Andres Lozano: Parkinson's, depression and the switch that might turn them off

Translator: Joseph Geni Reviewer: Morton Bast

譯者: Hao-Wei Chang 審譯者: Allen Li

One of the things I want to establish right from the start

演講前我想先澄清一下

is that not all neurosurgeons wear cowboy boots.

不是每位神經外科醫師都穿牛仔靴 (譯注：指已故名醫 Fred Epstein)

I just wanted you to know that.

我只是想讓你們知道這點

So I am indeed a neurosurgeon,

我確實是個神經外科醫師

and I follow a long tradition of neurosurgery,

追隨著神經外科手術的悠久傳統

and what I'm going to tell you about today

今天我要和各位分享

is adjusting the dials in the circuits in the brain,

如何調整大腦迴路中的旋鈕

being able to go anywhere in the brain

我們可以深入大腦的每個角落

and turning areas of the brain up or down

把該區域的訊號調高或調低

to help our patients.

以改善病況

So as I said, neurosurgery comes from a long tradition.

就像我說的 神經外科手術歷史悠久

It's been around for about 7,000 years.

7 千年前就已存在

In Mesoamerica, there used to be neurosurgery,

中美洲曾施行神經外科手術

and there were these neurosurgeons that used to treat patients.

這圖就是當時為病人動手術的情況

And they were trying to -- they knew that the brain was involved

他們嘗試這麼做—

in neurological and psychiatric disease.

因為知道腦和神經或精神疾病有關

They didn't know exactly what they were doing.

他們不太確定自己在做什麼

Not much has changed, by the way. (Laughter)

我們現在也差不多　（笑聲）

But they thought that,

但他們認為

if you had a neurologic or psychiatric disease,

如果你有神經或精神疾病

it must be because you are possessed

你一定是被

by an evil spirit.

惡靈附身

So if you are possessed by an evil spirit

附在你身上的惡靈

causing neurologic or psychiatric problems,

造成了神經或精神疾病

then the way to treat this is, of course,

治療方式當然就是

to make a hole in your skull and let the evil spirit escape.

在腦袋上打洞以釋放惡靈

So this was the thinking back then,

這是當時的思維

and these individuals made these holes.

這些人打了這些洞

Sometimes the patients were a little bit reluctant

有時病人不太願意接受手術

to go through this because, you can tell that

你們可以從

the holes are made partially and then, I think,

不完整的切口看出

there was some trepanation, and then they left very quickly

有些使用了環鋸術，但草草結束

and it was only a partial hole,

留下不完整的洞口

and we know they survived these procedures.

我們知道，手術後病人活了下來

But this was common.

這種手術在當時非常普遍

There were some sites where one percent

有些地區

of all the skulls have these holes, and so you can see

約 1% 的人頭骨上有這種洞

that neurologic and psychiatric disease is quite common,

可見當時神經和精神疾病很普遍

and it was also quite common about 7,000 years ago.

7000 年前就已如此

Now, in the course of time,

順著時間推移

we've come to realize that

我們逐漸瞭解

different parts of the brain do different things.

大腦的不同區域，有不同的功能

So there are areas of the brain that are dedicated

有特定區域負責

to controlling your movement or your vision

控制行動、視覺、

or your memory or your appetite, and so on.

以及記憶、胃口等

And when things work well, then the nervous system

如果一切正常，神經系統

works well, and everything functions.

就正常，每個功能也就正常

But once in a while, things don't go so well,

但偶爾會有問題

and there's trouble in these circuits,

迴路出現故障

and there are some rogue neurons that are misfiring

有些問題神經細胞沒訊號

and causing trouble, or sometimes they're underactive

會造成麻煩，有時則是訊號太弱

and they're not quite working as they should.

表現不如預期

Now, the manifestation of this

至於會造成什麼影響

depends on where in the brain these neurons are.

則和腦神經細胞所在位置有關

So when these neurons are in the motor circuit,

如果這些神經細胞在運動迴路

you get dysfunction in the movement system,

運動系統會無法正常運作

and you get things like Parkinson's disease.

因此會得到帕金森氏症之類的疾病

When the malfunction is in a circuit that regulates your mood,

當負責情緒的迴路出現問題時

you get things like depression,

會得到憂鬱症之類的疾病

and when it is in a circuit that controls your memory and cognitive function,

當控制記憶與認知的迴路故障時

then you get things like Alzheimer's disease.

會得到阿茲海默症之類疾病

So what we've been able to do is to pinpoint

我們能準確定位

where these disturbances are in the brain,

腦中的異常區域

and we've been able to intervene within these circuits

並能介入大腦中的這些迴路

in the brain to either turn them up or turn them down.

將其訊號調高或調低

So this is very much like choosing the correct station

很像在收音機上

on the radio dial.

先選擇想聽的電台

Once you choose the right station, whether it be jazz or opera,

例如選了爵士樂或歌劇電台

in our case whether it be movement or mood,

對我們來說，則是運動或情緒

we can put the dial there,

我們就可以在那裡放入調節器

and then we can use a second button to adjust the volume,

再用第二個旋鈕調整音量

to turn it up or turn it down.

調高或調低

So what I'm going to tell you about

所以我要和你們說的

is using the circuitry of the brain to implant electrodes

是藉由植入腦中的電極

and turning areas of the brain up and down

調整腦部某區域訊號的高低

to see if we can help our patients.

來看是否可以改善病況

And this is accomplished using this kind of device,

這都仰賴一種儀器

and this is called deep brain stimulation.

我們稱之為「深層腦部刺激」

So what we're doing is placing these electrodes throughout the brain.

將電極置入腦部各個區域

Again, we are making holes in the skull about the size of a dime,

同樣在頭骨打個硬幣大小的洞

putting an electrode in, and then this electrode

置入電極

is completely underneath the skin

這些電極完全在皮膚底下

down to a pacemaker in the chest,

像是胸腔內的心律調節器

and with a remote control very much like a television remote control,

遙控器就像電視的遙控器

we can adjust how much electricity we deliver

我們能調整電流強度

to these areas of the brain.

以及刺激的腦部區域

We can turn it up or down, on or off.

可以調整強、弱、開、關

Now, about a hundred thousand patients in the world

現在全球約有 10 萬個病患

have received deep brain stimulation,

接受深層腦部刺激

and I'm going to show you some examples

接下來要展示一些案例

of using deep brain stimulation to treat disorders of movement,

利用深層腦部刺激治療運動失調、

disorders of mood and disorders of cognition.

情緒失調、認知失調

So this looks something like this when it's in the brain.

它在腦中看起來就像這樣

You see the electrode going through the skull into the brain

你可以看到電極穿過頭骨進入腦部

and resting there, and we can place this really anywhere in the brain.

放置在那裡—可以放到任何地方

I tell my friends that no neuron is safe

我曾和朋友說，沒有任何神經細胞

from a neurosurgeon, because we can really reach

是神經外科醫師碰不到的 我們現在可以…

just about anywhere in the brain quite safely now.

安全的對大腦任何部位手術

Now the first example I'm going to show you is a patient

我要展示的第一個例子

with Parkinson's disease,

是位帕金森氏症的病患

and this lady has Parkinson's disease,

這位女士患有帕金森氏症

and she has these electrodes in her brain,

而她腦部有這些電極

and I'm going to show you what she's like

若把電源關掉

when the electrodes are turned off and she has her Parkinson's symptoms,

她就會出現帕金森氏症的症狀

and then we're going to turn it on.

然後我們開啟電源

So this looks something like this.

看起來就會像這樣

The electrodes are turned off now, and you can see that she has tremor.

電源關閉，你可以看到她在抖動

(Video) Man: Okay. Woman: I can't. Man: Can you try to touch my finger?

（影片）男：好的　女：我做不到 男：請試試看碰我的手指

(Video) Man: That's a little better. Woman: That side is better.

（影片）男：有好一點 女：這邊表現比較好

We're now going to turn it on.

現在要把電源打開

It's on. Just turned it on.

打開了，只要打開

And this works like that, instantly.

立即見效

And the difference between shaking in this way and not --

抖動和穩定的…

(Applause)

（掌聲）

The difference between shaking in this way and not is related to the misbehavior

抖動和穩定的差別，和她腦部

of 25,000 neurons in her subthalamic nucleus.

視丘下核的 2 萬 5 千個 神經細胞異常有關

So we now know how to find these troublemakers

我們已知道怎麼找出問題神經細胞

and tell them, "Gentlemen, that's enough.

並告訴它們：「嘿！這太超過了，

We want you to stop doing that."

我們希望你們停止。」

And we do that with electricity.

我們藉由電流刺激達成

So we use electricity to dictate how they fire,

我們用電流控制神經細胞的反應

and we try to block their misbehavior using electricity.

也用電流阻斷其失常行為

So in this case, we are suppressing the activity of abnormal neurons.

此例是抑制不正常神經細胞的反應

We started using this technique in other problems,

我們將這個技術用在其他問題上

and I'm going to tell you about a fascinating problem

下面是我們碰到的一個很棒的案例

that we encountered, a case of dystonia.

稱為肌張力不全症

So dystonia is a disorder affecting children.

肌張力不全症是影響兒童的病變

It's a genetic disorder, and it involves a twisting motion,

是遺傳性疾病，會有扭轉的動作

and these children get progressively more and more twisting

而這些兒童的動作會越來越扭曲

until they can't breathe, until they get sores,

直到不能呼吸、直到覺得疼痛、

urinary infections, and then they die.

泌尿系統感染，然後走向死亡

So back in 1997, I was asked to see this young boy,

1997 年我被找去看這個小男孩

perfectly normal. He has this genetic form of dystonia.

看來正常，但有肌張力不全症基因

There are eight children in the family.

他家中有八個小孩

Five of them have dystonia.

其中五個有肌張力不全症

So here he is.

這是他

This boy is nine years old, perfectly normal until the age six,

這時男孩九歲，他六歲前完全正常

and then he started twisting his body, first the right foot,

從右腳開始，他開始扭轉肢體

then the left foot, then the right arm, then the left arm,

然後是左腳、右手、左手

then the trunk, and then by the time he arrived,

接著是軀幹，當他被送進來時

within the course of one or two years of the disease onset,

距離病發只有一到兩年的時間

he could no longer walk, he could no longer stand.

他已經不能行走或站立

He was crippled, and indeed the natural progression

他的腿跛了，事實上隨著疾病惡化

as this gets worse is for them to become progressively twisted,

肢體扭曲的情形會加重

progressively disabled, and many of these children do not survive.

殘障日漸嚴重，許多孩子無法存活

So he is one of five kids.

他是五個孩子之一

The only way he could get around was crawling on his belly like this.

他想行動時，只能趴在地上爬行

He did not respond to any drugs.

他的病情不能藉由藥物控制

We did not know what to do with this boy.

我們對他的病症無計可施

We did not know what operation to do,

我們不知該對他腦部的

where to go in the brain,

哪個區域進行手術

but on the basis of our results in Parkinson's disease,

但從治療帕金森氏症的經驗

we reasoned, why don't we try to suppress

我們推論：為何不抑制

the same area in the brain that we suppressed

造成帕金森氏症的同一區域？

in Parkinson's disease, and let's see what happens?

並觀察後續發展

So here he was. We operated on him

他當時像這樣，我們動了手術

hoping that he would get better. We did not know.

希望他能好轉，但我們沒有把握

So here he is now, back in Israel where he lives,

他現在像這樣，回到以色列的家

three months after the procedure, and here he is.

這是他手術過後三個月的樣子

(Applause)

（掌聲）

On the basis of this result, this is now a procedure

藉由這次經驗，這項手術

that's done throughout the world,

已在全世界施行

and there have been hundreds of children

已經有數百名兒童

that have been helped with this kind of surgery.

受惠於這項手術

This boy is now in university

這個孩現在已上大學

and leads quite a normal life.

過著正常的生活

This has been one of the most satisfying cases

這是我從醫多年來

that I have ever done in my entire career,

最有成就感的個案

to restore movement and walking to this kind of child.

使這類病童恢復移動和行走的能力

(Applause)

（掌聲）

We realized that perhaps we could use this technology

我們瞭解到這項科技

not only in circuits that control your movement

不只可以用來控制運動

but also circuits that control other things,

也可以控制其他事情

and the next thing that we took on

下一個我們著手的

was circuits that control your mood.

是控制情緒的迴路

And we decided to take on depression,

我們決定針對憂鬱症

and the reason we took on depression is because it's so prevalent,

我們選擇憂鬱症是因為它很普遍

and as you know, there are many treatments for depression,

而且你們也知道

with medication and psychotherapy,

雖然有藥物、心理治療、

even electroconvulsive therapy,

甚至電痙攣治療

but there are millions of people,

但是在數百萬人中

and there are still 10 or 20 percent of patients with depression

仍有 10 到 20% 的患者無法治癒

that do not respond, and it is these patients that we want to help.

這些患者就需要我們的幫忙

And let's see if we can use this technique

讓我們來看看這項科技

to help these patients with depression.

能否改善憂鬱症的病情

So the first thing we did was, we compared,

首先我們比較

what's different in the brain of someone with depression

憂鬱症患者腦部和

and someone who is normal,

正常人的不同之處

and what we did was PET scans to look at the blood flow of the brain,

我們用正子掃描腦部血流 (PET scan)

and what we noticed is that in patients with depression

我們注意到憂鬱症患者

compared to normals,

與正常人相較

areas of the brain are shut down,

腦部有些地方停工了

and those are the areas in blue.

這些地方呈現藍色

So here you really have the blues,

所以你就感到憂鬱了 (譯註：憂鬱與藍色為雙關語)

and the areas in blue are areas that are involved

這些藍色區域

in motivation, in drive and decision-making,

和動機、驅力、決策有關

and indeed, if you're severely depressed as these patients were,

如果你的憂鬱和病人一樣嚴重

those are impaired. You lack motivation and drive.

你會缺乏動機和驅力

The other thing we discovered

我們發現的另一件事是

was an area that was overactive, area 25,

有個區域過度活躍

seen there in red,

就是呈現紅色的第 25 區

and area 25 is the sadness center of the brain.

第 25 區是腦部的悲傷中心

If I make any of you sad, for example, I make you remember

如果我讓你感到悲傷

the last time you saw your parent before they died

例如讓你回想起親人或朋友

or a friend before they died,

去世前的最後一面

this area of the brain lights up.

這個區域就會活化

It is the sadness center of the brain.

這是大腦的悲傷中心

And so patients with depression have hyperactivity.

憂鬱症患者發病時

The area of the brain for sadness is on red hot.

大腦的悲傷中心運作到達高峰

The thermostat is set at 100 degrees,

好像溫度被設定在 100 度

and the other areas of the brain, involved in drive and motivation, are shut down.

動機和驅力等區域則完全停工

So we wondered, can we place electrodes in this area of sadness

我們想，如果把電極置於悲傷中心

and see if we can turn down the thermostat,

調降溫度調節器的溫度

can we turn down the activity,

以隆低這個區域的活性

and what will be the consequence of that?

會產生什麼後果呢？

So we went ahead and implanted electrodes in patients with depression.

我們將電極植入憂鬱症患者腦部

This is work done with my colleague Helen Mayberg from Emory.

我和艾默瑞大學 (Emory) 同事 海倫梅伯格 (Helen Mayberg) 合作

And we placed electrodes in area 25,

將電極置於第 25 區

and in the top scan you see before the operation,

上面那張是手術前的掃瞄

area 25, the sadness area is red hot,

25 區，即悲傷中心，呈現紅色

and the frontal lobes are shut down in blue,

前額葉完全停工，呈現藍色

and then, after three months of continuous stimulation,

24 小時持續刺激三個月、

24 hours a day, or six months of continuous stimulation,

六個月後

we have a complete reversal of this.

情況完全逆轉

We're able to drive down area 25,

25 區的活化程度

down to a more normal level,

已降低到正常水準

and we're able to turn back online

前額葉則

the frontal lobes of the brain,

重新開機上線

and indeed we're seeing very striking results

我們在重度憂鬱症患者身上

in these patients with severe depression.

的確看到了驚人的效果

So now we are in clinical trials, and are in Phase III clinical trials,

我們現在正進行第三期臨床試驗

and this may become a new procedure,

有可能成為新的治療方式

if it's safe and we find that it's effective,

只要證實能安全有效的

to treat patients with severe depression.

治療重度憂鬱症患者

I've shown you that we can use deep brain stimulation

剛才展示了使用深層腦部刺激

to treat the motor system

治療運動系統相關疾病

in cases of Parkinson's disease and dystonia.

如帕金森氏症、肌張力不全症

I've shown you that we can use it to treat a mood circuit

也可以治療情緒迴路疾病

in cases of depression.

如憂鬱症

Can we use deep brain stimulation to make you smarter?

那是否可用深層腦部刺激 讓你變聰明？

(Laughter)

（笑聲）

Anybody interested in that?

有人有興趣嗎？

(Applause)

（掌聲）

Of course we can, right?

當然沒問題，對吧？

So what we've decided to do is

我們決定

we're going to try to turbocharge

要試著

the memory circuits in the brain.

替腦中的記憶迴路充電

We're going to place electrodes within the circuits

將電極植入

that regulate your memory and cognitive function

控制記憶與認知的迴路中

to see if we can turn up their activity.

看是否可增加其活性

Now we're not going to do this in normal people.

我們不會拿正常人實驗

We're going to do this in people that have cognitive deficits,

而是用在有認知缺陷的患者身上

and we've chosen to treat patients with Alzheimer's disease

我們嘗試治療阿茲海默症患者

who have cognitive and memory deficits.

他們有認知和記憶的問題

As you know, this is the main symptom

如各位所知，這是

of early onset Alzheimer's disease.

阿茲海默症早期的主要症狀

So we've placed electrodes within this circuit

我們把電極放在

in an area of the brain called the fornix,

腦中一個稱為穹窿的區域

which is the highway in and out of this memory circuit,

是進出記憶體迴路的高速公路

with the idea to see if we can turn on this memory circuit,

看看是否可以開啟記憶迴路

and whether that can, in turn, help these patients

進而能幫助

with Alzheimer's disease.

阿茲海默症的患者

Now it turns out that in Alzheimer's disease,

先前發現，阿茲海默症患者的腦部

there's a huge deficit in glucose utilization in the brain.

利用葡萄糖有嚴重缺陷

The brain is a bit of a hog when it comes to using glucose.

腦部是大量消耗葡萄糖的地方

It uses 20 percent of all your --

儘管只佔體重的 2%

even though it only weighs two percent --

卻消耗了人體總量的 20%

it uses 10 times more glucose than it should based on its weight.

腦的葡萄糖消耗量是重量的 10 倍

Twenty percent of all the glucose in your body is used by the brain,

20% 的葡萄糖用在腦部

and as you go from being normal

從正常的腦部

to having mild cognitive impairment,

到輕微的認知失常

which is a precursor for Alzheimer's, all the way to Alzheimer's disease,

再發展成阿茲海默症

then there are areas of the brain that stop using glucose.

腦部有些區域停止利用葡萄糖

They shut down. They turn off.

停工了、關機了

And indeed, what we see is that these areas in red

事實上，我們可以看到

around the outside ribbon of the brain

腦中央帶狀區的外圈，由紅色

are progressively getting more and more blue

逐漸變藍

until they shut down completely.

直到完全停工

This is analogous to having a power failure

好像是腦中停電了

in an area of the brain, a regional power failure.

形成區域性供電異常

So the lights are out in parts of the brain

阿茲海默症患者的部分大腦

in patients with Alzheimer's disease,

好像停電而陷入黑暗

and the question is, are the lights out forever,

問題是，電力中斷是永久性的呢

or can we turn the lights back on?

還是我們有辦法恢復？

Can we get those areas of the brain to use glucose once again?

可以讓這些區域再利用葡萄糖嗎？

So this is what we did. We implanted electrodes in the fornix

我們把電極植入穹窿

of patients with Alzheimer's disease, we turned it on,

活化阿茲海默症患者此一區域

and we looked at what happens to glucose use in the brain.

然後觀察大腦利用葡萄糖的狀況

And indeed, at the top, you'll see before the surgery,

上面那張是手術前

the areas in blue are the areas that use less glucose than normal,

藍色區域葡萄糖用量比正常值少

predominantly the parietal and temporal lobes.

主要是在患者的顳葉

These areas of the brain are shut down.

腦的這些區域停工了、

The lights are out in these areas of the brain.

停電了

We then put in the DBS electrodes and we wait for a month

我們放入深層腦部刺激電極

or a year, and the areas in red

一個月後、一年後再觀察

represent the areas where we increase glucose utilization.

紅色區域表示葡萄糖消耗量增加

And indeed, we are able to get these areas of the brain

所以我們確實可讓

that were not using glucose to use glucose once again.

本來不使用葡萄糖的區域恢復使用

So the message here is that, in Alzheimer's disease,

結果顯示，阿茲海默症患者腦部

the lights are out, but there is someone home,

雖然停電了，但仍有人在家

and we're able to turn the power back on

而我們可以

to these areas of the brain, and as we do so,

讓這些區域的電力恢復

we expect that their functions will return.

我們預期功能也會恢復

So this is now in clinical trials.

這正在臨床試驗階段

We are going to operate on 50 patients

我們要對 50 位

with early Alzheimer's disease

早期阿茲海默症病患進行手術

to see whether this is safe and effective,

確認是否安全有效

whether we can improve their neurologic function.

是否可改善他們神經的功能

(Applause)

（掌聲）

So the message I want to leave you with today is that,

我想傳達給各位的訊息是

indeed, there are several circuits in the brain

腦部不同迴路的異常

that are malfunctioning across various disease states,

和不同的病變有關

whether we're talking about Parkinson's disease,

我們討論了帕金森氏症、

depression, schizophrenia, Alzheimer's.

憂鬱症、精神分裂症和阿茲海默症

We are now learning to understand what are the circuits,

我們正學習了解這些迴路

what are the areas of the brain that are responsible for

還有對應的腦部區域

the clinical signs and the symptoms of those diseases.

以及對應的臨床症狀

We can now reach those circuits.

我們有能力觸及這些迴路

We can introduce electrodes within those circuits.

並在這些迴路中放入電極

We can graduate the activity of those circuits.

我們可調節這些迴路的活動

We can turn them down if they are overactive,

如果太活躍，並造成腦部的問題

if they're causing trouble, trouble that is felt throughout the brain,

我們可以將它調低

or we can turn them up if they are underperforming,

如果活躍程度不足，則可調高

and in so doing, we think that we may be able to help

我們認為藉此可幫助

the overall function of the brain.

腦部的整體功能

The implications of this, of course, is that we may be able

這些結果顯示

to modify the symptoms of the disease,

我們可以緩和疾病的症狀

but I haven't told you but there's also some evidence

我還沒告訴你們有證據顯示

that we might be able to help the repair of damaged areas of the brain using electricity,

電流可協助修復腦部損傷

and this is something for the future, to see if, indeed,

這些都是未來的展望

we not only change the activity but also

我們不只可以調整腦部活躍程度

some of the reparative functions of the brain

也可以看到大腦修復受損功能

can be harvested.

的成果

So I envision that we're going to see a great expansion

我預期未來將會廣泛應用

of indications of this technique.

這項科技

We're going to see electrodes being placed for many disorders of the brain.

將看到用電極改善多種腦部問題

One of the most exciting things about this is that, indeed,

而其中最令人興奮的

it involves multidisciplinary work.

是它包含了跨領域的合作

It involves the work of engineers, of imaging scientists,

包括工程師、影像學家、

of basic scientists, of neurologists,

基礎科學家、神經學家、

psychiatrists, neurosurgeons, and certainly at the interface

精神醫師、神經外科醫師通力合作

of these multiple disciplines that there's the excitement.

跨領域合作是令人興奮的

And I think that we will see that

我想我們會看到

we will be able to chase more of these evil spirits

隨著時間推移，越來越多惡靈

out from the brain as time goes on,

會被趕出腦袋

and the consequence of that, of course, will be

結果當然就是

that we will be able to help many more patients.

我們可以幫助更多的病患

Thank you very much.

謝謝大家