Trailblazers in neuroscience Dr. Christof Koch and Dr. John Donoghue reveal mind-blowing insights on how the brain turns thought into voluntary behaviors and how that knowledge is empowering victims of neurological trauma with regained physical abilities.
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Transcript
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.
Christof Koch: 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.
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... Very reliable, on each trial. The
neuron didn't respond at the time she was married to another famous
actor, and, uh... 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... 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.
John Donoghue: 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. Imagine you're opening your hand. Relax. Close
your hand.
Donoghue: See, it shuts off.
Man: Relax. 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. 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.” 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. 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.