Shocking evidence shows people in vegetative states may be conscious

“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 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?”). 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.

“Many people in a vegetative state may be trapped. Their bodies lie still, but their minds are active”

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 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 life-sustaining treatment, a misdiagnosis might result in limited rehabilitation that thwarts an opportunity for recovery.

“We’re not screening patients for this level of higher function – and it’s not hard to find them when we do”

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 head-mounted 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, placebo-controlled 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 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”). The thalamus sits just above the brain stem, which connects the brain to the spinal cord and acts like a central station. It relays 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.