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Common Anaesthetic Could Work By Inducing Chaos In The Brain

July 15, 2024 by Deborah Bloomfield

How do anesthetics stop us from perceiving the world around us? Some may knock us out by making the brain temporarily more unstable, a new study focusing on the drug propofol suggests.

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Anesthesia: the word itself comes from the ancient Greek “an” (without) and “aesthesis” (sensation). Anesthesia is medically described as a combination of paralysis (the lack of movement), analgesia (the lack of pain), amnesia (the lack of memory), and unconsciousness. It is a chemically induced brain state that has been a powerful tool in medicine, making many surgical procedures possible. 

In everyday life, our brains go through a number of brain states, for example, being awake or asleep. One way these states are different is how they process sensory stimuli, perturbations to the state of our brain. For example, the sound of a notification on your phone causes a cascade of neural activity: cells become more active, and signal to other cells. That same sound will have completely different effects on the brain’s activity and your sensory perception depending on your state. You might not hear it at all if you’re asleep. Or under anesthesia.

How does our brain respond to sensory stimuli under anesthesia and why can we not consciously perceive them? A study published today tried to understand the differences between an awake brain and one under anesthesia by looking at the stability of the brain’s activity. 

They used principles of a branch of mathematics called dynamical systems theory that allowed them to measure stability. Stability is a system’s ability to recover from disturbances and return to a baseline state. A stable system is a pendulum with friction: you can change the position from which you drop it, but eventually, it will come to rest in the same position. 

An example of an unstable system is the weather: a small perturbation can lead to big changes in the system over time, This effect is often metaphorically described as a tornado caused by the flap of the wings of a butterfly

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“The brain has to operate on this knife’s edge between excitability and chaos. It’s got to be excitable enough for its neurons to influence one another, but if it gets too excitable, it spins off into chaos.” said Professor Earl Miller, one of the senior authors on the study, in a press release, explaining how stability can be a useful metric to quantify the state of the brain.

In the study, researchers recorded from the brains of two macaques while they were administered propofol, an injectable anesthetic commonly used in surgery. As the primates went deeper into anesthesia the activity in their brains became increasingly unstable.

The stability of the awake brain is in part due to a balance between excitation and inhibition. Broadly speaking, there are two classes of neurons in your brain: ones that increase the activity in other neurons (excitatory) and ones that decrease it (inhibitory). Propofol acts on the inhibitory system, enhancing it and bringing the system out of balance.

The researchers then played sounds to the macaques and found that, under anesthesia, the responses in the brain were slower and longer. The sensory stimulation led to a prolonged perturbation in the state of the system. This somewhat erratic activity could mean that the brain can no longer process information effectively. This could be why we can’t perceive our environment under anesthesia – and can’t feel pain. 

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This new method for describing brain states by looking at their stability could be used to study “different brain states, different types of anesthetics, and also other neuropsychiatric conditions like depression and schizophrenia”, said Professor Ila Fiete, another senior author on the study.

This article is published in the journal Neuron.

Deborah Bloomfield
Deborah Bloomfield

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