The Brain Implant That Could Change Medicine
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Visit your local Kia dealer today. Kia. Movement that inspires. See retailer for warranty details. Always drive safely. Limited inventory available. My guest today is a brain surgeon who also has a PhD in electrical engineering from MIT.

Which is to say he is extremely well prepared to figure out how to implant electronic devices in people's brains, which is what he's doing. And in fact, as it happens, he's actually been preparing to do this kind of his whole life.

you know i sort of was born into the business my dad is a neurologist who started out his career as an electrical engineer you know electrophysiology clinical neuroscience and you know neurology and neurosurgery have been a part of my life forever as far as i can remember and um you know brain computer interfaces the way we talk about them today didn't exist in the 1980s but the fundamentals were there and so that's been percolating in some way forever

I'm Jacob Goldstein, and this is What's Your Problem? The show where I talk to people who are trying to make technological progress. My guest today is Ben Rapoport. He's the co-founder and chief science officer at Precision Neuroscience. Ben's problem is this: Can you build a device that allows someone who is paralyzed to use a computer with only their thoughts? And can you do it without sticking needles into their brain? Before he started Precision, Ben was a co-founder of Neuralink.

Neuralink is probably the best known brain computer interface company. And it was founded in 2016, right around the moment when modern AI was just emerging. And Ben told me the AI revolution was really what inspired the foundation of Neuralink.

The kind of founding principles of Neuralink were, you know, here's a point in time when we're thinking broadly about how the human brain is going to interact with artificial intelligence. And if breakthroughs in artificial intelligence are scaling at an exponential rate, you know, how's the human brain going to keep up with that? How are we going to keep communicating with artificial intelligence in a way that is feasible and productive?

So that's a really different... That's not how can we help people who are paralyzed. That's a much more...

Sort of cognitive-centric. It's about the nature of human thought in the context of AI. Is that right? Maybe so. That's kind of the raison d'etre of Neuralink. And it was a little different from a human-focused, medically-oriented focus that Precision has taken. And these different focuses can and will coexist in an ecosystem in which multiple brain-computer interface exists.

core technologies become widely available and are the standard of become the standard of care. But it became clear to me that that there was a need to also focus

effort within the community of brain-computer interfaces on treating patients with untreatable diseases. That was the origin of brain-computer interfaces, was really bringing the science and technology to a point where people who today we think of as having really no treatment options, people with paralysis or inability to speak, for example, from ALS,

really unlocking a world of possibilities for those people. But we really wanted to focus on those applications within brain-computer interfaces, and doing that, in my view, required making a few different design decisions than what we'd made at Neuralink. So those were the founding principles of precision. You leave Neuralink to found precision.

Tell me about what you're setting out to create at Precision when you're launching the company. What is it that you want to do, and how is it different than what everybody else is doing? Yeah. The goal then and is today to build a safe, scalable brain-computer interface that can become the standard of care in the treatment of patients.

patients, people with a variety of diseases of the brain and nervous system that today are untreatable, that includes various forms of paralysis and inability to communicate. And tell me about the technology. Tell me about the thing you're building and how it's different from what other people are building. Our philosophy has been that in order for a brain-computer interface to really work

in the real world and to unlock the potential of this technology for many millions of people. First, of course, it has to be incredibly safe. We see the term minimally invasive a lot, but really, in my view, it has to not damage the brain. So what does that mean in practice? Yeah, the tissue interface with the electrode involves kind of like little needles,

- Well, the electrodes are little needles and they penetrate into the brain. And there's been a lot of innovation in doing it, trying to do that very safely. But in my view, the most safe version of that is a version that just kind of caresses the brain, but doesn't penetrate it.

was at first thought, you know, certainly when we found precision, many people thought that it was not possible to extract high quality signals from the brain without penetrating. And we and others have shown that in fact, it's not only possible to do but has many advantages. So not that it's the only way or necessarily better or worse, but from the standpoint of people who have untreatable diseases and already have a very low threshold for damage to the brain, not doing any incremental damage to the brain, for us,

is very, very important. So that was sort of part one of precision. Before we get to part two, is there a trade-off? I mean, do you lose some amount of sensitivity or resolution? Is that the basic trade-off? So we always get this question, you know. It's a reasonable question. Right, no, it's absolutely, it's a good question, right? And so there's this

false dichotomy. I think that more penetration into the brain equals higher quality signal. And if you don't do that, then you somehow sacrifice signal quality. But it's really not a one dimensional as one dimensional as that. If you're a neuroscientist, then there's a trade off.

If you care about recording from one neuron at a time and you're studying the behavior of individual neurons and you care about that, then you want what we call intercortical penetrating microelectrodes, the ones that can come up close to an individual neuron and listen to those individual action potentials. And that's something that neuroscientists care about. So you don't want to use the...

same electrodes that we use for precision. But if what you care about is treating paralysis or disorders of communication, what you care about is stable, high-quality signals over a long period of time. And in that area, arguably, just based on the data, the cortical surface electrodes that we use at precision are at least as good, if not better. And I think time will tell because

There's a few of these different systems that are now out there in the real world. What's really exciting is that this has come out of the laboratory, out of animal experiment territory, into human pilot clinical trials that we and Neuralink and Synchron and others are engaged in. And that's really where it's at. So tell me where you are now. I know you've done some amount of research.

experimental work in people, right? What is the frontier of your work right now? Yeah. We've now implanted our electrode arrays in almost 30 patients over the last two years. These are pilot studies across four major medical centers in the U.S. that are partnering with us. And all of those studies are really, they're temporary replacements of the electrodes. So they're studies that are run in patients who have volunteered for

to have the electrodes placed alongside clinical standard electrodes as part of a neurosurgical procedure that they're already undergoing. And we've been using those opportunities to basically validate the quality of the electrode activity that we can record on those electrodes and to demonstrate that our algorithms can in fact basically decode intention and thought as intended by essentially healthy volunteers. So...

The array itself, like, what's it look like? So the brain lives in the skull. So it is a soft tissue that's kind of

jelly-like in consistency. And so the best way to generally interface with it is with something also that is soft and flexible. And the surface of the brain, as many of us have seen in pictures, is curved or undulating. And so our electrode array is a thin polymer that's many times thinner even than a human hair. So it's a film. And embedded in that film are tiny little dots of platinum that

Each one connected to a very, very, very thin platinum wire. And so that film with the tiny little dots of platinum inside can be placed over the brain surface and it conforms to that curved surface. So each of those little platinum electrodes touches the surface of the brain at a very discrete point. And so it can record the electrical activity from the area of the brain just under that it's touching basically.

Okay, so in these trials, you put this implant on a patient's brain, and then what?

So let me describe maybe one of the paradigms that we use at one of our partner sites. So Ian Fahigas is the neurosurgeon at Penn, who's our partner, and he is a surgeon who specializes in the treatment of Parkinson's disease. One of the ways of treating Parkinson's disease is a procedure called deep brain stimulation in which electrodes are placed deep within the brain to stimulate those areas that are responsible for modulating the tremor.

Dr. Cahigas, among many others, performs these procedures, at least a part of them awake.

in order to make sure effectively that the exact right place is being targeted. And the brain doesn't feel pain, and so it's not only possible but beneficial to do these procedures, at least partially awake. So in those procedures, we take basically a 15-minute window, and Dr. Ahigis places the precision electrode directly over the motor cortex, a portion of the motor cortex that controls hand movement.

And this has provided, you know, for us and for the community, the highest resolution picture of the human motor cortex in the awake human ever in the history of the world. So, you know, the area of the brain of the motor cortex that controls hand movement is about the size of a postage stamp. Of a postage stamp, okay. And critically to understand is the neurons that are responsible for coordinating those movements

they all live within a two millimeter layer of tissue that's just tissue.

at the surface of the brain. So all that critical computation and activity is happening very, very close to the surface. And so-- - That's good for you. - Good for us. - Good for your method. So what actually happens? So you have a patient who's there. You put your array on the portion of their motor cortex that controls hand movements. And then you say, wiggle your finger? - Exactly. So we say basically, we walk the patient through making a certain number of gestures.

you know, open hand, close hand, make a peace sign. And we watch, and I say metaphorically, we watch what the patient is doing and we watch what is happening on the surface of the brain. And here is, you know, where modern machine learning plays a tremendous role because this, exactly, this is the AI portion of it because this is a technology

so the so-called training data. So this is a calibration phase in which our algorithms learn what the brain's signals to the hand look like in a given patient. So there's a characteristic signature, electrical signature that happens in the moments before an action is done. And it's a little bit different in each person. And learning that signature for that person allows us to recognize when the brain is telling the hand to make a particular gesture, when the fingers are supposed to move in a

particular way when the hand opens and closes. And after about three to five minutes of training, we then have a trained algorithm that can recognize not just movement, but the intention to move. And so we then use the balance of the time that we have with those patients to ask the patient to move and validate that we're predicting the correct movement, and then to imagine movement without moving.

And that too, we can accurately predict. And so these procedures become the basically healthy volunteer test bed for patients who can't actually move, the paralyzed patients that we'll be treating within the next couple of years. So that's the nature of this first phase of pilot trials. You mentioned that each person is different in terms of the patterns of neuron activity for each patient.

hand motion in this context. How different? Is it like kind of like a southern accent versus a New York accent? Is it like an entirely different language if that kind of metaphor works? Yeah, no, that's a perfect metaphor. And it's kind of like that. So, you know, if you're trying to learn a new language or a dialect, you know that there are words.

And you know that they're spoken in a particular frequency range. So you kind of know what to listen for and you kind of know the cadence. So when there's a word, you know, that's a word, but you might not know what it means until you listen in to conversation and you've seen the context. So, so,

Like, pretty different. Like, it wouldn't work to just make a generic algorithm and put it on my brain because...

pretty well, right? Like talking to your iPhone. It works, right? It works pretty well. And then you need to train it to make it better. And then it listens to you in the background and gets even better. And so that's a good analogy. So it is possible for us to build

you know, a translation algorithm that works somewhat out of the box. But we build into it a calibration phase that knows something about the structure of brain signals and how they interact with and relate to movement or speech. And that's what basically allows us to

use only relatively small amounts of calibration data. I mean, we can do a lot with a small amount of calibration data. So you're doing a sort of pilot study now. What's the next big step?

So I want to be careful about what I say before it happens, but we do anticipate being able to, in the very near future, extend what are now short-duration pilot studies that last only the span of time that we have access to the brain within a standard neurosurgical procedure, which is relatively short.

We anticipate having ways of extending that with regulatory approval to hopefully many days and weeks within the calendar year. And then, of course, this is all in the service of permanent implants that wirelessly communicate with the outside world. And that will be the basis of our pivotal clinical trial a couple of years hence. Still to come on the show, Ben and I discuss the possibility of using brain-computer interfaces in healthy people.

Also, the meaning of consciousness. This year at Pushkin, we've been able to work with some of the world's biggest brands on creating bespoke content. Whether it's a custom episode in partnership with a brand or a creative ad campaign, we want to be sure that our content reaches people. But the ad space is incredibly noisy. How do we ensure our content reaches the right audience?

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Just before the break, Ben mentioned that pivotal clinical trial that they're building up to. And so I asked him what exactly they're going to be doing in that trial.

So the first clinical application is going to be for the treatment of severe paralysis. Okay. And the device will be an implant that has the electrodes on the brain and an implant within the chest wall that provides power and data transfer to the outside world to communicate with the external devices like a computer. And that system will allow, for example, a person with a spinal cord injury really to hold the desk job. That

that will allow them to operate effectively a word processing program, email, surf the internet, have a Zoom conversation, operate an Excel spreadsheet, use PowerPoint, have the ability to reenter the workforce with a level of personal and economic self-sufficiency that allows them to, you know, certain freedoms that they don't have and that are core to being a part of modern society. That is, for us, a major goal, number one.

I'm quite sure that as the technology becomes provenly safe and effective, that other disorders and conditions that are perhaps less dramatic, you know, will benefit from this and other forms of technology. And part three is there's a lot that I'm sure that we're not even imagining right now. You know, the brain-computer interface

at least the precision system is really in some ways a platform technology because it translates the wet and difficult to access delicate biological signals of the brain into robust digital bit streams and allows us to compute on them in a scalable way.

The brain-computer interface is not a substitute for a keyboard and a mouse. It's not a substitute for a gestural interface or a voice interface. It's another kind of interface with the brain, just like...

it would have been impossible to predict based on the keyboard alone or the graphical user interface alone all of the different applications that have emerged. I think as long as we build a safe, reliable interface and make that responsibly available, kind of the sky's the limit. And I can't even hazard a guess at some of the things that will come next. So I think there's a whole generation of discovery and innovation waiting to happen after we get this across the line into patients to become standard of care.

Could you imagine it being used in healthy people for, you know, the computer and the brain issues?

Yeah, I could eventually. In a sense, I would love that to be the case. I think I'm ambivalent about that one. Tell me why you'd love that to be the case. Well, because it will have meant that we've... Well, yes, it'll mean your thing works really well and is wildly safe. Yes, that's true. Right. So we build with that goal in mind in a way, right? Just because in order for something to be accepted by an able-bodied person who has...

Zero risk tolerance, right? And basically only downside if something goes wrong or doesn't work properly, you need it to work just in a bulletproof way. And that's the kind of system that we're trying to engineer. Yes.

From that point of view, it makes perfect sense. If that is true, then you have built a wildly safe and effective device. Exactly. So if you and I were having this conversation and you said to me, gosh, I would love to, right? I mean, that would mean that all of those doubts had been erased. And in order to erase those doubts, we have to prove certain things to the world. And that's really our job.

Would you want, if you were healthy, would you want to have your device in your brain if it were safe and effective? I would have to do certain things that the device can't do yet. Yeah, sure. But I definitely wouldn't rule it out when we get there. I mean, it's like...

Sometimes with technology, it's hard to wrap your mind around what's going to happen in a generation, right? Yeah. Of two little kids. And we're always talking about, like, should the kids actually get to use an iPhone? Hold out for as long as you can. So, right, because it's not exactly a choice, right? That's the thing. You think, like, oh, an iPhone. Great. That's my point. By the way, I'm very, very permissive. Yeah.

Me too. You know what finished me was COVID. Like, we held out really strong, and then COVID hit and did us in. So, but the reason I bring that up is that, you know, like, our parents could not even have conceived of even that question, right? Yes. But I mean, the other way to think about that is like, you know, I'm pro-progress and pro-technology, but like...

Having kids makes me wish iPhones didn't exist, right? It makes me wish, like, sure, give them a flip phone so they can text their friends and call me if something goes wrong. But I don't know. But on the other hand, I make podcasts for a living. It's an interesting discussion, right? And we sometimes joke, but somehow kids are born now knowing how to swipe and navigate the phone interface, right? So my point is that in 20 years, it's going to be a different conversation. There's a lot of kids of people in the company and

They know what we're doing. You know, my girls know what we're doing. And their view on the technology is different. They see it as something that exists. And when you're born into it, you have kind of a different sense of what's okay and what's normal. And that's the generation that's growing up today is going to grow up with brain-computer interfaces just being a normal thing. Yeah, maybe your grandkids will feel about brain-computer interfaces the way your kids feel about iPhones. It's going to happen faster than that. We'll be back in a minute with The Lightning Rank.

This year at Pushkin, we've been able to work with some of the world's biggest brands on creating bespoke content. Whether it's a custom episode in partnership with a brand or a creative ad campaign, we want to be sure that our content reaches people. But the ad space is incredibly noisy. How do we ensure our content reaches the right audience?

That's where LinkedIn ads come in. With LinkedIn ads, you can precisely reach professionals who are more likely to find your ad relevant as you will have direct access to a billion members, 130 million decision makers, and 10 million C-level executives.

You can target your audience by job title, industry, company, and more, ensuring your ads reach the right people for your business. Start building the right relationships and reach your audience in a respectful environment with LinkedIn ads. We'll even give you a $100 credit on your next LinkedIn ads campaign. Go to linkedin.com slash Malcolm to claim your credit. That's linkedin.com slash Malcolm. Terms and conditions apply.

Who doesn't love Reese's peanut butter cups? Answer? Nobody. They've been one of the most delicious parts of your life forever. Everybody knows they can't get any better, right? Well, after you try the new Reese's chocolate lava big cup, a delicious twist on your favorite treat, you might change your mind. The Reese's chocolate lava big cup is the perfect combination of creamy milk chocolate, delicious peanut butter, and an ooey gooey chocolatey filling. It's a different kind of delicious, you know, the

The chocolate filling just takes it to a whole extra level. It's a totally, completely new kind of Reese's Peanut Butter Perfection. Lucky you. Lucky everyone. So you really just have to ask yourself how you like your peanut butter cup. The way you've always loved it? Or with a gooey chocolate lava center? Or don't choose and have both. Yeah, that sounds like a plan. Shop Reese's Chocolate Lava Big Cup now at a store near you. Found wherever candy is sold.

Tell me about the metabolic factors limiting performance in marathon runners. Okay, right. So, um...

That was a paper that I wrote now more than a decade ago. So I'm a dedicated marathon runner. I've run 40-something marathons over 20-plus years. There's a longer story, which we don't have time for now, as to why I wrote that paper. What's the short version of that story of why you wrote the paper? The short version is it shouldn't be metabolically possible to run a marathon. Oh, interesting. Because everybody thinks the paradox is that you can't eat enough pasta to get through 26 miles.

Uh-huh. Just like if you do the math, there's not enough energy stored in the body? If you do the simple math, there seems to be a paradox that you can't eat enough pasta to run the marathon, right? Everybody thinks you've got to eat pasta before you run the marathon. It turns out that you can't really eat enough pasta to run a marathon.

So how is it even possible? And the reason it's possible is that you're burning some fat as you go. And then everybody knows that there's this phenomenon of hitting the wall where many runners collapse or have a major impact at some point along the way, usually about two-thirds of the way through the race, where they just can't keep going or can't keep going at the same pace that they started the race. And why does that happen? That happens

Because they're not burning carbohydrates as the fuel substrate. Or they can't burn them at the same rate that they started the race. So how do you not hit the wall? How do you avoid that phenomenon? And basically, you need to run at a pace that basically burns both fuel substrates, the fat and the carbohydrate, at a rate that basically you just exhaust your carbohydrate stores at mile 26.2. So that's one of the core rate limiting mechanisms.

metabolic factors in marathon running. - And so, I mean, so what was it that you figured out that got published in whatever it was, PLOS? - Yes, I figured that out. - Oh, okay. - And I figured out how to model that mathematically.

And did it affect the way people run marathons? It affected the way I run marathons. How did you change your running strategy based on your own research? I learned how to pace myself in a more quantitative way. And I learned how to

have structure my pre-race diet and my training diet in a way that was much better than i had in in the years before that did you get faster oh i got i got significantly faster yeah i run a bunch of sub three hour marathons around the time i figured that all out that is a very fast marathon and for a period of time i don't know if it's still the case but maybe embarrassingly that was my it still is i think my only single author paper and for a period of time it was i i

Most cited paper. Well, you know, Einstein's most cited paper is the one where he describes entanglement and basically says this proves that quantum is not a complete description of reality because there's no way it could be true. And he was wrong, right? Can't aspire to that necessarily. But anyway.

What's one tip that comes out of that? Is there a model I could plug in? I ran my first marathon this year. I did not know about your paper. Is there something you can tell me just qualitatively from it that I'm doing wrong? Yeah, take a look. There's a little formula there basically that allows the average person to estimate their optimal marathon pace. Okay.

Boston Marathon or New York Marathon? What do you like better? Well, you know, I'm a native. I've run both many times. Uh, I've run Boston for the last 24 years consecutively and I've run New York. I think I forget now how many times, but more than 10. And, uh, I love them both and I'm not going to go, I'm not going to say in public which one I love more, but they're very different. Uh, they're very different. And, uh,

Yeah, that's all I'll say. But they're wonderful races and a lot of special things about both. What is one thing we don't understand about the brain that you wish we understood? So the question of what is consciousness, I think, has been a big one in philosophy and neuroscience for centuries.

a long, long time, right? You know, I think that the tools of brain computer interfaces are probably have already given, but certainly will be giving us in the next couple of years, ways to answer that in a really rigorous and quantitative way. And not just that, but I think to have an impact in disorders of consciousness. And so I think that's an area where brain computer interfaces are going to have a perhaps a surprisingly major impact.

What's a disorder of consciousness? I don't think I know that phrase. What does that mean? Well, you know, I think many people are familiar with the coma, right? So people who are alive but not accomplishmentous in the ways that you and I are when we're talking. That's just a dramatic example of that. Has the work you've done, I mean, either as a brain surgeon or in developing brain-computer interfaces, how has that changed the way you think about consciousness?

If it has. I'm not sure it has yet, but at least not in ways I want to talk about in public. But I mean, watch this space carefully.

Say one more thing about that. It's very intriguing to me. I feel like there's something you're thinking that you're not saying. A lot of it is public, and I think in really, really interesting ways. So I'd highlight some recent work or recently published work by, you know, Niko Schiff and others demonstrating that some people who seem to be in a minimally conscious state actually have the ability to communicate if you give them the tools to do so.

And that just has profound implications for the diagnosis of certain types of severe brain injury, for prognosticating, you know, the subsequent course of people who have such injuries and all kinds of philosophical, ethical, and really just most importantly, practical aspects of how do we take care of people with that kind of severe brain injury, many of whom pose

tremendously difficult questions to family and caregivers who can't predict what's going to happen next and can't communicate with their loved ones. And there's always this question in such situations, you know, is that person, the person we knew still there? And will that person come back, so to speak, or not? And answering that question is one aspect of

getting at what is consciousness and how does it fluctuate and how do we quantify it and how do we treat or restore it when it's lost or damaged so you know that has been the realm of philosophy for most of human history and um I think it is very exciting for me now that that's

That's changed in the last several years. And I do think that the technology of brain-to-beater interfaces is going to have an impact in making some of the discoveries that have come to light actionable. Ben Rappaport is the co-founder and chief science officer at Precision Neuroscience. Today's show was produced by Gabriel Hunter-Cheng. It was edited by Lydia Jean Cott and engineered by Sarah Bouguere. You can email us at problem at pushkin.fm.

I'm Jacob Goldstein, and we'll be back next week with another episode of What's Your Problem?