Researchers studying the effects of death on the brain have finally identified the sequence of events that lead up to the permanent cessation of neural activity. Not only do these findings shed light on the strange phenomena reported by people who have undergone near-death experiences, but they could also lead to new medical interventions designed to reverse the process of brain death.

Until now, scientists have struggled to pinpoint the moment of cerebral expiration because, unlike the body, the brain doesn’t just stop working in a single instant. Rather, when oxygen supplies run out, neurons rapidly deplete their stores of cellular fuel - known as ATP - and become destabilized.

This triggers a massive release of the excitatory neurotransmitter glutamate, leading to a burst of neural activity as a person dies. “Neural circuits seem to shut down at first... Then we see a surge in brain activity – specifically an increase in gamma and beta waves,” explained study author Séverine Mahon in a statement. 

“These waves are usually associated with a conscious experience,” Mahon says. “In this context, they may be involved in near-death experiences reported by people who have survived cardiorespiratory arrest.”

After a short while, this neural activity fades to electrical silence – although even that isn’t the end of the story, as the stillness is then suddenly interrupted by a high-amplitude wave that spreads across the brain, causing permanent functional and structural changes. Known as the "wave of death", this phenomenon is caused by neurons becoming depolarized in their final moments.

“This critical event, called anoxic depolarization [AD], induces neuronal death throughout the cortex,” said study author Antoine Carton-Leclercq. “Like a swan song, it is the true marker of transition towards the cessation of all brain activity.”

Fortunately, this whole process can be reversed if the brain can be reoxygenated before the wave of death completes its work. However, until now, researchers didn’t know where in the brain this mortal ripple begins, or how it spreads.

To investigate, the study authors measured electrical activity in the brains of rats as they underwent AD. In doing so, they discovered that the wave of death begins in the excitatory neurons within the deeper cortical layers, probably because these nerve cells have particularly high energy demands.

“The onset of AD was not uniform across layers. AD initially occurred in layer 5 or 6 and then propagated bidirectionally in the upward and downward direction,” write the researchers.

However, when the researchers reoxygenated the rats’ brains, the entire process was reversed as ATP stores became replenished and neurons became repolarized. “We have observed this same dynamic under different experimental conditions and believe it could exist in humans,” said Mahon.

By teasing out the steps that the brain goes through in its final moments, the study authors have demonstrated that death is anything but a clean cut, and that a person can potentially be brought back from the brink even after their brain activity readings have flatlined. More importantly, by tracking the course of the "wave of death", this work provides new insights into how to better protect the brains of patients who undergo cardiorespiratory failure. 

The study has been published in the journal Neurobiology of Disease.