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Hidden consciousness
PETER STRAIN
38 | New Scientist |29 June 2019
Features
Hidden consciousness One in 10 people believed to be permanently unconscious may actually be aware. How do we rescue them from their limbo? Helen Thomson investigates
“
I
HAVE pictures of five patients on my wall,” says Nicholas Schiff. “They all seem to be in a vegetative state, but we know they are conscious. It’s to remind me they are out there and we are not helping them.” Schiff, based at Weill Cornell Medical College in New York, is one of the world’s leading experts in disorders of consciousness. Many of his patients are in a vegetative state. Their injuries have left them with no awareness of themselves or of the world around them. Or so we thought. In 2006, it was discovered for the first time that a woman believed to be in a vegetative state was actually conscious, after brain scans revealed she could imagine different things on request. That breakthrough was quickly followed by a devastating revelation: our ability to determine whether someone is conscious based on their behaviour alone isn’t accurate enough. It is now known that some people have what is called “covert consciousness”, in which they have awareness that comes and goes, but can’t move any of their body. At first, it was believed to be a tragic but rare misdiagnosis. Now, results from a 10-year investigation suggest that many people could be trapped in this way. Their bodies lie still, but their minds are active. This creates an urgent need to find techniques that could awaken them. It also raises ethical questions about what we need to ask these people, and ourselves, when they do manage to make themselves heard.
As recently as the late 1990s, it was assumed that people in a vegetative state, by definition, had no conscious awareness. They would show signs of sleep and wake cycles, and occasionally open their eyes or make involuntary movements, but weren’t aware of themselves or the people around them. However, Adrian Owen, then at the MRC Cognition and Brain Sciences Unit in Cambridge, UK, had a worrying thought: what if we were wrong? Neurologists have long been aware of locked-in syndrome, in which people are awake and aware but unable to move almost all of their body. It was first defined in medical textbooks in 1966, but must have been known about much earlier; it was described in Alexandre Dumas’s 1844 tale, The Count of Monte Cristo. People who are locked in need help breathing and many can communicate only using eye movements. But they aren’t
“Many people in a vegetative state may be trapped. Their bodies lie still, but their minds are active”
classed as having a disorder of consciousness, because, unlike people in a coma, vegetative or minimally conscious state, they are fully conscious (See “Consciousness confusion?”, page 40). Still, a diagnosis can take months, or even years if eye movement is limited. Owen wondered whether people in a vegetative state could also have a hidden awareness. At the time, this was dismissed as a “bonkers idea”, he says, not least because it made people feel uncomfortable that someone might be trapped inside their body without anyone knowing. Nevertheless, Owen’s team began to test his theory. Their first patient was Kate, a woman left in a vegetative state by a virus. In 1997, they scanned Kate’s brain using positron emission tomography (PET), which can measure brain activity, while showing her pictures of her family or playing familiar speech. To their surprise, her brain responded just as you might expect a healthy person’s brain to respond. But Owen’s team faced a problem: a lot of neural activity happens automatically, so the result didn’t necessarily prove she was conscious. It took another decade to work out a solution. In 2006, Owen and his colleagues showed that a 23-year-old woman in a vegetative state could respond to instructions, by asking her to imagine walking around her house or playing tennis. These two mental tasks require different brain activity, which can be identified from brain scans. It confirmed, beyond any doubt, that she was consciously aware of > 29 June 2019 | New Scientist | 39
CONSCIOUSNESS CONFUSION? Brain dead A person is brain dead when they no longer have any brain activity. They won’t regain consciousness or be able to breathe without artificial life support.
Coma Someone in a coma is unconscious and has low levels of brain activity. They will be unresponsive to sound and pain and will have greatly reduced reflexes such as swallowing or coughing. They may be able to breathe on their own.
Vegetative state A state in which a person may have some reflexes, including yawning and eye movements, but shows no awareness of themselves or their environment.
Minimally conscious As a person begins to show intermittent awareness of themselves or their environment, they are said to be in a minimally conscious state. As they develop the ability to communicate, they are said to have emerging consciousness.
Covert consciousness Some people who are diagnosed as being in a coma, vegetative or minimally conscious state may have periods of awareness that they are unable to reveal because they can’t make any purposeful movements. This differs from locked-in syndrome because the person still has cognitive troubles, such as memory loss, or inconsistent consciousness.
Locked-in syndrome A person who is locked in is fully conscious, so isn’t classed as having a disorder of consciousness, but is unable to move most of their body. Sometimes they can communicate through eye and facial movements. Their condition is normally associated with an injury to the brain stem.
40 | New Scientist | 29 June 2019
herself and the researchers, and that she had the ability to respond to their requests. Disorders of consciousness are notoriously difficult to diagnose. Most doctors use variations of the Glasgow Coma Scale to assess someone’s ability to open their eyes in reaction to various stimuli, and their verbal responses and motor movements. And they can use brain scans to identify physical damage. However, to identify covert consciousness, you need to use functional MRI (fMRI) or several EEG tests over time to verify brain activity that reflects comprehension and the capacity to follow commands. “But we’re just not screening patients for this level of higher function,” says Schiff. “And it’s not that hard to find them when we do.” The real canary in the coal mine, says Schiff, was a study carried out in 2017 by Brian Edlow at Massachusetts General Hospital. Edlow knew that covert consciousness had been discovered in people who’d had months or years to recover from their injuries, but he wondered whether it might exist in people with more recent brain injuries. He and his colleagues scanned the brains of 16 seemingly unconscious people with severe head injuries. During the scans, he asked them to do mental tasks, such as “imagine squeezing your right hand”. Of eight people who had no behavioural evidence of awareness, four could follow his instructions. It was a small study, but it had massive ramifications. “These people were in intensive care,” says Schiff. “What if you’d withdrawn their care?” Even for those who are provided with lifesustaining treatment, a misdiagnosis might result in limited rehabilitation that thwarts an opportunity for recovery. In Schiff’s own studies, he has identified 16 people with covert consciousness. For some, this diagnosis was life-changing. For instance, one man, thought to be in a vegetative state, made sporadic head movements that had been dismissed as random. Once the team became aware of his covert consciousness, however, these movements were given more attention. A researcher at the hospital developed a headmounted computer mouse for him, which he used to control a keyboard. Eventually, he was able to write Schiff an email to give his own consent to join his next study. How many more people might be in this
situation? There is no data on the exact number of people with disorders of consciousness across the world, but for the past 10 years, Schiff has been involved in an international investigation into rates of misdiagnosis. The latest conservative estimate is that one in 10 people who appear to be in a coma, vegetative or minimally conscious state actually has covert consciousness. “It’s a big problem,” says Schiff. “And now we know it’s not a rare problem.”
Coming around Twenty years ago, there wasn’t a lot you could do for people in a vegetative state other than hope that they would slowly recover, or have a rare, spontaneous awakening. That changed with Louis Viljoen. In 1996, when he was 24, a truck crashed into him on his bike. The trauma left him in a vegetative state for three years. One day, when visiting him at his care home, his mother noticed that he seemed restless. She called his doctor who prescribed him a sleeping pill called zolpidem to calm him. His carers crushed it up into some water and got him to swallow it. Fifteen minutes after taking the drug, Louis opened his eyes, turned his head, and said: “Hello Mummy.” From that day on, Louis could be woken once a day, for 3 hours. He would interact with his family before drifting back into unconsciousness. After six years, he awoke permanently. His story proved something important: that some people in a vegetative state have the capacity to be awoken with the right intervention. Zolpidem appears to “switch on” areas towards the front of the brain involved in higher-level thinking and initiation of movement. This outweighs the sedative effect of the drug on other brain regions. Unfortunately, excitement over zolpidem’s potential was short-lived. A small, placebocontrolled trial found that it benefited just four of 84 patients with disorders of consciousness. John Whyte, director at the Moss Rehabilitation Research Unit in Pennsylvania, says that despite a few families who use it every day to wake their loved ones, most find the effects diminish with repeat dosing. Not to be deterred, Leandro Sanz, a doctor at the University of Liège in Belgium, and his colleagues have begun testing another
“We’re not screening patients for this level of higher function – and it’s not hard to find them when we do”
drug, called apomorphine. The drug mimics dopamine and is regularly prescribed to help people with Parkinson’s initiate movements. Results from the three people treated so far in a pilot trial look promising: one participant was unable to communicate at all at the start. By the end, she could move her hands in response to commands. “There’s this moment, when they squeeze your hand for the first time, and you know they’re there, really there, with you,” says Sanz. “It’s like this presence has stepped into the room.” A second participant has started to turn his head when you call his name, and a third, who was attempting, unsuccessfully, to use his thumbs at the beginning of the trial, can now say “yes” and “no” and dress and shave with help. Sanz is now recruiting for a larger study. Drugs aren’t the only option. In 2007, Schiff and his colleagues wondered whether they could kick-start the damaged brain using electricity. There was growing support for his “mesocircuit hypothesis”, which attempted to explain how consciousness is recovered after a brain injury, and how cognition can outpace recovery of motor abilities. The hypothesis involves several networks associated with the thalamus (see diagram, below). The thalamus sits just above the brain stem, which connects the brain to the spinal cord and acts like a central station. It relays
YOU MAGAZINE/GALLO IMAGES/GETTY
Several drugs are being tested to wake people from coma - including the pill that roused Louis Viljoen (centre)
information towards the basal ganglia, which is involved in movement and reward, and the forebrain, made up of the two hemispheres of the brain, the thalamus and the hypothalamus. Together, these areas are responsible for learning, memory, personality, our senses and regulating breathing and other autonomic functions. It is thought that brain trauma disrupts this network, decreasing activity in the forebrain. A drop in activity also happens in the forebrain as we drift off to sleep or go under with anaesthetic. It is also the last part of the brain to come back “online” when a person emerges from a disorder of consciousness.
The network that underlies consciousness The mesocircuit hypothesis suggests that signals from a vast network of brain regions together create our experience of consciousness. Researchers are trying to spur this network into action using two main stimulation techniques, A and B Frontal lobe Complex behaviours, communication, memory, attention and personality Prefrontal cortex Emotion regulation, intuition, insight, empathy
Basal ganglia Movement, reward and emotion
Parietal lobe Language, attention and senses
A
Globus pallidus interna Regulation of voluntary movement Temporal lobe Memory and senses
Motor cortex Planning and control of voluntary movement
B
Thalamus Central station of sensory input Occipital lobe Vision
Pedunculopontine nucleus Initiation of movement
A Scientists use non-invasive brain
stimulation called tDCS over the prefrontal cortex, an area involved in our most complex behaviours, thoughts and personality
Striatum Involved in diverse aspects of behaviour and movement
B Deep brain stimulation targets the thalamus, an integral part of the mesocircuit thought to control consciousness
To see if they could kick-start this network after injury, Schiff’s team implanted electrodes in the thalamus of a man who had been in a minimally conscious state for six years following an assault. Improvements were seen straight away. By the end of the six-month trial, the man could eat, speak and watch a movie. Despite every major news outlet in the world reporting the result, Schiff’s research in this area halted. No funding agency was prepared to pay the huge amounts of money required for the participants’ rehabilitation and care during such a long study. “Talk about an uphill battle,” says Schiff. “No one wants to pay for it, and researchers can’t do this alone.” It wasn’t until 2016 that Martin Monti at the University of California, Los Angeles, and his colleagues attempted something similar, this time using low-intensity ultrasound, a noninvasive technology that modulates the thalamus without the need for surgery. Once again, the results were impressive: his patient was a 25-year-old man who had received a severe brain injury after being hit by a car and was in a minimally conscious state for three weeks. The morning after the treatment, the man tried to communicate with vocalisations and gestures. Three days later, he started answering questions by nodding or shaking his head. A week later, he got out of bed and attempted to walk. Monti’s team has since used the technique with other patients and is now moving ahead with a clinical trial. Meanwhile, Angela Sirigu of the French National Centre for Scientific Research in Bron and her colleagues were trialling another technique. It focuses on stimulating the vagus nerve, which runs between the brain, the thalamus and several areas of the body. They implanted electrodes to stimulate the vagus nerve along the neck of a man who > 29 June 2019 | New Scientist | 41
Going home Now Thibaut intends to use EEG to scan the brain, alongside software that is trained to spot when a patient is most vigilant. At this point, the stimulation will kick in, in the hope that it is more effective. “It’s challenging from an engineering point of view, but in a few years, the idea is that this is something that would be relatively inexpensive, that these patients could wear permanently at home,” she says. These advances raise new ethical questions. Some people may see surviving a brain injury with some degree of consciousness as worse than being in a vegetative state, because you can experience pain and have some awareness of your predicament. Do we need to question whether to awaken people in the knowledge that it is only temporary? And what about those families who discover that their loved one has covert consciousness, but can’t offer any means of continuing the conversation? Whyte says that one of his patients had been in a vegetative state for two years, but he started interacting with his parents after a single dose of zolpidem. After several hours, he lapsed back into unconsciousness. Unlike with Viljoen, the effect couldn’t be repeated. “It was enormously emotional, as you can imagine,” says Whyte. “The family went from having given up hope, to learning that their loved one had the ability to be conscious, to discovering that they just couldn’t realise that ability.” He believes we should be trialling as many therapies as possible – as long as we are 42 | New Scientist | 29 June 2019
Techniques that track glucose metabolism show stark contrasts in brain activity between people in vegetative, minimally conscious and fully conscious states
Vegetative state
Minimally conscious state
Fully conscious
STENDER ET AL
had been in a vegetative state for 15 years. By the end of the trial, he was able to smile and to answer questions using his eyes. “There was a reactivation of networks important for consciousness,” says Sirigu, adding that it might be possible to combine this treatment with drugs like apomorphine. In other work, Aurore Thibaut at the University of Liège has been using noninvasive transcranial direct current stimulation (tDCS) to deliver low-level electrical stimulation to switch brain cells on and off. In initial experiments involving 55 people, just one day of brain stimulation over areas of the forebrain allowed some minimally conscious patients to answer questions by moving their eyes or head. Two patients emerged from a minimally conscious state altogether. When they extended the trials, patients were able to communicate for at least a week at a time before losing consciousness again. They gave some families tDCS machines to use at home.
confident that we won’t cause a patient any harm. “Unfortunately, there’s going to be a lag period where the people you study today aren’t going to be helped by the results,” he says. For those that can be awakened, we also need to consider what questions we ask. “Your first question is always ‘are you in any pain?’,” says Sanz. “Normally, other questions that the families ask are quite simple, ‘Do you want the TV on? Are you cold?’” Is it possible for people with disorders of consciousness to have a more meaningful conversation about their welfare? “Once a person shows signs of awareness, can they decide whether to live or die?” asks Joseph Fins, a medical ethicist at Weill Cornell Medical College. Historically, we have thought about patients making decisions as all or nothing – they are either capable of consenting to treatment or not, he says. But now, he says, we have this third scenario, a person who may be aware enough to answer difficult questions some of the time. “Now that people with brain injuries are emerging and communicating, we have to listen to what they say,” says Fins. Most people with covert consciousness still wouldn’t satisfy requirements to provide legal
“Once a person shows signs of awareness, can they decide whether to live or die?”
consent, though, says Fins. “So we should be trying to engage them in the decision-making process, but not ask them to participate in a way that is beyond their capabilities.” The answer, perhaps, is to plan for the worst. Steven Laureys, head of the Coma Science Group at the University of Liège, says that until we have a brain-computer interface that can help people with disorders of consciousness communicate better, the best thing that anyone can do is to express their wishes ahead of time. “Tell your family and friends exactly what you want in a will, or at least talk to them about the subject – it would all help if something like this happens to you.” And when you are considering your options, it may surprise you to hear that a locked-in life isn’t necessarily a miserable life. A small survey of people who could only communicate using eye movements found that the majority were happy, and the longer they had been locked in, the happier they were. But that stems from their ability to engage those around them regularly. Without that, Schiff fears people with disorders of consciousness face extreme isolation. What is life like for the people in his pictures? “There hasn’t been a formal study of well‑being in people with disorders of consciousness,” says Ralf Clauss at the Royal Surrey County Hospital, UK, who was one of Viljoen’s doctors. “But anecdotally from what people have told me during periods of awareness, they are happy.” ❚
Helen Thomson is a New Scientist consultant and author of Unthinkable: An extraordinary journey through the world’s strangest brains
38 | New Scientist |29 June 2019
Features
Hidden consciousness One in 10 people believed to be permanently unconscious may actually be aware. How do we rescue them from their limbo? Helen Thomson investigates
“
I
HAVE pictures of five patients on my wall,” says Nicholas Schiff. “They all seem to be in a vegetative state, but we know they are conscious. It’s to remind me they are out there and we are not helping them.” Schiff, based at Weill Cornell Medical College in New York, is one of the world’s leading experts in disorders of consciousness. Many of his patients are in a vegetative state. Their injuries have left them with no awareness of themselves or of the world around them. Or so we thought. In 2006, it was discovered for the first time that a woman believed to be in a vegetative state was actually conscious, after brain scans revealed she could imagine different things on request. That breakthrough was quickly followed by a devastating revelation: our ability to determine whether someone is conscious based on their behaviour alone isn’t accurate enough. It is now known that some people have what is called “covert consciousness”, in which they have awareness that comes and goes, but can’t move any of their body. At first, it was believed to be a tragic but rare misdiagnosis. Now, results from a 10-year investigation suggest that many people could be trapped in this way. Their bodies lie still, but their minds are active. This creates an urgent need to find techniques that could awaken them. It also raises ethical questions about what we need to ask these people, and ourselves, when they do manage to make themselves heard.
As recently as the late 1990s, it was assumed that people in a vegetative state, by definition, had no conscious awareness. They would show signs of sleep and wake cycles, and occasionally open their eyes or make involuntary movements, but weren’t aware of themselves or the people around them. However, Adrian Owen, then at the MRC Cognition and Brain Sciences Unit in Cambridge, UK, had a worrying thought: what if we were wrong? Neurologists have long been aware of locked-in syndrome, in which people are awake and aware but unable to move almost all of their body. It was first defined in medical textbooks in 1966, but must have been known about much earlier; it was described in Alexandre Dumas’s 1844 tale, The Count of Monte Cristo. People who are locked in need help breathing and many can communicate only using eye movements. But they aren’t
“Many people in a vegetative state may be trapped. Their bodies lie still, but their minds are active”
classed as having a disorder of consciousness, because, unlike people in a coma, vegetative or minimally conscious state, they are fully conscious (See “Consciousness confusion?”, page 40). Still, a diagnosis can take months, or even years if eye movement is limited. Owen wondered whether people in a vegetative state could also have a hidden awareness. At the time, this was dismissed as a “bonkers idea”, he says, not least because it made people feel uncomfortable that someone might be trapped inside their body without anyone knowing. Nevertheless, Owen’s team began to test his theory. Their first patient was Kate, a woman left in a vegetative state by a virus. In 1997, they scanned Kate’s brain using positron emission tomography (PET), which can measure brain activity, while showing her pictures of her family or playing familiar speech. To their surprise, her brain responded just as you might expect a healthy person’s brain to respond. But Owen’s team faced a problem: a lot of neural activity happens automatically, so the result didn’t necessarily prove she was conscious. It took another decade to work out a solution. In 2006, Owen and his colleagues showed that a 23-year-old woman in a vegetative state could respond to instructions, by asking her to imagine walking around her house or playing tennis. These two mental tasks require different brain activity, which can be identified from brain scans. It confirmed, beyond any doubt, that she was consciously aware of > 29 June 2019 | New Scientist | 39
CONSCIOUSNESS CONFUSION? Brain dead A person is brain dead when they no longer have any brain activity. They won’t regain consciousness or be able to breathe without artificial life support.
Coma Someone in a coma is unconscious and has low levels of brain activity. They will be unresponsive to sound and pain and will have greatly reduced reflexes such as swallowing or coughing. They may be able to breathe on their own.
Vegetative state A state in which a person may have some reflexes, including yawning and eye movements, but shows no awareness of themselves or their environment.
Minimally conscious As a person begins to show intermittent awareness of themselves or their environment, they are said to be in a minimally conscious state. As they develop the ability to communicate, they are said to have emerging consciousness.
Covert consciousness Some people who are diagnosed as being in a coma, vegetative or minimally conscious state may have periods of awareness that they are unable to reveal because they can’t make any purposeful movements. This differs from locked-in syndrome because the person still has cognitive troubles, such as memory loss, or inconsistent consciousness.
Locked-in syndrome A person who is locked in is fully conscious, so isn’t classed as having a disorder of consciousness, but is unable to move most of their body. Sometimes they can communicate through eye and facial movements. Their condition is normally associated with an injury to the brain stem.
40 | New Scientist | 29 June 2019
herself and the researchers, and that she had the ability to respond to their requests. Disorders of consciousness are notoriously difficult to diagnose. Most doctors use variations of the Glasgow Coma Scale to assess someone’s ability to open their eyes in reaction to various stimuli, and their verbal responses and motor movements. And they can use brain scans to identify physical damage. However, to identify covert consciousness, you need to use functional MRI (fMRI) or several EEG tests over time to verify brain activity that reflects comprehension and the capacity to follow commands. “But we’re just not screening patients for this level of higher function,” says Schiff. “And it’s not that hard to find them when we do.” The real canary in the coal mine, says Schiff, was a study carried out in 2017 by Brian Edlow at Massachusetts General Hospital. Edlow knew that covert consciousness had been discovered in people who’d had months or years to recover from their injuries, but he wondered whether it might exist in people with more recent brain injuries. He and his colleagues scanned the brains of 16 seemingly unconscious people with severe head injuries. During the scans, he asked them to do mental tasks, such as “imagine squeezing your right hand”. Of eight people who had no behavioural evidence of awareness, four could follow his instructions. It was a small study, but it had massive ramifications. “These people were in intensive care,” says Schiff. “What if you’d withdrawn their care?” Even for those who are provided with lifesustaining treatment, a misdiagnosis might result in limited rehabilitation that thwarts an opportunity for recovery. In Schiff’s own studies, he has identified 16 people with covert consciousness. For some, this diagnosis was life-changing. For instance, one man, thought to be in a vegetative state, made sporadic head movements that had been dismissed as random. Once the team became aware of his covert consciousness, however, these movements were given more attention. A researcher at the hospital developed a headmounted computer mouse for him, which he used to control a keyboard. Eventually, he was able to write Schiff an email to give his own consent to join his next study. How many more people might be in this
situation? There is no data on the exact number of people with disorders of consciousness across the world, but for the past 10 years, Schiff has been involved in an international investigation into rates of misdiagnosis. The latest conservative estimate is that one in 10 people who appear to be in a coma, vegetative or minimally conscious state actually has covert consciousness. “It’s a big problem,” says Schiff. “And now we know it’s not a rare problem.”
Coming around Twenty years ago, there wasn’t a lot you could do for people in a vegetative state other than hope that they would slowly recover, or have a rare, spontaneous awakening. That changed with Louis Viljoen. In 1996, when he was 24, a truck crashed into him on his bike. The trauma left him in a vegetative state for three years. One day, when visiting him at his care home, his mother noticed that he seemed restless. She called his doctor who prescribed him a sleeping pill called zolpidem to calm him. His carers crushed it up into some water and got him to swallow it. Fifteen minutes after taking the drug, Louis opened his eyes, turned his head, and said: “Hello Mummy.” From that day on, Louis could be woken once a day, for 3 hours. He would interact with his family before drifting back into unconsciousness. After six years, he awoke permanently. His story proved something important: that some people in a vegetative state have the capacity to be awoken with the right intervention. Zolpidem appears to “switch on” areas towards the front of the brain involved in higher-level thinking and initiation of movement. This outweighs the sedative effect of the drug on other brain regions. Unfortunately, excitement over zolpidem’s potential was short-lived. A small, placebocontrolled trial found that it benefited just four of 84 patients with disorders of consciousness. John Whyte, director at the Moss Rehabilitation Research Unit in Pennsylvania, says that despite a few families who use it every day to wake their loved ones, most find the effects diminish with repeat dosing. Not to be deterred, Leandro Sanz, a doctor at the University of Liège in Belgium, and his colleagues have begun testing another
“We’re not screening patients for this level of higher function – and it’s not hard to find them when we do”
drug, called apomorphine. The drug mimics dopamine and is regularly prescribed to help people with Parkinson’s initiate movements. Results from the three people treated so far in a pilot trial look promising: one participant was unable to communicate at all at the start. By the end, she could move her hands in response to commands. “There’s this moment, when they squeeze your hand for the first time, and you know they’re there, really there, with you,” says Sanz. “It’s like this presence has stepped into the room.” A second participant has started to turn his head when you call his name, and a third, who was attempting, unsuccessfully, to use his thumbs at the beginning of the trial, can now say “yes” and “no” and dress and shave with help. Sanz is now recruiting for a larger study. Drugs aren’t the only option. In 2007, Schiff and his colleagues wondered whether they could kick-start the damaged brain using electricity. There was growing support for his “mesocircuit hypothesis”, which attempted to explain how consciousness is recovered after a brain injury, and how cognition can outpace recovery of motor abilities. The hypothesis involves several networks associated with the thalamus (see diagram, below). The thalamus sits just above the brain stem, which connects the brain to the spinal cord and acts like a central station. It relays
YOU MAGAZINE/GALLO IMAGES/GETTY
Several drugs are being tested to wake people from coma - including the pill that roused Louis Viljoen (centre)
information towards the basal ganglia, which is involved in movement and reward, and the forebrain, made up of the two hemispheres of the brain, the thalamus and the hypothalamus. Together, these areas are responsible for learning, memory, personality, our senses and regulating breathing and other autonomic functions. It is thought that brain trauma disrupts this network, decreasing activity in the forebrain. A drop in activity also happens in the forebrain as we drift off to sleep or go under with anaesthetic. It is also the last part of the brain to come back “online” when a person emerges from a disorder of consciousness.
The network that underlies consciousness The mesocircuit hypothesis suggests that signals from a vast network of brain regions together create our experience of consciousness. Researchers are trying to spur this network into action using two main stimulation techniques, A and B Frontal lobe Complex behaviours, communication, memory, attention and personality Prefrontal cortex Emotion regulation, intuition, insight, empathy
Basal ganglia Movement, reward and emotion
Parietal lobe Language, attention and senses
A
Globus pallidus interna Regulation of voluntary movement Temporal lobe Memory and senses
Motor cortex Planning and control of voluntary movement
B
Thalamus Central station of sensory input Occipital lobe Vision
Pedunculopontine nucleus Initiation of movement
A Scientists use non-invasive brain
stimulation called tDCS over the prefrontal cortex, an area involved in our most complex behaviours, thoughts and personality
Striatum Involved in diverse aspects of behaviour and movement
B Deep brain stimulation targets the thalamus, an integral part of the mesocircuit thought to control consciousness
To see if they could kick-start this network after injury, Schiff’s team implanted electrodes in the thalamus of a man who had been in a minimally conscious state for six years following an assault. Improvements were seen straight away. By the end of the six-month trial, the man could eat, speak and watch a movie. Despite every major news outlet in the world reporting the result, Schiff’s research in this area halted. No funding agency was prepared to pay the huge amounts of money required for the participants’ rehabilitation and care during such a long study. “Talk about an uphill battle,” says Schiff. “No one wants to pay for it, and researchers can’t do this alone.” It wasn’t until 2016 that Martin Monti at the University of California, Los Angeles, and his colleagues attempted something similar, this time using low-intensity ultrasound, a noninvasive technology that modulates the thalamus without the need for surgery. Once again, the results were impressive: his patient was a 25-year-old man who had received a severe brain injury after being hit by a car and was in a minimally conscious state for three weeks. The morning after the treatment, the man tried to communicate with vocalisations and gestures. Three days later, he started answering questions by nodding or shaking his head. A week later, he got out of bed and attempted to walk. Monti’s team has since used the technique with other patients and is now moving ahead with a clinical trial. Meanwhile, Angela Sirigu of the French National Centre for Scientific Research in Bron and her colleagues were trialling another technique. It focuses on stimulating the vagus nerve, which runs between the brain, the thalamus and several areas of the body. They implanted electrodes to stimulate the vagus nerve along the neck of a man who > 29 June 2019 | New Scientist | 41
Going home Now Thibaut intends to use EEG to scan the brain, alongside software that is trained to spot when a patient is most vigilant. At this point, the stimulation will kick in, in the hope that it is more effective. “It’s challenging from an engineering point of view, but in a few years, the idea is that this is something that would be relatively inexpensive, that these patients could wear permanently at home,” she says. These advances raise new ethical questions. Some people may see surviving a brain injury with some degree of consciousness as worse than being in a vegetative state, because you can experience pain and have some awareness of your predicament. Do we need to question whether to awaken people in the knowledge that it is only temporary? And what about those families who discover that their loved one has covert consciousness, but can’t offer any means of continuing the conversation? Whyte says that one of his patients had been in a vegetative state for two years, but he started interacting with his parents after a single dose of zolpidem. After several hours, he lapsed back into unconsciousness. Unlike with Viljoen, the effect couldn’t be repeated. “It was enormously emotional, as you can imagine,” says Whyte. “The family went from having given up hope, to learning that their loved one had the ability to be conscious, to discovering that they just couldn’t realise that ability.” He believes we should be trialling as many therapies as possible – as long as we are 42 | New Scientist | 29 June 2019
Techniques that track glucose metabolism show stark contrasts in brain activity between people in vegetative, minimally conscious and fully conscious states
Vegetative state
Minimally conscious state
Fully conscious
STENDER ET AL
had been in a vegetative state for 15 years. By the end of the trial, he was able to smile and to answer questions using his eyes. “There was a reactivation of networks important for consciousness,” says Sirigu, adding that it might be possible to combine this treatment with drugs like apomorphine. In other work, Aurore Thibaut at the University of Liège has been using noninvasive transcranial direct current stimulation (tDCS) to deliver low-level electrical stimulation to switch brain cells on and off. In initial experiments involving 55 people, just one day of brain stimulation over areas of the forebrain allowed some minimally conscious patients to answer questions by moving their eyes or head. Two patients emerged from a minimally conscious state altogether. When they extended the trials, patients were able to communicate for at least a week at a time before losing consciousness again. They gave some families tDCS machines to use at home.
confident that we won’t cause a patient any harm. “Unfortunately, there’s going to be a lag period where the people you study today aren’t going to be helped by the results,” he says. For those that can be awakened, we also need to consider what questions we ask. “Your first question is always ‘are you in any pain?’,” says Sanz. “Normally, other questions that the families ask are quite simple, ‘Do you want the TV on? Are you cold?’” Is it possible for people with disorders of consciousness to have a more meaningful conversation about their welfare? “Once a person shows signs of awareness, can they decide whether to live or die?” asks Joseph Fins, a medical ethicist at Weill Cornell Medical College. Historically, we have thought about patients making decisions as all or nothing – they are either capable of consenting to treatment or not, he says. But now, he says, we have this third scenario, a person who may be aware enough to answer difficult questions some of the time. “Now that people with brain injuries are emerging and communicating, we have to listen to what they say,” says Fins. Most people with covert consciousness still wouldn’t satisfy requirements to provide legal
“Once a person shows signs of awareness, can they decide whether to live or die?”
consent, though, says Fins. “So we should be trying to engage them in the decision-making process, but not ask them to participate in a way that is beyond their capabilities.” The answer, perhaps, is to plan for the worst. Steven Laureys, head of the Coma Science Group at the University of Liège, says that until we have a brain-computer interface that can help people with disorders of consciousness communicate better, the best thing that anyone can do is to express their wishes ahead of time. “Tell your family and friends exactly what you want in a will, or at least talk to them about the subject – it would all help if something like this happens to you.” And when you are considering your options, it may surprise you to hear that a locked-in life isn’t necessarily a miserable life. A small survey of people who could only communicate using eye movements found that the majority were happy, and the longer they had been locked in, the happier they were. But that stems from their ability to engage those around them regularly. Without that, Schiff fears people with disorders of consciousness face extreme isolation. What is life like for the people in his pictures? “There hasn’t been a formal study of well‑being in people with disorders of consciousness,” says Ralf Clauss at the Royal Surrey County Hospital, UK, who was one of Viljoen’s doctors. “But anecdotally from what people have told me during periods of awareness, they are happy.” ❚
Helen Thomson is a New Scientist consultant and author of Unthinkable: An extraordinary journey through the world’s strangest brains