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A

Welcome to the Huberman Lab podcast, where we discuss science and science based tools for everyday life.

B

I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, my guest is Doctor Matthew McDougall. Doctor Matthew McDougall is the head neurosurgeon at Neuralink. Neuralink is a company whose goal is to develop technologies to overcome specific clinical challenges of the brain and nervous system, as well as to improve upon brain design, that is, to improve the way that brains currently function by augmenting memory, by augmenting cognition, and by improving communication between humans and between machines and humans. These are all, of course, tremendous goals, and Neuralink is uniquely poised to accomplish these goals because they are approaching these challenges by combining both existing knowledge of brain function from the fields of neuroscience and neurosurgery with robotics, machine learning, computer science, and the development of novel devices in order to change the ways that human brains work for the better. Today's conversation with Doctor Matthew McDougall is a truly special one because I and many others in science and medicine consider neurosurgeons the astronauts of neuroscience and the brain. That is, they go where others have simply not gone before and are in a position to discover incredibly novel things about how the human brain works because they are literally in there probing and cutting, stimulating etcetera, and able to monitor how peoples cognition and behavior and speech changes as the brain itself has changed structurally and functionally. Todays discussion with Doctor McDougall will teach you how the brain works through the lens of a neurosurgeon. It will also teach you about neurolinks specific perspective about which challenges of brain function and disease are immediately tractable, which ones they are working on now. That is, as well as where they see the future of augmenting brain function for sake of treating disease and for simply making brains work better. Today's discussion also gets into the realm of devising the peripheral nervous system. In fact, one thing that you'll learn is that Doctor McDougall has a radio receiver implanted in the periphery of his own body. He did this not to overcome any specific clinical challenge, but to overcome a number of daily, everyday life challenges, and in some ways, to demonstrate the powerful utility of combining novel machines, novel devices with what we call our nervous system and different objects and technologies within the world. I know that might sound a little bit mysterious, but you'll soon learn exactly what I'm referring to. And by the way, he also implanted his family members with similar devices so while all of this might sound a little bit like science fiction, this is truly science reality. These experiments, both the implantation of specific devices and the attempt to overcome specific movement disorders, such as Parkinson's and other disorders of deep brain function, as well as to augment the human brain and make it work far better than it ever has in the course of human evolution, are experiments and things that are happening now at Neuralink. Doctor McDougall also generously takes us under the hood, so to speak, of what's happening at Neuralink, explaining exactly the sorts of experiments that they are doing and have planned, how they are approaching those experiments. We get into an extensive conversation about the utility of animal versus human research in probing brain function and in devising and improving the human brain, and in overcoming disease in terms of neurosurgery and Neuralink's goals. By the end of today's episode, you will have a much clearer understanding of how human brains work and how they can be improved by robotics and engineering, and you'll have a very clear picture of what Neuralink is doing toward these goals. Doctor McDougall did his medical training at the University of California, San Diego, and at Stanford University school of medicine, and of course, is now at neuralink. So he is in a unique stance to teach us about human brain function and dysfunction, and to explain to us what the past, present and future of brain augmentation is really all about. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast.

A

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In fact, in order for your neurons.

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To function properly, all three electrolytes need to be present in the proper ratios. And we now know that even slight reductions in electrolyte concentrations or dehydration of the body can lead to deficits in cognitive and physical performance. Element contains a science back to electrolyte ratio of 1000 milligrams. That's 1 gram of sodium, 200 milligrams of potassium, and 60 milligrams of magnesium. I typically drink element first thing in the morning when I wake up in order to hydrate my body and make sure I have enough electrolytes. And while I do any kind of physical training and after physical training as well, especially if I've been sweating a lot, if you'd like to try element, you can go to drink element. That's lmnt.com huberman to claim a free element sample pack with your purchase. Again, that's drinkelementlmnt.com Huberman Today's episode is also brought to us by waking up. Waking up is a meditation app that includes hundreds of meditation programs, mindfulness trainings, yoga, NiDRa sessions, and NSDR non sleep deep rest protocols. I started using the waking up app a few years ago because even though I've been doing regular meditations since my teens and I started doing yoga Nidra about a decade ago, my dad mentioned to me that he had found an app turned out to be the waking up app, which could teach you meditations of different durations and that had a lot of different types of meditations to place the brain and body into different states and that he liked it very much. So I gave the waking up app a try and I too found it to be extremely useful because sometimes I only have a few minutes to meditate, other times I have longer to meditate. And indeed, I love the fact that I can explore different types of meditation to bring about different levels of understanding about consciousness, but also to place my brain and body into lots of different kinds of states depending on which meditation I do. I also love that the waking up app has lots of different types of yoga Nidra sessions. For those of you who don't know, yoga Nidra is a process of lying very still but keeping an active mind. It's very different than most meditations. And there's excellent scientific data to show that yoga Nidra and something similar to it called non sleep deep rest, or NSDR, can greatly restore levels of cognitive and physical energy, even with just a short ten minute session. If you'd like to try the waking up app, you can go to wakingup.com huberman and access a free 30 day trial. Again, that's wakingup.com huberman to access a free 30 day trial.

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And now for my discussion with doctor Matthew McDougall.

A

Doctor MacDougall, welcome.

C

Good to be here. Nice to see you.

A

Andrew, great to see you again. We'll get into our history a little bit later, but just to kick things off, as a neurosurgeon and as a neuroscientist could you share with us your vision of the brain as an organ as it relates to what's possible there? I mean, I think most everyone understands that the brain is, along with the body, the seat of our cognition, feelings, our ability to move, et cetera. And that damage there can limit our ability to feel the way we want to feel or move the way we want to move. But surgeons tend to view the world a little bit differently than most, because, as the not so funny joke goes, they like to cut and they like to fix, and they like to mend, and they, in your case, have the potential to add things into the brain that don't exist there already. So how do you think about and conceptualize the brain as an organ, and what do you think is really possible with the brain that most of us don't already probably think about?

C

Yeah, that's a great question. Thinking about the brain as this three pound lump of meat trapped in a prison of the skull, it seems almost magical that it could create a human set of behaviors and a life merely from electrical impulses. When you start to see patients and see, say, a small tumor eating away at a little part of the brain and see a very discreet function of that brain go down in isolation, you start to realize that the brain really is a collection of functional modules pinned together, duct taped together in this bone box attached to your head. And sometimes you see very interesting failure modes. So one of the most memorable patients I ever had was very early on in my training. I was down at UC San Diego and saw a very young guy who had just been in a car accident. We had operated on him, and as is so often the case in neurosurgery, we had saved his life, potentially at the cost of quality of life. When he woke from surgery with bilateral frontal lobe damage, he had essentially no impulse control left. And so we rounded on him after surgery, saw that he was doing okay to our first guess at his health, and we continued on to see our other patients. And we were called back by his 80 year old recovery room nurse, saying, you've got to come see your patient right away. Something's wrong. We walk in to see him, and he points at his elderly nurse and says, she won't have sex with me. And it was apparent at that moment his frontal lobes were gone, and that person is never going to have reasonable human behavior again. And that's one of the most tragic ways to have a brain malfunction. But anything a brain does, anything from control of hormone levels in your body to vision to sensation, to the most obvious thing, which is muscle movement of any kind, from eye movement to moving your bicep. All that comes out of the brain, all of it can go wrong. Any of it, any part of it or all of it. So, yeah, working with the brain is the substance of the brain. As a surgeon, very high stakes. But once in a while, you get a chance to really help. You get a chance to fix something that seems unfixable. And you have Lazarus like miracles. Not too uncommonly so. It's extremely satisfying as a career.

A

Could you share with us one of the more satisfying experiences?

C

Sure.

A

Or perhaps the top contour of what qualifies as satisfying in neurosurgery.

C

Yeah. One of the relatively newer techniques that we do is if someone comes in with a reasonably small tumor somewhere deep in the brain, that's hard to get to. The traditional approach to taking that out would involve cutting through a lot of good, normal brain and disrupting a lot of neurons, a lot of white matter, the wires connecting neurons. The modern approach involves a two millimeter drill hole in the skull down which you can pass a little fiber optic cannula and attach it to a laser and just heat the tumor up deep inside the brain under direct MRI visualization in real time. This person is in the MRI scanner. You're taking pictures every second or so as the tumor heats up, you can monitor the temperature and get it exactly where you want it, where it's going to kill all those tumor cells, but not hurt hardly any of the brain surrounding it. Not uncommonly. Nowadays, we have someone come in with a tumor that previously would have been catastrophic to operate on, and we can eliminate that tumor with leaving a poke hole in their skin with almost no visual after effects.

A

So that procedure that you just described translates into better clinical outcomes, meaning fewer, let's call them, side effects or collateral damage.

C

Exactly right. Yeah. Even in cases that previously would have considered totally inoperable, say, a tumor in the brain stem or a tumor in primary motor cortex or primary verbal areas, Broca's area, where we would have expected to either not operate or do catastrophic damage, those people sometimes now are coming out unscathed.

A

I'm very curious about the sorts of basic information about brain function that can be gleaned from these clinical approaches of lesions and strokes and maybe even stimulation. So, for instance, in your example of this patient that had bilateral frontal damage, what do you think his lack of regulation reveals about the normal functioning of the frontal lobes? Because I think the obvious answer to most people is going to be. Well, the frontal lobes are normally limiting impulsivity, but as we both know, because the brain has excitatory and inhibitory neurons as sort of accelerators and brakes on communication, that isn't necessarily the straightforward answer. It could be, for instance, that the frontal lobes are acting as conductors and are important, but not the immediate players in determining impulsivity. So two questions, really. What do you think the frontal lobes are doing? Because I'm very intrigued by this human expanded real estate. We have a lot of it compared to other animals. And more generally, what do you think damage of a given neural tissue means in terms of understanding the basic function of that tissue?

C

Yeah, it varies, I think, from tissue to tissue. But with respect to the frontal lobes, I think they act as a filter. They selectively are saying, sh backward to the rest of the brain behind them. When part of your brain says, that looks very attractive, I want to go grab it and take it out of the jewelry display case or whatever the frontal lobes are saying, you can if you go pay for it first. Right. They're filtering the behavior. They're letting the impulse through, maybe, but in a controlled way. This is very high level, very broad thinking about how the frontal lobes work and that that patient I mentioned earlier is a great example of when they go wrong. You know, he had this impulse, this sort of strange impulse to be attracted to his nurse, that normally it would be easy for our frontal lobes to say, this is completely inappropriate, wrong setting, wrong person, wrong time, sh. In his case, he had nothing there. And so even the slightest inclination to want something came right out to the surface. So, yeah, a filter calming the rest of the brain down from acting on every possible impulse.

A

When I was a graduate student, I was running what are called, you know, what these are. But just to inform you what are called acutes, which are neurophysiological experiments that last several days, because at the end, you terminate the animal. This isn't. My apologies to those that are made uncomfortable by animal research. I now work on humans. So a different type of animal. But at the time, we were running these acutes that would start one day and maybe end two or three days later. And so you get a. A lot of data. The animal's anesthetized and doesn't feel any pain the entire time of the surgery. But the one consequence of these experiments is that the experimenter, me, and another individual are awake for several days with an hour of sleep here or an hour of sleep there. But you're basically awake for two, three days, something that really, I could only do in my teens and twenties. I was in my twenties at the time, and I recall going to eat at a diner after one of these experiments, and I was very hungry, and the waitress walking by with a tray full of food for another table. And it took every bit of self control to not get up and take the food off the tray, something that, of course, is totally inappropriate and I would never do. And it must have been, based on what you just said, that my forebrain was essentially going offline or offline from the sleep deprivation because there was a moment there where I thought I might reach up and grab a plate of food passing by simply because I wanted it and I didn't. But I can relate to the experience of feeling like the sh response is flickering in and out under conditions of sleep deprivation. So do we know whether or not sleep deprivation limits forebrain activity in a similar kind of way?

C

I don't know specifically if that effect is more pronounced in the forebrain as opposed to other brain regions, but it's clear that sleep deprivation has broad effects all over the brain. People start to see visual hallucinations. So the opposite end of the brain, as you know, the visual cortex in the far back of the brain, is affected. People's motor coordination goes down after sleep deprivation. So I think if you force me to give a definitive answer on that question, I'd have to guess that the entire brain is affected by sleep deprivation, and it's not clear that one part of the brain is more affected than another.

A

So we've been talking about damage to the brain and inferring function from damage. We could talk a little bit about what I consider really the holy grail of the nervous system, which is neuroplasticity, this incredible capacity of the nervous system to change its wiring, strengthen connections, weaken connections, maybe new neurons, but probably more strengthening and weakening of connections. Nowadays, we hear a lot of excitement about so called classical psychedelics like LSD and psilocybin, which do seem to, quote unquote, open plasticity. They do a bunch of other things, too, but through the release of neuromodulators like serotonin and so forth. How do you think about neuroplasticity? And more specifically, what do you think the potential for neuroplasticity is in the adult? So let's say older than 25 year old brain, with or without machines being involved? Because in your role at neuralink and as a neurosurgeon in other clinical settings, surely you are using machines, and surely you've seen plasticity in the positive and negative direction. What do you think about plasticity? What's possible there without machines? What's possible with machines?

C

So, as you mentioned or alluded to, that plasticity definitely goes down in older brains. It is harder for older people to learn new things, to make radical changes in their behavior, to kick habits that they've had for years. Machines aren't the obvious answer. So implanted electrodes and computers aren't the obvious answer to increase plasticity, necessarily, compared to drugs. We already know that there are pharmacologics, some of the ones you mentioned, psychedelics, that have a broad impact on plasticity. Yeah. It's hard to know which area of the brain would be most potent as a stimulation target for an electrode to broadly juice plasticity compared to pharmacologic agents that we already know about. I think with plasticity in general, you're talking about the entire brain. You're talking about altering a trillion synapses, all in a similar way, in their tendency to be rewirable, their tendency to be up or down weighted. An electrical stimulation target in the brain necessarily has to be focused with a device like, potentially, neuralinks. There might be a more broad ability to steer current to multiple targets with some degree of control, but you're never going to get that broad target ability with any electrodes that I can see coming in our lifetimes, say, that would be coating the entire surface and depth of the brain the way that a drug can. And so I think plasticity research will bear the most fruit when it focuses on pharmacologic agents.

A

I wasn't expecting that answer, given that you're at Neuralink. And then again, I think that all of us, me included, need to take a step back and realize that while we may think we know what is going on at Neuralink, in terms of the specific goals and the general goals, and I certainly have in mind, I think most people have in mind a chip implanted in the brain, or maybe even the peripheral nervous system that can give people super memories or some other augmented capacity. We really don't know what you all are doing there. For all we know, you guys are taking or administering psilocybin and combining that with stimulation. We really don't know. And I say this with a tone of excitement, because I think that one of the things that's so exciting about the different endeavors that Elon has really spearheaded, SpaceX, Tesla, etcetera, is that early on, there's a lot of mystique. Mystique is a quality that is not often talked about, but it's, I think, a very exciting time in which engineers are starting to toss up big problems and go for it. And obviously, Elon is certainly among the best, if not the best, in terms of going really big. I mean, Mars seems pretty far to me. Electric cars all over the road nowadays are very different than the picture a few years ago when you didn't see so many of them, rockets and so forth, and now the brain. So, to the extent that you are allowed, could you share with us what your vision for the missions at Neuralink are and what the general scope of missions are? And then, if possible, share with us some of the more specific goals I can imagine. Basic goals of trying to understand the brain and augment the brain. I could imagine clinical goals of trying to repair things in humans that are suffering in some way, or animals, for that matter.

C

Yeah, it's funny what you mentioned neuralink, and I think Tesla and SpaceX, before it, end up being these blank canvases that people project their hopes and fears onto. And so we experience a lot of upside in this. People assume that we have superpowers in our ability to alter the way brains work, and people have terrifying fears of the horrible things we're going to do. For the most part, those extremes are not true. We are making a neural implant. We have a robotic insertion device that helps place tiny electrodes the size smaller than the size of a human hair all throughout a small region of the brain. In the first indication that we're aiming at, we are hoping to implant a series of these electrodes into the brains of people that have had a bad spinal cord injury. So people that are essentially quadriplegic, they have perfect brains, but they can't use them to move their body. They can't move their arms or legs.

A

Because of some high level spinal cord damage.

C

Exactly right. And so this pristine motor cortex up in their brain is completely capable of operating a human body. It's just not wired properly any longer to a human's arms or legs. And so our goal is to place this implant into a motor cortex and have that person be able to then control a computer. So a mouse and a keyboard, as if they had their hands on a mouse and a keyboard. Even though they aren't moving their hands, their motor intentions are coming directly out of the brain into the device. And so they're able to regain their digital freedom and connect with the world through the Internet.

A

Why use robotics to insert these chips? And the reason I ask that is that, sure, I can imagine that a robot could be more precise or less precise, but in theory, more precise than the human hand. No tremor, for instance, more precision in terms of maybe even a little micro detection device on the tip of the blade or something that could detect a capillary that you would want to avoid and swerve around that the human eye couldn't detect. And you and I both know, however, that no two brains, nor are the two sides of the same brain identical. So navigating through the brain is perhaps best carried out by a human. However, and here I'm going to interrupt myself again and say, ten years ago, face recognition was very clearly performed better by humans than machines. And I think now machines do it better. So is this the idea that eventually, or maybe even now, robots are better surgeons than humans are?

C

In this limited case, yes. These electrodes are so tiny and the blood vessels on the surface of the brain so numerous and so densely packed, that a human physically can't do this. A human hand is not steady enough to grab this couple micron width loop at the end of our electrode thread and place it accurately, blindly, by the way, into the cortical surface, accurately enough at the right depth to get through all the cortical layers that we want to reach. And I would love if human surgeons were essential to this process, but very soon, humans run out of motor skills sufficient to do this job. And so we are required, in this case, to lean on robots to do this incredibly precise, incredibly fast, incredibly numerous placement of electrodes into the right area of the brain.

A

So in some ways, neuralink is pioneering the development of robotic surgeons as much as it's pioneering the exploration and augmentation and treatment of human brain conditions.

C

Right. And as the device exists currently, as we're submitting it to the FDA, it is only for the placement of the electrodes. The robot, as part of the surgery, I, or another neurosurgeon, still needs to do the more crude part of opening the skin and skull and presenting the robot a pristine brain surface to sew electrodes into.

A

Well, surely getting quadriplegics to be able to move again, or maybe even to walk again, is a heroic goal, and one that I think everyone would agree would be wonderful to accomplish. Is that the first goal because it's hard but doable, or is that the first goal because you and Elon and other folks at Neuralink have a passion for getting paralyzed people to move again?

C

Yeah. Broadly speaking, the mission of neuralink is to reduce human suffering, at least in the near term. There's hope that eventually there's a use here that makes sense for a brain interface to bring AI as a tool embedded in the brain that a human can use to augment their capabilities. I think that's pretty far down the road for us, but definitely on a desired roadmap in the near term. We really are focused on people with terrible medical problems that have no options right now with regard to motor control. Our mutual friend, recently departed Krishna Chenoy, was a giant in this field of motor prosthesis. It just so happens that his work was foundational for a lot of people that work in this area, including us, and he was an advisor to Neuralink. That work was farther along than most other work for addressing any function that lives on the surface of the brain. The physical constraints of our approach require us currently to focus on only surface features on the brain. So we can't say go to the really very compelling surface. Deep depth functions that happen in the brain like mood, appetite, addiction, pain, sleep. We'd love to get to that place eventually, but in the immediate future, our first indication or two or three will probably be brain surface functions like motor control.

A

I'd like to take a quick break and acknowledge one of our sponsors, athletic greens. Athletic greens, now called ag one, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking athletic greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking athletic greens, and the reason I still take athletic greens once or usually twice a day, is that it gets me the probiotics that I need for gut health. Our gut is very important. It's populated by gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long term health. And those probiotics and athletic greens are optimal and vital for microbiotic health. In addition, athletic greens contains a number of adaptogens, vitamins and minerals that make sure that all of my foundational nutritional needs are met and it tastes great. If you'd like to try athletic greens, you can go to athleticgreens.com Huberman and they'll give you five free travel packs that make it really easy to mix up athletic greens while you're on the road, in the car, on the plane, etcetera. And they'll give you a year's supply of vitamin D. Three, k, two again, that's athleticgreens.com Huberman to get the five free travel packs and the year's supply of vitamin D. Three, k, two so, for those listening, the outer portions of the brain are filled with or consist of, rather, neocortex. So the bumpy stuff that looks like C coral, some forms of see coral look like brains, or brains look like them, and then underneath reside a lot of the brain structures that control what Matt just referred to, things controlling mood, hormone output, how awake or asleep the brain is. And would you agree that those deeper regions of the brain have, in some ways, more predictable functions? I mean, that lesions there or stimulation there lead to more predictable outcomes in terms of deficits or improvements in function?

C

Yeah, in some way, yes. I mean, the deeper parts of the brain tend to be more stereotyped, as in more similar between species than the outer surface of the brain. They're kind of the firmware or the housekeeping functions to some degree. Body temperature, blood pressure, sex, motivation, hunger, things that you don't really need to vary dramatically between a Ydezenhe fox and a human being, whereas the outer, more reasoning functions of problem solving functions between a fox and a human are vastly different. And so the physical requirements of those brain outputs are different.

A

I think I heard Elon describe it as the human brain is essentially a monkey brain with a supercomputer placed on the outside, which sparks some interesting ideas about what neocortex is doing. We have all this brain real estate on top of all that more stereotyped function type stuff in the deeper brain, and it's still unclear what neocortex is doing. In the case of frontal cortex, as you mentioned earlier, it's clear that it's providing some quieting of impulses, some context setting, rule setting, context switching. All of that makes good sense. But then there are a lot of cortical areas that sure are involved in vision or touch or hearing, but then there's also a lot of real estate that just feels unexplored. So I'm curious whether or not in your clinical work or work with neuralink or both, whether or not you have ever encountered neurons that do something that's really peculiar and intriguing. And here I'm referring to examples that could be anywhere in the brain where you go, wow, these neurons, when I stimulate them or when they're taken away, lead to something kind of bizarre but interesting.

C

Yeah. Yeah. The one that comes immediately to mind is, unfortunately, in a terrible case in kids that have a tumor in the hypothalamus that lead to what we call gelastic seizures, which is sort of an uncontrollable fit of laughter. There's been cases in the literature where this laughter is so uncontrollable and so pervasive that people suffocate from failing to breathe or they laugh until they pass out. And so you don't normally think of a deep structure in the brain like the hypothalamus as being involved in a function like humor. And certainly, when we think about this kind of laughter in these kids with tumors, it's mirthless laughter is the kind of textbook phrase humorless laughter. It's just a reflexive, almost zombie like behavior, and it comes from a very small population of neurons deep in the brain. This is one of the other strange loss of functions, you might say, is, it's nice that you and I can sit here and not have constant disruptive fits of laughter coming out of our bodies. But that's a neuronal function, thank goodness, due to neurons properly wired and properly functioning. And any neurons that do anything like this can be broken. We see this in horrifying cases like that from time to time.

A

So I'm starting to sense that there are two broad bins of approaches to augmenting the brain, either to treat disease or, for sake of increasing memory, creating superbrains, et cetera. One category you alluded to earlier, which is pharmacology, and you specifically mentioned the tremendous power that pharmacology holds, whether or not it's through psychedelics or through prescription drug or some other compound. The other approach are these little microelectrodes that are extremely strategically placed into multiple regions in order to play, essentially, a concert of electricity. That is exactly right. To get a quadriplegic moving. That sparks. Two questions. First of all, is there a role for, and is neuralink interested in combining pharmacology with stimulation?

C

So not immediately. Right now, we're solely focused on the extremely hard, some might say the hardest problem facing humans right now of decoding the brain through electrical stimulation and recording. That's enough for us for now.

A

So, to just give us a bit fuller picture of this, you were talking about a patient who can't move their limbs because they have spinal cord damage. The motor cortex that controls movement is, in theory, fine. You make a small hole in the skull, and through that hole, a robot is going to place electrodes, obviously motor cortex. But then where? How is the idea that you're going to play a concert from different locations? You're going to hit all the keys on the piano in different combinations and then figure out what can move the limbs? What I'm alluding to here is I still don't understand how the signals are gonna get out of motor cortex, past the lesion and out to the limbs, because the lesion hasn't been dealt with at all in this scenario.

C

So just to clarify there, I should emphasize we're not in the immediate future talking about reconnecting the brain to the patient's own limbs. That's on the roadmap, but it's way down the roadmap a few years. What we're talking about in the immediate future is having the person be able to control electronic devices around them with their motor intentions alone.

A

Right, prosthetic hand and arm, or just mouse and keys on a mouse and.

C

Keys on a keyboard, for starters. So you wouldn't see anything in the world move as they have an intention. The patient might imagine, say, flexing their fist or moving their wrist. And what would happen on the screen is the mouse would move down and left and click on an icon and bring up their word processor. And then a keyboard at the bottom of the screen would allow them to select letters in sequence and they could type. This is the easy place to start.

A

Easy in quotes, I would say, because the transformation of electrical signals from motor cortex through the brainstem into the spinal cord and out to the muscles is somewhat known through 100 years or more of incredible laboratory research. But the transformation, meaning how to take the electrical signals out of motor cortex and put it into a mouse or a robot arm, that's not a trivial problem. I mean, that's a whole other set of problems.

C

In fact, we're unloading some of that difficulty from the brain itself, from the brain of the patient, and putting some of that into software. So we're using smarter algorithms to decode the motor intentions out of the brain. We have been able to do this in monkeys really well. So we have a small army of monkeys playing video games for smoothie rewards, and they do really well. We actually have the world record of bitrate of information coming out of a monkey's brain to intelligently control a cursor on a screen. We're doing that better than anyone else. And again, thanks in no small part due to Krishna Chennai and his lab and the people that have worked for him that have been helping Neuralinken. What you can't do with that monkey is ask him what he's thinking. You can't ask him.

A

You can ask him, but you won't get a very interesting answer.

C

You can't tell him to try something different. You can't tell him to, hey, try the shoulder on this. Try the other hand and see if there's some cross body neuron firing, that gives you a useful signal. Once we get the people, we expect to see what they've seen when they've done similar work in academic labs, which is the human can work with you to vastly accelerate this process and get much more interesting results. So, one of the things out of Stanford recently is there was a lab that, with Krishna and Jamie Henderson and other people, decode speech out of the hand movement area in the brain. So what we know is that there are multitudes of useful signals in each area of the brain that we've looked at so far. They just tend to be highly expressed for, say, hand movement in the hand area. But that doesn't mean only hand movement in the hand area.

A

Okay, so here's the confidence test. There's a long history, dating back, really, prior to the 1950s, of scientists doing experiments on themselves, not because they are reckless, but because they want the exact sorts of information that you're talking about, the ability to really understand how intention and awareness of goals can shape outcomes in biology. If that is vague to people listening. What I mean here is that for many, probably hundreds of years, if not longer, scientists have taken the drugs they've studied or stimulated their own brain or done things to really try and get a sense of what the animals they work on or the patients they work on might be experiencing. Psychiatrists are sort of famous for this, by the way. I'm not pointing fingers at anybody, but psychiatrists are known to try the drugs that they administer, and some people would probably imagine that's a good thing, just so that the clinicians could have empathy for the sorts of side effects and not so great effects of some of these drugs that they administer to patients. But the confidence test I present you is, would you be willing, or are you willing, if allowed, to have these electrodes implanted into your motor cortex? You're not a quadriplegic, you can move your limbs, but given the state of the technology at Neuralink, now, would you do that? Or maybe in the next couple of years, if you were allowed, would you be willing to do that and be the person to say, hey, turn up the stimulation over there. I feel like I want to reach for the cup with that robotic arm, but I'm feeling some resistance, because it's exactly that kind of experiment done on a person who can move their limbs and who deeply understands the technology and the goals of the experiment that, I would argue, actually stands to advance the technology fastest, as opposed to putting the electrodes first into somebody who is impaired at a number of levels and then trying to think about why things aren't working. And again, this is all with the goal of reversing paralysis in mind. But would you implant yourself with these microelectrodes?

C

Yeah, absolutely. I would be excited to do that. I think for the first iteration of the device, it probably wouldn't be very meaningful. It wouldn't be very useful because I can still move my limbs and our first outputs from this are things that I can do just as easily with my hands. Right. Moving a mouse, typing in a keyboard. We are necessarily making this device as a medical device. For starters, for people with bad medical problems and no good options, it wouldn't really make sense for an able bodied person to get one in the near term. As the technology develops and we make devices specifically designed to perform functions that can't be done even by an able bodied person, say, eventually refine the technique to get to the point where you can type faster with your mind and one of these devices than you can with text to speech, or speech to text and your fingers. A use case that makes sense for someone like me to get it. It doesn't really make sense for me to get one when it allows me to use a mouse slightly worse than I can with my hand currently. That said, the safety of the device I would absolutely vouch for. From the hundreds of surgeries that I've personally done with this, I think it's much safer than many of the industry standard, FDA approved surgeries that I routinely do on patients that no one even thinks twice about their standard of care. Neuralink has already reached in my mind a safety threshold that is far beyond a commonly accepted safety threshold, along the.

A

Lines of augmenting one's biological function or functions in the world. I think now's the appropriate time to talk about the small lump present in the top of your hand. For those listening, not watching, it looks like a small lump between Doctor McDougall's forefinger and thumb, or index finger and thumb placed on skin on the top of his hand. You've had this for some years now, because we've known each other for, gosh, probably seven years now or so, and you've always had it in the time they've known you. What is that lump? And why did you put it in there?

C

Yeah, so it's a small writable RFID tag.

A

What's an Rfid? What does RFID stand for?

C

Yeah, radio frequency identification. And so it's just a very small implantable chip that wireless devices can temporarily power. If you approach an antennae, they can power and send a small amount of data back and forth. So most phones have the capability of reading and writing to this chip. For years, it let me into my house, it unlocked a deadbolt on my front door. For some years it unlocked the doors at Neuralink and let me through the various locked doors inside the building. It is writable. I can write a small amount of data to it. And so for some years, in early, the early days of crypto, I had a crypto private key written on it to store a cryptocurrency that I thought was a dead offshoot of one of the main cryptocurrencies. After it had forked, I put the private wallet key on there and forgot about it, remembered a few years later that it was there and went and checked, and it was worth a few thousand dollars more than when I had left it on there. So that was a nice finding. Change in the sofa in the 21st century.

A

And then when you say you read it, you're essentially taking a phone or other device and scanning it over the lump in your hand, so to speak, and then it can read the data from there, essentially. What other sorts of things could one put into these rfids, in theory? And how long can they stay in there before you need to take them out and recharge them or replace them?

C

Well, these are passive. They're coated in biocompatible glass, and as an extra, I'm a rock climber, and so I was worried about that glass shattering during rock climbing. I additionally coated them in another ring of silicone before implanting that. So it's pretty safe. They're passive, there's no battery active electronics in them, so they could last the rest of my life. I don't think I'd ever have to remove it for any reason at some point. The technology is always improving, so I might remove it and upgrade it. That's not inconceivable. Already there's ten x more storage versions available that could be a drop in replacement for this if I ever remove it. But it has a small niche use case, and it's an interesting proof of concept, tiptoeing towards the concept that you mentioned of you have to be willing to go through the things that you're suggesting to your patients in order to say with a straight face that you think this is a reasonable thing to do. So a small subcutaneous implant in the hand is a little different than a brain implant, but yeah.

A

What's involved in getting that RFID chip into the hand, is it. I'm assuming it's an outpatient procedure. Presumably you did it on yourself.

C

Yeah, yeah. This was a kitchen table kind of procedure.

A

Any anesthetic or is or. No.

C

You know, I've seen people do this with lidocaine injection. For my money, I think a lidocaine injection is probably as painful as just doing the procedures.

A

A little cut in that thin skin on the top of the hand.

C

Right.

A

Some people are cringing right now. Other people are saying, I want. Because you'll never worry about losing your keys or passwords. I actually would like it for passwords because I'm dreadfully bad at remembering passwords. I have to put them in places all over the place, and then it's like, I'm like that kid in remember that movie stand by me, where the kid hides the pennies under the porch and then loses the map? Spends all summer trying to find them. So I can relate. Yeah. So a little. It was just a little slit, and then put in there. No local immune response. No, no, no pus, no swelling.

C

All the materials are completely biocompatible that are on the surface exposed to the body. So no bad reaction. It healed up in days, and it was fine.

A

Very cool. Since we're on video here, can you just maybe raise it and show us? So, were you not to point out that little lump, I wouldn't have known to ask about it. And any other members of your family have these?

C

A few years after having this, seeing the convenience of me being able to open the door without keys, my wife insisted that I put one in her as well. So she's walking around with one.

A

Fantastic.

C

We consider them our version of wedding rings.

A

Love it. Well, it's certainly more permanent than wedding rings in some sense. I can't help but ask this question, even though it might seem a little bit off topic. As long as we're talking about implantable devices and Bluetooth and RFID chips in the body, I get asked a lot about the safety, or lack thereof, of Bluetooth headphones. You work on the brain. You're a brain surgeon. That's valuable real estate in there. And you understand about electromagnetic fields. And any discussion about EMFs immediately puts us in the category of uh oh, like, get their tin foil hats. And yet, I've been researching emfs for a future episode of the podcast.

C

Sure.

A

And EMFs are a real thing. That's not a valuable statement. Everything's a real thing at some level, even an idea. But there does seem to be some evidence that electromagnetic fields of sufficient strength can alter the function of, maybe the health of, but the function of neural tissue, given that neural tissue is electrically signaling among itself. So I'll just ask this in a very straightforward way. Do you use Bluetooth headphones or wired headphones?

C

Yeah, Bluetooth.

A

And you're not worried about any kind of EMF fields across the skull?

C

No. I mean, I think the energy levels involved are so tiny that, ionizing radiation aside, we're way out of the realm of ionizing radiation that people would worry about tumor causing EMF fields, even just the electromagnetic field itself, as is very well described in a Bluetooth frequency range. The power levels are tiny in these devices, and so we are awash in these signals. Whether you use Bluetooth headphones or not, for that matter, you're getting bombarded with ionizing radiation in a very tiny amount. No matter where you live on earth, unless you live under huge amounts of water, it's unavoidable. And so I think you just have to trust that your body has the DNA repair mechanisms that it needs to deal with the constant bath of ionizing radiation that you're in as a result of being in the universe and exposed to cosmic rays. In terms of electromagnetic fields, it's just the energy levels are way, way out of the range where I would be worried about this.

A

What about heat? I don't use the earbuds any longer for a couple of reasons. Once, as you know, I take a lot of supplements, and I reached into my left pocket once and swallowed a handful of supplements that included bluetooth. An airpod pro. I knew it. I swallowed it the moment after I gulped it down. By the way, folks, please don't do this. It was not a good idea. It wasn't an idea. It was a mistake. But I could see it on my phone as registering there. Never saw it again. So I'm assuming it's no longer in my body. But anyway, there's a bad joke there, to be sure. But in any event, I tend to lose them or misplace them. So that's the main reason. But I did notice when I used them that there's some heat generated there. I also am not convinced that plugging your ears all day long is good. There's some ventilation through the sinus systems that include the ears. So it sounds to me like you're not concerned about the use of earbuds. But what about heat near the brain? I mean, the cochlea, the auditory mechanisms that sit pretty close to the surface there? Heat and neural tissue are not friends. Sure, I'd much rather get my brain cold than hot in terms of keeping the cells healthy and alive. Should we be thinking about the heat effects of some of these devices or other things? Is there anything we're overlooking?

C

Well, think about it this way. I use cars as an analogy a lot, and mostly internal combustion engine cars. So these analogies are going to start to be foreign and useless for another generation of people that grow up in the era of electric cars. But using cars as a platform to talk about fluid cooling systems, your body has a massive distributed fluid cooling system similar to a car's radiator. You're pumping blood all around your body all the time at a very strictly controlled temperature that blood carries. It's mostly water, so it carries a huge amount of the heat away or cold away from any area of the body that's focused heating or focused cooling. So you could put an ice cube on your skin until it completely melts away, and the blood is going to bring heat back to that area. You can stand in the sun under much more scary heating rays from the sun itself that contain uv radiation that's definitely damaging your DNA. If you're looking for things to be afraid of, the sun is a good one.

A

Now you're talking to the guy that tells everybody you get sunlight in their eyes every morning. But I don't want people to get burned or give themselves skin cancer. I encourage people to protect their skin accordingly. And different individuals require different levels of protection from the sun. Sure, some people do very well in a lot of sunshine, never get basal cell or anything like that. Some people, and it's not just people with very fair skin. A minimum of sun exposure can cause some issues. And here I'm talking about sun exposure to the skin. Of course, staring at the sun is a bad idea. I never recommend that.

C

Thinking about the sun just as a heater for a moment, to compare it with bluetooth headphones. Your body is very capable of carrying that heat away and dissipating it via sweat evaporation or temperature equalization. Any heat that's locally generated in the ear. One, there's a pretty large bony barrier there, but two, there's a ton of blood flow in the scalp and in the head in general, and definitely in the brain that's going to regulate that temperature. So I think certainly there can be a tiny temperature variation, but I doubt very seriously that it's enough to cause a significant problem.

A

I'd like to go back to brain augmentation. You've made very clear that one of the first goals for neuralink is to get quadriplegics walking again and again. What a marvelous goal that is. And I certainly hope you guys succeed.

C

Well, again, just to be very clear, the first step is we aren't reconnecting the patient's own muscle system to their.

A

Motor cortex, allowing them, excuse me, agency over the movement of things in the world. Yes, and eventually their body.

C

And you're exactly right. Yeah, eventually their body. We would love to do that. And we've done a lot of work on developing a system for stimulating the spinal cord itself. And so that gets to the question that you asked a few minutes ago of how do you reconnect the motor cortex to the rest of the body? Well, if you can bypass the damaged area of the spinal cord and have an implant in the spinal cord itself, connected to an implant in the brain and have them talking to each other, you can take the perfectly intact motor signals out of the motor cortex and send them to the spinal cord, which most of the wiring should be intact in the spinal cord, below the level of, say, the injury caused by a car accident or motorcycle accident or gunshot wound or whatever. And it should be possible to reconnect the brain to the body in that way. So not out of the realm of possibility that in some small number of years, that neuralink will be able to reconnect somebody's own body to their brain.

A

And here I just want to flag the hundred years or more of incredible work by basic scientists. The names that I learned about in my textbooks as a graduate student were like georgiopolis, and that won't mean anything to anyone unless you're a neuroscientist. But Georgiopoulos performed some of the first sophisticated recordings out of motor cortex. Just simply asking what sorts of electrical patterns are present in motor cortex as an animal or human moves a limb. Krishna Chennoy being another major pioneer in this area and many others, and just really highlighting the fact that basic research where an exploration of neural tissue is carried out at the level of anatomy and physiology, really sets down the pavement on the Runway to do the sorts of big clinical expeditions that you all at Neuralink are doing.

C

Yeah, it can't be said enough that we, broadly speaking, in industry, sometimes are and sometimes stand on the shoulders of academic giants. They were the real pioneers that they were involved in the grind for years in an unglorious, unglamorous way.

A

No stock options.

C

No stock options. And, you know, the reward for all the hard work is a paper at the end of the day that is read by dozens of people. And so they were selfless academic researchers that made all this possible. And we all, humanity and neuralink, owe them a massive debt of gratitude for all the hard work that they've done and continue to do.

A

I agree along the lines of augmentation. Early on, in some of the public discussions about neuralink that I overheard between Elon and various podcast hosts, et cetera, there were some lofty ideas set out that I think are still very much in play in people's minds. Things like, for instance, electrical stimulation of the hippocampus that you so appropriately have worn on your shirt today. So for those beautiful. Looks like either it looks like a Golgi or a cajal, rendition of the hippocampus translates to seahorse, and it's an area of the brain that's involved in learning and memory, among other things. There was this idea thrown out that a chip or chips could be implanted in the hippocampus that would allow greater than normal memory abilities. Perhaps that's one idea. Another idea that heard about in these discussions was, for instance, that you would have some chips in your brain, and I would have some chips in my brain, and you and I could just sit here looking at each other, or not nodding or shaking our heads and essentially hear each other's thoughts, which sounds outrageous, but, of course, why not? Why should we constrain ourselves to, as our good friend Eddie Chang, who's a neurosurgeon who was already on this podcast once before, said, speech is just the shaping of breath as it exits our lungs. Incredible, really, when you think about it. We don't necessarily need speech to hear and understand each other's thoughts, because the neural signals that produce that shaping of the lungs come from some intention. I have some idea, although it might not seem like it, about what I'm going to say next. So, is that possible, that we could sit here and just hear each other's thoughts? And also, how would we restrict what the other person could hear?

C

Yeah, well, so, absolutely. I mean, think about the fact that we could do this right now. If you pulled out your phone and started texting me on my phone and I looked down and started texting you, we would be communicating without looking at each other or talking. Shifting that function from a phone to an implanted device, it requires no magic advance, no leap forward. It's technology we already know how to do. If we, say, put a device in that allows you to control a keyboard and a mouse, which is our stated intention for our first human clinical trial.

A

Or against I'm deliberately interrupting. Or I can text an entire team of people simultaneously, and they can text me, and in theory, I could have a bunch of thoughts, and 510 50 people could hear, or probably more to their preference, they could talk to me.

C

Yeah. And so texting each other with our brains is maybe an uninspiring rendition of this, but it. It's not very difficult to imagine the implementation of the same device in a more verbally focused area of the brain that allows you to more naturally speak the thoughts that you're thinking and have them rendered into speech that I can hear, maybe via a bone conducting implant.

A

So silently hear or not silently. Let's say I was getting off the plane, and I wanted to let somebody at home know that I had arrived. I might be able to think in my mind, think their first name, which might queue up a device that would then play my voice to them and say, just got off the plane, I'm going to grab my bag, and then.

C

I'll give you a call on their home, Alexa.

A

So that's all possible. Meaning, we know the origin of the neural signals that gives rise to speech. We know the different mechanical and neural apparati, like the cochlea eardrums, et cetera, that transduce sound waves into electrical signals. Essentially, all the pieces are known. We're just really talking about refining it. Yeah, refining it and reconfiguring it. I mean, it's not an easy problem, but it's really an engineering problem rather than a neuroscience problem.

C

For that use case, nonverbal communication, you might say that's a solved problem in a very crude, disjointed way. Some labs have solved part one of it. Some labs have solved part two of it. There are products out there that solve, say, the implanted bone conduction part of it for the deaf community. There are no implementations I'm aware of that are pulling all that together into one product that's a streamlined package from end to end. I think that's a few years down the road, and we, I think, have.

A

Some hints of how easily or poorly people will adapt to these. Let's call them novel transformations. A few years ago, I was on Instagram, and I saw a post from a woman. Her name is Kasar Jacobson, and she is deaf since birth and can sign and to some extent, can read lips. But she was discussing neosensory. So this is a device that translates sound in the environment into touch sensations on her hand or wrist. She's an admirer of birds and all things avian and I reached out to her about this device because I'm very curious because this is a very interesting use case of neuroplasticity in the sensory domain, which is a fascination of mine. And she said that, yes, indeed, it afforded her novel experiences. Now, when walking past, say, pigeons in the park, if they were to make some, whatever sounds that pigeons make, that she would feel those sounds, and that indeed it enriched her experience of those birds in ways that obviously it wouldn't otherwise. I haven't followed up with her recently to find out whether or not ongoing use of neosensory has made for a better, worse or kind of equivalent experience of avians in the world, which for her is a near obsession. So she delights in them. What are your thoughts about peripheral devices like that? Peripheral meaning outside of the skull, no requirement for a. Yeah. Surgery. Do you think that there's a more immediate or even a just generally potent use case for peripheral devices? And do you think that those are going to be used more readily before the brain surgery requiring devices are used?

C

Yeah, certainly. The barrier to entry is lower, the barrier to adoption is low. If you're making a tactile glove hard to say no to when you can slip it on and slip it off and not have to get your skin cut at all. Again, there's no perfect measure of the efficacy of a device, of one device compared to another, especially across modalities. But one way that you can start to compare apples to oranges is bitrate, useful information in or out of the brain as transformed into digital data. And so you can put a single number on that and you have to ask, when you look at a device like that, is, what is the bitrate in? What is the bitrate out? How much information are you able to usefully convey into the system and get out of the system, into the body, into the brain. And I think there's, what we've seen in the early stabs at this is that there's a very low threshold for bit rate on some of the devices that are trying to avoid a direct brain surgery.

A

Could you perhaps say what you just said, but in a way that maybe people who aren't as familiar with thinking about bitrates might be able to digest? There I'm referring to myself. I mean, I understand bitrate. I understand that adding a new channel of information is just that, adding information. Are you saying it's important to understand whether or not that new information provides for novel function or experience? And to what extent is the newness of that valid and adaptive?

C

Well, I'm saying more. It's hard to measure utility in this space. It's hard to put a single metric, single number on how useful a technology is. One crude way to try to get at that is bitrate. Think of it as back in the days of dial up modems. The bitrate of your modem was 56k or ninety six k. I can still.

A

Hear the sound of the dial up in the background.

C

That was a bitrate that thankfully kept steadily going up and up and up. Internet service provider gives you a number that is the maximum usable data that you can transmit back and forth from the Internet. That's a useful way to think about these assistive devices. How much information are you able to get in, into the brain and out of the brain usefully? And right now, that number is very small, even compared to the old modems. But you have to ask yourself, when you're looking at a technology, what's the ceiling? What's the theoretical maximum? And for a lot of these technologies, the theoretical maximum is very low, disappointingly low, even if it's perfectly executed and perfectly developed as a technology. And I think the thing that attracts a lot of us to a technology like Nuralink is that the ceiling is incredibly high. There's no obvious reason that you can't interface with millions of neurons as this technology is refined and developed further. So that's the kind of wide band, high bandwidth brain interface that you want to develop. If you're talking about a semantic prosthetic, an AI assistant to your cognitive abilities, the more Sci-Fi things that we think about in the coming decades. So it's an important caveat. When you're evaluating these technologies, you really want it to be something that you can expand off into the Sci-Fi so.

A

Let'S take this a step further, because as you're saying this, I'm realizing that people have been doing exactly what Neuralink is trying to do now for a very long time. Let me give you an example. People who are blind, who have no pattern vision, have used canes for a very long time. Now, the cane is not a chip. It's not an electrode. It's not neosensory, none of that stuff. What it is is essentially a stick that has an interface with a surface, so it's swept back and forth across the ground and translating what would otherwise be visual cues into somatosensory cues. And we know that blind people are very good at understanding, even when they are approaching, say, a curb edge, because they are integrating that information from the tip of the cane up through their somatosensory cortex and their motor cortex, with other things, like the changes in the wind and the sound as they round a corner. And here I'm imagining, like a corner in San Francisco downtown. As you get to the corner, it's a completely different set of auditory cues, and very often we know. And this is because my laboratory worked on visual repair for a long time. I talked to a lot of blind people who use different devices to navigate the world that they aren't aware of the fact that they're integrating these other cues, but they nonetheless do them subconsciously, and in doing so, get pretty good at navigating with a cane. Now, a cane isn't perfect, but you can imagine the other form of navigating as a blind person, which is to just attach yourself or attach to you another nervous system. The best that we know, being a dog, a sighted dog that can cue you, again with stopping at a curb's edge, or even if there are some individuals that might seem a little sketchy. Dogs are also very good at sensing different arousal states, and others threaten danger. I mean, they're exquisite at it, right? So here what we're really talking about is taking a cane or another biological system, essentially a whole nervous system, and saying, this other nervous system's job is to get you to navigate more safely through the world.

C

Right?