A New Frontier? Novel Brain Activity Observed in Flatlined Patient

Anyone who has observed a relative or friend in a coma knows just how eerie the phenomenon can be. Individuals in such a state have lost their higher cognitive abilities yet can remain generally functional, even normal-seeming otherwise. Some comatose individuals have been observed laughing and crying, although unaware of or at least unable to respond to external stimuli. Physicians and visitors are even encouraged to speak with comatose patients in the sustaining hope that they might hear and remember they are alive.

Such cautious, hopeful measures are only taken until a flatline appears on the patient's electroencephalogram (EEG) -- an indicator of a lack of electrical activity in the cortex, the large outer surface layer of the brain, and a generally accepted indication of brain death.

However, a study published on September 18 suggests that the flatline may not be the end of the road for some comatose patients.

A Romanian team of researchers led by Dr. Bogdan Florea observed one patient who, after receiving powerful anti-epileptic medication for seizures, had fallen into an extreme deep hypoxic coma. After exhibiting a flatline, however, brain death did not occur -- rather, the patient plunged into a deeper coma still, and his EEG began to show repeating v-shaped spikes. The researchers contacted Dr. Florin Amzica, the director of the study and professor of neurophysiology at University of Montréal, after observing the inexplicable activity.

Dr. Amzica's team was subsequently able to reproduce this activity in cats, using the anesthetic isoflurane to induce very deep (but completely reversible) comas in the subjects. Sure enough, after passing the flatline, 100 percent of cats exhibited the same cerebral activity, which the team has dubbed "nu-complexes" for the shape of the spike.

While the EEG flatline is associated with absent cerebral activity, the study's findings challenge common wisdom, suggesting it may only indicate silence among the cortical neurons, whilst subcortical structures may remain active. The nu-complexes seem to originate in the hippocampus, a key brain structure involved in the formation and consolidation of memories. Thus, the presence of this oscillatory activity indicates that in a deeper state of coma, subcortical structures such as the hippocampus can gain initiative and may impose their activities on the cortex.

"I think that this is the most important thing that we learned from this study," says Dr. Amzica, "That there is this crossing, this over reaching of the control from the cortex to the hippocampus, and that this very deep state of coma might not be the last one." He adds that the nu-complex state may have not been recorded before due to the practice of recording the EEG in coma patients in "snapshots" rather than constant monitoring.

Dr. Amzica notes, however, that if the cortical neurons are silent because of their deterioration or death, which often occurs due to traumatic brain injury, there would be no activity beyond the flatline: "The way the diagnostic of brain death is posed in, let's say, advanced societies and civilized societies, does not create any ambiguity... You can't miss a brain death if you are a responsible physician." The controlled laboratory environment allowed the team to induce a coma while maintaining the integrity of the cats' cortical neurons.

One potential implication of the findings is in the area of neuroprotection. During coma, the brain, like any muscle, will atrophy due to lack of use. Dr. Amzica hypothesizes that the nu-complex state may help keep cells active, preventing that same deterioration.

Lead author of the study and Research Fellow in Neurology at Harvard Daniel Kroeger says, "Immediate implications are that there is a new field to be studied because we don't know anything about what this activity is, what it means." He emphasized that the findings are far from clinical application -- more testing will be necessary to determine whether the nu-complex state is safe or even sustainable for longer periods.

He adds that there may be an opportunity to study how the brain learns and forms memories: "We don't really know too much about the pathways and mechanisms where this is happening, so observing our activity going from the hippocampus to everywhere else in the brain, especially the cortex, might help us understand how memories are transferred from one place to another."

Dr. Joseph Antognini, Professor in the Department of Anesthesiology and Pain Medicine at University of California Davis, is intrigued by the study's findings, but preaches caution regarding its applications: "I believe in this. There is a fair amount of evidence indicating that there is still brain activity occurring even in deep coma. The evidence that Dr. Amzica has produced here adds to that body of literature... But to try to translate this data to the clinical arena is fraught with difficulty for obvious reasons."

When we spoke, Dr. Amzica challenged me to propose a figure for incidence of coma. The answer? 100 percent. "Everyone goes through at least one coma, if it's the last one, right? Some people go through two, three or more comas: every surgery is an induced coma under anesthesia; some people have accidents; some people have intoxications and so on. Coma is with us and is much more present than what we think it is and what we might like to think it is. As such an extended biological phenomenon, I think it deserves study."