MIT neuroscientists have made a groundbreaking discovery regarding propofol, a widely used anesthesia drug, revealing how it induces unconsciousness. Propofol, known for its role in facilitating general anesthesia, affects the brain's equilibrium between stability and excitability. The study, published in Neuron, offers new insights into how this drug disrupts neural dynamics, providing a clearer understanding of its effects on consciousness.
The research team, led by Earl K. Miller, Picower Professor of Neuroscience at MIT’s Picower Institute for Learning and Memory, and Ila Fiete, a professor at MIT’s McGovern Institute for Brain Research and director of the K. Lisa Yang Integrative Computational Neuroscience Center, has used a novel approach to study how propofol alters brain activity. Graduate student Adam Eisen and postdoctoral researcher Leo Kozachkov also contributed significantly to the research. Their work centers on how propofol destabilizes the brain’s normal state, leading to loss of consciousness.
Propofol functions by binding to GABA receptors in the brain, which inhibits neuronal activity. This inhibition affects a brain state known as “dynamic stability,” where neurons maintain enough excitability to respond to stimuli while avoiding excessive excitation that could lead to chaos. The researchers discovered that propofol disrupts this balance, causing an increasingly unstable brain state that ultimately results in unconsciousness.
Previous studies on anesthesia have yielded conflicting results regarding whether unconsciousness results from excessive stability or heightened excitability. This study used electrical recordings from animal brains subjected to propofol over an extended period, revealing that as propofol’s effects increased, the brain took longer to return to its baseline state after sensory inputs, indicating escalating instability.
To validate their findings, the researchers created a computational model of a neural network. They observed that increasing inhibition within this model, analogous to propofol's effect, led to destabilized network activity. This confirmed their hypothesis that heightened inhibition can lead to destabilization, thus contributing to loss of consciousness.
The implications of this research extend to improving anesthesia monitoring and control. If other anesthetic drugs induce unconsciousness through similar mechanisms, it may be possible to develop unified systems for adjusting anesthesia dosages based on real-time brain dynamics. This would enhance patient safety and reduce the need for multiple monitoring systems for different anesthetics.
The team plans to apply their dynamic stability measurement technique to other brain states and neuropsychiatric conditions, including depression and schizophrenia. This could lead to further advancements in understanding and treating a range of neurological and mental health disorders.
The study was supported by various institutions including the Office of Naval Research, the National Institute of Mental Health, and the National Science Foundation, highlighting its broad impact on the fields of neuroscience and anesthesia research.
