Some people thought to be in a vegetative state–a persistent lack of awareness following brain injury–may be more aware than previously thought, even able to communicate, according to new research. One patient in the study, published today in the New England Journal of Medicine (NEJM), was able to correctly answer a series of yes or no questions, his responses interpreted via brain imaging.

The research highlights how difficult it can be to diagnose people in this condition and how new technologies may be able to help. It also opens new avenues for communicating with those thought to be lost to the waking world, and raises a host of ethical and philosophical questions over the definition of consciousness and how to assess it.

“In my view, this paper is a breakthrough in cognitive science and in neurology, and it will probably be the basis for a more open discussion of what it means to be awake, alert, and human,” says Allan Ropper, a neurologist at Brigham and Women’s Hospital in Boston, who wrote a commentary accompanying the paper in the NEJM.

In 2006, Adrian Owen, a neuroscientist at the Medical Research Council (MRC) in Cambridge, England, and colleagues published a startling discovery. Functional magnetic resonance imaging, an indirect measure of brain activity, revealed that a patient who showed no outward signs of awareness several months after a car accident could mentally respond to a complex series of commands in much the same way a healthy person could. The new study builds on this research, showing that the previous case was not an isolated incident, and that brain imaging can actually be used to communicate with unresponsive patients.

These conditions, called disorders of consciousness, are often mistakenly referred to as comas. However, comas typically last just days or weeks. After that, patients either wake up or transition into a vegetative state (in which they are totally unaware of their environment) or a minimally conscious state (in which they may occasionally laugh or cry, reach for objects, or even respond to simple questions). Patients are typically diagnosed at the bedside via a series of neurological exams that assess their level of awareness of their environment.

In the current study, patients diagnosed as either vegetative or minimally conscious were asked to either imagine playing tennis–a motor task–or to imagine walking through the streets of a familiar city or their home–a spatial task. In healthy people, each of these tasks activates a characteristic part of the brain, allowing scientists to determine just from the brain scan which of the two situations the person is visualizing. The task is also cognitively complex: the patient must comprehend the command, remember it during the test, and then carry out the visualization.

The researchers found that five of 54 patients presumed to be in a vegetative state were able to willfully control their brain activity, suggesting that, while rare, some people with little or no outward signs of awareness have measureable signs of consciousness. All of those five had suffered brain damage as a result of head trauma rather than oxygen deprivation, confirming that this group has more promising prospects for recovery.

The team went on to show that in one patient, a 22-year-old man who had been diagnosed as vegetative after a car accident five years prior, this imagery task could be used to communicate. The patient was instructed to imagine playing tennis if the answer to a question was yes, and to imagine his house if the answer was no. He was able to answer five of six questions, and answered them all correctly. Scientists did not know the answer to the questions prior to the test, confirming them later with the patient’s mother. For the last question, rather than giving an incorrect answer, he showed no brain activity at all. Researchers say he might have fallen asleep, lapsed out of consciousness, or chosen not to answer.

“This is a first case, but at least it shows that technology is challenging the boundaries based on clinical bedside examination,” says Steven Laureys, head of the coma science group at the University of Liege, in Belgium, and one of the authors of the paper. “I’m convinced that we need to adapt our standard of care and our ethical and legal framework to take account of this new technology.” The researchers did not test the other four patients who could do mental imagery, mainly because of the difficulty of carrying out the tests.

The findings open the possibility that some of these patients may be able to participate in decisions about their medical care, though a number of scientific, ethical, and legal issues will need to be discussed before taking this step. In the recent experiment, for example, scientists did not ask the patient whether he was in pain, instead sticking to factual questions with answers they could later confirm. “Before we tackle important issues such as pain, treatment, end of life, and so on, there are a lot of things we need to discuss among the medical community as whole,” says Laureys.

Exactly how aware such patients may be remains unclear. People in a minimally conscious state tend to have fluctuating levels of awareness, responding to simple questions or commands unreliably. And unlike patients with locked-in syndrome, in which a specific type of brain-stem stroke leaves the person profoundly paralyzed but largely cognitively intact, these people have clear brain damage and likely suffer severe cognitive impairments. “Even if they could say yes or no to a simple question, whether they retain enough cognitive capacity to respond to more complicated questions, we just don’t know,” says Martin Monti, a postdoctoral researcher at MRC and the lead author on the paper.

Intriguingly, before the recent experiment, medical practitioners had been unable to establish any kind of communication with the 22-year-old patient. . (Some patients, for example, can blink in response to yes or no questions.) “It must mean that somewhere his system cannot produce behavior that matches the level of cognitive functioning,” says Monti. “He clearly could understand speech, and could hear us and imagine things. These are all fairly complicated behaviors.”

Researchers are now trying to develop alternative methods of measuring brain activity in these patients. Functional MRI is expensive, time-consuming, and technically challenging–subjects must lie still during the scan, a problem for those who can’t reliably follow directions. Electroencephalography (EEG) devices, which measure the brain’s electrical activity via sensors on the surface of the scalp, are much cheaper and more portable than MRI scanners and are currently under study by Laureys and others. Researchers also aim to develop brain cognitive interfaces that will allow patients to interact with their environment, similar to those under development for severely paralyzed people.

“I think you’ll see these tools will be developed relatively quickly, because there is a sense of urgency,” says Nicholas Schiff, who is conducting similar research at Weill Cornell Medical College, in New York. “We want to know how reliably they can communicate, and whether you can give them different methods to initiate communication.”