I'm June Gruber, an associate professor of psychology at the University of Colorado Boulder and director of this mental health experts series. I'm delighted to be here today with Dr. Greg Siegel, a professor of psychiatry at the University of Pittsburgh School of Medicine. Thanks for being here today Greg. Thank you, June. I was wondering if we could just start by having you tell us a little bit about the kind of work you do in the mental health sciences. My group researches brain mechanisms of psychological disorder and how they change as people recover. We try and apply this work to both personalizing medicine and developing new interventions or treatments that better address the brain mechanisms we uncover. Excellent. How did you first go about getting started in this work? At first, I was an artificial intelligence researcher, and we were finding that we could create models of how people responds to information, especially emotional information. Sometimes when the models broke down a little bit, they looked and acted in the way that people with depression and anxiety do. As we were fixing them, they started acting less and less like that, more back like the healthy people do and we said, "Hey, can we use these intuitions about how to heal computer models to actually treat people?" Neuroscience has been a way of validating what we were doing with the models and applying the work to directly helping people and that's been a rewarding pathway. I love that pathway from artificial intelligence to helping human beings. Thanks. Along this way, starting from the beginning until this very moment now, what have been some notable frustrations or failures along the way as well successes you've been able to savor? Sure, so the successes are easy. We found that if we know about brain mechanisms, we can predict who responds to treatments like being in therapy and drugs. We've found that we can drive interventions that actually treat people more efficiently or if you add them to conventional treatments, people get more better. The frustration and in many ways, the failure of all of this research has been that the work we're doing doesn't get out to actual people. That is to say there is a notorious gap between what goes on in the lab and what goes on in the clinic. I did sabbatical back in 2017 to just try and understand this and it turns out that we're speaking different languages. The researchers of the world, especially in neuroscience, are speaking languages of what brain mechanisms change and how symptoms change and that is not what patients are telling their providers they want, they want more days at work. They want more days free of presenteeism, for example. Providers also are speaking a different language, they have different concerns. Getting providers to use our predictive algorithms is super hard. They're not using them. Even getting them to use a questionnaire is hard, much less for example, a brain scan. As one really good example, we made a new intervention a way to train people's brains to stop ruminating. We did a couple of studies on it, showed that it worked. That work has been now replicated in 16 studies on three continents. It keeps working, but it's not available to actual people yet because nobody's done a definitive studies and nobody's taken the time to actually translate it. We have to be the ones to do that. We started partnering a bit with industries and that's helped. A postdoc in my lab, spun off a company to actually commercialize some of the work we're doing. That's in many ways a great idea, and in some other ways it's not easy, the company has to be completely different from the academic work for reasons of conflict of interests. You wouldn't want me working on something and making money from it. They've got our ideas out in the real world, our publications are actually lagging behind, and we're having to lead parallel lives. This gap between the lab and the clinic is my big frustration, and the thing we're trying to address. With the frustration of this gap between the science and the practice, what do you see as some notable successes along the way? Things that have made you feel hopeful and that you've been able to savor in this journey. The successes are that we find everytime we test stuff in the lab, we can improve treatment outcomes. We can predict who's going get better. When we have gotten things out in the real world, people love our interventions. People find that using technology is something they enjoy and they will do it. We made a little device to put on people's wrists that vibrates in a way that recruits certain brain mechanisms. People were using it hundreds of times over a couple of weeks because they found it palatable and they found that it helped them to do the things that current interventions can't. I feel like we're very close, it's something people want. It's a matter of just jumping over a small gap rather than bridging a canyon in many ways. As you look forward, and you've spoken about this, about a small gap getting us to the next place we need to go. I wonder if you could speak more about these important next steps for the field. Sure. Sure. So to my mind, and we've now done a bunch of work asking experts what would you need to use what we're coming up with? It's focusing on implementation and dissemination right from the very beginning. That is to say, when you're starting the research, don't start it and say, ''I'm going to do something and hope somebody picks it up,'' as much as talking to stakeholders first and saying, ''What would you want? Am I doing the thing you would want?'' Then seeing who would actually use it and talk to them and say, ''Develop it in lockstep with somebody who has the potential to take it to that next step.'' I think we've got to stop with what we're calling quote-unquote personalized medicine, which means often saying who will and won't respond to an intervention. If we think somebody is not going to do well in school, you don't say, ''Well, just don't go to school,'' right? Treatment preference matters. If somebody wants therapy, they're going to do way better in therapy than for example, if you say, ''No, you should have this drug instead.'' I think next steps are going to be focusing on how do we help people to get the interventions they want, and to do better in those interventions. I'm focusing on pre-treatments; I'm focusing on augmentation of treatments. I'm focusing on things that are low technology, things that are a low-hanging fruit that people could actually use in their real lives, ideally at home. Fortunately, the technology is getting there. We have all sorts of psychophysiology and brain measurements people can increasingly do at home, and we've been publishing saying we can actually get measures that have some level of validity. These are amazing and inspiring responses, really thinking about how we can enact real change in real human beings' lives. My final question touches on this theme, which is what advice might you have for others who are watching this interview today? Students, mental health professionals, the public, who are interested in the field and want to get involved? Good. Let me first speak to students. Do it. Learn the neuroscience, learn psychology. These are powerful technologies that we have for making people better. Then, do the thing that our graduate programs don't always tell us to do, which is focus on impact early. Talk to stakeholders. If you're doing your dissertation on how brain mechanisms change when people get better from PTSD, talk to people with PTSD, and say, ''If I come up with something, would you care? Am I asking questions that you care about?'' Talk to doctors, talk to psychologists in the field and say, ''If I do something with this, am I answering questions you want, or should I change the way I'm going?'' Every time I've done that, my research changes, my questions change and my answers change. In terms of clinicians and talking to clinicians, the advice I would give is don't think of academia as a separate world. Think of it as people who actually want to work lockstep with you and talk to them, read the journals. We have just put out on the website for the Association for Behavioral and Cognitive Therapists references on how clinicians can use neuroscience in their practice today for neuro-literacy, for emerging technologies. Read it, it's there, it's accessible, and we're trying to make it as accessible as possible. Then finally, for people who are suffering, know that we're working for you; we're trying, and we need your help. We need your help actually engaging in research. We need your help knowing what we should research, so reach out to clinicians, reach out to researchers. I want to give a specific shout-out to communities who have specifically been excluded from research in the past. Increasingly, we know there are a lot of communities that have been excluded and treated poorly by research for many years, and we're striving as hard as we can to make up for lost time and really include everyone in our research. You're going to see increasing focus on trying to recruit people from diverse communities and trying to really understand and become part of the communities we're trying to research. What I would ask is that you allow us to do that. We're reaching out. I would love it if people hear us and talk to us. We want all of the feedback, so we can begin addressing everybody's concerns as quickly and as validly as we possibly can. Thank you so much, Greg, for an inspiring interview and for taking the time to speak today. Thank you, June. Good luck with the rest of your series.