Parkinson's, depression and the switch that might turn them off
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0:00 - 0:03One of the things I want to establish right from the start
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0:03 - 0:06is that not all neurosurgeons wear cowboy boots.
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0:06 - 0:08I just wanted you to know that.
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0:08 - 0:10So I am indeed a neurosurgeon,
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0:10 - 0:14and I follow a long tradition of neurosurgery,
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0:14 - 0:16and what I'm going to tell you about today
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0:16 - 0:18is adjusting the dials in the circuits in the brain,
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0:18 - 0:20being able to go anywhere in the brain
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0:20 - 0:23and turning areas of the brain up or down
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0:23 - 0:25to help our patients.
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0:25 - 0:28So as I said, neurosurgery comes from a long tradition.
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0:28 - 0:31It's been around for about 7,000 years.
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0:31 - 0:35In Mesoamerica, there used to be neurosurgery,
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0:35 - 0:39and there were these neurosurgeons that used to treat patients.
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0:39 - 0:43And they were trying to -- they knew that the brain was involved
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0:43 - 0:45in neurological and psychiatric disease.
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0:45 - 0:47They didn't know exactly what they were doing.
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0:47 - 0:50Not much has changed, by the way. (Laughter)
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0:50 - 0:52But they thought that,
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0:52 - 0:54if you had a neurologic or psychiatric disease,
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0:54 - 0:56it must be because you are possessed
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0:56 - 0:59by an evil spirit.
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0:59 - 1:01So if you are possessed by an evil spirit
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1:01 - 1:04causing neurologic or psychiatric problems,
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1:04 - 1:06then the way to treat this is, of course,
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1:06 - 1:11to make a hole in your skull and let the evil spirit escape.
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1:11 - 1:13So this was the thinking back then,
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1:13 - 1:17and these individuals made these holes.
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1:17 - 1:20Sometimes the patients were a little bit reluctant
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1:20 - 1:22to go through this because, you can tell that
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1:22 - 1:25the holes are made partially and then, I think,
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1:25 - 1:27there was some trepanation, and then they left very quickly
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1:27 - 1:29and it was only a partial hole,
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1:29 - 1:31and we know they survived these procedures.
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1:31 - 1:32But this was common.
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1:32 - 1:33There were some sites where one percent
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1:33 - 1:36of all the skulls have these holes, and so you can see
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1:36 - 1:39that neurologic and psychiatric disease is quite common,
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1:39 - 1:44and it was also quite common about 7,000 years ago.
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1:44 - 1:46Now, in the course of time,
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1:46 - 1:48we've come to realize that
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1:48 - 1:50different parts of the brain do different things.
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1:50 - 1:52So there are areas of the brain that are dedicated
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1:52 - 1:54to controlling your movement or your vision
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1:54 - 1:57or your memory or your appetite, and so on.
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1:57 - 2:00And when things work well, then the nervous system
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2:00 - 2:02works well, and everything functions.
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2:02 - 2:04But once in a while, things don't go so well,
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2:04 - 2:06and there's trouble in these circuits,
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2:06 - 2:09and there are some rogue neurons that are misfiring
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2:09 - 2:12and causing trouble, or sometimes they're underactive
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2:12 - 2:15and they're not quite working as they should.
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2:15 - 2:17Now, the manifestation of this
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2:17 - 2:19depends on where in the brain these neurons are.
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2:19 - 2:22So when these neurons are in the motor circuit,
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2:22 - 2:24you get dysfunction in the movement system,
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2:24 - 2:26and you get things like Parkinson's disease.
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2:26 - 2:30When the malfunction is in a circuit that regulates your mood,
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2:30 - 2:32you get things like depression,
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2:32 - 2:36and when it is in a circuit that controls your memory and cognitive function,
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2:36 - 2:38then you get things like Alzheimer's disease.
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2:38 - 2:41So what we've been able to do is to pinpoint
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2:41 - 2:43where these disturbances are in the brain,
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2:43 - 2:46and we've been able to intervene within these circuits
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2:46 - 2:50in the brain to either turn them up or turn them down.
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2:50 - 2:52So this is very much like choosing the correct station
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2:52 - 2:54on the radio dial.
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2:54 - 2:57Once you choose the right station, whether it be jazz or opera,
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2:57 - 2:59in our case whether it be movement or mood,
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2:59 - 3:01we can put the dial there,
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3:01 - 3:04and then we can use a second button to adjust the volume,
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3:04 - 3:06to turn it up or turn it down.
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3:06 - 3:07So what I'm going to tell you about
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3:07 - 3:11is using the circuitry of the brain to implant electrodes
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3:11 - 3:14and turning areas of the brain up and down
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3:14 - 3:16to see if we can help our patients.
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3:16 - 3:18And this is accomplished using this kind of device,
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3:18 - 3:20and this is called deep brain stimulation.
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3:20 - 3:23So what we're doing is placing these electrodes throughout the brain.
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3:23 - 3:27Again, we are making holes in the skull about the size of a dime,
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3:27 - 3:30putting an electrode in, and then this electrode
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3:30 - 3:32is completely underneath the skin
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3:32 - 3:34down to a pacemaker in the chest,
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3:34 - 3:38and with a remote control very much like a television remote control,
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3:38 - 3:41we can adjust how much electricity we deliver
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3:41 - 3:43to these areas of the brain.
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3:43 - 3:46We can turn it up or down, on or off.
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3:46 - 3:49Now, about a hundred thousand patients in the world
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3:49 - 3:51have received deep brain stimulation,
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3:51 - 3:52and I'm going to show you some examples
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3:52 - 3:55of using deep brain stimulation to treat disorders of movement,
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3:55 - 3:59disorders of mood and disorders of cognition.
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3:59 - 4:02So this looks something like this when it's in the brain.
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4:02 - 4:04You see the electrode going through the skull into the brain
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4:04 - 4:07and resting there, and we can place this really anywhere in the brain.
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4:07 - 4:10I tell my friends that no neuron is safe
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4:10 - 4:12from a neurosurgeon, because we can really reach
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4:12 - 4:15just about anywhere in the brain quite safely now.
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4:15 - 4:17Now the first example I'm going to show you is a patient
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4:17 - 4:19with Parkinson's disease,
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4:19 - 4:21and this lady has Parkinson's disease,
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4:21 - 4:23and she has these electrodes in her brain,
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4:23 - 4:24and I'm going to show you what she's like
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4:24 - 4:28when the electrodes are turned off and she has her Parkinson's symptoms,
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4:28 - 4:30and then we're going to turn it on.
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4:30 - 4:33So this looks something like this.
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4:33 - 4:37The electrodes are turned off now, and you can see that she has tremor.
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4:37 - 4:41(Video) Man: Okay. Woman: I can't. Man: Can you try to touch my finger?
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4:41 - 4:45(Video) Man: That's a little better. Woman: That side is better.
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4:45 - 4:49We're now going to turn it on.
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4:49 - 4:53It's on. Just turned it on.
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4:55 - 4:58And this works like that, instantly.
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4:58 - 5:01And the difference between shaking in this way and not --
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5:01 - 5:05(Applause)
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5:05 - 5:10The difference between shaking in this way and not is related to the misbehavior
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5:10 - 5:13of 25,000 neurons in her subthalamic nucleus.
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5:13 - 5:16So we now know how to find these troublemakers
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5:16 - 5:17and tell them, "Gentlemen, that's enough.
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5:17 - 5:19We want you to stop doing that."
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5:19 - 5:20And we do that with electricity.
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5:20 - 5:23So we use electricity to dictate how they fire,
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5:23 - 5:27and we try to block their misbehavior using electricity.
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5:27 - 5:30So in this case, we are suppressing the activity of abnormal neurons.
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5:30 - 5:33We started using this technique in other problems,
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5:33 - 5:34and I'm going to tell you about a fascinating problem
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5:34 - 5:37that we encountered, a case of dystonia.
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5:37 - 5:40So dystonia is a disorder affecting children.
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5:40 - 5:43It's a genetic disorder, and it involves a twisting motion,
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5:43 - 5:46and these children get progressively more and more twisting
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5:46 - 5:48until they can't breathe, until they get sores,
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5:48 - 5:50urinary infections, and then they die.
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5:50 - 5:53So back in 1997, I was asked to see this young boy,
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5:53 - 5:56perfectly normal. He has this genetic form of dystonia.
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5:56 - 5:58There are eight children in the family.
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5:58 - 6:02Five of them have dystonia.
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6:02 - 6:04So here he is.
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6:04 - 6:08This boy is nine years old, perfectly normal until the age six,
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6:08 - 6:13and then he started twisting his body, first the right foot,
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6:13 - 6:16then the left foot, then the right arm, then the left arm,
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6:16 - 6:19then the trunk, and then by the time he arrived,
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6:19 - 6:22within the course of one or two years of the disease onset,
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6:22 - 6:24he could no longer walk, he could no longer stand.
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6:24 - 6:27He was crippled, and indeed the natural progression
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6:27 - 6:31as this gets worse is for them to become progressively twisted,
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6:31 - 6:36progressively disabled, and many of these children do not survive.
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6:36 - 6:38So he is one of five kids.
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6:38 - 6:43The only way he could get around was crawling on his belly like this.
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6:43 - 6:44He did not respond to any drugs.
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6:44 - 6:46We did not know what to do with this boy.
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6:46 - 6:49We did not know what operation to do,
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6:49 - 6:51where to go in the brain,
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6:51 - 6:54but on the basis of our results in Parkinson's disease,
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6:54 - 6:56we reasoned, why don't we try to suppress
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6:56 - 6:59the same area in the brain that we suppressed
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6:59 - 7:02in Parkinson's disease, and let's see what happens?
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7:02 - 7:04So here he was. We operated on him
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7:04 - 7:08hoping that he would get better. We did not know.
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7:08 - 7:12So here he is now, back in Israel where he lives,
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7:12 - 7:16three months after the procedure, and here he is.
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7:16 - 7:21(Applause)
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7:25 - 7:27On the basis of this result, this is now a procedure
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7:27 - 7:29that's done throughout the world,
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7:29 - 7:30and there have been hundreds of children
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7:30 - 7:34that have been helped with this kind of surgery.
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7:34 - 7:36This boy is now in university
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7:36 - 7:38and leads quite a normal life.
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7:38 - 7:41This has been one of the most satisfying cases
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7:41 - 7:43that I have ever done in my entire career,
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7:43 - 7:46to restore movement and walking to this kind of child.
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7:46 - 7:52(Applause)
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7:52 - 7:55We realized that perhaps we could use this technology
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7:55 - 7:57not only in circuits that control your movement
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7:57 - 7:59but also circuits that control other things,
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7:59 - 8:00and the next thing that we took on
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8:00 - 8:03was circuits that control your mood.
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8:03 - 8:05And we decided to take on depression,
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8:05 - 8:08and the reason we took on depression is because it's so prevalent,
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8:08 - 8:10and as you know, there are many treatments for depression,
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8:10 - 8:12with medication and psychotherapy,
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8:12 - 8:14even electroconvulsive therapy,
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8:14 - 8:16but there are millions of people,
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8:16 - 8:18and there are still 10 or 20 percent of patients with depression
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8:18 - 8:22that do not respond, and it is these patients that we want to help.
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8:22 - 8:24And let's see if we can use this technique
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8:24 - 8:26to help these patients with depression.
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8:26 - 8:28So the first thing we did was, we compared,
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8:28 - 8:30what's different in the brain of someone with depression
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8:30 - 8:31and someone who is normal,
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8:31 - 8:35and what we did was PET scans to look at the blood flow of the brain,
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8:35 - 8:37and what we noticed is that in patients with depression
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8:37 - 8:39compared to normals,
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8:39 - 8:41areas of the brain are shut down,
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8:41 - 8:42and those are the areas in blue.
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8:42 - 8:44So here you really have the blues,
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8:44 - 8:47and the areas in blue are areas that are involved
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8:47 - 8:50in motivation, in drive and decision-making,
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8:50 - 8:52and indeed, if you're severely depressed as these patients were,
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8:52 - 8:55those are impaired. You lack motivation and drive.
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8:55 - 8:57The other thing we discovered
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8:57 - 8:59was an area that was overactive, area 25,
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8:59 - 9:01seen there in red,
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9:01 - 9:04and area 25 is the sadness center of the brain.
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9:04 - 9:07If I make any of you sad, for example, I make you remember
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9:07 - 9:09the last time you saw your parent before they died
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9:09 - 9:10or a friend before they died,
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9:10 - 9:12this area of the brain lights up.
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9:12 - 9:13It is the sadness center of the brain.
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9:13 - 9:17And so patients with depression have hyperactivity.
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9:17 - 9:19The area of the brain for sadness is on red hot.
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9:19 - 9:21The thermostat is set at 100 degrees,
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9:21 - 9:25and the other areas of the brain, involved in drive and motivation, are shut down.
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9:25 - 9:28So we wondered, can we place electrodes in this area of sadness
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9:28 - 9:30and see if we can turn down the thermostat,
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9:30 - 9:32can we turn down the activity,
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9:32 - 9:34and what will be the consequence of that?
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9:34 - 9:37So we went ahead and implanted electrodes in patients with depression.
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9:37 - 9:39This is work done with my colleague Helen Mayberg from Emory.
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9:39 - 9:41And we placed electrodes in area 25,
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9:41 - 9:44and in the top scan you see before the operation,
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9:44 - 9:46area 25, the sadness area is red hot,
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9:46 - 9:48and the frontal lobes are shut down in blue,
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9:48 - 9:51and then, after three months of continuous stimulation,
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9:51 - 9:5424 hours a day, or six months of continuous stimulation,
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9:54 - 9:55we have a complete reversal of this.
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9:55 - 9:58We're able to drive down area 25,
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9:58 - 10:00down to a more normal level,
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10:00 - 10:02and we're able to turn back online
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10:02 - 10:04the frontal lobes of the brain,
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10:04 - 10:06and indeed we're seeing very striking results
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10:06 - 10:08in these patients with severe depression.
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10:08 - 10:11So now we are in clinical trials, and are in Phase III clinical trials,
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10:11 - 10:14and this may become a new procedure,
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10:14 - 10:16if it's safe and we find that it's effective,
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10:16 - 10:20to treat patients with severe depression.
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10:20 - 10:23I've shown you that we can use deep brain stimulation
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10:23 - 10:25to treat the motor system
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10:25 - 10:27in cases of Parkinson's disease and dystonia.
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10:27 - 10:29I've shown you that we can use it to treat a mood circuit
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10:29 - 10:31in cases of depression.
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10:31 - 10:36Can we use deep brain stimulation to make you smarter?
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10:36 - 10:38(Laughter)
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10:38 - 10:40Anybody interested in that?
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10:40 - 10:43(Applause)
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10:43 - 10:46Of course we can, right?
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10:46 - 10:48So what we've decided to do is
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10:48 - 10:50we're going to try to turbocharge
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10:50 - 10:52the memory circuits in the brain.
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10:52 - 10:55We're going to place electrodes within the circuits
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10:55 - 10:58that regulate your memory and cognitive function
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10:58 - 11:01to see if we can turn up their activity.
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11:01 - 11:03Now we're not going to do this in normal people.
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11:03 - 11:07We're going to do this in people that have cognitive deficits,
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11:07 - 11:10and we've chosen to treat patients with Alzheimer's disease
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11:10 - 11:12who have cognitive and memory deficits.
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11:12 - 11:14As you know, this is the main symptom
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11:14 - 11:17of early onset Alzheimer's disease.
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11:17 - 11:19So we've placed electrodes within this circuit
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11:19 - 11:21in an area of the brain called the fornix,
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11:21 - 11:24which is the highway in and out of this memory circuit,
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11:24 - 11:27with the idea to see if we can turn on this memory circuit,
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11:27 - 11:30and whether that can, in turn, help these patients
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11:30 - 11:33with Alzheimer's disease.
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11:33 - 11:35Now it turns out that in Alzheimer's disease,
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11:35 - 11:39there's a huge deficit in glucose utilization in the brain.
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11:39 - 11:42The brain is a bit of a hog when it comes to using glucose.
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11:42 - 11:44It uses 20 percent of all your --
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11:44 - 11:46even though it only weighs two percent --
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11:46 - 11:49it uses 10 times more glucose than it should based on its weight.
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11:49 - 11:51Twenty percent of all the glucose in your body is used by the brain,
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11:51 - 11:54and as you go from being normal
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11:54 - 11:56to having mild cognitive impairment,
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11:56 - 11:58which is a precursor for Alzheimer's, all the way to Alzheimer's disease,
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11:58 - 12:01then there are areas of the brain that stop using glucose.
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12:01 - 12:03They shut down. They turn off.
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12:03 - 12:06And indeed, what we see is that these areas in red
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12:06 - 12:08around the outside ribbon of the brain
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12:08 - 12:10are progressively getting more and more blue
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12:10 - 12:13until they shut down completely.
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12:13 - 12:15This is analogous to having a power failure
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12:15 - 12:18in an area of the brain, a regional power failure.
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12:18 - 12:20So the lights are out in parts of the brain
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12:20 - 12:23in patients with Alzheimer's disease,
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12:23 - 12:25and the question is, are the lights out forever,
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12:25 - 12:28or can we turn the lights back on?
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12:28 - 12:31Can we get those areas of the brain to use glucose once again?
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12:31 - 12:34So this is what we did. We implanted electrodes in the fornix
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12:34 - 12:37of patients with Alzheimer's disease, we turned it on,
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12:37 - 12:40and we looked at what happens to glucose use in the brain.
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12:40 - 12:43And indeed, at the top, you'll see before the surgery,
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12:43 - 12:47the areas in blue are the areas that use less glucose than normal,
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12:47 - 12:49predominantly the parietal and temporal lobes.
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12:49 - 12:51These areas of the brain are shut down.
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12:51 - 12:53The lights are out in these areas of the brain.
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12:53 - 12:56We then put in the DBS electrodes and we wait for a month
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12:56 - 12:58or a year, and the areas in red
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12:58 - 13:01represent the areas where we increase glucose utilization.
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13:01 - 13:03And indeed, we are able to get these areas of the brain
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13:03 - 13:07that were not using glucose to use glucose once again.
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13:07 - 13:09So the message here is that, in Alzheimer's disease,
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13:09 - 13:11the lights are out, but there is someone home,
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13:11 - 13:13and we're able to turn the power back on
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13:13 - 13:16to these areas of the brain, and as we do so,
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13:16 - 13:19we expect that their functions will return.
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13:19 - 13:21So this is now in clinical trials.
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13:21 - 13:23We are going to operate on 50 patients
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13:23 - 13:25with early Alzheimer's disease
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13:25 - 13:27to see whether this is safe and effective,
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13:27 - 13:30whether we can improve their neurologic function.
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13:30 - 13:37(Applause)
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13:37 - 13:40So the message I want to leave you with today is that,
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13:40 - 13:43indeed, there are several circuits in the brain
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13:43 - 13:47that are malfunctioning across various disease states,
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13:47 - 13:49whether we're talking about Parkinson's disease,
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13:49 - 13:52depression, schizophrenia, Alzheimer's.
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13:52 - 13:55We are now learning to understand what are the circuits,
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13:55 - 13:57what are the areas of the brain that are responsible for
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13:57 - 14:00the clinical signs and the symptoms of those diseases.
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14:00 - 14:02We can now reach those circuits.
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14:02 - 14:05We can introduce electrodes within those circuits.
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14:05 - 14:08We can graduate the activity of those circuits.
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14:08 - 14:11We can turn them down if they are overactive,
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14:11 - 14:14if they're causing trouble, trouble that is felt throughout the brain,
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14:14 - 14:16or we can turn them up if they are underperforming,
-
14:16 - 14:19and in so doing, we think that we may be able to help
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14:19 - 14:21the overall function of the brain.
-
14:21 - 14:24The implications of this, of course, is that we may be able
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14:24 - 14:26to modify the symptoms of the disease,
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14:26 - 14:28but I haven't told you but there's also some evidence
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14:28 - 14:32that we might be able to help the repair of damaged areas of the brain using electricity,
-
14:32 - 14:34and this is something for the future, to see if, indeed,
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14:34 - 14:37we not only change the activity but also
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14:37 - 14:39some of the reparative functions of the brain
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14:39 - 14:40can be harvested.
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14:40 - 14:43So I envision that we're going to see a great expansion
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14:43 - 14:46of indications of this technique.
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14:46 - 14:49We're going to see electrodes being placed for many disorders of the brain.
-
14:49 - 14:52One of the most exciting things about this is that, indeed,
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14:52 - 14:53it involves multidisciplinary work.
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14:53 - 14:56It involves the work of engineers, of imaging scientists,
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14:56 - 14:58of basic scientists, of neurologists,
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14:58 - 15:01psychiatrists, neurosurgeons, and certainly at the interface
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15:01 - 15:04of these multiple disciplines that there's the excitement.
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15:04 - 15:07And I think that we will see that
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15:07 - 15:10we will be able to chase more of these evil spirits
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15:10 - 15:12out from the brain as time goes on,
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15:12 - 15:14and the consequence of that, of course, will be
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15:14 - 15:16that we will be able to help many more patients.
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15:16 - 15:18Thank you very much.
- Title:
- Parkinson's, depression and the switch that might turn them off
- Speaker:
- Andres Lozano
- Description:
-
Deep brain stimulation is becoming very precise. This technique allows surgeons to place electrodes in almost any area of the brain, and turn them up or down -- like a radio dial or thermostat -- to correct dysfunction. A dramatic look at emerging techniques, in which a woman with Parkinson's instantly stops shaking and brain areas eroded by Alzheimer's are brought back to life. (Filmed at TEDxCaltech.)
- Video Language:
- English
- Team:
- closed TED
- Project:
- TEDTalks
- Duration:
- 15:34
Thu-Huong Ha edited English subtitles for Parkinson's, depression and the switch that might turn them off | ||
Thu-Huong Ha approved English subtitles for Parkinson's, depression and the switch that might turn them off | ||
Thu-Huong Ha edited English subtitles for Parkinson's, depression and the switch that might turn them off | ||
Morton Bast accepted English subtitles for Parkinson's, depression and the switch that might turn them off | ||
Morton Bast edited English subtitles for Parkinson's, depression and the switch that might turn them off | ||
Joseph Geni edited English subtitles for Parkinson's, depression and the switch that might turn them off | ||
Joseph Geni edited English subtitles for Parkinson's, depression and the switch that might turn them off | ||
Joseph Geni added a translation |