Andres Lozano: Parkinson’s, Depression and the Switch That Might Turn Them Off (Transcript)

Man: That’s a little better.

Woman: That side is better.

We’re now going to turn it on.

It’s on. Just turned it on. And this works like that, instantly.

And the difference between shaking in this way and not —

The difference between shaking in this way and not is related to the misbehavior of 25,000 neurons in her subthalamic nucleus. So we now know how to find these troublemakers and tell them, “Gentlemen, that’s enough. We want you to stop doing that.” And we do that with electricity.

So we use electricity to dictate how they fire, and we try to block their misbehavior using electricity. So in this case, we are suppressing the activity of abnormal neurons. We started using this technique in other problems, and I’m going to tell you about a fascinating problem that we encountered, a case of dystonia.

So dystonia is a disorder affecting children. It’s a genetic disorder, and it involves a twisting motion, and these children get progressively more and more twisting until they can’t breathe, until they get sores, urinary infections, and then they die.

So back in 1997, I was asked to see this young boy, perfectly normal. He has this genetic form of dystonia. There are eight children in the family. Five of them have dystonia. So here he is.

This boy is nine years old, perfectly normal until the age six, and then he started twisting his body, first the right foot, then the left foot, then the right arm, then the left arm, then the trunk, and then by the time he arrived, within the course of one or two years of the disease onset, he could no longer walk, he could no longer stand. He was crippled, and indeed the natural progression as this gets worse is for them to become progressively twisted, progressively disabled, and many of these children do not survive.

So he is one of five kids. The only way he could get around was crawling on his belly like this. He did not respond to any drugs. We did not know what to do with this boy. We did not know what operation to do, where to go in the brain, but on the basis of our results in Parkinson’s disease, we reasoned, why don’t we try to suppress the same area in the brain that we suppressed in Parkinson’s disease, and let’s see what happens?

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So here he was. We operated on him hoping that he would get better. We did not know.

So here he is now, back in Israel where he lives, three months after the procedure, and here he is.

On the basis of this result, this is now a procedure that’s done throughout the world, and there have been hundreds of children that have been helped with this kind of surgery. This boy is now in university and leads quite a normal life. This has been one of the most satisfying cases that I have ever done in my entire career, to restore movement and walking to this kind of child.

We realized that perhaps we could use this technology not only in circuits that control your movement but also circuits that control other things, and the next thing that we took on was circuits that control your mood. And we decided to take on depression, and the reason we took on depression is because it’s so prevalent. And as you know, there are many treatments for depression, with medication and psychotherapy, even electroconvulsive therapy, but there are millions of people, and there are still 10% or 20% of patients with depression that do not respond, and it is these patients that we want to help.

And let’s see if we can use this technique to help these patients with depression. So the first thing we did was, we compared, what’s different in the brain of someone with depression and someone who is normal, and what we did was PET scans to look at the blood flow of the brain, and what we noticed is that in patients with depression compared to normals, areas of the brain are shut down, and those are the areas in blue.

So here you really have the blues, and the areas in blue are areas that are involved in motivation, in drive and decision-making, and indeed, if you’re severely depressed as these patients were, those are impaired. You lack motivation and drive.

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The other thing we discovered was an area that was overactive, area 25, seen there in red, and area 25 is the sadness center of the brain. If I make any of you sad, for example, I make you remember the last time you saw your parent before they died or a friend before they died, this area of the brain lights up. It is the sadness center of the brain.

And so patients with depression have hyperactivity. The area of the brain for sadness is on red hot. The thermostat is set at 100 degrees, and the other areas of the brain, involved in drive and motivation, are shut down.

So we wondered, can we place electrodes in this area of sadness and see if we can turn down the thermostat, can we turn down the activity, and what will be the consequence of that?

So we went ahead and implanted electrodes in patients with depression. This is work done with my colleague Helen Mayberg from Emory. And we placed electrodes in area 25, and in the top scan you see before the operation, area 25, the sadness area is red hot, and the frontal lobes are shut down in blue, and then, after three months of continuous stimulation, 24 hours a day, or six months of continuous stimulation, we have a complete reversal of this.

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