Twenty years ago groundbreaking research showed that a woman in a vegetative state was actually conscious – and since then these findings have been repeated in many more patients.
Yet in the past two decades progress in treating individuals occupying this twilight zone of wakefulness without obvious awareness has remained slow.
“I think this is one of the most difficult areas of clinical medicine that exists today, for lots of reasons,” says Prof Nicholas Schiff, a neurologist at Weill Cornell Medicine, the medical school of Cornell University in New York.
“Personally I think one of the reasons is that it makes people very uncomfortable, because we haven’t yet shown very clearly how to help people who are in this condition.”
But could brain-computer interfaces, which translate a person’s thoughts into an output in a computer, change all this?
In the coming years patients could, says Prof Schiff, be “put into a situation where they’re able to have their intentions of mind and thought read directly from neuronal activity”.
Work by Prof Adrian Owen, professor of cognitive neuroscience at Western University in Canada, has been pivotal in helping to improve the understanding of people in a vegetative state.
Breakthrough discovery
In 1997, while a research fellow at the University of Cambridge in the UK, Prof Owen began using scanners to analyse the brains of patients.
When shown pictures of friends and family, Kate Bainbridge, a patient at Addenbrooke’s Hospital in Cambridge who was in a vegetative state at the time, showed activity in the fusiform gyrus, part of the brain linked to facial recognition.
“I was really excited about this – the fact you had a patient who was completely non-responsive but her brain was activating to familiar faces,” Prof Owen says.
“It really blew my mind. I thought, ‘What does it mean?’ Is she really there or is her brain on some kind of autopilot where it can recognise faces? It initiated this fascination in this question of whether any of these patients were more than they appeared to be.”
Each time a suitable patient came into Addenbrooke’s Hospital, which is the major trauma centre for the east of England, Prof Owen would carry out tests – and many patients showed brain activity in response to speech or faces.
After seeing several dozen individuals, Prof Owen and his colleagues sought to confirm that the patients were actually conscious.
“Rather than being something automatic, it had to be something that came from the will of the person,” he said.
In work carried out two decades ago using functional magnetic resonance imaging scans, the brain of a vegetative state patient lit up in one region when she was asked to imagine playing tennis, and in another region when she was asked to pretend that she was walking around her home.
The results tallied with findings from healthy volunteers, indicating that the patient could understand and act upon the instructions she had been given.
“It’s fascinating that 20 years later, imagining playing tennis is still the gold standard,” says Prof Owen, who is the author of the book Into the Grey Zone: A Neuroscientist Explores the Border Between Life and Death.
“We’ve done it in different ways and so have other people, but no one has improved on it. It still seems to be the most straightforward way of determining if someone is aware or not.”
A 2024 paper, whose authors include Prof Schiff and Prof Owen, analysed findings from 353 patients to confirm earlier results that about a quarter of people regarded as being in a vegetative state are actually aware.
Someone may end up in a vegetative state for a variety of reasons, such as a stroke, a cardiac arrest − which can cause a loss of oxygen to the brain − or asphyxiation, perhaps from a swimming pool accident, from being buried under snow in an avalanche or from a failed hanging attempt.
Being in a vegetative state is not the same as being brain dead, because, as the UK’s National Health Service notes, with the vegetative state the brain stem is functioning and the person usually breathes unaided. While awake, people in a vegetative state typically cannot interact with their surroundings.
The brain imaging work, however, opened up the possibility of having interactions with those 25 per cent or so of patients who show awareness: they might be asked to think of playing tennis to answer yes to a question, or to think of walking round their home to answer no.
A lifeline for loved ones
The realisation that some of patients may actually be conscious has been, Prof Owen says, “amazing” for their relatives.
“It’s really changed the way families treat patients. You can see that every day,” he says. “Because these patients are largely inanimate and don’t really do anything, I think there was a time when they were treated more like objects than people.
“But they much more get treated like people now, certainly by the families that we interact with.”
While families may treat vegetative state patients differently, and nurses may, Prof Owen says, talk to them as if they are conscious, medical care has not moved on significantly.
Tests, such as the one about playing tennis versus walking round the house, have yet to be standardised so that they can be used routinely by clinicians to find out which patients are conscious.
Turning to technology
Key to further progress could be brain-computer interfaces, which allow the brain to communicate directly with an external device.
While a decade ago these might have let a person to control a mouse over a keyboard, today they can enable a patient to talk just by thinking in a certain way.
Prof Schiff, the senior author of the 2024 study, describes the field as being “just pre-tipping point”.
“For the last 10 years it’s been obvious to me that we have tools to try, in the form of brain-computer interface technologies, that could work in some people,” he says.
“We’re trying to partner with people to do that, trying to get the resources to do that. It’s going to be complicated, it’s probably going to fail a lot and it’s going to be costly.”
He predicts that, five years from now, some vegetative state patients will have been able to express themselves through a brain-computer interface, providing testimony that could spur further progress.
“They will be able to advocate for others who are not yet able to do that,” he says. “It may take more than one or two people. It may take a while. This takes a long time for people to get their minds around. This is not an easy space to navigate.”
Just as this area of medicine may be poised for a breakthrough in clinical practice, the original work led by Prof Owen continues to captivate observers.
“There’s interest in making a movie now, which is quite exciting,” Prof Owen says. “There is a script being circulated and financing in place, so I think a movie will appear in the next couple of years, which is quite exciting.
“It’s such a fascinating story – a fascinating science story, but I think the fact people continue to be interested in it shows it’s a really interesting human-interest story as well.”
