 Man: We're gonna talk
 about a pivotal moment
 that we're at in
 the history of neuroscience,
 in the history
 of science really,
 because scientists
 are helping to decipher
 what you could arguably say
 is the most complex structure
 in the universe.
( applause )
When I was still
a tenured professor,
now I'm just a mere mortal,
when I was still
a tenured professor at Caltech
and I could leap over
tall buildings,
I was, um... My main pursuit
was studying consciousness
the neural basis
of consciousness.
And in particular I felt
the best way to pursue that
was to work on theoretical
ideas, but also to pursue
experiments in humans,
'cause if there's one thing
we know for certain
about consciousness,
is that most of us are
conscious most of the time.
In order to understand
anything about the brain
and ultimately about psychology,
we have to understand neurons.
We know a lot about nerve cells
in post-mortem, in dead brains
and of course in animals.
But there's a rare occasion
when you can
actually listen in
to the way neurons
talk to each other,
and that's during neurosurgery.
So in some subset of patients,
that have epileptic seizures,
there's an idea
that if you can locate
from the place in the brain from
which the seizure originates,
and if you can then
surgically remove that,
then in many cases depending on
the type of epileptic seizure
the seizures will go away.
Now in some patients you can't
locate it from the outside,
so then what the neurosurgeon
does, implants up to
12 microelectrodes
into the patient's head.
And so you can
essentially triangulate.
When the patient has a seizure
you can triangulate,
and then you can pinpoint
where the seizure originates.
So now in principle we can
listen to individual neurons.
And I say listen because
the way they talk to each other
is they're sending out
these brief electrical pulses
called action potential
or spikes.
You can put them
on a monitor
and you can actually
listen to them.
( popping noises )
So these are actually neurons,
nerve cells,
in a brain of a patient that
are chatting to each other.
We don't--we're only
beginning to understand
the code that they use
to talk to each other.
But we can pick up
this signal
and it's very similar
in animals.
So the patient is conscious,
you can do all sorts of games
with the patients or you can
show him or her images.
So what we did, we probed
and we showed different things
to the patients because
we wanted to uncover
what is the trigger, what turns
these individual neurons on?
See here, what you can see,
we show this image of a spider,
of an animal,
of the Eiffel Tower,
of a bunch of Kobe Bryant,
of a bunch of other
famous people,
and here, of an actress
called Jennifer Aniston.
Some of you may know her, she's
a famous Hollywood actress.
But now, if you show images
of Jennifer Aniston
the neuron will respond...
( makes buzzing noise )
Very reliable,
on each trial.
The neuron didn't respond
at the time she was married
to another famous actor,
and, uh...
( audience laughing )
And the neuron
didn't respond to that.
This is now in the textbook
and is called
"Jennifer Aniston neurons".
So the idea is that things
that you're very familiar with
like actresses or actors,
politicians,
your spouse, your kids,
your workers, your car,
your dog, anything that
you see again and again
your brain abstracts
and represents
by a bunch of neurons.
Not one, this isn't just one
Jennifer Aniston neuron.
There may be 10,000,
or maybe even more neurons
that respond
relative specifically
to Jennifer Aniston.
And so the idea
is this tells us something
about the way neurons...
The things that
neurons care about.
So in this high-level
part of the brain,
they care about things
that we care about.
It's not surprising. I mean,
we care about abstract things
like people
and the relationship,
or like idea,
concept things
like justice or democracy
or America or Afghanistan,
all those things, and there
will be groups of neurons
that very specifically
respond to that
when you think about
those things.
So you can do a lot of
research at that level.
Um, so this is a neuron.
Here you have its
sort of input region.
This is called
the dendrite, in red.
And then here
at the cell body
there's a lot
of electric machinery
that we understand quite well.
It generates this action--
this pulse
when it's sufficiently excited,
and then it sends out
that pulse onto the wire.
This is the output wire,
it's very complicated.
And every time
there's a connection
this is indicated in yellow
and that's a synapse.
The synapse is a contact point
between two neurons.
And how much one neuron
influences the next neuron
is encoded in the strength
of that synapse.
And all the evidence
shows that a memory,
like the memory
of my first kiss,
or the memory that I know
what Julius Caesar said
when he was killed
by his friend Brutus,
all that sort of memory
is encoded
in the strength of
billions of synapses
that constitute memory
and that also ultimately
give rise to consciousness,
the feeling of something.
What really gives rise to
thought and consciousness
and memories is
the cerebral cortex.
The cerebral cortex
is really a sheet.
It's a pizza.
It's pretty much...
Think of a pizza that's two
to three millimeters thick,
pretty much like my vest here,
two to three millimeter.
It's this size,
and we've got two of them,
but they're highly folded.
And this is
a computational tissue
that evolution invented
roughly 200 million years ago.
It's common to all mammals,
and it gives rise
to our identity, who we are,
our feelings, our memory
our sense of selves.
And we at the Allen Institute
and many, many other scientists
are trying to understand
what is the universal...
what is the,
sort of the algorithm,
what is the computation
that's performed
within this dense forest
of 100 billion neurons?
It's 100 billion trees
that give rise to all of this.
So now what we're gonna do,
we're gonna zoom in
in this last movie
I'll show you.
We're gonna zoom in onto
one piece, a sliver here
that's incredible thin.
It turns out for those of you
who know about numbers,
twelve micrometers
in thickness.
That's maybe a tenth of
the width of a human hair.
It's very, very thin but we're
gonna zoom in, in great detail
because the more we look,
the more details we see.
I show this
because the one thing
that you're confronted with
is overwhelming complexity.
Each new generation
of measurement techniques,
of microscopes, reveals
more and more complexity.
It has to be complex because
ultimately it has to give rise
to the subtlety
of the human mind.
So what we'll see here
is a piece of cortex
from the mouse brain. Here
again is one of those neurons
just like the one
we showed before.
You'll see a whole bunch of
them, so we're gonna take a trip
with cool music,
that starts up here
and that goes
slowly down here.
And it visualizes
every single synapse,
so what you're gonna see
are three colors.
You'll see in high detail,
you see magenta.
Each magenta pointer,
each point is a synapse.
As I said, they are--
In this piece
there's gonna be
a couple of billion synapses.
Green is a subset of one
particular type of neuron,
and the blue color you see
is tubulin.
It's dendrites and axons
of other neurons.
This is one millimeter again,
so the millimeter
is half the size of
the width of a grain of rice.
All right, and now...
( music playing )
So it's a mouse brain.
The common laboratory mouse.
The size of the brain
is roughly a sugar cube.
And that's where
we'll zoom in.
Just remember, the magenta
are the synapses.
The green is
one set of neurons.
They happen to be called
Layer Five for the experts.
And blue is tubulin that
shows the wiring of axons.
And now we'll go
through this cortex.
( applause )
Good evening.
So you might think
after seeing that movie
that it's hopeless, that we
can never understand anything
about something
so complicated.
Um, so what I want to do
is to say that in fact
we have learned enough
not only to understand
some fundamental things
about how the brain works,
but also to intervene in
ways where we can restore
lost functions,
and I want to give you
just two examples
of the kinds of things
that we can do because of
our understanding of the brain.
So the first one
is one in which...
where technology we have
is going to allow us,
allows us to write
into the brain,
to actually do something
to transform the brain
by intervening
in brain circuits.
So, let me just explain.
So every day
when you move around,
your brain is working
to produce movements,
and there's a very important
chemical in your brain
called dopamine that comes
from the bottom of the brain
in the brain stem,
and it comes up
and basically dopamine
is oozed all over your brain,
and in many areas
it's sort of, uh...
...your brain is taking
a bath in dopamine.
In some cases, the dopamine
neurons degenerate, they die.
In fact, in all of us, we
lose a little bit as we age.
But if these neurons die,
the circuits don't work properly
and you get something
that James Parkinson
described in 1817
as "the shaking palsy".
And what happens here is,
you can see this lady
who has lost many of
her dopamine neurons.
She has the shaking palsy.
You have a tremor, you
can't move, you're rigid,
and you have difficulty
initiating movement.
It's a severely
debilitating disease,
and it's because of
the loss of dopamine.
Now we can't put dopamine
back in the brain very well.
There are some pills,
but it doesn't work
exceptionally well
in all cases.
But what we can do,
is we can put
a stimulating electrode about
the size of a small soda straw
that has the ability
to electrically stimulate
at the end,
and we can, by turning on
this stimulator
we can tickle these brain
circuits and make them act
as if they had
dopamine back again,
so they work again.
And as a consequence, we have
a very remarkable result
when we turn on
this stimulation.
So here is the same lady,
after the electrical stimulation
has been turned on,
and you can see
the shaking, the tremor,
the rigidity is gone.
And this is
an amazing reawakening
of these motor circuits.
They are no longer held slave
to this disruption that's there
with the lack of dopamine.
This kind of intervention
in brain circuits
to rebalance, or what
we call "neuromodulation",
modulating these brain
circuits back to normal,
is now being tried in a large
number of other disorders,
and as far ranging as dementia,
Alzheimer's disease.
Imagine now we could
bring that circuit back
into control so that instead
of having cognitive decline,
you could allow a person
to retain their memory
throughout life
instead of losing it
as happens with
Alzheimer's disease.
So the second disorder
I want to tell you about
is the loss of the ability
to move, paralysis.
And there are a large number of
ways you can become paralyzed,
and that basically cuts off
a brain that functions
from the body.
So, let's just sort of see
what happens when you move.
So basically, when
you're thinking about
planning to say, pick up a pen
and jot down a phone number
or take some notes here,
your brain, many areas of
your brain collaborate together
and work to produce a plan and
that plan is turned into action,
and it largely engages
this one important area
called the motor cortex.
It's a strip that runs
from the top of your head
down to your cheekbone,
about an inch wide or so.
And if you're thinking
about jotting down a note
to control your arm,
there's a region at about
the middle third of this area
that controls your arm.
And that sends out a bundle
of fibers, these axons.
It's a compact bundle about
the size of a pencil lead
that has a million
of these fibers.
It runs down
through the brain stem
and down into
your spinal cord,
and it's the requisite pathway,
it's the important pathway
to send commands from your brain
to move out to your muscles.
So, for example, if you were
to have a spinal cord injury,
that would interrupt this path
you would be paralyzed.
You couldn't move
your arms and legs.
If it was the whole path
destroyed, you would think
about moving, but
nothing would happen.
We call that tetraplegia.
And even more devastating
damage can happen
with destruction
in the brain stem,
where it still interrupts
the pathways, but because
it's higher up in the brain,
it not only will
render a person tetraplegic,
they cannot speak
and sometimes they can't move
at all in the worse condition.
We call that
a locked-in syndrome.
They can only move their eyes
up and down and that's it.
So, I'm gonna tell you
about two people.
Cathy Hutchinson,
who had a brain stem stroke
about 15 years before
this picture was taken
when she was sitting
on her couch.
She was completely
locked-in for a while,
and then was able to move
her face and eyes and head,
but not able
to speak any longer
and not able to move.
And Matt Nagle had
a spinal cord injury
when he was involved in a fight
and a knife went into his neck
and severed his spinal cord.
So he can talk
and he can move his head
but he cannot
move his body at all.
And what I'm going
to tell you about
is a project which
we call "Braingate",
but it's a kind of
brain-computer interface.
Our attempt to take signals
from the motor cortex,
take them outside the body
and allow people to run machines
and control devices
to free them up,
to give them independence
to control again.
And what we do is we have
created this electrode array
that is implanted in the arm
area of your motor cortex.
Now the electrode array
is a tiny,
baby aspirin-sized implant,
and it has a lot of these
little prongs sticking out.
These are electrodes
that are actually inserted
into the cortex to get up
close to these neurons
that you just saw.
And the reason we have to
put this into the brain
is the action potentials,
the spikes,
the electrical impulses that
come out of individual neurons
only go a very short distance.
So in order for us to
listen in to those impulses
we have to put electrodes
up very close.
But those impulses are
the message of movement.
So what I'm gonna do
is let you listen in
to a recording
in which a technician
is telling... In this case,
it's Cathy,
he's telling her to imagine
opening and closing your hand,
and you'll hear the spikes
change their firing rate.
So it'll get higher and lower,
and you can hear that there is,
in fact, a code there.
High means that
the hand is open,
and low means
the hand is closed.
So just listen in
for a second.
 Man: Relax.
( popping noises )
 Imagine you're
 opening your hand.
 Relax.
 Close your hand.
Donoghue: See, it shuts off.
 Man: Relax.
( popping resumes )
 Open your hand.
So, this is the basis of
the device that we've created.
Not only recording
from one cell,
but taking the pattern
of many, many neurons
and trying to relate what
the person is thinking about
to what something
in the real world will do.
And this is the set-up
that we have.
The person has
this electrode array
implanted in their arm area
of the motor cortex,
We have now in this rather
crude, primitive version
because it's just
an early stage version,
they had a plug in their head.
The electronics
are connected by a cable
that amplifies those
little, tiny signals,
takes them through a computer
and the computer basically
counts up and measures
those spikes,
and tries to figure out,
well, that means up,
or that means open
or that means closed.
And what I'm gonna do
is show you some videos
that show what the patients
have been able to do.
Of course, we were
very excited,
and we asked Matt to do
a whole bunch of things
Here, he is gonna
draw a circle, then he's
gonna tell us what it's like to
be able to control something.
So he's controlling that
cursor with his thoughts.
And this is actually the
world's first art, I think.
Neurally drawn circle.
Oh, man, I can't
put it into words.
It just...
I used my brain...
I just thought it.
I said, "Cursor,
go up to the top right"
and it did.
And now I got control of it
all over the screen.
-It's wild.
-Actually, this is...
He was using his consciousness
to manipulate his neurons,
but he actually didn't really
understand what was going on.
Something happens
when you think,
and it manifests
as those spike changes,
but what's really going on
is the mystery.
So, he hadn't moved anything
in a long time,
so we were able to get
this prosthetic hand.
And it doesn't
really do anything,
it's just a motorized hand
that can open and close,
so we ran a brain command
into it,
and told him tell us
what you're doing,
and imagine opening
and closing that hand.
And you're gonna
hear his reaction
to the first time
he's moved something
in a couple of years
because remember,
he's completely paralyzed.
And you'll listen to
his strong reaction.
Whoa, holy shit.
( audience laughing )
So, just if you missed that.
Whoa, holy shit.
Close.
Nice. Open.
Close.
Not bad, man.
Not bad at all.
He really became a star
by doing these things.
Now, of course those aren't
very practical actions,
and what we really want
to do is enable people
to do things
that are meaningful,
and for people like Cathy,
who can't speak,
communication is
extremely important.
So, my colleague Leigh Hochberg
and others in our group
have created...
If you can move a cursor,
you can choose
words on a screen.
Instead of using a keyboard
in which you have to move
a cursor all over the screen,
we made a radial keyboard
with word prediction,
and this is actually Cathy
spelling out a sentence.
So just to show that
she can use this spelling
interface to convey messages.
But we'd really like to see
something even
more sophisticated
to do things that you can't--
she can't do.
She can't do things
with her arms.
So here, Cathy is
controlling a robot arm
and we're doing
something simple.
We just elevated
these little foam balls
and told her to reach out
and grab them.
And because of our ability
to make some sense
of the way the arm is coded
and reaching space,
she was able to do that.
So what we did is we said,
"Let's do something practical
and meaningful for you."
And so we gave her
her morning coffee,
and we said, "Okay, Cathy,
for the first time
in 15 years you're gonna feed
yourself your morning coffee
and not have to rely
on another person
to come in and do that."
So, here she is with
the control of the robotic arm,
on her own taking her
first drink of coffee.
We found out in the afternoon
she actually sometimes had
Kahlua in the coffee as well.
( audience laughing )
Of course, they only use it
in a research setting so far.
What we want to do is make it
available all the time.
And in fact, what we
really want to do
and really strive to do
over the coming decades
is to be able to take
a person who can't move
and reanimate
their own muscles.
To basically create
a physical nervous system
where their biological one
is irreparable.
So here's an example of
what we're aiming to do.
The idea here is that
there's an implanted array.
It generates signals, it
comes down to something like
a smartpack on your belt
like a cell phone,
that then communicates to
an electric nervous system
and it activates a stimulator
which then stimulates
the nerves and causes
the muscles to activate.
So it's what your nervous
system normally does,
but it's all done with
physical components.
And one of the next
important steps
is to create something that
is basically a smartphone
inside the head, and
my colleague Arto Nurmikko
has created this device,
which is something
that will allow us
to wirelessly transmit
all of those complex
brain signals outside.
And here in now
nice, bloodless surgery
done in a kitchen no less,
there's the implant.
The transmitter sits
underneath the skin
and it transmits
all that information out.
And this is not
in humans yet,
but it will be
in the next coming years,
but has been
tested in animals.
And this is feasible now.
It has more sophistication than
what you have in your cell phone
to be able to communicate,
be able to tell us
what's going on,
and to get that information
to the outside.
So, this is coming, the ability
to rewire the nervous system.
And I asked Cathy
to send me a note
about what does it mean...
What would she like to do again.
And so she sent me this note,
she typed it out:
"I would love to garden again.
I really miss gardening,
canning and cooking.
I also wanted to be able
to hold a book with both hands,
or even a robot arm.
I really hope someday
I'll be able to use my voice.
I can handle paralysis,
but lack of communication
is torture. Thank you."
So, I would say thanks to them,
these brave patients
and thank you. I think
I'll conclude with that.
( applause )
