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Scientists discover how drugs like ketamine induce an altered mental state: strokes



Scientists used light to control the activation of specific cells to artificially create a rhythm in the brain, which acted like the shocking drug Ketamine.

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enjoy it / Getty Images

Scientists used light to control the activation of specific cells to artificially create a rhythm in the brain, which acted like the shocking drug Ketamine.

enjoy it / Getty Images

Out-of-body experiences are all about rhythm, a team reported in their diary Wednesday Nature.

In mice and one person, scientists were able to reproduce the altered state often associated with ketamine by causing certain brain cells to fire together slowly and rhythmically.

“There was a rhythm that appeared and it was an oscillation that appeared only when the patient was dissociating,” says Dr. Karl Deisseroth, a psychiatrist and neuroscientist at Stanford University.

Dissociation is a brain state in which a person feels separated from their thoughts, feelings and body. It is common in people with some mental illness or who have experienced a traumatic event. It can also be induced by certain medications, including ketamine and PCP (angel dust).

The study linking dissociation to brain rhythms represents “a great leap forward in understanding how these drugs produce this unique state,” says Dr. Ken Solt, an anesthetist at Harvard Medical School and Massachusetts General Hospital. Solt is the co-author of an article that accompanied the study, but was not involved in the research.

The discovery could also be a step towards finding non-pharmacological methods to control states of consciousness, Solt says.

Deisseroth’s lab made the discovery while studying the brains of mice that had been given ketamine or other drugs that caused dissociation. The team used technology that allowed them to monitor cell activity throughout the brain

“It was like pointing a telescope at a new part of the sky,” Deisseroth says. “And something really unexpected jumped at us.”

What emerged was a very distinct rhythm produced by cells in an area involved in learning and navigation. Those cells were firing three times per second.

To find out more, the team used a tool called optogenetics, which Deisseroth helped invent. It uses light to control the activation of specific cells in the brain.

As a result, the team was able to artificially generate this rhythm in the brains of the mice.

The mice then behaved as if they had received ketamine. And once the slow pace started, the scientists could see that the areas of the brain that had previously worked together were now out of sync.

We could see, right before our eyes, the dissociation taking place, “says Deisseroth.

But that was in the mice. Deisseroth wanted to know about people.

And he got the chance, thanks to some luck and sandwiches. The sandwiches, provided by Deisseroth, were part of a regular but informal gathering of scientists in his laboratory.

“One day they were talking about their work and one of the neurosurgeons said, ‘Hey, you know, we have a patient,'” Deisseroth says.

The patient had a form of epilepsy which sometimes caused dissociation. And as part of the treatment, the doctors had temporarily implanted electrodes in the patient’s brain.

This gave Deisseroth’s team a way to monitor brain cells in the same area they had studied in mice. And once again, they found something important.

“There was a rhythm that appeared and appeared only when the patient was dissociating,” says Deisseroth.

To confirm their finding, the team sent pulses of electricity to areas where they had seen the pace. The patient immediately reported having an out-of-body experience.

Research appears to explain how mammalian brains are able to temporarily decouple mind and body, although it is not yet clear why they have this ability.

The research could also lead to ways to control dissociation without using drugs. This could eventually help a wide range of patients, Solt says.

“In the operating room we would like to have a drug like ketamine that produces only the pain relieving properties without having these other psychological manifestations,” he says.

Preventing dissociation could also help patients who have certain mental illnesses or who are recovering from a traumatic experience.

But dissociation can be helpful, Solt says.

For example, ketamine appears to help people with severe depression in part because it temporarily decouples certain areas of the brain.

“There appears to be this link between dissociation and the antidepressant effect of ketamine,” he says, noting that doses too low to produce even a mildly altered state appear to offer less benefit to people with depression.


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