Investigators exploring consciousness have successfully utilized a drug to reveal the complex brain structures associated with the unconscious state, providing a rare glimpse into brain elements that have typically been challenging to research.
In surgical theaters and intensive care units, propofol stands out as a preferred medication, commonly administered to sedate patients for their comfort or to induce complete unconsciousness for surgical interventions.
Propofol acts swiftly and is generally well-tolerated by most individuals under the care of an anesthesiologist. However, what occurs in the brain during the period of unconsciousness, and what insights does this offer regarding consciousness itself?
Researchers at the University of Michigan (U-M) investigating the essence of consciousness have effectively used this drug to uncover the complex brain architecture behind the unconscious state, presenting an exceptional opportunity to examine brain structures that are generally hard to analyze.
“Consciousness has been scrutinized from various viewpoints, and grasping the neurobiological underpinnings of consciousness is crucial across numerous medical fields, including neurology, psychiatry, and anesthesiology,” mentioned Zirui Huang, Ph.D., a Research Assistant Professor within the Department of Anesthesiology at U-M Medical School.
Researchers have long debated how anesthetics like propofol induce unconsciousness. Specifically, they question whether the primary site of action is in the thalamus, a centrally located structure in the brain that processes sensory data from our eyes, skin, and ears, or in the cerebral cortex, which interprets this data in innovative ways.
A recent study published in the journal Nature Communications, directed by Huang along with George Mashour, M.D., Ph.D., and Anthony G. Hudetz, Ph.D., from the U-M Center for Consciousness Science, outlines for the first time in humans how connections among neurons in these critical areas are altered by propofol.
In healthy participants, they monitored shifts in brain structure before, during, and after sedation with propofol using functional magnetic resonance imaging (fMRI). This method allowed them to observe blood flow changes in various brain regions as study participants transitioned in and out of the unconscious state.
Initially, Huang explained that the thalamus maintains a balanced activity level among specific nuclei (groups of brain cells) that direct sensory information to particular cortex areas, termed unimodal processing, and nonspecific nuclei, which disseminate information more broadly to higher cortical layers, known as transmodal processing.
The research team discovered that under deep sedation, the thalamus exhibited a significant decrease in activity within the clusters of brain cells responsible for transmodal processing, resulting in a prevailing unimodal pattern. This finding implies that although sensory signals are still received, they are not being integrated.
“For over two decades, attention has been given to the anesthetic effects in the thalamus and cortex. I believe this study marks a significant advancement in neurobiology,” stated George Mashour, M.D., Ph.D., Professor of Anesthesiology and Pharmacology, and founder of the U-M Center for Consciousness Science.
Furthermore, they identified specific cell types that contributed to the transition into the unconscious state and how these relate to modifications in thalamic processing. Huang noted that the thalamus comprises at least two distinct cell types: core cells and matrix cells.
Hudetz, a Professor of Anesthesiology at U-M and the current director of the Center for Consciousness Science, insists, “We now possess compelling evidence indicating that the extensive connections of thalamic matrix cells to higher-order cortex areas are vital for consciousness.”
Visualizing the cortex as a layered onion, core cells connect to lower layers, while matrix cells reach out to higher layers more diffusely. By analyzing mRNA expression profiles—akin to identification tags for the cells—they discovered that a disruption in matrix cells was more critical in the shift toward unconsciousness than that in core cells. Additionally surprising was the finding that GABA, a major inhibitory neurotransmitter usually believed to be fundamental to propofol’s effects, did not play as significant a role as anticipated.
“The findings indicate that the loss of consciousness during deep sedation primarily revolves around the functional disturbance of matrix cells throughout the thalamus,” Huang concluded.
