What does it mean to be conscious? People have been thinking and writing about this question for millennia. Yet many things about the conscious mind remain a mystery, including how to measure and assess it. What is a unit of consciousness? Are there different levels of consciousness? What happens to consciousness during sleep, coma, and general anesthesia?
As anesthesiologists, we think about these questions often. We make a promise to patients every day that they will be disconnected from the outside world and their inner thoughts during surgery, retain no memories of the experience and feel no pain. In this way, general anesthesia has enabled tremendous medical advances, from microscopic vascular repairs to solid organ transplants.
In addition to their tremendous impact on clinical care, anesthetics have emerged as powerful scientific tools to probe questions about consciousness. They allow us to induce profound and reversible changes in conscious states—and study brain responses during these transitions.
But one of the challenges that anesthesiologists face is measuring the transition from one state to another. That’s because many of the approaches that exist interrupt or disrupt what we are trying to study. Essentially, assessing the system affects the system. In studies of human consciousness, determining whether someone is conscious can arouse the person being studied—confounding that very assessment. To address this challenge, we adapted a simple approach we call the breathe-squeeze method. It offers us a way to study changes in conscious state without interrupting those shifts.
To understand this approach, it helps to consider some insights from studies of consciousness that have used anesthetics. For decades researchers have used electroencephalography (EEG) to observe electrical activity in the brains of people receiving various anesthetics. They can then analyze that activity with EEG readings to characterize patterns that are specific to various anesthetics, so-called anesthetic signatures.
Such research reveals that most anesthetic drugs slow the brain’s rhythms and increase their size, effects that impair the communication between brain regions. For example, a recent study found that propofol, the most commonly used drug for general anesthesia, can disrupt the way brain regions typically work together to process sensory information.
Consciousness, this and other research reveals, is not simply a binary—on or off, conscious or unconscious—but instead something that can encompass a continuum of different states that involve different kinds of brain functioning. For instance, consciousness can be connected to the environment through our senses and behavior (connected consciousness), as in most of our waking hours, or disconnected from our surroundings (disconnected consciousness), as when we dream during sleep.
Unconsciousness—as when someone is in a coma—is more difficult to study than connected or disconnected consciousness, but it is generally understood as a state of oblivion, void of subjective experience or memory. When we prepare a patient for surgery, we adjust the levels of anesthetic to render them unconscious. When someone is under general anesthesia, they are experiencing a temporary and reversible coma during which they feel no pain and after which they will have no memories of their procedure.
Understanding the transitions between these states is essential to ensure adequate levels of general anesthesia and to illuminate questions in anesthesiology, consciousness, sleep and coma research. To better map the transition out of connected consciousness, we recently adapted a new approach for monitoring a person’s ability to generate volitional behaviors without external prompting.
Generally, researchers track the onset of sedation by issuing verbal commands and recording behavioral responses. For instance, a scientist might periodically ask someone to open their eyes or push a button while receiving an anesthetic infusion. Once the person stops responding to this command, the scientist assumes they have lost connected consciousness.
This technique has proven useful in contrasting the connected and disconnected conscious mind. But when it comes to understanding the transition between these states, there are several drawbacks. For one, the auditory cue is not standardized: the inflection and volume of the voice, what is said, and how frequently it is repeated all vary across and even within studies. A more fundamental problem is that these commands can arouse people as they drift into a disconnected state. This limitation means that researchers often need to wait several minutes between issuing verbal commands and assessing the response—adding uncertainty to the exact timing of the transition.
In our study, we wanted a more sensitive and precise approach to measuring the onset of sedation without the risk of disrupting the transition. So we turned to a method first described in 2014 by sleep researchers at Massachusetts General Hospital and Johns Hopkins University. In that work, the investigators asked participants to squeeze a ball whenever they breathed in. The researchers tracked each person’s squeezes using a dynamometer, a tool for measuring grip strength, and an electromyography sensor, which measures muscle response. In this way, they were able to precisely track the sleep onset process without disrupting it.
For our study, we trained 14 healthy volunteers in that same task and presented the breathe-squeeze exercise as a kind of mindfulness meditation. We instructed the participants to focus on their breathing and to squeeze a handheld dynamometer whenever they breathed in. After a few minutes of training for each person, we placed an intravenous catheter in their arm to deliver the sedative and set up vital sign monitors and a fitted 64-channel EEG cap to record brain waves throughout the experiment.
All participants reliably synchronized their squeezes with breathing during an initial baseline period without any sedation. They then received a slow infusion of dexmedetomidine, a sedative commonly used in operating rooms and intensive care units. As brain concentrations of dexmedetomidine increased, participants occasionally missed a squeeze or mistimed it. Eventually, they stopped squeezing altogether.
Following some additional tests, we turned off the dexmedetomidine infusion, allowing participants to recover from sedation. To our astonishment, after a period of 20 to 30 minutes, everyone remembered the task and began spontaneously squeezing in synchrony with their breath without any prompting. This allowed us to analyze both the sedation-onset and sedation-offset timing and compare them with previous studies that used verbal commands to assess consciousness.
The breathe-squeeze task was clearly a more sensitive approach to measuring the transition out of connected consciousness. Participants stopped performing the task at lower dexmedetomidine concentrations than those at which people had been observed to stop responding to auditory cues in other studies—highlighting the arousing effects of external cues on the system. These findings may also indicate that connected consciousness can be further broken down into internally generated behaviors (such as reminding yourself to squeeze a ball as you inhale) and externally prompted behaviors (such as responding to verbal commands) with separate transition points—an idea that refines our understanding of the continuum of consciousness.
by Christian Guay and Emery Brown in scientificamerican.com on January 26, 2024
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