You might think that answering questions such as whether you have any sisters is relatively easy for your brain to do, but it’s actually quite complicated. Answer the question yourself. Do you have any sisters? I bet that felt easy. The answer doubtless came to you almost without thinking about it. Knowing whether you have any sisters comes easily because it’s typically a situation that we have lived with for our whole lives. There are exceptions; maybe you had a sister, but she has passed away, making the question a little harder to answer without adding additional detail. But for most of us it’s a simple yes or no. Yes, you do have a sister, or no, you don’t.

  But how does your brain do that? How does it know? The answer is, it doesn’t just know, at least not in the sense that most of us feel that we, as people, just know certain things. Your brain can’t just “know” that you have a sister any more than your computer can “just know” that you have a sister. It has to find out. Your brain has to search your memory for any evidence that you have a sister. That evidence can come in two general forms. It may be autobiographical, in the sense that you may have memories of growing up, playing with a person who looked a bit like you, and who answered to the same parents. Perhaps you remember your sister’s twenty-first birthday and the present you bought her. That’s an autobiographical memory that your brain can use to determine whether you have a sister.

  The other kind of evidence that your brain may find is what psychologists call a declarative memory, or put more simply, knowledge. Somewhere in your brain a piece of data says that you do, or do not, have a sister. It has nothing to do with the experiences that you might have had with your sister; it’s just a stored fact that you can pull out anytime you need to answer the question “Do you have any sisters?” It’s a piece of knowledge, such as that Paris is the capital of France—knowledge that you probably know whether or not you’ve ever been to France. You learned that fact, just as you learned that you have a sister.

  The distinction between autobiographical memory and declarative memory is of great interest to neuropsychologists because brain damage can affect one type of memory and not the other. In fact, my colleague Brian Levine at the Rotman Research Institute in Toronto has described a whole new condition known as severely deficient autobiographical memory syndrome, whereby the ability to vividly recollect past events is impaired, while other memory abilities are spared. These people might have no childhood recollection of their sister at all, no shared sibling experiences that they can report, no fond twenty-first-birthday memories. Yet they know that they have a sister because they have not lost the factual knowledge, the declarative memory for that information, and this allows them to lead more or less normal lives, their memory deficit often passing almost unnoticed even to themselves. Brian’s cases typically have no history of brain injury or neuroimaging evidence of brain damage. So the root of the problem remains a complete mystery.

  One conclusion that we could draw, then, is that John retained memories laid down before his accident, including where he had last been on vacation. Whether he used his autobiographical memory or his declarative memory we do not know, but one or both of these cognitive processes was intact, allowing him to answer the questions. And we were able to conclude a whole lot more about John’s brain than that. Think about what else you need to do to answer the question “Do you have any sisters?” At the very least, you need to understand spoken language. If you don’t understand the question, you certainly can’t answer it. In addition, you need to hold that question in working memory for however long it takes your brain to retrieve the answer. What if you had no working memory, no ability to hold on to information until it’s needed—in this case, to answer a simple question? Your brain would go off in search of an answer only to find that it had forgotten the question!

  In fact, quite a lot more working memory was required for John to achieve what he did on that day because it wasn’t only the questions he had to keep in mind. Throughout the scan, which lasted well over an hour, he had to remember what he had to do if the answer to a question was yes (imagine playing tennis) and what he had to do if the answer was no (imagine walking around his house). More important, John’s responses that confirmed that these cognitive processes had to be intact also told us a lot about which parts of his brain were still functioning normally. If he could comprehend language, then the speech areas in his temporal lobe must have been working just fine. He could retain information in his working memory, which told us that the parts of his frontal lobe that are responsible for the highest forms of cognition were still responding as they should. He could also recall events from before his accident, which told us that the medial temporal lobe regions and the hippocampus deep within his brain were all still intact.

  These mental processes are all things that you and I do routinely, moment to moment, without even thinking about them. But to witness this kind of elaborate scaffolding of consciousness announce itself in a patient who everyone had assumed was vegetative for five years was revelatory!

  Though John could reliably and effectively “communicate” with us from within the scanner, Steven’s team were unable to establish any form of communication whatsoever at his bedside. Communication via fMRI was all there was for John; it was the only option. Nevertheless, after the fMRI analysis was completed, a thorough retesting using standard neurological techniques led doctors to change his assessment to “minimally conscious.” Somehow, knowing that John was in there must have made it easier for Steven’s team to spot subtle signs of partial awareness, signs that had eluded detection before the scan.

  John was only in Liège for a week. He’d been transferred from Eastern Europe for his assessment by Steven’s group, and it was time for him to return home. We were out of time and out of luck. Many years later I asked Melanie what had become of him. After he returned home, Audrey had lost touch with the family. The phone numbers they had provided were disconnected, and there was no other way to make contact. John had disappeared as suddenly as he had appeared. After a few hours in the light, he was back in the gray zone, with no way to break out again.

  These chance encounters with patients that came and went were frustrating, but it was a frequent occurrence back then. We were casting our net far and wide and sometimes transporting patients over great distances. Often, the logistics and the economics just got ahead of the science. As badly as any of us might have wanted to hold on to John, to explore his situation further, to delve even deeper into his inner world, it was impossible—we had to work with the circumstances, whatever they were. We were opportunistic wherever we could be, but frequently we were left disappointed. Science is often a random business, and progress frequently happens serendipitously, rather than through intelligent design. Nevertheless, it made me uncomfortable that we’d lost contact with John—I resolved to change things, to create a situation where we could follow patients indefinitely, regardless of their circumstances.

  When our paper describing John’s case was published, my lab was once again deluged with frenzied media attention. My phone at the Unit wouldn’t stop ringing. Camera crews came and went. I lost track of the number of times I appeared on some foreign radio station, recounting the story of the vegetative patient who could finally communicate with the outside world. The public seemed to have an insatiable appetite for the story, and the timing couldn’t have been better. Martin was on the job market, and the very day he interviewed at UCLA, the Los Angeles Times ran with the headline “Brains of Vegetative Patients Show Life.” It was no surprise that he got the job.

  As has so often been the case, all of the attention influenced the science, and it influenced those of us whose careers depended on it. From our initial scan of Kate in 1997, when I had no funding at all to support this kind of research, to 2010, when John’s story broke, the flow of money from grants and institutional support had changed considerably. The James S. McDonnell Foundation in the United States had awarded Niko Schiff, Steven Laureys, and me $3.8 million to develop a combined program of research. A group of us in Europe, including Steven, had picked up a grant worth almost 4 million euros ($4.5 million) to develop brain-computer interfaces for behaviorally nonresponsive patients, and the Medical Research Council had given me an extra £750,000 ($1 million) to extend our fMRI work in vegetative-state patients. Plus, much of my research program at the Unit was now focused on and funded for research on disorders of consciousness. In terms of research dollars, times were good.

  With all of this attention came another game-changing hand. Out of nowhere, Canada came calling again. I was approached by Mel Goodale, a cognitive neuroscientist at the University of Western Ontario in Canada, famous for his work on visual perception and motor control. He told me about a recent scheme, initiated by the Canadian government, to bring foreign scientific “talent” into Canada. Successful candidates would be awarded $10 million in funding from the Canada Excellence Research Chairs (CERC) program, with matching funds from the host institution.

  I seized the opportunity to move back across the Atlantic, start again from scratch, and set up Gray Zone II at Western’s world-renowned Brain and Mind Institute, a new lab with better resources, better funding, and a whole new world of possibilities.

  Shortly after arriving in Canada, I got a call from a former colleague of mine, Dr. Christian Schwarzbauer, a physicist who was now working in Aberdeen, Scotland.

  “We’ve been using your fMRI methods to scan patients who are in a vegetative state up here in Scotland,” he said, “and we’ve recently scanned an old friend of yours.” I immediately knew that he must be talking about Maureen. Her parents had made the connection between Christian and me and asked whether I would be prepared to comment on the results of her scans. Christian was also keen to seek my opinion.

  It was the least I could do. But when it came to evaluating the scans, I was churning inside. I shut my office door: I needed solitude. Peering at the images of Maureen’s brain felt like peering into the depths of my distant past. It was the strangest feeling—like touching some faraway emotional part of myself that I had buried years before. I was staring down at the brain of someone I had once been so close to. As I stared, I realized that the overwhelming animosity I had felt for our relationship had long gone. I was peering into Maureen’s brain, looking for signs. Not of the person who had left me frustrated and confused, but the person I had once loved.

  Christian had asked Maureen to imagine playing tennis and then to imagine walking through the rooms of her house. What was I going to do if her scan showed a response? I pushed the question to the back of my mind and peered once again at the screen in front of me. All I could see was darkness. A void. There was nothing there. Nothing of the Maureen I had once known. Nothing of Maureen at all. Ever elusive, ever unknowable—she was still a mystery.

  CHAPTER TEN

  ARE YOU IN PAIN?

  It would be better to die once and for all than to suffer pain for all one’s life.

  —Aeschylus

  On December 20, 1999, a young man pulled away in his car from his grandfather’s house in Sarnia, Ontario, with his girlfriend in the passenger seat beside him. Scott had studied physics at the University of Waterloo and had a promising career in robotics ahead of him. But at an intersection just a few blocks from his grandfather’s house, a police cruiser traveling to the scene of a crime T-boned their car, hitting the driver’s side full on. The police officer and Scott’s girlfriend were taken to the hospital with minor injuries. Scott wasn’t so lucky; his injuries were devastating. He was admitted to Sarnia General Hospital, and within hours his score on the Glasgow Coma Scale—a neurological scale that is used all over the world for measuring a person’s conscious state—was rapidly dropping. Three indicators of awareness are rated: the eyes (from “does not open eyes” to “opens eyes spontaneously”), speech output, and motor responses. The lowest score possible is 3, indicating “does not open eyes,” “makes no sounds,” and “makes no movements.” The highest score, 15, indicates that you are fully awake, conversing normally, and obeying commands. Scott was already a 4, just one step away from complete shutdown. Despite no outward signs of head or facial injury, his brain was badly beaten. The impact of the police cruiser into the side of Scott’s car had slammed his brain against the inside of his skull, squeezing it into herniation and bruising it beyond recognition. Scott was in a bad way.

  Twelve years later, soon after arriving in London, Ontario, I heard about Scott. I had contacted Bill Payne, a doctor at Parkwood Hospital, a long-term-care facility on the south side of the city, asking whether he knew of any patients who might be suitable for our studies. Originally established in 1894 as the Victoria Home for Incurables, Parkwood Hospital was still home to many “incurables” in practice, if not in name. Scott was first on Dr. Payne’s list. “He’s an interesting guy,” Bill said. “His family are convinced he’s aware, but we’ve seen no signs of it, and we’ve been observing him for years!”

  I took a look at Scott. He certainly looked vegetative to me. But I needed an expert second opinion, and no one could provide a better opinion than Professor Bryan Young, a senior neurologist in the area. Approaching retirement with many years of experience with vegetative and comatose patients, he was possibly the nicest person you could ever meet.

  I gave him a call: “What do you think of Scott?”

  “Very interesting guy.” This was starting to sound familiar. “His family are convinced he’s aware, but we’ve seen no evidence of that.”

  I probed a little more deeply. Bryan had been seeing Scott regularly since his accident twelve years earlier. As the local neurologist with the most experience of disorders of consciousness, Bryan had naturally been the one who had examined Scott most closely. Bryan had immense experience by any measure, and an international reputation for meticulous and careful assessment of patients. If he thought Scott was vegetative, then I knew chances were that he was. I told Bryan that I was thinking of putting Scott into the fMRI scanner, and Bryan agreed that this was a good idea. “Please tell me what you find,” he said.

  I set off to Parkwood to assess Scott more thoroughly along with Davinia Fernández-Espejo, one of the postdocs who had moved with me to Canada from Europe. In a quiet room off the ward where Scott was staying, a nurse introduced us to his parents, Anne and Jim.

  Anne, who had worked as a lab technologist, gave up work on the day of Scott’s accident. Her husband, Jim, was a former banker and trucker. They were a lovely couple, clearly devoted to Scott and his life, such as it was, postinjury. Following the accident, they had relocated to a one-story bungalow outside London, Ontario, where Scott could stay when he wasn’t being cared for full-time at Parkwood.

  Jim and Anne told us that, despite his diagnosis, they believed that Scott, who loved listening to music from The Phantom of the Opera and Les Misérables, was responding to them.

  “His face is expressive,” Anne insisted. “He blinks. He does thumbs-up for positives.”

  Given Bryan’s multiple assessments over the years, coupled with our own evaluation of Scott’s condition, this was a curious comment indeed. We couldn’t make Scott do thumbs-up no matter how hard we tried. I checked his official medical history. Neither Bryan nor any of the other doctors who had examined Scott over the years had indicated that he could do thumbs-up since his injury. Nevertheless, his family were adamant: Scott was responsive, and therefore Scott was aware.

  Curious as it was, I had seen this scenario many times over the years. A family is convinced that the person they love is aware in the absence of any clinical or scientific evidence to support it. The family speak and interact with that person as though he or she is fully conscious. Why? Do these families have some kind of heightened sensitivity to the patient’s mental state? A kind of sixth sense for detecting consciousness that eludes even highly trained professionals such as Bryan Young? The family would certainly know the patient a whole lot better, which might explain their sensitivity to subtle signs of awareness.

  One consequence of the brutality and abruptness of most serious brain injuries is that the doctor who assesses the patient—usually a trained neurologist—has generally not met the person in his or her former, healthy life. All the doctors “know” of the patients is what they see after the accidents. The family has the benefit of years of experience, a much more complete picture of the person within. Families also typically spend a lot more time with the patient after the accident. Neurologists, like all doctors, are busy and have a pile of clinical commitments and patients. That limits how much time they can devote to any one person. By contrast, many family members sit at the bedside for hour after hour, day after day, clutching to the faintest glimmer of hope, watching for the tiniest sign of awareness. It’s natural that if it is there, they will be the first to see it.

  But all that time, effort, and hoping is also sure to fuel wishful thinking, and the slightest hint of a response can alter a family’s entire sense of reality. We’re all terribly susceptible to what psychologists call confirmation bias, and confirmation bias is a real thorn in the side for gray-zone science. We tend to search for, interpret, favor, and recall information in a way that confirms our preexisting beliefs. If the person you love most is lying beside you in a hospital bed, her life hanging by a thread, you desperately want her to pull through. And you desperately want her to know that you’re there. You ask her to squeeze your hand if she can hear you—and it happens! You feel a distinct increase in pressure as her hand gently squeezes yours. Your immediate reaction? She did what you asked, she responded, she’s aware! It’s a perfectly natural but unfortunately not scientific response. Science demands reproducibility.