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  • 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 )

Man: We're gonna talk about a pivotal moment

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ナショナルジオグラフィックライブ! - 脳のマッピング (National Geographic Live! - Mapping the Brain)

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    稲葉白兎 に公開 2021 年 01 月 14 日
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