What investigating neural pathways can reveal about mental health | Kay M. Tye

Transcriber: Ivana Korom Reviewer: Krystian Aparta

譯者: Lilian Chiu 審譯者: Lo Hsien Huang

I'm going to start by saying something you think you know to be true.

一開始，我要先說一個 大家都認為是正確的想法。

Your brain creates all facets of your mind.

大腦負責創造出心智的各個面向。

So then why do we treat mental and physical illnesses

如果我們認為心智來自大腦，

so differently,

那為什麼我們治療心理 和身體疾病的方式差這麼多？

if we think we know that the mind comes from the brain?

As a neuroscientist, I'm often told

身為神經科學家，別人常告訴我， 我不能去研究內在狀態，

that I'm not allowed to study how internal states

like anxiety or craving or loneliness

如焦慮、渴望、寂寞，

are represented by the brain,

在大腦中的呈現方式，

and so I decided to set out and do exactly that.

所以我決定，我偏偏就要這麼做。

My research program is designed to understand the mind

我的研究計畫

是透過研究大腦迴路來了解心智。

by investigating brain circuits.

Specifically, how does our brain give rise to emotion.

明確來說，是探究 大腦如何引發情緒。

It's really hard to study feelings and emotions,

要研究感覺和情緒真的很困難，

because you can't measure them.

因為無法測量它們。

Behavior is still the best and only window

行為仍然是一窺他人情緒體驗的

into the emotional experience of another.

最佳窗口，也是唯一的窗口。

For both animals and people,

對動物和人類都一樣，

yes, self-report is a behavioral output.

是的，自我報告是一種行為上的輸出。

Motivated behaviors fall into two general classes:

有動機的行為一般而言 可以分為兩類：

seeking pleasure and avoiding pain.

尋求歡愉以及避免痛苦。

The ability to approach things that are good for you

去接近對你有益的事物、

and avoid things that are bad for you

避開對你無益的事物，

是一種很重要求生能力。

is fundamental to survival.

And in our modern-day society,

在我們的現代社會中，

trouble telling the difference can be labeled as a mental illness.

無法分辨出這種差別， 就可能會被貼上心理疾病的標籤。

If I was having car trouble,

如果我的車出了問題，

and I took my car to the mechanic,

去找修理技工來看我的車，

the first thing they do is look under the hood.

他們會做的第一件事 就是打開引擎蓋來看。

But with mental health research,

但，就心理健康研究而言，

you can't just pop open the hood with the press of a button.

就不能只是按下按鈕 把引擎蓋彈開。

So this is why we do experiments on animals.

這就是為什麼我們要做動物實驗。

Specifically, in my lab, mice.

明確來說，我的實驗室 做的是老鼠實驗。

To understand the brain, well, we need to study brains.

若要了解大腦， 我們就得研究大腦。

And for the first time, we actually can.

這是史上頭一回我們真的能做到。

We can pop open the hood.

我們能把引擎蓋彈開。

We can look inside

我們可以看到內部，

and do an experiment and see what comes out.

進行實驗，看看會產生什麼結果。

Technology has opened new windows into the black box that is our minds.

我們的心靈是個黑盒子， 而科技已經為它開啟了新窗戶。

The development of optogenetic tools

光遺傳學工具的發展

has allowed us unprecedented control over specific neurons in the brain

讓我們能做到前所未見的事： 控制大腦中特定的神經元，

and how they talk to each other by firing electrical signals.

以及它們如何放出 電訊號來與彼此交談。

We can genetically engineer neurons to be light sensitive

我們可以用基因工程 製造對光敏感的神經元，

and then use light to control how neurons fire.

接著用光來控制神經元如何放電。

This can change an animal's behavior,

這樣做就能改變動物的行為，

giving us insight into what that neural circuit can do.

讓我們能深入了解 神經迴路能做什麼。

Want to know how scientists figure this out?

想知道科學家如何 想出這種方法的嗎？

Scientists developed optogenetic tools by borrowing knowledge

科學家借用其他 基礎科學領域的知識，

from other basic science fields.

開發出了光遺傳學工具。

Algae are single-celled organisms that have evolved to swim towards light.

水藻是單細胞有機體， 已經演化成會朝光的方向游去。

And when blue light shines onto the eyespot of an algae cell,

當藍光照在水藻細胞的眼點上時，

a channel opens, sending an electrical signal

有一個管道會打開，送出電訊號，

that makes little flagella flap

讓小鞭毛拍動，

and propels the algae towards sunlight.

將水藻推向光的方向。

If we clone this light-sensitive part of the algae

如果我們複製水藻 對光敏感的這個部分，

and then add it to neurons through genetic modification,

用基因編輯把它加到神經元上，

we can make neurons light-sensitive, too.

我們就能讓神經元也變成對光敏感。

Except, with neurons,

不過，就神經元來說，

when we shine light down an optical fiber deep into the brain,

當我們透過光導纖維 把光照到大腦深處時，

we change how they send electrical signals to other neurons in the brain

我們會改變神經元發送電訊號 給大腦中其他神經元的方式，

and thus change the animal's behavior.

因而改變動物的行為。

With the help of my colleagues,

在我的同事協助之下，

I pioneered the use of optogenetic tools

我把光遺傳學工具 做了開創性的應用，

to selectively target neurons that are living in point A,

選擇性地針對在 A 點的神經元，

sending messages down wires aimed at point B,

透過連結發送訊息到 B 點，

leaving neighboring neurons going other places unaffected.

讓周圍的神經元完全不受影響。

This approach allowed us to test the function of each wire

這個方法讓我們能在 大腦的一團亂當中

within the tangled mess that is our brain.

測試每一個連結的功能。

A brain region called the amygdala

大腦有個區域叫杏仁核，

has long been thought to be important for emotion,

長久以來公認對情緒很重要，

and my laboratory discovered

我的實驗室發現，

that the amygdala resembles a fork in the road

杏仁核就像是道路上的分叉，

where activating one path can drive positive emotion and approach,

啟動一條路徑就會驅動 正面的情緒和接近，

and activating another path can drive negative emotion and avoidance.

啟動另一條路徑則會驅動 負面的情緒和迴避。

I'm going to show you a couple of examples --

讓我用幾個例子跟各位說明——

a taste of raw data --

體驗一下原始資料——

of how we can use optogenetics to target specific neurons in the brain

我們如何用光遺傳學 來鎖定大腦中的特定神經元，

and get very specific changes in behavior.

並造成非常特定的行為改變。

Anxiety patients have abnormal communication

焦慮病人在杏仁核的兩個部分之間

between two parts of the amygdala,

會有異常的溝通，

but in people, it's hard to know if this abnormality is cause or effect

但在人類身上，很難確定

這種異常是焦慮的因或果。

of the disease.

We can use optogenetics to target the same pathway in a mouse,

我們能使用光遺傳學 在老鼠身上鎖定同樣的路徑，

and see what happens.

看看會發生什麼事。

So this is the elevated plus maze.

這是焦慮測試中 常用的高架十字迷宮。

It's a widely used anxiety test

that measures the amount of time

用來測量老鼠在密閉管道的 安全設施中待了多久，

that the mouse spends in the safety of the closed arms

並與花在開放管道的時間做比較。

relative to exploring the open arms.

Mice have evolved to prefer enclosed spaces,

老鼠已經演化成偏愛密閉空間，

like the safety of their burrows,

比如老鼠洞的安全空間，

but to find food, water, mates,

但為了找食物、水、配偶，

they need to go out into the open

牠們必須要出去到開放空間中，

where they're more vulnerable to predatory threats.

在那裡，牠們容易 受到獵食動物的威脅。

So I'm sitting in the background here,

我坐在背景這裡，

and I'm about to flip the switch.

準備要去打開開關。

And now, when I flip the switch and turn the light on,

當我打開開關，把光打開，

you can see the mouse begins to explore the open arms of the maze more.

各位可以看見老鼠變得 更會去探索迷宮的開放管道。

And in contrast to drug treatments for anxiety,

和焦慮藥物治療不同，

there's no sedation, no locomotor impairment,

這種方式沒有鎮靜作用， 沒有造成行動上的困難，

just coordinated, natural-looking exploration.

只有協調且看起來自然的探索。

So not only is the effect almost immediate,

這個效應幾乎是立即性的，

but there are no detectable side effects.

且沒有發現任何副作用。

Now, when I flip the switch off,

當我把開關關掉，

you can see that the mouse goes back to its normal brain function

老鼠的大腦功能就恢復正常，

and back to its corner.

老鼠會躲回角落。

When I was in the lab and I was taking these data,

我在實驗室記錄這些資料時，

I was all by myself, and I was so excited.

只有我一個人，我好興奮。

I was so excited, I did one of these quiet screams.

我好興奮，所以我 像這樣安靜地尖叫。

(Silently) Aah!

（安靜地）啊！

(Laughter)

（笑聲）

Why was I so excited?

為什麼如此興奮？

I mean, yeah, theoretically, I knew that the brain controlled the mind,

我的意思是，我知道理論上 心智是由大腦所控制，

but to flip the switch with my hand

但我親手打開開關

and see the mouse change its behavioral state

看見老鼠快速改變行為狀態，

so rapidly and so reversibly,

而且是可逆的，

it was really the first time that I truly believed it.

這是我第一次真正相信這個理論。

Since that first breakthrough,

從那第一次突破之後，

there have been a number of other discoveries.

還有一些其他發現。

Finding specific neural circuits that can elicit dramatic changes

我們發現特定的神經迴路能夠

引發動物行為的重大改變。

in animal behavior.

Here's another example: compulsive overeating.

再舉一個例子：強迫性過度飲食。

We can eat for two reasons.

有兩個理由會讓我們想吃。

Seeking pleasure, like tasty food,

尋求歡愉，比如美食，

or avoiding pain, like being hungry.

或者避免痛苦，比如挨餓。

How can we find a treatment for compulsive overeating

我們要如何找出治療 強迫性過度飲食的方法，

without messing up the hunger-driven feeding

同時不要擾亂了我們生存 所需要的飢餓進食機制？

that we need to survive?

The first step is to understand

第一步是要了解

how the brain gives rise to feeding behavior.

大腦如何引起進食行為。

This fully-fed mouse is just exploring a space

這隻完全吃飽的老鼠 只是在探索空間，

completely devoid of any food.

這裡完全沒有任何食物。

Here we're using optogenetics to target neurons living in the hypothalamus,

在這裡，我們用光遺傳學 來鎖定丘腦下部的神經元，

sending messages down wires aimed at the midbrain.

透過連結發送訊息到中腦。

When I turn the light on, right here,

當我把光線打開，就是這時候，

you can see that the mouse immediately begins licking the floor.

各位可以看見， 老鼠馬上開始舔地板。

(Laughter)

（笑聲）

This seemingly frenzied behavior

這種似乎很瘋狂的行為

is about to escalate into something I find really incredible.

即將逐漸變成我覺得 非常不可思議的狀況。

It's kind of trippy, actually.

其實有點像吸了毒。

Ready?

準備好了嗎？

It's right here.

就是此時。

See, he picks up his hands as if he is eating a piece of food,

看，牠把手舉起來， 好像牠正在吃食物，

but there's nothing there, he's not holding anything.

但牠手上什麼也沒有。

So this circuit is sufficient to drive feeding behavior

用這個迴路就足以 驅使牠做出進食行為，

in the absence of hunger,

即使牠根本不餓，

even in the absence of food.

甚至沒有食物也沒關係。

I can't know for sure how this mouse is feeling,

我無法知道這隻老鼠有什麼感覺，

but I speculate these neurons drive craving

但我推測，這些神經元會根據

based on the behaviors we elicit when we target this pathway.

我們鎖定這條路徑 所造成的行為來驅動渴望。

Turn the light back off --

再把光關掉——

animal's back to normal.

動物又恢復正常。

When we silence this pathway,

當我們壓制這條路徑，

we can suppress and reduce compulsive overeating

我們就能阻止及減輕 強迫性過度飲食症，

without altering hunger-driven feeding.

且不需要改變 由飢餓驅使的進食。

What did you take away from these two videos

從剛才播放的兩支影片中， 我們學到什麼？

that I just showed you?

That making a very specific change to neural circuits in the brain

對大腦中的神經迴路做特定的改變，

can have specific changes to behavior.

就能造成行為的特定改變。

That every conscious experience that we have

我們所有有意識的體驗，

is governed by cells in our brain.

都是由大腦中的細胞所掌管。

I am the daughter of a physicist and a biologist,

我的父母是物理學家和生物學家，

who literally met on the boat coming to America

他們搭船來美國求學，

in pursuit of an education.

在船上相遇。

So naturally,

所以，很自然，

since there was "no pressure" to be a scientist ...

既然「沒有壓力」 必須要成為科學家……

(Laughter)

（笑聲）

as a college student,

我大學時，

I had to decide whether I wanted to focus on psychology, the study of the mind,

必須決定我要投入 心理學，研究心智，

or neuroscience, the study of the brain.

還是要投入神經科學，研究大腦。

And I chose neuroscience,

而我選擇了神經科學，

because I wanted to understand how the mind is born

因為我想要了解心智是怎麼

從生物組織中產生出來的。

out of biological tissue.

But really, I've come full circle to do both.

但其實我很圓滿地做到了兩者。

And now my research program

現在，我的研究計畫

bridges the gap between the mind and the brain.

銜接了心智和大腦之間的缺口。

Research from my laboratory

根據我實驗室所做的研究，

suggests that we can begin to tie specific neural circuits

我們可以開始把特定的神經迴路

to emotional states.

連結到情緒狀態。

And we have found a number of circuits

我們已經發現很多迴路的功能 是在控制焦慮相關行為、

that control anxiety-related behavior,

compulsive overeating,

強迫性過度飲食、

social interaction, avoidance

社交互動、逃避，

and many other types of motivated behaviors

以及許多其他動機性行為，

that may reflect internal emotional states.

它們都有可能反映出 內在的情緒狀態。

We used to think of functions of the mind as being defined by brain regions.

我們以前認為心智的功能 是由大腦區域來定義。

But my work shows that within a given brain region,

但我的研究指出， 在一個大腦區域內，

there are many different neurons doing different things.

會有許多不同的神經元 在做不同的工作。

And these functions are partly defined by the paths they take.

這些功能有一部分是由 它們所走的路徑來定義的。

Here's a metaphor to help illustrate

讓我用個比喻來說明

how these discoveries change the way that we think about the brain.

這些發現如何改變 我們對大腦的看法。

Let's say that the brain is analogous to the world

讓我們把大腦比喻成世界，

and that neurons are analogous to people.

把神經元比喻成人。

And we want to understand how information is transmitted across the planet.

我們想要了解資訊 如何在地球上傳遞。

Sure, it's useful to know

當然，如果在記錄 一個人說什麼的時候

where a given person is located when recording what they're saying.

還能知道他的所在，會很有幫助。

But I would argue that it's equally important

但我認為，同樣重要的是

to know who this person is talking to,

要知道這個人在對誰說話，

who is listening

誰在聆聽，

and how the people listening respond to the information that they receive.

以及聆聽的人對於他們 接收到的資訊有什麼反應。

The current state of mental health treatment

心理健康治療的現況

is essentially a strategy of trial and error.

基本上是在用嘗試錯誤的策略。

And it is not working.

但是這沒有效果。

The development of new drug therapies for mental health disorders

針對心理健康疾病的新藥物治療

has hit a brick wall,

發展已經碰到瓶頸，

with scarcely any real progress since the 1950s.

從五○年代之後就幾乎 沒有什麼真正的進展。

So what does the future hold?

那麼，未來如何？

In the near future,

在不遠的將來，

I expect to see a mental health treatment revolution,

我預期會發生一場 心理健康治療革命，

where we focus on specific neural circuits in the brain.

我們會把焦點放在 大腦中特定的神經迴路。

Diagnoses will be made based on both behavioral symptoms

診斷的根據會是行為症狀

and measurable brain activity.

以及可測量的腦部活動。

Further in the future,

再遠一點的未來，

by combining our ability to make acute changes to the brain

結合我們急劇改變大腦的能力，

以及急劇改變行為的能力，

and get acute changes to behavior

with our knowledge of synaptic plasticity to make more permanent changes,

還有我們對於突觸可塑性的知識， 來做出更持久的改變，

we could push the brain into a state of fixing itself

那麼我們就可以把大腦推向

透過神經迴路程式改寫的方式 來自我修復的夢想。

by reprogramming neural circuits.

Exposure therapy at the circuit level.

那就是「迴路層級的暴露療法」。

Once we switch the brain into a state of self-healing,

一旦我們把大腦切換到 自我治癒的狀態，

this could potentially have long-lasting effects

就可能可以發揮持久的效果，

with no side effects.

且沒有副作用。

I can envision a future where neural circuit reprogramming

我能想像，在未來， 神經迴路的程式改寫

represents a potential cure, not just a treatment.

代表的不只是治療方式， 也是一種具有潛力的解藥。

OK, but what about right now?

但是，現在呢？

If from this very moment forward,

如果，從此刻之後，

each and every one of you left this talk

在座各位離開這場演講後，

and truly believed that the mind comes entirely from cells in your brain,

真心相信心智是完全 來自於大腦中的細胞，

then we could immediately get rid of negative perceptions and stigmas

那麼我們可以馬上擺脫 負面感知和汙名，

that prevent so many people

不要再讓它們阻擋許多人 取得他們需要的心理健康支持。

from getting the mental health support that they need.

Mental health professionals,

心理健康專業人士總是在想著

we're always thinking about what's the next new treatment.

下一個新的治療方式是什麼。

But before we can apply new treatments,

但，在我們能應用 新的治療方式之前，

we need people to feel comfortable seeking them.

我們得讓大家能覺得 尋求治療是很自在的。

Imagine how dramatically we could reduce the rates of suicides

想像一下，我們能把自殺

和校園槍擊的比率降低多少，

and school shootings

if everyone who needed mental health support actually got it.

只要讓需要心理健康支持的人 能真正得到支持。

When we truly understand exactly how the mind comes from the brain,

當我們能真正了解 大腦如何創造心智，

we will improve the lives of everyone

我們就能為所有在將來人生中

who will have a mental illness in their lifetime --

會得到心理疾病的人， 改善他們的生活。

half the population --

這些人佔了一半的人口。

as well as everyone else with whom they share the world.

和他們共同生活在世界上的其他人， 生活也能得到改善。

Thank you.

謝謝。

(Applause)

（掌聲）