The drug propofol causes loss of consciousness by altering the normal balance of the brain.

There are a variety of drugs that anesthesiologists can use to induce unconsciousness in patients. But exactly how these drugs work on the brain remains a mystery. Now neurobiologists at the Massachusetts Institute of Technology (MIT) in the US have answered that question using a widely used anaesthetic drug. The new findings, which appear in ‘Neuron‘, could help researchers develop better tools for monitoring patients during general anesthesia.

In particular, thanks to a new method of analyzing neuronal activity, Researchers have found that the drug propofol causes loss of consciousness by altering the brain’s normal balance between stability and excitability. The drug causes brain activity to become increasingly unstable until the brain loses consciousness.

“The brain must operate on a knife edge between excitability and chaos. It must be excitable enough that its neurons can influence each other, but if it is too excited, it spins out of control and out of control. “Propofol appears to alter the mechanisms that keep the brain in this narrow range of functioning,” ” says Earl K. Miller, the Picower Professor of Neurobiology and a member of the Picower Institute for Learning and Memory at MIT.

Miller and Ila Fite, a professor in the Department of Brain and Cognitive Sciences, director of the C. Lisa Young Center for Integrative Computational Neuroscience (ICoN), and a member of MIT’s McGovern Institute for Brain Research, are senior authors of the new study. MIT graduate student Adam Eisen and MIT postdoc Leo Kozachkov are the paper’s lead authors.

Propofol is a drug that binds to GABA receptors in the brain and inhibits neurons that have these receptors. Other anesthetics act on different types of receptors, and the mechanism by which all of these drugs cause loss of consciousness is not fully understood.

Miller, Fiete and their students hypothesized that propofol and possibly other anesthetics affect a brain state known as “dynamic stability”. In this state, neurons are excitable enough to respond to new signals, but the brain is able to quickly regain control and prevent them from becoming overexcited.

Previous studies of how anesthetic drugs affect this balance have shown conflicting results: Some have suggested that during anesthesia the brain becomes too stable and unresponsive, leading to loss of consciousness. Others have found that the brain becomes overexcitable, leading to a chaotic state and loss of consciousness.

Part of the reason for these conflicting results is that it has been difficult to accurately measure the brain’s dynamic stability. Measuring dynamic stability during loss of consciousness will help researchers determine whether unconsciousness is the result of too much or too little stability.

In this study, the scientists analyzed electrical recordings made in the brains of animals given propofol for an hour, during which they gradually lost consciousness. The recordings were made in four areas of the brain which are involved in vision, sound processing, spatial perception, and executive functions.

These recordings captured only a small portion of the overall brain activity, so to address this issue, the researchers used a technique called delayed embedding. This method allows researchers to characterize dynamic systems based on limited measurements by augmenting each measurement with measurements that were previously recorded. Using this method, the researchers were able to quantify how the brain responds to sensory cues, such as sounds, or to spontaneous disturbances in neural activity.

In a normal waking state, neural activity increases sharply after any stimulus and then returns to baseline activity. However, after propofol was administered, the brain took longer to return to baseline activity after these stimuli, remaining in a hyperaroused state. This effect became increasingly pronounced until the animals lost consciousness. This suggests that Suppression of neuronal activity by propofol leads to increased instability, causing the brain to lose consciousness, researchers say.

To see if they could reproduce this effect in a computational model, the researchers created a simple neural network. When they increased inhibition of certain nodes in the network, as propofol does in the brain, the network’s activity became destabilized, similar to the unstable activity the researchers observed in the brains of animals treated with propofol. “We looked at a simple model of a chain of interconnected neurons, and when we detected inhibition, we saw destabilization. So one of the things we’re proposing is that Increasing braking may cause instability, and this is later associated with loss of consciousness,” says Eisen.

As Fiete explains, “This paradoxical effect, in which increased inhibition destabilizes the network rather than silencing or stabilizing it, occurs through disinhibition. When propofol increases the inhibitory effect, “This impulse suppresses other inhibitory neurons, and the result is an overall increase in brain activity.”

The researchers suspect that other anesthetics that act on different types of neurons and receptors may produce the same effect through different mechanisms. They are currently exploring this possibility. If true, it could help researchers develop ways to more precisely control the level of anesthesia a patient experiences.

These systems, which Miller is working on with Emery Brown, the Edward Hood Taplin Professor of Medical Engineering at MIT, work by measuring brain dynamics and then adjusting drug doses accordingly in real time. “If you find common mechanisms that are at work across different anesthetics, you can make them safer by changing some settings, rather than having to develop safety protocols for all anesthetics one by one,” Miller says. “You don’t need a separate system for every anesthetic that will be used in the operating room. You need a system that does it all.”

The researchers also plan to apply their technique for measuring dynamic stability to other brain conditions, including neuropsychiatric disorders. “This method is quite powerful, and I think it will be very interesting to apply it to different brain conditions, different types of anesthetics, and also to other neuropsychiatric disorders such as depression and schizophrenia,” The fite is ending.