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Researchers Find Brain Activity Beyond the Flat Line
Tue, 10/01/2024 - 1:54pm
Cynthia Fox

“Fascinating,” says medical resuscitation expert Sam Parnia of a recent PLOS One study finding highly unexpected electrical activity in the hippocampus of one man, and 26 cats, with flat-lined “isoelectric” electroencephalograms (EEGs).

The isoelectric flat line—so popular in movies and on TV shows—helps determine if patients are in a brain death they can’t recover from.

“The brain may survive in deeper states of coma than the ones found during the isoelectric line,” says study lead author Florin Amzica.  Agrees Ari Joffe, a critical care physician and University of Alberta ethicist who researches this issue: "I believe this study shows the electroencephalogram, which records superficial cortical activity, does not tell us what is happening in subcortical nor brainstem areas.  (It) suggests that the limbic system, specifically hippocampus and dentate gyrus, are active when the EEG is isoelectric (no activity) in their human case, and in the cats."

Religions that tolerate clinic use of embryonic stem cells—from discarded IVF clinic embryos—tend to be those defining life’s start as a process, not a single bright line. Neuroscientists trying to nail the elusive neural correlates of thought similarly describe consciousness as a process, not a single bright line.

Increasingly, scientists are referring to the end of life that way, too. “Doctors assume that after clinical death, the brain is dead and inactive,” University of Michigan neuroscientist Jimo Borjigin said after publication of her August PNAS study finding that nine rats dying of cardiac arrest experienced brain activity for 30 seconds after death. Talking to science writer Ed Yong, she said: “They use the term ‘unconscious’ again and again. But death is a process. It is not a black or white line.”

Similarly, the recent PLOS One study found that 26 cats, placed in a flat-lining deep coma, still experienced significant brain activity in their hippocampus, the ancient seat of memory storage. This occurred when researchers added more anesthesia after the isoelectric flat line occurred. “Nobody had tried this before, probably because they ‘knew’ that there was no point in passing the flat line, thought to be the last frontier of the living brain,” says Amzica, a researcher with the University of Montreal. “Since this is false, as we know now, the first one to go beyond the flat line was doomed to find something new--as we did. But this was only possible in a brain whose flat line was not reflecting death, but silence. Not much of a linguistic difference, but quite a difference, in fact.”

The unexpected activity was so boisterous it overflowed and spilled into the outer frontal cortex—the main area of cognitive thought. Consciousness is gone when the flat line occurs in tandem with extensive brain damage, says Amzica. But when there is less brain damage, neuroprotection may be going on, he postulates.

Regardless of the reason for it, the startling amount of brain activity—which Amzica’s team calls “the Nu-complex state”—surprised many. It has been prompting, with the other study, revival of talk about that flat line, and whether it truly represents death.

“We think the Nu-complex state has a greater neuroprotective potential than the ones used up to now by generating a periodic pattern of synaptic activities that could maintain a rudiment of cortical functionality, certainly more efficient that the one encountered during the flat EEG,” says Amzica, referring to the current practice of placing some patients--on ventillators, for example--in artificial comas to protect them. “But this requires further study. The revisiting of brain death criteria would also be refreshing. I do not believe we bring anything that questions the present criteria used in clinical practice. However, whenever the present set of tests are not available, the attempt to induce the Nu-complex state might be useful in determining whether that brain is still functional or not.”

Scientists have speculated for a while that the birth of consciousness is far messier than it appears. Now some researchers say the same may be true of the end of consciousness.

Parnia is chief of resuscitation medicine at Stony Brook University Hospital, and head of the Human Consciousness Project’s AWARE study which scientifically documents after-death experiences in 25 hospitals in North America and Europe. In his 2013 book, Erasing Death, he repeatedly refers to death as a process, “not a moment in time.” Among the reasons: brain cells can remain viable for up to eight hours after blood flow stops.

Parnia’s group has found that, of the ten percent of people revived after being declared dead post-cardiac arrest, two to three percent report an ability to recall things they shouldn’t, like conversations held by clinicians when the patients were flat-lined. Increasing studies like these indicate that "eventually we may have to relook at death," Parnia says.

He actually believes the cat study says more about life than death, since the feline patients weren't dead, just in isoelectric comas with their hearts still beating, when their hippocampal regions were jolted into activity. "The study is fascinating because it implies drugs like the anesthetic used may be able to stimulate people out of deep coma," he says. "There may be a real application there."

Some others interpret the cat study as elucidating the power of drugs to mask, or tamp down, electrical activity in the brain. 

Regardless, "an understanding has gradually been accumulating over decades that, in the early stages of death in the traditional sense of the word, all brain cells are not instantly annihilated, consciousness is not instantly annihilated," Parnia says. "This in itself is significant." 

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