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

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after suffering for a very
long time from a stroke.

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One day, she collapsed.

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A few days later she woke up
in the hospital

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

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

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but it had a life-altering
implication for her

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where now she could
no longer move her own body.

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

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and went through extensive
rehabilitation therapy,

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at the end of which she could barely walk

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on her own with an extensive
help of a walker.

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

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before she passed away this year.

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Watching her suffer through this very
painful and devastating disease,

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

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

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to give her back what she had lost

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when the small blood vessel
burst in her head

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

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

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what do we do?

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

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

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Well, yes, I sometimes do that.

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

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

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If there is a broken software,
we reprogram it.

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If there is a broken wire, we rewire it.

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

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

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There are many different forms
of brain diseases.

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Some of which includes the following.

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

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There's also a disease called epilepsy,

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where you suddenly have
uncontrollable activity

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that happens inside your brain
without any warning,

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where you are no longer able to
control yourself.

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

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but this is something
that can happen to any of you

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

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Another important brain disease,
psychiatric disease,

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includes depression, where you feel
hopelessness and sadness.

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There is also a form called autism,

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where children find it difficult
to relate to other people.

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And there's also a category of
neurodegenerative diseases,

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which includes Parkinson's
and Alzheimer's disease,

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where in the Parkinson's disease case

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

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and in the case of Alzheimer's disease,

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

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While there are these many forms
of neurological diseases,

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

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Despite the increasing
prevalence and cost,

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

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You see all of these numbers
on the screen?

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These are very, very large numbers.

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For example,
in the Alzheimer's disease case,

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we are expected to spend
about 1.1 trillion dollars by 2050

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on treating Alzheimer's disease

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

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and we just keep providing support.

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This is over 6% of the US GDP.

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This is not a sustainable number.

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

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we also need to have a solution for this

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

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

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The answer to that boils down
to this one question:

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How does the brain work?

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Does anybody have an answer to that?

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Unfortunately, none of us do.

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

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the task of trying to fix it
becomes impossible.

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Well, it's too early to give up.

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

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to perhaps fix this situation.

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First thing that we know about the brain

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

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This is a very special kind of cell.

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

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And these inputs are
processed inside the cell,

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

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what's called an action potential,

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

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

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And many of these neurons
are put together in our brain

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forming a brain circuit.

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And this brain circuit
does dynamic electrical signaling

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

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So, then the task is pretty simple now.

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What we need to do is to understand

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how exactly these neuronal circuits work
to elicit our behaviors

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and perhaps fix it when it goes wrong.

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

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

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Let's look at some of these reasons.

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Some of these reasons are quite obvious.

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

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This is there to protect our brain.

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

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it makes it extremely difficult.

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

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

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

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which is that it has extreme complexity.

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

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

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you can think of the world's population.

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

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

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

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

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but there are also many different
kinds of neurons.

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

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And they are densely
intermingled inside your brain,

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where you can't really say

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this part of your brain
has this type of neuron,

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and the other part
has another kind of neuron.

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To make matters worse on top of that,

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every one of your neurons,

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they don't just talk to
neighbors surrounding them,

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

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making very large-scale connections,

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

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

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And so all of this combined,

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

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However, given this situation,

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

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of understanding this brain.

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If you want to understand
a complex system,

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there are many different approaches.

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But let's think of two different ones.

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

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Let's say this is a cell phone.

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

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is to sit there and passively
observe what happens.

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Depending on whose cell phone I gave you,

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you might sit there for hours
and nothing happens,

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and conclude that it's actually a clock.

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A much better way to try and understand

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and get meaningful information
out of a system

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is to try and play with them.

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

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

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if you press a button
and see what happens,

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

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So to do something like that
for the brain,

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what we need to be able to do,

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

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and measure its dynamic activity
across this whole intact system.

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

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We need two components.

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

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

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and that they communicate
with electrical signal.

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If you put an electrode

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

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and put an input into this brain.

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But because there are
many different cell types,

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it is very difficult
to decipher what that means.

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For example, if you are trying
to figure out

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the volume up and down button
on your cell phone,

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

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It might not do anything.

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It might go up, it might go down.

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

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

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and see that one button increases volume,

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the other one decreases the volume,

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which gives you a clear idea
of what that does.

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And so to have something
similar for the brain,

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

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What this does is genetically engineer
the cells inside the brain

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

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responds to light upon stimulation.

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That way, now we have a tool

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to specifically press
a button in our brain

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so that we might understand what it does.

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To give you an example of what this means,

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we'll look at an experiment

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where we stimulate
two different types of neurons

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that are placed in the same location
within the brain.

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These are called medium spiny neurons.

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

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but these two neurons
are placed in the same location,

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

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And what this does is, upon stimulation,

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even though these are
neurons in the same location,

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

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

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and generally increases activity.

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And in the other case,

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

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and it will stay generally still,

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

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

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

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have volume up and down buttons separately

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so that we might understand
what this does.

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That's great!

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We have one problem solved

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

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

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

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To do that, we combine
this optogenetics stimulation technology

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with the functional MRI methods,

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where we can now selectively control
specific cell types

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with temporal precision in a live subject.

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You want to monitor this in a live brain

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

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and monitor its brain wave
activity responses.

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And so here is an example
of an experiment

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where we can now stimulate -

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You see the blue line in the image there?

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This is where we specifically target
a set of neurons

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that are called excitatory neurons
of the hippocampus.

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This is a very special area of the brain

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that is implicated
in Alzheimer's disease and epilepsy

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and other important neurological disease.

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

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

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all the way throughout.

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

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as a result of provoking
this particular type of neuron.

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What this means for us 
is that now we have tools

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to start and investigate, see,

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

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What this means is
that we now can perhaps open

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a new era of neuro-
information technology.

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

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

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

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Where in the case of diseases,

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

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

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

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is called neurostimulation therapy.

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Because the brain is
an electrical circuit,

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

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we attempt to get rid of the symptoms,

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such as tremoring in
the Parkinson's disease,

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and restore its normal function.

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The keyword here is "disrupt."

246
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We call it disrupt because we really
don't know what we're doing.

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It was doing something
that we didn't like.

248
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We put it there and zapped it,

249
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and somehow it gave us
a desirable result - sometimes.

250
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But now that we have access to
information directly inside the brain.

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What this means is
that, instead of disrupting,

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we can reprogram what our brain can do.

253
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On top of that,

254
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if the damage was more extensive,
where you actually need to replace parts,

255
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which is what stem cell
therapy promises us,

256
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despite the fact that we have
the powerful stem cell therapy option,

257
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one of the reasons
why we could not make progress

258
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in treating brain disease
with the stem cell therapy

259
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was the fact that there was
no way to know exactly

260
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what it does once it enters the brain.

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And by having programmable stem cells

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

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

264
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And so with all of these technologies

265
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that allows us to get into the realm
of neuro-information technology,

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we might be able to open a new era

267
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where we no longer need to be frustrated

268
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with our inability
to control our own brains.

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Beyond being able to fix diseases,

270
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the future of being able to have access to
neurological information and data

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promises much more
than just treating diseases.

272
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This is one of my favorite scenes
from the movie "Avatar"

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

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

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

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but by having the ability to access
your neurological information,

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

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It deeply saddens me to think
about the fact that

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

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However, it is my hope and dream

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that she will live on in our memory

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

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Thank you very much.

284
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(Applause)