Neuroscientists have uncovered the source of a "wave of death" in the brain that appears at the end of consciousness.
The latest findings, published in the journal Neurobiology of Disease, shed new light on the process of dying and the accompanying changes that occur in the brain.
Clinically and legally, death is generally considered to be a well-defined state characterized, at least, by a complete and irreversible cessation of brain activities and functions. According to this view, the moment of death is represented by a discrete event in which all brain processes abruptly cease.
But from a neurological point of view, death is a difficult concept to define. A growing body of evidence is demonstrating that the phenomenon is not marked by an abrupt switch from life to death but involves a process that can last several minutes and is accompanied by a complex set of changes in brain activity and, in some cases, is reversible.
The latest findings were the result of a study in rats. But the authors believe the research could help scientists understand which groups of neurons, or nerve cells, in the brain are most vulnerable in the event of cardiorespiratory arrest. Ultimately, this could reduce the risk of neurological complications, they say.
Previous research has shown that after a long period of oxygen deprivation, known as anoxia, activity in the brain undergoes a series of successive changes.
When the brain stops receiving oxygen, its stores of ATP—a critical molecule that serves as the primary energy source for all cellular activities—are rapidly depleted. This causes disruption in the brain's neurons and a massive release of a compound known as glutamate—an essential neurotransmitter that sends signals in the brain and throughout nerves in the body.
"Neural circuits seem to shut down at first...then we see a surge in brain activity—specifically an increase in gamma and beta waves," neuroscientist Séverine Mahon, who is with the Paris Brain Institute (PBI) and one of the study's authors, said in a press release.
"These waves are usually associated with a conscious experience. In this context, they may be involved in near-death experiences reported by people who have survived cardiorespiratory arrest," Mahon said.
After this, the activity of neurons gradually diminishes until a state of perfect electrical silence in the brain is reached. This state corresponds to flat lines on an electroencephalogram (EEG)—a test that measures electrical activity in the brain using small electrodes attached to the scalp.
But this silence is quickly interrupted by a wave of death appearing on the flat EEG, which reflects a sudden phenomenon that scientists call "anoxic depolarization." This phenomenon appears to initiate cell death in a region of the brain known as the cortex.
"This critical event, called anoxic depolarization, induces neuronal death throughout the cortex. Like a swan song, it is the true marker of transition towards the cessation of all brain activity," Antoine Carton-Leclercq, an author of the study who is also with the PBI, said in the press release.
The slow-moving wave of death—characterized by massive electrical flows inside the brain—spreads throughout the cortex until consciousness is finally extinguished.
"Recovering from such a cataclysm requires so much energy that neurons often die in the minutes and hours following the wave of death. This is why, before our work, the wave of death was thought to be irreversible," Mahon and Stéphane Charpier, another author of the study who is with Paris' Sorbonne University, told Newsweek.
But the wave of death does not always mark the definitive loss of brain functions. If the brain is rapidly re-oxygenated, the effects of anoxic depolarization can be reversed. This process, previously discovered by the team in 2020, is marked by a "wave of resuscitation," which heralds a slow recovery of brain functions.
Until now, researchers did not know where the wave of death was initiated in the cortex or whether it spread evenly throughout all layers of this region, which makes up the outer layer of the brain's surface.
But the latest study, which measured brain activity in rats before, during and after anoxic depolarization induced by respiratory arrest, managed to identify specific groups of neurons in a layer of one part of the cortex—called the neocortex—where the wave appeared. They also found that the wave spread in two directions—upward and downward—from this location at a speed of a few millimeters per minute.
"We have observed this same dynamic under different experimental conditions and believe it could exist in humans," Mahon said.
These findings also suggest that the deeper layers of the cortex where the wave of death is initiated are the most vulnerable to oxygen deprivation.
"This new study advances our understanding of the neural mechanisms underlying changes in brain activity as death approaches," Charpier said in the press release. "We now need to establish the exact conditions under which these functions can be restored and develop neuroprotective drugs to support resuscitation in the event of heart and lung failure."
The latest results, which provide a detailed description of what happens in neurons at the time of death, could provide a path to the development of new therapies, according to the researchers.
Update 12/21/23, 7:50 a.m. ET: This story was updated with additional comments from Séverine Mahon and Stéphane Charpier.
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Aristos is a Newsweek science reporter with the London, U.K., bureau. He reports on science and health topics, including; animal, ... Read more
