Neuro Information Technology: Can We Take Control of Our Brain Circuit | Jin Hyung Lee | TEDxKFAS

This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at http://ted.com/tedx

When our brain circuits fail, the outcome is life shattering. We lose our ability to remember, walk, talk, or even breathe. While we now live in a world where we can access information and make contact with people everywhere in real time, currently available solutions to brain disease are extremely limited. Neuro information technology expert Dr. Jin Hyung Lee shares a moving personal story that inspires her to find cures for brain disease and help us take control of our brain circuit.

Dr. Jin Hyung Lee is Assistant Professor of Neurology and Neurological Sciences, Bioengineering, Neurosurgery, and Electrical Engineering (Courtesy) at Stanford University. She received her Bachelor’s degree from Seoul National University and Masters and Doctoral degree from Stanford, all in Electrical Engineering. She is a recipient of the 2010 NIH Director’s New Innovator Award, the 2011 NSF CAREER Award, the 2012 Alfred P. Sloan Research Fellowship, the 2012 Epilepsy Therapy Project award, the 2013 Alzheimer’s Association New Investigator Award, and the 2014 IEEE EMBS BRAIN young investigator award.

My beloved grandmother passed away
earlier this year on February 28th

after suffering for a very
long time from a stroke.

One day, she collapsed.

A few days later she woke up
in the hospital

to find herself completely paralyzed
on the right side of her body.

It was just a small little vessel
that burst inside her head,

but it had a life-altering
implication for her

where now she could
no longer move her own body.

For the next three-and-a-half years
she was hospitalized,

and went through extensive
rehabilitation therapy,

at the end of which she could barely walk

on her own with an extensive
help of a walker.

Then, she returned home and stayed
bed-bound for another eight years

before she passed away this year.

Watching her suffer through this very
painful and devastating disease,

the most difficult thing,
the most painful thing for me,

was the fact that there was nothing
that any of us could do

to give her back what she had lost

when the small blood vessel
burst in her head

so that she can have control
over her own body again.

When we have a device broken,
like a computer or a cellphone,

what do we do?

Do we just put it on a place,
comfortable somewhere,

and just press the button repeatedly
until maybe it starts working again?

Well, yes, I sometimes do that.

But if we really want it fixed,
that's not what we should do.

When we have a device broken,
what we do is we directly go in.

If there is a broken software,
we reprogram it.

If there is a broken wire, we rewire it.

If there is a worn out
or broken part, we replace it.

The question is: Can we do
something like this for our own brains?

There are many different forms
of brain diseases.

Some of which includes the following.

It includes stroke, where your blood
vessel bursts and damages your brain.

There's also a disease called epilepsy,

where you suddenly have
uncontrollable activity

that happens inside your brain
without any warning,

where you are no longer able to
control yourself.

And this seems like a very foreign
concept to most of us,

but this is something
that can happen to any of you

by simply hitting your head
in the wrong place at the wrong time.

Another important brain disease,
psychiatric disease,

includes depression, where you feel
hopelessness and sadness.

There is also a form called autism,

where children find it difficult
to relate to other people.

And there's also a category of
neurodegenerative diseases,

which includes Parkinson's
and Alzheimer's disease,

where in the Parkinson's disease case

you start to tremor and you can no longer
control your body movements,

and in the case of Alzheimer's disease,

you have memory loss, where ultimately
you forget even who you are.

While there are these many forms
of neurological diseases,

there is one thing that is
common to all of these.

Despite the increasing
prevalence and cost,

there is one common thing
which is that there is absolutely no cure.

You see all of these numbers
on the screen?

These are very, very large numbers.

For example,
in the Alzheimer's disease case,

we are expected to spend
about 1.1 trillion dollars by 2050

on treating Alzheimer's disease

if we go at the current rate
where we can't cure anything

and we just keep providing support.

This is over 6% of the US GDP.

This is not a sustainable number.

In addition to the fact that we have
the need to treat our loved ones,

we also need to have a solution for this

in order to not get completely bankrupt
by our need to treat our patients.

So the question is: Why do we not know
how to treat any of these diseases?

The answer to that boils down
to this one question:

How does the brain work?

Does anybody have an answer to that?

Unfortunately, none of us do.

And so because we do not know
how the brain works,

the task of trying to fix it
becomes impossible.

Well, it's too early to give up.

Let's think about what we know
and what we can do

to perhaps fix this situation.

First thing that we know about the brain

is the fact that it consists
of this unit called the neurons.

This is a very special kind of cell.

It has inputs that come in with a signal
through what's called the dendrites.

And these inputs are
processed inside the cell,

where it produces an output,
an electrical signal in a digital form,

what's called an action potential,

that is sent throughout the axon
to send this message to the next neuron.

It's a little device
that does this simple processing.

And many of these neurons
are put together in our brain

forming a brain circuit.

And this brain circuit
does dynamic electrical signaling

to control all of the things that we do,
all of our behaviors.

So, then the task is pretty simple now.

What we need to do is to understand

how exactly these neuronal circuits work
to elicit our behaviors

and perhaps fix it when it goes wrong.

As easy as that sounds,
it's actually quite complicated.

There is a very good reason
why we do not have a solution to this.

Let's look at some of these reasons.

Some of these reasons are quite obvious.

One is the fact that our brain
is surrounded by a skull.

This is there to protect our brain.

But for those of us who are trying
to figure out what's going on inside,

it makes it extremely difficult.

All of our fancy microscopic imaging tools
cannot be really used to look inside

because of the fact that
it's surrounded by the skull.

Once you go inside the skull
you have an even greater problem,

which is that it has extreme complexity.

The number of neurons inside your brain
are about a hundred billion.

To give you an idea of what
a hundred billion means,

you can think of the world's population.

A hundred billion is an order of magnitude
larger than the whole world's population.

We talk about big data,
network of all of these different people,

but in fact we have something that's much
more complex sitting inside our skull.

On top of that, I told you about a neuron,

but there are also many different
kinds of neurons.

They're not all the same.
They do different things.

And they are densely
intermingled inside your brain,

where you can't really say

this part of your brain
has this type of neuron,

and the other part
has another kind of neuron.

To make matters worse on top of that,

every one of your neurons,

they don't just talk to
neighbors surrounding them,

they have connections going all the way
to different sides of the brain,

making very large-scale connections,

which means that if you just go in
and look at one part of your brain,

there is no way to understand
what this neuron is doing.

And so all of this combined,

it makes the task of understanding
how the brain works extremely difficult.

However, given this situation,

we need to start thinking about
how we might fix this situation

of understanding this brain.

If you want to understand
a complex system,

there are many different approaches.

But let's think of two different ones.

Let's say I gave you a new device
that was given to you on your hand.

Let's say this is a cell phone.

One way you can try to figure out
what this device is,

is to sit there and passively
observe what happens.

Depending on whose cell phone I gave you,

you might sit there for hours
and nothing happens,

and conclude that it's actually a clock.

A much better way to try and understand

and get meaningful information
out of a system

is to try and play with them.

Press the button, give it input,
and see what happens.

Even if this is a cell phone
that never receives any calls,

if you press a button
and see what happens,

you will know that it makes calls
and that it is a cell phone.

So to do something like that
for the brain,

what we need to be able to do,

is to provide test inputs
to specific parts of the brain circuit

and measure its dynamic activity
across this whole intact system.

So, to do this task, what do we need?

We need two components.

One is to be able to stimulate every
circuit elements with high specificity.

I just told you earlier that the circuit
consists of many different types of cells,

and that they communicate
with electrical signal.

If you put an electrode

- that's one strategy that you can use
to perturb the system -

and put an input into this brain.

But because there are
many different cell types,

it is very difficult
to decipher what that means.

For example, if you are trying
to figure out

the volume up and down button
on your cell phone,

if you press both buttons
at the same time, what would you see?

It might not do anything.

It might go up, it might go down.

You'll be very confused
as to what this button does.

What you need to be able to do
is to press these buttons separately

and see that one button increases volume,

the other one decreases the volume,

which gives you a clear idea
of what that does.

And so to have something
similar for the brain,

there is a novel technology that
allows us to do that called optogenetics.

What this does is genetically engineer
the cells inside the brain

so that only a specific cell type,
only the volume up button,

responds to light upon stimulation.

That way, now we have a tool

to specifically press
a button in our brain

so that we might understand what it does.

To give you an example of what this means,

we'll look at an experiment

where we stimulate
two different types of neurons

that are placed in the same location
within the brain.

These are called medium spiny neurons.

One is a D1 receptor type,
the other is a D2 receptor type,

but these two neurons
are placed in the same location,

and have very important implications
for things like Parkinson's disease.

And what this does is, upon stimulation,

even though these are
neurons in the same location,

when you stimulate one of the neurons
on the left side,

you will see that the mouse starts
to rotate in the clockwise direction,

and generally increases activity.

And in the other case,

you will see that the mouse
starts rotating in the opposite direction,

and it will stay generally still,

where you might even think that the video
has stalled but it actually hasn't.

And so these are two different cell types,
exactly in the same location,

but because we have this new genetic tool,
we could manipulate them separately,

have volume up and down buttons separately

so that we might understand
what this does.

That's great!

We have one problem solved

of being able to specifically manipulate
important buttons of the brain.

Next, what we need is to be able to read
out what is happening inside the circuit.

We want to press this button and
see what happens in the overall system.

To do that, we combine
this optogenetics stimulation technology

with the functional MRI methods,

where we can now selectively control
specific cell types

with temporal precision in a live subject.

You want to monitor this in a live brain

- once you take out the tissue
it doesn't do what it was designed to do -

and monitor its brain wave
activity responses.

And so here is an example
of an experiment

where we can now stimulate -

You see the blue line in the image there?

This is where we specifically target
a set of neurons

that are called excitatory neurons
of the hippocampus.

This is a very special area of the brain

that is implicated
in Alzheimer's disease and epilepsy

and other important neurological disease.

And now by stimulating them specifically
and monitoring what happens throughout -

these are brain images from the front
to the back of the brain,

all the way throughout.

And you can now see what happens
in every part of the brain

as a result of provoking
this particular type of neuron.

What this means for us
is that now we have tools

to start and investigate, see,

have access to the data
of what goes on inside the brain.

What this means is
that we now can perhaps open

a new era of neuro-
information technology.

We no longer have to wonder about:
What is it that the brain does?

Is this a property of the brain?
Is that the property?

Instead, we can have direct access
to the information there.

Where in the case of diseases,

we might attempt to directly restore
what has gone wrong inside the brain.

One of the most promising therapies
that are being tested right now,

and some are being used in
the clinic for brain disease,

is called neurostimulation therapy.

Because the brain is
an electrical circuit,

by putting an electrode inside the brain
and disrupting the erroneous signal,

we attempt to get rid of the symptoms,

such as tremoring in
the Parkinson's disease,

and restore its normal function.

The keyword here is "disrupt."

We call it disrupt because we really
don't know what we're doing.

It was doing something
that we didn't like.

We put it there and zapped it,

and somehow it gave us
a desirable result - sometimes.

But now that we have access to
information directly inside the brain.

What this means is
that, instead of disrupting,

we can reprogram what our brain can do.

On top of that,

if the damage was more extensive,
where you actually need to replace parts,

which is what stem cell
therapy promises us,

despite the fact that we have
the powerful stem cell therapy option,

one of the reasons
why we could not make progress

in treating brain disease
with the stem cell therapy

was the fact that there was
no way to know exactly

what it does once it enters the brain.

And by having programmable stem cells

that we can put in and look at with
access to all the information,

we might be able to also enter an era
where we can replace parts.

And so with all of these technologies

that allows us to get into the realm
of neuro-information technology,

we might be able to open a new era

where we no longer need to be frustrated

with our inability
to control our own brains.

Beyond being able to fix diseases,

the future of being able to have access to
neurological information and data

promises much more
than just treating diseases.

This is one of my favorite scenes
from the movie "Avatar"

where you have the human brain and
the avatar brain that is being synced up.

In this particular scene,
the syncing is 40.665% complete.

This is just a fantasy, a movie,
for us right now,

but by having the ability to access
your neurological information,

the power of what we can do
with that is limitless.

It deeply saddens me to think
about the fact that

I could not help my grandmother
in the time of her desperate need.

However, it is my hope and dream

that she will live on in our memory

as we make bold and brave steps towards
this new era of information technology.

Thank you very much.

(Applause)