Unlocking Neuroplasticity: Dr. Joshua Brown on the Evolving Science and Practice of TMS

Join Dr. Trevor Brown as he interviews Dr. Joshua Brown, Assistant Professor of Psychiatry at Harvard Medical School, for an in-depth conversation on the latest advances in transcranial magnetic stimulation (TMS) and neuroplasticity. Dr. Brown shares personal stories from his journey in neuroscience, reflects on the legacy of Dr. Nolan Williams, and discusses the mechanisms behind TMS, including the role of synaptic plasticity, protocol selection, and the importance of sleep and brain health in treatment outcomes.

Whether you’re a clinician, researcher, or someone interested in mental health innovation, this episode offers practical insights into optimizing TMS therapy, understanding individual differences, and the future of brain stimulation. Discover how neuroplasticity shapes learning, memory, and recovery - and why the field of TMS is on the brink of transformative change.

Topics covered:

• The legacy of Dr. Nolan Williams in TMS
• Dr. Brown’s career and research journey
• Neuroplasticity: what it means for clinicians and patients
• How TMS protocols are evolving
• The impact of sleep and lifestyle on treatment outcomes
• Advice for clinicians and patients
• Exciting new directions in TMS research

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Transcript

speaker-0 (00:00)
This is a conversation with Dr. Joshua Brown, Assistant Professor of Psychiatry, Harvard Medical School. In this interview, Josh tells us what key things clinicians should know before implementing TMS. He delves into the working mechanisms of TMS treatment at the neuroplastic level and explains why he believes TMS will soon be the gold standard treatment for depression in the near future, paving the way for its use in other disorders that will quickly follow.

I'm sure you'll enjoy listening to our conversation.

Hi, and thanks for joining me on Dr. Trevor Brown Academy major for Neurocare groups. So thanks again to Neurocare for sponsoring this and allowing me to speak to Dr. Joshua Brown, who is assistant professor of psychiatry at Harvard Medical School. Joshua, how are going?

speaker-1 (00:48)
I'm going well, mate. How are you? Good day.

speaker-0 (00:51)
Good. Straight away, the Australian colloquialism. Love it. Thank you very much. it's, we're so happy to have you join us today, Joshua. And in this interesting time for the field of TMS, in fact, I think I'll just straight away off the bat, just mentioned that the passing of Dr. Nolan Williams, of course, and just recognizing that he did come onto the show a few years ago and I interviewed him.

very sad the whole field. Joshua, did you know Nolan at all? Get to work with him?

speaker-1 (01:24)
Yeah, knew Nolan, I would say fairly decently actually. So I did a neurology and psychiatry program, a combined program at MUSC for residency, Medical University of South Carolina. And Nolan actually was leaving that same program at the same time that I came in. And when I started, there's only like four of these in the country. so when I...

Identified this I contacted the program director and he's like before he pretty much said anything. He's like, let me put you in contact with our chief resident Nolan and so no one I talked for I would as I remember maybe like an hour and a half or something on like the first call and then we had a series of calls before I actually came out and interviewed or did anything else and you know, one of the reasons that I went there was no one had actually like kind of trailblazed away where he

And I had lot of similar interests. wanted to get into brain stimulation. I was aware of Mark George being there, the combined program being there. And so we had a lot of talks about those things. And Nolan had, in kind of the Nolan way, figured out how to not only do the already existing neurology psychiatry program, bring in an NIH R25 funded fellowship. So this is something that

⁓ MUSC had, and then residents can join into that. And so you basically get a baked in research fellowship. And then on top of that, an interventional psychiatry track, ⁓ which had been put in there. so as I ⁓ calculate it, it's like 13 years of training if you were to kind of do it sequentially and separately packed into six years. essentially I saw what he did and that was, you like that's what I want to do.

of went in there. then, know, essentially know was pretty good at staying in touch kind of over time, over the years. I've heard from a lot of people that he kind of had a similar mentorship kind of role with things. was able to actually, Mark George held a ceremony, like a memorial service for him, and was actually able to be there in Charleston and, you know, heard remarks from him and

from friends of his childhood and things like that. so along with many of the people that he touched working closely with, without question, regardless of what anyone's opinion was of Nolan, he certainly, I don't think it's arguable that he left a hole or gap in the field. hopefully kind of brings our

our thinking and our attention to some of the things that are easy to forget as we get very much caught up in all the things we're trying to do, which are important, but it's so important to still take care of our own health and also to be able to reach out and ask others when help is needed. I think that would have been hard to do, but...

I think all of us really wish that he would have. And that's one thing that's kind of become even more clear than I would have expected is so many people really just wish, and myself included, that I had this thought and I'm not the closest person to no one. He's much closer to others, but I still feel like, if I could have talked to him, I feel like I could have maybe said something or whatever. I can't imagine the way that a lot of others feel.

and kind of having the chance to hear from Mark and his thoughts on that. What I think is, I've actually told this story a number of times because I think it's really funny. And then the story turned when this happened and I was kind of thinking about it and I didn't get a chance to say it in the memorial service, but it sort of took on a new meaning after this happened. He and I were...

⁓ at Aspen, ⁓ skiing, snowboarding, and we were meeting up and we met like up at the top of this ridge, to, to start. And I didn't know how he was. And so I pointed down this hill and I had been told by Sean Siddiqui that this, shouldn't tell this story because it's like an indirect boast. So I'll just say off the bat, like I'm a good skier. I'm not trying to beat around that or anything, but there's this like, you know, good pitch, decent mogul field kind of a thing. And I'm like, what do you think about that?

He's like, yeah, let's do it. like, great. know, like I didn't get a chance to assess his, his, uh, snowboard or anything, but kind of went down it. And, know, he was kind of making his way down, uh, kind of slowly. And so we kind of realized at the bottom is like, yeah, let's, we'll avoid that kind of stuff, uh, in the future. then that was it. And we kind of went and did other things like, you know, the rest of the day, and then like a year, the funny part of story is like a year later, uh, he's describing us and he's, uh, Sean, um, and, Nolan and I were in.

Boston and he's describing me, like, yeah, he took me down this hill like this. I'm like, what are you talking about? Like you looked at it, you could have just said, no, I don't want to do it. And he's like, what am I going to say? I'm scared. You know? And so I thought it was like, just like, it was so funny just because it kind of struck me as like a funny part of Nolan. And the thing that kind of switched for me is that I was then thinking about it a little bit after and it's like a double edged sword. was like, that's part of what

made Nolan Nolan is that he, not necessarily that he was fearless, but he had the courage to like push through the fear. And, you know, he's got a lot of experiences through his life. think that, as I sort of learned, you know, and learning from others that kind of led to that, like the Taekwondo and kitesurfing and things that he overcame, you know, in his own childhood and his own life. And so that's part of what allowed him to kind of push forward and do the things that he did.

and be a real trailblazer because he was able to sort of swallow and overcome those fears and just go for it. The flip side of it is that, it almost kind of gives a little bit of insight into maybe the person that didn't ask for help, right? And that didn't say, okay, I need to step back or I need to take a break. And I remember him some years ago saying, he's like, yeah, this pace is too much. He's like, I'm gonna have to slow it down.

once you kind of start in that process, it's almost impossible to slow it down. It's got so much inertia. the more that he did, the more that people would reach out and bring him in and have him involved with things. so, yeah, mean, I'm glad you brought it up just because I think it's such a, it's central to what we're doing really, not only just him as a figure, but his work that we can honor and then also him and the way that we can

even the way that he died and the way that we can essentially honor him by taking that time ourselves and to learn from that lesson that we can reach out, that we can slow down, that we can look for help. Thanks for raising. It's certainly not something to avoid and perhaps he can help us learn in this way as well.

speaker-0 (08:27)
Yeah, thanks Joshua. ⁓ look, thanks for sharing that. ⁓ it's it's a great, ⁓ insight into, ⁓ into Nolan and what we can, ⁓ appreciate from it, from his life and learn from it and, yeah, help, help others of course. So, thanks very much. and, yeah, it was great to have Nolan on, to, interview him here in neuro care. And, ⁓ we won't, you know, we won't,

We're going to forget, know, the holies left, like, like you said, he was the founder of the, the same protocol from Stanford university. And that will remain for a long time, a large piece of, know, an ITPS, a large piece of TMS care and how our thoughts go out to his wife and kids, course. Now, Josh, today we're going to get to know a little bit about you, about yourself.

And you've already mentioned you're a good skier, so I'm looking forward to hearing a bit more about that. But we're going to just talk a little bit about your background, current things you're working on in the field of TMS. Particularly, we're going to focus on the key things that clinicians should know about before implementing TMS regarding the understanding of how TMS actually works, the working mechanisms.

Also how sleep improvement in TMS patients can change outcomes. Because knowing these things can help us explain things better to patients, help us deliver TMS in a way so that we can optimize our treatment and get better outcomes. So, but first of all, before we get into that, tell me a little bit about yourself, your sporting acumen, where you were born and raised, that sort of thing, Josh.

speaker-1 (10:08)
Sure. So yeah, about me, guess. Born in ⁓ Salt Lake City, Utah. Grew up in, you know, mostly around that area. Graduated from the University of Utah in psychology. Actually was planning on being a family marriage therapist. And then I was in a cognitive psychology class. Learned about the physiology vision and like, you know, actually mechanistically how it worked and...

That was a very clear, pivotal moment for me where sitting before the next class, like, I knew that I was going to change the direction that I was headed. That was a guiding decision for doing a, I then did an MD, PhD combined degree at the Medical College of Wisconsin. That was a pivotal part of that decision. Then that also was a similar.

driving force in deciding to do both neurology and psychiatry to understand the brain. And so those were kind of the motivating forces behind that. I mentioned that was at MUSC. then from there, I went to Brown. I was there for two and half years. And then I've been at Harvard Medical School and McLean Hospital for the last three years. as far as skiing acumen, I played a lot of sports, actually.

So pretty much any, pretty much any sport I'm interested in and I enjoy doing, skiing. I had good access to it growing up in Utah and, dad, kind of did part-time ski instructing. So we get a season pass and you know, you can't really beat that. And, wasn't really good at, water sports, ⁓ in Utah. We don't have a lot of that. and then when I went to MUSC actually, through Nolan, Nolan taught Mark George how to kitesurf who then

had a little group of trainees of, and myself included, and we had like a Tuesday evening kite surfing group. So we'd go out, learn to kite surf for a little bit and then have pizza and stuff. So that started a new love for me as well. now I, know, kite surfing sort of rivals up there with skiing is the favorite, but I like, you know, biking, triathlons, mountain biking, rock climbing, you know, kind of all the recreations, enjoy that lot.

It's, it's for me, it's, it's kind of how I, ⁓ stay sane. And, you know, another kind of big part of me is, ⁓ my family, which I don't know if it helps me to stay sane or if it drives me towards insanity, but, have four kids. they're on the older side now, teenage years. So, you know, it's, it's fun and also a little bit, of, you know, I probably have lost some hair.

know, due to those guys, but you know, a great supportive wife and so that's me.

speaker-0 (12:37)
Well, things grow for letting us know a little bit about you, Josh and Andrew, you're sporting acumen. That's very cool. I've actually never skied in my life. So I don't have access to here in Melbourne and I spent my time doing other sports, course, which kept me indoors. But yeah, I won't go skiing downhill with you. That's for sure. All right. Now that we've gotten to know you, Josh, let's have a

It's, which is, it's interesting because when we read your research, it's very complicated, right? There's a lot of basic neuroscience in there, lot of neuroplasticity, a lot of, you know, yeah, and for receptors and this and that, and, the, you know, the, really basic neuroscience of mechanisms, BDNF, or all sorts of things. So, all sorts of coil.

⁓ angles and, and magnetic fields, ⁓ E field, representations. So, so you do get into some very, very complicated neuroscience. So, so let's try to keep it as, understandable as possible and lead people through, I guess, ⁓ what's, know, what's important to the, to the clinician. and so that leads us to, your, your papers in neuroplasticity you've tried to.

make it a little bit more basic for us. A great paper is called Synaptic Plasticity 101, the story of the AMPA receptor for brain stimulation practitioner, the role of BDNF, cetera, chronic caffeine consumption, and how that curbs RTMS plasticity. You've done a lot in the area of neuroplasticity. Why do you think that's relevant to the team as practitioner? Do you think that helps us provide care?

in a better way and make decisions and explain things to our patients.

speaker-1 (14:22)
⁓ the short answer is yes. ⁓ I do think that neuroplasticity is important as a psychiatrist. ⁓ and, and, and even within neurology, but I would say even, I would say, especially with psychiatry, I, found myself just in a general clinic and inpatient units and so forth. I feel like it's essential to understand it and like people use that term and they throw it around the time. And it was actually in residency that I wrote that paper. and, and it was.

In talking with a number of people, I almost universally would hear something like, yeah, like I know about, or I know what synoptic plasticity is, or I'm kind of vaguely familiar with it, but I don't really understand what it's talking about, or what's actually involved with it, or even how it relates to things. The importance of it, at the most basic level,

Synaptic plasticity has now been well established as the cellular basis of learning and memory. And learning memory, not just like, can I memorize something, but learning memory is in the CBT that we're doing and all the types of therapy, the sports training and even traumatic memories, Synaptic plasticity is in both directions. And not saying that it's like a simple process and it involves

⁓ networks and circuits that are imposing on one another, which becomes even more complicated than the animal models that I studied. So that was the motivation actually for that article that you referenced was trying to explain in a way that in my mind, you know, it kind of boils it down to kind of the essential components and to build to actually

understand like, how does this actually play out? And so that was the intention there. So I use it a lot from even just a kind of a counseling standpoint, you know, at a general patient level and understanding, okay, when we, you know, to bring up Nolan, like he, you know, talked about kind of the space theory when he would give talks about SAINT, he would describe, you know, the 50 minute interval is if we're studying flashcards, you know, we don't just do it straight through.

through the day is similar like if we're working out, we don't necessarily just work out for 24 hours straight and then take a few months off or something. We have it broken apart because that's one of the... It's on the basis of learning and memory. There's decades of prior research on synaptic plasticity. So that's what I studied. And then it kind of became a big part of my current career.

sort of always knew that I wanted to move from the basic, you know, foundational science, neuroscience ⁓ with animal models and to kind of move into like translational research with humans. And when I started to learn more about brain stimulation, first with deep brain stimulation, and then later learned about TMS that, you know, this was like a perfect application for that. And that was part of why I like, I knew that in residency, for example, I wanted to pursue this

find some place that was strong in brain stimulation and of course no place really better than MUSC for that. that was a, synaptic plasticity was sort of a part of that background. then I remember also sitting with Mark in one of the of the earlier parts of residency and I was thinking about, okay, what am I going to do?

for this research track that I had mentioned. I still remember him pointing out, he asked about what I did and what I studied and I kind of explained how we learned how LTP, long-term potentiation works and how LTD, long-term depression works and kind of what's involved in that. he's like, John Rothwell just gave this talk. John Rothwell, for any that don't know, is from England and he's kind of a sort of a father of TMS neurophysiology, I would say.

and knows among the most, I'd say, in the world about TMS mechanisms. And so he was giving a talk at the Brain Stimulation Meeting in Barcelona in 2017 and said, we've been saying that TMS works through LTP, synaptic plasticity. LTP is just one of the most commonly studied forms of synaptic plasticity. He's saying, we think that it works through this, but we have two studies with

you know, very small studies that really have looked at this at all. so, and you can only look at a couple of components of it in that way. And so, you know, the point is that we really don't know a lot about it. at that point, I hadn't really started getting into the, to the TMS literature at all. And so was like, oh, you can imagine my excitement that the thing that I, that I knew well from before and the thing that I was wanting to get into, like there's this convergence point. And so that was what led to the first study that I did.

was combining D-cycloserine and NMDA receptor partial agonist. This had been used in a couple studies before, it been used in a TDCS study. The reason the NMDA receptor is important is because it's one of these critical rate-limiting steps in the synaptic plasticity pathway. It's really the regulator for do we let plasticity happen or do we not as just a synaptic event?

animal stuff that by enhancing the activity of an endereceptor, and technically this just keeps open longer, and combining that with TMS, could enhance the effects of it. And also, what was really kind of centrally important to me is that it would test the mechanism by seeing if it's sufficient, if decyclocyrene was sufficient to enhance TMS effects. When, like in basic science experiments,

You want to see if something is necessary for that thing to happen. So, you know, if we're going to look and see, does TMS work through LTP? Is NMDA receptors one of those critical things? Lots of experiments will look at, they'll use an NMDA receptor blocker and see, okay, can you block the effects of whatever we're testing? And, know, if it's working through LTP by blocking the NMDA receptor and, and

That only shows if it's necessary. There's quite a few things that are necessary, but there's not very much. There's only like three molecules that are sufficient to increase it. NMDA is one of those. And we use these terms like necessary and sufficient. Necessary of course means that it's required. And I'll use the analogy sometimes, like if you, to become a psychiatrist, it's necessary to go to grade school.

but it's not sufficient to become a psychiatrist. You're not a psychiatrist at the end of grade school, right? But a psychiatrist, you know, in college similarly, but a psychiatry residency, you you to medical school, is necessary but not sufficient, but a psychiatry residency is both necessary and sufficient. So that really gives you an insight into, this is how you become a psychiatrist, psychiatry residency. So similarly, how do you induce synaptic plasticity?

both LTP and LTD both depend on NMD receptor and NMD receptor is sufficient for both as well. So that was the idea with testing that. And we found that in a motor physiology experiment that we could enhance the effects. So it did show that kind of very specific data that you could enhance or I should say that the NMD receptor was sufficient to increase the motor plasticity.

And we found a few other things as well that have other LTP kind of properties to them. then really importantly, Alex McGurr at the University of Calgary, I don't know if you've met with him yet, but I'd recommend meeting with him for sure. So he did ⁓ the first clinical trial taking this same approach using decyclocerine and found that clinical effects were dramatically improved.

You're comparing standard of care TMS, intermittent theta burst, 600 pulse, and two to three fold remission and response rates, markedly decreased symptoms. And then found the same thing with OCD as well. And suggesting that it's transdiagnostic. In other words, it's not just making up for a plasticity deficit or for NMD receptor deficit or something that's specific to depression.

major depressive disorder, but seems to be more specific to enhancing TMS effects. that's kind of a more concrete and a more like, you know, I've talked about how it helps with counseling with patients for me to, you know, include synaptic plasticity and understanding like why things happen the way they do, both maladaptively and adaptively.

And in a more concrete way, we've been able to leverage this to improve TMS function and TMS ⁓ efficacy and how well it works. so, you know, we've seen it replicate a number of times in our lab doing a few different things, different kinds of protocols with these cycloserine. And now we're looking at accelerated protocols with it. And it actually highlights

something that I think is pretty important as well, which is TMS parameter space. So, you know, overall the goal of our lab is to understand, learn and understand how TMS works and then apply that to pharmacologic augmentation and to parameter space. I think, and I'm learning more that they also sort of interact with each other. You know, we don't really see a big difference clinically between 600 and 1800 pulses of ITBS, for example.

People have tested that either formally or informally, both with accelerated and daily protocols. And ⁓ it doesn't seem to make a huge difference. you know, Downer and kind of the recent case series that they have with really compelling results, just really strong response and remission rates.

adding D-cycloserine and plus or minus Vyvanse with ITBS in 20 sessions in a day and saw these really strong results. Well, we tried, we were first interested in doing, understanding better the SYNC protocol and that mechanism of action. And so we did just one day of 1800 pulses a day, 10 times in a day. just like the same protocol, we weren't focused on the network stuff or the targeting as much.

wanted to look at like the local plasticity and interesting we did see Improvements like a modest, you know 20 % or so Improvement in clinical responses a week out and we didn't go out further like like Jonathan had you know up to three months or six weeks even But we didn't see any difference with the de-cycloserine versus placebo. So we actually did a randomized controlled trial and that's this is data that we're Submitting hopefully this week. It's you know, we've been working on

It's, most stages keeps taking forever to get it out. But that's something that, you know, we had talked, we had had a number of participants that had gone through and we had talked to Jonathan back when he was conceptualizing the protocol that he was interested in trying to implement clinically. you know, so, and then in turn, what he found there has inspired kind of our next phase of research where we're looking at the same thing and comparing.

DLPFC and precuneus targets. Precuneus is another story that I can talk to you about if you want, but we have some reason to think that that might be pretty helpful. There's so much going on. When you start it off and it's such a wild time in the field right now, both for really sad reasons, tragic reasons like Nolan, but...

things are changing so rapidly and we're learning a lot and there's been some, you know, recent breakthroughs it feels like that things are just kind of, you know, I could see the field being quite different in the next five years.

speaker-0 (25:54)
Yeah. Well said. Look, it's, it's a great understanding of how neuroplasticity can impact our care. And we don't know how to choose protocols and exact scheduling of patients at the moment. You mentioned Jonathan Downer in his 1D trial and he did, sessions every 30 minutes, whereas the Saint does it every one hour. And classically we've done one session per day for, for, for months on end. And, but.

One thing is that we tend to see, one thing Jonathan saw in his 1D trial is that the results of his TMS of his ITBS plus D-cycloserine were a little bit later, about the same time after that, than if you did just a regular once per day. So how would you, if you were to help a clinician understand this and explain it to a patient that.

TMS is working on a neuroplasticity basis. And what we're trying to do is stimulate neuroplasticity to help your brain in some way. And I'll let you describe what that is. And we're going to do it in this type of schedule. And with this type of parameter, with this type of part of the brain, we're going to work on the left DLPFC or the right DLPFC rather than the motor cortex, because it's related to our

one of the depression networks, we're going to do it 12 times every half an hour, right? 12 times a day, every half an hour, or we're going to do it once a day for five weeks. How would you, how would you help a clinician explain why we're doing these different parameters when we choose the different parameters? Are we there yet in understanding which ones and when, and how can this help a patient understand that TMS isn't just a magic bullet that works straight away? Right? Yeah.

It's not something that you're just going to come in, get a session and suddenly feel better. Help us talk through that bad understanding for a patient.

speaker-1 (27:49)
Yeah, it's a good question. First answer, you know, do we understand the best way? Definitely not. Like there's so much work to be done there and a lot of low-hanging fruit. you know, a lot of impactful studies, I think yet to come out. But we are learning things and we are also inferring things from other, you know, elements and trying to incorporate these. So I think that we like, I think the learning curve will be exponential because we have more to build on than ever before.

And we're standing on the, you know, the, shoulders of those that have come before us. ⁓ you know, I remember Nolan having a con, you know, we were having a conversation and as I was kind of coming out of residency into the field and he's talking about how he was able to stand on the shoulders of, those that came before him and able to elevate the field. And that's kind of where all of us are at now is we're able to, to additionally stand on Nolan shoulders and the things that he had done. you know, and, and one of the, you know, Nolan kind of took this idea of being able to.

you know, there was a lot of safety concerns with TMS initially. so, so really pushing, you know, the, don't know the upper end of that LD 50 curve. And, by pushing that, like it kind of opened the door for everyone to be like, okay, we can actually give a lot more stimulation and I, and it, and it appears to be quite safe still. So we don't quite know if we're at the upper plateau of that or not yet. and then to the part of your question about how to,

you know, how to talk to patients. the things you were describing, it reminds me of actually a conversation that I have most of the time with patients. And that's kind of the main thing that I do clinically. I direct our clinic at McLean and see folks there. And I'm always trying to kind of explain and educate so that they have an understanding of what

you what we're trying to do, you mentioned that it's not a magic bullet. We always, of course, spell out, is not a cure. This is, this is a treatment tool. And the way that I describe this and synaptic plasticity has a lot to do with it is that, you know, explain that there's networks in the brain that are, you know, can be over or underactive that are basically not functioning as they should be, or as we would want them to be in optimal health.

And, you know, in terms of where we stimulate, one of the reasons that we, what I describe, what we target, the left dorsal otoprefrontal cortex in most cases, although this is, you know, also kind of expanding as well. There's, you know, a number of potentially new targets that might be better for certain components or certain aspects. And all of them, in theory, have the same common element, which is that

It's like a node of multiple networks coming together. know, one of the things that I think justifiably raises suspicion about TMS to people, especially outside the field, is how does the left ELPFC seem to treat everything? And one of the reasons for that is because it is so connected. It's like the central train station or something where everything kind of goes through it. And so by, you know, either enhancing the

the efficiency of it there or clogging it up, like either way, it's going to have a big impact on things far and wide, you know, throughout the brain in this case. so, so that's, you know, I explained that's why we choose to target this region because of its high connectivity to important networks that are involved in depression and in healthy mood. And then the synaptic plasticity part comes in because

You know, it's like, it's of course not just one pulse, we're giving many pulses. And when we repeatedly activate something, it's engaging these mechanisms where the brain is learning, okay, this is an important pathway and it's going to increase receptor levels there. That leads to more efficiency so that when you have a synaptic event, it responds more easily than it would previously.

And when that's the case, it's able to essentially complete that circuit or propagate that thought pattern or emotional memory or whatever it may be. The same kinds of things, I think of it very similar to something like cognitive behavioral therapy. It's just that cognitive behavioral therapy is, I think it's more precise but less robust.

⁓ And but it's the same idea as you're you're focusing more on like fine-tuning like which exact circuit But you're here you have to keep doing it, you know repeatedly over and over Takes a little bit longer. It's a little bit more slow where TMS is a little bit more You know, you're hitting tons of like big swaths of tissue And in in all of that, you know, you're hitting the kind of the important Pathways that are involved in this so it's

There's a lot of good analogies, whether it's repeatedly like lifting a muscle or whatever.

speaker-0 (32:35)
And like that learning progress that you talking about that Nolan used in his analogies of using flashcards and repeatedly learning something every hour. So in the same way, would you say that with TMS we're repeatedly doing this to improve that neuroplastic process in the area? And is that a similar thing with, for example, a 10 Hertz protocol, an ITBS protocol, ⁓ a 1 Hertz protocol on the right side?

we, don't, we, there aren't any clear decision rules in the field that after the next amount of sessions, we change protocol or we do that. It's a little bit of trial and error because on an individual level, we have a patient who may not be responding. If they respond, great. We stay now. Right. If they're not responding, we tend to try and maybe do the right side one, one host protocol or we'll do, an accelerated protocol. How would you, is that.

Is that something that you know we're beginning to understand more about or you could give any advice on in terms of neuroplastic effect?

speaker-1 (33:36)
Yeah, it's a really great question. you know, unfortunately, I don't feel like I have a great answer as to what, you know, how to make clinical decisions about switching protocols, switching targets. This is something that we discuss quite a bit in our own TMS rounds. The, you know, and we also have these sort of traditional ways of thinking of

of high frequency left or ITBS left and CTBS low frequency right. And, you know, it's like there's some kind of increasing evidence that that may not actually be as important as we thought either. And that's not just in depression, but like in PTSD and, and, and other things. so it, you know, I think we have quite a bit still to learn about what happens with this. There's, there's some evidence that both in animal and then we kind of see it in human where it may just be that

repeatedly disturbing what is otherwise kind of a rut or something, right? Like a maladaptive process that it kind of can normalize, whether it's low frequency or high frequency. I think that we tend to see if we're focusing in on, you know, part of the reason that we have these old terms like inhibitory and excitatory for various protocols. you know, I think we've largely moved away for that because it's not a

one size fits all. Not only is there inter-individual variability, which is certainly the case, maybe 60-70 % of people might have an excitatory motor physiology response to ITBS or 10 Hz or something, but the others don't. But then you also have the fact that you change some other component of it, like you double the pulse number or you change the intervals or something like that.

You know, one simple example is a well-known paper by Gambo, Walter Paul's group, believe that doubled the ITBS pulse number and flipped the kind of potentiation of the 600 protocol and with 1200 pulses, I it was inhibitory. so it's just, it's, you know, it's, still ITBS, but it's depending on how you use it.

And even the brain state that you're using it in, that can change whether it's inhibitory or excitatory. So that's why we don't use that term or those terms anymore, because unless you kind of show, if you do an experiment and you show it's an excitatory thing, then you'd say it, right? But otherwise there's too many other factors involved if you haven't actually shown it to say it that way. And so, you know, what does that mean for clinical application of...

You know, the, the TMS protocol that we're using and, and, know, when do we change from one thing to another? You know, we, we've, we've looked at kind of doing some randomized things ourselves, like at 15 sessions or even 20 sessions, you know, having one group where we keep it, one group where we switch it. just as a matter of course, it's, it's just so challenging, right? Because of the kind of every individual is different and it feels like one of those areas where it's going to be difficult to actually see a signal.

come out of there and you wonder, if you switched someone and they didn't get better, it's like, ⁓ what if we kept them there and just kept giving, you know, pulse, kept giving sessions, maybe we get there. or if you switched them and they got better, it's like, well, was it just getting more sessions that got them better or was it the switch? So it's really difficult to know on a, know, even if you did the same person a year later or something like that, it's still a different circumstance in life. You know, there's things going on at home or not.

It's just like a really challenging thing to really parse out. I think more work in animals could be maybe a little bit guiding and helpful. And we're actually working on some things also with computational modeling that might be to provide some insight into the parameter space. I think it's a really, you know, like I mentioned, it's kind of one of the two main applications of what we're trying to do in our lab and the augmentation and the parameter space. so, you know, I think it's really important.

There's some parameters that don't seem to be that important and some that probably are and do seem to be pretty important. And then if we're changing the brain state with something like decyclocerine, that also seems to change it further. Like I mentioned with the 18 versus 600 pulses. so hopefully we'll be able to kind of clarify that point a little bit soon, but yeah, this is one of those things that is really challenging to sort out. And I should mention that we...

So as a field, know that there's an infinite parameter space. We know that some of these probably matter a fair bit and maybe it depends somewhat on the target, the disorder that we're trying to treat, et cetera. I don't know if you're aware of the, say a little over a year old now, the TMS journal, transcranial magnetic estimation journal, we are...

forming a special issue where we will be focusing in on parameters. So specifically like head-to-head trials, we'll have a series of systematic reviews that go over each of these parameters. within each of those kind of expert opinion on interpreting what these trials tell us and sort of what domain, what areas would be considered

reasonable to try clinically or to use clinically. We already use a number of off-label things like 1 Hertz, for example. And which things would be maybe things that should only really be tried if we're going to really test them and inform patients we want to test this thing, right? And so we don't want to just give it to them as standard of care. We want to let them know that we don't know enough about this and we want to know more. That's why we're to try it. We think it could be helpful.

And so basically to kind of lay out a little bit more clearly to the field, because I've, you know, I, feel like I'm in this field as much as anybody and it's not clear to me either. Like it's, you know, there's a lot of ambiguity. There's a lot of, uncertainty and there's a lot of things out there that, you know, on counter stuff and like, how did I not know about that? and things that, you know, I was talking to one of your, one of your mates down there in the land down under Robin Cash, you know, and he's like,

He did a randomized trial, controlled trial with four different inter-train intervals. And he's like, why didn't anyone pick that up? Why don't clinicians use that? it's like, there's just things out there kind of floating around. so I think if we're going to try to solve this space, we first need to identify what we have and then...

And then we can kind of identify, here's the next steps forward. So that's one of the things that I think is really important to me with the journal to try to move the field forward.

speaker-0 (40:12)
Yeah. Thanks, Josh. It's, it's, clinicians are placed in a really difficult situation, I guess, with scheduling. They might have allocated from, from Medicare or insurance, a certain number of sessions, and then they have to decide at which point they, they make a, they, they pivot and they, they, they make a decision. And it's good to know that, you know, nobody has the answer, especially since there are so many inter-individual differences. One person might have different plasticity.

in their brain and, and I, I found it really interesting to, to look at your research on, on athletes and musicians and the plasticity that they had and the outcomes you had there relative to the presumed extra plasticity that, that they had prior to TMS. Would you like to, just, just give us a quick hint about what that research told us in your plasticity, but also where the field of TMS in performance is at this date.

speaker-1 (41:09)
Yeah, I think that was the study on musicians and athletes was actually the idea of Jamie Kwan, who was a research assistant in my lab and just left to do an MD PhD. she, you know, we had these experiments that we'd ran with folks and this was a retrospective study where we wanted to look back and see, okay, of those that like use their hands, like pianist, violinist, or, you know, a volleyball player kind of a thing like. ⁓

did they have any difference in plasticity among those that did not and found that they had like a really clear increase relative to those that didn't have that. And so to me, that was really interesting, not just from a performance enhancement standpoint, because I actually don't think, you know, it suggests that those that do something a lot have increased ability

in plasticity, and it's not so surprising. We kind of see that with someone that's really good at maybe one element, either language or an instrument or a sport or something like that. They tend to be able to pick up other things better because that part of their brain that's doing that, they've increased the potential for plasticity. I looked into this, it's likely they have more NMD receptors that are...

able to respond to a signal and a stimulus and induce that plasticity. So that's what we found with them. And what I speculate about is that people that have gotten really good with therapy, really good with mindfulness, CBT, whatever, they've kind of trained their brains to sort of think a certain way. And then when we stimulate with TMS, does this enhance that capacity to respond?

So that's still an unanswered question ultimately, but it's one of the things that made me excited to look at that. So anyway, I thought it was a really interesting result that came from Jamie's study.

speaker-0 (42:58)
Yeah, great. And, ⁓ look, you mentioned brain state and, and I talk a lot to, to clinicians when I'm teaching TMS about current brain state and trying to keep your patient activated during TMS. and also does, does a lot of mental health patients, I guess, are in a rut in the term that you used before and potentially not as activated and

potentially not stimulating that plasticity before TMS. So we talk a lot about conducting psychotherapy during a TMS session, potentially that activates brain state. Maybe it's not the exact CVT or what you're talking about makes a difference. Maybe it's the overall activation of brain state that increases plasticity and the effect of TMS. There's still lots of unanswered questions there, of course. But what would you say about ⁓ advice to give clinicians about

About way to increase plasticity the best during TMS, both within session and between session. What advice to give patients while they're doing a course of TMS.

speaker-1 (44:02)
The advice that I would give overall, so during session is a bit of a different answer than between session. I generally agree with the idea of engage, like we don't have clear randomized evidence about this either. And that's one of those things that's like, we kind of all know it, but we haven't proven it. We haven't shown it. And so, you know, I think it's very likely that, that engaging these networks that are involved with, you know, positive thinking and so forth would

would be beneficial while delivering TMS. I think the thing that would, you know, but again, that's hasn't, you know, we really need to kind of demonstrate that and identify like, you know, what kind of approach, what kind of protocol might be best. Like that's some of that low-hanging fruit that is, you know, would be really pretty easy to implement in almost any clinic, even in a randomized way. So, you know, hopefully there will be more that will come out on that. Between sessions, I usually

talked to people both during, you know, at the beginning, during and after a course of TMS, just about brain health. And I think that when we optimize the brain health, it would be similar to, you know, if you're training for, and I know that you were a Olympic athlete, right, Trevor? Yes. And so, you know, it's like, as an athlete, if you're malnourished, then ⁓

it's going to be hard to really, no matter, even if you're trying to do the same workouts and the same training, it's not going to have the same effect on your body as if you're in a healthy state. So I focus on brain health and just kind of the basic things that we sort of all know, and none of it's really a big surprise, but can easily be forgotten or not thought about, especially for a patient that's already in a depressed state. So the things I usually focus on are sleep, diet,

exercise both cardiovascular and strength training because they both have independent evidence that that's helpful and then social and cognitive engagement. so trying to do those things, ⁓ during, well, while people are not getting the TMS, I think is what, is most likely to be helpful. So just providing the right environment for the TMS to have its effect. otherwise it might be like, you know, trying to do the really intense training.

in a malnourished Olympic athlete.

speaker-0 (46:18)
Yeah. And you touched on sleep there, Josh. So that you have done a couple of, a couple of papers on sleep, believe, and how it affects TMS outcomes. The treatment of insomnia during, during TMS that was, you found that to be pretty important, I believe.

speaker-1 (46:35)
Yeah, actually that was another idea from Jamie Kwan who had ⁓ done those things. So we looked at just our naturalistic clinic cohort and, you know, of course we know that insomnia is a big part of depression. So we needed to separate out insomnia from depression and see, okay, how do depression scores compare to insomnia scores? And they really kind of travel together. The thing that was kind of interesting that jumped out from that

And the thing that I think would be a take-home point for clinicians is that, you know, if you looked at insomnia and like non-insomnia people and insomnia people, and then you broke both of those up into took meds for sleep and didn't take meds for sleep. The only group that didn't really have the same trajectory of recovery was the, and they did worse, was the group that was insomnia and that did not get meds for sleep.

So basically, even if someone has insomnia and they're not getting great sleep, but if they're getting meds for it, and this is not just the sleep scores, it's actually separating out the sleep scores, just the depression minus sleep scores, they get better if they're taking meds for sleep, but not if they're not. so, it kind of highlighted in my mind the importance of, in my mind, it probably has to do with the brain health idea of being able to

⁓ have the optimal environment, you know, and we know how important sleep is for consolidation of, of memory. And I, and again, I think these are the same thing, like learning and memory is the same process at the cellular level as synaptic plasticity is. so whether we're inducing it through TMS or inducing it through, you know, therapy, CBT, it would be, you know, as an example of therapy, it would be, ⁓ you know, important in that way.

speaker-0 (48:14)
And of course, you know, that's the variable you used in the study about taking meds for sleep. That's not the only way we can improve sleepers as well. Medication is a large portion of that. But CBT-I, CBT for insomnia and sleep education is extremely important. sleep medication can be very good temporarily and potentially damaging long-term as well. So there's a ⁓ large interplay of sleep intervention if that is an issue.

for the

speaker-1 (48:42)
Yeah,

that was not like an intervention study. It was just naturalistic. And so it's like, okay, here's some factors that we have available to us that we can look at. I agree about CBTI and I feel the same way ever since residency. It's like every so often I'll just have like a night of crappy sleep. And I think that seems like everyone that kind of went through a neurology residency kind of feels the same way. But if you...

I think it can be, it's ideal if we can use behavioral therapies like CBTI in lieu of medications. But I do think it's quite underutilized. ⁓ It seems like a very small minority of patients that we have. And part of that is access. There's not a lot of therapists that are trained in that and it's difficult to get access to them in the first place.

Maybe there will be methods with artificial intelligence or some sort of scalable way that people can get access to that information. I don't know if it would be as effective or not without another human being to be accountable to and to other people to work with along in the process. But yeah, important.

speaker-0 (49:56)
very important. And we spent a large portion of our training time with our staff members and other clinicians that we teach on sleep and the importance of it. last question, you've been very generous with your time, Josh. Thanks very much. This is, I'm just sort of ⁓ pivoting a little bit away from what we've been talking about, but I found this very interesting. Everybody in my courses ask about coil orientation.

And when you're placing the TMS coil on the DLPFC on the frontal lobe, that 45 degree angle, is it important? What is it doing? Is it related to the way that it was first described over motor cortex? Is it the same issue between DLPFC and the motor cortex? in that article you mentioned, fact, changing the orientation may in fact give access to different

networks like the frontal parietal network or the default mode network. Can you elaborate on the importance of coil orientation for us?

speaker-1 (50:53)
Yeah. Coral orientation is, it's a tricky one because we know it's important, but we don't quite know how to ⁓ best implement it. And I'll explain that. So we know it's important because, you know, even doing motor physiology experiments ourselves, we'll, you know, be getting some pulses like this, and then we'll switch it 30 degrees and they'll...

The amplitudes of the motor of a potentials will be three times what they were just by that rotation. And actually just we had a journal club today in our lab on an article from Andres Flocos' group. they actually in slices, hippocampal slices, they changed the orientation of their coil 90 degrees. And they were looking at C-FOS expression, just like neuronal activity expression.

And they had this large increase in the normal paradigm they had, and then they switched it and it totally lost it, abolished it. so both animal and human, we know that it has a big effect. And that's kind what the review that was actually led by a couple of your nearby colleagues in Melbourne, Leo Chen and his postdoc, Andra Serenstead.

wrote that or led that article. we kind of, it's that article identifies the importance of it in a number of different ways, but how to get the right angle is going to depend on the brain morphology of each individual. So, you know, we tend to have this 45 degrees because we have a fairly consistent motor strip in the way that this comes down. And so, you we want to hit, you can kind of get the

best activation by hitting perpendicular the axonal fibers and a gyro crown. so the reason we move that forward, because that's what we had here. And so we're just moving it forward, but it doesn't necessarily mean that that's the best thing or that's going to get the biggest activation when we're in the DLPC because it's in the prefrontal cortex, it's much more...

multi-directional, we'll say. so, you know, that's one of the things that we've, when we do structural targeting in our research, we don't really use that clinically much, though some do. We will identify the location and then we'll look at the job ground and we'll basically go perpendicular to it. So we will adjust the coil in that way, but you know, for scout-based targeting, of course, that's not possible. And even,

Even we do some functional connectivity guided targeting as well in our accelerated patients and that's not a part of the protocol. That's not a part of what's done. So this is again, I think we see a common theme here where there's, we have some ideas of some things that are probably and seem pretty convincingly to be important, but we don't yet have a clear established way to do that.

I would contend that using scalp-based targeting, it'll never be possible to know what someone's... Because it's like, could be here and it's going to go one way and you could move forward a half a centimeter and it's going to be a totally different direction because we've seen brain anatomy. But if we are able to access imaging guided targeting, whether it's structural or functional or whatever, that...

that could potentially provide some insight in the future. And ultimately, like at least in depression, we do have some evidence for other indications, other conditions, but I think that we could use a randomized controlled trial to sort of demonstrate this is the clinical response with this and this is with the clinical response without it. Because ultimately with all of these parameters and so forth, some of them...

seem convincing and then when it gets to clinic, it doesn't actually seem to make a difference. had another RA of ours, Meg Vigny, had led this exploration of caffeine. ⁓ You asked about that before. Kind of the same retrospective analysis, postdoc analysis of our motorboat potential studies, caffeine use blunted plasticity.

And we thought, okay, well, if TMS works through plasticity, then maybe caffeine use will blunt TMS clinical responses. we actually just today or yesterday, I think it was finally published, a clinical where we just asked what clinically what they were using. Doesn't make any difference. They did exactly the same inpatient outpatient no matter what. there's things that we see that, there's a lot of things we see that don't.

translate to clinical difference. There's only been a couple things that seem to actually translate over. Decyclocerin is one of those. Session number is one of those. Those are some of the things that I think we see that are pretty clearly and consistently showing their effect.

speaker-0 (55:35)
Yeah, you mentioned the parameters that are clearly showing the effect. also the dosage of number of pulses per session seems to not make too much difference. There seems to be a large variability of number of pulses in a session that all turns out to be as clinically effective. But, won't go into that. Maybe to conclude now, Josh.

I know I'll let you go after all this time. You've been very, very generous with all your information for us. Thank you. What should clinicians know about the working mechanisms of TMS before using it? If they're starting out with TMS, how can they describe what TMS is doing when they're describing it for a patient? How do you teach that?

speaker-1 (56:22)
yeah, I mean, that's, that's a very, ⁓ you know, important fundamental question. ⁓ obviously I think one of the first things that everyone learns is, is that it works through producing magnetic waves, right? By this, sort of, time, walked, ⁓ electrical, ⁓ pulse of the coil. get these, time varying magnetic waves and these magnetic waves activate, primarily axons, ⁓ but

you know, neurons that cause firing. And when we repeatedly fire neurons, it tends to create a difference or a change in the strength. And depending on the pattern and the frequency that can, can potentially push things lower towards an LTD like effect or higher towards an LTP like effect. We see LTD like and LTP like because we're not actually, that's, LTP is really like a basic animal experiment phenomenon.

⁓ and so, but, but it, it's a similar kind of effect. And so we, we, you know, recognize that it's inducing these kinds of effects in important networks that are involved in depression or involved in, OCD, or they're involved in pain modulation or whatever other indication where we're trying to treat. ⁓ and you know, there, we don't know all of the optimal ways, like we're, trying to work towards optimizing.

⁓ how we deliver TMS and to who we deliver it to. But I think that it's important to understand from a plasticity standpoint that in the process of delivering these repeated pulses, this changes the strength of the synaptic connections. And when the synaptic connection of the synapse is strengthened, becomes, whether it's the receptor numbers that are increased, and so it's more sensitive to a

presynaptic release, or there's more neurotransmitter being released presynaptically, whichever side of the coin you're looking at, it makes it so that these function either more efficiently or less efficiently, moving that towards what is healthy for that brain circuit. so we're essentially trying to use plasticity to bring the brain back into its proper balance and into health.

speaker-0 (58:29)
Right. Which then flows onto a behavioral change. we're talking about neuroplastic change from the TMS pulses leading onto more of a network change that helps our brain function in a more adaptive fashion that then leads onto behavioral change. then, of course that process takes time. And that's why TMS isn't a magic bullet in one or two sessions. So we're trying to explain to clinicians and patients that this is the process that takes place.

And it does take time and that's why we need the commitment from patients over a longer period of time. So it's a different mechanism of action to medication.

speaker-1 (59:07)
Exactly. you hit it right on, is that, you know, the network level changes are what lead to behavioral changes and it's underlying the network level changes, you know, the circuits being a part of those networks, underlying those are the cellular changes and it's activity at the synapse that really drives, you know, if you look at the whole vertical column of neuroscience, it's the synaptic events that are driving DNA transcription, protein slide

translation and those don't just go diffusely everywhere, they go to where this activity is happening, which is strengthening these circuits and those underly these, you know, circuit and network level changes. So we see it structurally and functionally as well. One thing that I think is like a useful analogy when we talk about mechanisms of TMS, there's two approaches or two ways to kind of think about, you know,

You could say, there is multiple mechanisms of TMS in the sense that you have things happening at a network level and you have things happening at a cellular synaptic level. But as we just discussed, those are really the same thing. It's just at a more, you you're focusing in on the more microscopic kind of scale of things. And we talked about how, you know, protocols like the same protocol and extended sessions. We didn't talk so much about that, but

You know, giving more sessions we know also increases the response. And so when we kind of talk about mechanisms, I have started thinking a lot about how it's like a car. And, you know, if you ask like, how does a car work? you're looking at it from the outside, you might be like, well, a car works by the wheels. The wheels turn around and around and it drives the car forward, right? Or if you're looking at it from the inside, you might be like, well,

you push down on the gas pedal and that accelerator pedal makes the car go faster. And then it's of course when you actually kind of look in to the engine and you recognize, this is the thing where if we took an old car from the earliest days, it goes 10 miles an hour and we took one of our cars now. If we were to take, say the wheels or the axle or something and we put it on the old car,

it probably wouldn't go very much faster, you know, maybe a couple miles an hour or something different for being a little bit more efficient. But if we took one of our engines and put it in the old car, then it would go, you know, 10 times what it's going. And so it's, you know, that rate limiting step, that rate limiting mechanistic engine, that is the synaptic plasticity from the evidence that I have seen so far.

⁓ and the, you know, that we've looked at, that's kind of the engine of what really drives and makes TMS, effective as it is. And so it's important to do, it's important to deliver TMS where it needs to be delivered. ⁓ otherwise it's like, you know, you have to get to a destination, but you have no map and you don't know how to get there. ⁓ doesn't matter how good your car is, right? If you're going the wrong direction, and if you're in the right spot, but you're not giving an effective protocol, then it's.

It's like you know where you're getting, but you're having to push the car along. It's not going to get there very efficiently either. So I think there's good interplay between those and what we're trying to deliver to our patients.

speaker-0 (1:02:18)
Yeah, fantastic. So look, we're definitely in a very, very interesting field, trying to discover all the different parameters of a water make a team as more effective, not only a group level, but on an individual level, which is even harder. And if we can understand some of those basic mechanisms, ⁓ the neuroplastic level, then we can really change that engine as ⁓ you're saying.

So thanks for that analogy. That's great. Any, just very, very last thing, any exciting things that you're working on to, know, in the field of TMS, it's constantly evolving things where you don't even know about pop up, you said. What's, what's, ⁓ what's exciting you at the moment in your research and in the field,

speaker-1 (1:02:59)
I alluded briefly, you know, the thing that I think I'm feeling pretty excited about right now is, you know, we're looking into these one-day protocols. So, sort of building off of the work that we did previously with kind of the 1800 Pulse 10 session and Jonathan Downer's, you know, clinical work and implementing these 20-session-a-day protocols.

So we're testing that in the percuneus and the dorsolateral perveno cortex and, you know, seeing some really interesting results from that so far. And so very excited to have that. That's a randomized control study that we're doing with that. we have neurophysiology markers with TMS evoke potentials and motor potentials and, you know, multiple imaging scans before and after and so forth.

Hopefully we'll not only kind of get a good sense of what the clinical result is, but we'll also understand a bit about how it's happening, which is one of the things that is missing is we might have a really great clinical trial, but we don't have the mechanistic things going on with it. Or we have just a single session neurophysiology protocol, but we're not really getting like with the clinical connection. So we're hoping to be able to kind of bridge those two and then...

There's a lot of other, you know, one of the other things that we're excited to, we're getting started up right now is an R01 that's focused on mechanisms of continuous theta burst. So, you know, does this work through long-term depression or does this work through GABAergic mechanisms? And, you know, we've, as a field, we know much, much more about ITBS and high-frequency protocol is much less about these. And they can be ⁓ quite useful for a number of things, whether it's like decreasing rumination or anxiety or

traumatic memories or epileptic focus or various things. so I'm excited to get some more on that as well. yeah, looking forward to, you know, in six months to nine months time, being able to have kind of a whole new set of things that we can talk about as we're going around. it's a very exciting time in the field. It's such a great field to be in because we learned so much about the brain, neuroscience, but we also have this most powerful and effective tool. And I think that we honestly

are really close, like right around the corner to being the gold standard in efficacy for depression. depression I see as sort of the of the poster child, the model on which we can build, in which we've learned a lot that we can then implement in other disorders as well.

⁓ Hey, yeah, I, I'm excited to see the field and even one or two years, especially five years, 10 years, I think that we'll really, see a ton of growth. And as we get much more effective, such as through, you know, de-cycloserian augmentation, for example, you know, how well will this apply to other disorders? And suddenly we have the efficacy that we need to push things through and get regulatory body approval and so forth.

speaker-0 (1:05:56)
Fantastic. And you mentioned there's six or nine months, you might have some further information for us that will you welcome back anytime. We'll have a chat here and, and chew the fat Josh about what you've, what you've accomplished. it's been a real pleasure being a real pleasure, to have you, Josh. It's been great to chat with you. So thank you very much for your time.

speaker-1 (1:06:15)
Thank you for the time, Trevor. Really appreciate it. Honor to be here.

speaker-0 (1:06:18)
Great, thanks, Josh, bye.

Thanks for listening. We hope you got something out of this conversation and maybe it sparked an interest in developing your skills as a therapist. If you're interested in taking the next step, head to lms.neurocaregroup.com to access a range of professional online training courses in neuromodulation techniques such as TMS, TDCS and neurofeedback. If you're looking for where to access these therapies, head to neurocaregroup.com to find our network of clinics throughout the world.

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