TMS for PTSD: Does Protocol Actually Matter? - Dr. Noah Philip

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Welcome to the Neurostimulation Podcast.

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I'm Dr.

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Michael Passmore, clinical associate

professor in the Department of Psychiatry

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at the University of British Columbia

in beautiful Vancouver, Canada.

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The Neurostimulation Podcast is all

about exploring the fascinating world of

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neuroscience, clinical neurostimulation,

interventional mental health, and

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general mental health and wellness.

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We consider the latest research

breakthroughs and most importantly,

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how that research is being translated

into real world treatments that

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can improve health and wellbeing.

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So whether you're a healthcare

professional, a student, a researcher, or

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just someone who's curious about how our

brains work and what we can do to help

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them work better, this podcast is for you.

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My mission is to make the

science accessible, inspiring

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and relevant to your life.

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This podcast is separate from my clinical

and academic roles and is part of my

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personal effort to bring neuroscience

education to the general public.

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So I would like to emphasize that the

information shared in this podcast is

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for educational purposes only and is not

intended as medical advice or a substitute

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for professional medical guidance.

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Always consult with your healthcare

provider to discuss your specific

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health needs and treatment options.

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Today on the Neurostimulation Podcast,

I'm joined by one of the leading

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voices in psychiatric neuromodulation.

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Dr.

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Noah Philip is a professor of psychiatry

at Brown University, section chief of

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psychiatric neuromodulation at the VA

Providence, and a leader at the VA Center

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for Neurorestoration and Neurotechnology.

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His work sits right at the cutting

edge, bringing together clinical

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psychiatry, neuroscience, and emerging

technologies to better understand and

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treat conditions like depression and

post-traumatic stress disorder, or PTSD.

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And so in today's episode,

I'm really looking forward

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to the conversation with Dr.

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Philip, where I'm hoping that we'll

dive into a fascinating new multi-site

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study from his lab looking at

transcranial magnetic stimulation,

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or TMS, for post-traumatic stress

disorder, and specifically whether

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different protocols actually matter

in real world clinical outcomes.

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We'll also explore where the field

is heading from accelerated TMS

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to focused ultrasound, and what

a truly precision-based approach

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to neuromodulation might actually

look like in the next decade.

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So Dr.

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Philip, thanks so much for joining me.

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I'm really excited for this conversation.

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Welcome to the podcast.

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Speaker 2: Thank you

so much for having me.

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I'm absolutely delighted to be here.

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Speaker: That's great, yeah.

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you've built one of the leading

neuromodulation programs in the VA,

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and so I'm just curious, maybe you can

help us to understand how that came

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about and, a little bit about your

background and what got you to this point.

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Speaker 2: Yeah, so absolutely.

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So as you heard in the beginning, I'm one

of the associate directors of this Center

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for Neurorestoration and Neurotechnology.

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Really some words that, we can use to

always win a good game of Scrabble.

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And so that's-- this is a group,

and really this is a laboratory that

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I've been building for the better

part of the last fifteen years.

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And the goal is to design, develop,

and deploy neuromodulation treatments,

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really focusing on non-pharmacologic

neuroscience-based interventions, that

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leverage what we know about physics, and

about the brain to come up with better

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treatments than what we have right now.

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and we've been pretty successful.

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This started, really as just me, back

in around twenty eleven when we started

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things when I moved over to the VA.

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and through a series of grants, awards,

and development, and I recruited a large

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number of faculty and have grown the team.

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Everyone really with a shared purpose

and a shared goal towards moving the

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field forward and helping our patients.

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Speaker: Yeah, amazing.

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Yeah, really.

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And I think, it's really inspiring.

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it's…

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to build a program like that and, as you

say, to have the vision to want to explore

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these technologies because I think, a lot

of the psychiatrists and clinicians in

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mental health that I talk to, one of the

things that is a common refrain, I know

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I've certainly lived this for many years,

is the frustration with legacy treatment

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options, medication, psychotherapy.

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Sure, those are very valuable for

a lot of people, but there are many

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people who have treatment-resistant

conditions, treatment-resistant,

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because those particular options

leave them with persistent symptoms.

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And so the neuromodulation technologies

are really exciting in a way that

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allows people a different option,

to be able to maybe even combine

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with these other modalities, so

expanding the toolkit, so to speak.

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Speaker 2: You know, one of the things--

I wanna highlight something you just said

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and dive in, if you will, for a minute.

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Not necessarily about neuromodulation,

but I think it's a really important

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thing for the conversation for listeners.

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and you used that term

treatment-resistant, and that's a phrase

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that we use often in psychiatry, and we

use that to define or describe individuals

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who have not responded to a treatment.

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But the truth of the matter

is we don't know what that is.

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That doesn't have a definition aside from

that they haven't responded to the thing

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that we've given them really arbitrarily.

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and it-- we don't really know if

people are in fact resistant to

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treatments because we don't know

if we gave them the right treatment

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at the right time, right person.

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And that's the goal of

precision psychiatry, right?

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To find a better way to do it.

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And, it's actually my hope as we dive into

this field more that this thing that we

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call treatment resistance, maybe we can

understand it a little bit better and move

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away from a Move away from a phrase that

sort of describes, really more of a lack

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of our understanding rather than a lack

of, what we can do with our treatments.

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Speaker: Yeah, thank you

for highlighting that.

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I'm partway through Dr.

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Chris Aiken's book on difficult

to treat depression, right?

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And so he promotes the use of those

other different kinds of terms-

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Speaker 2: Yeah

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… Speaker: difficult to treat,

challenging to treat, because

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exactly as you say, it's, yeah.

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It's part of, I think it's…

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The metaphor that I sometimes use is that

is if you're following a recipe, it's

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great when the cake turns out the way that

you expect it based on the recipe that you

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follow, but people aren't cakes, right?

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And so when you follow a recipe, that

might be the recipe according to the DSM

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and/or the latest treatment guidelines.

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There's gonna be that significant

minority of patients that don't

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respond, that don't get better.

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And so what we really need is an

expanded toolbox, as you say, precision

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mental health, precision psychiatry.

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And so yeah, thank you for bringing

that to our attention right off

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the bat- Yeah … 'cause the words

that we use are really important.

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Speaker 2: I think so.

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I think so.

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I, and I love it, right?

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The, our patients', our patients' brains

and their lives, don't read the recipe.

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Yeah.

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And, Totally … that's

the world we live in.

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Yeah.

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it's-

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Speaker: Yeah.

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Absolutely.

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how about if we, if you don't mind,

maybe can we talk a bit about your

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lab's paper there about the- Absolutely

what you found with the, rTMS and

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the different approaches with PTSD?

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That would be super interesting.

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Speaker 2: Yeah.

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Yeah.

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let me start with, if you will, the

bottom line up front-… which is when

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we're thinking about what treatment

paradigm, what form of transcranial

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magnetic stimulation to give to someone

who has post-traumatic stress, the

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answer really is whatever the device

is that you have in front of you.

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And that's really the bottom line

up front, and we'll build up into

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that and we'll get there, in a bit.

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but, before we get to there, what

we need to think about is where-

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what's the frame of the question?

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So why would we care?

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And the reason we would care is there's a

long line of, papers, clinical work, and

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what have you, that have examined what

are different outcomes with transcranial

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magnetic stimulation for post-traumatic

stress and, different parameters where,

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energy is put on different parts of the

head, different settings, what have you.

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and there's always a question

of what works the best or what

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do we hope might work the best.

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And that's really the framing of the

question, just to, to get us started.

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Speaker: Yeah, definitely.

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Again, there's just such a variety.

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Part of it is the

complexity and the variety.

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I do a lot of old age mental health,

and i- it's just a little limitless,

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the complexity and the variety.

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And I think so similarly with

conditions like PTSD, the…

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not to mention the complexity,

the variety, the individual

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nature of the story that person

brings, but then their particular

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trauma is unique to them, right?

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In many ways, right?

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So it's how to align those

specific individual needs with

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these different treatment options.

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And so what was it that you found with

this particular study that was, leading to

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that conclusion around using the machine

that's in front of the clinician as

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opposed to being fussy perhaps about what

kind of approach or what kind of machine

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or, ITBS or any of these other kinds

of approaches that are being explored?

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Speaker 2: Yeah.

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So we had, over the years, we've

done a number of different clinical

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trials using different machines,

different settings, what have you.

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I believe we were the first to do a

randomized controlled trial looking

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at theta burst stimulation for

post-traumatic stress, among others,

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and lots of other people have been

in the space in different settings.

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And, and one of the, one of the,

within all of this, there's a lot of

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discussion on what are the different

devices that are around, and that

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comes down to an access question.

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So early days, the machines,

several machines, matter of

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fact, couldn't do theta burst.

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So it was an issue with their capacitors,

a w- a issue with their electronics.

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and actually, while that's no longer

an issue here in the States, if

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we think about other places that

are resource poor, so this is a

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segue, I'm gonna come back to it.

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One of the other things I've

been doing over the last couple

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years is teaching transcranial

magnetic stimulation in Ukraine.

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And, they, in those situations, don't have

access to machines that are able to do

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the sorts of things that we might have, in

the States or in Canada or what have you.

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And trying to figure out what you could

do in all the different environments to

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make sure that we can meet the needs of

our patients, is critically important.

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and, if you'd asked me these sorts

of questions about 10 years ago, I

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would've given you a different answer.

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I would've said, okay, so for d- for

post-traumatic stress, we should be

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stimulating with a low frequency on

the right-hand side of the brain, and

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maybe for depressive senses, we should

be simulating the higher frequency

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on the left-hand side of the brain."

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That was based on a series of studies,

actually early PET work, that showed

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some asymmetry between the left and

right sides of the brain, in both

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of those illnesses respectively.

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and the idea and the hope was to enhance

activity or suppress activity according

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to what those early scans, showed.

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Truth of the matter is if you really

go back and read some of these

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older studies and you dive into

the supplements, the story is not

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quite as clear as we would like.

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and, so moving forward, so we had, we'd

done, a study here, a study there, our

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colleagues had done different studies.

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and what we were seeing though was a

common story that was starting to emerge,

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that really it always seemed to work.

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I think to my personal chagrin, the,

maybe the things that I had come

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up with didn't seem to be working

any better than anything else.

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and, whenever you have these kinds of

situations, then it's time to take a big

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step back and do a really good study,

and figure out what's the ground truth

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that might be underneath all of this.

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and that's really lays the foundation

for what it is that we went and did.

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Speaker: yeah.

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Thanks for that.

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That's very helpful to

get that background.

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And I'd like to circle back to hear

more about your adventures in Ukraine.

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That's so inspiring.

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but before we leave the study, so I'll

put, the study, I'll put a link to the

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study in the show notes for folks, and

we'll flash a visual of this for viewers.

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but the study is called Effectiveness

of Transcranial Magnetic Stimulation

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for Post-Traumatic Stress Disorder: A

Multi-Site Propensity-Matched Cohort

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Study of Treatment Parameters, and

that was published in the journal

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Brain Stimulation earlier this year.

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what I'm understanding then from the study

basically is that there was a comparison.

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So this was a multi-site VA cohort of

around 756 veterans, and there was a

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comparison of approaches with rTMS, not

r- the three approaches that were compared

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were the 10 Hz rTMS, ITBS, and deep TMS.

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Is that correct?

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Oh, yeah.

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Speaker 2: What we did was we tried to

take advantage of, a naturalistic s- a-

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application of the use of the stimulation.

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So we have a, we have a program across

the US, through the Veterans Affairs

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system, that, allows large-scale

deployment of this technology.

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And Through, if you will, artifacts

of time, different people have

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different devices, different

settings, honestly different

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comforts with different settings.

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And so what we did was we took a cohort

of individuals, so right, so seven

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hundred and fifty some odd, that had

recently-- that had gotten stimulation

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over a large number of different

sites, incredibly both geographically

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diverse, and, and otherwise.

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because we really wanted to do the

sort of study that ultimately, would

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be very challenging to do in any other

environment, both in terms of the sample

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size and in terms of the approach.

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and so what we looked at, so it's

naturalistic treatment across, many

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different sites of, thirty-five or

so, if my memory serves me correctly.

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and then what we did was we did

propensity matching, which let

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me unpack a little bit here.

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Which essentially-- So we took

individuals, and it w- we, we-- it's

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a series of mathematical formula

that essentially what we do is we are

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matching them as if they were coming

into a randomized control trial and

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randomized based on things that we

want to make sure that we are maybe

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not controlling for, but adjusting for.

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So things like age and

sex and symptom severity.

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And then, and then, and then comparing the

clinical outcomes and essentially doing

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a comparison against, against the two.

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And in this case, we're using a--

we're using ten hertz as the reference.

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and the reason we're using

ten hertz as the reference is

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that's been around the longest.

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and so we felt that was a fair

sort of common comparator.

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intermittent theta burst has only

been around since twenty eighteen.

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the deep TMS systems, depending on

how you-- it's been around a little

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bit longer than that, depends on

what the access and availability is.

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and, and the goal here

really was to s- to query…

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So it's a different frequency,

so ten hertz versus ITBS, both

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higher frequencies, but then

all-- and both on the left side.

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And also compare that to the broader,

very broad deep TMS application,

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which is really depolarizing

most of the prefrontal cortex.

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and so what is a test, right?

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That allows us to test differences

in frequencies, differences in,

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in placement of coil, and also the

distribution of the induced electrical

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field, which is the common thing that

we think is driving much of the effects

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of transcranial magnetic stimulation.

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So this in essence is creating a

naturalistic experiment with a very

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large sample size, also in, in people

who typically, Don't respond, quite

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as well to, treatments in general.

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have a lot of real world

comorbidities, in terms of medical

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and psychiatric comorbidities,

and are generally quite sick.

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and then lining them up and comparing

each group against each other.

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Speaker: Yeah, that's fantastic.

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I think there's so much value in these

kinds of studies to be added into the

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mix with more typical sort of strictly

randomized double-blind controlled

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trials in that, because it does--

There's something really significant

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to be said for this idea of experience.

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Not, I'm not saying that this is strictly

experience-based medicine, but to balance

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an experience-based naturalistic kind of

study with the other more like hardcore

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evidence-based medicine types of studies,

I think that balance is very valuable.

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And yeah, 'cause as you say, I think

that, commonly people with PTSD that

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I'm sure viewers and listeners know

who are clinicians and researchers,

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and even people themselves who are

struggling with these disorders,

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they're complex disorders.

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There's lots of comorbidity.

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There's people are being, like

I said before, their own unique

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stories to these situations.

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And yeah, this is fascinating that, the

study as a naturalistic study r-resulted

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in these really interesting findings.

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And so what I was noticing then

was that there was consistency

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across the approaches.

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So the 10 hertz, rTMS was

the response r- the…

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Sorry, the response rates were 63% for the

10 hertz rTMS, 65% for the intermittent

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theta burst stimulation, and then

78% for deep TMS, but non-inferiority

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across all protocols, basically.

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Speaker 2: Yeah, that's correct.

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Just-- And just before we dive in, I

just wanna-… I wanna highlight and

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underscore one other thing, which is

even though it's a naturalistic study,

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this is a nice hybrid in between a

sort of sham controlled, randomized

307

: 00:17:20

controlled trials and an unblinded

follow of just how people do over time.

308

: 00:17:24

So this is a, it's a nice mix, between

the two that brings a little bit extra

309

: 00:17:28

rigor into the naturalistic space and

sets up a testable hypotheses, hypothesis.

310

: 00:17:33

And right, so here we were

looking at non-inferiority.

311

: 00:17:37

and just as a reminder for

listeners, what is that saying?

312

: 00:17:40

It is, it's saying that certainly

one is not worse than the other.

313

: 00:17:43

and essentially, it's not the same thing

as saying that things are the same.

314

: 00:17:47

That's equivalence testing.

315

: 00:17:48

And actually equivalence testing is the

two-sided version of inferiority testing.

316

: 00:17:54

and, which we did both too, but

essentially to, to your point, right?

317

: 00:17:59

What we find is w-when we look at, the

three different groups, that there is

318

: 00:18:05

very clear statistically significant

non-inferiority across the three

319

: 00:18:10

groups, and I would say a really good

response rate across all of the above.

320

: 00:18:17

and each of these are translating

just also just a- unpack

321

: 00:18:21

this a little bit more too.

322

: 00:18:23

Each of these is translating to

about a 20-point reduction on

323

: 00:18:27

the PTSD checklist for DSM-5.

324

: 00:18:29

It's plus or minus on

the different groups.

325

: 00:18:31

and what does that mean?

326

: 00:18:33

and that is something real and

something really meaningful.

327

: 00:18:36

That's not looking at a result and,

squinting at it, finding some statistical

328

: 00:18:42

significance that, that is a little bit

hard to interpret in the real world.

329

: 00:18:45

A 20-point reduction on this rating

scale, is really enough for a

330

: 00:18:50

non-clinician to look at a patient

and say, "This person, this is…

331

: 00:18:55

This person is better."

332

: 00:18:56

so yes, it's statistically significant

in terms of the improvements

333

: 00:19:00

and things like that, but it

is very clinically meaningful.

334

: 00:19:04

And that's actually…

335

: 00:19:05

It's well over the bar that we

would consider to be a clinically

336

: 00:19:08

meaningful change on that rating scale.

337

: 00:19:10

And I think that's a really important

point that, it is-- We do-- I think

338

: 00:19:13

we do, as a field, do a better job

emphasizing, the clinical significance

339

: 00:19:17

as well as the statistical significance.

340

: 00:19:19

but it's a big drop.

341

: 00:19:21

and, that's a really meaningful

change for a lot of people in

342

: 00:19:24

their lives, which is just great.

343

: 00:19:27

Speaker: it's fantastic.

344

: 00:19:28

Yeah.

345

: 00:19:28

Congratulations on that.

346

: 00:19:29

And thanks again for

walking us through that.

347

: 00:19:31

I confess, I'm a knuckle-dragging

clinician, so you know, I'm the kinda,

348

: 00:19:35

I'm the kind of clinician that n- usually

would just skip to the, conclusion section

349

: 00:19:39

of any journal article and the abstract.

350

: 00:19:41

And even more so now, I'm

outsourcing my critical appraisal

351

: 00:19:44

to ChatGPT and other, LLMs.

352

: 00:19:48

but, but yeah, no, that is a very

helpful way of explaining the

353

: 00:19:53

advantages of the way that the

study was designed and executed.

354

: 00:19:57

I think it's so fascinating.

355

: 00:19:58

So yeah.

356

: 00:19:58

So e- what I'm understanding is, as

you're saying, a remission rate of up

357

: 00:20:02

almost 50% across all groups, so 47

to 49%, which is phenomenal and really

358

: 00:20:08

exciting just for all the people that

need this kind of help and people who…

359

: 00:20:13

because PTSD is that

kind of condition, right?

360

: 00:20:15

It's debilitating.

361

: 00:20:16

It's chronic.

362

: 00:20:17

there's ripple effects in terms of

families and all kinds of different,

363

: 00:20:21

challenges that people end up

with, So it's no surprise that

364

: 00:20:24

there's been exploration with these

different kinds of treatment options,

365

: 00:20:28

whether it's neuromodulation or

psychedelic-assisted psychotherapy,

366

: 00:20:32

different kinds of approaches, right?

367

: 00:20:34

Yeah.

368

: 00:20:34

I think it's, it's so interesting.

369

: 00:20:36

Were you somewhat surprised by

the outcomes that you found?

370

: 00:20:40

Speaker 2: This wa- this was the direction

I had hypothesized we were going.

371

: 00:20:43

We had seen enough in a different,

enough different spaces that I didn't

372

: 00:20:47

really expect that we're gonna see a

large amount of meaningful difference.

373

: 00:20:51

the other thing we saw in this, by the

way, was also non-inferiority across the

374

: 00:20:54

board in terms of, depression outcomes.

375

: 00:20:57

which I think actually, and maybe

one of your future commentators

376

: 00:21:01

will tell me I'm wrong about this.

377

: 00:21:02

I think it's also the first time that

people have shown non-inferiority,

378

: 00:21:07

not just with theta burst and 10

hertz, which has been shown, but

379

: 00:21:10

also with deep TMS theta burst

and, standard, if you will, TMS.

380

: 00:21:14

It's funny, I don't use

the abbreviation rTMS.

381

: 00:21:17

The reason I don't is I'm from Boston

originally, and every once in a while

382

: 00:21:21

the R starts sounding a little funny

and people are wondering what the

383

: 00:21:24

heck I'm actually speaking about.

384

: 00:21:26

but, it's rTMS, right?

385

: 00:21:27

If you're…

386

: 00:21:28

but, I gotta be a little

bit careful with that.

387

: 00:21:31

but to your question, right?

388

: 00:21:32

so this was a hunch.

389

: 00:21:34

we had set this really up to, to test at

least non-inferiority, if not equivalence.

390

: 00:21:39

and, this was generally where I

thought we were going to be seeing it.

391

: 00:21:44

and the other thing that you'll, that

you'll notice if you take a look at the

392

: 00:21:47

paper is that the curves, so the changes

over time are also, look very similar.

393

: 00:21:52

So we know that not just the outcomes at

the end of treatment are the same, but

394

: 00:21:57

really people's trajectory of improvement

is comparable across the board.

395

: 00:22:01

and so that's also a really important

thing when we talk to patients and

396

: 00:22:05

educate them about what they can expect

over the trajectory of their treatment

397

: 00:22:08

and resultant effects on their illness.

398

: 00:22:12

Speaker: Yeah.

399

: 00:22:12

Yeah.

400

: 00:22:12

It's fascinating.

401

: 00:22:13

it's really exciting for

people who are just looking for

402

: 00:22:15

different treatment options.

403

: 00:22:17

And I'm curious now, I'm understanding

that your lab focuses on precision

404

: 00:22:21

neuromodulation, and yeah, what…

405

: 00:22:23

be- before- Yeah … we started, we had

a little bit of an offline conversation

406

: 00:22:26

about some other studies that your lab

has been working on and, maybe you can

407

: 00:22:31

walk us through a little bit about other

projects that your lab's involved- Yeah

408

: 00:22:34

with now and how that might actually

start to, translate into treatments that

409

: 00:22:38

can be implemented- Yeah … in practice.

410

: 00:22:40

Speaker 2: Yeah.

411

: 00:22:41

you could- we could almost take a…

412

: 00:22:42

This is a bit of a jumping off point,

because what we found in this study

413

: 00:22:45

really is not precision, right?

414

: 00:22:48

What we found is the three different

approaches actually doing the same thing,

415

: 00:22:52

and yet, really to turn that argument

on its head, what all of these are doing

416

: 00:22:58

are delivering large amounts of energy

to pathologically affected parts of the

417

: 00:23:02

brain and fundamentally disrupting a

homeostatic- pathology that we call PTSD

418

: 00:23:09

or we call depression or what have you.

419

: 00:23:12

and I suspect, the common theme across

all these protocols is as long as the

420

: 00:23:17

energy is getting in, that's what matters.

421

: 00:23:20

And I think what it also does is

it sets a really important floor.

422

: 00:23:25

So we know now that there-- we can

get a 20-point reduction on, PTSD

423

: 00:23:29

symptoms with these different forms

of transcranial magnetic stimulation,

424

: 00:23:33

and yet we need to do better.

425

: 00:23:36

And so the, the next-- the, the closest

thing, if you will, to this study is our

426

: 00:23:41

work developing, developing accelerated

TMS for post-traumatic stress, as well

427

: 00:23:46

as depression, but really primarily

focused on post-traumatic stress.

428

: 00:23:49

And, and there what we're doing is

we are, delivering large amounts of

429

: 00:23:54

stimulation in a short period of time.

430

: 00:23:56

In this case, we're using a protocol

that we, in the system developed during

431

: 00:24:00

COVID, where we deliver stimulation

five times a day for five days.

432

: 00:24:05

and, and what we can do, we published,

I'm gonna call it a case series.

433

: 00:24:09

we published a case series of about

120-some-odd individuals, earlier this

434

: 00:24:13

year or late last year, showing that

we could get in one week a, actually

435

: 00:24:18

a little bit larger than 20-point

reduction on that same rating scale.

436

: 00:24:22

I think that has to do

with the sample size.

437

: 00:24:24

I suspect once we start studying

larger amounts of people, it's

438

: 00:24:27

gonna look closer to 20 points.

439

: 00:24:28

but we can at least do that

in a short period of time.

440

: 00:24:32

So that's great.

441

: 00:24:33

and that will help reduce the access and

barriers to care, which is very important.

442

: 00:24:38

because precision, and we're gonna

get into the neuroscience in a sec

443

: 00:24:41

'cause that's really what I love,

but precision is also about, meeting

444

: 00:24:45

people where they're at, right?

445

: 00:24:46

It's the right person, right place, right

time, and that includes people's lives.

446

: 00:24:51

And many people don't have the capability,

resources, wherewithal to come to

447

: 00:24:58

a clinic once a day for six weeks.

448

: 00:25:02

Elder care, childcare, life,

illness, what have you.

449

: 00:25:06

and I think that it's a, we've got a

great option with transcranial magnetic

450

: 00:25:10

stimulation as it exists right now.

451

: 00:25:13

But in order for it to do the

good that we need it to do, we

452

: 00:25:16

do need to change our model.

453

: 00:25:19

and so part of what we've started

thinking about incorporating with

454

: 00:25:21

precision is also the person's life,

and making sure that it matches what

455

: 00:25:26

they need when what they can do.

456

: 00:25:28

So that's one side.

457

: 00:25:30

what you and I spoke about briefly

beforehand were some of the other

458

: 00:25:34

really much higher neuroscience-based

precision technologies or different

459

: 00:25:38

approaches that we've been using to what

we hope will advance the field of, brain

460

: 00:25:43

stimulation for post-traumatic stress

and all the things that come with it.

461

: 00:25:47

the first of which that's worth talking

about is, trying to bring precision to

462

: 00:25:52

the context of how we stimulate people.

463

: 00:25:56

And so this was a piece, this was

published in JAMA Psychiatry a year

464

: 00:26:00

and a half ago at this point, where we

took veterans with combat-related PTSD,

465

: 00:26:04

combat exposures-related PTSD, and we

gave them a combination of transcranial

466

: 00:26:12

direct current stimulation plus an

exposure done in virtual reality.

467

: 00:26:18

so we had a lot of a high degree

of control of the virtual reality

468

: 00:26:22

space in terms of what people

were being exposed to over time.

469

: 00:26:26

and the-- really the difference

there is this is a low amount

470

: 00:26:31

of electrical stimulation, much,

much lower, than what we do in

471

: 00:26:35

transcranial magnetic stimulation.

472

: 00:26:37

And if we did that three times a week

really for two weeks, again, that's

473

: 00:26:41

much less of a treatment burden.

474

: 00:26:43

We could meaningfully reduce symptoms

and we showed a very strong active

475

: 00:26:47

versus sham, effect in that study.

476

: 00:26:52

Speaker: No, that's incredible.

477

: 00:26:52

This is-- it's a great example

of how combining tools from this

478

: 00:26:56

expanding toolkit, these are not

necessarily competing treatments.

479

: 00:27:00

These are often complementary treatments.

480

: 00:27:02

And I think it was so interesting

how before, describing that

481

: 00:27:06

particular study, you mentioned

considerations about the commonalities.

482

: 00:27:10

So what we can infer about the perhaps

pathophysiology based on commonalities of

483

: 00:27:16

treatment Approaches, with non-inferiority

at least, or similar effectiveness.

484

: 00:27:21

and it makes me think about studies,

more recent headline-catching studies

485

: 00:27:25

th- that show similarities, for example,

with respect to ade- adenosine being

486

: 00:27:30

important for ketamine improvement as well

as ECT improvement, Yeah in depression.

487

: 00:27:35

And so the…

488

: 00:27:36

Yeah, it's really interesting to think

about what are these commonalities and

489

: 00:27:39

what does that teach us about how we

think about these disorders and the

490

: 00:27:43

pathophysiologies in the first place.

491

: 00:27:45

But, yeah, it's super interesting.

492

: 00:27:47

Speaker 2: And it, it also reminds us

that we have a lot of ways that we can

493

: 00:27:50

help if we think carefully and know a

little bit more about the brain, right?

494

: 00:27:54

That there's actually an enormous

number of things that we can do, and I

495

: 00:27:57

think to your comment in the beginning,

about being a clinician and b- being

496

: 00:28:02

challenged by, the availability

really of legacy treatments, I'm

497

: 00:28:05

also, and I'm also a clinician and

I struggle with the same things.

498

: 00:28:09

and it's, when we take a little bit

of a step back and look at the things

499

: 00:28:12

that we can do, the neuroscience

gives us, a tremendous amount of hope

500

: 00:28:18

and gives us a lot of new options.

501

: 00:28:20

And so even if everything that we do right

now that we have available today might not

502

: 00:28:26

work for someone, which can still happen,

it doesn't mean that the next thing

503

: 00:28:31

that we come up with isn't gonna work.

504

: 00:28:32

And we might…

505

: 00:28:33

We really can start coming up

with, eventually, things that

506

: 00:28:37

will suit each person depend-

depending upon their own biology.

507

: 00:28:42

We're not there yet.

508

: 00:28:43

I really wish we were.

509

: 00:28:45

but that's really the…

510

: 00:28:45

that's the mission of the…

511

: 00:28:47

mission of my group, and also

I would say a shared mission

512

: 00:28:50

across many people in the field.

513

: 00:28:54

let me…

514

: 00:28:54

One other thing I just wanna say about the

transcranial direct current stimulation

515

: 00:28:57

and, this actually gets to, some

questions around access and use, and the

516

: 00:29:02

neat thing about it is essentially the

stimulation that we give there is what

517

: 00:29:06

you can get out of a nine-volt battery.

518

: 00:29:08

and, the…

519

: 00:29:09

we set it up where there's an anode where

the electricity goes into the brain and

520

: 00:29:13

a cathode where electricity comes out

of the brain, and that creates a very

521

: 00:29:16

simple circuit that delivers just a tiny

little bit of electricity into the brain.

522

: 00:29:21

and then what we can do is we can

take very complicated electric field

523

: 00:29:25

modeling, figure out where to put that

anode and that cathode so we're getting

524

: 00:29:29

the brain regions that we want to, and

that, that does bring in a whole lot.

525

: 00:29:33

and we've, We've actually shown

that even when you put, an anode in

526

: 00:29:36

the front of the head and a cathode

in the back of the head, there is,

527

: 00:29:39

there are current gradients that are

going through, core areas involved in

528

: 00:29:44

post-traumatic stress, like the insula,

like the hippocampus, like the amygdala.

529

: 00:29:49

and we can engage those very deep

brain targets, although with,

530

: 00:29:53

with no spatial specificity.

531

: 00:29:55

So we're just, we're really just

bathing the brain in a electro-

532

: 00:29:59

really an electrical gradient.

533

: 00:30:01

the nice thing about that is that

when we're doing that, essentially

534

: 00:30:04

we are biasing neurons in a

direction that we want them to go.

535

: 00:30:09

and so that's when adding in a behavioral

component, we use virtual reality.

536

: 00:30:13

You could do therapy too.

537

: 00:30:15

but what it allows people to do is engage

more fully or perhaps get that behavioral

538

: 00:30:22

intervention to depolarize the neurons

that we want to train to depolarize.

539

: 00:30:26

and that helps the brain to, to move

into a more, more healthy state.

540

: 00:30:31

We really do need these neurons in,

for example, the medial prefrontal

541

: 00:30:35

cortex to be reliably working, when

in fact they're not in illnesses like

542

: 00:30:41

post-traumatic stress and many others.

543

: 00:30:44

the neat thing about this and,

which you bring up also is that

544

: 00:30:46

many of the things that we're doing

here are not diagnosis specific.

545

: 00:30:50

they're really shared features

across many illnesses.

546

: 00:30:53

Speaker: Yeah, it's really interesting.

547

: 00:30:54

I'm a big…

548

: 00:30:55

I think tDCS is very interesting.

549

: 00:30:57

Transcranial direct current stimulation.

550

: 00:30:59

I have a handful of devices that I use

clinically and, it's been really helpful.

551

: 00:31:04

I think, again, talking about

accessibility, remote MD supervised

552

: 00:31:08

home-based use is really an

advantage for a lot of people.

553

: 00:31:12

yeah, it's just more accessible.

554

: 00:31:13

it's less of a cost barrier.

555

: 00:31:15

But I also think that it's- You

know, considering all of these

556

: 00:31:18

different approaches and what you're

describing, again, it's this definition

557

: 00:31:22

of precision neuromodulation as

meeting the person where they're at.

558

: 00:31:26

And so I wonder also in terms of maybe

even, I had a hat tip to AI just now,

559

: 00:31:31

and so maybe even using the LLMs to help

us to generate more, specific kinds of

560

: 00:31:38

approaches towards individuals based on

their particular family history, personal

561

: 00:31:43

history, symptom complex, as you say,

biomarkers, anything that could be plugged

562

: 00:31:47

in, and then, you could get perhaps some

output around, okay, likely to respond

563

: 00:31:52

to this, less likely to respond to that,

so that people are less and less-- the

564

: 00:31:56

people and their clinicians are not

as likely to be going down wild goose

565

: 00:32:01

chases with treatments that are unlikely

to work, that we can give people more

566

: 00:32:05

of, a map around, what treatments are

likely to work or what combination of

567

: 00:32:09

treatments are likely to work and what,

out of those, what fits best with their

568

: 00:32:12

particular lifestyle this, these days or

what kind of challenges they're facing.

569

: 00:32:18

Speaker 2: Yeah.

570

: 00:32:18

We've, we, I'm very excited about

how we're gonna be able to use AI

571

: 00:32:23

in this space in a number of ways.

572

: 00:32:25

I think there are some opportunities

for particularly synthesis across

573

: 00:32:29

many different levels of analysis.

574

: 00:32:32

I think there are opportunities here

for people to essentially have a

575

: 00:32:35

personalized living medical record,

that is a learning medical record that

576

: 00:32:40

they can have with them at all times,

in ways that we don't quite have yet,

577

: 00:32:45

but it's not that hard to imagine that.

578

: 00:32:47

and, the challenge, this is a

separate conversation, the challenges

579

: 00:32:51

of course will be related to

privacy and things in that space.

580

: 00:32:53

And, unfortunately, we don't

have necessarily a great track

581

: 00:32:56

record of that kind of stuff.

582

: 00:32:58

and we really do-- That, that's part

of what we gotta figure out in this.

583

: 00:33:00

But, and also, there is, I think,

a very exciting future in using,

584

: 00:33:07

different kinds of AI, particularly

facial decoding, speech decoding, to

585

: 00:33:12

help us understand when people actually

are starting to respond to treatment.

586

: 00:33:17

We have some stuff we're

launching in a lab.

587

: 00:33:19

We and many others.

588

: 00:33:19

we're not unique in that.

589

: 00:33:21

but I do think, there's a tremendous

potential for us to be leveraging

590

: 00:33:27

these tools for some real good.

591

: 00:33:29

And in the near term.

592

: 00:33:30

I don't think this is a-- this is not a

far away, not a far away thing either.

593

: 00:33:35

Speaker: yeah, it's super exciting.

594

: 00:33:36

And speaking of leveraging for real

good, maybe we can talk a bit about

595

: 00:33:39

your experience delivering this

kind of education and technology

596

: 00:33:43

to help people in Ukraine.

597

: 00:33:44

That's so interesting.

598

: 00:33:45

Speaker 2: Yeah.

599

: 00:33:46

No, absolutely.

600

: 00:33:47

and then I think if we have time, we

can get into super precision, which will

601

: 00:33:50

be focused ultrasound sort of stuff.

602

: 00:33:52

But let's-- But the Ukraine, So I've

been to, I've been to Ukraine, twice

603

: 00:33:57

now in the last couple of years.

604

: 00:33:58

we were gonna go back, recently.

605

: 00:34:00

That's-- the current situation has been

a little bit challenging and complicated.

606

: 00:34:04

And let me actually start off by saying

that I don't have any connection to the

607

: 00:34:09

people in Ukraine aside from understanding

their, the, what has happened through

608

: 00:34:13

media outlets and what have you.

609

: 00:34:15

And so I was giving a grand rounds,

some time ago, and, in response to that,

610

: 00:34:21

someone basically cold called me and

said, "You s- seem to know something

611

: 00:34:28

about TMS for post-traumatic stress.

612

: 00:34:30

We have some colleagues in

Ukraine that were gifted some

613

: 00:34:33

devices that don't entirely…

614

: 00:34:36

They're not entirely sure how

to use them or how to optimize

615

: 00:34:39

them, and would you help?"

616

: 00:34:42

And, that was a, it was a

profoundly moving outreach.

617

: 00:34:48

And, and the first thing I did actually

was I went, I went home and I asked

618

: 00:34:52

my wife what she thought about that.

619

: 00:34:54

and, and also asked, asked my kids.

620

: 00:34:57

and I made sure that everybody

in the family, had a veto, and

621

: 00:35:01

if anyone felt overly concerned

about it, I wasn't gonna do it.

622

: 00:35:06

but w- but one of the things, and

sometimes kids really delight you.

623

: 00:35:10

what my kids said was, you know

something about this, and you have

624

: 00:35:14

an opportunity to do some good."

625

: 00:35:18

and, and so I set up a call with, the,

it's the, it's the Unbroken group.

626

: 00:35:23

It's in Lviv.

627

: 00:35:23

and, it's e- it's essentially

a very large, rehabilitation,

628

: 00:35:28

hospital or rehabilitation group.

629

: 00:35:30

Its primary focus, is on psychiatric

and medical, and they do a

630

: 00:35:34

whole bunch of different things.

631

: 00:35:35

and they had been gifted, some devices

early in the war, that were not

632

: 00:35:40

well-suited to clinical use, and were

s- using it in s- different ways.

633

: 00:35:47

and they were hoping that I could

come over and help them out and

634

: 00:35:51

help figure out how to use them.

635

: 00:35:55

Speaker: Yeah.

636

: 00:35:56

Very cool.

637

: 00:35:57

Yeah, that's, yeah, fantastic.

638

: 00:35:59

Yeah.

639

: 00:35:59

this is part of it as well is that

as the-- 'cause the technology's been

640

: 00:36:02

around for a few decades now, right?

641

: 00:36:04

So as, as the devices, it's

just obvious now that the, these

642

: 00:36:10

technologies can help so many people.

643

: 00:36:11

And so as you say, it's just a matter

of getting the devices into as many

644

: 00:36:15

hands of as many people to use them

as possible all around the world,

645

: 00:36:18

and then getting people the training

and, But it is, it's so exciting.

646

: 00:36:22

I can just think back to a little over

a year ago at the Brain Stimulation

647

: 00:36:26

Conference in Kobe, Japan, and

just seeing how there's just this

648

: 00:36:29

explosion of research and interest

in all these different technologies

649

: 00:36:33

like transcranial focused ultrasound

that you touched on just now.

650

: 00:36:37

So maybe you can, walk us through

a little bit about what your lab is

651

: 00:36:40

involved with respect- Yeah … to

this particular technology.

652

: 00:36:43

Speaker 2: Yeah.

653

: 00:36:44

So we, so we have just wrapped up,

recruitment in all of our human subjects

654

: 00:36:49

procedures doing a-- We're doing a

first-in-human study of low-intensity

655

: 00:36:53

focused ultrasound to the amygdala, in

people who have depression and anxiety and

656

: 00:36:59

all the things that come along with it.

657

: 00:37:01

So this is, so because it's a

first-in-human study, so it's funded

658

: 00:37:05

by the National Institutes of Mental

Health, and it's overseen, by the

659

: 00:37:10

US Food and Drug Administration.

660

: 00:37:12

So whenever we're taking something that

is completely experimental, like focused

661

: 00:37:17

ultrasound, we make sure that the, the

FDA is the one that allows us to put an

662

: 00:37:22

experimental device in someone's head.

663

: 00:37:24

And focused ultrasound is very

different than the other things

664

: 00:37:28

that we've talked about here.

665

: 00:37:28

so transcranial magnetic

stimulation is magnetic.

666

: 00:37:31

Transcranial direct current

stimulation is electrical.

667

: 00:37:34

And this is acoustic.

668

: 00:37:35

This is mechanical.

669

: 00:37:37

So it's an entirely

different set of physics.

670

: 00:37:39

And so in transcranial

magnetic stimulation, we have a

671

: 00:37:42

reasonable degree of focality.

672

: 00:37:45

When we put a coil over someone's

dorsolateral prefrontal cortex,

673

: 00:37:47

w-we're getting a, a fist-sized field

of what it is that we're delivering.

674

: 00:37:52

It's not a laser.

675

: 00:37:52

It's not all that focal,

but it's reasonably focal.

676

: 00:37:56

and it does, and it really lives

at the surface of the cortex.

677

: 00:38:00

Transcranial direct current

stimulation goes all through the

678

: 00:38:02

brain, but it is completely unfocal.

679

: 00:38:05

And in focused ultrasound, I like to

think brings together the best aspects

680

: 00:38:10

of both in that it gets, can get deep

into the brain, at least we hypothesize

681

: 00:38:14

that it can, get deep into the brain

and with a high degree of focality.

682

: 00:38:21

And so for the first time, we can

start to think about directly and

683

: 00:38:26

noninvasively modulating deep brain

areas that we, are aware of in

684

: 00:38:31

terms of their impact in depression,

anxiety, PTSD, any psychiatric illness.

685

: 00:38:37

And really it's, it-- the hope

is that this can be a noninvasive

686

: 00:38:41

form of deep brain stimulation.

687

: 00:38:44

Speaker: Yeah, it's fascinating.

688

: 00:38:46

it's fascinating also, just now when we

were talking about perhaps extracting

689

: 00:38:51

unexpected, more synthesis-type

conclusions from study results, like

690

: 00:38:57

commonalities of effect and what that

might tell us about pathophysiology.

691

: 00:39:01

Even more so with when we're

talking about differences in how

692

: 00:39:04

the actual biophysics are impacting

on different brain structures.

693

: 00:39:07

So this idea about how acoustic energy

and mechanical energy can actually change

694

: 00:39:14

neural function and neural networks,

it's, that's fascinating too, isn't it?

695

: 00:39:19

It, it- Yeah … it almost challenges

the idea of what, obviously the

696

: 00:39:22

neurotransmitter hypothesis of

consciousness is there's a reason

697

: 00:39:26

why it's there and it's- but, I'm

a you know, I'm guilty of going

698

: 00:39:30

down rabbit holes into alternative

theories of consciousness as well.

699

: 00:39:32

And so this kind of thing makes me think

about, maybe some of these little kind

700

: 00:39:36

of, out there theories of consciousness,

there's something to be said there.

701

: 00:39:39

we, it's, one of those

philosophical questions- Yeah

702

: 00:39:41

to a large extent.

703

: 00:39:42

Speaker 2: There is, maybe we

can put this in the show notes.

704

: 00:39:45

there's a theory of, microtubule

resonance- underlying, consciousness.

705

: 00:39:49

Speaker: Stuart Hameroff and,

706

: 00:39:49

Speaker 2: Yeah.

707

: 00:39:49

Yeah.

708

: 00:39:50

Speaker: Yeah.

709

: 00:39:50

Speaker 2: Yeah.

710

: 00:39:50

and so who knows?

711

: 00:39:53

Well- … which I think is great.

712

: 00:39:54

Yeah

713

: 00:39:54

Speaker: Yeah.

714

: 00:39:55

I think, I, again, I think maybe I'll

definitely put links to the show notes,

715

: 00:39:57

but with a significant caveat as these

are outside-of-the-box theories for sure.

716

: 00:40:01

but I've- That's a- … I've

heard a lot about- … very

717

: 00:40:03

Speaker 2: accurate,

very accurate statement

718

: 00:40:05

… Speaker: yeah, Dr.

719

: 00:40:06

Hameroff's hyperbolic, I'll dare

say, claims about, ultrasound and

720

: 00:40:09

treatments, for Alzheimer's and stuff.

721

: 00:40:10

But anyways, I think it's important to

have outside-of-the-box approaches, right?

722

: 00:40:14

Without- Yes … maybe-

723

: 00:40:14

Speaker 2: Yes

724

: 00:40:15

Speaker: broadcasting promises on a

overly we'll put it that way perhaps.

725

: 00:40:19

Yeah

726

: 00:40:19

Speaker 2: So that's, and that's why

we do very careful first-in-human

727

: 00:40:24

studies with a lot of oversight from a

lot of agencies, because we know that

728

: 00:40:29

ultrasound, out-of-the-box hypotheses

aside, we know that ultrasound

729

: 00:40:33

can really, can damage the brain.

730

: 00:40:36

folks right now across the world

can go to, tertiary academic

731

: 00:40:40

medical centers and get, ablative

focused ultrasound for their tremor.

732

: 00:40:45

It's a, it's a proven treatment.

733

: 00:40:47

It's available.

734

: 00:40:48

so it's FDA, cleared in the

States, available across the world.

735

: 00:40:52

and it's very effective.

736

: 00:40:53

and in that sense, what it's doing

is it's taking large amounts of

737

: 00:40:56

ultrasound, focusing them to a

single point in the brain, and

738

: 00:41:00

inducing coagul necrosis, better

known as burning, and putting a hole.

739

: 00:41:05

and, very effective for tremor,

but it's not something that we

740

: 00:41:08

want to have happen by accident.

741

: 00:41:11

and- The other thing I'll say is that

when we think about electromagnetic,

742

: 00:41:16

so some of the laws of physics in the

electromagnetic spectrum, so Faraday's

743

: 00:41:20

law and Pierce law, things, those are,

and I'm going to get some pushback for

744

: 00:41:25

saying this, but I'll go there anyway.

745

: 00:41:27

Those are simple laws of physics.

746

: 00:41:30

When we start thinking

about wave equations, those

747

: 00:41:33

are much more complicated.

748

: 00:41:36

And there are a lot of ways that

things can go wrong in ways that

749

: 00:41:42

are nonlinear and not expected

and can go wrong very fast.

750

: 00:41:48

And we've already seen this.

751

: 00:41:51

So there's already, there's one case

report of a serious adverse event

752

: 00:41:55

of using not low intensity focused

ultrasound, I'll call it a medium

753

: 00:42:00

intensity focused ultrasound, in a

study of substance use disorders,

754

: 00:42:04

inducing what is a cavitation event.

755

: 00:42:08

So essentially a bubble induction and

collapse in someone's subcortical areas.

756

: 00:42:14

So in their nucleus accumbens.

757

: 00:42:16

And that was reported last fall.

758

: 00:42:18

And there's been a lot of

discussion around that.

759

: 00:42:19

So this is a technology

that can hurt people.

760

: 00:42:22

And I think it's really

important to understand that.

761

: 00:42:26

And so finding what therapeutic,

hopeful therapeutic uses is great.

762

: 00:42:32

But the first thing that we have to

do is we really have to drill down

763

: 00:42:35

for safety and things in that space.

764

: 00:42:38

And so in this study, so we have a

number of people come in, we give them

765

: 00:42:47

focused ultrasound to their amygdala.

766

: 00:42:50

And in order to get to that point,

we ask lots of questions, lots of

767

: 00:42:55

assessments, lots of brain scans.

768

: 00:42:57

We get CAT scans because what we

need to understand is the structure

769

: 00:43:00

of their skull, which is not

something we have to do in any other

770

: 00:43:04

sort of area of brain stimulation.

771

: 00:43:08

Because every time the, the skull

is dense and so sound, the speed

772

: 00:43:13

of sound, sound will accelerate as

it goes through a more dense media.

773

: 00:43:17

And so we have to be really careful

about what the skull is doing.

774

: 00:43:21

And then after we do our ultrasound,

we do essentially a stat MRI scan

775

: 00:43:29

immediately thereafter at 24 hours

after and one week after as we do

776

: 00:43:34

a number of other clinical things.

777

: 00:43:35

So we're really very careful

and thoughtful about safety.

778

: 00:43:39

Speaker: yeah, for sure.

779

: 00:43:41

y- 100%, yeah.

780

: 00:43:42

And then I guess that's the key with any

emerging technology is establishing the

781

: 00:43:45

safety first and then going from there.

782

: 00:43:48

But, yeah, that's, It's exciting to think

about a non-invasive option that can

783

: 00:43:53

target deep brain s- structures for sure.

784

: 00:43:56

Speaker 2: We-- And we've seen now

in the last, actually I think week or

785

: 00:43:59

two, we've seen two studies in healthy

individuals, using focused ultrasound,

786

: 00:44:04

low-intensity focused ultrasound.

787

: 00:44:06

So that's amount of energy

that you can typically get out

788

: 00:44:09

of a diagnostic ultrasound.

789

: 00:44:11

Two different studies that have

shown that we can non-invasively

790

: 00:44:14

modulate the amygdala in healthy

people, and that's great.

791

: 00:44:18

and nothing bad happened.

792

: 00:44:19

and, gave us some very important

insights into how the amygdala functions.

793

: 00:44:24

and so actually I'm really excited.

794

: 00:44:26

We had planned this, but I'm excited

in the context of the data that's gonna

795

: 00:44:29

come out from our group, where we're

gonna describe the w- not just clinical

796

: 00:44:35

outcomes from this, but also, the

various different neuroscience outcomes.

797

: 00:44:39

So we're gonna describe, how ultrasound

changes brain perfusion, brain

798

: 00:44:45

activity, and things in that space.

799

: 00:44:48

and we did, and I'm, and the other thing

I'll say is, and, the reason I'm not

800

: 00:44:51

going into the details, in too much is

it's not yet peer-reviewed, and I really

801

: 00:44:55

don't wanna get ahead of the findings.

802

: 00:44:57

and but one of the things I do

feel comfortable saying is that

803

: 00:45:00

we, we had one person get worse,

from a psychiatric perspective.

804

: 00:45:04

There was no injury.

805

: 00:45:06

and, so we had one person whose

symptoms definitely got worse,

806

: 00:45:09

and they got worse within about

24 hours of getting ultrasound.

807

: 00:45:13

and we have also seen that

in some of our colleagues'

808

: 00:45:16

studies with focused ultrasound.

809

: 00:45:17

so as we hope all these things can

get, people better, we have to also

810

: 00:45:21

make sure we have a structure by

which we can observe and capture

811

: 00:45:25

when things don't go as planned.

812

: 00:45:27

I'm sounding a little

bit negative about this.

813

: 00:45:28

I'm actually extremely excited

about the field, but I also, I

814

: 00:45:31

feel, I take the do no harm about

what we do just so seriously.

815

: 00:45:37

Speaker: Absolutely, yeah, and

I think that's so valuable,

816

: 00:45:39

and I really appreciate that.

817

: 00:45:40

I respect that.

818

: 00:45:41

I think part of it is that it's, it,

as you say, it helps to clarify the map

819

: 00:45:45

of where we, where we're referring to

in terms of the map of what treatment

820

: 00:45:49

options that hopefully we can review

with clients and patients, reviewing

821

: 00:45:53

the potential for side effects as well

as the potential for benefits, right?

822

: 00:45:56

And not overpromising and, yeah.

823

: 00:45:58

Because anytime that there's this sort

of a hyperbole again around miracle

824

: 00:46:02

cures and what have you, there's

always some reason to be somewhat

825

: 00:46:05

skeptical about that kind of promise

that's perhaps not realistic either.

826

: 00:46:09

Speaker 2: Yep.

827

: 00:46:10

And, I certainly have seen, I have

certainly started to see some offerings

828

: 00:46:16

of ultrasound from medical spa situations.

829

: 00:46:20

and, and that's really dangerous.

830

: 00:46:22

that's just really dangerous.

831

: 00:46:23

Yeah.

832

: 00:46:24

and the hyperbole doesn't

help anybody, right?

833

: 00:46:26

and, and the, the nice thing, about

being an academic and doing this is we

834

: 00:46:32

take our time, we do it slowly, we do it

thoughtfully, and we figure what works and

835

: 00:46:37

what doesn't, and we lay it all out there.

836

: 00:46:40

which is,… I'm grateful, and I am,

mindful of the blessings inherent

837

: 00:46:45

of the a- the ability to be able

to do that kind of stuff as well.

838

: 00:46:49

Speaker: Yeah.

839

: 00:46:50

it's fantastic.

840

: 00:46:50

It really is inspiring.

841

: 00:46:52

So yeah, really just wanna thank you

so much, and congratulations to you

842

: 00:46:55

and your team and your lab there.

843

: 00:46:57

maybe before we wrap up, what would

be the, the, I suppose the prospect

844

: 00:47:01

that excites you the most about the

next five to 10 years in this field?

845

: 00:47:05

Do you think, is it FUS, TFUS?

846

: 00:47:07

Speaker 2: I do think there's an

enormous promise in focused ultrasound.

847

: 00:47:12

I think five-year window

might be too optimistic.

848

: 00:47:14

I think there's some

849

: 00:47:15

I th- I do think there are some key

challenges that we have not yet fixed,

850

: 00:47:20

primarily how do we get the energy through

the skull safely and things like that.

851

: 00:47:24

That all said, the prospect of

non-invasive deep brain stimulation,

852

: 00:47:29

the prospect of being able to do that

is … And with a technology that can

853

: 00:47:34

travel, that can go we have a,… My

wife is a veterinarian, and, so they

854

: 00:47:39

have portable ultrasound devices they

put on their belts, and that's the same

855

: 00:47:43

amounts of energy that we're using.

856

: 00:47:45

So we're talking about deep

brain stimulation that can go

857

: 00:47:50

where it needs to go, and-… and

that makes me truly excited.

858

: 00:47:54

Speaker: Yeah.

859

: 00:47:54

what a great way to end off a positive,

optimistic message, trying to get these

860

: 00:47:59

helpful cutting-edge therapeutic tools

into the hands of clinicians to treat

861

: 00:48:04

clients and patients where they're at,

meeting people where they're at in a way

862

: 00:48:08

of personalizing treatment, expanding

the therapeutic toolbox to help get

863

: 00:48:12

people better as soon as possible.

864

: 00:48:14

Dr.

865

: 00:48:15

Noah Philip, this was an incredibly rich

and clinically meaningful conversation.

866

: 00:48:20

what I think stands out most from your

work and your lab's work is this idea

867

: 00:48:24

that neuromodulation is moving beyond

rigid protocols and towards something

868

: 00:48:28

much more flexible, personalized,

and scalable as we're discussing.

869

: 00:48:32

And so these studies are really

challenging us, I think, to rethink

870

: 00:48:36

how we might deliver treatment options

like TMS, not as a one-size-fits-all

871

: 00:48:41

protocol or a miracle cure, but as a

tool that just as an artisan might use

872

: 00:48:45

a tool to really refine the approach

to creating a work of art, that we're

873

: 00:48:51

adapting the treatment based on the client

and patient that's sitting in front of

874

: 00:48:55

us, So with emerging technologies like

accelerated TMS and focused ultrasound,

875

: 00:49:00

it feels to me like we're just at

the beginning of what's possible.

876

: 00:49:03

So thank you again for joining us.

877

: 00:49:05

It was just such a great conversation.

878

: 00:49:07

Speaker 2: I, absolutely

delighted to be here, and thank

879

: 00:49:10

you so much for this invitation.

880

: 00:49:12

Speaker: Yeah.

881

: 00:49:12

Yeah.

882

: 00:49:12

And I'm l- speaking of

Boston, you mentioned Boston

883

: 00:49:14

earlier and being from there.

884

: 00:49:16

I'm looking forward to being in Boston

in June for the TMS conference there, so

885

: 00:49:19

maybe I'll- I'll s- I'll see- … bump

into you or some of your colleagues.

886

: 00:49:21

I'll see you

887

: 00:49:21

Speaker 2: there.

888

: 00:49:21

Yeah.

889

: 00:49:22

Speaker: Okay.

890

: 00:49:22

Fantastic.

891

: 00:49:23

Speaker 2: Yeah.

892

: 00:49:23

Speaker: All righty.

893

: 00:49:24

Take care.

894

: 00:49:25

Good.

895

: 00:49:25

All r- Bye now.

896

: 00:49:26

Thanks a lot.

897

: 00:49:26

It's a

898

: 00:49:26

Speaker 2: pleasure.

899

: 00:49:27

Have

900

: 00:49:27

Speaker: a good one.

901

: 00:49:27

Okay.

902

: 00:49:27

Thanks, Noah.

903

: 00:49:28

Bye.

904

: 00:49:28

Appreciate it.

905

: 00:49:28

Cheers.

906

: 00:49:29

Okay.

907

: 00:49:29

Bye.

908

: 00:49:30

Speaker 2: Of course.

909

: 00:49:30

Bye-bye.

910

: 00:49:31

Speaker: Dr.

911

: 00:49:31

Noah Philip, this was an incredibly rich

and clinically meaningful conversation.

912

: 00:49:36

What I think stands out most from your

work is this idea that neuromodulation

913

: 00:49:40

is moving beyond rigid protocols

and towards something much more

914

: 00:49:44

flexible, personalized, and scalable.

915

: 00:49:47

Your study really challenges us

to rethink how we deliver TMS, not

916

: 00:49:51

necessarily as a one-size-fits-all

protocol, but more as a tool that

917

: 00:49:55

we can adapt based on the patient

that's sitting right in front of us.

918

: 00:49:59

And with emerging technologies like

accelerated TMS and focused transcranial

919

: 00:50:03

ultrasound, it feels like we're just at

the beginning of what's actually possible.

920

: 00:50:08

Thank you so much for joining us

today on the Neurostimulation Podcast.

921

: 00:50:11

I hope that you enjoyed this

conversation into the fascinating

922

: 00:50:14

field of TMS and PTSD as much as I did.

923

: 00:50:21

Thank you so much for joining us

today on the Neurostimulation Podcast.

924

: 00:50:24

I hope that you enjoyed this

fascinating conversation about

925

: 00:50:28

cutting-edge neuroscience and

neurostimulation as much as I did.

926

: 00:50:32

If you found today's episode

interesting, don't forget to like

927

: 00:50:35

and subscribe to the podcast.

928

: 00:50:37

It really is the best way to make

sure that you never miss an episode,

929

: 00:50:40

and it also helps us to reach

more curious minds like yours.

930

: 00:50:44

If you think that today's episode might

resonate with a friend, a family member,

931

: 00:50:48

or a colleague, please share it with them.

932

: 00:50:50

This kind of knowledge really is better

when it's shared, and you never know

933

: 00:50:54

who might find this information helpful

or inspiring For more details about Dr.

934

: 00:50:59

Phillips' lab's work and the particular

study that we discussed today, as

935

: 00:51:04

well as the technology and other

relevant content, please do check out

936

: 00:51:08

the links in the show notes below.

937

: 00:51:10

You'll find everything that you

need to dive deeper into the topic.

938

: 00:51:14

And I would love to hear your

thoughts, so please do join the

939

: 00:51:17

conversation in the comment section

or reach out on social media.

940

: 00:51:21

Your questions, comments,

ideas, and feedback really

941

: 00:51:24

do make this podcast better.

942

: 00:51:26

Finally, don't forget to

tune in to the next episode.

943

: 00:51:28

It's gonna be another exciting

journey into the cutting edge of

944

: 00:51:31

neuroscience, clinical neurostimulation,

interventional mental health, and

945

: 00:51:36

general mental health and wellness.

946

: 00:51:37

So thanks again for listening.

947

: 00:51:39

I really appreciate your time,

your interest, and your attention.

948

: 00:51:42

Take care, stay curious, and I'll see you

next time on the Neurostimulation Podcast.