Scientists Improve Mood By Stimulating A Brain Area Above The Eyes

Nov 29, 2018
Originally published on November 30, 2018 3:23 pm

There's new evidence that mild pulses of electricity can relieve depression — if they reach the right target in the brain.

A study of 25 people with epilepsy found that those who had symptoms of depression felt better almost immediately when doctors electrically stimulated an area of the brain just above the eyes, a team reported Thursday in the journal Current Biology.

These people were in the hospital awaiting surgery and had wires inserted into their brains to help doctors locate the source of their seizures.

Several of the patients talked about the change they felt when the stimulation of the lateral orbitofrontal cortex began, says Kristin Sellers, an author of the paper and a postdoctoral researcher at the University of California, San Francisco. One person's response was: "Wow, I feel a lot better. ... What did you guys do?"

The stimulation only lasted a few minutes. After it stopped, the effect on mood quickly faded.

To be sure that the effect was real, the researchers also pretended to stimulate the lateral OFC in the same patients without actually running current through the tiny wires implanted in their brains. In those sham treatments, there was no discernible change.

The results add to the evidence that patients with depression can be helped with an approach known as deep brain stimulation.

DBS is an approved treatment for tremors, including those associated with Parkinson's disease. But results with depression have been less consistent, and DBS isn't approved for this purpose by the Food and Drug Administration.

The latest study represents "another piece in a very complicated puzzle, a very important piece," says Dr. Helen Mayberg, a pioneer in the use of DBS to treat depression.

The study also offers strong evidence that stimulating the OFC can temporarily improve the mood of a person who is feeling depressed, says Mayberg, who directs the Center for Advanced Circuit Therapeutics, which is part of the Mount Sinai Health System in New York.

But it's unclear whether the stimulation can produce long-lasting changes, she says. Also, the study couldn't answer a critical question because it only looked at people who were reporting transient symptoms of depression.

"What happens if you did this in people who actually have failed every kind of treatment for a major depressive episode and are chronically and intractably ill," Mayberg says.

Meanwhile, her own team has been able to help about 80 percent of those patients by stimulating a different area of the brain — one that happens to share many connections with the OFC.

The latest study offers "more evidence that [DBS] is something that is real and will work for depression," says Al Fenoy, an associate professor of neurosurgery at the University of Texas Health Science Center at Houston.

Fenoy is part of a team that has had success treating depression by stimulating yet another brain area that shares connections with the OFC. "We're all (working) along a very similar pathway," he says. "One of the common denominators might be this orbitofrontal area."

But it's also possible that different types of depression will require different targets, Fenoy says.

All of the research on brain stimulation reflects a move away from the long-held view that depression is caused by a chemical imbalance in the brain.

"A more sort of modern conception is thinking of depression as a circuit dysfunction, meaning that there's something about the way cells in the brain are talking to each other that is not quite right," says Dr. Vikram Rao, an author of the new study and an assistant professor of clinical neurology at UCSF.

So researchers have been trying to identify faulty circuits and make them work better using electrical pulses. The challenge has been to find areas that have a really good connection to the malfunctioning circuit

"The way that I like to think about it is we're trying to get onto a highway and there's a lot of different on-ramps," Sellers says.

The UCSF team took a novel approach to this task by studying patients with epilepsy who were awaiting surgery. That meant they already had wires inserted into their brains to help doctors locate the source of their seizures.

In a previous, related study, UCSF researchers had used a different group of epilepsy patients to identify circuits in the brain that indicated whether people were happy or sad. This time, they were able to use these wires to not only monitor various brain circuits involved in mood but also electrically stimulate some of those areas.

The researchers were able to use the technique in many different areas in the brain. And Sellers says they got an immediate response when they stimulated the OFC.

"What we found was that consistently, stimulation in the lateral OFC was improving mood in symptomatic patients," Sellers says. What's more, more powerful stimulation produced a more dramatic improvement in mood, she says. There were no issues with side effects, including mania, which has been seen in some previous experiments with brain stimulation.

That's probably because the OFC offers a really good on-ramp to brain networks involved in depression, Rao says. "It does seem to be a crossroads for connecting many different brain regions that had been implicated in regulating our mood."

And Rao says the results suggest that stimulation of this area is improving the function of a faulty circuit, rather than just making everyone happier.

"Only the people who had symptoms [of depression] to start with improved their mood, which suggests that perhaps the effect of what we're doing is to normalize activity that starts off abnormal," Rao says.

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AILSA CHANG, HOST:

Next, an update on using mild pulses of electricity to relieve the symptoms of depression. NPR's Jon Hamilton reports on a new study showing that these pulses can help if they reach the right brain circuit.

JON HAMILTON, BYLINE: Scientists used to think depression was caused by a chemical imbalance in the brain, but Dr. Vikram Rao of the University of California, San Francisco says that idea is outdated.

VIKRAM RAO: A more sort of modern conception is thinking of depression as a circuit dysfunction, meaning that there's something about the way cells in the brain are talking to each other that is not quite right.

HAMILTON: So researchers have been trying to identify those faulty circuits and make them work better. One approach is called deep brain stimulation which delivers pulses of electricity to a specific area in the brain. Kristin Sellers, a postdoctoral researcher who works with Rao, says the trick is to stimulate an area that has a really good connection to the malfunctioning circuit.

KRISTIN SELLERS: The way that I like to think about it is we're trying to get onto a highway, and there's a lot of different on-ramps.

HAMILTON: To find the right on-ramp, Sellers, Rao and a team of researchers studied 25 people with severe epilepsy. These people were in the hospital awaiting surgery and had wires inserted into their brains to help doctors locate the source of their seizures. Many of them also had symptoms associated with depression. The researchers used the implanted wires to stimulate different areas in the brain. And Sellers says they got an immediate response when they stimulated an area called the lateral orbitofrontal cortex or OFC.

SELLERS: What we found was that, consistently, stimulation in the lateral OFC was improving mood in symptomatic patients.

HAMILTON: And as researchers increased the stimulation, the effect on mood became more pronounced. Sellers says one woman in the study described the change as it happened.

SELLERS: She said something to the extent of, wow, I feel a lot better; what did you guys do?

HAMILTON: The OFC is located behind the forehead and above the eyes. And Seller's colleague Vikram Rao says it offers an ideal on-ramp to the brain networks involved in depression.

RAO: It does seem to be a crossroads for connecting many different brain regions that have been implicated in regulating our mood.

HAMILTON: Rao says stimulating this area seems to make circuits work better, if they are faulty to begin with.

RAO: Only the people who had symptoms to start with improved their mood, which suggests that perhaps the effect of what we're doing is to normalize activity that starts off abnormal as opposed to nonspecifically elevating mood.

HAMILTON: The new study, which appears in the journal Current Biology, is just the latest to suggest that deep brain stimulation can help relieve depression.

HELEN MAYBERG: This is another piece in a very complicated puzzle.

HAMILTON: Dr. Helen Mayberg helped pioneer the use of deep brain stimulation for depression more than a decade ago. Now she directs the Center for Advanced Circuit Therapeutics at the Mount Sinai Health System in New York. Mayberg says the new study offers strong evidence that stimulating the OFC can improve the mood of a person who is feeling depressed, but it doesn't show whether the effect is lasting. And she says it doesn't answer an important question.

MAYBERG: What happens if you did this in people who actually have failed every kind of treatment for a major depressive episode and are chronically and intractably ill?

HAMILTON: Mayberg says she's been able to help about 80 percent of these patients by stimulating a different area of the brain, one that happens to share many connections with the OFC. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.