When a patient undergoes general anesthesia, the doctor has several drugs to choose from. Although each of these drugs acts on neurons in different ways, they all lead to the same result: a disruption of the brain’s balance between stability and excitability, according to a new study from MIT.
The researchers found that this disruption caused neural activity to become increasingly erratic, eventually causing the brain to lose consciousness. The discovery of this common mechanism may facilitate the development of new techniques for monitoring patients during anesthesia.
What’s interesting about this is the possibility of a universal anesthesia delivery system that could measure this one signal to tell you how unconscious you are, regardless of what drug is being used in the operating room. ”
Earl Miller, Picower Professor of Neuroscience and member of the MIT Picower Institute for Learning and Memory
Miller, Emery Brown, the Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience, and colleagues are currently working to develop an automated control system for anesthetic administration that uses EEG to measure brain stability and automatically adjust drug doses. This allows doctors to ensure that patients remain conscious without losing too much consciousness during surgery and without losing consciousness, which can have negative effects after surgery.
Miller and Ira Fite, professor of brain and cognitive sciences, director of the K. Lisa Yang Center for Integrative Computational Neuroscience (ICoN), and member of the McGovern Institute for Brain Research at the Massachusetts Institute of Technology, are senior authors of the new study, which was published today. cell report. MIT graduate student Adam Eisen is the paper’s lead author.
destabilize the brain
Exactly how anesthetic drugs render the brain unconscious has been a long-standing question in neuroscience. In 2024, research from Miller and Feete’s lab suggested that for propofol, the answer is that the anesthesia works by disrupting the balance between stability and excitability in the brain.
When a person is awake, the brain maintains this delicate balance, responding to sensory information and other input to return to a stable baseline.
“The nervous system has to work like a knife edge within this narrow excitability range,” Miller says. “You have to be excited enough so that the different parts influence each other, but if you get too excited you end up with a chaotic activity.”
In a 2024 study, researchers found that propofol takes the brain out of this state known as “dynamic stability.” As the drug dose increased, the brain took longer and longer to return to its baseline state after responding to new input. This effect became more and more pronounced until I lost consciousness.
For the study, the researchers devised a computational model to analyze neural activity recorded from the brain. This technique allowed them to determine how the brain responds to perturbations, such as auditory sounds or other sensory input, and how long it takes to return to baseline stability.
In the new study, researchers used the same technique to measure how the brain responded not only to propofol, but also to two additional anesthetics: ketamine and dexmedetomidine. The animals were given one of three drugs and their brain activity, including their response to hearing, was analyzed.
This study showed that the same destabilization caused by propofol also appeared during administration of the other two drugs. This “universal feature” appears despite the fact that the three drugs have different molecular mechanisms. Propofol binds to GABA receptors and inhibits neurons that have those receptors. Dexmedetomidine blocks the release of norepinephrine. Ketamine then blocks NMDA receptors and suppresses neurons that have those receptors.
The researchers hypothesize that each of these pathways influences the brain’s balance of stability and excitability in different ways, each leading to a global destabilization of this balance.
“All three of these drugs seem to work exactly the same way,” Miller says. “In fact, when you look at the destabilization measures that we use, you don’t know which agents are being applied.”
The researchers now plan to further investigate how each of these drugs causes the same pattern of brain destabilization.
“The molecular mechanisms for ketamine and dexmedetomidine are a little more complex than those for propofol,” Eisen says. “The future direction is to create meaningful models of what those biophysical effects are and see how that leads to destabilization.”
Anesthesia monitoring
The researchers showed that three different anesthetics cause similar patterns of destabilization in the brain, so they think measuring those patterns could provide a valuable way to monitor patients during anesthesia. Although anesthesia is a very safe procedure overall, it does come with some risks, especially for young children and people over 65 years of age.
For adults with dementia, anesthesia can worsen symptoms and can also worsen neuropsychiatric disorders such as depression. These risks are even higher if the patient enters a deep unconscious state known as burst inhibition.
To reduce these risks, Miller and Brown, who is also an anesthesiologist at MGH, are developing a prototype device that can measure a patient’s brain wave measurements while under anesthesia and adjust doses accordingly. Currently, doctors monitor patients’ heart rate, blood pressure, and other vital signs during surgery, but these do not accurately measure how unconscious a patient is.
“If we can limit people’s exposure to anesthesia, if we give them enough and not more, we can reduce the overall risk,” Miller says.
The MIT team is collaborating with researchers at Brown University to plan a small clinical trial of the monitoring device in patients undergoing surgery.
This research received funding from the U.S. Office of Naval Research, the National Institute of Mental Health, the Simons Center for the Social Brain, the Freedom Together Foundation, the Picower Institute, the National Science Foundation Computer Information Science and Engineering Directorate, the Simons Collaboration on the Global Brain, the McGovern Institute, and the National Institutes of Health.
sauce:
Massachusetts Institute of Technology
Reference magazines:
Iron, A.J. others. (2026). Neurodynamics are similarly destabilized under different general anesthesia conditions. cell report. DOI: 10.1016/j.celrep.2026.117048. https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00126-9
