Questions at the Edge of Consciousness: A review of “Into the Grey Zone”

Imagine (and I hope this is a theoretical scenario rather than a real experience) that a friend is involved in a road traffic accident. The collision leaves them in what neuroscientist Adrian Owen terms the “grey zone”; the patient is alive (and does not require artificial ventilation) but they are in a “vegetative” state. Their body has periods when they appear to be awake, but they do not demonstrate any awareness of their circumstances. In the absence of intentional movement, how can we be sure that they are not, in fact, conscious – hearing the conversations next to their hospital bed, maybe even experiencing pain?

ITGZFor a long while this question seemed unanswerable. However a flurry of scientific papers, published about a decade ago, demonstrated beyond reasonable doubt that it was possible to communicate with some patients in an apparently vegetative state. Now Professor Owen has published a memoir Into the Grey Zone capturing his experience at the heart of that groundbreaking work. (I couldn’t wait for publication of the Anglicised version, so I actually have “…Gray Zone“, but am assured that aside from spellings and the occasional idiom, the contents are the same. I notice on social media that Owen himself refers to the book at ITGZ which not only saves a few characters but neatly side-steps the issue of the different title.)

Whatever we choose to call it, this is a remarkable and moving read – I cannot think of any other book that has simultaneously thrilled me with the clear and logical presentation of scientific experiments and moved me to tears with their implications of the experiments for patients and their families. What follows is my rather lengthy summary of the book, followed by some specific reflections. If you want to skip directly to the latter, click here.

The book follows a general pattern in which each chapter introduces us both to the individuals who had slipped into the grey zone, and to the emerging tools of neuroinvestigation which enabled Owen to demonstrate that many of these patients, perhaps 15 to 20% of those previously considered as “vegetative”, do in fact retain some level of consciousness.

The first chapter The Ghost That Haunts Me is slightly different. It features two central characters who slip into the grey zone, but neither is a patient of Owen. Instead they are his mother, who developed a brain tumour, and his former lover Maureen who suffered a subarachnoid haemorrhage that left her in a vegetative state.

Their influence of Owen’s subsequent work has been profound; consciously, or perhaps initially sub-consciously, these experiences have caused him to reflect on the person who is trapped inside a non-responsive exterior. In particular, Owen recalls his professional divergence from Maureen, also initially a brain researcher, who chose to move into nursing and helping the brain injured to make the most of their circumstance in practical ways. Owen, however, continued to be fascinated by the underlying science of the brain and stuck with fundamental research (this actually reflects a highly contemporary tension, to which we will return later).

In chapter 2 we are introduced to Kate, who was declared vegetative after a viral infection. Seeking to determine whether Kate was conscious, Owen and colleagues decided to use the best currently available technique which was Positron Emission Tomography. PET involves injecting the subject with a radioactive tracer which allows you to monitor blood flow as a proxy for which areas of the brain are most active.

A clear advance of techniques available previously, PET nevertheless had a number of significant limitations. Most importantly, the fact that it involves delivering radioactive materials into the body of the subject means that you are in effect exposing them to potential harm. As a consequence of concerns about this “radiation burden”, there is a finite number of times any one individual can be exposed to PET. This is especially tricky, since the technique actually needs multiple repetition to generate confidence that any observation is genuine. The duration of each individual test is also problematic; obtaining an image takes 60 to 90 seconds, plenty of time during which the participant’s thoughts might have wandered from the intended activity to something different. Finally, there is concern that you are comparing the brain architecture of an individual, the patient, to reference data generated from multiple people. This dilemma has become known as the group to individual (g2i) inference.

Notwithstanding these difficulties, PET was the best tool available at the time (1997) and represented a radical step on from previous approaches. However, having the technology is one thing, knowing what to investigate with it is equally as important. In preparatory work involving healthy volunteers, Owen (and other) had demonstrated that their brains responded differently when shown photographs of families and friends compared to photos of fuzzy faces as controls. Of course the volunteers were de facto conscious. For a vegetative patient such as Kate, an initial level of assessment was necessary before the face recognition test. A lack of response might, for example, reflect damage to her visual processes that would be masking underlying consciousness. To confirm that Kate could see, they showed her the colourful flying images that were the screen-saver for the computer they would use to show the faces. Gratifyingly, the visual cortex of her brain responded.

Remarkably, when Kate was then shown familiar faces, activity could be detected in the fusiform gyrus of her brain, the area known to be responsible for face recognition. This response was not triggered by the control images. Kate was awake and aware of her circumstances! Owen points out in passing that there is much more to face recognition than meets the eye (as it were). Our ability to spot a familiar face on a crowded street, or conversely an unfamiliar face at what was supposed to be a private function for friends, means that we are constantly scanning our surroundings and comparing the faces we see against stored memories. This was solid evidence, for the first time, that a patient in VS was conscious.

As it happens, and this is not always the case, Kate did eventually awaken more fully from her condition such that she was able to write, and even speak about her experience. There are important lessons from her experience about how we treat, and interact with, patients in an unresponsive state. Kate was, for example, able to listen to conversations around her; she knew who had bothered to introduce themselves and who had not (something that has actually been highlighted as a weakness with health professionals interactions with patients they know to be conscious, as highlighted by the #HelloMyNameIs campaign). Disturbingly, Kate was also aware of pain whilst in VS. Fortunately this is not a universal experience in the accounts of those who have returned from the grey zone, but is nevertheless something to bear in mind in the care of those whose circumstances are unknown.

Unlike a laboratory research programme where work (e.g. with healthy volunteers) can be scheduled, clinical research is much more opportunistic; it relies on the random arrival of patients in an appropriate condition for study. After Kate, the team had to wait three years before another suitable patient. She was Debbie, whose brain had been starved of oxygen following a car accident.

Simplifying the test: switching from pictures to words
Owen’s team has an ongoing strategy to develop cognitive tests that are less burdensome, and therefore less prone to false negative findings in which the consciousness of patients is missed due to the task being too difficult for them to accomplish. Debbie was the first for whom they used an auditory rather than a visual task.  In consultation with psycholinguists, a series of words were carefully chosen. All were two syllable nouns (sofa, candle, table, lemon, etc) which would evoke a clear mental image. These were contrasted against signal-correlated noise. As seen with Kate in the previous study, Debbie’s brain responses to the nouns v noise exactly matched the patterns recorded with healthy volunteers. Debbie, it suggested, was also conscious. As with Kate too, however, the technique being used to conduct the study was PET and the investigation was curtailed when Debbie reached her threshold for exposure to radiation.

Truly conscious?
Despite careful construction of the tests and apparently clear results with both Kate and Debbie, scepticism remained – in some commentators, if not in Owen himself – that the observed phenomena might still be some kind of automated response rather than genuine evidence of consciousness. What further work could be done that would put the question beyond doubt? In short, what test could produce results that would unequivocally show understanding not just experience of the trigger intervention?

At this point, our next patient enters the story. Kevin suffered a major stroke, causing damage to both his thalamus and brain stem. Inspired again by the work of colleagues in linguistics, Owen played Kevin words that were easy to understand and others that were harder to distinguish over background babble. The principle reflects the extra effort you have to make to tune into a conversation on the next door table at a meal whilst ignoring the less engaging chatter on the table where you are actually sitting! Amazingly, Kevin’s left temporal lobe – the area associated with language comprehension – responded the same way it had with healthy controls undertaking the same test.

New technology, new potential
The evidence for something more significant than an automated response was growing. It was, however, the introduction of a new method for monitoring brain activity that was to be a real game-changer. The development of functional Magnetic Resonance Imaging (fMRI) offered a number of crucial advantages over PET. Firstly, the technique does not require radioactive materials. Instead the flow of blood to active areas of the brain is detected by differences in the magnetic properties of oxygenated blood compared with deoxygenated. Secondly, the generation of test results is much quicker, so much so that you can effectively obtain real-time data.

As well as changes in the technology, the diagnostic tests were also evolving. The team started to investigate processing of words with ambiguous meaning of the assumption that the brain will have to work harder, and require more oxygen, to distinguish words that sound the same, but have different meanings depending on context in sentences, e.g. “he was disturbed by a creak in the floorboards” v “the explorer paddled up the creek”. Sentences containing multiple ambiguous words could be constructed (Owen gives the example “the shell was fired towards the tank”). Processing of ambiguous sentences needs identification of the actual words, checking against the potential meaning of those words and the construction into a whole that makes sense. If a patient demonstrated the same brain activity as a healthy volunteer it was even stronger evidence of understanding.

Since the new fMRI was not adding to the radiation burden Kevin had experienced in the previous PET studies, Owen was able to include him in research using the new method. Contrary to external indicators, Kevin was able to respond appropriately to ambiguity in the sentences he was hearing. Sadly, despite evidence of consciousness, Kevin did not emerge from VS.

Memories are made of this
Before moving on to the next phase in the emerging understanding of consciousness, Owen takes us briefly into reflections on the cellular processes involved in laying down memory. We have an implicit understanding that there are differences in the ways that we learn information about our world; some of it just seems to get picked up by osmosis as we drift through life, other facts get stored in a more intentional way – such as trying to memorise the phone number of a new friend or revising for a test.

It turns out that these different sorts of memories involve different areas of the brain. “Recognition memory”, things that we pick up along the way, involves the temporal lobes but not the frontal lobes. In contrast “Intentional memory”, when we are deliberately setting out to remember something, requires the frontal lobes to be functional.

In a flash of insight, Owen registered that intentional memory was intrinsically linked with consciousness; you can’t wilfully be remembering something if you are not awake and aware. Demonstration of activity in the frontal lobes, therefore, could be considered a proxy indicator of consciousness. To test the potential relevance of the distinction between recognition memory and intentional memory as a measure consciousness, Owen and a postdoctoral assistant set up the following scheme. Healthy volunteers were given an fMRI-based test in which they were either shown a series of artworks or the same art but with an additional instruction to specifically remember the next painting that they see. Under the general test, their temporal lobes, but not the frontal cortex, were activated. However, when invited to study the next image more closely, the frontal lobes also responded. The difference between an invitation to simply remember a series of painting and the specific instruction to study one of them was triggering differences in the brain activation, differences that could only stem from conscious decisions.

Evidence of intent
What the team needed now was some kind of test involving an element of intentionality on the part of the patient, something that would involve them in actively thinking about a process for up to 30 seconds. From previous work it was already known that an area called the parahippocampal gyrus was activated when we think about ourselves moving within a familiar context. They compared the brain responses in healthy volunteers whilst they imagined walking through their house, as well as when they tried to sing nursery rhymes in their head, or imagined the face of a loved one.

Of these initial three tests, only navigating your house produced consistent results in the volunteers. The researchers needed an alternative second test, something which participant could think about in a consistent way for half a minute. Probably inspired by the fact that the Wimbledon Championships were taking place at that time, Owen came up with imaging playing tennis. Thinking about playing other sports was considered, but unlike the variety of manoeuvres you might imagine playing football (heading a ball, dribbling, saving a goal), tennis had the advantage that it pretty much boils down to waving your arms around in the air.

Amazingly the instruction to imaging playing tennis elicited a signal in the premotor cortex of every healthy participant. They now had two different instructions that could consistently generate a measurable response in distinct parts of the brain. The true importance of having TWO tests would different activation patterns would come later, but for now the team were looking for a suitable patient with whom to try these prompts.

That patient turned out to be Carol, a pedestrian involved in another RTA. Despite significant damage to her frontal lobes and no indicators of consciousness by traditional measures, Carol was able to consistently activate the correct part of her brain in response to both of the prompts. There could be no serious doubt that she was doing this intentionally – Carol was awake and aware. This is one of the points in his story where Owen looks most closely at the ethical dilemmas posed by this kind of study, and by the regulatory procedures necessary to undertake the work.

Ethics, consent and the unanticipated
The team had obtained consent from the appropriate ethics committee to conduct the test, but had not factored in what they would do if they detected consciousness. They had opened a communication channel that enabled the patient to demonstrate they were still there, inside an unresponsive shell, but they did not have clearance to pass this discovery on to her family. So they didn’t. This may seem heartless (and in later cases, informed by this situation, they did change their practice), but they exploring uncharted waters in this work and they could not know what the unintended consequences might for family members who discovered that Carol was aware. The team had, for example, no magic trick available to bring her out of this state.

Despite the careful way that Owen’s experiments had been done, there was still a sector of the neuroscience community suspicious about the validity of the observations. It is fair to say that some fMRI-based studies had been poorly designed and had tarnished the reputation of the field in general. The potential for fMRI to generate spurious results was highlighted in an infamous study in which Craig Bennett apparently detected brain activity in a dead Arctic Salmon (see here for one account of that story).

Owen, however, reflects on whether there was another motivation for some people to be sceptical about the findings. If it was true that a percentage of patients in a vegetative state were in fact aware of their surroundings then it raised the unpalatable notion that the “care” people in such conditions were typically receiving (described as being “warehoused”) was tantamount to neglect. And what did it mean for legal test cases such as that of Tony Bland in the UK and Terri Schiavo in the USA? In both cases, artificial feeding had been withdrawn, allowing them to die, on the understanding that they were never going to recover from a Persistent Vegetative State in which they were oblivious of the world around them? Observation of brain responses in some patients added further complexity to these already-controversial cases.

Playing the “yes-no” game
At this point the story gets even more exciting. We noted earlier that there were two different verbal prompts – “imagine playing tennis” and “imagine walking through your house” – which generated consistent but distinct activation patterns in the brain. This dichotomy offers the potential for communication with a patient in the grey zone. Clearly this was not a mechanism for free-flowing dialogue with the outside world, but by using these two prompts as a proxy for “yes” and “no” respectively it allowed for the patient to respond to questions constructed to have binary answers. Owen had the system tested on himself first and then 16 healthy volunteers – three questions each. A colleague was able to correctly interpret their answers to every single question.

Since the availability of suitable patients occurs randomly, it was actually Owen’s collaborators in Belgium who had the first opportunity to conduct the yes-no test with a vegetative subject, a man who was, once again, the survivor of an RTA. The team chose only questions with factual answers (e.g. about family relationships and previous travel destinations) rather than matters of taste or opinion, on which the “correct” response might be unclear.

Owen takes time to explain that even answering these straightforward questions is more complex than we might at first think. The subject needs to understand the question (e.g. there may be language issues here), they need functional working memory in which to retain the question, they need to be able to recall the relevant information (which may have been stored either in response to life events (“autobiographical memory”) or as factual knowledge (“declarative memory”), and to remember which surrogate brain process was required for “yes” rather than “no”. This is no trivial combination of tasks; failure at any one of them would scupper the test.

As it was, the man in the scanner gave clear and correct responses to all five questions; he was demonstrating more than mere awareness of his circumstances, he was processing complex information, requiring the correct functioning of several different regions within his brain. With time available to do one further test, the team took the controversial decision to ask the ultimate question – “Do you want to die?” Perhaps fortuitously, the answer was inconclusive. We cannot be certain why this test “failed” – there may have been technical issues, tiredness or indeed the subject wanted intentionally to convey “it depends”. Fundamentally, however, the research had demonstrated that you can establish communication with some vegetative patients, even without capacity for them to move. Unsurprisingly, publication of these observations produced a flurry of media interest. However, the next results were to be even more amazing.

Moving across the pond
By this stage, Owen had relocated (for a second time) to Canada. He was introduced to Scott, a man who had been unresponsive for twelve years following, yet again, an RTA. I say “unresponsive” as this was the official medical opinion. Scott’s devoted mother, did not agree – she was convinced she not only observed facial responses, but also an occasional thumbs up.

In another of his interesting asides, Owen reflects on why a difference of opinion between doctors and relatives is a fairly frequent occurrence:

  • with few exceptions, doctors only get to meet brain damaged patients after the traumatic event. In contrast, family members have experience of the “before” person as well
  • family have more time to devote to one patient, their relative, whereas clinicians inevitably have their attention spread over a larger number of people – so genuine observations may occur and be missed
  • sadly, there’s also the possibility of wishful thinking – with family’s desperation to see improvement colouring their interpretation of events.

On the face of it (no pun intended), Scott looked like an unlikely candidate for either of the first two options. On a standard assessment, the Glasgow Coma Scale, which rates (i) eye movement, (ii) speech and (iii) motor responses on a scale of 1 (none) to 5 (normal), Scott scored 4 out of 15. However, since Owen had been asked to conduct a test, and since appropriate research subjects only arise opportunistically, Scott became the latest person to be put through the fMRI yes-no analysis.

To add spice to the proceedings, a BBC television crew were in town to make a documentary about his work. The somewhat simplistic premise of their project was that if, as it was claimed, 20% of patients in a vegetative state were actually awake inside their motionless exterior, then filming Owen working with five patients ought to uncover one where communication was possible. They were about to hit the jackpot.

Owen and his colleague explained the procedures to Scott, and asked him to imagine playing tennis. Immediately the correct region of his brain lit up. They asked him to imagine walking through his house, and again the response was immediate – despite twelve years rated near the absolute bottom of the Glasgow Coma Scale, Scott was very much awake and aware. With the consent of his mother, they then pushed the boundary and asked him if he was in pain. He wasn’t.

All of these events were captured by the TV team. Their footage became the amazing documentary The Mind Reader: Unlocking my voice, which is available to watch via the companion website for the book. Combined with an earlier BBC Horizon episode The Secret You (which I have written about here) these programmes give fascinating insight into the working of the brain, and Owen’s breakthroughs in establishing channels of communication.

Over the following months, Owen’s team put a series of additional questions to Scott. Some were directly for his benefit (e.g. confirming that he still liked watching ice hockey on the TV), some were more geared towards improving our understanding of how the brain is functioning in people with conditions such as his. For example, his awareness of certain facts (e.g. the name of his primary care-giver) demonstrated that Scott was laying down fresh memories post-accident, not just recalling details from prior to the crash. In contrast to some famous cases of brain injury, in which the patient had become detached from the overarching timeline of their lives, Scott was not “an island of consciousness moving through time” (p166). Sadly, this window of communication was only open for a brief while; Scott died from medical complications the following year.

Ventilation, Artificial Nutrition & Hydration and End of Life Decisions
Two thirds of the way through ITGZ, Owen takes a sideways step from describing the evolution of methods to communicate with people in PVS and related states, to reflect on important philosophical questions. The potential for a patient to end up in the “grey zone” is almost entirely a phenomenon of modern medicine. The advent of artificial respiration/ventilation is keeping alive individuals who would previously have died fairly swiftly. In many cases, ventilation provides a period of time in which the patient can recover and return to (at least some measure of) normal life. It creates the  risk, however, that someone’s body makes sufficient recovery to survive without assistance, but their brain fails to reboot. Such individuals are in the grey zone.

Here we enter a legal and moral minefield. Whilst someone is on ventilation they are receiving life-sustaining treatment. If this is cancelled, then the individual is being allowed to die. However, if they move beyond a point where ventilation is required to keep them alive, then an intentional act (albeit an act of omission) is required for them to die, and this might be considered as killing them. This raises the question of whether provision of artificial nutrition and hydration (ANH) is medical treatment. Owen cites well-known cases from an American context, but in the UK this was the nub of Airedale NHS Trust v Bland. In 1993, the House of Lords decided that elective withdrawal of ANH was lawful (for more on the ethics of that case, see this link). They did, however, indicate that legal permission to withdraw ANH needed to be sought on a case by case basis. Since the Mental Capacity Act of 2005, this role has been conducted by the Court of Protection. However a recent ruling by the Supreme Court in the UK has watered down this requirement.

If it comes to a point where a decision needs to be made to start/stop a certain avenue or treatment, the current gold-standard (as far as patient autonomy is concerned) would be the existence of an “advanced directive“. Also known as a “living will”, an advanced directive is an opportunity for an individual to lay out their wishes in case they reach a point where they have lost capacity to give consent. In the absence of a living will, the views of a surrogate decision maker might be sought. If no formal advanced directive exists, there may be some other form of prior indication as to the likely wishes of the patient. In the absence of any other information a “best interest” view would have to be taken.

Of course, the innovation of the Yes-No fMRI test disrupts these classifications as it becomes possible to ask the patient for their current perspective. The nearest category of patients who do possess an established ability to communicate are those with “locked-in syndrome” who may be able to correspond via blinking or small finger twitches. Some limited work has been done asking the views of locked-in individuals about whether or not they are happy in their present state. 72% of respondents said they were happy. Owen is refreshing candid about the potential “selection bias” in the study. As is typical in that kind of opinion-seeking research, not everyone invited to take part did so, and those who elect to be involved are more likely to have strong views on the matter [a classically over-quoted and heavily skewed survey of this kind investigated use of cognitive enhancing drugs by academics was published in the prestigious journal Nature which, frankly, ought to be ashamed at their shoddy methodology]. Nevertheless, the survey results may reflect a genuine re-setting of their parameter for happiness, in much the same way that other people’s views evolve when they adjust to changes in their circumstances.

Think specifically about a PVS patient who had drawn up a living will, or whose prior thoughts on how they would want to be treated, are well documented. These can no longer be taken as authoritative, if it now proves possible to ask them directly for their views based on the fresh insight of lived experience. It might be that they now indicate they wish the doctors to continue with their treatment, even though their advance directive/established prior views suggested the opposite. As Owen observes  “Imagine the nightmare of leaving a ‘do not resuscitate’ order and being conscious as it is carried out against your (current) will” (p187).

Conversely, the reverse might be true; that they had previously indicated “continue at all costs”, but now suggest they want their life to be brought to an end. However, Owen points out there are additional complications with knowing how to act on this information. If an otherwise healthy person indicated a preference to die, you would likely seek an assessment of their mental well-being rather than simply complying with their stated wishes.

Other ways to talk with the grey zone
Owen is the first to admit that the tennis-v-house questioning is not a one-size-fits-all solution for communicating with people suffering from brain issues. For one thing it is not quantifiable, it provides yes/no, black and white answers rather than a measurable value that could be shown to improve over time. Secondly, as previously noted, a large number of different brain centres need to be functioning correctly for the test to work; it therefore carries a significant cognitive burden. Other patients would “fail” the tennis test, despite having greater consciousness that medicine is currently acknowledging. Owen and others in the field are therefore constantly seeking to develop other ways to break into the grey zone.

For example, a former colleague in Cambridge has devised a test in which patients are shown superimposed images of faces and buildings. Your brain still picks them out separately, a bit like your capacity to look towards a window and prioritise either the curtains and the smudges on the glass, or to look through it to the events unfolding outside. The choice of faces and houses is non-coincidental, recognition of faces and places activates different parts of the brain (the fusiform gyrus and the parahippocampal gyrus, respectively). Combinations of familiar people and buildings or unknown people and places could be offered and these two areas of the brain monitored by fMRI. The test does not have the communication dimension of the imagining tennis v imagining walking test, but it has “reportability”, the potential to reveal previously undiagnosed consciousness.

Going to the movies
Owen and his team were developing another new test. Having observed that healthy volunteers watching feature films whilst in an fMRI scanner demonstrated repeatable patterns of brain activity, they wondered if patient with PVS might also show the same results, thereby demonstrating awareness of the events depicted.

The choice of stimulatory film would be important; they needed to make sure that brain responses were not being triggered crudely by, say, loud noises or bright lights in an automated way. What was needed was an evolving and engaging plot, with strong characters. They settled on a short made-for-TV film Bang! You’re Dead directed by Alfred Hitchcock. The plot involves a small boy finding a gun which he thinks is a toy, but the audience knows is real. As well as giving insight into the test subject’s long term memory (e.g. do they recall how guns work, and the importance of the weapon being loaded?), this also offers an opportunity to probe their capacity to see the world from the perspective of someone else, a concept known as “theory of mind”. This was a valuable additional dimension, with potential diagnostic significance, because some individuals, e.g. autistic children, are known to struggle with this ability.

Two anecdotes about showing Bang! You’re Dead to test subjects are described. The outcomes were very different, but both turn out to be fascinating (and, in at least one case, very unexpected). The first patient discussed was Jeff, who was considered to have been in a vegetative state for 15 years following a fight (although Owen’s own pre-study assessment rated Jeff minimally conscious, since his eyes appeared to track a stimulus). This would have been of no surprise to Jeff’s father, who was convinced that his son was more aware than the formal diagnosis, and as part of his care had taken Jeff to the cinema every weekend for more than 10 years.

In the scanner, Jeff’s response to Bang! You’re Dead was unequivocal; he was responding in exactly the same way, with exactly the same timing, as the healthy volunteers, and was clearly following twists in the plot. Without the need to coach Jeff through the tennis test, they had shown he was awake and aware of his surroundings. This had an immediate effect on Jeff’s brother, who became more committed in his apparently one-sided conversations, talking to Jeff about things going on in his life, with greater belief that he was being heard and understood.

The second story involving the film test is about Juan, a lad who had choked on a late-night snack and appeared to have suffered significant brain damage arising from the loss of oxygen prior to being found unconscious the following morning. Unlike Jeff, Juan’s responses to the film were mixed at best; there was evidence he was hearing some of the film but seeing nothing. Even this might have been more than expected, since Juan had scored 3 on the Glasgow Coma Scale, the lowest score possible without being dead.

However, the reason Juan’s story is fascinating stems from what happened next. As part of their routine follow-up care of research subjects (and how much do I love that they do this), one of Owen’s team rang Juan’s mum to see how he was doing. To everyone’s amazement it transpired that Juan was not only awake but was capable of walking and talking. This offered an unprecedented chance to ask Juan what he recalled about the events from his contact with members of Owen’s lab seven months previous; what could he remember about the visit, and about his feelings. Of course there was a distinct possibility he would remember nothing, but any crumb of genuine memory would be evidence that Juan was conscious at the time. The fact that being subjected to both fMRI and electroencephalography (EEG) analysis was a unique novel experience made it more likely that Juan might recall details than if he had been asked specifics about more routine events in his life.

As part of Juan’s re-assessment, Owen’s team prepared a set of faces and places. They included faces of people Juan would have met on his first visit, and those he definitely had not. Similarly there were images of rooms and equipment Juan would have seen, and some of different venues and kit he would not have encountered. [Interestingly, we set up a similar test in a fictional scenario in our book Where Science and Ethics Meet, where we discuss the potential of brain imaging to convict a suspect on the basis of involuntarily recognising their crime scenes.]

In the event, they needn’t have worried about what Juan might have recalled; he was able to demonstrate very specific knowledge of who we had met and what he had been asked to do. Despite his minimal score on the Glasgow Coma Scale, Juan was very definitely aware at the time.

A further year later, Owen went to visit Juan at his Toronto home. It was clear that the boy had continued to make progress, with Owen ruminating that factual memories had returned sooner than emotional engagement. In particular, Juan was now able to describe the experience of his initial hospital treatment and his encounter with Owen’s team. Importantly, he was able to point out that he had received inadequate explanation about what was happening when he was put into the fMRI and why, and this had left him afraid. Owen instantly resolved to make sure future participants got fuller and more careful explanation. In the mid 1990s, the British Medical Journal ran a regular feature A patient who changed my practice. This, it seems to me, would have been a classic case study for that series!

Juan’s emergence from so deep in the grey zone is not unprecedented (Owen cites the well known examples of Jan Grzebski and Terry Wallis) but is certainly rare, and for Owen’s team it was new ground. As Owen notes “We finally had absolutely unassailable evidence that a patient could appear to be entirely vegetative, yet remain absolutely conscious” (p214). Reading this, I couldn’t help but think of Tony Bland, Terri Schiavo and others who had care withdrawn on the basis of seeming unresponsive using tests available at the time, but who might have been shown to be conscious on the basis of newer methods.

Bringing the test to the patient
The penultimate chapter of the book introduces the latest technological developments. Recognising that fMRI is an expensive procedure, and that the size of the scanner means that patients need to be brought to a test centre for assessment, Owen and others have been looking to adapt the principles of consciousness-testing to more portable technology.

The chosen approach is EEG, in which electrodes (128 in this instance) are placed over scalp of the patient/subject – there is a well-known image of Owen himself wearing the EEG cap in this article from Nature. EEG measures electrical activity in the brain arising from the coordinated response of thousands of neurons. It conveys less spatial information than fMRI (i.e. the details about which specific area of the brain is active are less refined), but if it can be developed as a tool to at least confirm consciousness in a robust way, then the reduced costs and increased accessibility would allow it to become an integral part of bedside assessment for patients in the grey zone. To help facilitate access, Owen and his team have a specially kitted out vehicle, the EEJeep, that allows them to go to the patient not vice versa.

Test questions for the EEG system aim to exploit a phenomenon known as “priming”. If a subject is presented with a pair of related words (e.g. “chair” and “table”), the brain response to the second word is smaller than if the second word is unrelated (e.g. “chair” and “monkey”); somehow the unexpected nature of the second word evokes a larger response. A similar effect is seen is a sentence contains an illogical twist (Owen uses the example “The man drove to work in his potato”).

The mobile EEG method was very new at the time Owen wrote the book (there is an inevitable delay in the publishing process), which may explain why the story chosen to illustrate this chapter actually described an unsuccessful attempt to reveal consciousness. The patient in question was an elderly man Leonard, who had slipped into the grey zone after a cardiac arrest. I suspect the other attraction for telling his story, despite no miraculous breakthrough, was the utter devotion of Leonard’s wife Winifred and her enthusiastic endorsement of Owen’s work in the phrase “People like Leonard need a voice”.

Where to from here?
As the book draws to a close, Owen indulges in a little horizon-gazing; where are current developments in neuroscience likely to lead in the next few years? In so doing, he reflects on the fact that (at present) studies of the physiological “signatures” of consciousness are really looking at evidence of being conscious, rather than consciousness per se. He also emphasises the distinction, which has already been apparent in earlier chapters, between showing someone is conscious, versus accessing that consciousness.

Technologies for thought-based control of artificial limbs and of vehicles have started to emerge. To illustrate growth in brain-computer interfaces (BCIs), Owen gives the example of tetraplegic Cathy Hutchinson, who could control a robotic arm with her mind using BrainGate technology. To achieve this, Cathy had electrodes implanted into her brain. This course of action is not without risks and should not be pursued in a trivial manner. Related developments (not discussed in the book) include the mind-controlled tablet computer and the mind-controlled car, At an interface of these technologies, Christian Kandlbauer with thought-controlled prosthetic arms sadly died when his car crashed into a tree.

Then there are applications associated with criminal law or forensics (this is something I go into in bit more detail in my book Biological Determinism, Free Will and Moral Responsibility). Will we be able to read minds to establish guilt? A lot of interesting work in this area has been done by Nita Farahany. In the example Owen picks up, his team was being readied to conduct fMRI analysis of a shooting victim to see whether they could ask who had shot him. In the event, the patient actually awoke and so this ground-breaking approach did not need to be invoked (although it did inspire the plot for a TV drama).

In a different direction, the idea of testing animal consciousness and machine consciousness are floated. All fascinating stuff.

Overall reflections
The preceding sections (nearly 7000 words in length) offer a detailed summary of the ground covered in Into The Grey Zone. The book truly is an excellent introduction to cutting-edge neuroscience research and it’s implication for patients (what is known in current jargon as Translational Research or a Bench-to-Bedside approach). What follows is a slightly eclectic mix of overall impressions having read the book.

Firstly, there is the importance of factors outside of the research itself. This includes Owen’s decision to pursue the area of study he has, which has been influence by his own illness, his mother’s brain tumour and his friend Maureen slipping into the grey zone.

Tied to this, secondly, is the fact that key breakthroughs can occur during “downtime”. Owen talks about a key insight that came to him whilst at the beach in Sydney. This reminded me both of the story of Kary Mullis who reportedly invented the Polymerase Chain Reaction whilst driving his car. It also made me think of colleague’s daughter, a theoretical mathematician, who claims her best breakthroughs come whilst rock climbing.

Thirdly, I was struck by the dedication of the relatives of those who are in the grey zone. Their commitment stretches to months and sometimes years caring for the patient, talking to them, maybe taking them out on trips, looking out for every hint of improvement.

This spills over, fourthly, to the care (or lack of it) experienced by patients with brain injuries. It is something of which Owen is clearly acutely aware. He talks about this at several points in the book, including in regard to his early patient Kate, and in regard to Juan’s post-awakening account of his experience being put through the tests. Despite the fact the patients may appear unaware, it is about treating them with dignity. It is best to assume that they are and to explain what is going on and why, to introduce bits of equipment and to introduce people. As noted in the earlier commentary, there is a broader issue with patients being given adequate information. This has been highlighted in the UK by the #HelloMyNameIs campaign launched by the late Kate Granger.

Demonstration of awareness sometimes changed attitude to the patient (we see this reported in the context of Jeff’s brother), but in a perfect world it ought not to – dignity and respect ought to be the norm (I was reminded here also of Martin Pistorius’s account of the abuse he suffered whilst a locked-in patient, as set out in his autobiography Ghost Boy and recent BBC feature.)

Fifth, there are several issues relating to the ethics of research in these areas. What are the consequences of making contact with someone who is in a vegetative state, minimally conscious or locked in? What about their involvement in the more experimental aspect of the work? They cannot give their consent and fundamental research may be unlikely to benefit them personally – who says that it is ok for them to be involved?

This dovetails somewhat with the sixth point, the interplay of experimental design, luck and wisdom. There is no doubt that Owen has struck lucky on several occasions – with only 1 in 5 patients demonstrating awareness, the fact that patients involved in early breakthroughs were often in that minority was definitely (in part) fortunate. The momentum for the programme could easily have been lost if they had begun with a whole string of negative responses.

Having said that, however, Owen is unduly humble in his account. The saying goes that you make your own luck, and what we see here is some well designed experiments and the capacity both to ask the right questions and to recognise the relevance of the observations being made (this is not always the case – famously the data that led Harry Kroto to discovery buckyballs were not the first results that ought to have pointed to their existence, but previous researchers had not spotted the relevance of their observations).

Like Harry Kroto, Owen brings in knowledge from his interest in other disciplines. His passing reference to the structured coffee breaks (and croquet) at the Applied Psychology Unit in Cambridge touches on the importance of mixing and mingling with people working in tangential fields and cross-fertilising ideas. Shared tea times, even communal spaces where this can happen, have sadly been lost from many universities and research institutes (in this story I did also chuckle at the role played by the mysterious Brian who seemed to do nothing other than organise tea. I did two months of my own PhD at a famous institution in the USA where the main role of a chap called David seemed to be to keep the coffee machine topped up.)

Seventhly, there is a tension between the value of basic research for its own sake, e.g. understanding the working of the brain, and both the philosophical (e.g. what is consciousness and when does it start?) and clinical applications (e.g. what does this knowledge tell us about our patients and how they should be cared for?). This dichotomy was evident in the divergent routes taken by Owen and Maureen; he took the research route, she headed towards care for the individual. In the end though (and this is hinted at in the epilogue) they were both right – care for the patient is paramount, but can be improved by application of knowledge emerging from the fundamental studies.

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1 Comment

  1. […] demonstrates through the extraordinary testimonies in his book ‘Into the Grey Zone’, reviewed here by Chris Willmott, some patients with PVS and MCS have far more awareness than we might possibly […]


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