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

Transcriber: Ivana Korom Reviewer: Krystian Aparta

翻译人员: Yanyan Hong 校对人员: Wanting Zhong

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

首先，我要说出一个 你认为是正确的看法。

Your brain creates all facets of your mind.

“你思想的方方面面 都源自你的大脑。”

So then why do we treat mental and physical illnesses

如果我们认为思想来自大脑，

so differently,

那为什么我们对待心理和身体疾病 的态度如此不同？

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

As a neuroscientist, I'm often told

身为神经科学家，别人常告诉我，

that I'm not allowed to study how internal states

我不能去研究内心状态，

like anxiety or craving or loneliness

如焦虑、渴望、孤独，

are represented by the brain,

是如何由大脑呈现的，

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

所以我决定，我偏偏要这么做。

My research program is designed to understand the mind

我的研究项目旨在

by investigating brain circuits.

通过研究脑回路来理解思维。

Specifically, how does our brain give rise to emotion.

具体来说，我在探究我们的 大脑是如何产生情感的。

It's really hard to study feelings and emotions,

要研究情感和情绪是非常难的，

because you can't measure them.

因为它们无法衡量。

Behavior is still the best and only window

行为仍然是最好且唯一

into the emotional experience of another.

能用于窥测他人情感体验的窗口。

For both animals and people,

没错，自我评估是一种行为输出，

yes, self-report is a behavioral output.

对动物和人都适用。

Motivated behaviors fall into two general classes:

动机行为可大致归为两类：

seeking pleasure and avoiding pain.

寻求愉悦和逃避痛苦。

The ability to approach things that are good for you

生存最根本的能力

and avoid things that are bad for you

就是去接近那些对你有益的事物，

is fundamental to survival.

并回避那些对你有害的事物。

And in our modern-day society,

而在我们现代社会中，

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

无法鉴别其中的差异， 就会被贴上心理疾病的标签。

If I was having car trouble,

如果我的车出了问题，

and I took my car to the mechanic,

我会把车送去技工那里，

the first thing they do is look under the hood.

他们会做的第一件事 就是检查引擎盖下。

But with mental health research,

但在心理健康研究中，

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

你不能只靠按下按钮 就把引擎盖弹开，

So this is why we do experiments on animals.

这就是为什么我们 要用动物进行实验。

Specifically, in my lab, mice.

准确来说，我的实验室 用小鼠做实验。

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

若要理解大脑， 我们就需要研究大脑。

And for the first time, we actually can.

这是史上头一回，我们能做到，

We can pop open the hood.

我们能打开引擎盖，

We can look inside

我们能够查看内部，

and do an experiment and see what comes out.

进行实验，看到结果。

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

我们的思维是个黑匣子， 而科技为其打开了新窗口。

The development of optogenetic tools

光遗传学工具的发展

has allowed us unprecedented control over specific neurons in the brain

让我们能前所未有地 控制大脑中特定的神经元，

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

以及它们如何发出电信号 进行彼此交流。

We can genetically engineer neurons to be light sensitive

我们可以用基因工程 制造对光敏感的神经元，

and then use light to control how neurons fire.

然后用光来控制神经元的激发，

This can change an animal's behavior,

从而改变动物的行为，

giving us insight into what that neural circuit can do.

让我们能深入了解 那个神经回路的作用。

Want to know how scientists figure this out?

想知道科学家是如何 想出这种方法的吗？

Scientists developed optogenetic tools by borrowing knowledge

科学家借用其他基础科学领域的知识，

from other basic science fields.

开发出了光遗传工具。

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

水藻是单细胞生物， 已经进化成向光而游的特性，

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

当蓝光照在水藻细胞的眼点上，

a channel opens, sending an electrical signal

有一个（离子）通道会打开， 产生电信号，

that makes little flagella flap

让小鞭毛拍动，

and propels the algae towards sunlight.

将水藻推向阳光方向。

If we clone this light-sensitive part of the algae

如果我们复制水藻对光敏感的部分，

and then add it to neurons through genetic modification,

通过基因编辑将其加入神经元，

we can make neurons light-sensitive, too.

我们也能让神经元变得光敏感。

Except, with neurons,

不过，对神经元而言，

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

当我们通过光导纤维， 把光照到大脑深处时，

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

我们会改变神经元如何将电信号 发送给大脑中其余神经元，

and thus change the animal's behavior.

从而改变动物的行为。

With the help of my colleagues,

在我同事的帮助下，

I pioneered the use of optogenetic tools

我率先使用光遗传工具，

to selectively target neurons that are living in point A,

选择性地锁定 A 点的神经元，

sending messages down wires aimed at point B,

通过连结发送信息到 B 点，

leaving neighboring neurons going other places unaffected.

让周围联结其他地方 的神经元不受影响。

This approach allowed us to test the function of each wire

这个方法能让我们测试大脑

within the tangled mess that is our brain.

这一团乱麻中每根连接线的功能。

A brain region called the amygdala

大脑有个区域叫做杏仁核，

has long been thought to be important for emotion,

大家一直认为它对情绪至关重要，

and my laboratory discovered

而我的实验室发现，

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,

启动一条路径就会 驱动积极的情绪和接近行为，

and activating another path can drive negative emotion and avoidance.

而启动另一条路径则会 导致消极的情绪和回避行为。

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

我给大家展示几个例子——

a taste of raw data --

体验一下原数据——

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

我们如何用光遗传学 来锁定大脑中特定神经元，

and get very specific changes in behavior.

并导致极其特定的行为变化。

Anxiety patients have abnormal communication

焦虑症患者的杏仁核 两个部分之间的

between two parts of the amygdala,

交流存在异常，

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

但在人类身上很难知道 这种异常是焦虑症的原因

of the disease.

还是后果。

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

我们能使用光遗传学 在小鼠身上锁定同样的通路，

and see what happens.

看看会发生什么。

So this is the elevated plus maze.

这是高架十字迷宫，

It's a widely used anxiety test

是一种广泛使用的 焦虑行为测试。

that measures the amount of time

它测量小鼠有多少时间

that the mouse spends in the safety of the closed arms

待在闭合通道的安全中，

relative to exploring the open arms.

与之相比又花多少时间 在开放通道中探索。

Mice have evolved to prefer enclosed spaces,

小鼠已经演化成偏爱密闭空间，

like the safety of their burrows,

比如安全的鼠洞，

but to find food, water, mates,

但为了觅食、找水、寻配偶，

they need to go out into the open

它们需要出去到开放的野外，

where they're more vulnerable to predatory threats.

在那里它们更容易受到天敌威胁。

So I'm sitting in the background here,

我坐在背景的这里，

and I'm about to flip the switch.

我准备要去打开开关。

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

现在，我打开了开关， 把光照打开。

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

大家可以看到小鼠开始 更频繁地探索迷宫中的开放通道，

And in contrast to drug treatments for anxiety,

与用药物治疗焦虑不同，

there's no sedation, no locomotor impairment,

它没有变得镇静， 也没有出现运动障碍，

just coordinated, natural-looking exploration.

只是在进行协调、 看起来自然的探索。

So not only is the effect almost immediate,

这个几乎是立即见效，

but there are no detectable side effects.

且没有任何可检测到的副作用。

Now, when I flip the switch off,

现在，我关上开关，

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

你们可以看见小鼠的 脑功能恢复正常，

and back to its corner.

且躲回了角落。

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

当我在实验室记录这些数据时，

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

我非常兴奋，却只有我一个人。

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

我太激动， 所以我安静地尖叫了一声。

(Silently) Aah!

（安静地）啊啊！

(Laughter)

（笑声）

Why was I so excited?

我为什么这么激动？

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

理论上，我知道 是大脑在控制思想，

but to flip the switch with my hand

但由我亲手打开开关，

and see the mouse change its behavioral state

看见了老鼠改变行为状态，

so rapidly and so reversibly,

如此迅速地，如此可逆的，

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

这是我第一次真正相信这个理论。

Since that first breakthrough,

自从那第一次突破，

there have been a number of other discoveries.

我们又有了很多新发现，

Finding specific neural circuits that can elicit dramatic changes

我们发现特定的神经回路能够引发

in animal behavior.

动物行为的戏剧性改变。

Here's another example: compulsive overeating.

再举另一个例子： 强迫性暴饮暴食。

We can eat for two reasons.

有两个理由让我们吃东西，

Seeking pleasure, like tasty food,

寻求愉悦，比如美味的食物；

or avoiding pain, like being hungry.

或者避免痛苦，比如饥饿。

How can we find a treatment for compulsive overeating

我们要如何找出 强迫性暴饮暴食的治疗方法，

without messing up the hunger-driven feeding

同时不扰乱我们生存所需的

that we need to survive?

由饥饿驱使的进食呢？

The first step is to understand

第一步是要了解

how the brain gives rise to feeding behavior.

大脑如何引起进食行为。

This fully-fed mouse is just exploring a space

这只完全吃饱的小鼠只是在探索

completely devoid of any food.

一个完全没有任何食物的空间。

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

这里我们用光遗传学 来锁定下丘脑中的神经元，

sending messages down wires aimed at the midbrain.

它们通过神经连结， 发送信息到中脑。

When I turn the light on, right here,

当我打开光照，就在此时，

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

各位可以看见， 小鼠马上开始舔地板。

(Laughter)

（笑声）

This seemingly frenzied behavior

这种看似很疯狂的行为

is about to escalate into something I find really incredible.

即将升级成我觉得 非常不可思议的情况。

It's kind of trippy, actually.

其实有点像幻觉。

Ready?

准备好了吗？

It's right here.

就是这里。

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

看，它把手举起来， 就好像它在吃一块食物，

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

但它手里什么也没有。

So this circuit is sufficient to drive feeding behavior

这个神经回路足以 驱使它做出进食行为，

in the absence of hunger,

即使它根本不饿，

even in the absence of food.

甚至也没有食物。

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

我不确定这只小鼠是什么感觉，

but I speculate these neurons drive craving

但根据我们锁定这条神经通路 所引发的行为，

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

我推测这些神经元 能够驱使渴望。

Turn the light back off --

再把光照关掉——

animal's back to normal.

动物归于正常。

When we silence this pathway,

当我们关闭这条通路时，

we can suppress and reduce compulsive overeating

我们就能抑制及减轻 强迫性暴饮暴食，

without altering hunger-driven feeding.

却不会改变饥饿进食的本能。

What did you take away from these two videos

从刚才我展示的两条短片中，

that I just showed you?

我们学到了什么？

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

那就是当我们对大脑 神经回路做出特定的改变，

can have specific changes to behavior.

就能让行为发生特定的变化。

That every conscious experience that we have

我们所有有意识的体验

is governed by cells in our brain.

都受大脑细胞的控制。

I am the daughter of a physicist and a biologist,

我的父母是物理学家和生物学家，

who literally met on the boat coming to America

他们在来美国求学的

in pursuit of an education.

船上相遇。

So naturally,

所以，很自然，

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

既然没有“压力” 必须成为一名科学家……

(Laughter)

（笑声）

as a college student,

当我还是大学生时，

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

我需要决定是专攻 心理学，研究思想，

or neuroscience, the study of the brain.

还是神经科学，研究大脑。

And I chose neuroscience,

而我选择了神经科学，

because I wanted to understand how the mind is born

因为我想要了解思想是怎样

out of biological tissue.

从生物组织中诞生的。

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

但其实，我很圆满地做到了两者兼顾，

And now my research program

现在，我的研究项目

bridges the gap between the mind and the brain.

连接了思想和大脑间的空隙。

Research from my laboratory

根据我实验室所做的研究，

suggests that we can begin to tie specific neural circuits

我们可以开始把特定的神经回路

to emotional states.

和情绪状态相关联。

And we have found a number of circuits

我们已经发现了若干回路

that control anxiety-related behavior,

可以控制焦虑相关的行为，

compulsive overeating,

强迫性暴饮暴食，

social interaction, avoidance

社交，逃避，

and many other types of motivated behaviors

以及其他种类的激励行为，

that may reflect internal emotional states.

它们或许都能反映内在的情绪状态。

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

我们曾认为思维的功能 是由大脑区域来定义的，

But my work shows that within a given brain region,

但我的研究指出， 在一个大脑区域内，

there are many different neurons doing different things.

会有许多不同的神经元 在做不同的工作，

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

这些功能有一部分是由 神经的路径来定义的。

Here's a metaphor to help illustrate

让我打个比方来说明

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

这些发现如何改变 我们看待大脑的方式。

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

让我们把大脑比作世界，

and that neurons are analogous to people.

把神经元比作人。

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

而我们想要了解信息是 如何在地球上传播的，

Sure, it's useful to know

当然，如果在记录 一个人说的话时，

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

还能定位他的位置， 会很有帮助，

But I would argue that it's equally important

但我认为同样重要的是，

to know who this person is talking to,

要知道这个人在对谁说话，

who is listening

谁在倾听，

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

以及听到的人对他们 收到的信息作何反应。

The current state of mental health treatment

心理健康治疗的现状

is essentially a strategy of trial and error.

基本上是在用试错策略，

And it is not working.

而且没有效果。

The development of new drug therapies for mental health disorders

针对心理健康疾病 的新型药物治疗方案

has hit a brick wall,

开发已经四处碰壁，

with scarcely any real progress since the 1950s.

从上世纪 50 年代以后， 几乎没有任何实质进展。

So what does the future hold?

那么，未来会如何？

In the near future,

在不久的将来，

I expect to see a mental health treatment revolution,

我期待看到一场 心理健康治疗的变革，

where we focus on specific neural circuits in the brain.

我们会专注于大脑中特定的神经回路。

Diagnoses will be made based on both behavioral symptoms

诊断依据将同时基于行为症状，

and measurable brain activity.

以及可测量的脑部活动。

Further in the future,

在更远的将来，

by combining our ability to make acute changes to the brain

我们不仅能够对大脑进行急性改变，

and get acute changes to behavior

从而让行为发生急性改变，

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

也可以藉由突触可塑性的知识， 实现更永久的改变；

we could push the brain into a state of fixing itself

将两者结合，我们就可以把大脑推向

by reprogramming neural circuits.

通过神经回路重新编程， 实现大脑自我修复的状态。

Exposure therapy at the circuit level.

在回路层面进行的暴露疗法。

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

一旦我们把大脑切换到自愈的状态，

this could potentially have long-lasting effects

就可能发挥持续的作用，

with no side effects.

没有任何副作用。

I can envision a future where neural circuit reprogramming

我能设想在未来， 神经回路的重新编程

represents a potential cure, not just a treatment.

代表的不只是治疗方式， 更是可能的解药。

OK, but what about right now?

好的，但现在呢？

If from this very moment forward,

如果从此刻以后，

each and every one of you left this talk

在座各位听完演讲后，

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

真的相信思想完完全全 源自你的大脑细胞，

then we could immediately get rid of negative perceptions and stigmas

那么我们可以立马甩掉 消极的观念和污名，

that prevent so many people

不再阻止许多人

from getting the mental health support that they need.

获得他们所需的心理健康支持。

Mental health professionals,

心理健康专业人士

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

总是在想，下一个新的疗法是什么，

But before we can apply new treatments,

但在我们应用新的疗法之前，

we need people to feel comfortable seeking them.

我们需要让人们能自在地寻求它们。

Imagine how dramatically we could reduce the rates of suicides

想象一下，只需让那些需要 心理治疗的人获得帮助，

and school shootings

我们能把自杀率

if everyone who needed mental health support actually got it.

和校园枪击案降低多少。

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

当我们真正了解思想是 如何从大脑诞生的，

we will improve the lives of everyone

我们就能为将来人生中

who will have a mental illness in their lifetime --

会出现心理疾病的每个人 改善他们的生活——

half the population --

他们占半数的人口——

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

也能改善其他与之共享 这个世界的人们的生活。

Thank you.

谢谢。

(Applause)

（掌声）