Marketing Italy Podcasts

A woman thought to be in a persistent vegetative state, unresponsive and unconscious to herself and the world, is asked to play a game of 'mental' tennis. Extraordinarily, brain scans reveal she can. In Australia, new ethical guidelines govern the care of people in this devastating situation. Besides new technologies and terminologies -- what prospects for those living frozen lives? TRANSCRIPT: Natasha Mitchell: All in the Mind on Radio National, your weekly excavation of the mental wilderness, Natasha Mitchell with a warm welcome. It´s a case of frozen lives and suspended selves on the program today, the plight of a life post coma and the perplexing nature of the vegetative state. Reading from Walking to the Moon by Kate Cole Adams: Memory. Anti-memory. I remember waking. That is all. I woke into the dark, and I thought I was dead. ... I woke from nothing into nothing. Nameless. I opened my eyes and closed them. Open. Closed. Nothing. But the words stayed in my body. Close. Open. And after a while the flickering darkness rearranged itself into slabs and passages, and I felt that I was in a small stone chamber which was an anteroom to a far greater chamber, and that in that other room was life, or death, I could not tell which. It was quite matter of fact. I had to decide whether to go there. There was nothing mystical or even mysterious about it. It was familiar. Like brushing up against someone you´ve sat next to all your life, and never noticed. It was only when I tried to move that I panicked. I felt cables from my throat, my wrist, between my legs. The world slipped and the separation was so vast I had to drag my spreading self into a pinprick of focus to find me again. I traced my outline from the inside. Starting at the right thumb and moving through my body I pushed myself into each digit, each limb, the small of my back, the space between my eyes. Fighting my way back to that fragile, glistening strand. I am the smallest, most delicate of spiders caught in the suck of the wind and below me my web hangs geometric and precise. I woke into blackness. No bedside lamp or radio or voice or shaky cigarette, I woke into blackness. Without. Cameron Stewart: I suppose the big fear—and this is a fear that a lot of relatives have is that they´ve been written off, that there´s nothing that can be done and so they´ll be put into nursing homes where they are not going to get appropriate care—that´s one fear. No only do they have no capacity to communicate but as we currently understand it they have no capacity to have higher brain function. So even if we could get across the technological barriers of communication, if we could discover new ways to communicate, in most cases of PCU, post-coma unresponsiveness, there will be no person to communicate with. Natasha Mitchell: So they are really unable to exercise their rights as a person in that state? Cameron Stewart: And for many people and even in the law, these people are described as being near death or in a state of living death. The technology has gone to the point where it can maintain life, but it doesn´t answer the ethical question of whether life should be maintained and that´s a job for not only lawyers but for ethicists and for the whole community. Adrian Owen: I mean image the situation: you were a patient who was, for example, minimally conscious; say you had some residual cognitive function, you might have some awareness of what is going on around you, but because of the nature of your injury, or your accident, you are unable to produce a response. You might be unable to raise your hand when you´re asked to. Now the beauty of the technique that we use, fMRI or functional magnetic resonance imaging, is that we can scan the brain and whether or not they are actually able to move matters less because we can see their brain responding. So in a sense we are using their brain as another index of behaviour. Natasha Mitchell: Neuroscientist Dr Adrian Owen with the Medical Research Council cognition and brain sciences unit in England. Before him Professor Cameron Stewart, Dean of Law at Macquarie University, and kicking off with a visceral excerpt from Australian writer Kate Cole Adams´s debut novel Walking to the Moon, about a woman who wakes from coma. But not all people emerge from coma, and diagnosing someone as being in a persistent vegetative state—now known in Australia as post-coma unresponsiveness—is a difficult process. In recent years a new clinical framework has been developed here to help and also just out are new ethical guidelines for care. One estimate though is that up to 40% of people are misdiagnosed. It´s not a case of negligent diagnoses rather that the often very subtle behavioural signs used can be difficult to detect. In response, Adrian Owen´s group is doing extraordinary, perhaps contentious work, they have turned to fMRI brain scans to bypass behaviour and look straight at the brain. Adrian Owen: The vegetative state is a condition that is often referred to as being a state of wakefulness without awareness. These patients appear to be awake, they open their eyes and sometimes they appear to go to sleep. Vegetative state often follows coma. A coma patient to you or I would appear to be asleep, again like vegetative state there´s no evidence that they are aware but they look like they´re asleep unlike the vegetative patients who open their eyes and appear to look around. The distinction between vegetative state and minimally conscious state is much more complicated and some vegetative patients will emerge into a minimally conscious state. But in practical terms the difference is really that a minimally conscious patient will show some evidence of being aware, being able for example to move a finger or a limb to command. Natasha Mitchell: How has the vegetative state traditionally been diagnosed, what sort of tools are used clinically to slot someone into that diagnosis? Adrian Owen: Well the assessment involves one of several scales. Different scales are used in different countries but they all essentially assess the same thing, which is they are looking for signs of either spontaneous or responsive behaviour. So a typical example would be to ask the patient to look from one side or look to the other side; or to see whether passing a mirror in front of their face the patient will fixate on the mirror and follow it with their eyes. So all of these things are behavioural, they all require that the patient is able to produce some kind of response. Natasha Mitchell: Adrian Owen, introduce us to a young woman, a 23-year-old who you published your work about a couple of years back now, because this has been a key case for you, hasn´t it? Adrian Owen: Yes it has. She was a young woman who was involved in a road traffic accident. She was assessed over several months and found to be in a vegetative state. She showed no behavioural signs of being aware of anything, of herself or of the surroundings. And about six months after her accident we were able to scan her in Cambridge and we asked her to perform a number of simple imagery tasks, tasks that we know activate specific areas of the brain when you think about them. The one that is most straightforward to describe is to imagine playing a game of tennis. Now we know that when you imagine doing something like tennis the parts of your brain that light up are actually the same parts that light up if you were to actually be playing tennis and actually moving your arms around. It´s a part of the premotor cortex that's known to produce movement of the upper body. And when we asked her to imagine playing tennis this is exactly what happened. Her premotor cortex lit up in exactly the same way we know that it does in a healthy volunteer who´s lying in the scanner imaging playing tennis. We had several tasks like this and of course we scanned her several times and each time, at each point in the scan that we asked her to imagine playing tennis this happened. Natasha Mitchell: You also got her to walk through the rooms of her home in her mind— made that request of her at least. Adrian Owen: That´s right, we needed a second task to make sure that this wasn´t just some general non-specific brain response. We had two quite different tasks that activate quite different areas of the brain. And imagining walking from room to room in your home activates an area known as the parahippocampal gyrus, which is deep within the brain and quite different to the premotor cortex. She was able to turn these areas of her brain on and off just by imaging these two tasks exactly when we asked her to do so. Her premotor cortex would start activating when we said to imagine playing tennis. Importantly it would continue to activate for the entire period before we asked her to relax and then it would stop. Natasha Mitchell: How long for? Adrian Owen: For 30 seconds, that´s just about as long as any of us can keep imagining playing tennis without any continuous reinforcement. Natasha Mitchell: Or play tennis in my case. How do you know that she was actually imagining playing tennis and it wasn´t just some other sort of set of brain processes going on in response to a verbal instruction, a complete sentence of some sort? Adrian Owen: Well the reason we know is she was instructed to do this before she went into the scanner, that when she heard the word tennis we´d like her to imagine playing the game. Natasha Mitchell: But you´d have no idea that she´s comprehending that, I mean this is a woman in a vegetative state. Adrian Owen: That´s right and that in many ways is why it was such an amazing result. But of course the fact that this area of the brain did respond when she was prompted with the word tennis means that we know she can understand language. She clearly had intact memory because we gave her these instructions before she went in the scanner, yet in the scanner she was able to do this exactly when prompted to do so. And she´s able to turn that information into what we think of as a wilful or voluntary act. Importantly we´ve tried these tasks in many healthy volunteers, you put people in the scanner, you ask them to imagine playing tennis, this same area of the brain lights up. Natasha Mitchell: Adrian Owen, working with these patients is a sensitive issue and how do you come at issues of consent in terms of them being involved in your study? And also the question of whether or not being involved in the study will have any actual tangible outcomes for them? Adrian Owen: Of course this is a very difficult issue, these patients can´t give us their own consent so we have to rely on the close relatives agreeing to the procedure. That said, fMRI is entirely non-invasive, there are no dangers for the patients. Natasha Mitchell: What do you take from this, because we have to really point out that this is one subject, one patient? Adrian Owen: And of course on the basis of one patient one shouldn´t draw any conclusions about all vegetative patients. It is important though because it gives us the way of establishing whether other patients in this condition are aware or not and that´s something that we didn´t have before. Now I can tell you that very soon after the first patient we found another patient who responded in a similar way but subsequent to that we scanned more than 15 patients and never found a third. So at the moment we know that she´s not unique, but we also think that it´s very unlikely that this is a common occurrence. Natasha Mitchell: Adrian what do you think for this particular woman the implications are of these findings? Adrian Owen: Clearly in her case the diagnosis was incorrect, again it was appropriate based on her behavioural signs but it was incorrect. And it´s important for the family and for the staff that are involved in her care to know that, that in fact she is aware of what´s going on around her and she has at least some level of consciousness. And the other point is that having established that she is aware we can start to work on turning that into some form of communication, some way of allowing her to register her responses to the outside world, or to just tell us about her needs and her wants. Natasha Mitchell: Tricky though, you can´t really slot her in a fMRI scanner for the rest of her life. Adrian Owen: But there are other techniques that could be used, very sophisticated, so-called brain computer interface, EG based, they are much cheaper than fMRI, they are much more portable. Natasha Mitchell: So you´re putting a cap of electrical wires on top of your scalp to register brain electrical activity? Adrian Owen: That´s right. They work with varying degrees of success and certainly a lot more work needs to be done before techniques like that will work very well in this particular patient population. But having established that the patient is consciously aware, we can then work on trying to adapt one of those techniques for their needs. Natasha Mitchell: This woman´s story is one of misdiagnosis of the persistent vegetative state and is likely rare, as Adrian Owen says, as are the numbers of people diagnosed in Australia. Figures are fuzzy but it´s considered to be less than 100 in any one year. This is All in the Mind on ABC Radio National, Radio Australia, online and as podcast with me Natasha Mitchell, exploring the ambiguities of states of unconsciousness, post coma. Now let´s go another step with this effort to get inside the head of a person who can´t express themselves. What if we could develop a language based on the neural signatures of brain activity? Dr Martin Monti is on the case, he´s a post-doctoral researcher with Adrian Owen´s team in the UK. You´ve been doing a very interesting study that will give people the willies, I think, and that is you´re trying to mind-read in a sense, or brain-read—give us a sense of the experiment you did. Martin Monti: Yes, so in a set of healthy volunteers we first characterised the neural signature of two specific tasks: motor imagery task, imagining for example playing tennis, and a spatial imagery task, imagining navigating a familiar environment such as one´s home. You´d put someone in the fMRI machine, so we first tried to detect the neural signature of each of these two tasks. And following that we asked a simple binary question which in this case was a simple as do you have any siblings? And we asked participants to answer by producing either of the two mental imageries. So the experiment would go we would for example we would ask them do you have any siblings—if we want to say yes, when we give you a cue imagine playing tennis—if you want to say no, imagine navigating around the rooms or your home. Natasha Mitchell: So how different is it though from saying imagining you were playing cricket as distinct from tennis, or image you were walking down the road swinging a handbag—a similar action to playing tennis perhaps? Martin Monti: So there may be a similar substrate that has to do with imagining, that has to do with producing motor plans. Probably there will be some difference in the specific motor plans that are being produced, but it is very clear that if you ask someone to imagine essentially moving his arms, to swing the racquet, versus imagine picturing an environment they know and navigating through it. Here it´s very, very clear that the patterns that are produced are very distinct. Natasha Mitchell: Okay, so with this study you then gave them a set of questions to respond yes or no to, what happened? Martin Monti: We could with 100% success rate detect what they were answering just by looking at their brain. So this leaves open the possibility that if someone cannot actually verbally respond to a question we could put them in a fMRI machine and just by looking in their brain see what the answer is. Natasha Mitchell: Not terribly realistic though clinically is it to pop someone in a fMRI every time you want to work out what their response to a question might be? Martin Monti: Well fMRI is a complicated technique that involves a lot of personnel, a lot of time, financially it is a cost. But it is clear that there may be a lot of applications in the clinical setting that will make all of this very worthwhile. The first would be of course in the act of finding the neural signature of these two tasks, this implies that we are probing if somebody is actually aware. So really the first step of this in some clinical populations is already a very big piece of information. But then you could think of very serious questions, for example, gathering whether someone is in pain. Just overall there is a set of questions about the inner state of patients that we cannot access. Natasha Mitchell: You can certainly imagine people getting rather nervous about this sort of development: well what if law enforcement agencies got hold of this technology and developed neural signatures for what I was thinking? And there´s certainly a lot of hype now around using fMRI as a marketing tool, you know, so you pop someone in a brain scan to ascertain what their unconscious buying desires might be. Or you give them a fMRI scan to ascertain whether they are lying or not, a kind of contemporary polygraph. Martin Monti: Yes, if something like this were to be developed it would still be quite far away and there are a number of reasons why. The first is that we may just not have the resolution to look into the brain and detect differences such as those you mention. The second is that our understanding of the brain may not be advanced enough yet for us to know what we would be looking for even if we could see it. Natasha Mitchell: Martin Monti where do you want to take the work next in the lab where you´re working with vegetative state patients? Martin Monti: There are two fundamental questions—one is can we enhance our ability to detect consciousness. And then a second very important stream of research will be on just understanding what are the cognitive abilities that are residually available to patients in these circumstances, which may have important repercussions in terms of how they´re treated, in terms of care they get access to and even just the environment the live in. Reading from Walking to the Moon by Kate Cole Adams: The next time a came awake, it was day, caramel light, a voice nearby. ... I kept my eyes shut, heart crowding my chest. The doctor tried a few more needles, one in my other foot, a couple in my arms, testing for responses. I lay very still, trying to slow my breathing. Then he said, 'Just a moment, I´ll try something else,' and the next thing I felt his fingers at my eye, smelled the disinfectant soap on him, and then I was looking straight into my own face. Just a moment. The reflected blue rim of the eye, the sloping lid pulled back by his fingers, and then I rolled my pupils back up into the darkness of my head and waited until he stopped. I heard him writing something on paper, packing his things into his bag—notes, needle, mirror—clicking it shut, crossing the room to the door. 'You can tell her family she´s awake,' he said on his way out. Natasha Mitchell: Recently I gather the term vegetative state itself has been reviewed and revised in Australia. What prompted that review? I gather it was actually a legal case. Cameron Stewart: It was, it was a case called Northridge. Natasha Mitchell: Cameron Stewart is Professor and Dean of Law at Macquarie University with a key interest in end of life decision making. Cameron Stewart: And in the Northridge decision we had a situation involving an unfortunate person who had been brought in to Royal Prince Alfred Hospital after a drug overdose. After some days a decision had been made by the treatment team to no longer provide active treatment to him because of severe anoxic brain injury. The family disputed that finding and wanted active treatment provided, over some months to-ing and fro-ing before the court eventually it was decided by the judge that an improper diagnosis had been made about the patient´s condition. Natasha Mitchell: So the court actually ordered treatment to recommence, I mean after five days treatment was withdrawn. Cameron Stewart: It was, after discussion with the judge it was recommenced. Then there were further iterations before the court and one of the arguments was that the patient was in as they called chronic vegetative state. Now the judge was very critical of that in the end and he was very critical generally of the Australian situation. We, as society hadn´t generated sufficient diagnostic material to determine when someone was in a state of unconsciousness from which they would not return. So he put it back to the medical profession and challenged the medical profession to come up with guidelines similar to what they have in the United Kingdom about how these types of brain injuries can be diagnosed. Natasha Mitchell: The key in this case was the fact that this patient was showing some responsiveness, that his rating on the Glasgow Coma Scale, which is a common scale used in this sort of assessment, shifted over time and there was some responsiveness to voice. Cameron Stewart: Yes, it shifted considerably. We often find that and part of the UK´s response to getting determinations of whether someone´s in a vegetative state from which they would not return is to wait. So they wait six months for a non-head injury and they´ll wait a year for head injury caused unconsciousness. Now in this particular case of Northridge, these diagnoses were being made after some days. And that was of a real concern to the judge and that´s why he asked for the medical bodies to come up with more certain diagnostic criteria. Secondly, it´s important because it was one of the first cases to highlight how disputes between families and practitioners should be resolved and how to avoid also disputes and ructions occurring between families and treatment teams. Natasha Mitchell: Interestingly, emerging from all that as part of this clinical framework that was set up a few years ago, the term 'vegetative state' is discouraged in Australia now and people suggest that you should use the term 'post-coma unresponsiveness' or 'minimally responsive state'. Is that mere semantics or is that a sort of considerable shift? Cameron Stewart: I think there´s a semantic edge to it but it can be viewed as pejorative to call someone vegetative, it does sound like the person is not being valued as a person. Natasha Mitchell: And what are the implications of removing the time factor, because persistent vegetative state sort of has this time dimension doesn´t it that´s saying this is going to be persistent, this is perhaps what this person´s reality will be for the rest of their existence. That´s gone now. Cameron Stewart: It is gone, but at the same time it creates the need for having some form of certainty in diagnosis and I think the NHMRC is trying to work towards that certainty. But given the state of technology, given our understanding of the brain and how it works, that´s difficult. So maybe what we should be working at instead of—before we can have a test or a diagnosis that is 100% certain—the best thing we can opt for is a certain and fair process and that´s what we should be looking at. Let´s have a process that gives everyone a say about what the best interests of this patient is. Natasha Mitchell: But this process is complicated in Australia with different guardianship laws in each state on decisions over treatment and its withdrawal. In the ACT and the Northern Territory for example families and spouses have no say, and the new ethical guidelines for care just out don´t consider the legal issues at all, much to Cameron Stewart´s disappointment. So legal uncertainties remain and so do the scientific uncertainties, as neuroscientist Adrian Owen knows all too well. It´s a delicate population you´re working with, isn´t it, because you´ve got families, loved ones who have incredible expectations and place a lot of hope in anything, any intervention with their loved ones. In what ways are you conscious of that so you don´t foster false expectations? Adrian Owen: Well it´s very important to address a number of technical problems in this area and one of them is—and there are many reasons why a patient in a vegetative state may not produce a response in the sorts of scanning studies that we do that have nothing to do with whether they are aware or not. So for example were a patient to fall asleep in the scanner—and that´s something that I do all the time, it´s quite a warm comforting environment in there, it´s very easy to just dose off. And similarly many of these patients have been involved in catastrophic brain injuries and they might be deaf and we often have no way of knowing. So we´re extremely careful about negative findings, and it would always be wrong to conclude that a patient was unaware if they didn´t respond in our scanning studies. On the other hand on those few occasions when a patient does respond it´s very exciting, it´s very important information that one is not able to obtain using other methods. Natasha Mitchell: Even if you did establish—what´s being done clinically so far with these patients probably isn´t sufficient on the basis of your research—you still don´t know what would be clinically sufficient to help them out. Adrian Owen: No we don´t, but of course these types of studies, sometimes present more questions than answers. But it does push us in the right direction I think, because we can now use this and hopefully we can use it diagnostically and prognostically perhaps to predict which patients are most likely to recover. But it´s very early days. Natasha Mitchell: There is a tendency for brain scan studies to sort of hit the headlines as ah, ha, we have found the spot for... We overstate the findings quite a bit in public conversation. Is there a risk with this, that if a case like the Terry Schiavo case comes up, hits the headlines and your work gets exploded out of proportion, that´s always a risk isn´t it? Adrian Owen: Yes this is a very important point. The patient that we saw was what we would call a traumatic brain injury, she had had a significant blow to the head. Terry Schiavo was a non-traumatic brain injury, her injuries were the result of loss of oxygen to the brain. Traumatic brain injuries are known to have a greater chance of recovery that non-traumatic brain injuries and certainly in a case like Terry Schiavo's where the patient has been in the condition for many years the chances of recovery are very, very much less than in our patient who had had a traumatic brain injury only several months prior to our scanning her. So until it is shown—and I suspect it may never happen—that a patient who has been in a vegetative state for many, many years and is perhaps a non-traumatic injury, until one of those patients is shown to imagine playing tennis then I think all we can say is this technique seems to be applicable to some patients in the early stages of vegetative state, particularly after traumatic brain injury. And we should be very careful not to extrapolate from that to all other patients that are in this same condition. Cameron Stewart: Obviously it´s incredibly important because it´s starting to unlock the secrets of the workings of the brain. As a lawyer, though, for me it still doesn´t change the ultimate question about the best interests, it´s always going to be that test, because even though the woman can imagine herself playing tennis she still can´t communicate. We can´t pluck it from her what she would decide, we know that she´s thinking about tennis but we can´t see what kind of tennis she is playing yet. For me it´s still the same question - what do we do, what is in the person´s best interest, what´s the fairest process for working that out and for protecting her interests? Until the good professor can tell me that she can make a decision and we can find out what it is then it does change it completely. Natasha Mitchell: Professor Cameron Stewart from Macquarie University and Dr Adrian Owen from Cambridge. Not an easy issue this one, as families experience a kind of limbo with loved ones whose lives have been effectively suspended. Lots of references on the All in the Mind website, your one stop spot for transcripts, podcasts, our email and my blog which I post to each week and love your thoughts there too. Don´t hold back I can´t always respond but the discussion between you is fantastic to read. All at abc.net.au/rn/allinthemind. Thanks to Julie Scott for the reading and to producer Anita Barraud and studio engineer Carey Dell, I´m Natasha Mitchell. More matters mind next week. read less