Universal Signature of Unconsciousness Found in General Anesthesia

When patients undergo general anesthesia, doctors can choose from several drugs. Despite each drug acting on neurons in different ways, they all lead to a common result: a disruption of the brain’s balance between stability and excitability, according to a new MIT study published in the journal Cell Reports.

Destabilizing the Brain

This disruption causes neural activity to become increasingly unstable, ultimately leading to a loss of consciousness, the researchers found. The discovery of this common mechanism could facilitate the development of new technologies for monitoring patients during anesthesia.

“What’s exciting about that is the possibility of a universal anesthesia-delivery system that can measure this one signal and tell how unconscious you are, regardless of which drugs they’re using in the operating room,” says Earl Miller, the Picower Professor of Neuroscience and a member of MIT’s Picower Institute for Learning and Memory.

Miller, Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience Emery Brown, and their colleagues are now working on an automated control system for delivering anesthesia drugs. This system would measure the brain’s stability using electroencephalography (EEG) and then automatically adjust the drug dose.

This could facilitate doctors ensure patients remain unconscious throughout surgery without inducing excessively deep unconsciousness, which can lead to negative post-operative effects.

How Anesthesia Drugs Affect Brain Waves

In 2024, research from Miller and Ila Fiete’s labs suggested that propofol works by disrupting the brain’s dynamic stability. When awake, the brain maintains a delicate balance, responding to stimuli and returning to a stable baseline. The nervous system operates within a narrow range of excitability; it must be excitable enough for different brain regions to communicate, but not so excitable that it descends into chaotic activity.

The 2024 study found that propofol disrupts this state, increasing the time it takes for the brain to return to its baseline after responding to input, eventually leading to unconsciousness.

The recent study utilized the same technique to analyze the effects of not only propofol but also ketamine and dexmedetomidine on brain activity in animals. The researchers found that all three drugs induced the same destabilization, despite their different molecular mechanisms: propofol affects GABA receptors, dexmedetomidine blocks norepinephrine release, and ketamine blocks NMDA receptors.

“All three of these drugs appear to do the exact same thing,” Miller says. “In fact, you could look at the destabilization measure we employ and you can’t tell which drug is being applied.”

Monitoring Anesthesia for Improved Patient Safety

Now that researchers have demonstrated that these three anesthesia drugs produce similar destabilization patterns, they believe measuring these patterns could provide a valuable way to monitor patients during anesthesia. While generally safe, anesthesia carries risks, particularly for young children and individuals over 65.

Anesthesia can worsen dementia and exacerbate neuropsychiatric disorders like depression, with higher risks associated with deeper states of unconsciousness, such as burst suppression.

To mitigate these risks, Miller and Brown, also an anesthesiologist at Massachusetts General Hospital (MGH), are developing a prototype device that measures EEG readings during anesthesia and adjusts drug dosage accordingly. Current monitoring focuses on vital signs like heart rate and blood pressure, which don’t accurately reflect the depth of unconsciousness.

“If you can limit people’s exposure to anesthesia, if you grant just enough and no more, you can reduce risks across the board,” Miller says.

The MIT team is planning a clinical trial with Brown University researchers to test their monitoring device on patients undergoing surgery.

Citation: Similar destabilization of neural dynamics under different general anesthetics, Cell Reports (2026). DOI: 10.1016/j.celrep.2026.117048. www.cell.com/cell-reports/full…2211-1247(26)00126-9