A new study from the US reveals for the first time, that the brain
has a distinct pattern of electrical activity as patients lose
consciousness during
anesthesia. The pattern shows very slow oscillations, reflecting a
breakdown of communication between the different regions of the brain,
each of which shows
shorts bursts of activity alternating with longer silences.
The researchers write about their findings in a paper published online first on 5 November in the Proceedings of the National Academy of
Sciences.
They hope that by improving understanding of what happens in the brain as it loses consciousness, the study will help anesthesiologists better maintain the right balance between too little and too much anesthetic.
Senior author Patrick Purdon, an instructor of anesthesia at Massachusetts General Hospital (MGH) and Harvard Medical School, says in a statement, clinicians will now know what to look for on the electroencephalograph (EEG) when putting a patient under anesthesia:
"We now finally have an objective physiological signal for measuring when someone's unconscious under anesthesia."
EEG Patterns in Epileptic Patients An EEG is a machine that records electrical activity of the brain through electrodes on the scalp. It measures changes in voltage resulting from the various currents flowing between neurons or brain cells.
For their study, Purdon and colleagues studied epileptic patients who had electrodes implanted in their brains to monitor seizures and were having an operation to remove them.
The patients received a common anesthetic known as propofol and had their brain activity monitored by EEG.
Propofol activates receptors on neurons, in a way that makes the brain cells less active, although exactly how this happens is not clear.
The researchers noticed the EEG showed a distinct pattern at the point where consciousness was lost. This was about 40 seconds after receiving the anesthetic, and was defined by the moment when patients stopped responding to sounds played to them every four seconds.
Distinct Pattern of Overall and Local Brain Activity
To record brain activity, Purdon and colleagues used two different sized of electrode, each size taking a different reading of brain activity. The larger electrodes, about the size of a large coin, were placed about 1 cm apart and recorded the overall EEG or brain wave pattern.
The smaller, more localized, electrodes were concentrated in a group of rows about 4 mm wide. Between 50 and 100 of these were implanted in each patient, in different brain regions.
These smaller electrodes recorded activity from individual neurons, and this study is thought to be the first to record neuron activity in patients as they lose consciousness.
The large electrodes showed that within one or two seconds of patients losing consciousness, the EEG pattern suddenly turned to low frequency oscillations, at about 1 cycle per second (about 1 Hz).
This coincided with the small electrodes showing a "flickering" pattern at individual neuron level. Individual neurons within localized brain regions were active for a few hundred milliseconds, then became quiet for a few hundred milliseconds. This created the oscillating pattern seen on the EEG, say the researchers.
"We show that propofol-induced unconsciousness occurs within seconds of the abrupt onset of a slow (< 1 Hz) oscillation in the local field potential. This oscillation marks a state in which cortical neurons maintain local patterns of network activity, but this activity is fragmented across both time and space," they write.
Periodic Silencing Prevents Communication in Brain One of the lead authors, Laura Lewis, a graduate student in the Department of Brain and Cognitive Sciences (BCS) at Massachusetts Institute of Technology (MIT), says:
"Within a small area, things can look pretty normal, but because of this periodic silencing, everything gets interrupted every few hundred milliseconds, and that prevents any communication."
"When one area was active, it was likely that another brain area that it was trying to communicate with was not active. Even when the neurons were on, they still couldn't send information to other brain regions," she explains.
Loss of Consciousness Could Be "Failure of Information Integration"
Michael Avidan is a professor of anesthesiology at Washington University School of Medicine, and was not involved in the study. He describes the findings as "exciting" and suggests they offer neurobiological evidence for the "information integration theory" of consciousness. This theory suggests large-scale brain networks integrate information from the senses to generate our overall impression of the world around us.
When we lose consciousness, there could still be information "coming into the brain, but that information is remaining localized and doesn't get integrated into a coherent picture," he explains.
Another lead author, Emery Brown, professor of brain and cognitive sciences and health sciences and technology at MIT and an anesthesiologist at MGH, says this mechanism of "failure of information integration" has been put forward before as a possible explanation for loss of consciousness, but it was not clear how it worked.
"This finding really narrows it down quite a bit. It really does, in a very fundamental way, constrain the possibilities of what the mechanisms could be," he adds.
Successful Anesthesia: Maintaing a Delicate Balance
The researchers hope the pattern will help anesthesiologists improve monitoring of patients as they receive anesthesia, thus preventing rare cases where patients wake up during operations or where too much anesthetic stops them breathing.
At present, anesthesiologists monitor patients under anesthetic with recordings that calculate an index from the EEG. But that index can hide the underlying physiology that can be seen directly in the slow waves.
Brown says their findings suggest they should be looking at and interpreting the oscillations in the raw EEG readings.
"If you do that, you have a physiologically linked way to know when someone is unconscious. We can take this into the operating room today and give better patient care," he adds.
The team is now going to look at what happens in the brain as it regains consciousness. They have already started looking at the effects of other anesthesia drugs, to see if they generate the same brain patterns.
Purdon says based on EEG studies there appear to be many other drugs producing the same slow oscillations. But there are also a number that are "doing something totally different," he adds.
Funds from the Nationa Institutes of Health (NIH), the Canadian Research Foundation, and the National Institute of Neurological Disorders and Stroke, helped finance the study.
They hope that by improving understanding of what happens in the brain as it loses consciousness, the study will help anesthesiologists better maintain the right balance between too little and too much anesthetic.
Senior author Patrick Purdon, an instructor of anesthesia at Massachusetts General Hospital (MGH) and Harvard Medical School, says in a statement, clinicians will now know what to look for on the electroencephalograph (EEG) when putting a patient under anesthesia:
"We now finally have an objective physiological signal for measuring when someone's unconscious under anesthesia."
EEG Patterns in Epileptic Patients An EEG is a machine that records electrical activity of the brain through electrodes on the scalp. It measures changes in voltage resulting from the various currents flowing between neurons or brain cells.
For their study, Purdon and colleagues studied epileptic patients who had electrodes implanted in their brains to monitor seizures and were having an operation to remove them.
The patients received a common anesthetic known as propofol and had their brain activity monitored by EEG.
Propofol activates receptors on neurons, in a way that makes the brain cells less active, although exactly how this happens is not clear.
The researchers noticed the EEG showed a distinct pattern at the point where consciousness was lost. This was about 40 seconds after receiving the anesthetic, and was defined by the moment when patients stopped responding to sounds played to them every four seconds.
Distinct Pattern of Overall and Local Brain Activity
To record brain activity, Purdon and colleagues used two different sized of electrode, each size taking a different reading of brain activity. The larger electrodes, about the size of a large coin, were placed about 1 cm apart and recorded the overall EEG or brain wave pattern.
The smaller, more localized, electrodes were concentrated in a group of rows about 4 mm wide. Between 50 and 100 of these were implanted in each patient, in different brain regions.
These smaller electrodes recorded activity from individual neurons, and this study is thought to be the first to record neuron activity in patients as they lose consciousness.
The large electrodes showed that within one or two seconds of patients losing consciousness, the EEG pattern suddenly turned to low frequency oscillations, at about 1 cycle per second (about 1 Hz).
This coincided with the small electrodes showing a "flickering" pattern at individual neuron level. Individual neurons within localized brain regions were active for a few hundred milliseconds, then became quiet for a few hundred milliseconds. This created the oscillating pattern seen on the EEG, say the researchers.
"We show that propofol-induced unconsciousness occurs within seconds of the abrupt onset of a slow (< 1 Hz) oscillation in the local field potential. This oscillation marks a state in which cortical neurons maintain local patterns of network activity, but this activity is fragmented across both time and space," they write.
Periodic Silencing Prevents Communication in Brain One of the lead authors, Laura Lewis, a graduate student in the Department of Brain and Cognitive Sciences (BCS) at Massachusetts Institute of Technology (MIT), says:
"Within a small area, things can look pretty normal, but because of this periodic silencing, everything gets interrupted every few hundred milliseconds, and that prevents any communication."
"When one area was active, it was likely that another brain area that it was trying to communicate with was not active. Even when the neurons were on, they still couldn't send information to other brain regions," she explains.
Loss of Consciousness Could Be "Failure of Information Integration"
Michael Avidan is a professor of anesthesiology at Washington University School of Medicine, and was not involved in the study. He describes the findings as "exciting" and suggests they offer neurobiological evidence for the "information integration theory" of consciousness. This theory suggests large-scale brain networks integrate information from the senses to generate our overall impression of the world around us.
When we lose consciousness, there could still be information "coming into the brain, but that information is remaining localized and doesn't get integrated into a coherent picture," he explains.
Another lead author, Emery Brown, professor of brain and cognitive sciences and health sciences and technology at MIT and an anesthesiologist at MGH, says this mechanism of "failure of information integration" has been put forward before as a possible explanation for loss of consciousness, but it was not clear how it worked.
"This finding really narrows it down quite a bit. It really does, in a very fundamental way, constrain the possibilities of what the mechanisms could be," he adds.
Successful Anesthesia: Maintaing a Delicate Balance
The researchers hope the pattern will help anesthesiologists improve monitoring of patients as they receive anesthesia, thus preventing rare cases where patients wake up during operations or where too much anesthetic stops them breathing.
At present, anesthesiologists monitor patients under anesthetic with recordings that calculate an index from the EEG. But that index can hide the underlying physiology that can be seen directly in the slow waves.
Brown says their findings suggest they should be looking at and interpreting the oscillations in the raw EEG readings.
"If you do that, you have a physiologically linked way to know when someone is unconscious. We can take this into the operating room today and give better patient care," he adds.
The team is now going to look at what happens in the brain as it regains consciousness. They have already started looking at the effects of other anesthesia drugs, to see if they generate the same brain patterns.
Purdon says based on EEG studies there appear to be many other drugs producing the same slow oscillations. But there are also a number that are "doing something totally different," he adds.
Funds from the Nationa Institutes of Health (NIH), the Canadian Research Foundation, and the National Institute of Neurological Disorders and Stroke, helped finance the study.
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