By using a computerized model to study an electroencepholagram (EEG) brain pattern called “burst suppression”, researchers in the US believe they have discovered a fundamental mechanism of how the brain behaves when the metabolic energy supply to brain cells is low. It is as if burst suppression is a type of intermittent standby mode, where a period of intense activity is followed by a period of inactivity, which endures until there is enough metabolic energy for cells to become active again.
The researchers, from Massachusetts General Hospital (MGH) in Boston, write about their discovery in the 7 February PNAS Early Edition. They hope it will help improve the design of anesthetics and ways to protect the brain.
Burst suppression is an electroencephalogram (EEG) brain pattern where episodes of high voltage activity (the bursts) alternate with periods of greatly reduced activity that last for 10 seconds or more.
Burst suppression occurs in a number of conditions, such as induced hypothermia, a medical treatment where doctors put a patient’s brain into a state of low activity to protect it from damage caused by trauma or reduced blood flow. It has also been observed in deep general anesthesia, comas, in babies with serious neurodevelopmental disorders, and for a short period in some babies born prematurely.
Previous studies have focused on examining the EEG patterns of burst suppression and the effect of external stimuli on the brain when in this state. But none had yet tried to explain what the underlying cellular mechanism might be.
Senior author Dr Emery Brown, of MGH’s Department of Anesthesia, Critical Care and Pain Medicine, told the press:
“The seemingly unrelated brain states that lead to burst suppression – deep anesthesia, coma, hypothermia and some developmental brain disorders – all represent a depressed metabolic state.”
“We believe we have identified something fundamental about brain neurochemistry, neuroanatomy and neurophysiology that may help us plan better therapies for brain protection and design future anesthetics,” he added.
In their study, Brown and colleagues propose a “unifying mechanism” for burst suppression that accounts for all the conditions in which it is observed.
To study the mechanism they created a computer-based “biophysical model” that took into account what all the conditions (induced hypothermia, coma, and so on) had in common: a significant reduction in the brain’s metabolic state.
The brain works because signals pass from one cell to another. For this to happen, the electrical chemistry has to be just right: there has to be a balance between sodium ions outside the cell and potassium ions inside the cell.
The balance is controlled by “ion pumps” fuelled by ATP, the molecule that supplies energy to cells.
When they played around with the model, the researchers discovered that when the energy supply goes too low and there isn’t enough ATP, the cells leak potassium and this stops the signals.
“In each condition, the model suggests that a decrease in cerebral metabolic rate, coupled with the stabilizing properties of ATP-gated potassium channels, leads to the characteristic epochs of suppression,” they write.
Lead author Dr ShiNung Ching, a postdoctoral fellow in Brown’s lab, said:
“It looks like burst suppression shifts the brain into an altered physiologic state to allow for the regeneration of ATP, which is the essential metabolic substrate.”
“During suppression, the brain is trying to recover enough ATP to restart. If the substrate doesn’t regenerate quickly enough, the system will have these brief bursts of activity, stop and then need to recover again,” said Ching.
The model suggests that the length of burst suppression depends on how long it takes to restore ATP levels. This matches what appears to happen when someone is anesthetized: the deeper the anesthetization, the longer the periods of suppression.
Brown said when they use general anesthesia to induce comas in patients with serious neurological injuries so their brains can heal, they take them down to a level of burst suppression.
“But there are a lot of questions regarding how deeply anesthetized an individual patient should be – how often the bursts should occur – and how long we should maintain that state,” he explained.
The model could help them find out more about what appears to be a fundamental way of preserving energy in the brain, and therefore how best to use burst suppression to guide induced coma and track recovery, said Brown.
“This is also a great example of how studying anesthesia can help us learn something very basic about the brain,” he added.
Written by Catharine Paddock PhD