Researchers observe never-before-detected brain activity in deep coma

September 25, 2013

Flat line and Nu-complex signals (credit: Daniel Kroeger et al./PLoS ONE)

University of Montreal researchers have found brain activity that kicks in after a patient’s EEG shows an isoelectric (“flat line”) EEG, according to their paper in PLoS ONE (open access).

The flatline EEG (brainwave) pattern is usually recorded during very deep coma and is considered to be one of the limit points in establishing brain death. In particular clinical conditions, it is accepted as the only criterion.

Beyond flatline

But is it? The new research challenged this conventional wisdom after Dr. Bogdan Florea from Romania observed a human patient in an extreme deep hypoxic (deprived of oxygen) coma under powerful anti-epileptic medication (required to control his seizures) and observed some unusual EEG (brain-wave) signals instead of just a flatline, and then contacted the University of Montreal team.

After looking at the EEG and other data, the team “realized that there was cerebral activity, unknown until now, in the patient’s brain,” said Dr. Florin Amzica, director of the study and professor at the University of Montreal’s School of Dentistry.

Amzica’s team then decided to recreate the patient’s state in cats, the standard animal model for neurological studies. Using a higher amount isoflurane anesthetic than normal, they placed the cats in an extremely deep coma (beyond what is. The cat EEG showed the expected flat (isoelectric) EEG line.

But then, the team observed something else: strong oscillations. The found that they were generated not in the cortex, but in the hippocampus, the part of the brain responsible for memory and learning processes. These oscillations, unknown until now, were also transmitted to the cortex.

The researchers concluded that the observed EEG waves, or what they called “Nu-complexes,” were the same as those observed in the human patient.

Are ‘therapeutic comas’ harming patients?

But the researchers were concerned about another issue. After a major injury, some patients are in such serious condition that doctors deliberately place them in an artificial coma to protect their body and brain so they can recover.

That could be a mistake. An extreme deep coma — based on the experiment on the cats — may actually be more protective, Amzica suggested, based on the research.

“Indeed, an organ or muscle that remains inactive for a long time eventually atrophies. It is plausible that the same applies to a brain kept for an extended period in a state corresponding to a flat EEG,” says Professor Amzica.

“An inactive brain coming out of a prolonged coma may be in worse shape than a brain that has had minimal activity. Research on the effects of extreme deep coma during which the hippocampus is active is absolutely vital for the benefit of patients.”

“As these functions fade at the onset of unconsciousness, the orchestrating powers are relinquished to more basic structures such as the thalamus (in the case of sleep) or the limbic system [per the current data in the experiment],” the researchers said in the paper. “When these structures are released from neocortical influence, they begin to pursue activity patterns on their own and proceed to impose these patterns on other brain regions including the neocortex.”

Pulling the plug

“Another implication of this finding is that we now have evidence that the brain is able to survive a an extremely deep coma if the integrity of the nervous structures is preserved,” said lead author of the study, Daniel Kroeger.

“At the very least, the current findings should serve clinicians in their assessment of patients’ depth of coma in case they encounter EEG activity patterns indicative of the Nu-complex state,” the authors said in their paper.

But what about patients in a coma whose doctors have “pulled the plug” based on the fact that their EEG showed a flatline (among other reasons)? Does this new finding call that into question?

“Those who have decided to or have to ‘unplug’ a near-brain-dead relative needn’t worry or doubt their doctor. The current criteria for diagnosing brain death are extremely stringent,” advised Amzica. “Our finding may perhaps in the long term lead to a redefinition of the criteria, but we are far from that.”

What do you think?

(As noted in a recent KurzweilAI news article, a University of Michigan animal study found that shortly after clinical death, in which the heart stops beating and blood stops flowing to the brain, rats display brain activity patterns characteristic of conscious perception. Is that related?)