How to tell if a brain is awake

Summary: Study finds EEG features may not always be accurate in being able to capture the level of consciousness in patients under anesthesia.

Source: Michigan Medicine

Remarkably, scientists are still debating just how to reliably determine whether someone is conscious. This question is of great practical importance when making medical decisions about anesthesia or treating patients in vegetative state or coma.

Currently, researchers rely on various measurements from an electroencephalogram, or EEG, to assess level of consciousness in the brain. A Michigan Medicine team was able to demonstrate, using rats, that the EEG doesn’t always track with being awake.

“EEG doesn’t necessarily correlate with behavior,” says Dinesh Pal, Ph.D., assistant professor of anesthesiology at the U-M Medical School.

“We are raising more questions and asking that people are more cautious when interpreting EEG data.”

Under anesthesia, an EEG will display a sort of signature of unconsciousness: reduced brain connectivity; increased slow waves, which are also associated with deep sleep, vegetative state and coma; and less complexity or less change in brain activity over time.

Building on data from a 2018 study, Pal and his team wanted to see what happened to these measures when a brain was awakened under anesthesia. To do so, they targeted an area of the brain called the medial prefrontal cortex, which has been shown to play a role in attention, self-processing and coordinating consciousness.

Using a drug in that part of the brain that mimics the activity of neurotransmitter acetylcholine, the team was able to rouse some of the rats so that they were up and moving around despite the fact that they were receiving continuous anesthesia. Using the same drug in the back of the brain did not awaken the rats. So, both groups of rats had anesthesia in the brain but only one group “woke up.”

Then, “we took the EEG data and looked at those factors that have been considered correlates of wakefulness. We figured if the animals were waking up, even while still exposed to anesthesia, then these factors should also come back up. However, despite wakeful behavior, the EEGs were the same in the moving rats and the non-moving anesthetized rats,” says Pal.

What does this mean for the EEG’s ability to reflect consciousness? “The study does support the possibility that certain EEG features might not always accurately capture the level of consciousness in surgical patients,” says senior author George A. Mashour, M.D., Ph.D., chair of the U-M Department of Anesthesiology.

However, “EEG likely does have value in helping us understand if patients are unconscious. For example, a suppressed EEG would suggest a very high probability of unconsciousness during general anesthesia. However, using high anesthetic doses to suppress the EEG might have other consequences, like low blood pressure, that we want to avoid. So, we will have to continue to be judicious in assessing the many indices available, including pharmacologic dosing guidelines, brain activity, and cardiovascular activity.”

This is a drawing of a brain

“The study does support the possibility that certain EEG features might not always accurately capture the level of consciousness in surgical patients,” says senior author George A. Mashour, M.D., Ph.D., chair of the U-M Department of Anesthesiology. Image is in the public domain.

Pal notes that there is physiological precedent for an EEG mismatching behavior; for example, the brain of someone in REM sleep is almost identical to an awake brain. “No monitor is perfect, but the current monitors we use for the brain are good and do their job most of the time. However, our data suggest there are exceptions.”

Their study raises intriguing questions about how consciousness is reflected in the brain, says Pal. “These measures do have value and we have to do more studies. Maybe they are associated with awareness and what we call the content of consciousness. With rats, we don’t know-we can’t ask them.”

About this neuroscience research article

Source:
Michigan Medicine
Media Contacts:
Kelly Malcom – Michigan Medicine
Image Source:
The image is in the public domain.

Original Research: Closed access
“Level of consciousness is dissociable from electroencephalographic measures of cortical connectivity, slow oscillations, and complexity”. Dinesh Pal [PhD.], Duan Li [PhD.], Jon G. Dean [M.S.], Michael A. Brito [B.A.], Tiecheng Liu [M.D.], Anna M. Fryzel [M.A.], Anthony G. Hudetz [D.B.M., Ph.D.] and George A. Mashour [M.D., PhD.].
Journal of Neuroscience doi:10.1523/ENEURO.0391-19.2019.

Abstract

Level of consciousness is dissociable from electroencephalographic measures of cortical connectivity, slow oscillations, and complexity

Leading neuroscientific theories posit a central role for the functional integration of cortical areas in conscious states. Considerable evidence supporting this hypothesis is based on network changes during anesthesia but it is unclear if these changes represent state-related (conscious vs. unconscious) or drug-related (anesthetic vs. no anesthetic) effects. We recently demonstrated that carbachol delivery to prefrontal cortex restored wakefulness despite continuous administration of the general anesthetic sevoflurane. By contrast, carbachol delivery to parietal cortex, or noradrenaline delivery to either prefrontal or parietal cortices, failed to restore wakefulness. Thus, carbachol-induced reversal of sevoflurane anesthesia represents a unique state that combines wakefulness with clinically relevant anesthetic concentrations in the brain. To differentiate the state-related and drug-related associations of cortical connectivity and dynamics, we analyzed the electroencephalographic data gathered from adult male Sprague Dawley rats during the aforementioned experiments for changes in functional cortical gamma connectivity (25-155 Hz), slow oscillations (0.5-1Hz), and complexity (<175 Hz). We show that higher gamma (85-155 Hz) connectivity is decreased (p≤0.02) during sevoflurane anesthesia - an expected finding - but was not restored during wakefulness induced by carbachol delivery to prefrontal cortex. Conversely, for rats in which wakefulness was not restored, the functional gamma connectivity remained reduced but there was a significant decrease (p<0.001) in the power of slow oscillations and increase (p<0.001) in cortical complexity, which was similar to that observed during wakefulness induced after carbachol delivery to prefrontal cortex. We conclude that the level of consciousness can be dissociated from cortical connectivity, oscillations, and dynamics.


SIGNIFICANCE STATEMENT

Numerous theories of consciousness suggest that functional connectivity across the cortex is characteristic of the conscious state and is reduced during anesthesia. However, it is unknown whether the observed changes are state-related (conscious vs. unconscious) or drug-related (drug vs. no drug). We employed a novel rat model in which cholinergic stimulation of prefrontal cortex produced wakefulness despite continuous exposure to a general anesthetic. We demonstrate that, as expected, general anesthesia reduces connectivity. Surprisingly, the connectivity remains suppressed despite pharmacologically-induced wakefulness in the presence of anesthetic, with restoration occurring only after the anesthetic is discontinued. Thus, whether an animal exhibits wakefulness or not can be dissociated from cortical connectivity, prompting a re-evaluation of the role of connectivity in level of consciousness.

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