Scientist Stories: David Ross, Integrating Neuroscience into 21st Century Psychiatry

See everyone on a Tuesday morning. For those who don't know me, my name is Eric Hong. I'm the residency program director here at UCSF. And it is my absolute, absolute honor and privilege to be able to not only play host but also to introduce our distinguished visiting lecturer today. Dr. David Ross. So as I was kind of chatting with David very quickly before this, I think there's an art to doing introductions for people that you feel really passionate and excited about. And as I was thinking about sort of how to sort of frame, I think, what Dave is going to talk to us today, I was reminded actually by an article that really changed the field of education and an article that really changed the way that education research is thought about and done. And that article was written by a gentleman by the name of Ernest Boyer. It was published in 1990. And that article was entitled Scholarship Rediscovered. And it really pushed the field to think about the scholarship not only of discovery, and that scholarship of discovery is a lot of what we talk about in our Grand Rounds series, but to really think about other types of scholarship. The scholarship of how we actually apply information, The scholarship of how we integrate information. And I think to the point of the talk today, the scholarship of how we teach information. Dave has been sort of revolutionized, been a revolutionary in many ways ever since he joined the faculty at Yale in 2009. He is a Yale lifer, at least as of now. And he did his medical school training, his residency training, his doctoral training at Yale, joined the faculty in 2009 at Yale, and has just been doing just really cool things over the course of the last 9 years. I was sort of struck by his doctoral work early on, which focused on the neurobiological underpinnings of music perception, with a specific focus on The Perfect Pitch, and really trying to understand the sort of phenomenon of the perfect pitch. And in some ways I sort of quickly made the link, at least in my mind, that Dave's work since his work in The Perfect Pitch has really been about how to create the perfect learning experience. And a lot of what we're going to hear about today is his focus on how do you really bring the learners with you in a way that is exciting, engaging, that's going to make them understand, and it's going to make them really absorb what we want them to be absorbing. When it comes to education, it is not about the teacher. So many of us think that being a good teacher is all about the skills of teaching. It is about that, but it's really about the learner and trying to understand where the learner is at and how to inspire and engage that individual. Dave's work at Yale has included completely changing the classroom curriculum in their residency training program. He has single-handedly sort of redesigned 12 courses and over 250 hours at Yale. His curricula have been adopted by countless residency training programs including ours over the course of the last 9 years. He has been a co-founder and also a co-chairperson for the National Neuroscience Curriculum, which really goes beyond a single institution and is about creating a national curriculum in the area of neuroscience to really bring residency programs and educators up to speed with the cutting-edge research that's happening in neuroscience right now. The NNCI has been, I think, one of the most powerful platforms for really disseminating neuroscience research. And it's not because the concepts are really cool, it's because the pedagogy is really cool. And what I mean by pedagogy is that Dave and the NNCI group makes learning fun. They think about how to actually bring people in, how to engage them, how to actually do exactly what we're not doing right now, which is keeping people out of the auditorium and actually interacting with each other. And that part, I think, is actually what's going to be changing the field in very drastic ways. The NNCI has created curriculum that has been adopted in over 100 residency training programs across the country. They have collaborated with the American Psychiatric Association, the Royal College of Psychiatrists in the UK, and several other neuroscience societies across the country. Dave himself has given over 80 international, national, and regional presentations. A very impressive feat for someone who's only 9 years into faculty life. He has over 60 peer-reviewed publications. And, I will say that his kind of, sort of, in some ways intimidation doesn't necessarily stop there. Our residency program has been very fortunate to actually adopt a platform that Dave created to help residency programs screen applicants in an era where, especially in psychiatry residency programs, we have just a record number of applicants coming to programs. And how do we effectively dive into applications in enough depth to actually get the folks that we want to interview here is no small feat. Dave's platform has enabled us to do that, and for that and for the over thousands of hours that he has saved our program over the last couple of years, I am eternally grateful. I will say that before I pass this over to Dave, that one of my most sort of awe-inspiring moments have been the moments where Dave and I have gone on trail runs at national conferences, and he has forced me to wake up at 4:30 or 5 o'clock in the morning to go on an 11-mile trail run in the Flatirons or some crazy place. And, Dave, you just continue to be just an inspiration, and I am constantly in awe of you. So with that, I'd like to introduce you to the stage and give a warm welcome for Dr. David Ross.

Thank you, Eric. Those are my fondest memories too. I am really grateful to be here and have the chance to speak with you all.

Thanks.

So, in 2012, then-director of the NIMH, Tom Insel, wrote an editorial entitled, "The Future of Psychiatry is Clinical Neuroscience." And in it, he captured some of the revolutionary changes that are transforming our field. And, I wanted to start with just one graph to illustrate the amazing change that's taking place. And so, if you look here, the x-axis is the year. And the y-axis is the number of articles in PubMed with the keywords neuroscience and psychiatry. And what you're seeing is exponential growth. And if you have really sharp eyes, you may actually notice that this ends in 2012, which was when the article by Tom was published. And since then, we've seen it more than quintuple. And it's not just The amount of work, the quality and impact of the work that's being done is just astonishing. And I was looking for a way to represent this visually. And so I couldn't help but put in a picture of Sigmund Freud alongside Carl Deisseroth. So Carl's the co-creator of Clarity and optogenetics. And if we're going to put Carl there, we should put one of his optogenetic critters alongside of him. And I don't show this to suggest that neuroscience is replacing psychotherapy or that they're mutually exclusive. Quite to the contrary, I think there's incredible synergy looking across reductionist levels. And Carl would be the first person to say that. But at this point, there is no doubt that our understanding of psychiatry is increasingly rooted in brain science. The thing is, though, if you look around the country and you look at residency programs, The vast majority of them are not teaching neuroscience in a way that could even remotely be considered substantive at this point. And it's not an academic question. So, if you can indulge me for just a minute, we're going to start by focusing on residency programs and residency education for two reasons. Foremost, because our residents today are going to be the leaders of our field for the next 50 years. And also because the challenges that we face in residency education are emblematic of the types of problems that the field as a whole faces for thinking about this. And so, when we're talking about this gap between how we think about psychiatry and how we're teaching psychiatry, it's really disturbing. This is a question about the identity of ourselves as psychiatrists, how we talk to our patients, how we talk with our colleagues. And we can't afford to wait. So, when Tom's talking about the future of psychiatry as clinical neuroscience, I think the real question is, why aren't we doing it this way today? And here, I think one very big piece of the puzzle is just how new everything is. So, this is the first week of the new year for residency programs. So, we just finished screening. I assume you guys had as many as we did, more than 1,000. We had 1,400 applications to our program. And as we read our applications, the average intern was born in 1991. So if we just think about how new everything is, and we just look at the life of our current interns' beginning, what's changed? So 1991 is 5 years after fluoxetine was first approved. But it's 2 years before it became the social phenomenon that really redefined the conversation in our country about medications and psychiatric illness. In 1991, the very first paper reported this newfangled technology called functional MRI. It was another 5 to 10 years before people were accepting that these signals corresponded with brain activity. Another 5 to 10 years before we started to be able to take advantage of the actual tool, looking at resting state imaging and being able to take advantage of more sophisticated structural imaging technologies as well. In 1991, the conventional limits of light microscopy were on the order of hundreds of nanometers. STORM imaging now lets us visualize the cell at 10 times that resolution, which really lets us see the inner workings of cells with unprecedented detail. Detail and resolution. We can establish connectivity maps at the cellular level. We can observe the firing of neurons real-time using calcium channel imaging. We can directly control the firing patterns of specific neurons. And what's really cool is we're seeing this progression from basic science into animal models and some, in some cases, into really dramatic human interventions. So, in the on the eve of the World Cup. This is an image from the last World Cup. And a man who had been paralyzed from the waist down for 9 years, and with the help of a brain-machine interface, kicked out the first ball to start the World Cup. It's just really cool. So, in 1991, we might have been talking about the search for the gene that caused schizophrenia. It's still a decade before the Human Genome Project was completed. Since then we've seen the cost of whole exome sequencing plummet to the point where we might reasonably expect somebody could show up in your office having already completed their own sequencing. Don't really advise that. But these are conversations that we have now. And of course the past decade has really opened our eyes to the complex ways in which our environment shapes gene expression. It's obviously critically important to understanding psychiatric illnesses. In 1991, we still had the DSM-III. We've now evolved all the way up to the DSM-V. And clearly this is progress. But, I don't think there's anybody who would argue that this book actually describes the diseases that we're treating in any meaningful biological way. And, you know, we've seen some projects like the RDoC which have attempted to look from the bottom up and start from biology to think about classification. It's a lovely thought. I don't think anybody would argue that this is quite there yet either. So one huge obstacle for us is just how new everything is in our field. But if we think about training, another piece is to start to think about the structures and the systems that guide our training. And for residency, this is the ACGME, the Accreditation Council for Graduate Medical Education. And they've put out this lovely document called the Program Requirements. And it's a 38-page document with more than 10,000 words that lists everything we have to do during the course of a residency training. Every type of therapy, all the different types of clinical experiences. There are two separate references to mandated nap time for residents while they're on call. Anybody want to guess what word does not appear in the ACGME program requirements for psychiatry?

Yeah, right.

So, if you're keeping score at home, naps 2, neuroscience 0. It's really astonishing. We now have the Milestones Project, which which is moving us the slightest bit in the right direction. They acknowledge the existence of neuroscience, but barely more than that. So, what impact does this have on programs? So, programs have to follow the requirements. And the requirements largely track with the history of our field. And as new ideas and topics have been developed, they've been sequentially added in. So, if you look at programs in sort of the traditional curriculum for psychiatry, you have a series of courses and each course is divided into a series of lectures. And these lectures kind of have this vestigial organization that reflects the history of our field. And so, if you wanted to think of a topic like PTSD, there might be one course on diagnosis and phenomenology, another on psychodynamics, psychopharm, CBT. If you're lucky, some psychosocial rehabilitation. And if you're really lucky, maybe you get a little bit of neuroscience tucked in. And I have to admit, as a program director, it would be convenient if we could parse the world into these neat little categories. It would appeal to the OCPD in all of us, at least me, to be able to neatly parse things. But this is not the way the world works. And we know that this isn't the way the world works. The beauty of psychiatry is how do all of the different pieces of the puzzle fit together for the person sitting in front of us. And so, if we wanted to think about a topic like PTSD today, fundamentally any conversation has to begin with what happens in the brain after a traumatic event. You get fear conditioning, you get dysregulation of the connectivity between the limbic system and the prefrontal cortex. And once you start to think about fear conditioning and these pathways, you realize that any meaningful treatment is going to have to include include some form of exposure therapy. And now we can start to think about all of this cool new neuroscience that's going on. So, what if we had a medication like D-cycloserine that could increase the intrinsic plasticity of the brain? So, you might be able to complete your exposure therapy in 5 or 6 sessions instead of 10 to 12, which is something that's been reliably shown possible for acrophobia. There's this whole new field that's looking at the idea of reconsolidation. Reconsolidation. So, anytime a memory is activated, it becomes momentarily labile and then needs to be reconsolidated. So, what if we had the ability to disrupt that reconsolidation process? Which you might be able to do pharmacologically, interventionally, or behaviorally. And, all of these have now been shown in humans. Behaviorally, pretty quickly. There's cool recent studies using ECT to disrupt reconsolidation. People who were already getting ECT for their depression, were fear conditioned before to innocuous lab stuff, but then they could disrupt it. And then a paper just a month or two ago in the Green Journal showing that you can give propranolol like an hour and a half before an exposure therapy, and over the span of, I think they looked at 6 weeks, shows a dramatic improvement in the progress of the exposure therapy. So, all of this really cool stuff. If we step back, for any particular type of trauma, it's actually only probably 20% of people who are going to go on to develop PTSD. So, how do we think about that? And it may be that it's not the event per se, but the way in which an individual is interpreting that event and contextualizing it within their own life narrative. And so we might want to start thinking about cognitive approaches to help people reinterpret these events. And as psychiatrists, as clinicians, we love talking about meds and therapy. How do we think about all of the data from psychosocial rehabilitation? So supportive employment, supportive housing, family psycho-ed, all of which have much larger effect sizes than the medications that we're prescribing. And really at the end of the day, how do we make this about the person who's sitting in front of us. So, what's it like to go to Iraq and spend 14 months where you're convinced every day that you're going to die? And then you try coming home and driving on a freeway that reminds you of an IED explosion. Or you try shopping in a mall where the crowd is just fundamentally too stimulating. So, the art of psychiatry today is how do we take all of these different data and be able to bring them to bear for the person sitting in front of us. So let's imagine you have a program that wants to implement a new curriculum. They still face a number of really intense challenges. So what should we actually be teaching? The field is vast and it's changing really quickly. So how do we even decide like what we should be teaching? And then once we've decided that, where and when are we going to fit it into the curriculum that's already overflowing with all of those other requirements that we have to be meeting. And who's going to teach it? So, at Yale and at UCSF, we have lots of neuroscience faculty who may be able to help. But the vast majority of programs around the country don't have that. When we surveyed program directors a couple years ago and asked them, how many neuroscience faculty do you have in your department? The median response was Zero. Right? So who's even going to teach it? And then critically, how do we teach it well? So most places where neuroscience is being taught, we have a series of experts come in and they lecture on their own narrow area of expertise. And we live with this fantasy that we could just line up our residents and we We could stage a dramatic reading of Charney and Nestler, or whatever favorite neuroscience content we have, and that our residents will just magically absorb everything that we say. It's completely untrue. So, there's a whole field of literature looking at how adults learn that would suggest that less than 5% of content presented in a lecture is going to be retained. Which, frankly, for neuroscience, I think is probably generous. It's a tragic irony if as the psychiatrists and neuroscientists studying how people learn, we fail to take it into account in the way that we're teaching our trainees. So, if we just look at the entirety of the traditional GME model, it's historically been a series of central regulations that have to be implemented by individual programs. And for cutting-edge content like neuroscience My argument would be it just doesn't work. Our regulatory systems are too complex to be able to adapt to a changing field and the burden of curriculum development is too high for any program to be able to do it on its own. So if we want to look forward and think about the future of JME, this has to be a question of how do we all work together to achieve a common goal. And my central argument would be In the same way that cutting-edge science requires teamwork and collaboration, so too does cutting-edge education. And so, this was the premise about 5 years ago when a group of us got together to create the National Neuroscience Curriculum Initiative. And the overarching goal was to create a set of open resources to help improve the teaching of neuroscience and psychiatry. And again, I said we're going to start by thinking about residents. But, really, this is a much broader issue. And, it's about how do we as an entire field think about integrating neuroscience into our clinical practice. This is work that I do with Melissa Arbuckle, who is the program director at Columbia, and Mike Travis, who is the program director at Pittsburgh. And, when we started, we started with a set of guiding principles. And, foremost was the idea that it has to be an integrative patient-centered approach. How do we bring neuroscience alongside all of the other rich traditions in our field alongside of psychotherapy, alongside of psychosocial rehabilitation, to bring everything together. The second piece is what Eric was alluding to before. It's not enough to lecture and live with this fantasy that we're doing something. We really have to think about adult learning theory and how do we meaningfully engage with our students in this mission. And how do we get them excited and really engaged? The third piece The other piece was it can't just be us, right? We have to be able to do this as a team. And we need to be able to create resources that anyone anywhere would feel comfortable being able to pick up and use in their program. And to do that, it was going to have to be a collaborative effort across sites and institutions. So this is where we started. And I guess you can sort of sum the whole thing up as what we called the "insel objective." So that when a resident is sitting with a patient, they're not just going to be thinking about DSM criteria, but what's the underlying biology behind this person's illness. And again, it's really not just about residents, it's about all of us and how do we bring this in. So, what does this curriculum actually look like? So, for the first couple years, we were really focused on teaching in the classroom and how are we going to do this effectively. And, but again, it's not enough to just throw the content out. The question is how do we use principles of adult learning? How do we come up with experiential exercises? How do we create materials that anyone can pick up and use? And this other piece that Eric brought up, how do we make it fun? I just heard Melissa giving an interview recently. It was just so lovely. She's this Remember when you were in kindergarten? You'd go to school and it was fun? When did learning stop being fun? Why do we think of this as this odious thing and what would it take to get it back to that level of excitement and joy? And we take that seriously, I think, actually. So, when we started this, we were thinking one of the most basic things is neuroanatomy and people need They need to know anatomy. And it is traditionally one of the most toxically boring topics to engage. Dry, inaccessible lectures. And so we approach it differently. We start by handing out Play-Doh and asking people to build a brain out of Play-Doh. And we give them a video so that they can watch and they can follow along.

Hello, my name is Josh Gordon from Columbia University, and I'm going to show you how to build your brain.

Play-doh. This is in fast-forward. If you ever wondered where the director of the NIH got his start, it's making play-doh videos. So the actual video is about 5 minutes long, and as he's going through, he's talking about each region, he's talking about the functional significance, he's talking about psychopathology that relates to dysfunction in that particular region. It's a really cool exercise. It's quick, it's fun, it packs a punch. It's much harder than you would think it is. And it's actually been hands down the most popular NNCI resource we've ever created. And we see these tweets that pop up from literally all over the world of people making Play-Doh brains. And being excited about neuroscience. And we're like, that's awesome. As far as basic stuff, again, thinking like how do we engage people so they're doing the work. One of our other favorites is this exercise called Find It, Draw It, Know It. So we start with some sort of video resource. So this is a film, this creepy little horror film, it's like 3 minutes long that somebody found online of a woman who's stuck in an attic and weird things happen. And we have them watch it. We say, okay, great, now draw the pathways that were active in her brain during this experience. See, that's actually pretty hard to do. And we let people try it, and then we have a 3 to 5 minute version of here's how you actually do it, and then go back and do it again. And by the time you're done with this, we're going to know that you can actually draw the pathways involved in fear response. So, really focusing on this is about them and their experience. The other, one of the other early ones that we focused on is this integrative case conference. So, coming back to this idea, the initial objective, that people will be able to incorporate the neuroscience perspective alongside everything else. We created this case conference series with a really simple setup. We always start with a case. We give the residents the chance, read the case on your own, form your formulate the case on your own. You're then going to come in, we're going to have a group discussion of the formulation, and then we're going to bring in a set of experts, typically a neuroscientist, a psychotherapist, and a social psychiatrist, each to comment from their discrete perspectives, and then have the chance to really bring this together for the person in front of them. So, one of our favorite cases is somebody with a psychotic disorder. And, in this case, we had Phil Korlik come in, who's a expert in the neurobiology of delusions. And we have him talking about that alongside of a psychotherapist who used to run our ER and then became an analyst, talking about what's it like doing psychotherapy with somebody who's chronically psychotic. Which is something we don't talk about frequently, but should, because we do it all the time. And then somebody who specializes, this is a person who is homeless, thinking about housing interventions, thinking about work interventions, and really How do we bring this all together? I think my other favorite course is Neuroscience and the Media. So, we've all had the experience of being at a party and somebody comes up to you and says, "Hey, did you see the article on the front page of the Times?" Or, I guess out here, the Chronicle. "Tetris cures PTSD." Or, my other favorite one recently, "Women who eat full-fat yogurt are happier, so don't believe this Muck Lady and Yoplait Light commercials." So, for us, a core learning objective is that residents will be ambassadors of psychiatry and neuroscience. So, when somebody comes up to them and asks them about this, that they will be able to speak thoughtfully and intelligently about it. So, we said, okay, let's do that in the classroom. So, we're going to start each session by reviewing some media together, whether it's from the Times or the Huffington Huffington Post, or BuzzFeed, or your favorite podcast, or your favorite TV show. And then we're going to start by critiquing the media portrayal itself. What biases were present? It's psychiatry, there's almost always biases, and they typically reflect the profound stigma towards our patients and our field. What do you imagine a patient or a family member would ask you if they were the ones who saw this media piece and they came into your office? What do you think the face validity is of the claims that are being made. And then we're going to go in and we're going to actually read the literature. And not to be the most comprehensive, but to find the answer to this particular question. And then we're going to give you the chance to role-play how would you communicate to a layperson about this. Okay, so if this is a 60-minute session, 58 of the minutes are residents in groups working on this problem and working on the specific skill that we've set out. So I think my favorite of these was a piece that we pulled from Radiolab. It's an awesome piece. So it's a journalist from the UK who travels to an Army base outside in the desert in San Diego, and they zap her brain with electricity to make her into a sniper. And it sounds pretty crazy when you hear it. And then you dig in, and It's actually pretty cool. So, it's a paper about tDCS and specifically using it for plasticity in this particular task. And the data are surprisingly good. Not the best in the world, but pretty good. And if you wanted to teach this session, we have answer keys that include all of the questions, all of the answers, specific script of how you might talk to somebody about this, video of somebody teaching that session. And to me it's one of these cool things. So when we've surveyed residents from around the country, here's where I'm going to watch Matt's face. The percent of people in our fields who have heard of TDCS, less than 20% consistently for audiences when we do this. So a great way to bring to life some of the stuff that's really to become cutting edge in the field and bring it to life for our trainees.

So that's a handful of some of the stuff we've done.

There's a bunch of other classroom settings. And I have to admit, after 2 years of this, we were feeling pretty good about ourselves. We said, all right, this is great. We have a nice curriculum. It's great. Then we stepped back and thought about it. And if we did everything perfectly, maybe in a dream world, We would have about 100 hours of classroom teaching on neuroscience. Dream world. And even if we do this, this is still the smallest fraction of what happens during the course of residency training. When they still have about 9,000 hours that they're going to spend in their clinics. And they go off to their clinics, and the majority of the people in their clinics are not neuroscientists. And, in all likelihood, they're not reinforcing the kinds of things that we might hope they would be. And what emerges is a hidden curriculum in which what we're really saying is neuroscience is this thing that we do sometimes in a classroom, but it doesn't really count in the real world. And so, we got really focused on this question of how do we bring neuroscience into the clinic and how do we help clinicians do this teaching as well. And we started with this module called Talking Pathways to Patients to really focus on the direct communication that we're having. And a lot of the things that we say to patients, we as a field, are just relics of the past. They're generic, they're out of date. We talk about chemical imbalances. We talk about diagnosis. Diagnostic labels that are syndromes but not diseases. We owe it to our patients to be able to describe for them what we actually believe is going on. And so, this session is really straightforward. We give you a case, we give you a chance to talk about the case, think about your formulation. We then have an expert brief video, usually 7 to 10 minutes of how this person would talk to a patient about that particular disease. And then we give everybody the chance to role-play talking to the patient. The other way we've really been thinking about this neuroscience in the clinic is through a session called Clinical Neuroscience Conversations. And here, we realize this tension of how do we do this in the environment. That there's this default hierarchical model as if the teacher is supposed to know everything and impart that knowledge down. And it's not, it's just not how, it doesn't work that way. And we can do better in this day and age with the internet, with all of the tools and resources that we have. We don't have to think of learning in this way. And we really wanted to level the playing field and say, how do we work together? How do we learn together? How do we think differently about these things? And how do we do so in a way that will feel immediately immediately clinically relevant. So, I'm going to pause right there. Because I started by saying that we don't believe in lectures. So, it would be a little ironic if I sat here and lectured. So, what I want to do instead is to give you guys a chance to experience what this session would be like. And so, what I'm going to ask you all to do is to pair up with somebody sitting next to you. And we're going to give you the chance to pretend that you were on a service and you're seeing a patient. And one of you can pretend to be the student and one of you can pretend to be the faculty member. Although again, the premise is that it doesn't really make the slightest difference. I'm going to hand out a case. And what I want you to do is read the case and then talk to your partner about the formulation. Then we're going to get back together and then we're going to show you a resource in a little bit. But start by, um, read the case and talk about formulation. It's a sign that people are so immersed in the discussion that I can't get people back. So when I'm teaching, it's one of my favorite things to do. One of my favorite things if everybody is so into it. Does anybody have any reactions to the case? What would it be like if this person were on your service today? Any brave souls want to jump in? Everybody is too scared to say anything. Yeah, go for it, Danny.

Because of the frustrations with our system, right?

So that kind of feeling like we're not addressing it, right?

The problem is—

we're trying to address at the individual level, but maybe not capturing the developmental history and— Yeah, thanks. I think, I mean, if there's one message of like how do we think about this person in the real world, it's frustration. It's a case that drives us bonkers, and some of it is the system level. If we're savvy, we're frustrated at the system level. I think some of it more commonly localizes to the patient and the encounter as well. Is there anybody? Oh, yeah, go for it.

So, the only thing I would add is just the beginning.

She has so many DSM diagnoses, which suggests to me that we don't really understand what she truly has, and therefore, we don't really understand how to appropriately treat her. I think that's such a lovely way to say it, right? When you have like 10 diagnoses, we clearly aren't getting it right, and we're missing it. And if we don't have the right diagnosis, we can't possibly have the right treatment for it. Yeah. Cool. All right. So what I'm going to do is I'm going to show you a video. It's about 11 minutes long. And then we're going to get back together and think a little bit more about the case.

So let's jump to an example and talk about how early life experience epigenetically programs the stress system. To briefly review, when our body encounters a stressor, it activates the hypothalamic pituitary the pituitary-adrenal axis, which results in the release of cortisol in the body, which has a variety of adaptive effects in the short term and is not terribly adaptive in the long term. So to keep this response short and sweet, there are negative feedback systems in the brain that serve to truncate the response, which terminates the cortisol release from the adrenal gland and resets the system for the next stressor. In certain clinical populations, this this system can actually go awry. And so the example that we will talk about is what we see in patient populations that have been exposed to early life trauma or stress. In these adult patients, we see that the same type of stressor, while it activates the HPA axis and results in cortisol release, there's a lack in the negative feedback mechanisms. And so what happens is you get this prolonged and more intense cortisol response, and the system has difficulty resetting. And it's this prolonged hyperarousal state that's thought to relate to the increased risk we see for borderline personality disorder, PTSD, and some affective disorders in patients that have experienced early life trauma or neglect. And this is really a fundamental question in psychiatric neuroscience. How does an early life experience like trauma or neglect biologically program a circuit in a clinically relevant way that lasts throughout the lifespan of the person? And yet, despite being a critically important question, it's actually really hard to answer in humans. We're so psychosocially complex that isolating the biological mechanisms is not an easy task. An easy task. And so Michael Meaney's group decided to jump to a different species that's arguably a little simpler from the psychosocial perspective, and that was by looking at rat maternal behavior. And so his group started off with a very simple question, which was, is all rat maternal care created equally? And it turns out it's not. There's actually a normal distribution of maternal care in rodents. And you might ask, how does a rodent show that it loves its little rodent children? And it turns out that licking and grooming is how rat moms show that they really love their rat pups. And so what his group found is that while most rats are sort of good enough mothers, there are two extremes in the licking and grooming categories. One, which are these these amazing, wonderful rat mothers who just love their pups like gangbusters, and then there's sort of this other extreme of the spectrum which are these sort of sad, you know, not so caring mothers that really only sporadically lick and groom their pups. So a high licking and grooming experience with lots of love on one extreme and a low low licking and grooming experience on the other extreme. So what do these babies actually look like? Well, much like the human condition, in the loving, high licking and grooming environment, we see low stress reactivity, so a system that's able to react to stress but then reset. And in this low licking and grooming group, we actually we actually see this increased stress reactivity, prolonged corticosterone responses, and just overall difficulty truncating that response. So very much like the human population that we talked about earlier. So now the question becomes, is it actually the experience that's programming the stress system in these animals? And so there's two experiments that were done to really get at that question. And the first is sort of these classic cross-fostering experiments, which are like little rat adoption agencies. So when you take the newborn pups from the low licking and grooming mom and have her adopted by the high licking and grooming mom on the first day of life, we find that she ends up looking a lot like the biological children of the high licking and grooming mom. And vice versa. So taking a high licking and grooming pup on the first day of life and giving her to this low licking and grooming, not so caring mom, we see the phenotype of the low licking and grooming offspring. So that's one piece of evidence, but Meaney's group actually took it a step further and wanted to show that it's actually the tactile experience and not something else about the environment of being with the high LG moms. And so they did an experiment using paintbrushes to actually mimic the experience of being licked and groomed. So you can imagine some poor graduate student sitting in the vivarium for the entire first 7 days of life with a paintbrush trying to do this experiment, but the results are really exciting. And that's that simulating the high licking and grooming environment— these are my paintbrushes— in a low LG pup for the first 7 days of life recapitulates the high LG experience. And so you see as adults those rats have lower stress reactivity and vice versa. Taking a high licking and grooming pup and only giving them a little paintbrush love recapitulates the low LG phenotype with this heightened stress reactivity. So what these experiments tell us what this poor graduate student in the vivarium with a paintbrush is leading us to is the point that experience matters. And this is probably not a shock to the clinical audience. But now using this model system, we actually get to the really cool part, which is how does this work? And to answer that question, we go to the neuroanatomy. So what are the brains of these animals look like. So, here again, we have the low-LG animals on the left and the high-LG animals on the right. And you can see my incredibly sophisticated artist rendering of hippocampi in both of these animals. So, Mimi's group decided to look at glucocorticoid receptor expression in the hippocampus. So, glucocorticoid receptors are those that actually sense these stress hormones, and thus are well-poised to regulate neural responses to them. And what they found was that in the high-LG animals, you saw a high density of glucocorticoid receptors in the hippocampus. In contrast, in the low-LG animals, they saw a much sparser distribution of glucocorticoid receptors in the hippocampus. And why do we care about this? We care about this because the hypocampus projects to the master regulator, the H and the HPA axis, and actually provides that negative feedback. And it's been shown that this high density of glucocorticoid receptors is associated with a very robust negative feedback response, whereas the low density of glucocorticoid receptors is associated with sort of a wimpy negative feedback response. And so these feedback responses make a lot of sense when we think about the phenotypes of the animal. So this high stress reactivity in the low LG animals because of the wimpy negative feedback response versus low stress reactivity in the high LG animals with this very robust, tightly regulated negative feedback response. And so now we get to the final piece piece of the puzzle, which is how do we get from this early life experience to glucocorticoid receptor expression? And this is where the epigenetic part comes in. So Meany's group decided to take a look at the glucocorticoid receptor gene and specifically the epigenetic decorations on the promoter region. And what they found was that at birth everybody's promoter is heavily methylated.. And if you remember from the first segment, heavy methylation of the DNA is associated with low transcriptional activity. So what impact does early life experience have on these epigenetic markers? Well, in the low licking and grooming animals, this promoter remains methylated for the life of the animal. And so this heavy methylation is associated with low transcriptional activity. Low glucocorticoid receptor expression, and low negative feedback to the HPA axis. In contrast, high licking and grooming actually causes a demethylation event at this promoter, removing the obstacle to the transcriptional machinery. Transcription factors like NGFIA are now able to bind, you get robust transcription of the glucocorticoid receptor, high expression in the hippocampus, and tightly regulated HPA responses. So lastly, we'll just tie this back to the clinical population by mentioning that there have been studies done now in humans with postmortem brains looking at epigenetic signatures of the GR gene and expression in the hippocampus. And they essentially recapitulate the findings that we've described for the rat. So in human beings that have been exposed to trauma or early life neglect, we find heavily methylated promoters, low GR expression, which correlates with the phenotype of poor negative feedback and high stress reactivity. Whereas controls that have had no trauma should demethylate promoters high gene expression and efficient regulation of the stress system. So the take-home points are, one, that experience matters, that experience shapes our brains. But two, that the study of epigenetics helps us understand how that process occurs on a biological level. And better understanding the system allows us to develop novel therapeutic targets and therapies that will help our patients.

Cool.

So, back with your partner. How does this change the way that you would think about the patient we talked about before? And take 2 minutes. Please come back. Any reactions that people have to the video? Any reactions? Yeah, please. Appreciate it. I think it really helps to sort of go down a particular pathway from your point on. I think if we remain in this gap between, like, there's so much going on with this patient and what we need to do necessarily in science and, like, following one pathway and understanding it thoroughly, but I think it, like, for me helps to provide a little bit more context on that up part of this person's experience. Yeah. Decreased a little bit of that I love that. I love the comment on many levels. So, the most frequent question we get about NCI stuff is, where's the direct clinical application? And, I think when people ask that, they're asking for the new medication or the new overt intervention. And, there are some of those. You know, like the propranolol study in PTSD is kind of cool and a direct application. To me, like, I think it comes back a lot to what Tony actually said before. Like, you have somebody who's carrying 10 diagnoses that make no sense. Even if we can just think about this person a little more parsimoniously, she has a disease of affect regulation. She struggles to do that. And if it helps us, thinking from an integrative perspective, be able to establish a better holding space So, we're less frustrated when we sit with her? That's fantastic. I'm actually pretty good with that. You know, and if it lets us not intervene in ways that would not be helpful, because every time she picks up a new diagnosis, they throw a new medication at her. I think psychoeducation, psychoeducation, this could be very useful as well. For people with borderline itself. Yeah. It's been one of the most interesting things with the NNCI is that a lot of the materials we design for residents get into the hands of patients and consumer groups. And they love them. Because they've never heard— I mean, like, I always think, like, can you imagine if you went to your doctor with abdominal pain and you said, you know, I'm having abdominal abdominal pain. And your doctor looked at you and said, "Yeah, you have abdominal pain." You'd be like, "Seriously?!" If I go to my doctor, I expect him to be able to tell me what's wrong. He might not be able to do anything about it, but at least he can tell me, "This is what we think the problem is. This is what we expect to happen next. This is what we're going to try to do for treatment." I expect some explanation of the phenomenon. It's not enough to pare it back to the symptoms that we were told.

Just have that basic approach? I think it's really simplistic.

I think that—

not to speak for anyone, this is what we think. I think patients will love it because it's not your fault, it's things that happened to you, and let me just show you what's going on. But it's not just affective dysregulation, it's impulsive dysregulation. This person is psychotic. This person is using substance abuses, which makes they have their own, if you can substitute, they have their own independent impact on this. So I think patients like it when you say it's not you, you know, it's your, you know, what happened to you.

Yeah.

But I'm not sure it's a huge improvement over some of the, what we know now, very simplistic explanations why people become borderline. Why they develop schizophrenia.

I mean, these are very old beliefs that now we can say it's neurotransmitter. And, I just think there's so many exceptions. Yeah, yeah.

So, so, so.

So many things that influence kids. Yes, I think there's lots of things you're saying I completely agree with. So, the first thing we said is that it has to be an integrative approach. So, how do we fit neuroscience into a broader context? And, it's a broad context. And for any individual, there's a lot of stories that are relevant here. And certainly there are many other neuroscience stories that are relevant to this. From an education perspective, what we found is that 95% of residents and clinicians around the country have never heard of any of this. Literally have never heard any part of this story. And when I do grand rounds, I ask people, how many people have ever heard of this? 95%. So, from an education From a teaching perspective, I think every resident in the country should know this story. I think they should understand that early trauma can have an impact on HPA axis regulation. And so from that perspective, I think it's 10 minutes that's worth investing in them. Yeah?

I just want to repeat your sentence. Early trauma has an effect on HPA regulation and how the person is currently able to function. In terms of identity coherence, relationship capacities, and emotions such as anger, which seems to be a problem.

Yeah. Anger itself and others.

And so I think it's a battle that's been won almost, how to teach biopsychosocial formulation. And even in your language, I think we have to include the psychosocial.

Oh, yeah, 100%.

If you get some neuroscience funded in education, I think you'd want the Nobel.

Thank you. So, it's complicated. And again, I mean, the other piece with the neuroscience being incomplete is, I would say most of our stuff is designed to be a teaser. So, again, it's a 10-minute intervention. So, I think I think Eric, did you already pass out? So the sheet that we just passed out, so hopefully you look at this and you say, wow, that's interesting, I want to know more. And there's 100 other resources that you can then turn to that are going to give you a deeper, richer, more complex version of the same story. I guess before we push on, the other question I would ask is just one of process. So it was a pretty thinly manifest roleplay, but where we asked you to imagine you were on a unit teaching. But any reactions to the paradigm of being able to say, hey, we don't expect you as a faculty member to necessarily be an expert, but here's an opportunity and a frame where you could learn together.

[INAUDIBLE] And I think that that's actually something to think about when we do this with neuroscience models and those applications is how it kind of—

Yeah, so, yeah, so to one piece, this is not intended for patients per se. If people choose to incorporate this into talking to patients, that's something you can talk about, but this is primarily intended for clinicians. Is it possible to incorporate neuroscience into increase or decrease data? And I think it depends on how you do it, right? So, this is not a closed story, right? Yes, there's something wrong, but you kind of already knew that. There are treatments that are based on this. Some of our medications have the ability to change methylation, right? Like, there's all sorts of lines of research that are aimed at correcting these problems. So, I don't think it's something that would instill a lack of hope or necessarily brokenness.. But hopefully it should be a conversation about here's how we conceptualize the problem and here's how we're going to work together and try to fix it. So I'm sensitive to that issue. Yeah.

Other reactions to the paradigm for cued speech?

Yeah, I guess I didn't see it as demoralizing because it's— I don't assume that it's a fixed state. We know that there's a lot about brain plasticity and we know that there are a lot of mitigating factors. And then things that can enhance resiliency. And so I think the searches for those kinds of things, so that people will say, "Yes, I've had a trauma." You don't deny the trauma happened, because you know it. But then you figure out what helps. And what helps the person return to at least their highest level of functioning.

[Speaker:DR. ELI GLAESER] Yeah. I kind of love, as a process point, that we are so stuck in the meat of this, which I think is great. We're actually running a study now to actually use these interventions with patient groups and then get feedback from them on what's it like for patients when they watch these videos across a range of diagnostic categories. But, I want to ask one more time to see if we can step out to the process. Any reactions to the idea of being able to incorporate neuroscience in a clinical setting using a brief video resource?

Yeah.—

to change a specific curriculum, but we have done it in one of my clinics, and it's really awesome to be able to have something that's already well constructed to bring in and foster a discussion and then have these types of discussions afterwards. Yeah.

I think a key question I would be asking myself from a perspective of if I were to be establishing a curriculum is whether the patient that we're presented is too sick and has all sorts of things wrong. And I don't see that the mini— I like the mini lecture. I thought it was kind of maybe related to the patient, but there's so many other things that it didn't really seem much related to the patient.

So the premise is you would pick a case on your unit, somebody that you actually see, that you thought might be— whether—

there's also the issue of are we just going to throw out our diagnostic syndrome altogether, or might we pair the mini lecture with a case that actually sounds like it might be related to the mini lecture? And that would be a question for how to set up your curriculum, you know, is that useful or not?

Yeah, Matt.

So, great talk.

I'm I guess I have a slightly different reaction, in part based on, you know, sort of where you stand depends on where you sit. I think when I look at this, I think for the 90-some-odd percent of folks who have no idea that neuroscience exists in psychiatry, which is a depressing thought among trainees, that using this kind of approach could be quite useful as a way to bring people in and Plato models and all that. I think what I worry about, and also I think what we've been trying to think about here at UCSF over the last few years since I've been chair, is that while that may solve one problem, there's a deeper problem, I think, which is that what's underneath that narrative, right? So, it's great kind of facile seductive storytelling about neuroscience, but really science underneath that, it is quite complex. Every single step of those experiments are things that, you know, people should be asking that question. The questions about what is the usefulness of face validity in order to try to think about, you know, a rat versus a human. How reliable are assays of methylation to tell whether or not there are really state differences. You know, I mean, so you get to a level where at least my hope would be that, you programs such as ours, that we would not only instill the ability of people to walk into a patient and say, well, you know, your brain is connected to your problem, but also to have at least an appreciation about kind of the underlying depth of the science, where we are as a field, and what the challenges are. So I can tell you, and we're really struggling with this, so we put together a 2-year neuroscience curriculum that's being taught really is essentially a straight neuroscience curriculum, right, with developmental neuroscience, systems neuroscience, neuroanatomy. We've got people from Stanford, from here, and we're just implementing now. We built it for our child fellows. It was well accepted. We've now— we're putting it into place for our 3s and 4s. And already, you know, so far the feedback that I'm getting is people are not showing up reliably. I understand why we had this experience at Yale, right, where people were like, you know, getting this deep into it, it's like, that's not for me. And so I do think that there may be separate questions in programs like Yale, Columbia, UCSF, where we have the resources to go as deep as anyone would possibly want to, to really explain where the fields of neuroscience and genetics with regard to psychiatric illness land. And then there may be a broader issue around just bringing along other folks. And I wonder, you know, this is, we could probably talk at lunch, how are you thinking about this at Yale now, you know, 5 years after I left?

No, I mean, I love all this. So, I guess I love is the meta-process, like, first that we have people with strong affect from the exact opposite sides spectrum. The people who are really invested in psychosocial models say, "Why are you putting this stuff that's interfering with the psychosocial?" And from the neuroscience side, people saying, "This isn't good enough, you need to do more." And so, it is the tension that we wrestle with, on both sides there's this affect.

[LAUGHTER] [Speaker:MALE_1] You play a lot of affective content, I found.

[Speaker:DR_MARCUS_WALTERS] No, no, no, no, I'm with you though. Like, I think it's I think it's totally true. I think even within our programs though, there's huge heterogeneity of residents, right? So, you know, we have 25% of our group are neuroscience people, and 75% aren't. And we can't pretend that a lecture is going to meaningfully engage that group. It's not physically, it's a joke, right? So you have to be able to say, okay, how do we engage, how do we meet people where they're at? And maybe you have a 10-minute lecture where different people go in different directions. And the neuroscientists go and they read the papers and they get really critical and focused on it. And the other people don't. Because it's a turn-off and they're not going to get there.

So, I just want to push on that and say, do you think that another model is to say in the 5 or 6 places in this country that have the depth to be able to do this, should we say we're just going to do this?

This is the Tom Insel model of we should not have psychiatry and neurology, we should have clinical neuroscience as a residency, and forget everything else. So, at Yale, we have a broad mission. We're not just interested in neuroscience, we're interested in public policy, and advocacy, and education, and we want leaders across the field of psychiatry.

I don't want to go back. The thing is that we teach other subjects more deeply.

What I'm saying is— So, my point is, I don't think it's possible. And the slides I showed yesterday, which I'm sorry they're not here today, we look at like, so the average neuroscience member, like SOBP, has had 20,000 hours of lived neuroscience experience that they bring. You've had 30, 40, 50,000 hours that you've spent thinking deeply about neuroscience. And our residents have had maybe 50 to 100 hours. It's not physically possible for them to do the things that the neuroscientists would expect. So one of the first Neuroscience in the Media sessions we did was a piece on opto. And it was opto for appetite regulation, optogenetics. And, you know, we went and we read the article, we talked about the article, and we looked at the Nature paper. And we tried to talk about it, and I had Ralph DeLeon, who spent 10 years doing optogenetics for appetite regulation, look at our answer key. And I said, Ralph, help me out, tell me if we got this right. And then I said, Ralph, how long did it take you to read this? He said, "It took me 3 hours to read the paper." I said, "You spent 10 years doing this and it took you 3 hours to read the paper. It's a joke if I pretend that my residents are going to be able to read that paper in any comprehensive way. And the amount of time and energy I would have to invest in them for them to be able to read that paper critically would be a waste." Okay, so I'm going to make my last comment because I'm— it's just— Okay.

So if you were sitting right now in cardiology of any other field. And you told me that as a residency, that the bottom line was it's too tough for us to give people the basic understanding of pathophysiology that we already understand in the field because we have other things to teach that we have to take care of other things.

You know, I— That's not what I'm saying. What I'm saying is that there's a lot to cover. I'm on your side. I think we should be doing this. I think that there's a lot and we should do as much as we possibly can. There is is a question at what threshold you stop digging. And for me, the threshold is different than where the threshold is for you. That's the tension we have. I agree completely. I have a couple more slides that I'd like to get through. And then we can continue this discussion. So— I love it, right? Let me show you like 3 more slides and then we'll come right back to this. So, you know, we spend a lot of time on this. We're happy with our class and we've started doing this clinical stuff. And we're feeling good, or not. And then we step back and again, like, even if we've completely transformed the classroom and clinical settings, there is a wide world outside of the ivory tower and our major academic centers. And it's not just a geographic thing, it's thinking about systems of care. And we started by focusing really deeply on residents, but this idea as if a psychiatrist can practice this alone in the world is just totally false. And so our question was, how do we start to engage with a broader audience? And this is my very sophisticated artist rendition of a psychiatry resident. You can tell because they're happy and because it has a label that says psychiatry resident. But as soon as we started this, we realized we need to be thinking about medical students and we need to be thinking about our attendings and we need to be thinking about other MDs and cardiologists who are treating our patients. And psychologists and social workers and APRNs and patients and family. And how do we start to get the same content out to all of these other stakeholders and bring neuroscience to everybody? And so, we spent a lot of time thinking about the standard social media kinds of outreach, doing direct faculty development. Because the reality is, if we're trying to do this as a teaching mission, the people we're asking to teach this might not be familiar with the content. And they probably aren't familiar with the types of pedagogy that we're asking them to engage in, to teach and engage in a totally different way. And so we spend a lot of time, one way is through the Brain Conference that Eric has been really amazing in helping with for the past 5 years where we've had 250+ program directors from around the country come in and have 8 hours of helping them learn how to do this well. We spend lots of time traveling and having the chance to go to conferences and talk to different audiences and engage directly with awesome people at awesome places to think, how do we do this better? And to work with a lot of the key stakeholder organizations. And we're really grateful, particularly to ACMP and SRDP, for providing funding. And for us, a big part of this has to be making content accessible to everybody. So we built a website, and there's a couple resources I just wanted to flag. So, one is a series of commentaries that we've been writing in the journal Biological Psychiatry. And each one is intended to be one core concept, clear, relevant, and accessible for a broad audience. So, we're writing these for the resident level. And they're narrative, they're engaging, they're fun. It's been cool to see for the past year for the journal, of the top 25 most downloaded of them were NNCI commentaries. So I think it speaks to the hunger to have this content presented in a way that would be accessible for people. The other— and I think there's now 35 of these that are in the journal. The other thing we've been doing is a series of— producing a series of brief talks that we initially conceptualized as being something of a hybrid between a MOTH story, so true stories told live in front of an audience without notes, a TED Talk, everybody knows and Pecha Kucha talks. So, these are 20 slides, 20 seconds per slide. So, 6-minute and 40-second talks. And so, each of these are intended to be these brief, one core concept in neuroscience that's going to make the audience say, "Wow, this stuff is really cool." So, we cleverly named them "This Stuff is Really Cool Talks." And this is work that we've now been doing with Liz Neely, who's the executive director of the Story Collider. If you haven't seen them, they are awesome. And we have now been running these with scientists, so to train scientists to be able to communicate more effectively through ACNP, through SOBP, and through a range of other settings. So as far as starting to think about outcomes for us, there are a couple of key things. So the first was, can we collaboratively make this happen? Can we generate content? In this regard, it is pretty cool. So we had more than 10 modules, 100 sessions that reflect 100 authors from 40 different institutions. So it has been a collaborative project doing this. And the biggest part for us was really can we actually start to move the needle as far as what is happening in the real world. And at this point the website has a lot of hits from a lot of different places. And as Eric mentioned at the beginning, for us the most gratifying thing is there's now 100 programs that have said because of this since we've started teaching more neuroscience in this particular way, which is really cool for starting to bring that bar up. And collaborating with a range of other folks, including the Royal College, which is now redesigning how they're teaching psychiatry in the UK and having a say in what that curriculum is going to look like. And some other international folks. So, lots of time thinking about expanding resources, thinking about dissemination, thinking about technology and assessment. We have a new app that's coming out shortly. It's currently being beta tested that would make it really easy to access all of these things that way. So I will now stop there and resume the conversation if we can.

Yeah, please.

[INAUDIBLE] You know, when I was hearing the work, I was like, how do we kind of—

first, I thought it was great.

I love your module.

But how do we hit into those training types, right? So bringing it to those who are more segregated in the claims line, how do you bring it into that work?

Those who are more policy inclined, how do you use this science as stones for policymakers to inform, like, how the foster care system is?

How have you, like, incorporated those kinds of thinking and how you kind of do your cases and do your work? Yeah. Have you thought about this? Yeah. So, one is the case conferences are awesome because you put people at the table together. And you have somebody who's a policy expert sitting at a table with a neuroscientist and you get that conversation directly. The BP columns have given us the chance to really focus on the topics that we think are important and aren't covered enough. And so we're actually— we have 3 pieces up right now. Our next 3 in the queue are all going to be exactly what we're talking about. So we have somebody talking about Mom's Project, a really cool research project looking at the impact of parenting on neurodevelopment, looking at socioeconomic factors and stress with that. So really cool little piece on that. There's one on immigration stress. Are coming out shortly. So we've been trying very hard to focus on that. And over the summer, we're working on a piece with Rick Summers to really get neurobiology and psychotherapy, which I think is an impossibly broad topic.

So I honestly don't know how we're going to even begin to approach that.

We're trying. It's really hard. But I think it forces the same conundrum where we were before, that you have to pick a narrow part of a very big story. And you have to accept that you can't do more than one thing at a time. 'cause if you try to do 20 things in a session, nobody remembers anything. So one idea and then you build on it.

Okay.

We had a slob rat for a couple of years from the Clinton Institute teach neuroscience in our curriculum, which we did with shots of happy thoughts. And we used a problem-based learning model. They engaged. We thought it was great. The biggest challenge was in going about understanding neuroscience, getting the formulation about saying, here's what's happening. And then kind of like neurologists would be, would say, that's it, you know, we've mapped out the brain, but what do we do now? And sometimes fellows or others would say, how do we translate this? And that often became a really good conversation, but it was the most difficult part of the conversation. They sometimes walk away saying, So, what? How's that going to change what I do?

I think it's harder.

Yeah.

It's harder.

We work hard and this is why, I mean, you know, some across the spectrum people are having this argument. I mean, there are neuroscientists who say you shouldn't be teaching any of this because we don't know anything. I get that perspective. Yeah, so, yeah, please. Is that in developing the curriculum that's happening here versus sort of the perspective of the curriculum that you've developed is that this sort of top-down approach that often is sort of political application of neuroscience or neuroscience in the media, that the fundamental problem with it is that from a lot of these professors' perspective that they don't have the jargon, they don't have the terminology of the basic neuroscience to even understand one level below, like you're talking about —optofigures have been invented. So, I think that integrated basic neuroscience, and that's the thing that actually gets asked for the most often, is after we have one of these sessions, the residents in 2 or 3 out of a class of 16 repeatedly in different ones every time ask for, can we have a boot camp in basic neuroscience? So, can we have the fundamentals of, you know, how does the basic anatomy or basic cellular anatomy of the nervous system actually work? So, we can start to go from the top to the bottom of this And so, I think that maybe a 2-year curriculum isn't even enough, but maybe you need to take a 4-year curriculum where at the input level, you're just looking at the relationship between each area. So, or something. You're learning about the basics of neuroscience long before you start thinking about what is it that you're promoting in that way. Yes. And you can do a PhD in neuroscience, then you can spend 8 years working on that question instead of— That's a really facile response though.

The bottom line is, No, you're not sure we're saying you can't teach it all. This is basic fundamental piece, and it's as fundamental as understanding the DSM, understanding what a medication does, and understanding how to formulate a case. And the idea that, you know, that kind of comment that we're going to have potentially a 4-year curriculum where you build from the ground up, that, yeah, well, you could, you know, it's so big that you can't touch it, or we could have a neuroscience PhD, I think it is really is a nihilistic thought about where we are in psychiatry. It's not enough. Where we are right now, where we're going to be 5 years from now, and if there are not 100, if there are not a handful of places right now that are saying, we're going to make a deep commitment to try to change the way that psychiatrists think about what it is that's expected of them when they come out of a residency, I don't think we're ever going to get there. And so to me, it strikes me that in some ways this idea that we can do it in sort of a light way and and only pick a handful of things so that we have a narrative that fits in with other things that we want to do.

So that's not fair either. Okay, so first of all, I'm not telling you what to do. You can do whatever you want. We're saying here are resources that we offer to anyone who wants to use them. Use them if you like, don't if you don't. Build a curriculum. So if these are useful to you in establishing fundamentals and then you do 100 hours above, that's awesome. Do it. We support that. That's fantastic. We're not saying people shouldn't do stuff. What I'm saying is What I'm saying is that we have to recognize that, so first of all, if the residents don't like it, they will be alienated and they will not come back. So foremost, you have to be able to engage them in a way that they will be excited. And part of the problem and why the longer curriculums are really tricky is our interns spend 40, 50, 60, 80 hours a week, whatever the number is, doing other things. And anything that conflicts with that is perceived as an intrusion. The preoccupation of a PGY-1 or a PGY-2 is, "Oh my God, I'm going to kill the person sitting in front of me." That's what they're scared about is, "I'm going to be on call in the emergency room and somebody's going to come in and I'm going to screw up and somebody's going to die." And action potentials don't meet that need in that moment. It's not that we shouldn't be talking about it, it's just, it's not in that moment. And so, one of the reasons we're focusing on the clinical stuff is what can we meaningfully accomplish in that moment with them. That's why we do it that way. Now we do a Brain Camp actually. So we have a session at the beginning, it's going to be part of Brain for this coming year, that is intended to be probably 4 to 6 hours in total, that is trying to establish that fundamental vocabulary. Because I think the fundamental vocabulary is imperative. But again, I'm mindful of the challenge that if it's not relevant, whatever the hell you Everything you say in the classroom is gone. So you have to, and so the other charm of this model is that it allows you to create a resource that they can go back to whenever they want. Here's a 7-minute video. If you don't remember it later, go back, watch it again. As opposed to an ephemeral lecture where they've heard it, but then poof.

I will end with that. I'm going to say, I love a good debate. And I want to first give David a huge round of applause for coming.