Tuesday, 05 March 2013 08:44

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Mar. 4, 2013 — Since the mid-1800s, doctors have used drugs to induce general anesthesia in patients undergoing surgery. Despite their widespread use, little is known about how these drugs create such a profound loss of consciousness.

In a new study that tracked brain activity in human volunteers over a two-hour period as they lost and regained consciousness, researchers from MIT and Massachusetts General Hospital (MGH) have identified distinctive brain patterns associated with different stages of general anesthesia. The findings shed light on how one commonly used anesthesia drug exerts its effects, and could help doctors better monitor patients during surgery and prevent rare cases of patients waking up during operations.

Anesthesiologists now rely on a monitoring system that takes electroencephalogram (EEG) information and combines it into a single number between zero and 100. However, that index actually obscures the information that would be most useful, according to the authors of the new study, which appears in the Proceedings of the National Academy of Sciences the week of March 4.

"When anesthesiologists are taking care of someone in the operating room, they can use the information in this article to make sure that someone is unconscious, and they can have a specific idea of when the person may be regaining consciousness," says senior author Emery Brown, an MIT professor of brain and cognitive sciences and health sciences and technology and an anesthesiologist at MGH.

Lead author of the paper is Patrick Purdon, an instructor of anesthesia at MGH and Harvard Medical School.

Distinctive patterns

Last fall, Purdon, Brown and colleagues published a study of brain activity in epileptic patients as they went under anesthesia. Using electrodes that had been implanted in the patients' brains as part of their treatment for epilepsy, the researchers were able to identify a signature EEG pattern that emerged during anesthesia.

In the new study, the researchers studied healthy volunteers, measuring their brain activity with an array of 64 electrodes attached to the scalp. Not only did they find patterns that appeared to correspond to what they saw in last year's study, they were also able to discern much more detail, because they gave the dose of propofol over a longer period of time and followed subjects until they came out of anesthesia.

While the subjects received propofol, the researchers monitored their responsiveness to sounds. Every four seconds, the subjects heard either a mechanical tone or a word, such as their name. The researchers measured EEG activity throughout the process, as the subjects pressed a button to indicate whether they heard the sound.

As the subjects became less responsive, distinct brain patterns appeared. Early on, when the subjects were just beginning to lose consciousness, the researchers detected an oscillation of brain activity in the low frequency (0.1 to 1 hertz) and alpha frequency (8 to 12 hertz) bands, in the frontal cortex. They also found a specific relationship between the oscillations in those two frequency bands: Alpha oscillations peaked as the low-frequency waves were at their lowest point.

When the brain reached a slightly deeper level of anesthesia, a marked transition occurred: The alpha oscillations flipped so their highest points occurred when the low frequency waves were also peaking.

The researchers believe that these alpha and low-frequency oscillations, which they also detected in last year's study, produce unconsciousness by disrupting normal communication between different brain regions. The oscillations appear to constrain the amount of information that can pass between the frontal cortex and the thalamus, which normally communicate with each other across a very broad frequency band to relay sensory information and control attention.

The oscillations also prevent different parts of the cortex from coordinating with each other. In last year's study, the researchers found that during anesthesia, neurons within small, localized brain regions are active for a few hundred milliseconds, then shut off again for a few hundred milliseconds. This flickering of activity, which creates the slow oscillation pattern, prevents brain regions from communicating normally.

Better anesthesia monitoring

When the researchers began to slowly decrease the dose of propofol, to bring the subjects out of anesthesia, they saw a reversal of the brain activity patterns that appeared when the subjects lost consciousness. A few minutes before regaining consciousness, the alpha oscillations flipped so that they were at their peak when the low-frequency waves were at their lowest point.

"That is the signature that would allow someone to determine if a patient is coming out of anesthesia too early, with this drug," Purdon says.

Cases in which patients regain consciousness during surgery are alarming but very rare, with one or two occurrences in 10,000 operations, Brown says.

"It's not something that we're fighting with every day, but when it does happen, it creates this visceral fear, understandably, in the public. And anesthesiologists don't have a way of responding because we really don't know when you're unconscious," he says. "This is now a solved problem."

Purdon and Brown are now starting a training program for anesthesiologists and residents at MGH to train them to interpret the information necessary to measure depth of anesthesia. That information is available through the EEG monitors that are now used during most operations, Purdon says. Because propofol is the most widely used anesthesia drug, the new findings should prove valuable for most operations.

In follow-up studies, the researchers are now studying the brain activity patterns produced by other anesthesia drugs.

The research was funded by the National Institutes of Health, including an NIH Director's Pioneer Award, New Innovator Award and K-Award, and the Harvard Clinical and Translational Science Center.

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Wednesday, 27 February 2013 08:09

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Feb. 26, 2013 — During sleep, our brains store what we have learned during the day ‒ a process even more effective in children than in adults, new research shows.

It is important for children to get enough sleep. Children's brains transform subconsciously learned material into active knowledge while they sleep -- even more effectively than adult brains do, according to a study by Dr. Ines Wilhelm of the University of Tübingen's Institute for Medical Psychology and Behavioral Neurobiology. Dr Wilhelm and her Swiss and German colleagues have published their results in Nature Neuroscience.

Studies of adults have shown that sleeping after learning supports the long-term storage of the material learned, says Dr Wilhelm. During sleep, memory is turned into a form that makes future learning easier; implicit knowledge becomes explicit and therefore becomes more easily transferred to other areas.

Children sleep longer and deeper, and they must take on enormous amounts of information every day. In the current study, the researchers examined the ability to form explicit knowledge via an implicitly-learned motor task. Children between 8 and 11, and young adults, learned to guess the predetermined series of actions -- without being aware of the existence of the series itself. Following a night of sleep or a day awake, the subjects' memories were tested. The result: after a night's sleep, both age groups could remember a larger number of elements from the row of numbers than those who had remained awake in the interim. And the children were much better at it than the adults.

"In children, much more efficient explicit knowledge is generated during sleep from a previously learned implicit task, says Wilhelm. And the children's extraordinary ability is linked with the large amount of deep sleep they get at night. "The formation of explicit knowledge appears to be a very specific ability of childhood sleep, since children typically benefit as much or less than adults from sleep when it comes to other types of memory tasks."

The above story is reprinted from materials provided by Universitaet Tübingen.

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