What investigating neural pathways can reveal about mental health
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0:01 - 0:05I'm going to start by saying something
you think you know to be true. -
0:07 - 0:10Your brain creates
all facets of your mind. -
0:11 - 0:15So then why do we treat
mental and physical illnesses -
0:15 - 0:16so differently,
-
0:16 - 0:19if we think we know
that the mind comes from the brain? -
0:20 - 0:22As a neuroscientist, I'm often told
-
0:22 - 0:25that I'm not allowed to study
how internal states -
0:25 - 0:29like anxiety or craving or loneliness
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0:29 - 0:30are represented by the brain,
-
0:30 - 0:34and so I decided to set out
and do exactly that. -
0:36 - 0:39My research program is designed
to understand the mind -
0:39 - 0:41by investigating brain circuits.
-
0:41 - 0:45Specifically, how does our brain
give rise to emotion. -
0:46 - 0:49It's really hard to study
feelings and emotions, -
0:49 - 0:51because you can't measure them.
-
0:51 - 0:56Behavior is still the best and only window
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0:56 - 0:58into the emotional experience of another.
-
0:59 - 1:02For both animals and people,
-
1:02 - 1:04yes, self-report is a behavioral output.
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1:06 - 1:09Motivated behaviors
fall into two general classes: -
1:09 - 1:11seeking pleasure and avoiding pain.
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1:12 - 1:15The ability to approach things
that are good for you -
1:15 - 1:16and avoid things that are bad for you
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1:16 - 1:18is fundamental to survival.
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1:18 - 1:19And in our modern-day society,
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1:19 - 1:23trouble telling the difference
can be labeled as a mental illness. -
1:24 - 1:26If I was having car trouble,
-
1:26 - 1:28and I took my car to the mechanic,
-
1:28 - 1:32the first thing they do
is look under the hood. -
1:33 - 1:35But with mental health research,
-
1:35 - 1:38you can't just pop open the hood
with the press of a button. -
1:39 - 1:42So this is why we do
experiments on animals. -
1:42 - 1:44Specifically, in my lab, mice.
-
1:46 - 1:49To understand the brain, well,
we need to study brains. -
1:50 - 1:53And for the first time, we actually can.
-
1:53 - 1:54We can pop open the hood.
-
1:54 - 1:56We can look inside
-
1:56 - 1:58and do an experiment
and see what comes out. -
2:00 - 2:05Technology has opened new windows
into the black box that is our minds. -
2:05 - 2:09The development of optogenetic tools
-
2:09 - 2:13has allowed us unprecedented control
over specific neurons in the brain -
2:13 - 2:17and how they talk to each other
by firing electrical signals. -
2:18 - 2:21We can genetically engineer neurons
to be light sensitive -
2:21 - 2:25and then use light to control
how neurons fire. -
2:25 - 2:28This can change an animal's behavior,
-
2:28 - 2:31giving us insight
into what that neural circuit can do. -
2:32 - 2:35Want to know how scientists
figure this out? -
2:36 - 2:39Scientists developed optogenetic tools
by borrowing knowledge -
2:39 - 2:41from other basic science fields.
-
2:42 - 2:47Algae are single-celled organisms
that have evolved to swim towards light. -
2:47 - 2:51And when blue light shines
onto the eyespot of an algae cell, -
2:51 - 2:54a channel opens,
sending an electrical signal -
2:54 - 2:55that makes little flagella flap
-
2:55 - 2:58and propels the algae towards sunlight.
-
2:58 - 3:02If we clone this light-sensitive
part of the algae -
3:02 - 3:05and then add it to neurons
through genetic modification, -
3:05 - 3:08we can make neurons light-sensitive, too.
-
3:09 - 3:11Except, with neurons,
-
3:11 - 3:14when we shine light down
an optical fiber deep into the brain, -
3:14 - 3:18we change how they send electrical signals
to other neurons in the brain -
3:18 - 3:21and thus change the animal's behavior.
-
3:22 - 3:24With the help of my colleagues,
-
3:24 - 3:27I pioneered the use of optogenetic tools
-
3:27 - 3:30to selectively target neurons
that are living in point A, -
3:30 - 3:34sending messages down wires
aimed at point B, -
3:36 - 3:39leaving neighboring neurons
going other places unaffected. -
3:40 - 3:44This approach allowed us to test
the function of each wire -
3:44 - 3:47within the tangled mess that is our brain.
-
3:48 - 3:50A brain region called the amygdala
-
3:50 - 3:52has long been thought
to be important for emotion, -
3:52 - 3:54and my laboratory discovered
-
3:54 - 3:56that the amygdala
resembles a fork in the road -
3:56 - 4:00where activating one path
can drive positive emotion and approach, -
4:00 - 4:05and activating another path
can drive negative emotion and avoidance. -
4:07 - 4:09I'm going to show you
a couple of examples -- -
4:09 - 4:11a taste of raw data --
-
4:11 - 4:15of how we can use optogenetics
to target specific neurons in the brain -
4:15 - 4:18and get very specific changes in behavior.
-
4:18 - 4:21Anxiety patients
have abnormal communication -
4:21 - 4:24between two parts of the amygdala,
-
4:24 - 4:29but in people, it's hard to know
if this abnormality is cause or effect -
4:29 - 4:30of the disease.
-
4:31 - 4:36We can use optogenetics
to target the same pathway in a mouse, -
4:36 - 4:37and see what happens.
-
4:37 - 4:40So this is the elevated plus maze.
-
4:40 - 4:41It's a widely used anxiety test
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4:41 - 4:43that measures the amount of time
-
4:43 - 4:46that the mouse spends in the safety
of the closed arms -
4:46 - 4:48relative to exploring the open arms.
-
4:49 - 4:52Mice have evolved to prefer
enclosed spaces, -
4:52 - 4:54like the safety of their burrows,
-
4:54 - 4:56but to find food, water, mates,
-
4:56 - 4:59they need to go out into the open
-
4:59 - 5:02where they're more vulnerable
to predatory threats. -
5:02 - 5:04So I'm sitting in the background here,
-
5:04 - 5:06and I'm about to flip the switch.
-
5:06 - 5:09And now, when I flip the switch
and turn the light on, -
5:09 - 5:13you can see the mouse begins to explore
the open arms of the maze more. -
5:14 - 5:18And in contrast
to drug treatments for anxiety, -
5:18 - 5:21there's no sedation,
no locomotor impairment, -
5:21 - 5:25just coordinated,
natural-looking exploration. -
5:25 - 5:29So not only is the effect
almost immediate, -
5:29 - 5:32but there are no detectable side effects.
-
5:32 - 5:34Now, when I flip the switch off,
-
5:34 - 5:38you can see that the mouse goes back
to its normal brain function -
5:38 - 5:39and back to its corner.
-
5:40 - 5:44When I was in the lab
and I was taking these data, -
5:44 - 5:47I was all by myself, and I was so excited.
-
5:48 - 5:50I was so excited,
I did one of these quiet screams. -
5:50 - 5:52(Silently) Aah!
-
5:52 - 5:54(Laughter)
-
5:54 - 5:55Why was I so excited?
-
5:55 - 5:59I mean, yeah, theoretically,
I knew that the brain controlled the mind, -
5:59 - 6:01but to flip the switch with my hand
-
6:01 - 6:03and see the mouse
change its behavioral state -
6:03 - 6:06so rapidly and so reversibly,
-
6:06 - 6:09it was really the first time
that I truly believed it. -
6:10 - 6:12Since that first breakthrough,
-
6:12 - 6:15there have been a number
of other discoveries. -
6:15 - 6:18Finding specific neural circuits
that can elicit dramatic changes -
6:18 - 6:20in animal behavior.
-
6:21 - 6:24Here's another example:
compulsive overeating. -
6:25 - 6:27We can eat for two reasons.
-
6:27 - 6:29Seeking pleasure, like tasty food,
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6:29 - 6:32or avoiding pain, like being hungry.
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6:33 - 6:36How can we find a treatment
for compulsive overeating -
6:36 - 6:38without messing up
the hunger-driven feeding -
6:38 - 6:40that we need to survive?
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6:40 - 6:42The first step is to understand
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6:43 - 6:46how the brain gives rise
to feeding behavior. -
6:46 - 6:50This fully-fed mouse
is just exploring a space -
6:50 - 6:53completely devoid of any food.
-
6:54 - 6:57Here we're using optogenetics to target
neurons living in the hypothalamus, -
6:57 - 7:01sending messages down wires
aimed at the midbrain. -
7:02 - 7:05When I turn the light on, right here,
-
7:05 - 7:09you can see that the mouse
immediately begins licking the floor. -
7:09 - 7:11(Laughter)
-
7:13 - 7:15This seemingly frenzied behavior
-
7:15 - 7:19is about to escalate into something
I find really incredible. -
7:19 - 7:21It's kind of trippy, actually.
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7:22 - 7:23Ready?
-
7:23 - 7:25It's right here.
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7:26 - 7:30See, he picks up his hands
as if he is eating a piece of food, -
7:30 - 7:32but there's nothing there,
he's not holding anything. -
7:32 - 7:36So this circuit is sufficient
to drive feeding behavior -
7:36 - 7:38in the absence of hunger,
-
7:38 - 7:40even in the absence of food.
-
7:42 - 7:44I can't know for sure
how this mouse is feeling, -
7:44 - 7:47but I speculate
these neurons drive craving -
7:47 - 7:51based on the behaviors we elicit
when we target this pathway. -
7:53 - 7:54Turn the light back off --
-
7:54 - 7:56animal's back to normal.
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7:57 - 8:00When we silence this pathway,
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8:00 - 8:03we can suppress and reduce
compulsive overeating -
8:03 - 8:06without altering hunger-driven feeding.
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8:09 - 8:11What did you take away
from these two videos -
8:11 - 8:12that I just showed you?
-
8:12 - 8:16That making a very specific change
to neural circuits in the brain -
8:16 - 8:19can have specific changes to behavior.
-
8:19 - 8:22That every conscious
experience that we have -
8:22 - 8:25is governed by cells in our brain.
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8:27 - 8:31I am the daughter
of a physicist and a biologist, -
8:31 - 8:34who literally met on the boat
coming to America -
8:34 - 8:36in pursuit of an education.
-
8:37 - 8:38So naturally,
-
8:38 - 8:41since there was "no pressure"
to be a scientist ... -
8:41 - 8:44(Laughter)
-
8:44 - 8:45as a college student,
-
8:45 - 8:50I had to decide whether I wanted to focus
on psychology, the study of the mind, -
8:50 - 8:53or neuroscience, the study of the brain.
-
8:53 - 8:54And I chose neuroscience,
-
8:55 - 8:57because I wanted to understand
how the mind is born -
8:57 - 8:59out of biological tissue.
-
8:59 - 9:02But really, I've come
full circle to do both. -
9:02 - 9:04And now my research program
-
9:04 - 9:06bridges the gap between
the mind and the brain. -
9:07 - 9:09Research from my laboratory
-
9:09 - 9:12suggests that we can begin
to tie specific neural circuits -
9:12 - 9:14to emotional states.
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9:14 - 9:16And we have found a number of circuits
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9:16 - 9:19that control anxiety-related behavior,
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9:19 - 9:20compulsive overeating,
-
9:20 - 9:23social interaction, avoidance
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9:23 - 9:25and many other types
of motivated behaviors -
9:25 - 9:28that may reflect internal
emotional states. -
9:30 - 9:34We used to think of functions of the mind
as being defined by brain regions. -
9:35 - 9:37But my work shows
that within a given brain region, -
9:37 - 9:40there are many different neurons
doing different things. -
9:40 - 9:45And these functions
are partly defined by the paths they take. -
9:46 - 9:48Here's a metaphor to help illustrate
-
9:48 - 9:52how these discoveries change the way
that we think about the brain. -
9:53 - 9:57Let's say that the brain
is analogous to the world -
9:57 - 9:59and that neurons are analogous to people.
-
9:59 - 10:04And we want to understand how information
is transmitted across the planet. -
10:05 - 10:07Sure, it's useful to know
-
10:07 - 10:10where a given person is located
when recording what they're saying. -
10:11 - 10:13But I would argue
that it's equally important -
10:13 - 10:16to know who this person is talking to,
-
10:16 - 10:17who is listening
-
10:17 - 10:21and how the people listening respond
to the information that they receive. -
10:22 - 10:24The current state
of mental health treatment -
10:24 - 10:27is essentially a strategy
of trial and error. -
10:28 - 10:30And it is not working.
-
10:31 - 10:35The development of new drug therapies
for mental health disorders -
10:35 - 10:36has hit a brick wall,
-
10:36 - 10:40with scarcely any real progress
since the 1950s. -
10:41 - 10:43So what does the future hold?
-
10:43 - 10:45In the near future,
-
10:45 - 10:48I expect to see a mental health
treatment revolution, -
10:48 - 10:51where we focus on specific
neural circuits in the brain. -
10:51 - 10:55Diagnoses will be made
based on both behavioral symptoms -
10:55 - 10:57and measurable brain activity.
-
10:58 - 11:00Further in the future,
-
11:00 - 11:04by combining our ability
to make acute changes to the brain -
11:04 - 11:06and get acute changes to behavior
-
11:06 - 11:10with our knowledge of synaptic plasticity
to make more permanent changes, -
11:10 - 11:14we could push the brain
into a state of fixing itself -
11:14 - 11:16by reprogramming neural circuits.
-
11:17 - 11:20Exposure therapy at the circuit level.
-
11:21 - 11:24Once we switch the brain
into a state of self-healing, -
11:24 - 11:27this could potentially have
long-lasting effects -
11:27 - 11:29with no side effects.
-
11:30 - 11:33I can envision a future
where neural circuit reprogramming -
11:33 - 11:37represents a potential cure,
not just a treatment. -
11:40 - 11:43OK, but what about right now?
-
11:44 - 11:46If from this very moment forward,
-
11:46 - 11:48each and every one of you left this talk
-
11:49 - 11:54and truly believed that the mind
comes entirely from cells in your brain, -
11:54 - 11:58then we could immediately get rid
of negative perceptions and stigmas -
11:58 - 11:59that prevent so many people
-
11:59 - 12:02from getting the mental health
support that they need. -
12:02 - 12:03Mental health professionals,
-
12:03 - 12:06we're always thinking
about what's the next new treatment. -
12:06 - 12:09But before we can apply new treatments,
-
12:09 - 12:12we need people to feel
comfortable seeking them. -
12:13 - 12:17Imagine how dramatically
we could reduce the rates of suicides -
12:17 - 12:19and school shootings
-
12:19 - 12:23if everyone who needed
mental health support actually got it. -
12:24 - 12:30When we truly understand
exactly how the mind comes from the brain, -
12:30 - 12:32we will improve the lives of everyone
-
12:32 - 12:35who will have a mental illness
in their lifetime -- -
12:35 - 12:36half the population --
-
12:36 - 12:40as well as everyone else
with whom they share the world. -
12:41 - 12:42Thank you.
-
12:42 - 12:47(Applause)
- Title:
- What investigating neural pathways can reveal about mental health
- Speaker:
- Kay Tye
- Description:
-
Neuroscientist Kay M. Tye investigates how your brain gives rise to complex emotional states like depression, anxiety or loneliness. From the cutting edge of science, she shares her latest findings -- including the development of a tool that uses light to activate specific neurons and create dramatic behavioral changes in mice. Learn how these discoveries could change the way you think about your mind -- and possibly uncover effective treatments for mental disorders.
- Video Language:
- English
- Team:
- closed TED
- Project:
- TEDTalks
- Duration:
- 12:59
marialadias edited English subtitles for What investigating neural pathways can reveal about mental health | ||
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Ivana Korom edited English subtitles for What investigating neural pathways can reveal about mental health |