Vegetative states: Is anybody in there? © Sébastien Thibault

Vegetative states: Is anybody in there?

Groundbreaking new research has discovered that 15 per cent of coma patients might be conscious and aware of their surroundings. Now, the race is on to find out ways to bring them back.

The rare occasions when people in vegetative states ‘wake up’ after years or even decades of unresponsiveness always make the news. We’re fascinated by the details behind the jubilant headlines: what was it like waking up from an extremely long sleep? What had been going on in their minds? Were they frozen in time? Or had they, perhaps, been aware of what was going on around them the whole time?

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It’s hard to gauge how many people are currently in a persistent vegetative state, languishing in a care-home bed, their inner lives a mystery. The causes of their brain injuries are diverse – from oxygen starvation (which could be due to stroke, heart attack, near-drowning and more) to trauma caused by a blow to the head – and there is no central register. But neuroscientists estimate there are thousands in the UK, and they are increasing in number, as doctors get better at saving lives in the aftermath of brain injuries.

Thankfully, doctors are also getting better at figuring out what is going on in these patients’ minds. “There have been huge discoveries over the last 15 years,” says Adrian Owen, a professor at the Brain And Mind Institute at Canada’s Western University. The first of these, he says, was “a 2006 paper where we showed that some of these patients are actually aware, and then the 2010 paper where we started to communicate with some of them.”

From the data so far, 15 to 20 per cent of patients show signs of concealed consciousness, and researchers are now making great strides in diagnosing the condition, understanding its mechanics and even working on treatments that could increase the chances of rehabilitation.

Disorders of consciousness

Technically speaking, coma usually only lasts for days or weeks after an injury. “Typically, you don’t go through the screen of a car and straight into a vegetative state,” says Owen. “First, your eyes are closed and you’re on life support.” This is a coma – an acute disorder of consciousness. It’s only after a patient emerges from the coma that they either wake up, are diagnosed with brain death (for which there are clear metrics), or enter a prolonged disorder of consciousness.

“This may be a vegetative state, or what we call a minimally conscious state, or MCS,” says Dr Davinia Fernández-Espejo, a senior lecturer at the University of Birmingham, whose study earlier this year identified the physiological cause of vegetative state, and who is developing a therapy to treat it.

Vegetative states: Is anybody in there? © Sébastien Thibault
© Sébastien Thibault

In a vegetative state, the patient is off life support, able to breathe on their own and digest food. “They often appear to be awake,” says Fernández-Espejo. “Their eyes are open and moving around a little bit.” They might startle if you blast some Led Zeppelin, or withdraw their hand if you poke them, she explains, “but they still don’t respond to the environment in any intentional way that may make us think that the patient is aware.”

Minimally conscious people show flickers of awareness, but “they’re still incapable of communicating – verbally or non-verbally.”

Detecting consciousness

So how can doctors tell if there is concealed consciousness? Owen has developed a method using an fMRI scanner. He asks a series of questions: to answer ‘Yes’, the patient imagines they’re playing tennis, while to answer ‘No’ they take a mental stroll around their home. If they’re conscious, different areas in the brain will light up: motor activity for ‘Yes’ versus spatial awareness for ‘No’.

It’s in intensive care units (ICU) where doctors and families often have to decide whether a patient has prospects for survival or whether life support should be turned off – and mistakes will have inevitably been made. But now, says Owen, “we can apply these techniques in the ICU, maybe a week after their injury, and both diagnose them more accurately and make predictions about who’s going to recover and who isn’t.”

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However, fMRI scanners can’t simply be wheeled into an ICU. So, in a small 2019 study, Columbia University-based neurologist Jan Claassen showed that an electroencephalogram (EEG) that measures brain waves, combined with machine learning, could be used instead to detect concealed consciousness in ICU patients.

Once again, the patients were asked questions and their brain activity was observed. Within four days of their injuries, 15 per cent of the 104 patients in the study were found to have hidden consciousness, despite being unresponsive. Of those patients, 44 per cent progressed out of their vegetative state, to some degree, within 12 months.

Owen, meanwhile, has developed a new portable technique, “based on a method called functional near-infrared spectroscopy, which like fMRI looks at the amount of oxygen in the blood, only with little lasers. It’s pretty cool. We had a paper out last year showing that we could use it effectively to communicate with a patient,” says Owen. The team asked the patient if he felt safe and if he was in any pain. “He wasn’t,” says Owen, “and he felt at peace with himself as much as one could.”

One of Owen’s Canadian patients, Juan Torres, had an acute brain injury after choking on vomit, but made an unprecedented recovery to the extent that he could clearly recount his three-month vegetative experience. He’d witnessed doctors declaring his brain irreparably damaged, and his family’s devastation. “He said he was always trying to move but it just wouldn’t happen,” says Owen.

It’s not that vegetative patients are paralysed – that’s a different condition called locked-in syndrome, where there is obvious consciousness but the connection between the brain and spinal cord is severed. Fernández-Espejo’s research group has discovered that vegetative patients with covert consciousness have “damage in some fibres connecting the thalamus in the centre of the brain, and the motor cortex, which controls movement. Because this pathway is injured, these patients are not able to voluntarily control their behaviour.”

Listen to Adrian Owen tell Jim Al-Khalili about his research on people in comas in this episode of The Life Scientific

life scientific

Many of these patients will have severe damage to other parts of their brains, too, “but the damage to other cognitive functions is not as severe as it looks from the outside, because of these problems with controlling the movement,” says Fernández-Espejo.

Her group is now recruiting patients to trial a non-invasive form of electrical stimulation. The hope is that this will encourage “the neurons that are still there to work harder to compensate for the ones that were lost, so the patient can make some small movements.” This could then enable patients to use technology to communicate, in the way many locked-in people can, and get them to a point at which rehabilitation therapies are possible.

“I’m really excited to be at this stage,” says Fernández-Espejo, “after years of being been able to say to relatives, ‘Yes, the patient is conscious,’ but then not being able to do anything about it. Now we have a mechanism that we can exploit to try to help patients get better.”

A new hope for vegetative patients

Dr Theresa Bender Pape, a clinical neuroscientist with the US Department of Veterans Affairs based at Northwestern University in Chicago, is currently trialling another non-invasive treatment called transcranial magnetic stimulation (TMS) to alter brain activity in vegetative patients. The results are due for publication in 2020, and are promising. The idea is, she says, “I get one neuron to talk to the next neuron to talk to the next neuron, so I’m altering neural activity in areas remote from the site of stimulation over time.”

Pape has also developed a treatment called Familiar Auditory Sensory Training (FAST). It involves close relatives recording well-worn family stories and jokes, and these recordings being played to the patient repeatedly. In 2015, a placebo-controlled study assessing FAST’s impact showed that patients who received the therapy recovered sooner and more extensively than those that didn’t. And in answer to relatives wanting to know whether their loved ones could hear them, MRI scans showed patients’ brains lighting up in response to the stories, in regions associated with language and long-term memory. “I love when patients tell me that they remember the stories,” says Pape.

Pape’s star TMS recoverer, Laura Gonzalez, is now sitting up, communicating non-verbally and living back at home, after more than 18 months in a vegetative state. After around 20 TMS treatments (out of 30), she recalls, “I walked in the room and said, ‘Hey Laura!’” When Laura looked back in acknowledgement, she says, “I thought: ‘Did I just see that?’ The hair on the back of my neck stood up.”

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