LATENT LEARNING?: If some vegetative patients can be shown to acquire conditional learning, should their status be reevaluated?
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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."