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Speaker 1: Martain Arnes, Welcome to the podcast.

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Speaker 2: Yeah, well thanks a lot for inviting me.

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Speaker 3: Look, the reason I invited you is I saw a

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Speaker 3: post of yours on LinkedIn, and I dove into the

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Speaker 3: post and end I looked into your background, and as

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Speaker 3: soon as I look into your background, I'm like, this

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Speaker 3: is the guy that I want to get in onto

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Speaker 3: my podcast because of the research that you're doing. But

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Speaker 3: you describe yourself as a biological psychologist, not a clinical psychologist.

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Speaker 3: So tell our listeners the difference between that those two things.

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Speaker 2: I think. I think that's quite a big difference. I mean,

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Speaker 2: at the time when I started studying, it was like

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Speaker 2: from the say three four hundred psychologists students a year,

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Speaker 2: that would only be like three to four maybe a

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Speaker 2: handful that would opt for studying physiological psychology or biological

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Speaker 2: psychology as we name it nowadays. And usually I tell

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Speaker 2: people I don't talk to people. I just want to

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Speaker 2: see their brain activity. So biological psychology is more really

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Speaker 2: the biological side of psychology where we're more interested in

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Speaker 2: interrelating behavior to brain. So it's not about checking checklists

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Speaker 2: or just talk therapy. I mean, although it could be

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Speaker 2: part of the interest when you want to see how

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Speaker 2: it works at the brain. But the primary viewpoint is

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Speaker 2: coming from the brain, which is been quite different from psychology,

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Speaker 2: which is more than a clinical psychology, which is more

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Speaker 2: the reverse.

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Speaker 3: Yeah, and so given our listeners a bit of a

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Speaker 3: journey through your background and spoke in academia and then

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Speaker 3: in the work that you do.

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Speaker 2: So when I finished my study, which is let me

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Speaker 2: count a long time ago, there was somewhere ninety ninety eight,

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Speaker 2: after having spend also some time and down Under and

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Speaker 2: some other research places. When I started studying, my specialty

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Speaker 2: was mostly educating people off to mostly get a role

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Speaker 2: in farmer industry because there was a lot of pre

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Speaker 2: clinical research going on where behavior of animals was very

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Speaker 2: important to inform if a drug would be an antidepressant

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Speaker 2: drug or an anti psychotic rug, etc. So I've worked

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Speaker 2: there for a very brief bit at that point in

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Speaker 2: time as well, But over and over again I was like, well,

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Speaker 2: I want to do more translational research. I want to

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Speaker 2: better understand how we can benefit from knowledge from the

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Speaker 2: brain and applying that to humans directly in order to

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Speaker 2: make a difference from treatment perspectives. So after I spent

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Speaker 2: doing research at various research institutes. For example, I did

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Speaker 2: my studies in Name and the Netherlands. Then I had

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Speaker 2: a tour in Sydney, Australia and the Westmead Hospital. I

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Speaker 2: joined the group of Evian Gordon and lie and Williams.

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Speaker 2: I think she joined it later.

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Speaker 3: Actually I know Evan Garden and lay Valliums so Avian

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Speaker 3: with the brilliant Resource Institute. I used to work with

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Speaker 3: those guys a decade ago.

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Speaker 2: Yeah, exactly, I find exactly. I mean that was also

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Speaker 2: a little bit of the way how I got started

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Speaker 2: several years later because ninety seven ninety eight I did

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Speaker 2: a project at the westmin Hospital and the supervision of

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Speaker 2: Evan Gordon. They really learned about applying collecting EG data

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Speaker 2: and lots of people. And then I made a bit

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Speaker 2: of a detour. I also went to the Max Plunk Institute,

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Speaker 2: which was more like memory research, and then I started

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Speaker 2: a PhD in Glasgow and in Scotland together with Oreganaude,

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Speaker 2: which was a farmer company at that time. And that

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Speaker 2: all results in effect of me realizing like, well, it's

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Speaker 2: all this fundamental research is too far away of where

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Speaker 2: we are going. And then after a couple of years

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Speaker 2: spending time in the it. This was like beginning of

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Speaker 2: the two thousands, where even a psychologist could get a

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Speaker 2: job in it and would all be over a good

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Speaker 2: salary and the car. I spent one and a half

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Speaker 2: years there, because of course scientists traveling the world doesn't

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Speaker 2: make you a lot of money, so I needed to

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Speaker 2: pay back some of my dad's at that time. So

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Speaker 2: then Evian Gordon indeed went IPO with the Brain Resource

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Speaker 2: Company and approaching again like if I was interested in

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Speaker 2: setting up at least in a Netland slash the some

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Speaker 2: of the European parts of the Brain Resource Company. And

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Speaker 2: that's how I got started with brain clinics in the

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Speaker 2: very early days. So I made a business plan at

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Speaker 2: that time, and the conclusion was like this no money

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Speaker 2: to be made me. So I thought, well that's a

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Speaker 2: great business plan, let's start doing it. So I jumped

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Speaker 2: into it and we started collecting some data for the

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Speaker 2: Brain Resource Company. But very early on I already realized like, well,

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Speaker 2: we have this brain scanning technique, we can compare brain

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Speaker 2: scans to a database and we have more objective information,

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Speaker 2: and therefore realizing like this could be a very interesting

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Speaker 2: jumping platform to branch out to other applications. And one

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Speaker 2: of the ideas I had at that time already is like,

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Speaker 2: rather than making a diagnosis on the outside based on

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Speaker 2: behavioral checklist like raiding, depression, etc. We need to look

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Speaker 2: under the hoods to better marry a patient to their

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Speaker 2: treatment or their drug of treatment, if you will. And

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Speaker 2: that's been the primary motivation ever since, and I think

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Speaker 2: we've come a long way across the journey ever since.

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Speaker 2: And that's basically how it got started, in starting my

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Speaker 2: own private research institute at that time, on the one hand,

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Speaker 2: collaborating with Brain Resource, but also getting to go with

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Speaker 2: our own research lines and advancing applied neuroscience. So that's

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Speaker 2: in a.

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Speaker 3: Nutshell, yes, very interesting because I actually studied in Glasgow

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Speaker 3: University as well. I did a master's in nutrition at

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Speaker 3: Glasgow Uni. Jesus, it's a cold, wet place in the

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Speaker 3: middle of winter, isn't it. Yeah.

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Speaker 2: You know. The funny thing is I've spent quite some

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Speaker 2: time in all these places, and to be honest, Munich

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Speaker 2: was my least favorite place, at least at that time

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Speaker 2: as a student. It's really hard to get integrated in.

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Speaker 2: Glasgow was the funniest place. Sorry, even above Sydney.

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Speaker 1: It's a lot of things.

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Speaker 2: It's a lot of people really go good, no matter

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Speaker 2: how dark and depressing it was outside inside of the

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Speaker 2: bars in places, they're really friendly, welcoming people. I had

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Speaker 2: the greatest time in Glasgow, to be honest.

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Speaker 3: Yes, yes, Meeter Ashton Lean a bit of time in there.

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Speaker 3: I'm sure I'm sure you've forquented ashtle Leon once or twice.

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Speaker 1: Tell me this before we dig into this.

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Speaker 3: Did you ever come across doctor Roy Sugarman in your

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Speaker 3: time in the Brilliant Resource company?

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Speaker 1: He worked with heavy Yeah.

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Speaker 2: I know, well exchanges with him. I mean this is

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Speaker 2: probably like more than twenty twenty five years ago that

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Speaker 2: that we had so lates.

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Speaker 3: Yeah, nah, very cool.

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Speaker 2: The name rings the bell for sure.

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Speaker 1: So so let's talk.

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Speaker 3: You mentioned something there about with psychiatric disorders the checklist.

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Speaker 3: Now my listeners will have heard me, Steph. Your listeners

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Speaker 3: say before that that psychiatry is the only branch of

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Speaker 3: medicine where people are diagnosed with conditions without a biological

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Speaker 3: signature at all. And are we any closer to biological signatures?

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Speaker 3: And and and if you could explain what that means

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Speaker 3: to people, you'll explain it a lot better than me.

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Speaker 3: And are we getting any closer to biological signatures for

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Speaker 3: different psychiatric conditions? And then and and how do we

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Speaker 3: use the brain and the information from the brand to

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Speaker 3: inform treatment. There's a few questions in there, take them

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Speaker 3: any order you want.

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Speaker 2: Well, it's going to be a longer answer. Yes and no,

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Speaker 2: it's the short answer, and the longer answer is indeed,

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Speaker 2: like you're suggesting, the running joke is a little bit

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Speaker 2: like the psychiatrist. You know, that's the only MD that

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Speaker 2: doesn't first inspect the organ he's treating. And that's that's

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Speaker 2: how it is in current medicine, and especially in PSYCHAI.

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Speaker 2: We take a checklist, we rate specific behaviors, we measure

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Speaker 2: to the DSM four very important. It's not the set

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Speaker 2: of behavioral criteria that make a diagnosis of depression or ADHD.

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Speaker 2: It's the final question. And the final question is clinical impairments.

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Speaker 2: So someone can have meet a list of criteria and

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Speaker 2: not being able to concentrate, impulsive, et cetera. But in

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Speaker 2: the end, if there's no clinical impairment, then the diagnosis

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Speaker 2: will not be made. And remember this because this is

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Speaker 2: a very important notion, because let's visualize two people. We

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Speaker 2: have one person with a CEO and a company, very impulsive,

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Speaker 2: very inattentive, probably has a PA to cover up for

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Speaker 2: all that inattentive behavior, et cetera, but this impulsiveness, et

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Speaker 2: cetera is one of his core strengths. Now let's take,

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Speaker 2: on the other hand, this other person white collar workers, say,

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Speaker 2: very inattentive in PILM and well, his job is, his

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Speaker 2: boss is not really happy with it, and therefore gets

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Speaker 2: reverred out to an MD or to a psychiatrist. They

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Speaker 2: do the checklist, and that they will note some clinical

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Speaker 2: impairment because his complaints are impacting on his job and

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Speaker 2: therefore this clinical impairment. So therefore that person might receive

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Speaker 2: a diagnosis of ADHD, of course a bit more complicated

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Speaker 2: like I'm painting the picture right now. But the CEO

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Speaker 2: on the other end will not get a diagnosis. And

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Speaker 2: this automatically will already tell you that a biomarker driven

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Speaker 2: psychiatry will be impossible because with my biomarker, I might

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Speaker 2: pick up on the level of inattention impulsivity. I could

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Speaker 2: pick up on all those complaints, maybe very reliably, but

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Speaker 2: I will never pick up on the clinical impairment, which

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Speaker 2: is more situational environmental, and that's why by definition, a

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Speaker 2: biomarker will never work. And this is the most important reason.

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Speaker 2: There's multiple other reasons of reliability that even raters could

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Speaker 2: could vary well in rating, and there's also environmental societal

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Speaker 2: changes where some behavior is seen more easily as deviating

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Speaker 2: from the norm than it would be ten twenty years ago.

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Speaker 2: But apart from that, I think this is the most

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Speaker 2: crucial reason why a biomark can never be used for

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Speaker 2: diagnosis as they are today. So we need to develop

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Speaker 2: ourselves to a new framework now with the other question

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Speaker 2: you asked, and I think this is a way more

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Speaker 2: important question, because why would we want to stick a

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Speaker 2: label to someone's forehead in terms of a diagnosi as well.

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Speaker 2: According to the DSM for DSM five, the only reason

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Speaker 2: to have these terminologies of depression, ADHD etc. Is to

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Speaker 2: foster communication among professionals. So it's only meant as a

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Speaker 2: language that if you and I talk about depression, that

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Speaker 2: we both understand what we're talking about. The DSM four

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Speaker 2: and five never developed to be a diagnostic framework to

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Speaker 2: be used to develop treatments upon. It was never designed

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Speaker 2: for insurance companies to exercise upon that was never behind it.

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Speaker 2: But still there was all industry that started building anti

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Speaker 2: psychotics and anti depressants, et cetera. Wherever, whereas it was

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Speaker 2: never intended intended for that purpose. Now it's just there

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Speaker 2: to foster.

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Speaker 1: So it's been so some margins.

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Speaker 3: It's my understanding though, that it's kind of it's been

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Speaker 3: hijacked a little bit by industry for them to develop

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Speaker 3: specific treatments.

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Speaker 2: What you're saying, yeah, I mean that's that's one one

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Speaker 2: way to look at it. I may not maybe purposely.

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Speaker 2: I mean, on the other hand, developing a drug. I'm

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Speaker 2: not saying hijacked in a negative sense. I mean, if

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Speaker 2: you develop a drug, you would like to ting onto

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Speaker 2: something to make understandable what it is that drug is doing.

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Speaker 2: So it's very understandable. But it's also I think has

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Speaker 2: put us on a trajectory where we are currently are

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Speaker 2: that the effectiveness of most treatments are very very low.

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Speaker 2: If we look at depression, and I can paint the

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Speaker 2: whole landscape from you ranging from psychotherapy, all anti press

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Speaker 2: and medications, brain stimulation techniques, ketamine psychedelics, et cetera. Overall

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Speaker 2: the response for mission rates on the group level are

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Speaker 2: roughly thirty forty forty five percent when you look at

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Speaker 2: the largest studies around. So if you go to the

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Speaker 2: casino and you know you're winning chances or a dead low,

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Speaker 2: I'm not sure that casinos will do good business well.

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Speaker 2: In psychiatry, that's what we have to deal with, and

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Speaker 2: that's why we have this stepped care model that we

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Speaker 2: keep on putting people on new drugs until we have

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Speaker 2: found a treatment that will benefit the majority, and when

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Speaker 2: going through four different steps, only two thirds of people

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Speaker 2: are actually helped. So it's a very excruciating process knowing

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Speaker 2: that you're dealing with patients that have co morbid suicideality

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Speaker 2: that are very impaired in their lives. So this is

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Speaker 2: really the worst discipline I think from an effectiveness point

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Speaker 2: of view. Maybe in the hall of metasine.

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Speaker 3: And yeah, look, I think that's pretty clear from the

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Speaker 3: data that the interventions in psychiatry are pretty poor compared

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Speaker 3: to other branches of medicine and unacceptable for some branches

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Speaker 3: of medicine.

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Speaker 1: But how is neuroscience helping?

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Speaker 2: Oh, this is I think the topic where we have

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Speaker 2: to be more optimistic because knowing that on the group level,

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Speaker 2: a treatment is only effective in thirty to forty percent,

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Speaker 2: and also knowing that if people that do not respond

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Speaker 2: to one treatment might be responding to another treatment. That's

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Speaker 2: where the real hope is and that's really really where

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Speaker 2: I think we can make a difference and consistently throughout

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Speaker 2: all the data we have collected in our lives. So

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Speaker 2: we've been part of the I spot D study that

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Speaker 2: was this large study that was funded by by Evan

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Speaker 2: Gordon and Brain Resource, the largest biomarker study to date,

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Speaker 2: and that study has been confirming what I just said.

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Speaker 2: If we make correlations between symptom profiles and baseline EG,

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Speaker 2: we never found something. But if you start making correlations

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Speaker 2: between brain activity at baseline and behavior in the future,

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Speaker 2: so like the symptoms in the future, we did find

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Speaker 2: a significant association. So that's already telling you that your baseline,

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Speaker 2: the way your brain activity is at this point in time,

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Speaker 2: is predictive of the trajectory to responding to a drug.

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Speaker 2: So if you're responding to a drug, you have a

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Speaker 2: different type of EG then relative to when you're not

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Speaker 2: responding to a treatment. So in the first quest, we

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Speaker 2: really started to asking the question can we predict people

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Speaker 2: that are responding and non responding to treatment? And the

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Speaker 2: simple answer is yes, and we can do quite some

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Speaker 2: substantial degree predicted.

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Speaker 3: However, when you develop what sort of accuracy, sorry, Mark,

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Speaker 3: what sort of accuracy are we talking here in terms

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Speaker 3: of predictive.

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Speaker 2: Yeah, that's why I wanted to get to get into

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Speaker 2: because it was not like in the eighty ninety or

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Speaker 2: a ninety plus kind of sensitivity, so we would still

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Speaker 2: be on the lower end of sensitivity and specifict you

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Speaker 2: have more like sixty seventy percent, which that's what I

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Speaker 2: wanted to explain as well, which indeed is clinically very

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Speaker 2: challenging because if you cannot be absolutely accurate that someone

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Speaker 2: will or will not respond, then you also cannot make

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Speaker 2: a decision to prescribe or to withhold a treatment. And

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Speaker 2: to prescribe a treatment can ethically be justified quite easily,

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Speaker 2: but you cannot very easily tell someone like, well, my

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Speaker 2: biomarket tells me you're not going to respond to this

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Speaker 2: treatment with an eighty percent accuracy, that still means that

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Speaker 2: someone has likely to twenty percent to respond to the treatment. Ethically,

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Speaker 2: you cannot make that, not until you have an alternative

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Speaker 2: to offer, and that's where we have also based on

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Speaker 2: a lot of the studies we conducted based on I SPOT,

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Speaker 2: based on these ethical and moral decisions we needed to

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Speaker 2: make as well, and that's why we've shifted to a

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Speaker 2: different way. Many people talk about precition psychiatry, personalized medicine

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Speaker 2: that deals with such questions, and we've moved away to

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Speaker 2: a model that we call stratified psychiatry and in stratified

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Speaker 2: psychiatry in depression. For example, we take the whole family

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Speaker 2: of antidepressant treatments and what we'll do will develop a

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Speaker 2: biomarker that might predict some responsiveness to say, antidepressant A,

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Speaker 2: and as long as the same biomarker does not predict

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Speaker 2: impaired response to another one, then we have a winner,

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Speaker 2: because what we can we can gain with one drug.

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Speaker 2: But if we have to then tell someone you cannot

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Speaker 2: use this drug, however we stratify you to the other

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Speaker 2: drug that at least is equally effective as the group

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Speaker 2: level response remission, then we still win because we take

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Speaker 2: away the drugs so of say that people are less

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Speaker 2: responsive to, and then we will never have to make

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Speaker 2: the life or death decision of withholding someone from a treatment,

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Speaker 2: and so it's a slightly different perspective, but clinically very important.

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Speaker 3: Yes, yeah, now that that that is important and it's

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Speaker 3: worthwhile excuse me, it's worthwhile just dubbing clicking on that

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Speaker 3: in that you can with what you're saying now is

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Speaker 3: you're moving towards well. Actually this is saying that this

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Speaker 3: treatment may not be good for you, or you may

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Speaker 3: not respond well to this treatment, so instead you should

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Speaker 3: have this one. Now that's important because a you can

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Speaker 3: potentially increase the effectiveness, but b the patient doesn't go

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Speaker 3: on to a drug that is not helpful, that often

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Speaker 3: has very very significant side effects. And I've been you

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Speaker 3: Professor John Reid on my podcast, who's done large studies

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Speaker 3: of real people with antidepressants and find that sixty plus

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Speaker 3: percent of them have a whole host of side effects,

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Speaker 3: including suicidal ideation. So if we can can basically go

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Speaker 3: this drug is not useful for you, or or are

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Speaker 3: our information is saying don't take this drug. Whereas if

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Speaker 3: they'd just gone to the doctor, the doctor could have say,

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Speaker 3: well let's try you on this one first, and they

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Speaker 3: go and they have a bad outcome and then they

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Speaker 3: have to go on to another treatment, but they could

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Speaker 3: potentially be worse off than when they started right exactly.

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Speaker 2: So, rather than patients coming to a psychiatrist and a

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Speaker 2: psychiatrist having a whole range of first line choices, have

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Speaker 2: first line treatments of psychotherapy and SSRIY in ten different

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Speaker 2: kinds and as NRI in several kinds. And then there's

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Speaker 2: second line treatments which is more like OURTMS for example,

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Speaker 2: treatment used for more treatment resistant patients. So rather than

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Speaker 2: doing a random pick out of one of these, you

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Speaker 2: take a simple biomarker, which most consistently we've shown with EG,

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Speaker 2: and you pick the one that someone is most likely

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Speaker 2: to respond to. And what we've seen is in replicated

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Speaker 2: studies that we've been publishing out there, and we've seen

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Speaker 2: that you could enhance based on a cop one or

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Speaker 2: two very simple biomarkers, enhance your remission rates from say

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Speaker 2: forty fifty percent to sixty sixty five percent. So we

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Speaker 2: see about a thirty percent gain in the remission rates

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Speaker 2: by simply using one biomarker and stratify people between an

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Speaker 2: evident between two evidence based treatments.

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Speaker 3: And that is really significant, right, that's thirty percent uplift.

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Speaker 2: And that's also what these studies have shown. If we

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Speaker 2: look at I spot where people were actually randomized to

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Speaker 2: three different drugs, two SSRIs, one s and ri I

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Speaker 2: and one drug with even a completely slightly different working

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Speaker 2: mechanism on the group level, remission rates were completely identical

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Speaker 2: for all all three groups. So the psychiatrist could as

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Speaker 2: well roll the dice and vside on a treatment based

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Speaker 2: on rolling the dice. And we know it doesn't make

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Speaker 2: a difference from any studies.

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Speaker 3: That's crazy and can you just let the listeners know.

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Speaker 3: So you mentioned ssrright, selective excuse me, serotonin reoptic inhibitors

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Speaker 3: and selective neurepinephron tell our listeners how those drugs are

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Speaker 3: different in terms of their mechanisms of action.

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Speaker 2: Well, the drugs usually impact on a specific neurotransmitter, and

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Speaker 2: a neud transmitter is like a small chemical in the

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Speaker 2: brain that facilitates communication between between urins, and some of

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Speaker 2: them are communicating via means of serotonin, other via means

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Speaker 2: of neu adrenaline. And we have very often heard about

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Speaker 2: dopamine as well, So some antidepressants have a preference for

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Speaker 2: more dopaminergic neurotransmitters. So we have multiple, maybe tens more

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Speaker 2: close to one hundred different antidepressants and they all have

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Speaker 2: a slight different preference for one of the other neurot

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Speaker 2: transmitted systems. However, on the group level, people are equally

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Speaker 2: responsive to one or the other. And that's really sobering

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Speaker 2: because in the old days we used to think like, well,

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Speaker 2: maybe we are more dealing with a subgroup of people

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Speaker 2: that have a more certnergic depression and other people have

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Speaker 2: a more say no other nergic depression. Well, all the

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Speaker 2: research in that specific area has not indicated any evidence

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Speaker 2: for that, and at this point in times, psychiatrists have

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Speaker 2: no means other than their gut feeling, other than their

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Speaker 2: experience with patients to prescribe people with a better treatment.

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Speaker 2: But overall, still you could as well randomize people to

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Speaker 2: the treatments because on the group level it's not going

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Speaker 2: to make a difference at all. And even this is

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Speaker 2: within antidepressants, but even if you would add psychotherapy or

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Speaker 2: TMS to it as well, we know tms relative to antidepressants,

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Speaker 2: tms relative to each other. There's multiple tms producols as well.

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Speaker 2: For the for rights prefrontal or less prefontal cortex, and

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Speaker 2: on a group level, they have identical results as well.

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Speaker 2: So it's not only true for for drugs, but for

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Speaker 2: any antidepressant treatment. We see group level remission rates being

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Speaker 2: quite identical.

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Speaker 1: And that's that's going to be really confusing.

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Speaker 3: Me as well for researchers when you're looking at different

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Speaker 3: drugs with different mechanisms of actions, and then when you

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Speaker 3: take a thousand people, same effectiveness, and so that that

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Speaker 3: begs the question as to when they are effective, what

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Speaker 3: is the mechanism of action. I've heard some people talk

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Speaker 3: that they think that it's nothing to do with the

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Speaker 3: serotonin and orap and effort, but it might be that

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Speaker 3: the these drugs are increasing BDNF and and helping the

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Speaker 3: brand that way. Any comments on that or have you

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Speaker 3: got any insights into this?

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Speaker 2: Yeah, I mean that's the final common pathway of any

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Speaker 2: antidepressant treatment, including electro convilsive therapy, psychedelics rTMS. The final

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Speaker 2: common pathway is b D and F or nerve growth

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Speaker 2: factors expressed in the hippocampus that supposedly can facilitate neural

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Speaker 2: growth and functioning of specific networks in the brain. So

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Speaker 2: they all have that. So it's not true. Serotonin it

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Speaker 2: was thought to be a final part of what was

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Speaker 2: explaining depression, and now we know it's not actually has

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Speaker 2: more specific networks and specific parts of the brain where

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Speaker 2: these nerve growth factors play play an important role. But

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Speaker 2: I think that the honor sensor is how do all

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Speaker 2: these treatments work. I mean, we know there's a final

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Speaker 2: common part way in BDNF, for example, but still knowing

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Speaker 2: that some treatments will be very ineffective, they might still

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Speaker 2: have this downstream effect that maybe you're not strongly enough.

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Speaker 2: I think the first question I would and that's why

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Speaker 2: I'm an applied neuro scientist. The first question I would

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Speaker 2: like to answer, can we first improve the remission rates

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Speaker 2: by using a stratified psychiatry approach before we start understanding it,

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Speaker 2: because our understanding will even get way more complicated. Where

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Speaker 2: we assume the whole family of treatments we have the

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Speaker 2: same effect. We're now seeing that within that family of treatments,

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Speaker 2: one drug has a supposedly different working mechanism relative to

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Speaker 2: another drug, even if it's the same family. So we're

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Speaker 2: complicating the whole story much more by taking individual variation

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Speaker 2: into account and that's really where we need to go to.

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Speaker 3: Right, I think what you're saying, so you're saying nis like,

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Speaker 3: let's let's do stratification, find the drug that is working better,

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Speaker 3: and then explore the mechanisms, rather than as what happened

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Speaker 3: twenty thirty years ago, propose a serotonin mechanism, make a

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Speaker 3: drug that has an action on it, and then use

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Speaker 3: that drug. So it's a kind of bit of reverse

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Speaker 3: way of doing things, which I get.

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Speaker 1: I actually get that.

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Speaker 3: But the BDNF story probably at least partly explains why

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Speaker 3: I would imagine you're a ware of the British Medical

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Speaker 3: Journal our BMJ studies comparing a whole different type of

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Speaker 3: exercise interventions to antidepressant therapy and find that every single

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Speaker 3: form of exercise had a greater effects size than antidepressants.

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Speaker 3: And we know that exercise is very potent at stimulating BDNF,

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Speaker 3: particularly more vigorous exercise, so that would kind of seem

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Speaker 3: to play into BDNF being the ultimate thing that might

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Speaker 3: make a difference.

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Speaker 2: Yeah, I mean, in that sense, it's not really surprising.

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Speaker 2: One of the most powerful psychological treatments is called behavioral activation.

436
00:26:07,440 --> 00:26:12,720
Speaker 2: As you imply any type of activation, especially in depression,

437
00:26:12,760 --> 00:26:16,600
Speaker 2: could be very powerful. Even so strongly, and I recall

438
00:26:16,640 --> 00:26:19,680
Speaker 2: this from a long time ago. There was the big

439
00:26:19,680 --> 00:26:23,679
Speaker 2: professor who was specialized in cogitive behavior therapy, and in

440
00:26:23,760 --> 00:26:26,600
Speaker 2: order to do concuaitive behavior therapy it requires a lot

441
00:26:26,600 --> 00:26:30,840
Speaker 2: of training, right, and he explained behavioral activation as being

442
00:26:30,920 --> 00:26:33,840
Speaker 2: so simple that you can even teach a psychiatrists how

443
00:26:33,880 --> 00:26:35,840
Speaker 2: to do it. Then he was a psychiatrist at that time.

444
00:26:36,119 --> 00:26:38,959
Speaker 2: As a behavioral activation is much simpler to do, and

445
00:26:38,960 --> 00:26:41,360
Speaker 2: they actually have done had to head studies in very

446
00:26:41,440 --> 00:26:46,760
Speaker 2: large numbers where behavioral activation is non inferior to CBT,

447
00:26:47,280 --> 00:26:49,560
Speaker 2: and so it's much simpler to do. And even there

448
00:26:49,840 --> 00:26:53,359
Speaker 2: that's similar to possibly medications, behavioral activation is a very

449
00:26:53,400 --> 00:26:58,800
Speaker 2: powerful technique to at least get some initial antidepressant benefit. Again,

450
00:26:58,880 --> 00:27:02,399
Speaker 2: if that's just to be f I think we should

451
00:27:02,400 --> 00:27:05,520
Speaker 2: also be cautious by just similar to in the past

452
00:27:05,560 --> 00:27:07,840
Speaker 2: saying oh, it's a bit of a certain one thing slow,

453
00:27:07,880 --> 00:27:09,760
Speaker 2: we're going to increase it. I think we need to

454
00:27:09,760 --> 00:27:13,200
Speaker 2: be cautious about it and not oversimplify things. It's probably

455
00:27:13,240 --> 00:27:16,639
Speaker 2: more complicated. Let's be humble, let's only start focusing on

456
00:27:16,680 --> 00:27:20,520
Speaker 2: all the mechanisms. Once we have identified the various subgroups,

457
00:27:20,920 --> 00:27:23,119
Speaker 2: and that makes more sense in my view, and anything

458
00:27:23,200 --> 00:27:24,880
Speaker 2: is simplification beforehand.

459
00:27:25,720 --> 00:27:29,399
Speaker 3: Yeah, no, that makes sense. So let's not talk about TMS. So,

460
00:27:29,680 --> 00:27:34,200
Speaker 3: because you have done a lot of work in the TMSPS, firstly.

461
00:27:34,600 --> 00:27:38,359
Speaker 1: Explain what it is and high and.

462
00:27:38,440 --> 00:27:43,359
Speaker 3: Actually what's its mechanisms of action? And then what sort

463
00:27:43,400 --> 00:27:46,240
Speaker 3: of conditions is it being used for?

464
00:27:46,600 --> 00:27:49,199
Speaker 1: And what the hell does heartbeat have to do with it?

465
00:27:50,680 --> 00:27:53,159
Speaker 2: Interesting question. I'll finish off with a heart rate and

466
00:27:53,359 --> 00:27:56,680
Speaker 2: keep the most exciting to the end. I think TMS

467
00:27:56,760 --> 00:28:00,359
Speaker 2: is a very exciting technique. And this was so remember

468
00:28:00,400 --> 00:28:05,240
Speaker 2: that what with brain clinics, we're onto doing EG research

469
00:28:05,400 --> 00:28:09,399
Speaker 2: and with EG we pick up the activity that's projecting

470
00:28:09,840 --> 00:28:13,720
Speaker 2: perpendicular to your scope. So at that point in time

471
00:28:13,800 --> 00:28:16,480
Speaker 2: two thousand and five, two thousand and six, I thought like, well,

472
00:28:16,840 --> 00:28:20,399
Speaker 2: there's this technique TMS, which is a very vocal, strong

473
00:28:20,480 --> 00:28:23,639
Speaker 2: magnetic field and it works in exactly the opposite direction

474
00:28:23,760 --> 00:28:25,800
Speaker 2: as the EEG that we're picking up. So I very

475
00:28:25,880 --> 00:28:28,520
Speaker 2: naively thought like, oh, that's interesting. I can see an

476
00:28:28,520 --> 00:28:31,639
Speaker 2: EEG where something is different and maybe I can use

477
00:28:31,680 --> 00:28:37,280
Speaker 2: this technique to then specifically in an individualized way modulate

478
00:28:37,320 --> 00:28:40,160
Speaker 2: brain activity. And so we bought our first TMS machine

479
00:28:40,880 --> 00:28:44,000
Speaker 2: in two thousand and six and we got started and well,

480
00:28:44,240 --> 00:28:47,080
Speaker 2: in the end it turned out to be completely different.

481
00:28:47,120 --> 00:28:51,200
Speaker 2: So with transcranial magnetic brain stimulation, and we generate a

482
00:28:51,240 --> 00:28:54,600
Speaker 2: magnetic fields in the strength of roughly one point five

483
00:28:54,640 --> 00:28:58,960
Speaker 2: to two testa that's very strong and very quickly build setting.

484
00:28:59,320 --> 00:29:02,560
Speaker 2: And because it's the magnetic or the decay of the

485
00:29:02,600 --> 00:29:06,160
Speaker 2: field is in the order of nanoseconds, we have a

486
00:29:06,280 --> 00:29:11,000
Speaker 2: very quick change which can elicit a small current in

487
00:29:11,080 --> 00:29:14,800
Speaker 2: the brain. And just to illustrate this, if I hold

488
00:29:14,800 --> 00:29:17,680
Speaker 2: it above my hand, my right cortex, so they say,

489
00:29:17,920 --> 00:29:21,920
Speaker 2: and I'm stimulating the area that's responsible for my left hand,

490
00:29:22,200 --> 00:29:24,680
Speaker 2: then I can also elicit a movement in my left hand.

491
00:29:25,120 --> 00:29:29,920
Speaker 2: So it's wow, physical stimulation exactly. So it's physical stimulation.

492
00:29:30,040 --> 00:29:32,760
Speaker 2: There's no people have done magnet therapies and stuff like that,

493
00:29:32,800 --> 00:29:37,360
Speaker 2: there's nothing related to that. This is really like physical

494
00:29:37,360 --> 00:29:40,440
Speaker 2: brain stimulation. So on the other hand, that's also the

495
00:29:40,480 --> 00:29:43,160
Speaker 2: only outcome we can get. We can stimulate your motor

496
00:29:43,200 --> 00:29:46,600
Speaker 2: areas and see motor movement, and that's it. So it's

497
00:29:46,640 --> 00:29:49,480
Speaker 2: always been very surprising to me if I move the

498
00:29:50,120 --> 00:29:53,640
Speaker 2: stimulation well to my prefrontal cortex where my high higher

499
00:29:53,760 --> 00:29:57,040
Speaker 2: order thinking processes that take place, that I can stimulate

500
00:29:57,120 --> 00:30:00,600
Speaker 2: whatever I want, but there's no conscious recollection. Get It's

501
00:30:00,600 --> 00:30:02,800
Speaker 2: not that I think like, oh my brain is working different,

502
00:30:03,040 --> 00:30:05,720
Speaker 2: my cognition is impaired. You really need to do very

503
00:30:05,840 --> 00:30:09,600
Speaker 2: very sophisticated behavioral algorithms to get some kind of a

504
00:30:09,640 --> 00:30:13,280
Speaker 2: readout from the prefrontal cortex on your Ownand we do

505
00:30:13,400 --> 00:30:16,760
Speaker 2: know that if you move your coil five centimeters interior

506
00:30:17,600 --> 00:30:21,240
Speaker 2: in the prefront or quartex and stimulate for say twenty

507
00:30:21,280 --> 00:30:24,280
Speaker 2: to thirty sessions, we know you get a very strong

508
00:30:24,320 --> 00:30:28,720
Speaker 2: and robust antidepressant effect in quite a number of people. Again,

509
00:30:28,800 --> 00:30:31,040
Speaker 2: on a group level, you get remission rates to say

510
00:30:31,120 --> 00:30:36,120
Speaker 2: forty to fifty percent, which is still meaningful. Also, and

511
00:30:36,160 --> 00:30:39,320
Speaker 2: this is a very important distinction taken into account. This

512
00:30:39,440 --> 00:30:43,360
Speaker 2: is mainly investigated in treatment resistant people, so people that

513
00:30:43,400 --> 00:30:47,080
Speaker 2: have filled all most other treatments before and getting such

514
00:30:48,200 --> 00:30:51,360
Speaker 2: a remission rate in that subgroup of patients, I think

515
00:30:51,400 --> 00:30:54,560
Speaker 2: it's very very encouraging because for these people the only

516
00:30:54,600 --> 00:30:57,920
Speaker 2: thing left will be electroc convulsive therapy or shock therapy,

517
00:30:58,000 --> 00:31:03,680
Speaker 2: which is not something you want to be considering too lightly, So.

518
00:31:02,880 --> 00:31:06,320
Speaker 3: Every s sorry, before you go any further, can I

519
00:31:06,400 --> 00:31:10,600
Speaker 3: ask why it is used as second line rather than

520
00:31:10,800 --> 00:31:16,320
Speaker 3: first line if its effectiveness appears to be as at

521
00:31:16,400 --> 00:31:19,040
Speaker 3: least effective as some of the first line drugs, and

522
00:31:19,080 --> 00:31:23,600
Speaker 3: these are on treatment resistant people that you're getting the

523
00:31:23,640 --> 00:31:27,479
Speaker 3: same effectiveness, So why isn't it used for first line treatment?

524
00:31:28,480 --> 00:31:32,600
Speaker 2: Yeah, very good question. Yeah, this is usually how research

525
00:31:32,680 --> 00:31:37,080
Speaker 2: goes have for ethical reasons. You're not going to be

526
00:31:37,200 --> 00:31:40,680
Speaker 2: experimenting in people that are feel still very likely to

527
00:31:40,800 --> 00:31:43,560
Speaker 2: respond at an early stage of the depression, and that's

528
00:31:43,560 --> 00:31:46,680
Speaker 2: why you always start with the toughest cases. But then

529
00:31:46,760 --> 00:31:51,080
Speaker 2: automatically the insurance mechanism kicks in again, and the insurance

530
00:31:51,120 --> 00:31:54,480
Speaker 2: mechanism then tells us to only start treating people if

531
00:31:54,480 --> 00:31:58,080
Speaker 2: they filled a couple of sessions, whereas personally, and again

532
00:31:58,160 --> 00:32:01,880
Speaker 2: don't take this as official advice, but personally I would

533
00:32:01,920 --> 00:32:07,040
Speaker 2: consider that we might make it available much more quickly

534
00:32:07,880 --> 00:32:10,480
Speaker 2: and to maybe first line patients as well. I think

535
00:32:10,480 --> 00:32:13,000
Speaker 2: in the Netherlands we have one of the few systems

536
00:32:13,280 --> 00:32:17,760
Speaker 2: where people could qualify for it quite early on, and

537
00:32:17,840 --> 00:32:21,960
Speaker 2: we require people to have filled two evidence based treatments,

538
00:32:22,320 --> 00:32:25,800
Speaker 2: which could be psychotherapy and medication. But if people don't

539
00:32:25,800 --> 00:32:28,640
Speaker 2: want to take medication, they could even have tried two

540
00:32:28,840 --> 00:32:32,000
Speaker 2: very different types of psychotherapy and then still qualify for

541
00:32:32,080 --> 00:32:34,720
Speaker 2: our TMS for example. And there's also based on the

542
00:32:34,760 --> 00:32:38,440
Speaker 2: evidence out there that that will really increase the likely

543
00:32:38,560 --> 00:32:41,920
Speaker 2: of people to respond to to TMS. But firstly, I

544
00:32:41,960 --> 00:32:44,440
Speaker 2: do think the future will be going there as well.

545
00:32:44,680 --> 00:32:47,480
Speaker 2: We will be going to a completely different model. Rather

546
00:32:47,520 --> 00:32:50,840
Speaker 2: than taking popping a pill every day that's the current model,

547
00:32:51,120 --> 00:32:53,640
Speaker 2: people will start moving, in my view, more to brain

548
00:32:53,680 --> 00:32:58,560
Speaker 2: stimulation treatments, short intensive treatment and then you're after treatment

549
00:32:58,680 --> 00:33:02,000
Speaker 2: for a longer period or maybe with some maintenance treatment

550
00:33:02,360 --> 00:33:05,480
Speaker 2: once every six months, people can maintain their remission, and

551
00:33:05,520 --> 00:33:08,440
Speaker 2: I think similar to psychedelics, model is probably going that

552
00:33:08,520 --> 00:33:12,440
Speaker 2: direction as well, even though the clinical outcomes might not

553
00:33:12,480 --> 00:33:14,560
Speaker 2: be blowing all the drugs out of the water. But

554
00:33:14,600 --> 00:33:17,360
Speaker 2: the big advantage of psychedelics is you have a one

555
00:33:17,440 --> 00:33:21,440
Speaker 2: time psychedelic experience which can keep your remission for at

556
00:33:21,520 --> 00:33:24,520
Speaker 2: least three to six months, and then you might redo it,

557
00:33:24,560 --> 00:33:27,760
Speaker 2: which is I think at least better than popping a

558
00:33:27,760 --> 00:33:30,680
Speaker 2: bill every day, which is all kinds of side effects

559
00:33:30,680 --> 00:33:32,920
Speaker 2: and other mechanisms associated it.

560
00:33:33,880 --> 00:33:34,840
Speaker 1: Yeah, yeah, absolutely.

561
00:33:34,880 --> 00:33:38,720
Speaker 3: And look, I actually know somebody who had treatment resistant

562
00:33:38,720 --> 00:33:43,000
Speaker 3: depression and did TMS and said, did ten sessions and

563
00:33:43,200 --> 00:33:45,840
Speaker 3: was like this is doing nothing. Said after the ten

564
00:33:45,960 --> 00:33:52,320
Speaker 3: session bomb complete and other shift and was just completely

565
00:33:52,400 --> 00:33:56,120
Speaker 3: blown away by it. And actually I interviewed on my

566
00:33:56,200 --> 00:33:59,880
Speaker 3: podcast a guy who's running the first sack of psych

567
00:34:00,080 --> 00:34:05,040
Speaker 3: delic lab in Australia and they're getting some really interesting results.

568
00:34:05,040 --> 00:34:08,800
Speaker 3: He so they use it with therapy and his words

569
00:34:08,840 --> 00:34:13,120
Speaker 3: are that the psychedelic the psychedelics act as a rocket

570
00:34:13,200 --> 00:34:16,000
Speaker 3: ship for the therapy. But he says, if you're going

571
00:34:16,080 --> 00:34:18,279
Speaker 3: to use a rocket, you need to know how to.

572
00:34:18,280 --> 00:34:19,200
Speaker 1: Steer a rocket.

573
00:34:19,520 --> 00:34:22,520
Speaker 3: That's that's his big thing, because he says they're so potent.

574
00:34:23,760 --> 00:34:27,560
Speaker 3: So so, wh is TMS being used we talked about depression.

575
00:34:28,320 --> 00:34:32,719
Speaker 3: Is it being used in other psychiatric conditions with any

576
00:34:32,719 --> 00:34:34,200
Speaker 3: effectiveness at this stage?

577
00:34:34,960 --> 00:34:37,680
Speaker 2: Yeah, it's for sure. It's being investigated pretty much in

578
00:34:38,440 --> 00:34:42,239
Speaker 2: almost any psychiatic disorder. I would say, although the effectiveness

579
00:34:42,920 --> 00:34:46,120
Speaker 2: varies quite a bit. We know there's very strong evidence

580
00:34:46,719 --> 00:34:50,600
Speaker 2: for a good use of rTMS in the treatment of depression,

581
00:34:51,600 --> 00:34:55,960
Speaker 2: in the treatment of obsessive compulsive disorder. Those I think

582
00:34:56,040 --> 00:34:59,160
Speaker 2: are the two main indications. Then when we cross over

583
00:34:59,200 --> 00:35:04,120
Speaker 2: to neurology, there's some indication in pain, in chronic pain,

584
00:35:04,280 --> 00:35:07,800
Speaker 2: But the question there is how sustainable are the effects,

585
00:35:07,840 --> 00:35:12,200
Speaker 2: because you can get an acute suppression of pain, but

586
00:35:12,360 --> 00:35:15,160
Speaker 2: if you need to do TMS every day, it might

587
00:35:15,280 --> 00:35:18,080
Speaker 2: not be as clinically meaningful there, And that's I think

588
00:35:18,080 --> 00:35:21,440
Speaker 2: still the jury is still out on that one. And

589
00:35:21,520 --> 00:35:24,160
Speaker 2: other than that, I think there's multiple PTSD is also

590
00:35:24,239 --> 00:35:28,479
Speaker 2: quite effectives as a treatment with with our TMS, using

591
00:35:28,560 --> 00:35:31,120
Speaker 2: quite similar approaches that we use for the treatment of

592
00:35:31,160 --> 00:35:35,000
Speaker 2: depression as well. The network seem to overlap to some degree,

593
00:35:35,960 --> 00:35:37,880
Speaker 2: but I think that's that's why we have the strongest

594
00:35:37,880 --> 00:35:39,080
Speaker 2: evidence at this point.

595
00:35:40,080 --> 00:35:45,120
Speaker 3: Okay, can we shift TAC now and and talk about

596
00:35:45,320 --> 00:35:50,680
Speaker 3: what is probably the fastest growing psychiatric condition that that's

597
00:35:50,719 --> 00:35:55,440
Speaker 3: just from what I'm observing and hearing, which is ADHD,

598
00:35:55,840 --> 00:35:57,520
Speaker 3: And there seems to be.

599
00:36:00,040 --> 00:36:03,160
Speaker 2: They wanted to touch out on a little bit because

600
00:36:03,160 --> 00:36:06,520
Speaker 2: I think we've now mainly described TMS, but I just

601
00:36:06,560 --> 00:36:08,719
Speaker 2: wanted to give this example because I think it's a

602
00:36:08,880 --> 00:36:12,319
Speaker 2: very nice example. Also about I think the field of

603
00:36:12,320 --> 00:36:15,840
Speaker 2: applied neuroscience I remember that with TMS we want to

604
00:36:15,880 --> 00:36:19,600
Speaker 2: stimulate the prefrontal cortex, but the current way of thinking

605
00:36:19,719 --> 00:36:23,120
Speaker 2: is that TMS is more about stimulating specific networks in

606
00:36:23,160 --> 00:36:26,600
Speaker 2: the brain, and that by stimulating the prefrontal cortex, the

607
00:36:26,680 --> 00:36:29,359
Speaker 2: signal will be carried through the whole network too much

608
00:36:29,480 --> 00:36:34,239
Speaker 2: deeper structures that are inaccessible, like the subgenuine interior singlet cortex.

609
00:36:34,520 --> 00:36:38,120
Speaker 2: We're also deep brain stimulations being done so in TMS.

610
00:36:38,160 --> 00:36:42,960
Speaker 2: When we talk about biomarkers and improving treatment response, the

611
00:36:43,040 --> 00:36:46,400
Speaker 2: most often heard way of doing that it's using fMRI,

612
00:36:46,800 --> 00:36:50,160
Speaker 2: and fMRI scans are very complicated scans where we can

613
00:36:50,200 --> 00:36:54,040
Speaker 2: look at connectivity from the subgeneral to prefrontal cortex. So

614
00:36:54,760 --> 00:36:56,960
Speaker 2: although this is the most evidence based at this point

615
00:36:57,000 --> 00:36:59,960
Speaker 2: in time and most investigated, we've been looking at the

616
00:37:00,160 --> 00:37:02,600
Speaker 2: for a long time and wanted to achieve a similar

617
00:37:02,680 --> 00:37:05,960
Speaker 2: kind of outcome, but without using the fMRI because in

618
00:37:06,000 --> 00:37:10,160
Speaker 2: my view, for clinical practices, it's not always feasible to

619
00:37:10,200 --> 00:37:13,080
Speaker 2: have an fMRI scan on premise and have every patient

620
00:37:13,120 --> 00:37:15,919
Speaker 2: goes through in the MRI scan. So this is also

621
00:37:15,960 --> 00:37:19,560
Speaker 2: where you alluded to that where the heart rates and

622
00:37:19,600 --> 00:37:22,080
Speaker 2: I think I think it's an interesting topic so by

623
00:37:22,120 --> 00:37:25,560
Speaker 2: doing a lot of research and also realizing that there's

624
00:37:25,600 --> 00:37:28,640
Speaker 2: a lot of overlap between the depression network and what

625
00:37:28,680 --> 00:37:32,120
Speaker 2: we call the frontal Viagel network or the network that's

626
00:37:32,200 --> 00:37:37,160
Speaker 2: involved in the brain in regulating heart rate, hard rate friability,

627
00:37:37,640 --> 00:37:40,480
Speaker 2: we realize there's a lot of overlap. And what we

628
00:37:40,600 --> 00:37:44,279
Speaker 2: found actually was that when you apply TMS acutely to

629
00:37:44,400 --> 00:37:47,400
Speaker 2: your brain and when you're hitting the right area that

630
00:37:47,520 --> 00:37:50,960
Speaker 2: you see in acute heart rate suppression. And that's very

631
00:37:51,480 --> 00:37:54,839
Speaker 2: opposite to what you would think because feeling TMS, it's

632
00:37:54,880 --> 00:37:57,359
Speaker 2: not painful, but it's also not the most pleasant thing

633
00:37:57,640 --> 00:38:02,960
Speaker 2: to undergo because muscle shoe will will be stimulated as well,

634
00:38:03,719 --> 00:38:06,560
Speaker 2: so you would expect herd rate to increase, but not decrease.

635
00:38:06,960 --> 00:38:09,239
Speaker 2: So we described it a long time ago. It's a

636
00:38:09,239 --> 00:38:11,440
Speaker 2: good long story short. We've done a lot of research

637
00:38:11,520 --> 00:38:16,680
Speaker 2: now actually validating it against fMRI based acquisitions, and we

638
00:38:16,800 --> 00:38:19,640
Speaker 2: found that the overlap by using heart rate as an

639
00:38:19,680 --> 00:38:26,320
Speaker 2: acute readout of TMS to identify the right connected areas,

640
00:38:26,760 --> 00:38:30,480
Speaker 2: it overlapped with fMRI with between eighty five and ninety percent.

641
00:38:31,239 --> 00:38:34,120
Speaker 2: So we have now developed an iPhone app where people

642
00:38:34,160 --> 00:38:37,440
Speaker 2: can use a simple polar heart rate strap together with

643
00:38:37,480 --> 00:38:40,360
Speaker 2: an iPhone app, do a five or ten minute procedure

644
00:38:40,400 --> 00:38:42,960
Speaker 2: with TMS look at the hard rate at the same time,

645
00:38:43,239 --> 00:38:46,960
Speaker 2: which we call heart brain coupling and apps called heart

646
00:38:46,960 --> 00:38:50,680
Speaker 2: brain connect and we're using that procedure, you can now

647
00:38:50,719 --> 00:38:55,680
Speaker 2: indeed target the individualized right brain network and an individual

648
00:38:56,280 --> 00:39:00,520
Speaker 2: increase likelihood of response and being as accurate as one

649
00:39:00,560 --> 00:39:03,279
Speaker 2: could be with m right. The reason why I wanted

650
00:39:03,280 --> 00:39:05,279
Speaker 2: to highlight this because I think this is really the

651
00:39:05,360 --> 00:39:07,919
Speaker 2: type of innovation that we need in psychiatry to make

652
00:39:07,960 --> 00:39:10,399
Speaker 2: things scalable as well, and we can have all kinds

653
00:39:10,440 --> 00:39:14,279
Speaker 2: of advances and over engineering things as we go, which

654
00:39:14,280 --> 00:39:17,320
Speaker 2: is happening a lot, to be honest, because over engineering

655
00:39:17,480 --> 00:39:21,080
Speaker 2: making more sophisticated stuff will earn companies more money. But

656
00:39:21,160 --> 00:39:23,960
Speaker 2: we also have to think in the opposite direction, like

657
00:39:25,480 --> 00:39:28,879
Speaker 2: disrupting the field of brain stimulation and making it way

658
00:39:28,920 --> 00:39:32,200
Speaker 2: more accessible. I would like to see that every first

659
00:39:32,239 --> 00:39:35,160
Speaker 2: line psychology practice would have access at some point in

660
00:39:35,200 --> 00:39:38,800
Speaker 2: time over a very simple stimulator, maybe only doing one HURTZ,

661
00:39:39,080 --> 00:39:43,040
Speaker 2: and have very simple targeting techniques like using heart rate

662
00:39:43,640 --> 00:39:46,560
Speaker 2: to improve the clinical outcomes to a large degree. Already

663
00:39:46,960 --> 00:39:50,160
Speaker 2: and therefore making it way more accessible to people. And

664
00:39:49,680 --> 00:39:51,719
Speaker 2: I think that's why I wanted to highlight this as

665
00:39:51,760 --> 00:39:56,480
Speaker 2: an example of how very sophisticated fMRI based neuroimaging can

666
00:39:56,520 --> 00:40:03,040
Speaker 2: also be re engineered if you will, to refrisatile clinical

667
00:40:03,239 --> 00:40:05,320
Speaker 2: clinically based utility using heart.

668
00:40:05,239 --> 00:40:08,799
Speaker 3: Rate that comes and the cost of a heart rate

669
00:40:08,840 --> 00:40:13,000
Speaker 3: monitor and an app versus an fMRI machine is a

670
00:40:13,000 --> 00:40:15,799
Speaker 3: little bit different, isn't it? And so is this is

671
00:40:15,880 --> 00:40:20,439
Speaker 3: this process mediated to the vegus nerve and because right

672
00:40:20,640 --> 00:40:25,480
Speaker 3: because it often depressed, people have got very suppressed heart

673
00:40:25,520 --> 00:40:28,759
Speaker 3: rate variability. Can you just dive into this little a

674
00:40:28,840 --> 00:40:31,919
Speaker 3: little bit more, that connection between the heart the heart

675
00:40:32,000 --> 00:40:35,600
Speaker 3: rate variability in the Brian and exactly high are you

676
00:40:35,840 --> 00:40:40,040
Speaker 3: using heart rate to inform the TMS or guide the tms?

677
00:40:40,320 --> 00:40:43,239
Speaker 3: This is fascinating, So just ridiculously fascinating.

678
00:40:43,560 --> 00:40:46,439
Speaker 2: Yes, So when you spend the whole network ranging from

679
00:40:46,440 --> 00:40:49,959
Speaker 2: the prefioto cortex that's accessible, you then do a deep

680
00:40:50,000 --> 00:40:53,000
Speaker 2: dive so it's between your eyes and then you go

681
00:40:53,040 --> 00:40:55,319
Speaker 2: a couple of centimeters to the back of the head.

682
00:40:55,360 --> 00:40:58,960
Speaker 2: That's where the subgenuale interior signal that is located. The

683
00:40:59,040 --> 00:41:02,640
Speaker 2: sub genuineteriors England is involved in the treatment of depression

684
00:41:02,719 --> 00:41:06,120
Speaker 2: because if people do deep brain stimulation, they lower some

685
00:41:06,200 --> 00:41:09,920
Speaker 2: electrodes into that area and start stimulating that pretty much

686
00:41:09,920 --> 00:41:13,239
Speaker 2: permanently in order to resolve your depression, which is very effective.

687
00:41:13,680 --> 00:41:15,200
Speaker 2: And then when we go to the back of the

688
00:41:15,239 --> 00:41:18,319
Speaker 2: head basically to the brain stem, there we have the

689
00:41:18,400 --> 00:41:21,520
Speaker 2: vagal nerve that will exit the brain and will be

690
00:41:21,560 --> 00:41:25,120
Speaker 2: going to your heart but also to the gut as

691
00:41:25,120 --> 00:41:28,920
Speaker 2: well as the heartbreak access bas And we also know

692
00:41:29,000 --> 00:41:31,840
Speaker 2: that when we take this vagal nerve and we encapsulate

693
00:41:31,880 --> 00:41:34,879
Speaker 2: it by an electrode and we start stimulating that called

694
00:41:34,960 --> 00:41:38,560
Speaker 2: vague nerve stimulation, that can also be a very powerful

695
00:41:38,600 --> 00:41:42,800
Speaker 2: antidepressant treatment. So we know that these three notes ranging

696
00:41:42,880 --> 00:41:47,200
Speaker 2: from the cortex to subcortical areas to the brain stem,

697
00:41:47,600 --> 00:41:51,160
Speaker 2: that there's the whole network that's being aligned that's functional,

698
00:41:51,480 --> 00:41:55,480
Speaker 2: has some functionality in the bet officienology of depression, and

699
00:41:55,520 --> 00:42:00,360
Speaker 2: indeed therefore mediates a heart rate heart friability heart with

700
00:42:00,520 --> 00:42:03,680
Speaker 2: friability levels. But also there's a big cross start between

701
00:42:03,680 --> 00:42:09,480
Speaker 2: cardiovascular disease and depression. People that experienced cardi vascular accidents

702
00:42:09,520 --> 00:42:12,319
Speaker 2: are more likely to develop a depression and people with

703
00:42:12,400 --> 00:42:16,160
Speaker 2: depression are more likely to develop cardiovascular accidents. So there's

704
00:42:16,200 --> 00:42:19,879
Speaker 2: a lot of overlap between those two networks. And that's

705
00:42:20,040 --> 00:42:24,400
Speaker 2: basically the network that we utilize. So imagine that the TMS.

706
00:42:24,400 --> 00:42:27,520
Speaker 2: We always thought that the TMS we're only stimulating local

707
00:42:27,600 --> 00:42:32,400
Speaker 2: focal areas. Not true. We're stimulating a prefont area and

708
00:42:32,560 --> 00:42:36,320
Speaker 2: the stimulation pattern that we apply on your prefonted cortex

709
00:42:37,080 --> 00:42:40,719
Speaker 2: is a pattern that your vaguel nerve is responding to

710
00:42:40,960 --> 00:42:44,319
Speaker 2: with an identical stimulation pattern that we can read out

711
00:42:44,360 --> 00:42:47,319
Speaker 2: on your heart rate, So we can even tell by

712
00:42:47,440 --> 00:42:50,319
Speaker 2: using one protocol or the other. I can tell by

713
00:42:50,360 --> 00:42:53,120
Speaker 2: looking at your heart rate. Only I can tell which

714
00:42:53,160 --> 00:42:55,640
Speaker 2: producol you're stimulated with if you hit the right area.

715
00:42:56,160 --> 00:42:59,759
Speaker 2: And we've tested this because many colleagues share data with us,

716
00:42:59,800 --> 00:43:02,600
Speaker 2: heard great data, and we did not know who we

717
00:43:02,600 --> 00:43:05,160
Speaker 2: were dealing with. But by simply looking at the heart rate,

718
00:43:05,280 --> 00:43:10,239
Speaker 2: we could unblind clinical trials within ninety percent accuracy, so

719
00:43:10,320 --> 00:43:13,200
Speaker 2: we could tell like, this is real, this is faced

720
00:43:13,239 --> 00:43:16,040
Speaker 2: and by just looking at heart rates, So that's how

721
00:43:16,160 --> 00:43:18,960
Speaker 2: profound these effects are as well. We're not looking at

722
00:43:18,960 --> 00:43:22,520
Speaker 2: a small correlation. We're looking about something that you can

723
00:43:22,840 --> 00:43:26,440
Speaker 2: individually apply and tell on an individual level as well.

724
00:43:27,840 --> 00:43:30,640
Speaker 3: Is there I mean that that is just unbelievable. Is

725
00:43:30,680 --> 00:43:33,560
Speaker 3: there Is there anybody looking at or is there any

726
00:43:33,600 --> 00:43:37,840
Speaker 3: intention to then look at whether the gut microbiome is

727
00:43:37,880 --> 00:43:43,239
Speaker 3: being affected as well? Because the vegus nerve stimulates the

728
00:43:43,280 --> 00:43:45,480
Speaker 3: gut and I know it has an impact on the

729
00:43:45,480 --> 00:43:49,080
Speaker 3: gut microbiom. I mean, anybody who has had had arable

730
00:43:49,120 --> 00:43:54,000
Speaker 3: bowel syndrome from stress knows that body brain and connection.

731
00:43:54,160 --> 00:43:57,040
Speaker 3: And we know that eating a shit do and changing

732
00:43:57,040 --> 00:44:01,440
Speaker 3: your microbiome can influence your brain function and drive depression

733
00:44:01,480 --> 00:44:04,560
Speaker 3: as well. So is there anybody looking at that or

734
00:44:04,640 --> 00:44:07,360
Speaker 3: is there any plans to look at the whether the

735
00:44:07,400 --> 00:44:08,799
Speaker 3: gut microbound was playing a role?

736
00:44:09,560 --> 00:44:12,719
Speaker 2: Well, very spot on. I mean two aspects there. I

737
00:44:12,719 --> 00:44:18,360
Speaker 2: think looking at the heart, brain, gut access. Some of

738
00:44:18,400 --> 00:44:21,760
Speaker 2: our colleagues in at Burn University in Switzerland are currently

739
00:44:21,840 --> 00:44:23,640
Speaker 2: running a study where they look at that, where they

740
00:44:24,000 --> 00:44:27,920
Speaker 2: look at TMS applied to the cortex, look at hardware changes,

741
00:44:27,960 --> 00:44:31,640
Speaker 2: but also looking at the electro gastrogram, which is like

742
00:44:31,680 --> 00:44:34,959
Speaker 2: the measuring the very slow electrical activity of the gut.

743
00:44:35,640 --> 00:44:38,840
Speaker 2: So that's one group that's the first kind of research

744
00:44:38,920 --> 00:44:42,120
Speaker 2: to see if that type of top down stimulation is

745
00:44:42,160 --> 00:44:45,280
Speaker 2: also arriving in the gut as the first first step,

746
00:44:45,640 --> 00:44:47,520
Speaker 2: but I think also a second step is that there's

747
00:44:47,560 --> 00:44:50,000
Speaker 2: a lot of overlap between the vegel system and vegel

748
00:44:50,040 --> 00:44:53,560
Speaker 2: integrity on one hand in immune function, and we know

749
00:44:54,320 --> 00:44:58,719
Speaker 2: inflammatory marks also highly elevated in subgroups of the PRESS

750
00:44:58,800 --> 00:45:02,000
Speaker 2: patients and to get with another group in Germany, they

751
00:45:02,000 --> 00:45:06,000
Speaker 2: are also looking at using hardware and coupling to tease

752
00:45:06,040 --> 00:45:10,759
Speaker 2: out how that relates to possible anti inflammatory effects or

753
00:45:10,800 --> 00:45:15,120
Speaker 2: inflammation in general. So yes, for sure this technique is

754
00:45:15,160 --> 00:45:18,239
Speaker 2: getting more widely available. It's very easy to do obviously,

755
00:45:18,520 --> 00:45:21,760
Speaker 2: but as multiple people currently diving into.

756
00:45:21,600 --> 00:45:26,120
Speaker 3: This much deeper and Martin, so just to clarify for

757
00:45:26,200 --> 00:45:31,200
Speaker 3: our listeners who may have miss missed that the immune system.

758
00:45:31,880 --> 00:45:34,040
Speaker 3: The reason why this is important is that about the

759
00:45:34,040 --> 00:45:36,560
Speaker 3: eighty percent of your immune system resides in the gut

760
00:45:37,560 --> 00:45:45,400
Speaker 3: because basically that barrier between the micoso barrier is the

761
00:45:45,480 --> 00:45:48,040
Speaker 3: last barrier between the outside world and the inside world

762
00:45:48,200 --> 00:45:52,000
Speaker 3: essentially and is a very easy way for pathogens to

763
00:45:52,080 --> 00:45:56,880
Speaker 3: get into our system. Hence, if people have an irritable

764
00:45:56,920 --> 00:45:59,560
Speaker 3: bile they can develop or they have leaky got they

765
00:45:59,560 --> 00:46:00,279
Speaker 3: can develop.

766
00:46:00,120 --> 00:46:02,360
Speaker 1: All sorts of autoimmune disorders.

767
00:46:01,880 --> 00:46:06,960
Speaker 3: So not only do so, these magnets then are applied

768
00:46:07,000 --> 00:46:12,239
Speaker 3: to the head, stimulating brilliant tissue and pathways that then

769
00:46:12,760 --> 00:46:15,960
Speaker 3: through the activate the nervous system, have an impact on

770
00:46:16,000 --> 00:46:19,759
Speaker 3: the heart also then can impact on the gut and

771
00:46:19,800 --> 00:46:24,400
Speaker 3: potentially modulate the immune system just from placing magnets on

772
00:46:24,440 --> 00:46:24,880
Speaker 3: the head.

773
00:46:25,400 --> 00:46:29,680
Speaker 1: Who would have known not fifty years ago. It's crazy exactly.

774
00:46:29,360 --> 00:46:31,920
Speaker 2: But this is also a very very new information. And

775
00:46:31,960 --> 00:46:35,480
Speaker 2: also I think it testifies to the fact that brain stimulation,

776
00:46:36,000 --> 00:46:38,800
Speaker 2: where we saw that was very focal and only one effect.

777
00:46:38,840 --> 00:46:43,440
Speaker 2: We now see this a multitudes of potential mechanisms that

778
00:46:43,560 --> 00:46:47,320
Speaker 2: might impact and therefore treats various subgroups of people as well,

779
00:46:47,320 --> 00:46:51,360
Speaker 2: maybe people with an inflammatory subtype or people with a

780
00:46:51,680 --> 00:46:55,080
Speaker 2: brain connectivity issue that can And that's why I stated

781
00:46:55,120 --> 00:46:59,120
Speaker 2: before trying to already jump the gun and start thinking

782
00:46:59,160 --> 00:47:02,400
Speaker 2: about war working mechanism or what is affecting what is

783
00:47:02,400 --> 00:47:05,040
Speaker 2: the final common pathway like BD and F in my

784
00:47:05,200 --> 00:47:08,680
Speaker 2: view of jumping again, we first need to split understand

785
00:47:08,719 --> 00:47:12,640
Speaker 2: the subgroups much better before we can really talk about

786
00:47:12,680 --> 00:47:16,120
Speaker 2: a final common pathway or a working mechanism, et cetera.

787
00:47:16,239 --> 00:47:18,759
Speaker 2: Because here, again we had one treatment where we thought

788
00:47:18,760 --> 00:47:21,759
Speaker 2: we only had one effect, but we've also already isolated

789
00:47:21,800 --> 00:47:26,239
Speaker 2: here a couple of potential mechanisms in how the press

790
00:47:26,280 --> 00:47:30,200
Speaker 2: of symptoms could be mediated, whether anti inflammatory, whether from

791
00:47:30,200 --> 00:47:31,439
Speaker 2: brain connectivity, et cetera.

792
00:47:32,480 --> 00:47:37,319
Speaker 3: Wow, that is just astounding. Let's not jump and talk

793
00:47:37,360 --> 00:47:45,399
Speaker 3: to ADHD. I have often said to people that if

794
00:47:45,480 --> 00:47:49,719
Speaker 3: your diet is shit, and you don't sleep well, and

795
00:47:49,760 --> 00:47:55,800
Speaker 3: you don't exercise well, and you will probably feel an

796
00:47:55,880 --> 00:48:01,719
Speaker 3: IDIOHD example. And what's your view on the lifestyle factors

797
00:48:02,600 --> 00:48:08,240
Speaker 3: playing into ADHD and this explosion that we are seeing

798
00:48:08,400 --> 00:48:13,920
Speaker 3: in ADHD diagnosis? And I'm not going to ask you

799
00:48:13,960 --> 00:48:17,600
Speaker 3: to put a figure on it, but is at least

800
00:48:17,680 --> 00:48:20,200
Speaker 3: some of that mediated by poor lifestyle?

801
00:48:22,160 --> 00:48:26,160
Speaker 2: Very good question. Well, lifestyle for sure, although I cannot

802
00:48:26,239 --> 00:48:29,319
Speaker 2: cover all aspects of lifestyle. I think there's one important one.

803
00:48:29,840 --> 00:48:34,080
Speaker 2: I was trained as in sleep medicine for a while

804
00:48:34,120 --> 00:48:37,520
Speaker 2: as well during my studies, and I've always found sleep

805
00:48:37,680 --> 00:48:40,160
Speaker 2: very fascinating. And we spent about thirty percent of our

806
00:48:40,200 --> 00:48:44,239
Speaker 2: whole life in this state called sleep, so that must

807
00:48:44,280 --> 00:48:48,880
Speaker 2: have ripercussions in our daily function, especially I think in

808
00:48:48,880 --> 00:48:53,280
Speaker 2: psychiatry where Unfortunately, psychiatry and sleep medicine are to completely

809
00:48:53,320 --> 00:48:56,200
Speaker 2: isolated fields and they don't really talk to one another,

810
00:48:56,600 --> 00:48:59,560
Speaker 2: whereas in my field. In my view, is very important

811
00:48:59,560 --> 00:49:03,399
Speaker 2: because the symptom checklist for depression and for ADHD, there

812
00:49:03,440 --> 00:49:06,440
Speaker 2: is questions relating to sleep, asking about it but not

813
00:49:06,520 --> 00:49:11,840
Speaker 2: acknowledging it could be an ethological factor in causing such symptoms.

814
00:49:12,160 --> 00:49:16,000
Speaker 2: In depression, the most powerful treatment we have is sleep

815
00:49:16,160 --> 00:49:19,520
Speaker 2: deprivation treatment. You keep someone up all minds the depression

816
00:49:19,520 --> 00:49:24,239
Speaker 2: has gone next morning. Unfortunately, unfortunately, when they fall asleep again,

817
00:49:25,160 --> 00:49:28,440
Speaker 2: their depression pops back up. There's a way to mitigate it,

818
00:49:28,480 --> 00:49:31,920
Speaker 2: but that's a whole different discussion. So sleep plays a

819
00:49:32,120 --> 00:49:36,279
Speaker 2: very very crucial role in my views in psychiatry. So

820
00:49:36,320 --> 00:49:39,960
Speaker 2: with ADHD we stumbled on this quite accidentally. We have

821
00:49:40,040 --> 00:49:43,239
Speaker 2: been involved in a field called neurofeedback for quite a

822
00:49:43,320 --> 00:49:45,480
Speaker 2: long while I will not dwell on it too long.

823
00:49:45,560 --> 00:49:47,960
Speaker 2: There has a lot of pros and cons about that field,

824
00:49:47,960 --> 00:49:50,400
Speaker 2: and know myself as well, but one of the things

825
00:49:50,400 --> 00:49:52,759
Speaker 2: we observed at that time was that when we did

826
00:49:52,760 --> 00:49:56,239
Speaker 2: a specific protocol called sensory motorator neuro feedback, which can

827
00:49:56,239 --> 00:49:59,520
Speaker 2: also be used in sleep, people sleep problems. That's the

828
00:49:59,560 --> 00:50:02,600
Speaker 2: most free wequ report. A side effect people reported was

829
00:50:03,000 --> 00:50:05,560
Speaker 2: improving sleep, and we were treating a lot of people

830
00:50:05,560 --> 00:50:10,440
Speaker 2: with ADHD, and after a while we started using actigraphy

831
00:50:11,440 --> 00:50:14,200
Speaker 2: similar to Apple watches and all the devices we have

832
00:50:14,360 --> 00:50:18,080
Speaker 2: to quantify sleep these days, and we started actually putting

833
00:50:18,080 --> 00:50:20,680
Speaker 2: a magnifying glass and did saying like, well, what's happening

834
00:50:20,719 --> 00:50:23,600
Speaker 2: with sleep? And when we started doing it, we found

835
00:50:23,640 --> 00:50:28,759
Speaker 2: that many people with ADHD actually were presenting with what

836
00:50:28,840 --> 00:50:33,400
Speaker 2: we call sleep onset insomnia, having difficulty falling asleep or

837
00:50:33,440 --> 00:50:36,960
Speaker 2: falling asleep at a time way too late for someone's

838
00:50:37,960 --> 00:50:41,919
Speaker 2: age group bedtime, so to say, but also disrupted sleep

839
00:50:41,960 --> 00:50:44,600
Speaker 2: in very short sleep in the second half of night. Well,

840
00:50:44,640 --> 00:50:46,759
Speaker 2: to cut a long story short, there's actually quite a

841
00:50:46,800 --> 00:50:51,280
Speaker 2: lot of research available right now, also out of Australia,

842
00:50:51,320 --> 00:50:54,040
Speaker 2: there's some some groups looking at it. But I think

843
00:50:54,080 --> 00:50:55,960
Speaker 2: what we now know is that when you look at

844
00:50:56,000 --> 00:50:59,799
Speaker 2: the population of ADHD, about seventy to eighty percent eight

845
00:51:00,040 --> 00:51:04,240
Speaker 2: zero of people with ADHD suffer from something called sleep

846
00:51:04,239 --> 00:51:08,200
Speaker 2: onset insomnia, which means that they take longer to fall asleep.

847
00:51:08,680 --> 00:51:11,799
Speaker 2: And we also know that's pretty much related to melatonin

848
00:51:11,920 --> 00:51:15,440
Speaker 2: because Melatonin is a sleep hormone that starts slowly to

849
00:51:15,520 --> 00:51:18,320
Speaker 2: be released in your brain to make you fall asleep

850
00:51:19,280 --> 00:51:22,320
Speaker 2: more likely to fall asleep, and that rhythm is often

851
00:51:22,360 --> 00:51:25,160
Speaker 2: delayed in ADHD. So not only do we have the

852
00:51:25,200 --> 00:51:29,360
Speaker 2: behavioral symptom of difficulty falling asleep, we also know that

853
00:51:29,400 --> 00:51:32,560
Speaker 2: the sleep hormone is significantly delayed for a couple of

854
00:51:32,600 --> 00:51:36,840
Speaker 2: hours in people with ADHD. So what we're seeing is

855
00:51:36,880 --> 00:51:42,000
Speaker 2: that these many people with ADHD. Basically, especially if we

856
00:51:42,080 --> 00:51:45,040
Speaker 2: focus on children, school times are the same for everyone,

857
00:51:45,360 --> 00:51:48,080
Speaker 2: but if you fall asleep two hours later, you are

858
00:51:48,320 --> 00:51:51,759
Speaker 2: chronically missing out on two hours of sleep per night.

859
00:51:52,800 --> 00:51:55,200
Speaker 2: So how can we link that to behavior? Well, that's

860
00:51:55,320 --> 00:51:57,400
Speaker 2: very simple. A lot of research has been done in

861
00:51:57,440 --> 00:52:00,960
Speaker 2: the United States, for example, with very simple question, if

862
00:52:00,960 --> 00:52:03,719
Speaker 2: we send our people out to a war zone, can

863
00:52:03,760 --> 00:52:06,640
Speaker 2: they do well with less sleep? And so they've done

864
00:52:06,680 --> 00:52:10,040
Speaker 2: a lot of sleep restrictions, that is, chronically sleep restricting

865
00:52:10,080 --> 00:52:13,399
Speaker 2: completely healthy people and measuring the consequences. Well, the very

866
00:52:13,440 --> 00:52:15,960
Speaker 2: simple answer is no, they cannot do with less sleep.

867
00:52:16,320 --> 00:52:19,720
Speaker 2: So they've taken healthy people and if you measure something

868
00:52:19,719 --> 00:52:23,000
Speaker 2: called the PVT lapses, which is like a neuside test,

869
00:52:23,280 --> 00:52:26,440
Speaker 2: you then observe how often they have lapse of attention.

870
00:52:27,120 --> 00:52:31,520
Speaker 2: Then people were submitted to sleeping eight hours for two weeks,

871
00:52:31,680 --> 00:52:34,719
Speaker 2: six hours or four hours, and there was also a

872
00:52:34,760 --> 00:52:36,799
Speaker 2: group of people that were not allowed to sleep at

873
00:52:36,800 --> 00:52:39,920
Speaker 2: all for two nights because you can't extend that much longer.

874
00:52:40,440 --> 00:52:44,080
Speaker 2: So after two weeks of sleep restricting people to let's

875
00:52:44,120 --> 00:52:47,120
Speaker 2: take the six hour example, and I think many people

876
00:52:47,160 --> 00:52:49,200
Speaker 2: listening to your show will say like, well, that's me.

877
00:52:50,160 --> 00:52:52,160
Speaker 2: Some people are proud of it. Personally, I would not

878
00:52:52,239 --> 00:52:56,680
Speaker 2: be too proud of it. And basically after two weeks,

879
00:52:55,440 --> 00:53:02,399
Speaker 2: their concentration would be as that after two weeks as

880
00:53:02,440 --> 00:53:04,840
Speaker 2: the people that did not sleep at all for two nights,

881
00:53:05,640 --> 00:53:08,160
Speaker 2: with the very big difference. If you ask them like,

882
00:53:08,200 --> 00:53:10,680
Speaker 2: how are you performing? How are you functioning, they would

883
00:53:10,680 --> 00:53:15,080
Speaker 2: say I'm doing fine. So sleep restriction is really a

884
00:53:15,160 --> 00:53:19,360
Speaker 2: silent killer because without you being aware of it, without

885
00:53:19,440 --> 00:53:23,480
Speaker 2: you knowing it, your cognitive performance, your working memory, your

886
00:53:23,520 --> 00:53:30,280
Speaker 2: concentration will significantly deteriorate after two weeks to a level

887
00:53:30,840 --> 00:53:33,840
Speaker 2: quite similar to someone being sleep deprived for two nights

888
00:53:34,280 --> 00:53:37,040
Speaker 2: you are not aware of it, and also recovering from

889
00:53:37,120 --> 00:53:40,680
Speaker 2: sleep debts, you can go to a bank and borrow money.

890
00:53:40,880 --> 00:53:43,680
Speaker 2: But your body is even worse than a bank. If

891
00:53:43,719 --> 00:53:45,880
Speaker 2: you build up a sleep debt, you need to pay

892
00:53:46,080 --> 00:53:48,600
Speaker 2: back your sleep debt. If you don't pay it back

893
00:53:48,600 --> 00:53:51,719
Speaker 2: in time, you will be suffering in terms of cognition,

894
00:53:52,320 --> 00:53:56,000
Speaker 2: et cetera. So the sleep debt that has been gradually

895
00:53:56,000 --> 00:53:58,919
Speaker 2: building up over two weeks, you need to pay it off,

896
00:53:58,960 --> 00:54:02,080
Speaker 2: and it takes often the same amount of time before

897
00:54:02,080 --> 00:54:04,440
Speaker 2: you have paid back the sleep debt. So it's not

898
00:54:04,480 --> 00:54:06,560
Speaker 2: true that sleeping in on the weekend for one or

899
00:54:06,600 --> 00:54:09,800
Speaker 2: two nights, which really is not like the same quality

900
00:54:09,800 --> 00:54:14,000
Speaker 2: of sleep that you've been lacking off. But that's not enough.

901
00:54:14,200 --> 00:54:17,160
Speaker 2: You need to have a consistent amount of sleep, which

902
00:54:17,200 --> 00:54:20,600
Speaker 2: is really between seven to nine hours for the majority

903
00:54:20,600 --> 00:54:24,400
Speaker 2: of people. So with this model, we now understand that

904
00:54:24,520 --> 00:54:27,560
Speaker 2: if people are missing out in two, one or two

905
00:54:27,560 --> 00:54:31,439
Speaker 2: hours of sleep every night, their concentration in school will

906
00:54:31,480 --> 00:54:35,080
Speaker 2: be disadvantage will be at a lower level. We also

907
00:54:35,160 --> 00:54:37,440
Speaker 2: understand that if you and I would have that night

908
00:54:37,480 --> 00:54:40,440
Speaker 2: of bad sleep for multiple times we're driving a car,

909
00:54:40,800 --> 00:54:43,160
Speaker 2: we know the likelihood of an accident increase. So what

910
00:54:43,200 --> 00:54:45,440
Speaker 2: do we do. We take a red bull? So what

911
00:54:45,480 --> 00:54:48,080
Speaker 2: are we doing with the kids we're prescribing psycho stimulant

912
00:54:48,120 --> 00:54:53,600
Speaker 2: medication like metal vanidades, which we know will improve their

913
00:54:54,040 --> 00:54:57,040
Speaker 2: neuropsych function at that time, but it's not a cure

914
00:54:57,160 --> 00:55:00,360
Speaker 2: for their symptoms. The cure you will need to seek

915
00:55:00,640 --> 00:55:05,640
Speaker 2: into the sleep promote moting effects and sleep enhancement effects.

916
00:55:06,040 --> 00:55:08,960
Speaker 2: And this is really I think complementing the whole circle

917
00:55:09,080 --> 00:55:13,000
Speaker 2: in how we understand how one lifestyle effactor. Imagine if

918
00:55:13,000 --> 00:55:15,520
Speaker 2: we focus on all the other ones, but things like

919
00:55:15,640 --> 00:55:20,080
Speaker 2: sleep can explain the behavior. And also the high peractivity

920
00:55:20,440 --> 00:55:23,320
Speaker 2: is very easily explained as well because people you probably

921
00:55:23,360 --> 00:55:26,680
Speaker 2: have observed small children and when they need when they're

922
00:55:26,680 --> 00:55:29,799
Speaker 2: approaching that a bad time, they're running around like crazy,

923
00:55:29,960 --> 00:55:33,719
Speaker 2: which is a compensateory behavior to keep yourself awake, and

924
00:55:33,840 --> 00:55:38,000
Speaker 2: so it's an utter regulatory behavior. And therefore the whole

925
00:55:38,040 --> 00:55:41,920
Speaker 2: symptom domain of ADHD can be for a maturity of people,

926
00:55:42,000 --> 00:55:44,840
Speaker 2: not for everyone, but for many people can be explained

927
00:55:45,120 --> 00:55:50,240
Speaker 2: by not getting enough sleep. So remember then, a small

928
00:55:50,280 --> 00:55:54,040
Speaker 2: rewind we came from the biological clock, this melotone in

929
00:55:54,040 --> 00:55:59,160
Speaker 2: transcription being coming up too late, So how can we

930
00:55:59,239 --> 00:56:03,799
Speaker 2: understand that, Well, there's many environmental influences these days, like

931
00:56:03,960 --> 00:56:09,600
Speaker 2: blue lights, iPads, big screens very close to your eyes

932
00:56:09,920 --> 00:56:12,319
Speaker 2: that are emitting a lot of blue light, and we

933
00:56:12,400 --> 00:56:17,759
Speaker 2: know that this blue light can acutely suppressure melatonin. On

934
00:56:17,800 --> 00:56:21,800
Speaker 2: the other hand, the biggest source of blue light is sunlight,

935
00:56:22,280 --> 00:56:24,719
Speaker 2: and when you have a jet leg, the best way

936
00:56:24,800 --> 00:56:27,120
Speaker 2: to beat your jet leg is get out and get

937
00:56:27,200 --> 00:56:30,440
Speaker 2: enough sunlight so you resynchronize again. So we know that

938
00:56:30,440 --> 00:56:33,600
Speaker 2: there's like a balance between blue leg exposure in the

939
00:56:33,640 --> 00:56:37,600
Speaker 2: evening on one hand, but especially getting enough sunlight in

940
00:56:37,640 --> 00:56:41,320
Speaker 2: the morning that will resink your brain. So we've published

941
00:56:41,360 --> 00:56:43,319
Speaker 2: one study and I think there might be a couple

942
00:56:43,320 --> 00:56:46,239
Speaker 2: of graphs online about it, where we've looked at the

943
00:56:46,280 --> 00:56:50,880
Speaker 2: prevalence rate of ADHD in the United States and the

944
00:56:50,960 --> 00:56:54,239
Speaker 2: amount of sunlight you get throughout the US as so

945
00:56:54,280 --> 00:56:56,120
Speaker 2: basically a map where do I need to put my

946
00:56:56,200 --> 00:57:00,600
Speaker 2: solar panels. So we merit these two maps. Could find

947
00:57:00,719 --> 00:57:04,560
Speaker 2: that the amount of sunlight in California, for example, relative

948
00:57:04,600 --> 00:57:07,960
Speaker 2: to New York, would explain twenty five percent of the

949
00:57:08,040 --> 00:57:12,319
Speaker 2: prevalence rates in ADHD. So this is way more than

950
00:57:12,360 --> 00:57:16,760
Speaker 2: the current geogenetic influences we have found. And we've replicated

951
00:57:16,760 --> 00:57:19,840
Speaker 2: this now about three to four times, and it still

952
00:57:19,880 --> 00:57:24,080
Speaker 2: holds for mainland Europe in the US. It does not

953
00:57:24,240 --> 00:57:28,640
Speaker 2: hold for Nordic countries like Scandinavia. That's a whole different story.

954
00:57:28,720 --> 00:57:32,920
Speaker 2: Probably has to do with genetic differences in people being

955
00:57:32,920 --> 00:57:36,280
Speaker 2: more protected against low levels of sunlight because they're close

956
00:57:36,360 --> 00:57:37,520
Speaker 2: to the north.

957
00:57:38,520 --> 00:57:40,720
Speaker 1: They're adapted in some way.

958
00:57:41,160 --> 00:57:44,880
Speaker 2: So again the conclusion should not be takeaway all these iPads,

959
00:57:44,880 --> 00:57:47,400
Speaker 2: et cetera. Prohibition is something that I'm not a big

960
00:57:47,440 --> 00:57:51,080
Speaker 2: fan of as a Dutch Dutchman. But get people, get

961
00:57:51,120 --> 00:57:54,320
Speaker 2: people out in the sunlight. If you have your child

962
00:57:54,680 --> 00:57:56,880
Speaker 2: and you have a dog, well ask your child to

963
00:57:56,960 --> 00:57:59,080
Speaker 2: walk the dog in the morning. And you know the

964
00:57:59,160 --> 00:58:02,160
Speaker 2: story about where often they would say in classrooms like

965
00:58:02,200 --> 00:58:05,680
Speaker 2: well that hyperactificate kids, don't put it close to the

966
00:58:06,680 --> 00:58:09,400
Speaker 2: window because you will get distracted. Now we need to

967
00:58:09,440 --> 00:58:12,120
Speaker 2: invert it and say, well, yes, put that kid near

968
00:58:12,200 --> 00:58:15,560
Speaker 2: to the window, because they will get more sunlight catching

969
00:58:15,600 --> 00:58:18,000
Speaker 2: their eye and they will normalize. They're more lightly to

970
00:58:18,080 --> 00:58:20,520
Speaker 2: normalize their sleep in the morning. So more in the

971
00:58:20,600 --> 00:58:23,280
Speaker 2: early morning sunlight I think is a very important thing.

972
00:58:23,440 --> 00:58:25,200
Speaker 2: It's not going to cost the thing, it doesn't have

973
00:58:25,240 --> 00:58:27,400
Speaker 2: any side effect, it's not going to work for everyone,

974
00:58:27,760 --> 00:58:30,600
Speaker 2: but it might at least have some improvements. And if

975
00:58:30,640 --> 00:58:33,040
Speaker 2: at least twenty to forty percent of the people will

976
00:58:33,080 --> 00:58:36,760
Speaker 2: sink below the clinical threshold and not have a diagnose

977
00:58:36,840 --> 00:58:39,560
Speaker 2: of ADC, then I think we've won a lot already.

978
00:58:40,320 --> 00:58:44,920
Speaker 2: And also, I'm not advocating against medication. It's the most

979
00:58:44,960 --> 00:58:50,200
Speaker 2: powerful psychiatric treatment we have available, but I do think

980
00:58:50,240 --> 00:58:53,760
Speaker 2: that for many people we need to zoom in more

981
00:58:53,800 --> 00:58:56,880
Speaker 2: on sleep. Psychiatrists need to do their work better and

982
00:58:57,240 --> 00:59:02,240
Speaker 2: ask more questions about sleep, and maybe wearables use some

983
00:59:02,320 --> 00:59:06,760
Speaker 2: sleep red questionnaires to see if there's an other explanation

984
00:59:07,400 --> 00:59:09,920
Speaker 2: they can find for the symptoms, which is according to

985
00:59:09,920 --> 00:59:13,120
Speaker 2: the deism, they need to ask those questions. But most

986
00:59:13,160 --> 00:59:16,600
Speaker 2: people are simply too unfamiliar with sleep medicine to do

987
00:59:16,680 --> 00:59:17,760
Speaker 2: it an objective fashion.

988
00:59:18,840 --> 00:59:22,440
Speaker 3: That is unbelievable that it explains twenty five percent. And

989
00:59:22,480 --> 00:59:25,480
Speaker 3: to your point, you're not saying we shouldn't be medicating,

990
00:59:25,560 --> 00:59:29,919
Speaker 3: but if a chunk of these people don't actually need

991
00:59:29,960 --> 00:59:32,600
Speaker 3: to be on the medication, if we can prevent them

992
00:59:33,080 --> 00:59:37,120
Speaker 3: going into that, that is clearly the way ahead. And

993
00:59:38,240 --> 00:59:40,640
Speaker 3: you know, I'm sure nobody's done the study yet, but

994
00:59:41,040 --> 00:59:46,120
Speaker 3: I would be willing to bet my house, my business,

995
00:59:46,160 --> 00:59:49,360
Speaker 3: and pawn my children on the idea that if you

996
00:59:49,680 --> 00:59:54,640
Speaker 3: also improve people's diet and getting them exercising, especially outdoors,

997
00:59:55,920 --> 00:59:59,440
Speaker 3: we would see a significant drop in those symptoms, particularly

998
00:59:59,440 --> 01:00:01,760
Speaker 3: when we we see some of the data coming out

999
01:00:01,800 --> 01:00:08,000
Speaker 3: that American and Australian kids are spending ninety percent of

1000
01:00:08,040 --> 01:00:13,000
Speaker 3: their time indoors, right. And you know, we have these

1001
01:00:13,160 --> 01:00:16,560
Speaker 3: circadian rhythms for a reason, and most people don't realize, Martin,

1002
01:00:16,680 --> 01:00:20,520
Speaker 3: lots of your hormones run off circadian biology as well.

1003
01:00:20,600 --> 01:00:25,200
Speaker 3: So it's not just the sleep, it's the widespread effect

1004
01:00:25,240 --> 01:00:28,840
Speaker 3: throughout that biological system that is the human being that

1005
01:00:29,080 --> 01:00:34,920
Speaker 3: is hugely important. So this has been absolutely fascinating. I

1006
01:00:34,920 --> 01:00:37,040
Speaker 3: could talk for hours about this, but before I do,

1007
01:00:37,200 --> 01:00:41,440
Speaker 3: let you go. I know you're involved in a number

1008
01:00:41,440 --> 01:00:45,640
Speaker 3: of spinoff ventures where you're actually taking this research technology

1009
01:00:45,720 --> 01:00:49,760
Speaker 3: and applying it. Tell me about some of the stuff

1010
01:00:49,800 --> 01:00:52,320
Speaker 3: that you're doing that you're finding quite exciting now for

1011
01:00:52,400 --> 01:00:52,880
Speaker 3: the future.

1012
01:00:54,800 --> 01:00:57,160
Speaker 2: Well, A Currently, we've had a couple of spin offlight like,

1013
01:00:57,240 --> 01:00:59,480
Speaker 2: for example, the Whole Clinic where we by any it's

1014
01:00:59,520 --> 01:01:03,800
Speaker 2: the TM since says what spun out as newer care group.

1015
01:01:04,120 --> 01:01:06,800
Speaker 2: I think they also have clinics in Melbourne, Sydney, across

1016
01:01:06,840 --> 01:01:09,400
Speaker 2: Europe and across the US as well, which I think

1017
01:01:09,480 --> 01:01:14,000
Speaker 2: was quite exciting. Recently we also span out the EG

1018
01:01:15,240 --> 01:01:20,280
Speaker 2: Prognostics department to Shineida where we do the stratification to

1019
01:01:20,400 --> 01:01:25,000
Speaker 2: treatments using EG actually, so that also has basically, yeah,

1020
01:01:25,440 --> 01:01:28,400
Speaker 2: given me a lot of time and then to think

1021
01:01:28,400 --> 01:01:32,120
Speaker 2: about new things. I'm currently we see where the new

1022
01:01:32,200 --> 01:01:34,160
Speaker 2: science is going to bring me some doing a sabbatical

1023
01:01:34,200 --> 01:01:37,800
Speaker 2: currently at Stanford University on one end, wanting to learn

1024
01:01:37,840 --> 01:01:40,600
Speaker 2: more about psychedelics, which I think is a really fascinating field,

1025
01:01:41,000 --> 01:01:43,560
Speaker 2: and on the other hand, still pushing the research at

1026
01:01:43,600 --> 01:01:47,000
Speaker 2: brain Clean's Foundation and collaboration with many partners on the

1027
01:01:47,040 --> 01:01:49,840
Speaker 2: heart brain coupling. I think there's heart brain coupling to

1028
01:01:50,240 --> 01:01:54,120
Speaker 2: form TMS is a very fascinating field. So that's mostly

1029
01:01:54,120 --> 01:01:56,920
Speaker 2: the stuff that we're trying to focus on at this

1030
01:01:56,960 --> 01:01:57,480
Speaker 2: point in time.

1031
01:01:59,000 --> 01:02:03,360
Speaker 1: That is some very cool stuff right there. I'll tell

1032
01:02:03,360 --> 01:02:03,560
Speaker 1: you what.

1033
01:02:03,600 --> 01:02:07,680
Speaker 3: When I was a kid, I always admired explorers, and

1034
01:02:08,240 --> 01:02:11,840
Speaker 3: there's not much exploration left to do in terms of

1035
01:02:11,920 --> 01:02:13,440
Speaker 3: geographical exploration.

1036
01:02:13,920 --> 01:02:16,400
Speaker 1: But oh my god, are you in an area where there's.

1037
01:02:16,200 --> 01:02:19,320
Speaker 3: A lot of exploration to be done, and you're doing

1038
01:02:19,360 --> 01:02:26,360
Speaker 3: some very very cool stuff. So so Martin, I tip

1039
01:02:26,440 --> 01:02:30,120
Speaker 3: my hat to you, sir, and I love everything that

1040
01:02:30,160 --> 01:02:32,080
Speaker 3: you've talked about here, the stuff that you're doing, it

1041
01:02:32,160 --> 01:02:36,160
Speaker 3: is super exciting and hopefully that time in your sabbatical

1042
01:02:37,520 --> 01:02:41,240
Speaker 3: spike some new neuronal connections and you'll be off onto

1043
01:02:41,240 --> 01:02:41,960
Speaker 3: your next venture.

1044
01:02:43,440 --> 01:02:44,120
Speaker 2: Looking forward to that.

1045
01:02:45,480 --> 01:02:47,400
Speaker 3: And where can people find out more about you? If

1046
01:02:47,400 --> 01:02:49,720
Speaker 3: they want to just look at your work words the

1047
01:02:49,720 --> 01:02:58,000
Speaker 3: beggst place to send them.

1048
01:02:58,160 --> 01:03:01,120
Speaker 2: The best place to look at this our website, which

1049
01:03:01,160 --> 01:03:06,360
Speaker 2: is brain clinics dot com so brain Clinics plural. Also

1050
01:03:06,360 --> 01:03:08,680
Speaker 2: on LinkedIn, you can find my profile and connect me

1051
01:03:08,760 --> 01:03:13,360
Speaker 2: via LinkedIn or reach out via email whenever people prefer. Now,

1052
01:03:13,360 --> 01:03:15,920
Speaker 2: for those of those people that have an interest in TMS,

1053
01:03:15,920 --> 01:03:20,520
Speaker 2: we have an upcoming TMS masterclass end of September beginning

1054
01:03:20,520 --> 01:03:23,440
Speaker 2: of October where we invited some of the world leading

1055
01:03:23,560 --> 01:03:27,760
Speaker 2: experts with very new insights on TMS. Some people are

1056
01:03:27,760 --> 01:03:31,120
Speaker 2: doing TMS in one day rather than spreading out across

1057
01:03:31,400 --> 01:03:36,080
Speaker 2: multiple days. Many new innovations will be shared. So for

1058
01:03:36,120 --> 01:03:38,880
Speaker 2: those interested to do real deep dive, we have this

1059
01:03:39,000 --> 01:03:40,120
Speaker 2: master glass coming.

1060
01:03:39,920 --> 01:03:43,680
Speaker 3: Up excellent Martin, thank you for your time. This has

1061
01:03:43,720 --> 01:03:44,600
Speaker 3: been awesome.