116. Elsa Fouragnan: Transcranial Ultrasound Stimulation, brain surgery, and French Polynesia

Elsa Fouragnan is an Associate Professor and UKRI Future Leader Fellow at the University of Plymouth. We talk mainly about her work on focussed transcranial ultrasound stimulation, a new non-invasive way other stimulating (human) brains, including deep areas that can't be reached with TMS. We also discuss her childhood in French Polynesia, how she started doing research, what it's like seeing a brain during surgery, and much more.

This was the first episode I recorded in-person. The audio quality is really good, with the minor exception that I made a really silly error during editing, such that quiet parts are sometimes not entirely audible. A few words are not audible, but this shouldn't affect comprehension.

BJKS Podcast is a podcast about neuroscience, psychology, and anything vaguely related, hosted by Benjamin James Kuper-Smith.

Support the show: https://geni.us/bjks-patreon

Timestamps

0:00:00: Elsa's childhood in French Polynesia and in mainland France

0:10:25: Why Elsa studied engineering and started doing research

0:19:04: How Elsa started working on Transcranial Focused Ultrasound Stimulation

0:23:08: What is Transcranial Focused Ultrasound Stimulation?

0:28:20: Is it safe?

0:36:12: What can you do with it/what kind of stimulations is it?

0:53:41: The practicalities of using TUS

1:04:42: What it's like to see brain surgery in the operating theatre

1:10:11: Back to the skull being a problem and which brains regions can be reached with TUS?

1:18:49: The future of TUS

1:27:59: A book or paper more people should read

1:30:13: Something Elsa wishes she'd learnt sooner

1:34:51: Advice for PhD students/postdocs

Podcast links

• Website: https://geni.us/bjks-pod
• BlueSky: https://geni.us/pod-bsky

Elsa's links

• Website: https://geni.us/fouragnan-web
• Google Scholar: https://geni.us/fouragnan-scholar
• BlueSky: https://geni.us/fouragnan-bsky

Ben's links

• Website: https://geni.us/bjks-web
• Google Scholar: https://geni.us/bjks-scholar
• BlueSky: https://geni.us/bjks-bsky

References and links

Ua Pou: https://en.wikipedia.org/wiki/Ua_Pou

Folloni, Verhagen, Mars, Fouragnan, ... & Sallet (2019). Manipulation of subcortical and deep cortical activity in the primate brain using transcranial focused ultrasound stimulation. Neuron.

Liptrot (2015). The Outrun.

Murphy & Fouragnan (2024). The future of transcranial ultrasound as a precision brain interface. PLoS Biology.

Yoo, Mittelstein, Hurt, Lacroix & Shapiro (2022). Focused ultrasound excites cortical neurons via mechanosensitive calcium accumulation and ion channel amplification. Nature Communications.

Yaakub, ... & Fouragnan (2024). Non-invasive Ultrasound Deep Neuromodulation of the Human Nucleus Accumbens Increases Win-Stay Behaviour. BioRxiv.

Chapters

• 0:00 Elsa's childhood in French Polynesia and in mainland France
• 10:25 Why Elsa studied engineering and started doing research
• 19:04 How Elsa started working on Transcranial Focused Ultrasound Stimulation
• 23:08 What is Transcranial Focused Ultrasound Stimulation?
• 28:20 Is it safe?
• 36:12 What can you do with it/what kind of stimulations is it?
• 53:41 The practicalities of using TUS
• 1:04:42 What it's like to see brain surgery in the operating theatre
• 1:10:11 Back to the skull being a problem and which brains regions can be reached with TUS?
• 1:18:49 The future of TUS
• 1:27:59 A book or paper more people should read
• 1:30:13 Something Elsa wishes she'd learnt sooner
• 1:34:51 Advice for PhD students/postdocs

Transcript

[This is an automated transcript that contains many errors]

Benjamin James Kuper-Smith: [00:00:00] Yesterday you did mention that you grew up on an island, which I

Elsa Fouragnan: I know, yes.

Benjamin James Kuper-Smith: very interesting. I don't know how boring it is to talk about it all the time, but,

Elsa Fouragnan: it is, it is not. I usually It's funny actually because I think when I, when I came back, uh, when we were, you know, I was a teenager, we came back when I was 13 and I had this very naive view that I was going to go back all the time, you know, when you're young, you don't realize the cost of even traveling and the time it takes.

So unfortunately we didn't go for a very, very long time and I had a very hard time with it. Because I, it suddenly hit me that I was never going to go back. So I actually never talked about it for a very long time. When people would say, where are you coming from?

I would say I was born in France. Done. And it, and it took me almost like a therapeutic going back there after 17 years, fully embraced that this is part of my life, you know. And now I'm an adult and I can make the effort. And then obviously my [00:01:00] parents moved back there. So that really helped as well. So obviously now we're going regularly.

And yeah, and I have less of an issue to talk about it. And I'm very proud of it.

Benjamin James Kuper-Smith: Yeah, it's interesting because like, I mean, I guess, I mean, because I was born in England, but grew up mainly in Germany and There's always like, there's always a point where I've, where I talk to people about it because they will ask and they're interested and I always find it, it's always the same conversation, you know, I guess it's always, I always find it boring, but I guess I don't have that kind of complication with it because it's just, I can just go

Elsa Fouragnan: It's also the fact that I'm white. So people won't assume that I'm from an island, so I guess there was this also other thing where you're from an island, really? It's like, yeah.

Benjamin James Kuper-Smith: Maybe we should clarify what, so when people think you You grew up in France on an island. They are definitely not thinking of the place where you grew up. So do you want to clarify? What's it called? Where is it? And also then maybe, how did your family end up there?

Elsa Fouragnan: Yeah, um, so my [00:02:00] father has always been passionate by constructing boats, and my mom could just follow him. And, uh, he, I think they decided very early on that that was the life they wanted for, for the family. So they, yeah, they just decided to go and we were very, very small. My

Benjamin James Kuper-Smith: so there was no, like, historical whatever, like, from It was just your

Elsa Fouragnan: I think they, they, they've, they've realized that very early on when they got married, that they both had this, um, idea of living far away from, um, a bit of the madness of civilization.

And, uh, if you wish. And yeah, they just took us with us. So the island I grew up in is called Ua Pou, it's very tiny. Uh, it's part of a group of island called Marquesas Island, and it's in between Tahiti and Hawaii. But it's also, I mean, it's actually really far from everything. When I say close to Tahiti, it's still three hour and a half of plane, you know, um, which would be the equivalent [00:03:00] of here going completely East Europe or, you know, it's, it's actually far.

Benjamin James Kuper-Smith: it's like flying to Turkey or something,

Elsa Fouragnan: Yeah.

Benjamin James Kuper-Smith: more than more than that, probably even

Elsa Fouragnan: Yeah, yeah.

Benjamin James Kuper-Smith: So what is it? So, um, so, uh, I mean, For context, you, you had, at the institute you gave a talk and you mentioned this in yesterday, so when you mentioned that yesterday, I just couldn't remember what it was called again, so I tried to, like, look

Elsa Fouragnan: To Google

Benjamin James Kuper-Smith: and I just couldn't, like, find any, so what is the, how big it is, what is, what was life like

Elsa Fouragnan: It's really, really small. I mean, the island in itself has maybe a thousand, nine hundred people. So, the village that I grew up with, which was the capital of the island, we were maybe nine hundred. I'm basically, I was known to absolutely everybody and even to this day, the really extraordinary thing about this island, if you do meet someone from the island, there is, you know, zero chance they don't know you.

Everybody

Benjamin James Kuper-Smith: often does that happen?

Elsa Fouragnan: It doesn't happen that often, but it did. Like once I was [00:04:00] in Lacanau close to Bordeaux and a surf sort of festival, and I heard the music and I immediately clicked. I knew this was Polynesian. And actually, it sounded Marquesan, so I went there and I said, I know that music. The guy said, well, there is this dancer that is in the, you know, back of the stage.

She's from Ua Pou. And I went there and she was actually much older than me, but.

Benjamin James Kuper-Smith: was like,

Elsa Fouragnan: Um, she asked me and I said, I, I'm Elsa, and she said, Oh, Denis daughter, are you? And I was like, yeah.

Benjamin James Kuper-Smith: I never knew

Elsa Fouragnan: And we spent the entire day together. She was like, oh, I remember you, we're tiny. But yeah, I remember your dad very well. He was making all of those boats for the island, you know.

Yeah, it's quite cool.

Benjamin James Kuper-Smith: I guess it happens very rarely, but if it happens,

Elsa Fouragnan: If it happens, it's immediate. Yeah, yeah, yeah. Yeah,

Benjamin James Kuper-Smith: if I understood you correctly earlier, then you actually moved back to

Elsa Fouragnan: when I was a

Benjamin James Kuper-Smith: you went to university or anything [00:05:00] like that.

Elsa Fouragnan: Yeah, yeah.

Benjamin James Kuper-Smith: so, so it wasn't, okay, my initial thought was then like, Oh, interesting. So you then decided to go to university, but you were already back in France and.

Elsa Fouragnan: I was back in France when I was a teenager, and the education we received, because those islands are still French, uh, is basically the same as what you would have, um, in, in France,

Benjamin James Kuper-Smith: three kids in your

Elsa Fouragnan: Metropole, so.

Benjamin James Kuper-Smith: but was it, did you still have like separate years for classes or was like everything kind of mixed together?

Elsa Fouragnan: uh, no, we had separate years, and, yeah, the education system was very good. We Actually, you know, yeah, frankly, a lot of people, they are very smart and they get into math or physics or things that might be relevant for building or, and, and it, it was actually, yeah, surprisingly a really, really high education.

Um,

Benjamin James Kuper-Smith: most people stay there on the island,

Elsa Fouragnan: no, actually a lot of people leave, they go to Tahiti, if not to [00:06:00] other countries, because there is not that much to do on the island except fishing, uh, and art. So there's a lot of art, a lot of, yeah, sculpting and tattooing and, yeah, working with stuff of nature, basically.

Benjamin James Kuper-Smith: As I'm assuming when you hear, I mean, I guess I'll, I'll put a link to something I can find so people can have a look, but. Is it, uh, I'm assuming it's like this kind of tropical paradise kind of, what you'd imagine, and, or, in terms of nature and that kind of stuff?

It's

Elsa Fouragnan: Bora Bora, where you have the big lagoon and it's just. perfect turquoise flat. Um, so those islands, the Marquesas Island are volcanic, much younger in terms of their evolution, and therefore there is no lagoon.

So it's more like big waves, surfing type. A lot of people are on horses, [00:07:00] you know, it's more that type of raw nature. There's a lot of climbing, a lot of, yeah, but, but the seas are, is more rough. Yeah, no, it was absolutely a privilege to grow up there. A hundred percent. Yeah.

Benjamin James Kuper-Smith: you know, every decade or so you meet someone from there randomly and then, but yeah, I just wonder

Elsa Fouragnan: think, I think it did shape for sure my, um, my personality and also having zero border, um, like literally not feeling that I had roots. So having zero issue in traveling everywhere. You know, I did my, uh, engineering degree in a country, then moved to San Diego for a few years and I was close to the Pacific Ocean and I felt this is great.

[00:08:00] Like I had zero, I didn't feel like attached to a place. So that gave me a lot of freedom and also a lot of, yeah, I guess. Even the way I approach opportunities that come in life, I just embrace them rather than just thinking too much about what, um, I'm maybe losing or leaving behind, if

Benjamin James Kuper-Smith: I mean, I, I understand that, but do you also, so then the one thing I have is that people ask me often, like, whether I feel more German or English. And to me, that's like a question that doesn't really make sense. Um, also because I also grew up like very close to Belgium and the Netherlands, so it's just like this,

Elsa Fouragnan: Feel

Benjamin James Kuper-Smith: concept of Germany to me is like a weird thing.

Um, apart from the unifying language, uh, presumably you have that even more, or?

Elsa Fouragnan: Yeah, exactly. I, I, um, And even maybe it's shaping the way I see, um, nationalities and you know, the fact that I would, I would so much love to live in a life where things don't have borders, [00:09:00] you know,

Benjamin James Kuper-Smith: on

Elsa Fouragnan: of course.

Benjamin James Kuper-Smith: So, it's something you still go back to, I mean, you know, regularly, but not frequently. Um, but

Elsa Fouragnan: It's very expensive and it takes a lot of time and you have an, an almost perfect 12 hour difference. And that take a good four to five days to get over with, so jet lag is painful. When we go, we take a good four or five weeks. Which is nice, but we don't do it often, like every four or five years.

Benjamin James Kuper-Smith: have kids, right?

Elsa Fouragnan: I have two

Benjamin James Kuper-Smith: Have they been?

Elsa Fouragnan: Yes.

Benjamin James Kuper-Smith: Do they like it? Did you, like, this is where I grew up, this is why.

Elsa Fouragnan: Well, they were too little,

Benjamin James Kuper-Smith: okay.

Elsa Fouragnan: To fully embrace it, and they are still little. But yeah, I'm sure that at some point they will. fully embrace it. Yeah.

Benjamin James Kuper-Smith: Pretty cool. Okay, so you're back in, in France.

Um, with a, with a weird accent or was [00:10:00] that not a, not a

Elsa Fouragnan: I, I mean, a tiny bit, but not, not too much. Um, and then, yeah, I think I, um, I, I really love a lot of things that come from work. And, you know, my dad is also on top of making boats. He teaches, uh, things to young adults. So I have always had a lot of respect for

Benjamin James Kuper-Smith: So like, he taught making boats or just other stuff?

Elsa Fouragnan: Yep. And, um, And, and so I'm, I'm actually quite, quite good at school and that's a feature, I suppose.

So quite early on, um, I had one year, uh, in advance and I started uni really thinking, I, I want to understand different things and I'm very passionate about engineering and robotics and AI and stuff like this. And AI before it became popular, I have to say. My, my engineering school was not that popular.

It was not that big. Now they are just. It's so vague,

Benjamin James Kuper-Smith: Yeah, I guess you were like in the, I don't know [00:11:00] exactly when this was, but I guess it was roughly in this time when they felt like AI wasn't going anywhere.

Elsa Fouragnan: That's exactly right. And I think we knew about the strong AI, 70s, 80s, uh, which then after came down. And the funny thing is, still to this day, thinking about the algorithms that are running, you know, uh, to create type GPT and so on, they're not that far from what I, I trained on. But it's just the enormous, you know, uh, computational capacities that we have now in the database are just humongous.

So the, the ideas remain the same, it's just that we didn't have the power to actually fully understand what was behind, uh, you know, the neural networks and so

Benjamin James Kuper-Smith: Yeah, I was saying because I had something like that once when I talked to someone who, uh, who was like a machine learning expert or something. And, uh, I think this was like 10 years ago or something, you know, like just after the DeepMind had started becoming famous and that kind of stuff, and I remember saying something like, you know, it's amazing, like all this progress, and he's like, [00:12:00] not really.

I mean, yes, but the ideas are the same, it's just now we actually have data to do something

Elsa Fouragnan: That's exactly right. A perceptron is still a perceptron. I mean, yeah.

Benjamin James Kuper-Smith: Okay, but so, was it a, uh, You wanted to do engineering? Or was it, uh, a very broad degree? Like, what was the

Elsa Fouragnan: It was actually cognitive neurosciences, uh, cognitive science I started with in, at the Uh, but then in France, you have quite a big distinction between the normal curriculum at the university and then, uh, engineering schools, and you have the possibility to jump between one and the other, um, and, and ultimately, engineering school is a bit more structured, um, the classes are, are, you know, less big, and it, it felt like the right thing to do, which will felt just maybe more secure in terms of finding a job after, uh, Because a lot of engineering schools are sponsored by big companies and [00:13:00] DNA is networking and so on.

So it just felt like a natural path.

Benjamin James Kuper-Smith: what, what are you going to do with cognitive science?

Elsa Fouragnan: Well, no, actually, I, this is

Benjamin James Kuper-Smith: I mean, it doesn't like

Elsa Fouragnan: me the most.

Benjamin James Kuper-Smith: no, of course. But I mean, like in terms of jobs, like there's not like an obvious, like it's the least applied, like psychology could at least do clinical stuff.

Elsa Fouragnan: Yep. Cognitive science is the odd one. But ultimately I came back to it. So that's the interesting thing. Um, so I got my first job as an engineer.

Benjamin James Kuper-Smith: job in, uh,

Elsa Fouragnan: Working for DARPA, it's the American Department of Research, um,

Benjamin James Kuper-Smith: yeah, you

Elsa Fouragnan: in San Diego.

So it was a company that was subcontracted by DARPA, and I worked there, uh, to classify basically EEG data. So, um, and, and to try to make something out of it. So I was basically implementing machine learning algorithms to EEG data. And after about a year, I realized I had zero idea about the brain, because I [00:14:00] really didn't know much about it, um, and somehow it was also quite frustrating to me that the results that I thought

Benjamin James Kuper-Smith: thought it

Elsa Fouragnan: going to be very powerful and easy, very naively, were actually not, it was very challenging.

Um, I was supposed to classify EEG along dimensions of attention, engagement, workload. Things that, to me, seemed quite obvious, like if you're tired, I should be able to know it easily from EEG. I mean, obviously, there is ways, right? Fatigue is something you can capture, but it was complicated and, um, and, and I,

Benjamin James Kuper-Smith: I really

Elsa Fouragnan: and I really thought I would love to know that more.

And the reality is that some people think that I, I actually made the decision to go from engineering to doing a PhD in neuroscience, but this is not true. I lost my job. Due to the financial crisis.

Benjamin James Kuper-Smith: live in now, and that

Elsa Fouragnan: But the reality was I wasn't happy at my job. And when I lost it because, you know, the situation was what it was, I felt relieved.[00:15:00]

And I felt extremely happy because I don't think I would have ever moved from my job. I was very well paid, you know, and, and I was, you know, I was useful. So, there was no reason for me to Get away. You know, that's the classic psychological bias of the sunken cost fallacy, right? You think because you've put so much energy and effort into doing something, it's worth staying, even if you're not really happy.

Benjamin James Kuper-Smith: So,

Elsa Fouragnan: But actually, it proved me completely wrong, because that was the beginning of something that I enjoyed much, much more.

Benjamin James Kuper-Smith: Lehman Brothers helped you out there quite a bit. Nice. Um, But then you end up in Trento,

Elsa Fouragnan: Yeah, then,

Benjamin James Kuper-Smith: none of the places we've talked about so far.

Elsa Fouragnan: well, no, actually, I went back to Lyon, I went back to France, uh, and I worked as a research engineer for the CNRS for about six months, during which time I created a proposal with my, uh, [00:16:00] next to be a PhD supervisor, Giorgio Coricelli, and he was a neuroeconomic guy, so it was all about decision making and the brain and Um, and I tried to get a position in Lyon, but, uh, didn't manage, and then I decided to do this European sort of concours, and it was the Trento one in Italy, um, and when I started my position in Italy, Giorgio got a position in LA.

So in fact, I spent half of my time in Trento, the other half in LA. back in California. Uh, and he was in the economic department in California, whereas I was in the neuroscience department in Italy.

Benjamin James Kuper-Smith: whereas

Elsa Fouragnan: So it was quite interesting as well to have the two sides of what I was actually studying, right? The economic theory on one end and then the more neuroscience, uh, on the other hand.

Benjamin James Kuper-Smith: was working in, um, in, um, I was [00:17:00] working in, um,

Elsa Fouragnan: Yeah, it was a long visit to LA, which lasted about like 10, 10 months. So, um, he worked at a, what was quite interesting to me is that the economic department, certain subdivision of it, they.

Benjamin James Kuper-Smith: uh, they,

Elsa Fouragnan: they were a bit reluctant to what we were bringing into the field. They, some people actually didn't believe it was useful in any way.

Uh, I guess more like the macro and economic type of, um, parts. And, and that to me was quite eye opening because obviously from the naive, you know, neuroscience point of view, I thought what we were doing was just really great and

Benjamin James Kuper-Smith: why

Elsa Fouragnan: Then I realized that, well, there are some people that have been thinking about decision making for decades without ever having to look into the brain, and they actually think it's useless.

You don't necessarily need to open the black box to resolve, you know, a decision making, at least at the macro scale, maybe that's true. [00:18:00] But I, to this day, still think it's valuable. It's very, very valuable to understand the brain because ultimately, if you shut it down, there is no us. So, there is no decision.

Benjamin James Kuper-Smith: Yeah, but this was also not exactly the start of Neuroeconomics, but pretty early on in Neuroeconomics, right? I mean, It

Elsa Fouragnan: Um, it was not that far from the start,

Benjamin James Kuper-Smith: start was maybe like, what, like late 90s or something, so this was like 10 years after that or

Elsa Fouragnan: yeah, yeah, exactly.

Benjamin James Kuper-Smith: Yeah. Thanks.

Elsa Fouragnan: gone in a long, in a long time. Long while now, so really know, 

Benjamin James Kuper-Smith: we're going to make a big jump now in your

Elsa Fouragnan: Yeah,

Benjamin James Kuper-Smith: Um, because I think if we,

Elsa Fouragnan: do

Benjamin James Kuper-Smith: I want to get to the stimulation part

Elsa Fouragnan: okay.

Benjamin James Kuper-Smith: take us quite a while to get [00:19:00] to that if we continue like this. Um, but yeah, so I guess the, the thing we'll mainly be talking about. For most of the rest of the conversation is your current work in particular, the work using transcranial focused on stimulation.

Um, maybe again, we can, we can start slightly biographically. How did that come about? for you personally, like when, when you first hear about it and when you decide to actually use it. So,

Elsa Fouragnan: Yeah, like a lot of things in life, there was a lot of like, um, so I did my, My second postdoc, uh, at the University of Oxford was Matthew Rochforth, and I was supposed to work on a certain project, and when I arrived, um, we were just afforded the chance to, to work with this new technique that just had, somehow came from France, a collaboration with Jean Francois Aubry and, and others.

Um, and Matthew had, because I was working on a human project, Matthew had very similar, [00:20:00] almost existing, uh, Uh, data from non human primates that basically were the, the animals were doing exactly the same thing as what I was interested in humans. And the data were there and they had been collected, they were fresh to be explored.

And Matthew asked me if I was interested and I, I obviously, obviously was. And midway through the question popped that, well, why don't we try to causally investigate those neural circuits? And we have this meeting.

Benjamin James Kuper-Smith: that's what

Elsa Fouragnan: And that's what we did. And it was, it was an extremely, um,

Benjamin James Kuper-Smith: kind of

Elsa Fouragnan: such an inspiring time to be in this, in this lab because a lot of people were trying different things.

And I think we were all converging towards the realization that, oh my God, this is really doing something quite, um, it's, well, almost like witnessing. Are we just witnessing the beginning of a revolution here? Like, is this thing real? And, and some of us. A [00:21:00] lot of us decided to move forward with this technology and apply it in humans, actually, most of us.

So that, that can maybe tell you to what extent, you know, what we discovered in non human primates was so striking. Uh, we replicated the effect over and over and over. Um, then there was this thing that not only you're changing brain connectivity profile of certain brain region, but you also change the behavior that's associated with it.

that is specific to the brain region you're stimulated and not just, you know, a neighboring region. Um, It was, it was incredible, so after that I decided to, um, apply for my own fellowship, my own, you know, to create my own lab, and I was successful at it, and that was the beginning.

Benjamin James Kuper-Smith: Yeah, so how, basically how developed was it at the time when you started using it? Was it really just as someone had this idea, like this could work, you know, I've tried [00:22:00] Was it already pretty, pretty far usable in that sense, or what was the kind of status?

Elsa Fouragnan: Well, to start with the, the equipment that we were using were, it wasn't like something you buy out of the shelf, um, The, the, the generator function and the transducer had been all put together by some engineers that somehow knew what they were doing, but it was very much a prototype. Uh, we were, you know, coupling the transducer to the head of the animal using silicone balloon.

I'm not going to tell you what, which type, but you can imagine, like, fill up with an uh, degassed water. So there were, it was still very much like, let's try this works type of things. Uh, there had been some work preliminary to us that had shown, especially in small animals, that, uh, ultrasound could be used for neuromodulation.

Uh, so it was not entirely new, but the fact that we were doing it [00:23:00] to very specifically modulate parts of the brain that are related to decision making, uh, that was new. Um, Um,

Benjamin James Kuper-Smith: I think we've all heard about that. Most famously, I guess, soft tissue imaging. With

Elsa Fouragnan: Yeah. The principle of, uh, ultrasound is that you're pulsing waveform,

Benjamin James Kuper-Smith: interested in what

Elsa Fouragnan: right? Um, but it also, it, it all depends as well how you, I mean, to what extent you're doing it.

So the cumulative effects to the, to the tissue. Ultrasound imaging. Uh, you basically deposit zero energy to the tissue at all. You just read echo Uh, and it's quite of a [00:24:00] diffused way of looking at the pictures whereas focus retrosound Actually, it's in the title. It's focused And the best way to think about it is like to think about the magnifying glass where you take the sun beam and you

Benjamin James Kuper-Smith: and the

Elsa Fouragnan: Focus them to a specific point and obviously if you put a little piece of paper or grass, you can, and you flame that, right?

You can increase the energy to the point where you actually, uh, rise the temperature and that can, that can do something to the medium you're interacting with. It's pretty much exactly the same. And interestingly enough, even when you are modeling it, um, there's a lot of relationship between sound waves and, and light.

Um, but So it's the same principle. You, you accumulate energy in a very specific area in space to the point where you stop. accumulating, you know, energy, [00:25:00] acoustic energy, and that energy can be, um, used, at least the neurons will sense that energy, uh, by mean of the, there is something in the brain that called osmotic pressure, and because we have this ability to sense pressure in our brain, uh, our neurons and other cells in the brain have evolved to have those mechanical sensitive ion channel, and they respond to pressure, they respond to little changes in

Benjamin James Kuper-Smith: in the community. And he

Elsa Fouragnan: And that acoustic energy is basically, you can

Benjamin James Kuper-Smith: to other things

Elsa Fouragnan: measure it as, as a, as a pressure change and neurons will respond to that pressure and they will also respond to other things that happen with, um, acoustic energy being deposited is there's a little bit of, uh, micro displacement of the tissue, the neurons will sense that they will bend the, the, the membrane will respond to that change in, maybe in capacitance,

Benjamin James Kuper-Smith: lot

Elsa Fouragnan: and, and so on and so forth.

So there is a lot of mechanic, [00:26:00] mechanic change that are happening at the neuronal level and that's how you get an effect. And that's how the, the neuron starts to fire, basically.

Benjamin James Kuper-Smith: not just neurons, right? I mean, it's funny. I once, you know, I had like psychology background. A bit of computation neuroscience. But I had this one in Paris, one week, like, course on neuron glia interactions.

And

Elsa Fouragnan: Um,

Benjamin James Kuper-Smith: I feel like this is one of the courses I cite so often just because it's such a different perspective on what the brain does. Um, and I'm pretty sure the VSAs also respond to

Elsa Fouragnan: That's absolutely

Benjamin James Kuper-Smith: So, um, so I guess you know that in the area you're stimulating stuff, like how specifically do you know what, I mean, you said neurons firing is, is that because of the direct application to the neurons? Is it because the VSAs around that are You know, releasing calcium or whatever, and then that leads to things, or But

Elsa Fouragnan: Well, there is a lot of study in vitro where, [00:27:00] uh, researchers have carefully, you know, extracted, you know, neurons or whatever, those very nice long neurons that you can manipulate and they've applied ultrasound to it and then they just looked at their ability to fire and they realized that well first a neuron can actually

Spontaneously fire as a response to ultrasound but also if you stimulate ultrasound neurons for a very long time and you look afterwards how they behave they also behave differently because they will the ultrasound will have to change relationship between certain protein alongside the membrane and other.

So for example, they will fire more. That's something that's been observed. So that's just at the neuronal level. And I suppose in neuroscience, we have this bias that we're mainly interested in neurons. We don't

Benjamin James Kuper-Smith: the, in the name.

Elsa Fouragnan: exactly, we don't exactly, exactly. Um, so. But you're absolutely right, and, and there is more and more evidence to [00:28:00] suggest that we need to consider the, the glee, the astrocytes, the oligodendrocytes, the microglee, they all have mechanical sensitivity and channel, uh, they might also be responsible for, you know, small changes in temperature that you also have with ultrasound.

So, yeah, that's, that's a very good observation.

Benjamin James Kuper-Smith: , I thought it was good.

Heating the brain, you're, you know, squishing the brain, you're moving a little, um, yeah.

Elsa Fouragnan: we can, there is, there is a way to really characterize risk in ultrasound, which is, is there a thermal risk? Is there something called cavitation risk? So cavitation is when you apply ultrasound, you have those. Waveform, which means that the tissue will be compressed and teased apart, um, as a [00:29:00] function of the, of the waveform.

So what could happen is the spontaneous microbubbles that start to oscillate, and sometimes they can explode. This is called cavitation. Um, so you don't want that,

Benjamin James Kuper-Smith: what's a micro bubble?

Elsa Fouragnan: Microbubbles will be, um, um, gas that are, that will, that will form in our brain. As a result of, um,

Benjamin James Kuper-Smith: Oh, of this. Okay.

Elsa Fouragnan: there is plenty, plenty, plenty of evidence to suggest this is not happening. Uh, what the low intensity ultrasound like where you were, you know, applying to the there is no cavitation risk, and there is no thermal rise.

It's very, very minimal, at least inside the brain. Um, however, you could also think, well, okay, let's [00:30:00] talk about what's happening. So what's happening is the tissue moves,

Benjamin James Kuper-Smith: I

Elsa Fouragnan: um, and there is changes in pressure. And you can think, okay, well, the tissue moves by, say, a nano, you know, millimeter, or a tiny bit ball.

It's maybe more than that. But think about you playing football, right? And you catch a ball in your head. The brain can move. Uh, it, it, it will be, it will be fine. Then there is also potentially the fact that, okay, well, the brain could move in, in its entirety, but if a tiny part of the brain inside the brain is moving and the rest is not moving, is that a problem?

Um, and, and, you know, we're very careful about this. I think there's a lot of people really looking at it. Uh, intensively to, to understand if this is safe or not. So there's an ongoing research, uh, looking at the safety of, of, of all of that. Um, but you also need to not forget the 20 odd, [00:31:00] 30 years of diagnostic ultrasound, which has really proven that, uh, at the intensity that we use,

Benjamin James Kuper-Smith: I

Elsa Fouragnan: right. You're right. You're absolutely right. It's still slightly different. We're accumulating, um, much more energy in a single point. And so you're right. Um, but ultimately we're still in the same sort of range of intensity of light. At least, you know, um, at the tissue where, where the transducer sits.

Um,

Benjamin James Kuper-Smith: You know, so maybe there's a contrast. You mentioned yesterday also that it's used

Elsa Fouragnan: For ablation. It's,

Benjamin James Kuper-Smith: use it at different levels and when it causes what damage.

Elsa Fouragnan: it's about like 10, 000 times [00:32:00] the intensity we apply for ablation, so we're really not in the same realm. Um, but yes, it's true. If you, if you're applying, uh, uterus arm focus to a point, Um, at a very high intensity, what you see is the thermal rise go really very quickly, uh, to a point where it will basically cook the tissue.

Um, so it, it burns the tissue and it creates those micro lesions where, where the, uh, it might not be just tumor, um, and tumor might also be complicated if they start. Bleeding or whatever, but you can actually use it to, uh, remove certain parts of the brain that are highly dysfunctional. So, say, an essential tremor, uh, you could go in some part of the brain, maybe the STN or whatever, and you could just ablate it entirely.

And that has been shown to help, uh, people from, at the [00:33:00] moment, the ultrasound is on and, uh, The part of the brain is lesioned, you can see the reduction of tremor, um, immediately. And it's, it's quite, it's frankly quite beautiful as well because it's a non invasive form of, uh, irreversible treatment. Um, but that's why ultrasound is quite, it's so powerful.

It can be used in so many different ways.

Benjamin James Kuper-Smith: Why did it take so long for it to become used in the form that you're using it because uh I can't remember exactly what it was but it's like since the 50s or 60s people have been using this right or like the first people have tried to like use it to stimulate it. Even neurons, right? Or

Elsa Fouragnan: Yeah, that's right, yeah, the Fry Brothers.

Benjamin James Kuper-Smith: 60 years until it actually came to, I don't know whether it's 60 years, but you know, like why did it take that long that people could actually use it

Elsa Fouragnan: It's the same than AI, really, uh, the technology has always been there.

Benjamin James Kuper-Smith: English language to

Elsa Fouragnan: we didn't really have [00:34:00] means to, um, have a very crisp image of the skull prior to, well, at least now, with even a, a, a normal scanner, let's say a 3D scan, you can, you can get very nice information about the skull, you don't even have to expose your participants to radiation or anything, so that's one, on the one hand, I would say the, um, advancement in, in imaging, imaging the brain, imaging the skull, And on the other hand, the capacity that we can run, acoustic simulations are quite heavy computationally.

So if you have, you know, multiple points per waveform, uh, and a grid that's the entire brain, and you're trying to compute, uh, the interaction with, with all the media and everything, that's a heavily, a heavy job. And only now, with the computers we have, uh, we can run it quickly.

Benjamin James Kuper-Smith: only now

Elsa Fouragnan: So I would say this is mainly the, the big difference.

Benjamin James Kuper-Smith: So I [00:35:00] would say this is a mix between the two.

Yeah.

Elsa Fouragnan: maybe because there was not this direct translation to humans at the time when it was discovered, the idea was somehow put aside for quite a long time. And then it was one researcher, uh, uh, William Taylor, Jamie. Who really resurrected this whole thing, um, I think in the 90s,

Benjamin James Kuper-Smith: he liked

Elsa Fouragnan: and he was working on, yeah, on a way to, you know, control neurons, uh, through multiple means, and then he, he thought, well, let's, let's bring back this ultrasound thing, because it seemed to be working, and, and it really is the, the work of this, um, man's group that completely changed the field again, and

Benjamin James Kuper-Smith: important that

Elsa Fouragnan: established it as something we need to think about very carefully and seriously.[00:36:00]

Benjamin James Kuper-Smith: establish

Elsa Fouragnan: And since then it's been pretty exponential.

Benjamin James Kuper-Smith: been

Elsa Fouragnan: The amount of interest and the number of people that are doing it and the evidence are growing very strong.

Benjamin James Kuper-Smith: then, um,

Elsa Fouragnan: being an American? Am I

Benjamin James Kuper-Smith: in a way, what kind of stimulation is it, is my question.

But what I mean is, um, Uh, you know, you can, if you think about like all sorts of different types of stimulation methods, you can have some that specifically, you know,

Elsa Fouragnan: really important thing.

Benjamin James Kuper-Smith: that you would use online during a task that can make certain areas fire or something like that, or you can have others that, uh, you know, create like in a way like a mini lesion or like a reduced function for a certain amount of time, um, and there are many more other ways, but, um, so like what kind of, uh, yeah.

Stimulation is it and if you want some examples from a study or something to show like make it a bit more

Elsa Fouragnan: Yeah, well, so there is traditional non invasive brain stimulation method like [00:37:00] TMS, transcranial magnetic stimulation, which obviously is very powerful, uh, but it remains limited by how deep you can go in the brain. So it's very much of a cortical, uh, you know, even superficial cortex sort of a method. Okay.

Um, and its spatial resolution is, is somehow good, but not like what you would call really precise. Then there is other techniques like TDCS, uh, direct current stimulation, where actually

Benjamin James Kuper-Smith: be

Elsa Fouragnan: even less precise. Um, there is new, new method like, um, temporal interference that also use electric current that can also go quite deep, uh, in the brain that also requires some, uh, some.

Simulation, uh, of, of the field and so on. But sometimes when I think about focused ultrasound, to me, even more relevant, um, is the comparison to deep brain stimulation, which actually is an invasive [00:38:00] form of stimulation. Because you can go deep, it's highly precise, 

And yeah, I just, I, I found myself reading more and more of that literature when I'm thinking about experiments that could work, and it almost feels like the roadmap to success would be, well, can we just replicate what, um, quite a lot of years of, of research now have been proving in, in the DBS world.

Benjamin James Kuper-Smith: And so just in context, that's for various clinical things. Uh, I mean, is it mainly for like Parkinson's and that stuff, but now they're applying it more to also psychiatric stuff or?

Elsa Fouragnan: FDA approved for Parkinson's essential tremor, as far as I know, um, for certain parts of the brain that there is a lot of, uh, clinical trial

Benjamin James Kuper-Smith: don't know. I

Elsa Fouragnan: on addiction, severe form of addiction, severe form of, um, anorexia of major depressive disorder.

Benjamin James Kuper-Smith: then I think

Elsa Fouragnan: To various parts of the brain again, um, depression, I think it's the subgenual ACC, part of the [00:39:00] anterior cingulate cortex, that's very close to the ventral medial part of the frontal cortex, in addiction it will be the nucleus accumbens, that's, you know, this first projection to dopaminergic cells from, um, the midbrain, and so on and so forth, and those,

They are also quite difficult, those studies to run because, What would be a sham, a perfect sham DBS?

And obviously there is, uh, it could be that there is such an enormous investment from the patient to go to have those electrodes implanted in their brain, that there might be a placebo effect. Um, that's something we cannot rule out. So somehow it's, it's a little bit hard to read those studies and fully understand what would be exactly the same thing happening if they had gone to the, the surgery and actually have not received stimulation for about six months.

Some studies do and it's really great. So what they do is that they invite everybody, [00:40:00] say 20 people, for the surgery. They implant the electrodes for half of the group. It will be on for the other group. It will be still off for another six months before it's turned on, but that is unknown to the And, and during the first six months, then they can really check, uh, how effective the, the stimulation is.

It's, it's a commitment to the patient. That's why those studies are rare.

Benjamin James Kuper-Smith: so the, , okay, so

Elsa Fouragnan: translate

Benjamin James Kuper-Smith: simulation can

Elsa Fouragnan: Um, If

Benjamin James Kuper-Smith: deep then as deep brain simulation, but is, I mean, is it as precise because it still seems to me that if you can place, you know, an electrode in a specific point. And you're, you know, a vaguely confident surgeon. You should be able to more or less hit the target.

I mean, that's what I guess, you know, all animal researchers do, right? You place an electrode in a specific place, and then you have very precise stimulation. Can you get that precisely? Or is [00:41:00]deep brain stimulation not as precise as I'm hoping?

Elsa Fouragnan: I think that you would be surprised. Sometimes surgeons are trying to reach a certain region, but actually they don't go deep enough or they're just, um, so there is maybe a tiny bit of variability, um, around the target site in DBS, because it's so complicated to do and the surgery might. You know, they, obviously they operate in the dark.

Uh, so, well, they have neuro navigation,

Benjamin James Kuper-Smith: Sorry. Oh, my sorry. For a second. I was like, why would it don't turn on the light? Sorry. Yeah, it wasn't, it wasn't a metaphor. Sorry.

Elsa Fouragnan: was a metaphor. Um, so focus ultrasound will vary depending on the device that you use. Those devices that I use for surgery that I was telling you about hypo. So high intensity focus ultrasound. They are highly precise, they have to be, because you don't want to lose, you don't want to miss the region you're targeting.

So how do they do it? [00:42:00] Uh, they send those pulses of ultrasound prior to surgery, that's actually in the realm of what we would call neuromodulation, because they don't ablate tissue, they just push the tissue, and then they use something called MR, Acoustic Radiation Force Imaging, to check where that displacement happens.

And if that displacement is in the area that they want to lesion, then they go for it. So actually, you can be highly, highly precise. That's, that's the bottom, you know, my, my take home message. But that will happen with this type of device that have more than a thousand elements, uh, distributed all over the head, um, and going to that one single point.

So it's beautiful little, you know, sphere. And it's about one millimeter, uh, large. So it is very, very precise.

Benjamin James Kuper-Smith: So you mentioned, you know, that's a very large setup that they use for that, um, and [00:43:00] not something that, from what I understand, you or other people in the research world would use. I'm curious, is that something that, um, will become, you think will become the norm? And, you know, because like basically like when you think of technology, right, it's often like first the very specialized and often rich, um, Places have a very complicated thing that then at some point as technology advances becomes the norm for many other places um, do you think that's gonna happen there or is that uh I don't know.

I guess you still don't I guess the question is on a scale like how many of these are we going to produce? Um, but yeah, i'm just curious like do you think that's something that is gonna become something that you know lab like yours can use Regularly or is it is that unlikely to happen? So, the,

Elsa Fouragnan: So, the, the device that you're referring to, the one I use in the lab, Only has four elements, and it has this quite elongated shape, um, and it's not fixed, you know, on the person's head, so there is much, much [00:44:00] more uncertainty around, first, whether or not you're on target, and, uh, the volume that actually, um, the biological, the volume that could be of biological interest is actually quite large, but

Benjamin James Kuper-Smith: it's thousands

Elsa Fouragnan: between these and the MR guided slides.

Thousands of elements, ifo system that I was telling you about that could be a middle range of device that, for example, look more like a helmet, something that you can actually put on and don't move while you're, uh, what, while it's in your head, which has a nice coupling with the skin, meaning that you still have to have some gel, but there is, this is just hardware problem, right?

And the hardware in ultrasound, um, is surprisingly cheap. So it is actually not very expensive at all to put together even a lot of

Benjamin James Kuper-Smith: a lot.

Elsa Fouragnan: little transducers or little elements, if you wish, um, in a helmet. [00:45:00] It, at the moment, it costs a lot of money because so very little companies have, uh, spent the time and effort to build this.

Benjamin James Kuper-Smith: and, it's,

Elsa Fouragnan: As you, as you say, it's, it's about, you know, uh, the scale at which you produce these things and to what extent you could, you could sell them. It's obviously because there is not that many that they remain expensive, but in terms of hardware that's used for creating the device, it's very cheap. Actually, going back to the ultrasound diagnostic world, you can have little Doppler now

That you can buy for home use with your, with your phone.

Benjamin James Kuper-Smith: the second one,

Elsa Fouragnan: And it's not that expensive at all. So I think we could go towards this world where it becomes You have a little helmet that has, um, I don't know, maybe a hundred, two hundred elements that still provide you with some, uh, specificity, but that can be used at home.

Benjamin James Kuper-Smith: I mean, I guess also, like, if the stuff that you do can be done with four, then having 100 or [00:46:00] 200 sounds like it would give you much, much more, I mean, so is there the, I was going to say much more precision is the main difference between having, you know, I mean, one difference is the. Power you could use, but that's not what you're interested in, um, right?

Like the actually burning tissue. But the other part is the, um, is it, is, is, is the main advantage just the, the, how small of an area you can stimulate or other, other differences that you get from these smaller versus larger. So,

Elsa Fouragnan: So, I mean, in theory, the, um,

Benjamin James Kuper-Smith: is

Elsa Fouragnan: uh, MR guided hemispheric, uh, you know, um, array that I was telling you for HIFU could also be exactly the same, uh, for TOS, right, for transcranial intracellular stimulation. So, in a sense, you could just imagine this is a neuromodulatory tool and that's it. Because it's, it's, it would be the same.

Uh, the, I think the interest with those device is that you're certain [00:47:00] of the position of your target, uh, of your focus. That's the main difference, really. Whereas with the, the one that we have in the lab, uh, you have much, much more uncertainty over where actually the, the focus of your. transducer is inside the brain.

Benjamin James Kuper-Smith: know, situation. Why

Elsa Fouragnan: Why? Because you have to use neuro navigation technique, you have to register the person face in, in space to your device, and even just doing this has inherent uncertainty, about one or two millimeter. That, that's what

Benjamin James Kuper-Smith: with the other one also? Or like, I mean you still have the, from what I imagine, you still have the same problem of like, a brain, and the device itself, and then you have to figure out how they relate to each other.

Elsa Fouragnan: is that you could do MR RFE with it, and you could see if your focus is where you are intending it to, because it's, it's MR. [00:48:00] I think that's why those device will not become the norm, because they have to be, they are inside an MR scanner, and an MR scanner is very expensive. Um, so yeah, relying on other methods to register a helmet. to a skull. I imagine this is going to be solved. It, it doesn't seem to be so complicated.

Benjamin James Kuper-Smith: And we have the same for MEG. Yeah.

Elsa Fouragnan: I don't think this is going to be a major problem for the very smart engineers that are working in this field. They will, they will crack that.

Benjamin James Kuper-Smith: Yeah., So one thing I was, um, I was reminded by repeatedly when you talked about the technological development was I had an interview with, uh, Gareth Barnes about the new MEG systems and it seemed like it was basically like it was word for word the same thing at times whereas like

Elsa Fouragnan: or

Benjamin James Kuper-Smith: [00:49:00] we have this thing and it, you know, seems to work and actually it should be pretty cheap to do but we don't have vendors who produce it really in that sense and there's questions of scale, raw values.

It's kind of in, and it's the same thing where also like, they also producing helmets to put on people so they can, it was just funny like how, uh, even though, I guess it's both neurotechnology, so it's not that surprising that there are similarities, um, yeah, I just had to smile a few times when he said that because it's just so similar. Um,

Elsa Fouragnan: but even like research organization that didn't exist, that now exist, that receive really a lot of support to create those device.

So I'm quite hopeful that we will come, [00:50:00] it will come, we will come to a place where those devices exist and we can, we can use them for research, which is another point of discussion. Because I, um, it, this is just the way it works for creating a medical device. Um, and having approval to actually use it in a clinical sense is that for, for example, with DBS,

Benjamin James Kuper-Smith: was approved

Elsa Fouragnan: not like DBS was approved

Benjamin James Kuper-Smith: for any type of

Elsa Fouragnan: stimulating the brain for any psychiatric disorder or neurological disorder, right?

It was, um, stimulation to the STN will be approved for Parkinson's. You have to prove this is safe. You have to prove this is working and you have to prove that the protocol you use or. With some range, you know, of, uh, is safe and it's fine, and that will be approved. And, and it might be that, uh, the, the, the industries that are wanting to create those device, they will have the same constraint where actually, [00:51:00] instead of creating a device that what we want in research, right?

You can simulate absolutely every single part of the brain. You can search the parameter space and you're free to do your beautiful research and you have the device that allow you to have this freedom. It might be that they will create a device that stimulate the nucleus accumbens, and that's it. With a very limited range of the, you know, of, of the parameter space.

Because that's the way they are going to have approval for using it, and therefore they are not going to really think, well, I don't care about all the other parts of the brain because I want something that will be used for addiction.

Benjamin James Kuper-Smith: can optimize it for their

Elsa Fouragnan: And I will just

Benjamin James Kuper-Smith: the question of

Elsa Fouragnan: Well, the question of optimization might actually be not true.

It might also be that they start with one protocol, one brain region, they see it works, boom, they create

Benjamin James Kuper-Smith: really

Elsa Fouragnan: 10,000 copy of that thing, and it might the, it might really be that then you end up in a bit of a local mini like, well, [00:52:00] this worked, but it wasn't fully explored like. So I would really hope that in parallel to the industries that are creating those very focused device that would work for one indication, um, with one setting, they could also think about us, the researchers, like, can you give us please something that allows us to try a lot of things and simulate every part of the brain?

That would be really cool.

Benjamin James Kuper-Smith: Yeah, do you have a lot of, uh, interaction with the manufacturers, or is that,

Elsa Fouragnan: Because the field is so new, yes, I, uh, I do interact with, uh, some people in the Silicon Valley, but also in France, um, and I can just see the, yeah, the burden of translating, uh, what we do in the real world is, it's something else. It's a whole different world. Yeah.

Benjamin James Kuper-Smith: But they've, you can repeatedly ask them, please do a better scientific one and

Elsa Fouragnan: Or just, yeah, just, just, um, in parallel [00:53:00] to what you want to sell to the clinic, give us something that we can use.

Benjamin James Kuper-Smith: I mean, my perspective seems like a very sensible idea, but I don't know, I don't run a

Elsa Fouragnan: We're just not a very big market, so I don't think that they

Benjamin James Kuper-Smith: Like how many can we sell like 15? No,

Elsa Fouragnan: That's not very appealing for a

Benjamin James Kuper-Smith: uh I mean, I don't know why I was I was just thinking of like car brands, you know, that's like more like Formula one kind of you produce like a couple of types that have a very powerful specific purpose, but It's not going to translate

Elsa Fouragnan: It's not the one that everybody would use. Yeah, to go to

Benjamin James Kuper-Smith: Yeah,

Elsa Fouragnan: exactly.

Benjamin James Kuper-Smith: yeah, yeah, so, uh, I wanted to ask a little bit about the practicalities of doing this kind of research.

So, um, you know, principle, this is very interesting to me. And I definitely have some ideas where this could be useful. Um, so I'm just curious, like, what are the, let's say I want to do this. What are the steps? [00:54:00]

Elsa Fouragnan: Yeah, Um, so say you wanted,

Benjamin James Kuper-Smith: you set that

Elsa Fouragnan: yeah, say you wanted to start and you're thinking about the practicality, it's, it's maybe not true that you need to have an expert in your team to, that has already done it. There is workshop training now, we actually run one in Plymouth where you could come and for three days you're gonna be hands on actually running the thing with us and we'll show you all the steps.

So one thing that I was saying, in my view, it would be better if you're, um, Intervention or your, uh, focus interest on your modulation session in the lab has been initialized by an MR scanner. So you get your structural image of that person's brain and then some indication of their skull density. You can all do this with a normal, you know, 3T scan.

So that's done prior to the participant coming.

Benjamin James Kuper-Smith: because

Elsa Fouragnan: Then, obviously, we have their brain [00:55:00] anatomy, and it's important because we are talking about precision neuroscience here, so I think it's important to have a brain. Um, so you have the brain image and you, you know, say, well, I want to go there. I want to go in the nucleus accumbens for that person.

And I'm going to just, um, simulate how the acoustic field would look like through a software. And you do this, you just say, well, I want to position my transducer here. Here's my target, press the button, check how the pressure field would look like. Is it, does it look safe? Does it look like it's efficient?

You know, there is enough going in. And then you're like, okay, that, that, that looks good. Let's invite this person forward. Person comes, sit down on the chair, has usually a neural navigation system in front of them with a camera on, on a screen. They will see their brain. Uh, we register them to space exactly like you would do with TMS.

We do the same with our device, which looks like a little, uh, small Circle, um, which with a certain thickness [00:56:00] and this thing called a transducer is plugged to a generator function. This has to be coupled to your head.

Benjamin James Kuper-Smith: of

Elsa Fouragnan: So it's registered in space and we know we can do neural navigation, but it also has to touch perfectly the skin through some medium.

Um, and a medium that would be close enough to the skin, for example, would be aqueous soft tissue, like gel, the gel that you would use for pregnancy. It's the same thing, you know, if you've ever seen it on movies or, um, we, we would get like this really thick amount of gel before the, the transducer, the probe is put on the belly to make perfect contact.

So we have to do this as well.

The issue is that we have the hair in between, so sometimes we spend a lot of time just really preparing the hair, making sure there is no bubbles. And the bubbles would be the problem of different types of tissue in between transducer and the skin. Um, and this, you know, medium air

Benjamin James Kuper-Smith: energy that

Elsa Fouragnan: mean a lot of reflection.

So [00:57:00] your energy will go back to the transducer and it could damage the transducer on top of not being efficient at all, because it's not going to where you want to go. Um, so we spend a lot of time preparing the hair. Um, and then we couple the transducer to the, to the head and we check the neural navigation, make sure we're on target, and then we press a button and we deliver the energy.

For how long, uh, your, you know, your simulation duration is. And after that, so it could be actually done at the same time as the person is doing a task.

You could, uh, use, for example, some, some ways of, of keeping the transducer to the head and for it not to move. And then you could maybe pulse every time someone sees something on the screen.

Um, so that's very much what you would do also with, uh, with TMS, sort of an acute effect you're interested in. Otherwise, you could also be interested in neuroplasticity, which are those much [00:58:00] longer lasting effects, in which case you, again, do exactly the same thing, put the transcript on the head, uh, send, you know, the, the waveform through,

for maybe a longer period of time, in order to have longer lasting effects.

Benjamin James Kuper-Smith: longer life. Longer lasting meaning,

Elsa Fouragnan: at one hour, two hours.

Benjamin James Kuper-Smith: wow, is, so, Isn't hair also a different medium? Or

Elsa Fouragnan: it's, it's brilliant, uh, yeah, some of us have done stuff like this where basically you, so you put ultrasound in a, in a, in a tank, it looks like a water bath. You have a hydrophone on one hand, which is a bit like your mic, basically, it will just record the, the ultrasound, in water,

Benjamin James Kuper-Smith: Why? Yeah.

Elsa Fouragnan: media and, uh, water will, uh, the ultrasound will propagate perfect.

Yeah, that's like almost your perfect, case [00:59:00] scenario. Even better would be that the water is the gas because there is this micro, micro bubbles in water that you don't see. But so what you could do is that between your transducer and your mic, your hydrophone. You could put some hair and just check, is the hair actually problematic?

And it's not. If you, well, if you put the hair in another, uh, water bath solution, put the whole thing in between the two, you will realize that the hair itself is not a problem.

Benjamin James Kuper-Smith: Okay, so it's like, yeah, but also, uh, one thing, um, 

Elsa Fouragnan: Um,

Benjamin James Kuper-Smith: and that's all kind of very nice, but there are certain problems in terms of reaching some areas depending on the angle of the skull and sinuses these kind of things, uh, so can you elaborate a bit a little bit on that kind of the Um, we haven't really talked about the skull yet um [01:00:00] So yeah, basically what how does that how can those I mean the sinuses again filled with air But like specifically what are the consequences of that and 

Elsa Fouragnan: so, uh, the sinuses would be exactly like big fat air bubble, it would mean a lot of reflection, if not all reflection entirely to the transducer, so that would be very inefficient. So you don't

Benjamin James Kuper-Smith: so why is air such a refractory thing if it isn't? I mean, we can talk right now with sound, right?

Elsa Fouragnan: Yeah, yeah, yeah, yeah. Um, so, ultrasound propagation depend, so it's the, the speed, the speed of sound depend on the impedance of the tissue that is traveling through.

Benjamin James Kuper-Smith: the

Elsa Fouragnan: So, for example,

the, so the impedance, uh, and also the resistance, uh, of the tissue to, uh, to compression. So, air, Or, uh, some medium are highly compressible,

Benjamin James Kuper-Smith: Like, there's

Elsa Fouragnan: meaning that the wave is going to propagate at a certain speed.

Uh, some [01:01:00] medium are really, really hard to compress, meaning that the waveform is going to propagate super fast.

Like bone, for example, or iron. You know, if you're on the, on the rail of a train, if you hammer it, it will just propagate at a speed. So. Yeah, that's the interesting thing. The frequency remained the same, but it's just the, the speed at which it transmits

Benjamin James Kuper-Smith: And so when we say speed of sound, we mean through air, or,

Elsa Fouragnan: any, uh,

Benjamin James Kuper-Smith: it says,

Elsa Fouragnan: through any medium. So this, the speed of sound, the speed of the, yeah, the speed of sound will change depending on the

Benjamin James Kuper-Smith: Yeah, that's what I mean. Um,

Elsa Fouragnan: That's right.

Benjamin James Kuper-Smith: again, the,

Elsa Fouragnan: Um, and so again, 

The, the transmission of the, of the sound will depend on the impedance of the tissue. And the issue is that the impedance of, of the skin and the brain is very much like water

and the impedance of air is very, very different than the one of water [01:02:00] and even more different than the bone, but that's another thing.

So anyway, you want to be able to couple, uh, your, your transducer to whatever First medium of interest will be. So that is the same.

Benjamin James Kuper-Smith: So it's more about the change of medium rather than

Elsa Fouragnan: That's exactly right.

Benjamin James Kuper-Smith: is that the, yeah, is that the same thing like when, you know, you look through water, through a glass of water, that kind of thing and it changes the angle?

Elsa Fouragnan: Well, that's actually the Snell law and this has to do with refraction. So this is, um, well, you're right. It's also a change of, , yeah, it has to do with the differences in, the speed of sound, you're right. Uh, and, but that will also, so that would mean that basically the, the waveform will be propagating at a different angle.

That's what we call refraction. Rather than reflection, 

Benjamin James Kuper-Smith: so from, it's about the sciences, so it just means, so what are the like precise consequences if you can't it at the, at the,

Elsa Fouragnan: [01:03:00] it's a bit

Benjamin James Kuper-Smith: so it just means you just can't, can you still get to frontal areas?

Or

Elsa Fouragnan: with the classical transducer that we have in the lab. So again, theoretically, with different types of transducer, maybe you could do it.

You could go from other parts. But with the classical one that you might end up using in your neuroscience lab, it will be one of the trickiest areas and it's the same with the ear, right? If you have a brain area that's right behind your ear, it's going to be quite hard to reach. So

Benjamin James Kuper-Smith: the angle of the skull or something like that.

Elsa Fouragnan: the angle of the skull is exactly

Benjamin James Kuper-Smith: [01:04:00] Also, just briefly first, the skull in general. Uh, why is the skull such a problem for you, for this kind of research?

Elsa Fouragnan: Yeah, the skull is just going to account for the bulk of, uh, of transmission loss, basically. So there will be a lot of differences between the gel, the skull, and then the brain. So because of that layer, and actually the bone in itself is not a single, uh, layer, it's made of multiple layers. That, uh, basically will translate into different types of losses.

And one that is particularly tricky in the bone is called the trabecular bone. And it's in between the two more If you have ever seen a skull, have you seen a skull? It's quite interesting.

Benjamin James Kuper-Smith: actually seen Skull being cut open live.

Elsa Fouragnan: Ooh!

Benjamin James Kuper-Smith: Yeah, it's a, it's a longer story, but I once, uh, spent almost a week in operating theater watching people's doing life of, uh, tumor removal.[01:05:00]

Elsa Fouragnan: Wow!

Benjamin James Kuper-Smith: Yeah. So yes, I have.

Elsa Fouragnan: So you've seen it, and, and, and it's a very complex bone. It's, uh, it's made of different layers, it's, there's a marrow, you

Benjamin James Kuper-Smith: Yeah. So I didn't, uh, I didn't see that. Uh, I just, I mean, to be fair also, I mainly, because that was the first time that you just take it out. Thank you. You have a square of skull that you cut through, I mean, draw through

Elsa Fouragnan: Did you faint the

Benjamin James Kuper-Smith: No, I didn't. I was slightly nervous about that because I have faint in the past.

Usually only actually my own blood for some reason. Um, not actually other stuff. No, so I was a bit, I was a bit nervous. I didn't tell anyone that I was like, I'm just gonna not pretend that this is a problem. Um, well, it might be a problem and it

Elsa Fouragnan: it could, it could also be that even if you don't want to faint, you faint, right? It's not like,

Benjamin James Kuper-Smith: but I feel like, you know, sometimes you can also, uh, it, it seemed to me like

Elsa Fouragnan: Um,

Benjamin James Kuper-Smith: a little bit on edge wouldn't help the situation.

Uh, so I was just like, if I, [01:06:00] if I have to, I'll just like sit down or whatever, but I know it was fine actually. I was, I was, I was surprised like how

Elsa Fouragnan: Yeah,

Benjamin James Kuper-Smith: I don't know, I, I find it very, uh, Quite calming in the operating theater. Because I mean, it's also like I have no responsibilities, nothing to do, right.

I'm just there to watch. Um, but no, the only, you know, the only funny thing is that, um, Oh, this is so embarrassing. So they, um, so the, the first time I saw one, right. Actually, it was two, two, two funny things. So first of all, the first thing I didn't know is that clinicians and neuroscientists, uh, look at the brain in different orientations.

So clinicians look at it from the bottom basically. So left and right are reversed. And so the first time I was like on like, because I had this image right of the MR MRI where the tumor is. I was like, yeah. I was like, is

Elsa Fouragnan: was like,

Benjamin James Kuper-Smith: I say something ? But I was like, [01:07:00] I'm not gonna, like, not the very first time I'm here, I'm not gonna say anything.

And then I figured it out at some point. Um, no, the other thing that was basically as embarrassing was so they, uh, you know.

Elsa Fouragnan: this call is because of,

Benjamin James Kuper-Smith: Remove the skull. And then, you know, just started cutting. I was like, oh, they're cutting into the brain and blah blah blah. Like, is that the way it's supposed to be? And then only after a while I was like, oh, that's not the brain, that's the deromata.

Elsa Fouragnan: like, I'm not like,

Benjamin James Kuper-Smith: But like in my like excitement of seeing the brain, because like obviously there's like blood on top and I'm not like right there. You know, I'm not like half as, you know, I was like. Two meters, three meters away or something, right? So like you couldn't see it as precisely. But yeah, for a second I thought like, they're just cutting into the Yeah, no, it wasn't the brain.

Elsa Fouragnan: they will do,

Benjamin James Kuper-Smith: Uh, they were doing, uh, tumor removal. Yeah, exactly. So this was, uh, which is weirdly enough looks different than you, I thought. Because you, you [01:08:00] No, so the weird thing is the tumor you can't actually see. From, from what I can tell it looks, the ones that they look kind of the same. Um, I think they have like some sort of way of making it look different.

I mean, so they have all sorts of things, right? They have a, their navigation to see where exactly they are and where the tumor is supposed to be. I think they also have some sort of way of correctly staining it a little bit. So you could see it, it would like, you know, reflect slightly differently, different types of tissue or whatever.

I don't know. Um, but the, no, the tumor looked the same. What was really surprised me is like the way they remove it because you think of it like, you know, I guess the, the thing that I thought of is more like, you know, Cutting into something, right? But it was more like a Little hoover, you know, like a vacuum more like sucking it up slowly like layer by layer Yeah, but I thought it would it would require more I mean, I guess the brain is very soft But I just never thought that it would be that easy in a way [01:09:00] to um Yeah

Elsa Fouragnan: So I assisted once to a surgery because I was quite friend with a neurosurgeon and he allowed me to be in the theater and I fainted.

Benjamin James Kuper-Smith: no,

Elsa Fouragnan: I didn't expect it to be so strong and I, and my body just didn't like it.

Benjamin James Kuper-Smith: smell it, but it was also like you're wearing like all sorts of stuff. And I don't know, I think, uh,

Elsa Fouragnan: But you quickly get used to it, that's the thing

Benjamin James Kuper-Smith: Yeah, I

Elsa Fouragnan: told, and it's very true, like, second time around, I'm fine. Then it

Benjamin James Kuper-Smith: Oh, so you went back again after the first, okay.

Elsa Fouragnan: makes you wonder about, like, yeah, how actually sad it is that you can get so quickly used to it. Yeah. Yeah.

Benjamin James Kuper-Smith: how it's like when [01:10:00] you go to surgery. Uh, yeah, anyway, so yes, sorry.

Elsa Fouragnan: So, the skull is a big problem, uh, so what you were saying about if you're coming at an angle, that was the, the problem of refraction. If your, if your incidence wave is coming at an angle with respect to the skull, it will just bounce back, but it's not exactly the same as reflection. So there is this type of loss.

Then there is something called attenuation, um, and attenuation will mean that, uh, the The, the energy will transform into heat, and that's quite problematic. Um, and there is, so basically, about more than half of the energy, much more than that actually, at least two third, will be lost at the skull interface.

And, and that's very problematic for us in this field, because we, obviously we would like all the energy to go through. And we also don't really want to have massive [01:11:00] temperature rise in the skull that could be problematic because, as you say, that there is the meninge not too far away. Well, you don't maybe want to boil the meninge at, you know, seven or eight degree or more.

Um, even if that means that the intensity that goes in is very safe. See what I mean? Is that

Benjamin James Kuper-Smith: stuck at one place,

Elsa Fouragnan: it just gets stuck in that one place. So you're constantly trading off. What you would want to do, which is maximize efficiency, but you also want to minimize the risk of, uh, heating up the surrounding tissue to the skull.

Because in a sense, we don't fully believe that the skull heating up is a problem, but there is the skin nearby, there is the meninges nearby, and there is a brain nearby, actually. You know, so you don't really want that to heat up. Um, And then there's the whole question of what is actually an acceptable thermal dose, or you know, if you go to the sun, to the Caribbean, in the middle of the summer, and you [01:12:00] lay down, uh, for two hours, sun full on in your head, I can tell you that your head is going to, is going to heat up.

Um,

Benjamin James Kuper-Smith: even if you just wear a hat.

Indoors. Well, yeah, yeah.

Elsa Fouragnan: yeah, exactly. Um, but then we also know that physiologically, you get a fever that's very problematic, and it's only two degree up. So, temperature, it needs to be monitored very, very carefully, and it's basically the main reason why, um, we, we feel that we're limited in case of what we, in terms of what we can do with ultrasound.

Benjamin James Kuper-Smith: is that also an advantage of having a big system with lots of,

Elsa Fouragnan: Yeah,

Benjamin James Kuper-Smith: because you get at it from different angles rather than,

Elsa Fouragnan: And you're distributed. Yeah, yeah.

Benjamin James Kuper-Smith: Yeah, I mean, so we, we, we've talked about the, you know, that you can reach, your brain region, that But we haven't been very specific about what exactly we mean here. Um, so yeah, maybe compared to, [01:13:00] Uh, let's say like TMS or something like that, Um, what, what are specifically some regions you can, So I guess there's two questions.

One is which, what can you reach? And the other is, um, which areas can you reach safely? You know, depending on, I think you mentioned yesterday, some, you know, some areas you don't want to stimulate because they're too close to some other regions that you definitely don't want to stimulate. So, so at least, but yeah, so kind of what, which regions can you kind of easily reach ?

Elsa Fouragnan: We, we have been very successful estimating many, many parts of the subcortex, which is very exciting. Uh, you know, the nucleus accumbens subdivisions of the thalamus, the amygdala, uh, the hippocampus,

Benjamin James Kuper-Smith: be. So, so, again, it's

Elsa Fouragnan: All, all those areas, the STN, subthalamic nucleus for Parkinson's, very exciting. Um, these have been explored and, and showed that it's quite safe.

So again, there is all the deep cortex, right, that we can't really, um, traditionally reach with [01:14:00]TMS or TBCS. We can also reach, of course, all those regions. Um, what I was mentioning yesterday, it's just that we don't know. Uh, we could, in theory, we could go much deeper, uh, midbrain. Um, Even the pons, uh,

now, I don't know if I really want to do it, like, right now, you know?

These are the parts of the brain that regulate your breathing, your heart rate. Do you really want to mess up with it? I don't know.

Benjamin James Kuper-Smith: of

Elsa Fouragnan: So, actually, it was more of a comment, um, than any proof that this is unsafe. I think it's more of a, I would be cautious to go there in the first instance, but But why not?

Obviously, the midbrain has all those nuclei that are projecting, you know, to, um,

well, the locus cerellus, the ventral tegmental area that are so important for learning and decision making, the substantial nigra. Um, and actually, some deep brain stimulation are going that deep. [01:15:00] Uh, so, so, It, it doesn't, um, frighten the neurosurgeon to go that deep and stimulate those, those regions, uh, with electrodes.

So, in theory, maybe this is where we're gonna go. I don't want to be the first one to do it.

Benjamin James Kuper-Smith: Yeah, I mean also there's so much other stuff you can do so why go to something that's even if just a little bit risky, if you can do all the other stuff first and learn stuff along the way then.

Elsa Fouragnan: Yeah. And maybe, you know, I'll change my mind and in a few years, I'll be, I'll be there.

Benjamin James Kuper-Smith: Yeah, there was an interesting point, um, about the difference in effect between stimulating the deeper regions versus the cortical regions. That seemed very interesting. Uh, can you elaborate on that? I

Elsa Fouragnan: Yeah, it's something I've, I've observed. I think it's, it's almost anecdotal. I haven't reported this in the paper or anything, but it seems to me that the effect we're observing when we're reaching deep in the brains are just stronger. than when we are going [01:16:00] in the cortex, um, with ultrasound. So obviously, ultrasound is highly, highly precise, and maybe there are some cortical regions that are so big that actually being very precise in big fields, like having a needle, trying to find a needle in a field, you know, it maybe just doesn't make so much sense.

And we would want to have, um, we would want to just stimulate more of the tissue if you're in the cortex to make sure that really you're covering the entire Brodmann area that you're interested in. So, generally, the,

Benjamin James Kuper-Smith: So just a brief interruption there, is the, I mean, but presumably can't, can't you also stimulate a larger area? I mean, do you, do you have to be precise, or can you also be broader in your stimulation? [01:17:00] Oh,

Elsa Fouragnan: I can just draw the, the area,

Benjamin James Kuper-Smith: you mean like, uh, sequentially.

Elsa Fouragnan: stimulate multiple times sequentially along

Benjamin James Kuper-Smith: really, really, really,

Elsa Fouragnan: part of it.

So I don't think this is problematic. I think we just need to think about it along those lines. Uh, the subcortex is generally more preserved across participants, and you have those condensed neurons into a very small area that are doing something very important for the entire brain. So this is maybe just what it is, that there is more specificity even in the brain in terms of structurally in the subcortex.

Benjamin James Kuper-Smith: and it's, yeah,

Elsa Fouragnan: So, and, and it's, they are actually also more well known. We know more about the role of the core of the nucleus accumbens and the shell of the nucleus accumbens than we know about two subdivisions of the ventromedial prefrontal cortex, right? Like, if you, if I point at the sub part of the [01:18:00] ventral medial prefrontal cortex and I ask you what is this part doing, you'll be like, well,

Benjamin James Kuper-Smith: Lots of different

Elsa Fouragnan: lots of different things.

Exactly. Um, whereas if I say the core of the nucleus accumbens, maybe that will resonate, you know, with some, some concept.

Benjamin James Kuper-Smith: Okay. So my, so there's a, there's a bunch of different, I mean, okay. I didn't actually realize, I thought it was a bit more established than, um, just something you observed. And, uh, it seems to be there, but anyways, but like, okay. That's the main reason that basically it, it might actually be more specific.

And we, um, It's more similar in each participant, so I guess meaning then also you're more likely to actually simulate the same kind of functional

Elsa Fouragnan: That's right,

Benjamin James Kuper-Smith: in that, yeah.

Elsa Fouragnan: Maybe easier to probe as well.

Benjamin James Kuper-Smith: Yeah. Um, okay, so that's basically the present.

Elsa Fouragnan: Yes?

Benjamin James Kuper-Smith: We've talked a little bit about the future, but, uh, I mean, maybe, you know, next kind of steps, what are you, uh, [01:19:00] what do you want to do next?

Elsa Fouragnan: Because I,

Benjamin James Kuper-Smith: gentleman, it doesn't

Elsa Fouragnan: yeah, yeah.

Benjamin James Kuper-Smith: You can have

Elsa Fouragnan: Because I truly believe that this, um, could completely transform the way we are doing

Benjamin James Kuper-Smith: be

Elsa Fouragnan: well, first, my job is cognitive neuroscience, right? So I, I'm not going to take the hat of someone that works in a hospital or anything. I'm just going to take the hat of someone who is interested in the brain.

Well, all of a sudden we can probe causally the role of certain parts of the brain and their relationship to behavior with high precision, and it just seemed, I mean, incredible to me. Just this in itself, to use it as a search tool to better understand the brain is, is amazing. And now I'm going to take the hat of someone who worked with patients from time to time, and I could say, well, this could also be transformative for people that are suffering Psychiatric disorders and neurological disorder because all of a sudden we have the precision of deep brain stimulation non invasively.

Um, [01:20:00] and if, if it works, um, whether it is through having something chronically implanted in your head that pulses ultrasound all the time, or whether you have at home a non invasive sort of helmet that you can use in conjunction with some cognitive therapy maybe, or that you have to go in a, in a clinic every week to receive your treatment that is personalized to your, um, disorder. I, I, I see ultrasound being everywhere. In a clinic, potentially at home, um, or of course in the lab.

Benjamin James Kuper-Smith: every lab.

Elsa Fouragnan: In every lab.

Benjamin James Kuper-Smith: god. Yeah, but that's because I don't know

Elsa Fouragnan: God, you're going to ask me the question that we're going to meet in 10 years and we'll be like, this was completely wrong.

Benjamin James Kuper-Smith: care of

Elsa Fouragnan: [01:21:00] Yes, exactly.

Benjamin James Kuper-Smith: the lab. That's completely wrong. Is it more the vendor technological side, where you just need someone to produce those things actually? Or is it, uh, conceptually of how to use it, how to work around certain problems?

Or like, what are the kind of, I guess the bottlenecks for this to become widely adopted? Yeah,

Elsa Fouragnan: You, I think you understand the problem of the, the whole space. It's. It is, it's true. Hardware needs to be pushed up by the industries working on that. Software side of things, it is possible that we would be becoming more and more clever in, uh, in doing acoustic simulation very, very quickly, in a matter of minutes or seconds even.

Benjamin James Kuper-Smith: should happen.

Elsa Fouragnan: That should happen. Uh, I think, I think that

Benjamin James Kuper-Smith: Because that's just Moore's law and better algorithms. So,

Elsa Fouragnan: right. So I think, I think this is going to happen. Then there is the adoption. So, say, in the clinical world, that's the, the adoption of, um, the, the [01:22:00] clinicians and practitioners.

Benjamin James Kuper-Smith: the clinical one,

Elsa Fouragnan: Again, I think because it's ultrasound, and in the medical world, ultrasound has been used already so much, the barrier to adoption might be less so than other techniques.

Um,

Benjamin James Kuper-Smith: then there's,

Elsa Fouragnan: yeah, and then there is a problem with the skull. And the problem with the skull might be solved by actually You don't necessarily need to put someone in an MR scanner to get the scan information. Maybe you can actually use other sensors, um, maybe even ultrasound that send and receive. So devices that are, that have include in it, something that can probe the density of the skull where it's supposed to go through,

Benjamin James Kuper-Smith: mean, like almost, I mean, it would want to be reflection or the other, just like sending it from one side of the brain to the other and seeing how much gets

Elsa Fouragnan: yeah, something like that. And then you could measure the loss. And you can say, well, I'm going to compensate for [01:23:00] that.

Benjamin James Kuper-Smith: aspect, it sounds to me like that might be a way, I mean, like an indirect way, a slightly awkward way to get vendors to care about it in the sense that like they then have something that they can, you know, if this becomes clinical routine practice. But. They're not going to sell 15 of those things, but thousands, right?

And obviously they're not going to do it exactly for your purposes, but it should still like help everyone in science too, right?

Elsa Fouragnan: I think if the industries really catch up on this, we'll benefit from it. So what

Benjamin James Kuper-Smith: uh, Um, Yes, yeah.[01:24:00]

Elsa Fouragnan: was the question here?

Benjamin James Kuper-Smith: Do you agree? No, I don't know. That wasn't really, it was, it was just, it was just an observation, Uh, that, um, I don't know, I guess, I guess the point was that like, So maybe I got this actually slightly wrong, but I always saw you as a basic scientist. I mean, I guess you are doing clinical stuff also, right?

Um, but I guess it was more the observation that, you know, for basic scientists to advance your own agenda, it can help to help other people if they hold much more power. So,

Elsa Fouragnan: No, no, a hundred percent. I think also, um, the people that are working in that field at the moment on the hardware point of view, they're engineers, they're not neuroscientists.

They don't fully understand the complexity of the brain, and, and we are only starting to scratch the surface of what we know in the brain.

We do know certain things, uh, we should give us some credit for that, we, we've [01:25:00] started to really understand very well how certain parts of the brain behave, but there, again, and you know, you're the first one to study psychology, and there is a huge variability across participants, or across people.

Because of maybe their genetic background, their context, their history, um, and even maybe simply the way their brain is organized. So you have those highly dimensional, um, complexity problem here of actually even just, We can go back to it, but psychiatry in general is ill posed in terms of treatment. So we know that some symptoms don't really necessarily, uh, predict very well treatment response.

So maybe we need to move from the DCM, you know, five or six or whatever, to more thinking about transdiagnostic traits like impulsivity, which are actually much better understood in terms of brain. [01:26:00] So this is going to take a long, long time for neuroscience to actually be listened to by the medical world.

But also by these guys that are creating those beautiful devices

Benjamin James Kuper-Smith: makes

Elsa Fouragnan: in a way that makes sense, um, because, yeah.

Benjamin James Kuper-Smith: because like, if, to show a clinical application, you know, if you have a very ill defined thing you're trying to improve, it's going to be very difficult to do that, even if the stimulation protocol is perfect.

Elsa Fouragnan: Exactly, that's exactly right. Or, say someone comes and say, I'm depressed. Well, what, you know, like, you need to do more. What sort of, biotypes are you talking about? Is that a rumination problem? Is it a apathic problem? And so on and so forth. And therefore you could say, well, actually for you, given the, your symptomology, but not just that, I think this treatment would work best.

And we don't even know how to do this to this day. Uh, so it's, you're [01:27:00] right. I think creating a device that will perfectly stimulate the nucleus accumbens for absolutely everybody might not be that useful for certain people that are suffering from. another disorder, right? So, I really hope that ultrasound will be a helpful, as I said, as a search tool in our world, in the world of better understanding the brain, because then after we can also communicate with the people that use ultrasound as a therapeutic method.

Say, well, we know that if we do this, this, this, this doesn't really work. So, um, yeah.

Benjamin James Kuper-Smith: it's a big ecosystem. Um, that just interacts at many different levels and, uh, and I guess your prediction is that ultrasound is going to be a major, not a major, but like, it's going to be an important part of that. Okay, cool. Um, anything else you want to add or should I go to the recurring questions?

Elsa Fouragnan: Um, no, I think we've covered it all. Yeah.

Benjamin James Kuper-Smith: Okay. so yeah, at the end [01:28:00] of each episode, I'll ask my guests the same three questions. The first is what's the book or paper you think more people could read?

Elsa Fouragnan: Yeah,

Benjamin James Kuper-Smith: whatever you want, uh, whether it's old or new or famous on that.

Elsa Fouragnan: me

Benjamin James Kuper-Smith: Uh, any recommend any reading recommendations for you? Yeah,

Elsa Fouragnan: few years back. It's

Benjamin James Kuper-Smith: Uh, any reading

Elsa Fouragnan: called The Out Run by Amy Lippert, um, absolutely gorgeous. It's when I started working with, uh, with patients that have severe alcohol use disorder. He just thought that that book would be relevant and it's, it's a, it's a young lady who depicts her journey through recovery.

And I guess the neuromodulatory, uh, you know, side of the story is actually nothing to do with technology. It has to do with nature and it has to do with birdwatching. And I very identify with this because I love birds and if I wasn't studying the human brain, I would study the bird's brain. [01:29:00] I think they are fascinating species and basically it's the story of that lady, um, yeah, through observing birds and it's extremely poetic, the whole, the whole book is, is a deep dive into the, you know, human consciousness across multiple phases of, uh, you know, yeah, recovery.

It's beautiful. And not too long ago, it was made up as a movie. Um, And the movie was good too, which is sometimes not the case when you really love a book. You think they're never gonna, you know, manage.

Benjamin James Kuper-Smith: be a bit risky to watch a film of a, of a book you like.

Elsa Fouragnan: But you, I think you should go for it. It's called The Outrun. And it's beautiful.

Benjamin James Kuper-Smith: Um, Uh, by the way, I guess you, you like that in Zürich on the lake, they have, have, I mean, lots of birds, but they also have these, like, informational things where they give you, like, images of all the different birds, a little bit of information about them. [01:30:00] Um, although, for me, it's always just ducks. I keep forgetting, like, what, there's so many different types of ducks here.

Um, but yeah. I guess you can, if you can see that, then you can maybe have a look at those later. Um, second question is, what's something you wish you'd learned sooner? This could be from, again, private work, whatever you want.

Elsa Fouragnan: I'll go back to what I was talking about at the beginning. You know that, um, very weird psychological bias we have, that when we have invested so much into something, we feel like we should stick to it. I think it's not entirely true. Uh, we, we need to be aware of that bias because, you know, it's not because you've been in a long, um, whatever.

It could be your career, relationship, whatever. It's not because you've invested so much into it. If you're, if you realize you're not happy, you should switch. You should really try to be aware of that. It's [01:31:00] called a status quo bias as well, right? The sunk cost fallacy. I wish I had known that a little bit more because I would have made the scarier choice earlier on.

Benjamin James Kuper-Smith: But how do you know that, uh, well, that's a big question, but I mean, it was, what I mean is like the, how should I put it, I mean, so I have the weird thing with, with the podcast, for example, where after basically the first year and a bit, when I did 50 episodes, I was just done,

Elsa Fouragnan: Yeah.

Benjamin James Kuper-Smith: that's the, I've done the [01:32:00] preparation, I might as well, you know, why not, yeah. So I did it and then I really enjoyed it and just continued and then like, you know, another couple episodes went well and then I was like, you know what, I think I'll continue, but just not as many episodes.

Elsa Fouragnan: Yeah. So

Benjamin James Kuper-Smith: how do you know that? Uh, because like,

Elsa Fouragnan: that, uh,

Benjamin James Kuper-Smith: yeah, I mean, I guess it's a fallacy if

Elsa Fouragnan: guess

Benjamin James Kuper-Smith: a way it's a bit of a circular thing, right? It's a fallacy only if it is truly something you should stop doing. But sometimes you're just like in this like valley when if you get out of it, it's actually really good to have all the, all the investments behind it.

Right.

Elsa Fouragnan: Yeah, yeah.

Benjamin James Kuper-Smith: yeah, it is a hobby, but yeah. So

Elsa Fouragnan: in a way, if you, if you stop, you can still restart, right? I think with carrier choices, you feel like, well, if I stop, that's a big, big, big, big change. I will, I'll never be able to go back to it.

Benjamin James Kuper-Smith: do, but [01:33:00] sometimes it's just you're doing things you're supposed to

Elsa Fouragnan: feel, you did feel

Benjamin James Kuper-Smith: that's why it was really hard for me. So you did it for

Elsa Fouragnan: you could also tell your, you know, uh, Listener, guys, I'm taking six months holiday. I'll come back in six months. Maybe.

Benjamin James Kuper-Smith: I think it felt like, yeah, I dunno, it just felt like either you do it or you don't.

And I have taken like periods where I didn't release an episode for two months or something like that. It has, you know, I'm, I'm very irregular in terms of like, uh, how I published them. But yeah. Anyway, so it's funny. It's just, it didn't seem like that at the time, but like, okay, so that's one factor to consider how.

Elsa Fouragnan: I've just seen people being very unhappy in their job. Um, and then I have very much often had this conversation with them where I asked them, um, like, why, why would you stay? Well, you know, I've I've done seven years of university, I got a doctoral degree, um, I, [01:34:00] like this is meaningful up to this point, but actually what is meaningful is right now what you're doing in your future forward, right?

It shouldn't be just looking back at the past and thinking, well, this is valuable for me to stay where I am. I think that's maybe the fallacy is the fact that you're less forward looking than you're backward looking. Yeah, I

Benjamin James Kuper-Smith: part of the fallacy to some extent is also not,

Elsa Fouragnan: so.

Benjamin James Kuper-Smith: what I have with my podcast, it's this or not this at all.

Elsa Fouragnan: The binary. Yeah, yeah, yeah, yeah.

Benjamin James Kuper-Smith: final question is, uh, so yeah, I'm still in the beginning of my postdoc. Um, any advice for people like me who are [01:35:00] like, you know, let's say late PhD to early postdoc who are, uh, yeah, anything in that kind of period.

Elsa Fouragnan: from what I've just said, uh,

Benjamin James Kuper-Smith: addition to

Elsa Fouragnan: I, um, I, I love my job. I wouldn't trade it. I wouldn't go back to industry. But I totally understand those people that would. Because maybe you make more money and it's, you're more guided towards what you should be achieving and so on. I really love the freedom that academia gives, gives me.

Um, and I really love to work with the people that I love to work with. And I think that's the most privileged part of my work. I decide with whom I want to work with. Um, and therefore I have just a lot of fun working and, um, having discussions with brilliant, brilliant people that I respect so much. But I think, um, [01:36:00] academia has also its flaws.

Uh, you know, it's not the pure world that you might expect when you're starting. You're very ideologist about what we can do and how we do it, and the fact that we're very non biased. And

Benjamin James Kuper-Smith: is a system

Elsa Fouragnan: think every system has its flaws, and science is not, you know, an exception to that. So

as long as you're,

inspired by what you do, passionate about what you do, um, just give it,

Benjamin James Kuper-Smith: can

Elsa Fouragnan: give it, give it a chance because you can really be very, very happy.

But also if, um,

if it, because it's, it's, it's difficult, um, and maybe sometimes you feel like

the results that you're getting will impact your career and maybe your success, which is terrible. Um, I would say just try to remain have some integrity with what you do and, and make sure that you're just doing the best you can because that will ultimately be something that will be rewarding [01:37:00] to

Benjamin James Kuper-Smith: it's not very rewarding when you get to the position because you, you know, close your eyes occasionally during your data analysis.

I don't know, but I'm assuming, you know, the integrity part is also what makes it fun, right? Okay, thank you very much

Elsa Fouragnan: You're very welcome. Yeah, it was fun. Thank you.