General anesthesia poses a twofold mystery: How it disrupts consciousness, including sensory perception, and what this might say about the nature of consciousness. A new study led by researchers at The Picower Institute for Learning and Memory at MIT provides evidence in animals that consciousness depends on properly synchronized communication in the cerebral cortex, and that the anesthetic propofol nullifies sensory processing by cutting it off.
In the Journal of Cognitive Neuroscience, The researchers report clear evidence that in anesthetized animals, sounds and tactile sensations still trigger neural activity in an area of the cortex that receives incoming sensory information. But just as clearly, measurements of neural spiking and broader oscillatory activity showed that these signals failed to propagate to three other cortical regions with higher-level processing and cognitive responsibilities, as seen during normal wakefulness.
“What this study shows is that the cortex is not on the same page,” said study corresponding author Earl K. Miller, the Picower Professor in the Department of Brain and Cognitive Sciences at MIT. “The information gets to the cortex. It’s recorded in primary sensory areas. It just doesn’t get to the rest of the cortex. Because of the anesthesia, it only makes it part of the way.”
The significance of this, said Emery N. Brown co-senior author Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience, is that “the study suggests that consciousness requires coordination of activities between cortical areas. Simply activating one or more of these areas is not enough.”
Lead study author John Tauber, who recently earned his Ph.D. at MIT in Brown’s lab, said the study could help efforts to improve anesthesia care. Brown is an anesthesiologist at Massachusetts General Hospital as well as a professor of Brain and Cognitive Sciences at MIT, a member of the Institute for Medical Engineering and Science, and a faculty member at Harvard Medical School.
“We hope our work further highlights the importance of actively monitoring what happens in the brain during anesthesia,” Tauber said. “Future studies along these lines will help us develop clear indicators of whether a patient is still processing sensory information. This will allow anesthesiologists to adjust drug dosage and prevent intraoperative sensitization from occurring.”
Sensory processing is inhibited
To conduct the study, the team worked with two animals to measure brain activity — both the electrical “spiking” of individual neurons and their collective rhythmic activity — via electrode arrays placed in four areas of the cortex, both before and after propofol administration. general anesthesia. The researchers chose cortical regions to represent the hierarchical continuum of its functions from initial sensation (the superior temporal gyrus or STG) to increasingly higher levels of cognition (the posterior parietal cortex or PPC, Area 8A and the prefrontal cortex , or PFC).
In both states of consciousness, the animals experienced specific stimuli: two sound tones, including one by itself and another in combination with a puff of air in the face. In the awake state, such stimulation caused an increase in alpha/beta frequency activity in all cortical regions. The STG also showed a strong increase in higher frequency oscillations. The response changed dramatically under anesthesia. While the alpha and beta frequency response was reduced in the STG, it essentially disappeared in all higher cortical regions.
“We expected to see a more gradual loss of responses and information,” Tauber said. “The drop in responses during anesthesia from the auditory cortex (STG) to the associative cortex (PPC) was striking.”
Along with the decrease in activity, the researchers measured a decrease in the sensory information being detected in the brain as it moved up the cortical hierarchy. The “decoder” software found sensory information in all areas of the cortex during wakefulness, but during unconsciousness, less and less information could be found the higher up the cortex the researchers looked.
An incoherent bark
When the researchers then measured the synchronization of activity between brain regions, they found that it also broke down under anesthesia. When the animals were awake, they showed a strong degree of synchrony in alpha/beta oscillatory activity, but when they were unconscious, “there was little or no stimulus-induced synchrony for either pair of cortical regions,” the researchers reported.
A characteristic of the propofol-anesthetized brain is that neural oscillatory activity takes on distinct “up” and “down” states of greater or lesser activity over time. To test whether sensory information is cut off in both states or only in the lower states, the researchers developed a statistical analysis. They found that while all neuronal firings were indeed low during the down states, even during the up states where sensory signals were measurable in the STG, they still failed to progress beyond this region.
“We expected that the responses in higher cortical regions would be disrupted at least during the arousal states, but it was a bit surprising to find that the responses disappeared almost entirely,” Tauber said. “Neural activity during arousal states is functionally quite different from the awake state, but we think we’ve only scratched the surface of understanding the differences between the two.”
In short, the new study’s evidence suggests that the loss of consciousness does not result from a wholesale shutdown of the cortex, but rather from suppression of communication within it, Miller said.
A key next question to be answered is how propofol exerts this sedation.
“What is it about these changing dynamics that blocks the flow of information through the cortex?” asks Miller. “What is the headwind that blows up this sensory information and holds it in the sensory cortex?”
Tauber added that the team only looked at sensory processing when they were sure the animals were completely unconscious. It could be informative, he said, to study how sensory processing changes during the transition from wakefulness to this fully unconscious state.
In addition to Tauber, Miller and Brown, other authors of the paper are Scott Brincat, Emily Stephen, Jacob Donoghue and Leo Kozachkov.
The National Institutes of Health, the Office of Naval Research, the JPB Foundation, and the Picower Institute for Learning and Memory funded the research.