Tuesday, November 6, 2012

General anesthesia may disrupt communication between brain areas

Propofol
A new study suggests that anesthesia drugs such as propofol work by disrupting communication between brain areas.

Researchers have moved one step closer to understanding how anesthesia drugs work by identifying a component of brain activity that could explain why we lose consciousness under the influence of the drugs, according to a study published Monday in the Proceedings of the National Academy of Sciences.

Though "going under" is an extremely common part of many medical procedures, the mechanism by which it works remains a mystery. This fact has practical ramifications: Some studies have shown that anesthesia can lead to loss of memory and other side effects, something researchers might be able to alleviate if they understand exactly what the drugs do in the body.

One hypothesis for why the drugs cause us to zonk out is that they cause different parts of the brain to lose their "functional integration" -- their ability to work together as a coherent whole. The brain is often thought of as a series of relatively independent areas -- parts of the organ are often referred to as the "face area" or the "vision region." But in order for the whole thing to work correctly, many different areas must work together. If something about anesthesia made this impossible, that could explain why we lose consciousness.

To test whether this was the case, a group of scientists from Harvard University and Massachusetts General Hospital studied the electrical activity of three patients while they were under anesthesia. The three patients were all epileptics, and had been in the hospital to have their epilepsy monitored. As part of the monitoring, doctors implanted an array of electrodes on a part of each patient’s cerebral cortex, the outer shell of the brain. When it came time for doctors to perform the surgery to remove the electrodes, the patients were put under anesthesia.

But before the electrodes were removed, the research team was allowed to use the electrodes to record their brain activity as the patient lost consciousness from the anesthetic propofol. The electrodes allowed the team to record brain activity on multiple spatial scales at once, from recordings of the activity of individual brain cells to the collected electrical activity of thousands of neurons. To keep track of when they lost consciousness, the researchers asked the subjects to push a button in response to a spoken command every so often.
Strikingly, when the subjects lost consciousness, a new element of brain activity, called a “slow oscillation,” immediately arose. A brain oscillation, when visualized, is like a landscape made up of a series of rolling hills. At the peak of the hill, large groups of neurons are firing simultaneously; at the trough, very few are firing. These oscillations are a major feature of normal human brain activity, and they usually occur multiple times per second.

But as soon as the patients lost consciousness, they began to have slow oscillations that occurred less than once per second, something that is not seen during waking brain activity. What’s more, when the researchers looked at a particular type of brain activity called “spiking,” which is generally related to information processing, they found that it only occurred during particular parts of the slow oscillation. In short, spiking had become “locked” to the slow oscillation.

More important, when the researchers compared different parts of the brain, they found that the oscillations were occurring at slightly different times. This likely makes it impossible for the areas to work together even though each individual area appeared to function quite normally.

The results provide a potential explanation for why we lose consciousness when we receive an anesthetic: Propofol prevented different parts of the brain from working together as a unit. If this turns out to be the case and researchers can zone in on the exact mechanisms by which the drugs work, it may be possible to develop more targeted anesthetics with fewer side effects.

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