The day is approaching when we will be able to contact apparently unconscious patients
My starting point in seeking to recognize non-responsive patients was a certain moment in 1997 when I met Kate, a young teacher from Cambridge, England. Kate fell into a coma after a flu-like illness. Within a few weeks, her doctors determined that she was a plant. This means that although she had cycles of sleep and wakefulness, she lacked conscious awareness. Her eyes opened and closed, her gaze seemed to sweep across the hospital room, but she showed no sign of inner life and did not respond when prompted by her family or doctors.
I was then involved in the development of new brain scanning methods in Cambridge. David Menon, a colleague of mine at Cambridge, who is an expert in severe brain injury, suggested that we examine Kate using a positron emission tomography (PET) scanner to see if we could detect any sign of brain activity in her. It was a low-probability gamble, but we had hints that some of our new brain imaging approaches might be successful. When Kate was in the scanner we projected pictures of her friends and family members in front of her on a computer screen and looked for any signs of a reaction in her brain. The results were extraordinary. Not only did her brain respond to the face images, but her brain activity pattern was surprisingly similar to what we and others have seen when we show healthy, conscious people the faces of their loved ones. What does this mean? Was Kate conscious, despite her outward appearance, or was the reaction reflexive? It took us more than ten years of research and method improvement to answer such questions.
Finding the answers became urgent. Due to improvements in trauma care in recent years, such as for victims of car accidents, both at the scene of the accident and in intensive care units, more and more victims survive even after a serious brain injury and end up in Kate's situation: living without any evidence that awareness was maintained. Such patients can be found in almost any city or town that has a skilled nursing facility. The decision regarding care and treatment - how much to support their lives, how to consider the wishes of the family members and the advance directives of the patients (if given) - is a complicated moral issue, involving suffering and sometimes lawsuits. Some of these injured recover to some extent, but it is difficult to predict in advance which of them will recover and to what extent; Others enter a state of minimal consciousness and exhibit incoherent, but infrequent, signs of awareness [See frame on opposite page]; And other victims remain in a vegetative state, sometimes for the rest of their lives, which can last for decades. The ability to distinguish between such situations is extremely important in order to make an optimal decision regarding the patient.
Imagine you are playing tennis
After Kate's brain scan, our team at Cambridge tried many methods of discovering hidden awareness, which we call latent consciousness, in patients who were declared "plants". We played them speech, like long sequences of spoken prose, and compared the response of their brains to that scanned when we played them speech-like noises that contained no message. However, as before, we were not sure whether apparently normal brain responses actually reflected covert cognition, or whether they were more basic, automatic neural signals that did not rely on higher-level cognitive processing.
Together with Menon and the neuroscientist Matt Davis and others at Cambridge I carried out very important follow-up experiments. We decided to anesthetize a group of healthy subjects, all anesthesiologists, and exposed them to the same combination of meaningful speech and speech-like noise that we showed earlier that it evokes normal patterns of brain activity in some of the patients in a vegetative state. We were surprised when the brain speech perception areas of the healthy subjects, rendered unconscious by the short-term anesthetic propofol, were activated at the same intensity as they were in the awake state. This vital evidence showed us that "normal" brain responses of patients in a vegetative state when they hear speech are not reliable evidence of covert consciousness. It seems that the brain processes speech automatically, even when we are not conscious and are not aware that we are doing it.
It was time to go back to square one. We had to look at the issue of hidden recognition in a different way. The real question was not how we activate the brains of these patients, but what activity we should observe to be convinced that the patient is conscious. We derived the answer from the classic clinical assessment of cognition: response on command. This is the familiar "squeeze my hand if you can hear me" test that is so often shown in TV medical drama shows. Our patients were, of course, too injured to respond physically to our commands. But will they be able to create a measurable brain response just by thinking about the command?
In our work with Melanie Boley, a neurologist in the laboratory of Steven Lauris at the University of Liege in Belgium, we measured brain activity in healthy subjects who imagined themselves performing various tasks, such as singing Christmas carols, walking from room to room in their home, and playing vigorous tennis. In many of these scenarios, mentally performing the tasks created a strong and reliable pattern of brain activity, similar to that created when the task is actually performed.
Using functional magnetic resonance imaging (fMRI), which unlike PET imaging does not require the injection of tracers, we found that the two best tasks were playing tennis and walking from room to room at home. And indeed, in every healthy subject we scanned, the tennis task produced strong fMRI activity in the premotor area of the cerebral cortex (cortex), which is responsible for movement planning. A mental tour of the rooms of the house, on the other hand, activated the parietal lobe and an area located deep in the brain, called the prehippocampal gyrus. These two areas are involved in spatial representation and navigation. Just like the TV doctor saying "Squeeze my hand if you can hear me," we found that we could elicit a reliable response to the command "Imagine you're playing tennis if you can hear me," which we could see with fMRI.
To our astonishment, this method was really successful the first time we tried it on a patient who appeared to be in a vegetative state. The young woman in question was involved, as a pedestrian, in a car accident. She had not responded at all to external stimuli for five months prior to her fMRI scan, and based on all internationally agreed criteria she was diagnosed as a vegetative state. During the scan we instructed her to perform two tasks using mental imagination. She had to repeat the tasks again and again, according to a certain order. Whenever she was asked to imagine a tennis match, brain activity in the premotor cortical area was very prominent, just like in the healthy subjects we tested earlier. When she was asked to imagine walking through the rooms of her home, considerable activity was seen in the parietal lobe and the prehippocampal gyrus, again as in the healthy subjects. Based on this finding, we concluded that despite her inability to respond physically to external stimuli, she was conscious. This finding changed the way people, including doctors, nurses and family members, treated her. Although I cannot give details about specific patients, I can say that in my experience, the discovery that a patient is conscious encourages others to communicate, visit, reminisce, joke, and generally improve the patient's quality of life.
Examining our method
A few years later we tried our method on many patients who allowed us to test its reliability and improve it. In 2010, in further collaboration with Lauris and his group in Blaise, we reported in the New England Journal of Medicine that in four of 23 patients diagnosed as herbivores (17%) we measured convincing responses in the fMRI scanner. For the purpose of the study, we examined the possibility of using mental tasks to allow patients to answer questions to which the answers are yes or no. One such patient had been severely brain damaged five years earlier and had been diagnosed several times as a plant. We told him, while he was inside the fMRI scanner, that we would ask him a series of simple questions and that he should answer them by imagining playing tennis (when his answer is "yes") or by imagining moving from room to room in his house (when his answer is "no"). Incredibly this patient gave answers to five questions about his life. He stated, for example, that "yes", he has brothers; "No", there are no sisters; And "yes", his father's name is Alexander (the name has been changed here to maintain confidentiality). He also confirmed the last place he visited during the last vacation before his injury. The researchers who interpreted the scans as "yes" or "no" did not know the answers to these questions, which were compiled based on information provided by the family [See frame on the right].
If you take into account the complexity of the tasks we used, it is clear that the cognitive occurrences in the patient's mind are more than those that only concern awareness of the environment. He preserved several functions at a high level: he could switch, maintain and choose his focus of attention, understand language and choose an appropriate response, save and manipulate information in working memory - for example, keep the instructions about "yes" and "no" in his head while he processes each new question - and recall the events that preceded the accident. Although this patient could "communicate" with us efficiently and reliably through the scanner, no one could develop any form of communication with him. Despite this, after the fMRI results were analyzed, repeated tests were conducted to examine his cognitive status using standard methods, and they resulted in changing the diagnosis to "minimum consciousness". This is a reminder that the diagnosis of consciousness in such patients is uncertain and subject to change.
In January 2011, I moved my entire research group to Western University in Ontario to continue investigating this problem with better resources, a larger team, and generous funding from the Canada Research Excellence Chair (CERC) program. This transition allowed us to expand and develop our research, and thus we were able to tackle some essential questions, including whether we can use our method to improve the relief provided to patients. For example, we could ask one young man, who was diagnosed as a plant for 12 years, questions that had the power to change his life; On the question "Do you suffer from any pain?" When asked in a dramatic moment filmed for television by a BBC documentary crew, he answered "no" and made it very easy for us.
Another essential question was more technical. Can we find a test that does not require an fMRI scanner? Performing an fMRI scan in patients with severe brain damage is an extremely difficult challenge. In addition to considerations of cost and availability of scanners, the physical pressure on patients can be very high, as they must be transported, usually by ambulance, to an fMRI facility with appropriate equipment. Some patients cannot lie still inside the scanner, and in others, metal implants, including plates and nails, which are common among severely injured people, may prevent the use of fMRI.
Our recent efforts have focused on a more portable and less expensive way to assess brain activity: recording the electrical activity in the brain (EEG)). This recording relies on non-invasive electrodes attached to the scalp and measures the electrical activity of groups of nerve cells in the cerebral cortex, the outer, convoluted layer of the brain. This test is not affected by metal implants, and perhaps most importantly, it can be performed while the patient is lying in bed. Unfortunately, EEG cannot easily distinguish changes that occur in deeper brain structures. Also, its spatial resolution (resolution), that is, its ability to detect clear responses in a certain area of the brain, is considerably lower than that of fMRI. To deal with these limitations we adapted our imagination tasks to generate activity on the surface of the cerebral cortex, in areas that control simple movements of the arms and legs. Damien Cruz, a postdoctoral fellow in my lab, found that if he asked healthy subjects to pinch their right hand or their toes, he could detect a difference in electrical activity through the EEG pattern these imagined actions produced. The method did not work on all subjects, but in 2011 it was reliable enough and we could start testing patients in their beds.
We bought a Jeep (which we called EEJeep), installed electrodes, amplifiers and laptop computers in it, the most powerful we could find, and drove to the patients. In November 2011 we published our findings in the medical journal Lantz (Lancet). They were similar to the results we obtained using the fMRI. Three of the 16 patients we tested with EEG (19%), who were diagnosed as vegetative, appeared conscious, according to their responses to commands to imagine contracting their hands or toes. Not everyone was convinced by this study. Analysis of EEG results is notoriously complicated, and another group of researchers questioned the complex new statistical algorithms we used. Fortunately, we were able to confirm awareness in the majority of patients who responded well in the EEG study using the more established fMRI method. After that we tested and published an improved version of our EEG method, which dealt with the findings raised in this matter. Through research budgets from the James S. McDonnell Institute we are collaborating with our colleagues in Belize and with other research teams in two different countries, including the research team that doubted us in the past, to develop a standard protocol for using fMRI and EEG to discover Covert recognition in patients in a vegetative state.
And what now?
Where are we headed now? The idea that we might one day communicate through thought alone has preoccupied scientists and science fiction writers for decades. The use of fMRI and EEG to discover awareness and begin to communicate with patients who do not respond in any other way paves the way for the development of brain-computer interfaces, which can transmit the patient's thoughts to the outside world. More and more it seems that such devices, when they become available, will be able to operate by translating certain thoughts into "yes", "no" and perhaps also into other concepts. However, creating such systems for people who have suffered significant brain damage will not be a simple task. Such patients rarely have control over their eye movements, so it is impossible to base such an interface on blink or gaze direction. The reduction of cognitive resources, a common result of a brain injury, may prevent any use of a method that requires extensive training, such as the current methods.
And despite all these pitfalls, it is very possible, and perhaps even inevitable, that fMRI, EEG, and newer technologies will increasingly be used to detect latent consciousness in unresponsive patients and raise some ethical and legal issues. It is possible that evidence of the existence of a hidden recognition in the patients that it was decided not to give them any more food and water would lead to the reversal of the decision. Already now it is possible to ask the patient through fMRI or EEG if they want to continue living in their current state. But are responses of "yes" or "no" enough to conclude that the patient has the cognitive and emotional capacity to decide on such an important question? How many times should the question be repeated and for how long? A survey conducted in 2011 with the participation of 65 patients with Locked in Syndrome), a condition in which consciousness is not impaired but the body is paralyzed, revealed that people have a surprising ability to adapt to extreme disability: most of them expressed satisfaction with their quality of life. It is clear that new moral and legal frameworks will be needed to guide exactly how and by whom such situations can be managed.
As for Kate, an amazing thing happened. Unlike the hundreds of vegetative state patients I've seen over the years, she started to recover a few months after her scan. She currently lives in her home with her family. She uses a wheelchair to get around and barely speaks, but her cognitive abilities have returned, including her sense of humor and her ability to appreciate the depth and importance of the role she, and her mind, played in the process of scientific discovery. Although she had no recollection of her brain scan, ever since she regained full consciousness, Kate had been an ardent follower of such scans. "It scares me to think what would have happened if I hadn't had that scan," she wrote in a recent email. "Please use my case to show people the importance of such scans. I want more people to know about them. It was like magic, the scan found me.”
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About the author
Adrian M. Owen holds the Canada Research Excellence Chair in Cognitive Neuroscience and Imaging at Western University in Ontario, where he studies brain injuries that cause cognitive impairment and the effects of neurodegenerative diseases on cognition.
in brief
The improvement of treatments for severe injuries has meant that more people survive brain injuries, but remain in a vegetative state or in a state of minimal consciousness. Researchers are developing imaging methods to determine which of these patients have any consciousness or which may regain consciousness.
Functional magnetic resonance imaging revealed, surprisingly, that some of the patients who were labeled with a plant are conscious. Some of them can answer questions by imagining a certain activity when their answer is "yes" and another activity when their answer is "no".
Researchers are currently turning to the method of recording the electrical activity of the brain (EEG) to develop an easier approach to detecting consciousness at the patient's bedside. In the more distant future, brain-computer interfaces may enable communication with patients who have latent consciousness.
More on the subject
Willful Modulation of Brain Activity in Disorders of Consciousness. Martin M. Monti et al. in New England Journal of Medicine, Vol. 362, no. 7, pages 579-589;
February 18, 2010.
Clinical Assessment of Patients with Disorders of Consciousness. Caroline Schnakers in Archives Italiennes de Biologie, Vol. 150, Nos. 2-3, pages 36-43; 2012.
Detecting Consciousness: A Unique Role for Neuroimaging. Adrian M. Owen in Annual Review of Psychology, Vol. 64, pages 109-133; January 2013.
Coma and Disorders of Consciousness. Marie-Aurélie Bruno, Steven Laureys and Athena Demertzi in Handbook of Clinical Neurology, Vol. 118, pages 205–213; 2013.
Eyes open, mind off, Steven Loris, Scientific American Israel, August 2007.
More information about the author's research: www.owenlab.uwo.ca
disorders of consciousness
Lost in the gray area
Consciousness seems to be all or nothing, like a light on or off. But actually there can be different degrees of recognition. Situations in which consciousness is impaired are known as disorders of consciousness (see above). They usually result from a head injury or events, such as a stroke or cardiac arrest, which result in a lack of oxygen to the brain. In most cases, lack of oxygen to the brain is worse than damage to it. Patients can advance or retreat from one definition to another, unless it is brain death, from which recovery is not possible.
Brain death:All functions of the brain and brainstem have completely ceased.
coma: complete loss of consciousness; Wake and sleep cycles disappear and the eyes remain closed. Coma, which rarely lasts more than two to four weeks, is usually temporary. After that, the patients regain consciousness or go into one of the states listed here.
Plant condition: There are cycles of wakefulness and sleep. The eyes can open spontaneously or in response to stimulation, but the only behaviors that appear tend to be reflexive.
A state of partial consciousness:Patients can appear in a vegetative state, but sometimes they show signs of awareness, such as searching for an object, following commands, or responding to the environment.
The locked-in syndrome: This is not a disturbance of consciousness because the patient is fully conscious. However, patients in this condition cannot move, so they may be mistaken for those who are in a vegetative state or minimally conscious. Many of the patients retain their ability to blink and move their eyes. Famous patient: Jean-Dominique Boby, who dictated his memoirs by blinking his left eye. (The memories were published in the book The Butterfly and the Diving Bell, and even received a film adaptation in the film of the same name - the editors)
The article was published with the permission of Scientific American Israel
