In patients who have survived severe brain damage, judging the level of actual awareness has proved a difficult process. And the prognosis can sometimes mean the difference between life and death.



New research suggests that some vegetative patients are capable of simple learning—a sign of consciousness in many who had failed other traditional cognitive tests. The findings are presented in a paper today in Nature Neuroscience (Scientific American is part of the Nature Publishing Group).



To decide whether patients are in a minimally conscious state (MCS), in which there is some evidence of perception, or intentional movement or have sunk into a vegetative state (VS), where there is neither, doctors have traditionally used a battery of tests and observations, many of which require some subjective interpretation, such as deciding whether a patient's movements are purposeful—to indicate a sullied feeding tube, for example—or just random.



"We want to have an objective way of knowing whether the other person has consciousness or not," says Mariano Sigman, senior study author and director of the Integrative Neuroscience Laboratory at the University of Buenos Aires.



Previous neuroimaging work had surprised doctors by showing that some vegetative patients, when asked to imagine performing physical tasks such as playing tennis, still had activity in premotor areas. In other patients, verbal cues sparked language sectors.



"It's really quite appalling that we don't have better techniques to evaluate cognitive and brain states on these individuals," says Joy Hirsch, a professor of neuroscience and psychology at Columbia University, who wasn't involved in the study.



Recent research has revealed that about 40 percent of vegetative state diagnoses is incorrect. That startling statistic reinforced the need for better tools to measure that which often eludes quantification—consciousness.



Training the mind

To study the ability of VS and MCS patients to learn via classical conditioned response, researchers built off the work of 19th-century Russian psychologist Ivan Pavlov, who famously conditioned his dogs to salivate at the ring of a bell by associating the sound with the presentation of food. In this case, they sounded a tone, which was followed about 500 milliseconds later with a light puff of air to the eye, a mild adverse stimulus. The air puff would cause a patient to blink or flinch his or her eye as a natural reaction, but after repeated trials over the course of half an hour, many of the patients would begin to anticipate the puff, blinking an eye after only hearing the tone.



If two stimuli are delivered at exactly the same time, even less conscious organisms, such as snails, can be conditioned to equate the stimuli. But delaying the second stimulus by more than 200 milliseconds is enough to demonstrate some learning, says Tristan Bekinschtein, lead study author and a researcher at the Impaired Consciousness Research Group at the University of Cambridge. To make that association, as brief as the time gap is, he says, "You need conscious processing."



To demonstrate the extent to which the vegetative and minimally conscious patients showed consciousness, the researchers also performed the test on people under general anesthesia (specifically, on patients who were on propofol for an endoscopic procedure). These individuals, considered to be entirely lacking awareness, showed no sign of learning.



What was more, current designation of either vegetative or minimally conscious did not determine how well patients learned. Some of those who were minimally conscious didn't learn as well as some who were classified as vegetative and vice versa. "I think there's some consensus that there is a [need for] revision in the way these patients are classified," Sigman says.



The new detection of learning also opens up questions about when patients should be classified as being in a persistent vegetative state—in which emergence isn’t predicted to be likely—as Terri Schiavo was determined to be at the time. Decisions to take people off of life support are often based in part on doctors' predictions of recovery and assessments of consciousness. If "someone shows the patients can learn," Bekinschtein says, "I think it would be a very clear argument" to keep them alive.



New signs of recovery

The findings might also have practical applications for patient recovery. At the outset, says Bekinschtein, "We wanted to test for capacity to learn and capacity for conscious processing." But once the study was underway, they found that learning ability and speed was about 86 percent accurate in predicting the extent of recovery within the next year.



"If you think about that in a subtle way," he says, "that they can change their brain network—[showing] some plasticity—it implies that there's room for at least some recovery."



Other researchers in the field are encouraged by the results. "This is a really important study," Hirsch says. "We don't know a lot about the neurocircuitry that is involved in classical conditioning," she says, but "the use of a learning paradigm to predict whether a patient would [recover] is a possibly important idea."



The researchers hope that similar tests will be widely adopted by hospitals all over the world. Functional magnetic resonance imaging (fMRI) machines and other diagnostic tests can be expensive and hard to come by in many places, the authors note. Much of the testing was completed in Argentina, where imaging capabilities can be less available than in the U.S. or U.K. For this test, "you just need two wires, and it costs $100," Sigman says. "In practical terms, it has strong implications."



Hirsch, who is also the director of Columbia's Program for Imaging and Cognitive Sciences, still thinks that "functional imaging is by far the tool of choice" because it can reveal "cognitive processes that are latent in these patients that aren't visible through [traditional] bedside tests."



Sigman is still cautious about declaring the test foolproof, but he asserts that their results could mean only two things: Either the patients "have consciousness or maybe the test is wrong." Determining whether anything—outside of ourselves—truly has consciousness quickly spirals into a philosophical debate. "It's an extremely difficult question in the end," Sigman says. But he hopes that their simple test will help pave the way for more definitive and accurate assessments of consciousness in the severely brain damaged.



Testing treatments

The revelation that some vegetative or minimally conscious patients can learn does not come as a surprise to all. That fMRI findings of cognitive processes in vegetative patients have been trickling in recently leads John Whyte, the principal investigator at the Neuro-Cognitive Rehabilitation Research Network, who wasn't involved in the research, to question the designation system itself. It may be that "there is a firm line" between vegetative and minimally conscious patients, "but our tools are too crude to tell us who is on which side of the line," he says. Or it may be that categories of consciousness are not so easy to define. "It seems quite plausible that people can have neurocircuits that are capable of doing something and [others] that are not."



Such a fuzzy future for assessing patients based on different abilities—rather than the current criteria, which are based on no demonstrable abilities—introduces more ethical dimness. If doctors can no longer give a black-and-white answer to whether a patient is conscious or not, but rather must proceed with a complex, gray-area assessment of cognitive capabilities, it will leave tenuous standards "to hang our ethical decisions on," Whyte says.



The current findings—and research that Whyte and his team have done—underscore the great individuality of each VS or MCS patient. Whyte's recent work has shown pharmaceuticals such as Ambien (zolpidem) help vegetative patients regain consciousness, but it hasn't proved to be a silver bullet. Even treatments that are found to be effective in some patients, Whyte notes, won’t work for everyone.



To Sigman and Bekinschtein, however, their discovery of even a little learning provides a glimmer of hope. "To show that someone can form a memory over half an hour is a way to start," Bekinschtein says. "If we could use this basic association paradigm and build from that, then it could be a form of rehabilitation," he adds. "That's where we're aiming to go."