What does it mean to be “brain dead”? For years one of the hallmarks has been a lack of electrical activity in the brain, which shows up on an electroencephalogram, or EEG, as a flat line. But what if inside the brain of a person who had already flat lined, there was still something going on—some murmur of electrical signals? Could the person still be considered brain dead?
These questions were thrown into relief when researchers investigated a heart-attack patient in a hospital in Romania in August 2011. The patient had lapsed into a coma, and was having seizures. Doctors placed the man on antiepileptic medication and an anesthetic. When they took an EEG recording they observed a pattern of activity they did not recognize: a series of small v-shaped signals. When they took the man off the antiepileptic after six days, his EEG readings briefly showed a flat line, also known as an isoelectric line, before returning to the pattern of activity characteristic of the coma state immediately preceding a flat line, a period called burst-suppression. Unable to interpret this phenomenon, the doctors asked a team of researchers at the Universite de Montreal for help.
To replicate the previously-unidentified v-shaped signals the Universite de Montreal researchers put 26 cats into comas by administering large doses of the anesthetic isoflurane. Once the cats registered flat EEG readings, the researchers upped the dose of isoflurane, placing the cats in deeper comas. At this point, they saw a “re-vitalization” of brain activity, characterized by sharp, low frequency EEG waves—the same activity the Romanian doctors had observed in their heart-attack patient, they say. The Montreal researchers called their discovery “v-complex” waves, partially because the waves resemble the Greek letter.
The v-complex electrical impulses most likely originated in the hippocampus, an ancient structure located in the middle of the brain thought to be involved in memory storage and consolidation. The pulses generated by the hippocampus were reverberating and rippling out to other brain structures, the researchers wrote, eventually reaching the outer cortex, which is responsible for higher-order cognitive processes like thought and language.
In a conscious, healthy brain, the cortex sends signals down to the older brain regions that govern our baser urges. The researchers hypothesize that by placing the cats in such a deep coma, they may have shut off all brain activity in the cortex, at which point the hippocampus took over, and electrical signals began to be transmitted from the bottom up rather than top down.
“Everybody thinks that the flat line is the ultimate frontier of living brain,” says Florin Amzica, a neurophysiologist at Universite de Montreal and coauthor on the paper. He suspects the waves have not been discovered before simply because no one bothered to look.
Amzica is quick to note that this brain activity does not mean that the patient is capable of cognition, however. “During a flat line, consciousness is abolished,” he says, adding that it does not make sense that consciousness would return in an even deeper coma state.
Furthermore, coma patients with significant brain damage are unlikely to move past a flat line to v-complex activity, which appears to occur only when the brain has not experienced extensive cellular death, according to Amzica. That includes most coma patients who have become unresponsive through some sort of traumatic event. For them, Amzica says, a flat line on the EEG probably represents true brain death from which they cannot return.
Amzica says he is not yet sure why the hippocampus continues to send signals to the rest of the brain, but for coma patients who have not experienced cell death, he thinks the pulses may be functioning as some sort of “neuroprotection.” Like any organ, when the brain is not used, the connections between the nerve cells atrophy. According to Amzica, v-complex pulses may serve to preserve a minimum level of brain function, mitigating the deterioration in a coma patient whose brain has gone through a prolonged period of disuse.
Other researchers think the results tell us more about how anesthesia works rather than true brain death. “There is nothing deeper than flat line. Brain dead people have a flat EEG, that’s it,” says Andrew Goldfine, a professor of neurology at Weill Cornell Medical College who specializes in disorders of consciousness.
Goldfine is not convinced the results have any significance for coma research. The case of the patient in Romania was highly unusual, he says. And since the EEG activity in both the patient and the cats was produced under the influence of pharmaceuticals, it is unlikely to occur naturally. “In reality it’s not an extra-deep coma, it’s coma plus anesthetics,” he says.
He notes that drugs have been known to produce odd effects at different doses, pointing to reports that some minimally conscious patients given the sleep drug Ambien appear to wake up from their comas for a short time.
Stephan Mayer, director of the neurological intensive care unit at Columbia University Medical Center, agrees the findings hold little insight into states beyond brain death, as the comas were produced under anesthesia, skipping over the trauma that put most coma patients in their condition. “I don’t believe it has huge implications for clinical practice,” he says. Mayer thinks that the study is interesting however, and that it shows "the way we conceptualize death is kind of more blurry than we thought in terms of what is actually happening physiologically.”