 Check. Okay. Okay. Well, why don't we get started since it's a little bit after the 1230 start time, but thank you all for coming. It is my pleasure to be hosting moderating this on-core performance of the NeuroEthics seminar series. The NeuroEthics seminar series was run by Dr. Thomas Cochran last year. There was sort of a grant house at the Center for Bioethics that grant has come to an end and so this is kind of our like I said, this is our on-core of the NeuroEthics seminar series and today our speaker will be Dr. Charles Vair. Charles is a professor in the Department of Philosophy, Medicine, and Epidemiology and Biostatistics and holds the Canada Research Chair in Bioethics at Western University in London, Ontario in Canada and his academic interests center on the ethics of medical research. He is the author of several influential articles on the duty of care and clinical research, the ethical analysis of study benefits and harms, and protecting communities in research. And from 2007 to 2012, Charles co-led a collaboration that produced the first international ethics guidelines for cluster randomized trials. In 2008 he founded the Rotman Institute of Philosophy, which is dedicated to fostering collaboration between the humanities and the sciences and he served as the Institute's first director. In 2014 he received Western's Helmuth Prize for Achievement and Research and in 2016 he was elected to the Royal Society of Canada. Our other speaker today will be Dr. Thomas Cochran, who is an assistant professor of Neurology at Harvard Medical School and associate neurologist at the Brigham and Women's Hospital and senior ethics consultant on the Ethics Consultation Service at Brigham and Women's and he received a combined MD and MBA from the Tufts University School of Medicine, completed his residency in Neurology in the Partners Neurology Program at Mass General and Brigham and Women's Hospital. And Dr. Cochran teaches medical students here at Harvard in their course on medical ethics and professionalism. He's given over a dozen, excuse me, a dozen, he's given over a hundred invited lectures and presentations and authored dozens of peer reviewed articles, book chapters and educational material for medical professionals, ethicists and lay people. He also co-edited the popular neurology board review first aid for the neurology boards as well as a book on medical ethics and professionalism intended for use in training physicians and other medical providers. So with that, I'd like to introduce our first speaker, Charles Bayer, who will be talking to us today, Consciousness Unbound, the Ethics of Neuroimaging After Severe Brain Injuries. So please join me in welcoming Dr. Bayer. Thanks very much, Spencer. Spencer didn't mention that he was actually my doctoral student at Western. It's a special privilege to be here at Harvard, but it's so nice to have time to catch up with a very talented former student. So I'm here to talk about some work that a team and I are leading at Western University, but I want to start by going back in time a bit. And all of you undoubtedly are familiar with the myth of Prometheus. And Prometheus, of course, was a titan who crossed Zeus, you might say, and he provided fire, and importantly, the knowledge of how to make fire to the mankind. Zeus was very upset by this and sentenced Prometheus to an eternity of physical bondage, chained to a rock as you can see here. In this talk, I'm going to talk about a different kind of bondage, not a bondage of the body, but a bondage of the mind. A very particular group of patients who are in vegetative or minimally conscious states, but who, despite the fact that they're behaviorally non-responsive, are covertly conscious. In particular, I want to talk about one patient named Scott Routley. Of course, everything I'm going to say about Scott is publicly available. He was the subject of a program on BBC and an article in McLean's, a Canadian news magazine, a few years ago. Scott was indeed a very talented young man. He studied physics at the University of Waterloo and had a promising career. One fateful day at the end of December in 1999, he and his girlfriend were in a car accident, and they collided with a police car, of all things. Everyone walked away from the accident except for Scott. He had an isolated brain injury, and unfortunately it was. There's a lot of traumatic brain injury, something like one and a half million emergency room visits in the United States, 275,000 hospitalizations, and every year 52,000 people die from traumatic brain injury. When it's severe, it's catastrophic. All of these patients, by definition, are comatose, intubated, ventilated. Outcome is highly variable and difficult to predict. Some patients make relatively good recoveries. Others enter into a vegetative state or a minimally conscious state, and about a third of these patients die of their injury. Of the survivors, about half are left with serious cognitive deficits and ongoing dependency for care and need. Everybody after a severe brain injury has a disorder of consciousness. It's useful to think of consciousness as being comprised of two main components, arousal and awareness. Arousal just refers to being awake. Awareness, on the other hand, refers to awareness of oneself, knowing who one is, being aware of one's environment and the things going on around you. In the hours after a severe brain injury, as I've said, all patients are acutely comatose, meaning they have neither arousal nor awareness. Some patients over a period of time emerge into a vegetative state, and that's an unusual condition where these two components of consciousness dissociate from one another. Though patients are awake, but they're not aware of either themselves or anything going around. It's a very unusual and confusing state. Some patients become minimally conscious, and these patients are awake but show fluctuating low levels of awareness of things in their environment. Families after a traumatic brain injury, of course, have questions about what's going to happen. What are the likely outcomes for their loved one? It's exactly the sort of questions that Scott had for his health care team and his neurologist. They want to know, first off, is he going to live? Will he regain consciousness? How much function is he likely to recover? Will he be able to communicate? Will he have relationships? Will he be able to work? And predicting these things is one of the most difficult challenges for neurologists working in critical care. There are a range of current predictors. The purpose of this chart is not the details, so don't worry about the small type. But it's really just to make the point that there are a range of predictors across a number of modalities. At the bottom of the chart are predictors related to structural neuroimaging, so CT or structural MRI findings are an important prognostic indicator. Clinical examination, biomarkers even, and electrophysiological testing, importantly, somatosensory evoked potentials are actually quite a strong predictor of negative evidence. So despite all of these current prognostic factors for patients after severe traumatic brain injury, at least at our center, our critical care neurologists estimate that about half of patients after a severe TBI are in kind of a gray zone, where really their prognosis remains quite uncertain. That, of course, is difficult. It's difficult for the healthcare team and it's difficult for families because this is a context where life or death decisions are being made in the hours and days after injury. I mentioned that about a third of these patients go on to die and 70 percent of these deaths are preceded by treatment with thralls. About half of these treatment with thralls occur within the first 72 hours of care. Turgion did a prospective cohort where they looked at patients with severe traumatic brain injury across six Canadian level one trauma centers and concluded that in some instances that withdrawals this early may be too early for accurate neuro prognostication. Remarkably in their study, mortality rates differed really substantially across six otherwise pretty similar level one trauma centers. In fact, the mortality rates varied fourfold among these centers. Those were differences that remained even when known prognostic indicators were adjusted. That caused the authors to conclude that this raises the concern that differences in mortality between centers may be partly due to variation in physicians' perceptions of long-term prognosis. Physicians' perception. There's an urgent need I think for better prognostic markers maybe particularly markers of good outcomes not only to inform health providers but to inform families for making. Well Scott survived this period of acute injury. His parents elected to continue the provision of life support ongoing treatment. He emerged from an acute coma into a vegetative state. As I said, this is a state of eyes open unconsciousness in which patients exhibit relatively normal sleep wake cycles. But they as I said have no awareness of themselves, their environment, what's going on. They exhibit no purposeful behavior. They're incapable of communicating with people around them. But beyond that they're very confusing patients for I think the healthcare team and for families as well because they open their eyes. They appear to look around the room. They move. They make sounds. They tear. They smile. They grimace. And that's exactly what Scott looked like. Sometime after he was transferred to a chronic care hospital, Parkview Hospital, which is in South London, Ontario where he resided for the next 12 years. Of course, traumatic brain injury particularly when it's severe isn't just catastrophic for patients, catastrophic for families. And this is Scott. They describe the day of the injury and they talk about how that was the day they both retired from their jobs. They do that to take care of them. They sold their house in Sarnia and moved to London to be close to Parkview Hospital so they could help take care of them. Okay. The healthcare team as I've said told parents that he was in a vegetative state and unaware of his parents for his parents being with Scott every day, seven days a week, like so many parents and family members of these patients had a different experience of Scott. They described him as actually being aware of enjoying listening to Phantom of the Opera and Mizorab, okay, reasonable things to enjoy. They describe his face as being his problem and they talk about how at least in some way the Scott communicated. And that is an uncommon for families of these patients. In fact, the earliest study that I could find talking about this in the early 90s and they surveyed dozens of families of vegetative patients and found that something like 90 percent believed that there was some degree of impact on patients either knew that family was in the room or could tell when their hand was being held or up to and including the leading. The difficulty becomes in a sense is assessing whether, you know, any of these families might be right that there is sort of more preserved cognitive function than the healthcare team perceives through bedside clinical examination. These patients are not behaviorally responsive and so it's very difficult to assess them. And that's where the idea of using neuroimaging comes in. These patients are incapable at the bedside of demonstrating intact cognitive capability. And so neuroimaging becomes a creative way, if you will, of accessing intact bits of the cognitive machinery. So I work with Adrian Owen at Western and he and his team are using a variety of neuroimaging techniques, including EEG if you want. And particularly functional magnetic resonance images. They're not just interested in determining whether these patients might be covertly conscious or not. They're actually interested in mapping a range of cognitive function, sound processing, word recognition, semantic processing, command following, the ability to follow a story in a movie clip so they're showing patients bits of a Hitchcock movie and serving their responses, listening to audio, digital audio stories, and even looking for their ability to find a joke funny. So this is the slide where I pretend to understand what functional MRI is. I really don't, I bet you many of you in the room could explain this far better than I can. I will just say there's a really big magnet. That's kind of where my understanding kind of ends a bit. But apparently by putting people in this really big magnet, it's possible to measure to what extent hemoglobin is deoxygenating in the brain. They actually are able to generate a very detailed three-dimensional map of neuronal activity within the brain. Please don't ask me any questions about however. Okay. So I said that the Owen team was really interested in assessing really many bits of the cognitive machinery. But a really important piece is whether some of these patients might be covertly aware or covertly conscious if I'm speaking a little more boldly. And it's really difficult to assess this in a way that's convincing. There are many difficulties with this. One of the difficulties is just consciousness itself is a contested concept. Philosophers build careers arguing about what consciousness is and means, right? So in fact what the Owen team has done is really just take the clinical standard for consciousness and that's just command. If a patient rides in an emergency department and the physician's trying to figure out whether the patient is conscious or not, he might say, please my hand. Open your eyes. Your name, John. And if someone can reproducibly do those things then for clinical purposes that's conscious. But there are more difficulties here that relate to the doing neuroimaging of these patients. For instance just speaking to patients and saying just the word tennis to patients can elicit brain activity in acoustic areas of the brain. So in fact what the Owen team needed to do was build, if you will, a really robust experimental design for assessing command following in the neuroimaging environment. What they did was invite patients to engage in mental imagery. They explained to the patients that when we say the word tennis what we want you to do is imagine hitting a tennis ball back and forth across the net until we tell you to stop. And that in healthy volunteers reproducibly elicit the signal from the supplement to the odor area. Second task, a spatial navigation task, invited patients to imagine walking from room to room in their house. And that predictably causes other areas of the brain related to the patient. Beyond this though there were 30 second blocks where patients were told to imagine playing tennis, keep imagining it for 30 seconds, and now stop, rest. So for 30 seconds stop. And furthermore these larger 60 second blocks were then random on. Importantly this was something that healthy volunteers are able to do very well. In fact with 100 percent sensitivity the healthy volunteers are able to both do these mental things. Just to go over this just briefly one more time. Patients then under the mental imagery task are invited to do one of two things. One with the word tennis they're invited to imagine if you will playing tennis. And in the fMRI context that results in motor areas of the brain lighting up and then they're invited to stop, relax, and that signal then goes away. And then they're invited to imagine walking from room to room in their house. That causes areas in the spatial navigation parts of the brain to light up. They're then invited to rest and those signals here. And the idea is that if a patient can do this reproducibly that this is reasonably robust evidence that they're capable of willfully modulating their neural activity. So what does this look like? Well these are functional MRI images overlaid of course on structural scans of a vegetative patient in the top panel and of a healthy control bottom panel. Tennis on your right is the responses back to Scott Rowley. He in fact was capable of performing this task repeatedly and reproducibly which is evidence that Scott Rowley was over. This perhaps surprised no one more than his neurologist who in fact is someone on our research team. Brian Young is a world leading expert on coma and stroke. And his response to this was, I was impressed and amazed that he was able to show these cognitive responses. He had the clinical picture of a typical vegetative patient and showed no spontaneous movement. I might add that's over 12 years of examination by Brian. The family wasn't surprised. They said it was just well now somebody believes it. We don't know how many patients who are in a vegetative state or who are minimally conscious are covertly aware. One study estimated but we really don't have a population level. There's another kind of problem with this though. I mean it's that command following gives us perhaps evidence that someone is covertly conscious but it doesn't give us direct access to the contents of their consciousness. And that really is one of the big remaining problems. It's sort of the what is it like to be vegetative and covertly aware. An important step in that direction was to modify the mental imagery task to allow for communication with some of these patients. And the idea is that we can ask a patient in the fMRI context a question which is amenable to a yes or no answer and instruct the patient that look if your answer is yes, imagine playing tennis. If your answer is no, imagine a house. And to date that's allowed for successful communication with pre-vegetative or patient. So these are the questions that were asked of Scott, Dead Scott, the banana yellow and his supplementary motor area. Is your name Scott? Spatial navigation areas. Is the year 1999? Is the year 2012? That was the year when he was being asked. What's your support worker's name? Bob, Sarah, Julia. His current support worker. Got this right. Do you like watching Ice Hockey on TV? He's Canadian. It's remarkable stuff. And I think it's just the ethical issues in this work are so on the surface. 2011 I started having conversations with Adrian Owen and his team and it really became clear that what was needed was in a sense a parallel research project, a parallel research team with integrating elements of the Owen lab with other people to begin to systematically suppress ethical issues relevant to researchers and families. Of course we involve neuroscientists, but we also involve neurologists, neuropsychologists, epidemiologists, medical sociologists, and yes, even philosophers. Basically we seek to identify and analyze ethical issues here and to provide guidance to researchers that are now funded by the IHR work, published our study protocol, if you want to have a look at it, in BMC ethics. So let me in my remaining time say something about, I guess four questions broadly that we thought about a bit. Where we've come to answers and where we haven't sort of come to final answers yet, sort of where we're at and what we're doing. The first question actually, when we sat down with the Owen lab, we sort of said so. What's an ethical issue for you? And this was actually the first question they asked us, which was we're sharing these results with families. Should we be doing that? And the issue there is of course that this testing, this fMRI sort of testing is not going on in a clinical care environment, would of course share the results with next again. It's happening in a purely research context. And it's unclear whether generally researchers have an obligation to close individual research results to research participants. I think there's a widely acknowledged obligation to share at least summary level results, but individual results are it's a little less clear. Families want this information. Now that's that much is plain, but is it reliable enough? Can families understand it to the benefit? Another of my doctoral students, Mackenzie Graham, led an analysis of this and came up with four broad criteria that should guide the disclosure of individual level research results. In fact, for any research study, the first criterion was that disclosure should not seriously impair the scientific validity of the study. And the concern here might be in sort of a randomized controlled trial where there might be really good reasons to not reveal individual level results, at least until after data analysis is complete and preferably until after the study is reviewed and published. But these neuroimaging studies are different, right? The level of inference here is not a group. The level of inference is actually the individual patient. All these experiments are trying to determine is whether the patient being tested now possesses these. And so that means once once they're done sort of testing a particular patient, disclosure of individual research results actually doesn't. Our second criterion was that the research result be reasonably informative and reliable. And here we think that it probably is that at least with regard to command following, it relies on an established model of awareness assessment and clinical practice. And as I've mentioned, the mental imagery task is something that healthy participants can do. The third criterion is that the benefits of disclosure outweigh the harms for the research participant. And we think actually that when someone can command follow in this setting, we learn a lot of important things about them. We learn that they've got intact hearing, some speech comprehension, short term memory executive function, and so on. And those are important. And more broadly, we learn that in some sense, these are moral person. We've got an obligation to acknowledge them such. Practically, this encourages not only family members, but members of the health care team to talk to the patients, interact with them. Why? Because they can hear you. The final criterion is that either the individual herself or the proxy decision maker. So we concluded that, in fact, the ON team should be sharing these results with families and then can use to be their practice. There's an important question, though, about what impact do these results have on families. And so that's another question we're working on. There's being some talk about this in the bioethics literature. Families, of course, play a very important role in the care of these patients and making decisions on their behalf. But we really don't know what impact results like this are going to have on families. Positive, that may lead to optimism, but it also might be patients can suffer. So maybe that'll be up to them. Negative results might be denial or confusion. And broadly, we just don't know how best to tell families. I guess our approach was to sort of say, well, if we want to figure this out, I guess what we should do. We're working with a couple of medical sociologists. We own a Webster and Sarah Munson in Toronto. And we're doing a qualitative interview study with them. And what we seek to do is to gain insight into families' knowledge of the patient's medical condition, including their beliefs about what preserve cognitive capacity the patients have, the reasons for enrolling in research and their experience in the patient. Thus far, we've completed and transcribed 10 pairs of interviews. And we're just interviewing an other family. All of these are family members of individuals who are vegetative or minimally conscious and participating in our neuroimaging study. All the patients are at least one year post-injury interviewing the surrogate decision maker. We're actually doing two interviews, one prior to neuroimaging. And the second interview is after the results of neuroimaging have been done. Families, it turns out, have an enormous amount to say. Across 10 pairs of interviews, we have over 600 pages of transcripts. Stories are, they're hard to read. Something catastrophic has happened. We have developed a coding framework and we're now starting to write up three papers. One on kind of health systems issues that these families are facing. In Canada, at least our health system is not well structured for dealing with young patients, predominantly young patients with brain injuries. Another paper is looking at caregiver burden. And a third paper is actually looking at the sort of perceptions that families have of the abilities of these patients. Let me just say a little bit about that. You know, families in our interviews said a lot about, you know, their relationship with the patient after injury. And almost all of them attribute some degree of consciousness to the patient. Many of them believe that the patient continues to communicate with them, at least in some way. Families are acutely aware of the fact that this is not the opinion of the health provider. And it's interesting to hear families reflect on it. The way that overwhelmingly they kind of describe that difference of opinion is in terms of how, is in terms of the fact that basically no one's spending as much time with the patient as they do. And they'll commonly say, well, you know, if the doctor were just here more hours of the day, they would see what we're doing. Right? And we've called that kind of explanation sort of epistemic privilege that the families are privileging sort of their time spent with the patient as an important force of the knowledge that they have. This notion of epistemic privilege allows us to theorize differences in perspective between caregivers and health providers in a way that remains respectful of families' ways of thinking. That's just one idea that's emerged. It's a lot of interest in using FMRI, brain-computer interfaces, for informed consent to treatment decisions. And that's another issue that we're thinking through. The response in the media and in the bioethics literature was, I don't know, you know, I guess kind of predictable, a bit disappointing in a way. And it's, it kind of goes like this. This is from East, written by Joe Fins and Neeta Jeff. They say, it's from the Hastings Center report to your back. Imagine rushing to the hospital because your loved one had a serious brain injury. You're asked about any end of life care preferences and whether you will agree to a do-not-resuscitate order. If only, you could ask. Now imagine rolling your loved one down to the hospital's MRI machine and asking him if he wants to live or die by reading his responses. I mean, I guess there's something appealing about the sort of breathless prose here and the dramatic nature of this imagined scenario. But it's really not the question that the Owen lab is facing. It's really not the question that any of these families whose loved one is engaged in a neuroimaging study are facing. None of these patients are acute patients in the hours or days after a traumatic brain injury. None of the communicators. In fact, as I said, you know, all of these patients are at least the year after the injury. Some of them as many as 20 years. So end of life decisions are not actually foremost in the minds. A lot of the decisions are quotidian issues like physio more kind of mundane high stakes. A lot of these are low or medium stakes. But even to ask patients about these decisions, we would need some reassurance that they've possessed decision-making capacity. And about that in the bioethics literature, there's been skepticism. Could we ever really adequately demonstrate? We know that patients after brain injury commonly lack decision-making capacity. The bandwidth here of the brain-computer interface is really, really narrow. We've only asked, have answered, yes or no questions. Answers might be subject to medication. So I guess all of this adds up to saying that if we manage to do this, it's just going to be really difficult. We've been working on this though and Andy Peterson who just finished his doctorate with me and has just taken up a faculty position at George Mason and continues to work on this problem has developed an approach that really involves three steps. The first is actually in a sense to take advantage of all of the cognitive testing that's going on when these patients are brought in. They're actually brought in for five days of pretty exhaustive testing. And some of these results I think are likely to be quite relevant to the question of decision-making capacity. Whether there's preserved language, comprehension, memory, executive function, those are all relevant decision-making capacity and we're thinking about adding in sort of a like a high level reasoning puzzle to the routine investment. If it seems that that patients have enough, you know, intact bits of the cognitive scene, it may then, that may then provide the grounds to go on and actually more formally assess capacity using a medical vignette series of yes or no questions addressing standing appreciation and choice, a list of perhaps 10 questions, which is probably about the limit of what anyone can respond to in a single piece of this. This puzzle is important and it's called medical trusteeship and I just want to say a little bit more about that. I mean our sense is that even in patients who prove to be reliable communicators who are able to address specific questions, addressing capacity for a particular medical decision, it's really unlikely that we're going to end up with very high confidence that someone possesses decision-making capacity. So what we've done is taken an idea from the philosophy of disability literature and that's the idea of involving a medical trustee and that would basically be the surrogate decision maker who would evolve into taking the role of medical trustee and provide supported decision-making for the patient. Their role is not to make decisions for the patient but rather to enhance the patient's voice. The final question actually doesn't depend on our ability to assess decision-making capacity at all. It really gets at this sort of crucial unanswered question, what is it like to be vegetative and covertly conscious? It's commonly presumed in the literature that these are lives of very poor quality. Consciousness is thought by some to be a reason to let people die. So Wilkinson and Fabulouske wrote a few years back that if such patients suffer they can be harmed by continuing treatment. There may be stronger reasons in terms of non-maleficent. The best interests of the patients just allow them and I guess if we could know all those things, if we could know that these patients were suffering severely and if there was nothing we could do about it then that argument might be true. But the problem is we don't have any access at all to the subjective experience of these patients. Or do we? And I think a really important feature of these cases they're just an instance where our moral imaginations fail us. We have no idea what it's like in this state and actually I think it's a mistake to just sort of sit in an arm chair as philosophers sometimes do and try really, really hard. Actually that's just the way. So what we'd like to do is we'd like to develop a quality of life instrument that we can administer through our brain interface. It complicates. Normally when one develops a quality of life instrument, one interviews patients, ask them about what they value in their life and so on. Take a range of items that are generated, distill these, and then validate them against the standard quality of measure. You can't do any and there is no existing instrument. So we're, you know, we're making something up. Reasonable. Other people may make up different things and interested in hearing about those. Our innovative approach involves a systematic review of similar instruments in the Delphi process. Briefly about that. What we did actually was we looked at almost a thousand quality of life instruments and we tried to pick out the ones that really address quality of life in relevant patient populations. Patients with brain injury, stroke, spinal cord injury, motor neuron disease. We picked out 51 quality of life instruments. We then took all of the dimensions of quality of life described in those and combined them. And what we ended up with was a list of 42 dimensions of quality of life. Again, here the port, the port says not the details. They run across the usual domains of quality of life, physical aspects including bodily pain, mental aspects such as whether someone's experiencing depression, social, personal relationships, psychosocial, spirituality, and so on. And this in effect gave us a set of potentially relevant dimensions for these patients. We're then taking all 42 of these and feeding this into a Delphi process. We've handed these over to an expert panel to help us figure out what they think the key dimensions of quality of life are behaviorally. Patients, our expert panel is comprised of 35 members, a neurologist, neurocritical care specialist, quality of life methodologists, philosophers, neuroscientists, and crucially of course family members. And so in the first round of the Delphi, they're given these 42 items and asked to rank how important they think they are. We take out items on which there is consensus and on the remaining items we feed back to individuals sort of the summary of the group results and then we do that kind of over again. We've just completed the second round of the Delphi and the third round is out with our with our expert panel. And basically what we're hoping to get here is a list of their sort of top ranked five to ten items they think are most relevant to the patient population. And then I think if our project has demonstrated anything it's the importance of collaboration. You know I think neuroimaging holds real promise to improve our ability to diagnose patients directly and to determine their prognosis accurately. But there's a real really difficult issue that I haven't even we haven't even begun to deal with and that's the question of the responsible adoption of such technology in clinical practice. How do we integrate this in clinical practice in a responsible manner? Who should who should receive sort of additional neuroimaging evaluation? And and crucially when should that happen? In probably 20 years after injury. I think dealing with those issues is going to require continuing collaboration among neuroscientists. Lossford was a remarkable young man. He taught us very important things about patients with severe brain injury. He taught us that some patients in fact are overtly conscious of where some patients are capable of communication. Scott actually has answered more questions via brain computer interface than any other patient in the world. What a what a remarkable man. Unfortunately I started out to talk talking about the myth of Prometheus and this is a portrait of Percy but Shelley and travels in Italy you can reasonably infer from the background and that actually is when he was finishing his epic poem Prometheus on down and as the romantic poet tended to do he changed the story of Prometheus somewhat. Prometheus wasn't merely someone who disobeyed Zeus but but in fact Prometheus overthrew Zeus the tyrant in his epic poem and so for Shelley Prometheus had become a kind of a kind of romantic revolutionary and I guess I'll conclude by by saying that that's that's kind of how I think of Scott Radley as as a kind of revolutionary who's overthrown a tyrant if you will overthrown our understanding of just what patients who are in a vegetative state are are capable of and Scott at least in some sense truly has brought us. Thank you Charles that was that was really something and that patient is really sort of a shocking example of how potentially revolutionary this research is in terms of our thinking about consciousness and detection of consciousness I should I should say at the beginning that I am not a neuroscience researcher myself I'm a neurologist but I specialize in neuromuscular disease and I don't do bench research or neuroimaging research so I'm I'm not I'm probably not much more of an expert on MRI than than you are so no questions on that topic please I am a clinical neurologist so I'm involved in a lot of clinical decision-making for patients and I'm also a professional medical ethicist and an ethics consultant and so from two angles I'm I'm frequently involved in decision-making for patients who find themselves with disorders of consciousness and boy if I were allowed to I could probably talk for an hour about all the possible implications of work like this but I really want to keep it brief so that we have plenty of time to discuss the research and to discuss amongst ourselves what we think the implications of this are so I've got a set of sort of loosely related points to make about about this topic and the but the the underlying gist of what I'm going to say is that when this research first started being publicized I was I was skeptical that we were yet ready to even think about transitioning into the clinical setting but gradually as we learn more and more about this topic I'm beginning to shift a little bit and think that there may be some clinical situations in which research like this could be applied at the bedside so so let me in in a real particular order first a bit of a throwaway point but when you're reading media accounts about this research don't believe what you're reading and in fact it's probably better to actively disbelieve what you're reading just assume that every single sentence is wrong until you've heard it from multiple sources and preferably from authoritative sources the diagnoses get named wrong the commentators journalists and even the scientists forget to talk about the chronicity of the injury and forget to talk about what the prognosis for the patient is and those are really really crucial factors for understanding how to think about the care of a patient with a disorder of consciousness and I'll say a little bit more about each of those factors so as I said I think I think cases like like scott's and some of a few other cases in the literature that are like his do hold a lesson in humility for us potentially if we're willing to accept it but I would say that the lesson in humility was there for us to have even before this research came along so one thing to note is that we've known for a lot longer than this research has been around that it is extremely difficult to detect awareness at the bedside in some patients who who on at first blush look like they're unaware so we would classify them as vegetative the error rate the clinical error rate is thought to be somewhere you know in the range of 20 to 45 percent especially if you're not using sort of the most modern clinical assessment tools to try and detect consciousness so there were some papers from the 1990s that showed error rates like that if you had a a team of dedicated experts who examine patients very very carefully over multiple days you could you would catch you know 20 to 45 percent of the seemingly vegetative patients had signs of awareness so you know the smart clinician should should long before all of this have been very humble about what they said about the the awareness or lack of awareness of a patient at the bedside so we had that available to us and then the second lesson that this case has for us is we should be very reluctant to dismiss family members reports of signs of awareness this we didn't need fmri for that lesson either really I learned this lesson when I was a first-year neurology resident and took care of a young man who had developed a viral encephalitis and I met him six weeks after after he became comatose and then eventually became vegetative and we all knew that he was completely unaware that he was vegetative it was obvious you know you just have to look at him examine him a couple times and you know that he's vegetative right well the family members were saying to the nurses that they were detecting some evidence of awareness and of course the nurses and the rest of us all thought that they were you know just being wishful but over the course of a few days well then the nurses started to say you know I think maybe there is some evidence of awareness at the bedside it's very subtle but we're starting to see it and of course all the physicians said well no you're you know the family is sort of infecting your thinking here and you're just you're empathizing too much with them and then the junior resident started to notice it and you can see in the in the order of how much time you spend in the room the entire team became convinced that there was evidence of awareness and it actually convinced us to treat is a very special case it's an infectious case so it's a different type of problem we actually treated him with steroids and and he woke up and has a job he wasn't quite himself but you know six years later he was he had finished college and was holding down a job etc so I had learned to be humble about detecting consciousness at the bedside very early on and I think most clinicians learn that and if they don't they would be wise to learn it so I've already hinted that I that I think one of the crucial factors here to keep in mind is the distinction between diagnosis and prognosis and so far with this research all you can do with these tools is change a patient's diagnosis and maybe in the future findings like positive findings from research like this may be able to alter the prognosis of a patient but not yet we're not yet able to to make any confident prognostic statements based on a finding like this and that's that's really crucial I think to keep in in mind and to keep in focus because for most people making decisions about life sustaining therapy for these patients the question isn't which precise disorder of consciousness does my loved one have it's will they recover right so if you told me you're going to be permanently stuck in either a vegetative state or a minimally conscious state um you know which would you prefer I'd my at first blush I would say it doesn't matter for both of them if I'm stuck there I don't want to be kept alive in those states and so once the prognosis becomes sufficiently clear you should stop life support for me and so far these you know a finding a positive finding on a scan like this wouldn't actually change the prognosis until we link the findings up to the eventual prognosis of patients like this another thing to say about diagnosis in in this case because Charles focused mainly on this one patient the diagnosis here in the end was not vegetative and it probably shouldn't even be minimally conscious right this patient this patient is actually better than either of those because he could answer yes no questions fairly reliably and that's one of the things that moves you out of minimally conscious state into a better state so this is an unusual case where the diagnosis was moved from bedside vegetative to better than minimally conscious so this this patient was much more like a locked in patient um than than someone with a severe disorder of consciousness right you know and maybe i would need a few more yes no questions to be really persuaded that he had a very high level of awareness but it's it seems clear that he's better than minimally conscious so very very unusual case there are only a handful of patients who could who could answer yes no questions in the scanner with using a protocol like this that probably is going to grow but still very very small slice another distinction to keep your eyes on the distinction between traumatic brain injury and hypoxic ischemic brain injury so scott's from scott's an example of a traumatic brain injury and it's not a coincidence that that that or let me say it this way i would have predicted before knowing that traumatic brain injury was the cause here rather than a hypoxic ischemic injury and the reason is that the vast majority of research subjects who have been shown to be able to do this have been traumatic brain injury there's some physiologic reasons that i won't go into why that actually kind of makes some sense hypoxic ischemic brain injury patients have a much poorer prognosis that becomes certain of a much shorter period of time than patients with traumatic brain injury so that's a factor to keep in mind and then finally the time course is really crucial and often gets left out of cases like this so it's probably you know the first pass is probably to separate patients into acute and chronic patients and you could get more frangrine than that but but that's the biggest first pass in the chronic setting so more than a more than a year later what potential utility would have would would scans like this have well you could imagine many many patients for whom this actually wouldn't matter too much so but for the vegetative patient who's in a chronic state and for whom the decision has already been made to continue life support indefinitely i could actually see i could be persuaded that it would be very important to know if that patient is actually more aware than they look mainly not because it would change what you do because you've already sort of committed to long-term life support but because it might alter how people act at the bedside now that's also a lesson that i think we don't really need fmri to learn which is treat the seemingly unconscious patient like they're a conscious patient so that you don't make the error of you know subjecting an actually conscious patient to humiliation or pain or suffering but you know that lesson we is available to us already but it's actually that one's actually a hard one to learn and to really get ingrained into your into your practice and so i could imagine a clinical scenario in which boy it would be really helpful to prove that this patient who seems unaware is actually aware so that we stop treating them like a like a vegetable okay i want to i want to wrap up what i'm saying quickly so that we can so that we can have a discussion i do want to say a little something about the acute phase about whether this has some utility in the acute phase and that that may actually have some impact on the research that's getting done so patients in the acute phase are having usually have an endotracheal tube and a nasogastric feeding tube an oral gastric feeding tube and if they're going to transition to the chronic phase they're going to need some procedures they're going to need a tracheostomy and a gastrostomy and so usually it's in the acute care setting that we're making the first big decisions about life sustaining therapy usually within the first two weeks and i used to say that there's no role for putting people in the scanner and doing this sort of protocol to them and i'm still more or less there except that in patients with traumatic brain injury in whom you're contemplating stopping life support i could eventually see a role for using this technology partly because the the a positive finding would be so physiologically persuasive of better brain function and a higher likelihood of recovering consciousness later that even in the absence even before we actually get the the epidemiologic data on this i could envision myself being ready and willing to continue life support in a traumatic patient who actually showed evidence of awareness in the acute setting because i don't know it yet i don't know it to be true yet but i think it's neurologically it's so it's so plausible that there's got to be a link between a positive finding and a better prognosis i'm on the fence because it hasn't actually been scientifically proven but i'm ready to accept that as the data as the data come in let me let me stop there because i want to spend the rest of our time having a discussion with the audience so thank you very much thanks to toss and charles both we'd like to open up the floor for questions and i will keep a you know a list so you know wave your hand to me and i'll yeah the point the point about negative results is is very important and thank you for for raising that i mean i think i think with regard to the mental imagery task of you know it's the thing to remember about it is it's quite a high bar it's it's difficult i mean if you can just sort of think about it yourselves to to imagine sort of playing tennis right but keep doing that for 30 seconds right and each of these patients has to do that five times interspersed with with rest periods so i mean a lot has to be be working sort of in the cognitive machinery for people to be able to to do that there there are lots of reasons why one might have a negative result in this setting one is that that the patient is not consciously aware but but the patient may also have just fallen asleep right or or perhaps they have difficulties with with short-term memory and they can't remember the instructions right so so it's a it's a high bar that gives us actually pretty reliable evidence that someone is is covertly conscious negative results actually tell us very little with regard to the minimally conscious patients i don't think it's surprising that a lot of them could not perform this task again it's it's because it's a it's a high bar to be to be minimally conscious all you need to do to be able to do is to is to visually track an object if you can do that you're minimally conscious well that that's merely being able to do that as well below the bar of a mental imagery task right it'd be very it'd be very tricky to say we'll tell you if it's positive but if it's negative we'll say nothing they'll know they'll know what the result is and and brian edlow at mass general is is working in this field and has sort of the fmri tools available and has considered using it he's been asked by the intensive care team to use the the technology in the acute care setting um and has said yes but only after very careful discussions with the family making it very clear that a negative result doesn't mean anything right a negative result means nothing a positive result um means something about the clinical function but it doesn't yet mean anything about the prognosis in the in the case and so yeah I think eventually we're going to know more and it'll be easier to have that sort of conversation for now if you're going to use it you better be very very careful about what you convey to patients about the families and the expectations that you said before you even consider it but everybody if you could push the button mic in front of you that'll help with well I that's that's a that's a really important question it's a very big question too because I think there are there are distinct groups or distinct points in the timeline I think that we might think where where this sort of technology may you know over time proved to be useful I really liked how how how TOS spoke of a group of patients sort of more than a year out where there's been a decision to to continue with with life support and and and in that group it it might be very useful to um more systematically study those individual and see what see what bits of the cognitive machinery are are intact I think pragmatically the breakthrough there is going to come with advances in in bedside technology um adapting sort of EEG for for bedside assessment of patients fMRI is patients have to travel often to to to fMRI um it's not just the MRI machine it's the team that goes with it that's experienced enough to to administer these tests and certainly communication that's something that that to be practically useful has to be possible at the bedside so I think I think that is tech that is that is sort of a an area of application that we may see if if um if technology can be adopted for bedside use um I think another group for for whom this this sort of technology might be important are are are patients after injury you know have survived the initial injury but we're you know we're trying to we're trying to figure out how much how much intensity of resources to dedicate towards their their rehabilitation and I think you know currently at least in canada people get sort of a six month or six week I should say sort of run at rehab and if there isn't progress then you're kind of out you know I I think it'd be very interesting to to sort of evaluate patients before during and after more intensive rehab programs to to really begin to identify where we should be investing our rehab resources finally the the question of acute patients like in the ICU life and death decisions are are being made those aren't the patients I was talking about in fact the Owen lab is in a separate study scanning patients within hours of injury and looking for you know intact cognitive processing it's very challenging to do in the ICU environment to take someone safely safely enough at least down to a scanner and and evaluate them you know that's a study that's ongoing and and I think it in select patients it it could provide important new prognostic indicators importantly perhaps positive prognostic indicators so if a patient had sort of intact semantic processing in the hours after injury maybe you know maybe give them another week and see how they do kind of thing right and that's but but you know you're absolutely right about the overall picture here these are catastrophic injuries and I and I think families need to be making big picture decisions that incorporate the values of the patient in you know in the way that toss explains so well so Bob as I think you know I I'm with you in thinking that there's been an excessive amount of hype and sort of over extrapolating from from these findings to conclusions about what we should do in the clinical setting on the other hand I'm reluctant to argue that we should pull back because knowing too much would have bad consequences right this is what I did this is what made me uncomfortable about the Prometheus analogy which is Prometheus is you know his his fault was for being too curious or you know he wanted too much knowledge or power and you know I don't want to hold back from learning that we that we've been wrong about consciousness because I'm worried about the the consequences I think we have to we we have to go where the data lead us and accept the consequences as they are now I but then I would say that the consequences are not what some people are saying right the consequences are not as profound people like fins and and certainly the media fail to put these data into context and then apply it to you know and then the risk is that you'll be taking data like these and applying it to patients to whom it really shouldn't apply so I think we're dealing with with a very select group of patients in the in the chronic patients who we see for for neuroimaging these are these are families who who've made the decision to to continue care and a lot of families don't you know as you rightly point out knowing the values of the patient herself or or perhaps acting on an advanced directive that that individual had left so so we're dealing with with families who who have have decided to continue care it is an interesting I think interaction between questions of of faith and different religious or cultural views that that that may cause families to to continue care under under these under these circumstances I think though there's the question of quality of life is is is enormously important it's very tempting for for those of us including myself who would who would not elect to to continue treatment in a condition like this it's very tempting for us to sort of you know kind of want to impose our values on these kind of cases and go well that's not a good life right I mean what what is this family thinking right I think it's very important that we resist wasn't wasn't able to he wasn't asked the only quality of life relevant question that he was asked was whether whether he was in pain and that was really a first step I think our group wanted to wanted to take some time to really think through what a responsible and informative series of questions would be and it's taken us a while to to to head down that road I I still think though that that it's it's it's enormously important that to the extent that they're able that we give we give some voice to these patients and and we need to hear about where we can their subjective experience a group of patients that I worry about maybe agents like Scott or are those who are covertly conscious but but unable for whatever reason to to kind of communicate what it's like to be them so they're they're conscious enough to to suffer or experience pleasure but but but they don't they're not able to to tell us about it even with brain computer interface and we don't know how many of these patients there are and to me they they strike me as a particularly vulnerable yeah I that is a that is a difficult problem it's one can certainly imagine a scenario in which in which a you know a patient who's covertly conscious comes to have a different view about continuing sort of food and fluids than perhaps his or her family members do I think I think our our response has been to I don't know I think just to approach this with with humility and just say wow this is a really difficult problem and and yeah and and to sort of and to sort of say you know if we're going to demonstrate capacity anywhere and maybe we can't demonstrate it anywhere but if we're are able to demonstrate it anywhere it's going to be for low stakes decisions and I think for chronic patients those are you know they're day to day lives those are the kinds of decisions that are that are that are common for them so we've decided to start there I think I think our group feels that we're far away from being able to demonstrate that someone is capable of making a high stakes decision maybe we'll get there one day but we're quite far from that right now just maybe as a way of of reassuring you it seems a long way off before we can get to a place where we can interrogate not interrogate but but interview a patient with a technology like this in a way that we would get any real confidence about their capacity and and the reason I say that with some confidence of my own is that even with a patient who you know is locked in and is cognitively intact it takes a long time and a lot of work to establish a reliable communication method with them and then have long enough conversations and repeated conversations until you get to a point where you can even start to have a conversation about competence and and then you're only beginning the conversation because withdrawing life support from the locked-in patient early on after their injury is actually problematic in and of itself we see this in high spinal cord injury right like in the first two months six months maybe a couple of years we should be reluctant to withdraw life support from the patient who's telling us that they don't want life support right so it actually gets even trickier and so for this population that problem is many steps down the road I think I get that I mean that's what that's what everybody wants to know right I mean the family too right and but I think in order to be able to responsibly ask a patient a question we need to know what to do with their answer and if we don't know what to do with the answer we shouldn't ask the question so I'd say even again even in the setting of high cervical spinal cord injury where you can get a clear answer the patient will tell you you know yes or no to that question I would say you should be reluctant to accept their answer at base value right especially early on now later on after conversations and learning what life with a spinal cord injury is like you know then maybe you're ready to have that conversation and listen to the answer and say okay well you know now you know and you've had some time to adjust and you're still saying you don't want to live okay we can accept your answer but on day three after you know the trauma even if the patient said no I don't want to live I'm not sure that we should be accepting their answer when they say no I don't want to live so that's a whole can of worms but I again I think that problem for this population is several steps down the road because we can't even really ask them yet this is a rare patient a laborious protocol so I mean yeah I can't even conceive it yet I know there are more questions we are at our time though I'm afraid but I'd like to thank the Center for Bioethics for hosting this event I want to thank the staff I think maybe they're not in the room for putting the event together and making sure that it happens and of course I want to thank our two speakers Dr. Bayer and Dr. Cochran