Many patients in vegetative
states can learn to pair a
tone with a puff of air
to the eyes

Vegetative, But Not, Perhaps, Unconscious

September 23, 2009
by Brendon Nafziger, DOTmed News Associate Editor
Many people in vegetative states can still learn, suggesting they might retain some level of awareness, according to a study published in Nature Neuroscience this week.

Research in Argentina and England on people with disorders of consciousness (DOC) -- a diverse population of patients who are awake but seemingly lack awareness following severe brain trauma -- found that many were able to learn with a type of Pavlovian conditioning.

In the experiments, scientists worked with 22 vegetative and minimally conscious patients. They played a tone for the patients that, after a brief delay, was followed by a puff of air into the eyeballs. They also played a different tone that was not followed by the air puff to the eyes. They found that over half the DOC patients learned to blink (as measured by electromyography) in anticipation of the puff once the correct tone sounded, but not when the wrong one sounded. Some of the patients showed less discriminating learning, and would blink in response to either tone.

As a control, the experimenters tested subjects under anesthesia during laparoscopic surgeries who were asleep but not under muscle relaxants. They showed a hearty eye blink response when air was puffed into their eyes, and separate tests suggested they could still hear. Nonetheless, these patients could not learn to associate the tone with the air puff.

DOC patients who learned were also 86 percent more likely to show signs of improvement when tested a month or a year later, such as moving from a vegetative to a minimally conscious state, or rising in the coma recovery scale.

"When you do a drug trial, they use hundreds of patients, and they get a small effect," Tristan Bekinschtein, Ph.D., lead author of the study and a researcher at Cambridge University, tells DOTmed News. "We used just a few patients, and the [EMG] machine alone was telling us the patients were getting better."


True Pavlovian classical conditioning -- say, getting a dog to salivate at the sound of a bell that's usually paired with the slopping of dog food into a bowl-- is not a test of consciousness, Dr. Bekinschtein explains. But he believes trace conditioning, the kind used in the experiment, is.

In trace conditioning, an arbitrary stimulus, such as a tone, is separated from the reflex-producing stimulus, such as the air puff to the eyes, by a short delay, in this experiment one of about 500 milliseconds. This interval is key, because this is where conscious attention might be required to make the association between the two stimuli.

When Dr. Bekinschtein did trace conditioning experiments on healthy, conscious volunteers, who were distracted by a silent movie as they were getting puffs to the eyes, he found that those who seemed to pay more attention to the tone and air puff were more likely to learn to blink pre-emptively when the correct tone sounded.

"People who tell you details about the relationship between the tone and air puff show more learning [measured in eye blinks] than those who cannot tell you. There's a good agreement between conscious report and the stimuli we are using," he says.

Dr. Bekinschtein says that since the paper was published, he has gotten letters arguing that flies must now be conscious, as they can also demonstrate trace conditioning learning. But Dr. Bekinschtein cautions that trace conditioning in non-mammals might depend on vastly simpler neural processes, and that "in humans, [trace conditioning learning] correlates quite well [with consciousness]: people who don't show conscious processing, don't use learning."

Nonetheless, Dr. Bekinschtein says that while his team is "sure about the learning and recovery" findings, whether trace conditioning is related to consciousness is open for discussion.

Meanwhile, Dr. Bekinschtein hopes to expand his study into a proper clinical trial, as he hopes his technique could be used to help identify patients who might make better recoveries.