with some basic tests and an MRI of your brain,” Alvaro had explained. “That will allow us to make sure you are okay for the study and target the TMS precisely where we want.” What he didn’t say but what I imagined he meant was “We’ll also make sure there are no tumours or extra things growing in there that make you the way you are.”
With some trepidation, I drove the now familiar route to Beth Israel on the afternoon of my MRI appointment. I met Shirley and Lindsay at the TMS lab first for the testing. They sat me down at a computer.
“You’re going to see a person on the monitor who will say something to you,” Shirley said. “All you have to do is push the front button if what they say makes sense and the back button if what they say is nonsense. Let’s try a practice run.”
“The sky is green,” the face on the monitor said. I felt them watching as I pondered what to do. Where I came from, the sky was not generally green. I pressed the rear button for nonsense and the next question arrived.
“Eat the cake.” Makes sense.
“Drink the highway.” Nonsense.
“Okay,” Shirley said. “That’s great.” But then the questions turned strange. After a few minutes, I began to wonder . . . maybe they did drink highways in Shirley’s world. I thought back to my rock and roll days, and suddenly all of the questions seemed a lot more ambiguous.
“Choke me.” Okay, I thought, I’ll say this one makes sense; I’ll choke you if you want. I pushed the front button.
“The road is bumpy.” Another front button.
“The dog is blue.” That made me think of the pampered dogs I’d seen in my time. I was a fan of the movie Best in Show, but I could not recall any blue canines on parade. Either way, it was a good movie. When I recommended it to Shirley, she told me to stay focused on the test. The words kept pouring by, some strange and others not.
“Throw me out the window.” I paused for a second. This was the kind of phrase we used to program into Milton Bradley games when we set up talking demos for management. Our other favourites were “Smash me!” and “You’re a real dummy!” With a small smile I remembered how our best efforts had never escaped the scrutiny of the engineering manager, and then I turned my attention to the task at hand and pressed the front button.
Finally the questions came to an end. I was sure there was some deeper purpose, and I hoped I had passed. If this was an intelligence test, it was surely a strange one. I very much wanted the TMS to work, and I was afraid my answers might disqualify me.
No one said anything, so I asked how I’d done. “Fine,” Shirley told me, as if the questions and responses had been the most casual and natural conversation in the world.
It would be six months before I learned the true purpose of those strange questions. The nonsense questions were a red herring. They were actually trying to learn how much I mirrored what I heard with my body. They theorized that a prompt like “Pet the cat” would involve reaching out, so I’d move my arm quickly to the front button when I heard that. “Brush your hair,” in comparison, involved a pulling back and up, so they were watching to see if it took me a tiny bit longer to overpower that pull-back impulse before extending my arm to the front button.
Mirroring had sounded like a simple concept when it was presented as seeing a smile and smiling in response. Once we got into tests like this, though, I realized how incredibly subtle and complex it was. And as for the
test . . . I never did learn how I scored; I was just glad I didn’t flunk out before I’d even had a chance to begin.
None of them had any idea how vulnerable I had started to feel, now that they had raised the possibility of changing my brain. I realized that my acceptance of how I was—up till now—had largely been founded on the idea that I had no other choice. You might have compared me to a prisoner who made the best of his surroundings, only to run for the gate the moment it was left ajar.
The next stop was a room where they did the brain stimulation. Shirley pointed to a chair and indicated I should sit. Right next to it I saw a large white box on a cart—the TMS machine. On my best behaviour, I resisted the temptation to turn the knobs on the machine, pick up accessories on the cart, or give the thing a test run on my own. Instead, I meekly sat down and waited for what came next.
“Today we’re going to measure your response to TMS. Everyone is a little different. What we’re going to do is stimulate your motor cortex with a single pulse at a very low level. We use the motor cortex for this test because it’s the easiest part of your brain to measure. We stimulate there, and your muscles move. We’re going to find the spot that moves your index finger, decrease the TMS level until your finger doesn’t twitch anymore, and then record the setting where that happens. That will help us calibrate for the actual experiments. This isn’t going to have any effect on how you think or feel, because today’s stimulation isn’t hitting those parts of your brain. It’s like an alignment session for our equipment. By measuring your brain’s sensitivity in a simple test, we get an idea of how much power we’ll need to use for the actual study.”
“Why the index finger?” I asked her. That question elicited a very interesting response. It turns out that some of the neurons in the brain’s motor cortex have microscopic tendrils that reach all the way to the index finger. Most of our appendages are connected through several nerve cells in series, like relay circuits in the spinal cord. They had chosen the index finger circuit for the directness of its wiring.
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