797: Examining How Our Brains Make Decisions About Investing Effort and the Impacts of Mental Illness - Dr. Michael Treadway
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Hello and welcome to Episode 797 of People Behind the Science. I'm your host, Dr. Marie McNeely, and today I'm excited to introduce you to our guest, Dr. Michael Treadway. Listeners, if you like this episode and you want to check out more stories from amazing people doing great science,

You can find more episodes of our show on Apple Podcasts, Spotify, or wherever else you like to listen. And today, Michael has some fantastic stories to share with all of us. So get ready to meet another one of our brilliant people behind the science.

Every day, discoveries are made that will change our understanding of the world around us. Dr. Marie McNeely is here to bring you the brilliant minds who are making these discoveries so they can share their incredible stories and take you on an amazing journey. Welcome to People Behind the Science. ♪

Hello, everyone, and welcome to People Behind the Science. Today, I am excited to be speaking with our guest researcher, Dr. Michael Treadway. So, Michael, welcome to the show today. How are you? Doing great, thanks. It's really good to be here. Well, thank you so much for joining us today. We're excited to learn more about you and the work that you do. But first, let me take a moment to tell our listeners a little bit

more about you and how you got to where you are today. So listeners, Michael is the Winship Distinguished Research Professor in Psychology and Director of Clinical Training in the Department of Psychology at Emory University. He is also affiliated with the Department of Psychiatry and Behavioral Sciences at Emory. Michael received his PhD in Clinical Psychology from Vanderbilt University, and he completed his clinical internship and postdoctoral fellowship at McLean Hospital and Harvard Medical School.

Michael joined the faculty at Emory in 2015, and he's received numerous awards and honors over the course of his career, including the Distinguished Scientific Award for Early Career Contribution in the Area of Psychopathology from the American Psychological Association, or APA, the Randolph-Blake Early Career Award from Vanderbilt University, the Janet Taylor Spence Award for Transformative Early Career Contributions from the Association for Psychological Science, or APS,

the Early Career Impact Award from the Federation of Associations in Behavioral and Brain Sciences, or FABBS, and the Rising Star Award from the APS. And today, Michael, we're excited to hear more about your life as a scientist, but also more about your life outside the lab. So can you tell us what do you like to do when you're not doing science?

My wife and I have two young kids, seven and one. And so at this sort of stage in life, I'd say a lot of what we like to do is just spend time together as a family. We love games, play a lot of games together. My oldest has just recently become old enough to do sort of more complex games. And that's been a lot of fun. The other main hobby, I guess, is I love music. I am an amateur pianist.

pianist and was actually a music major in my undergrad years. So playing, listening, going to performances, another thing I really love to do outside of science. That's wonderful. I love that you have these multifaceted interests and hobbies. What are some of your favorite games that you play with the family these days?

Growing up in my family, we actually did a lot of card games. We would often spend time together in sort of camping or other situations where it wasn't possible to bring complex board sets or whatever. So deck of cards is what we had. So games like Bridge, Euchre, a game called Oh Hell, which I won't try and go into the rules, but my son now seven just became old enough to kind of grasp Oh Hell, which has been a lot of fun.

That sounds wonderful. It's great to get a window into your life outside of the lab. And I know you're doing remarkable work on the scientific side. So how do you describe your research to someone who is outside of your field or outside of science altogether? So our lab has really two overarching and intersecting aims. One, we really are trying to understand how the brain makes decisions about

about where to invest your effort. This sort of cost-benefit decision process of this thing I want will take this much work to get it. How do I decide if that's worth it? We look at that in a whole variety of different ways. Most of the types of decisions we focus on are what I call taxable.

temporarily local. So where am I going to put my effort next? Easy example is maybe where you work. There's a place down the hall from your office where you can get a cup of coffee. You've been putting in a good morning. You feel you want a break. You walk down the hall to get the coffee and you see that they're out. And now you have to decide, do I want the coffee enough to justify going out to the store or

going down three blocks to a coffee shop? Or does that not really feel worth it? That type of decision-making process is really what we study. To study it, we draw a lot of inspiration from studies done in animal models, but our lab does everything in human participants.

And we mostly use neuroimaging, recording brain activity that seems to track with certain aspects of these types of decisions. And then to experimentally manipulate these decisions, we'll use things like pharmacological manipulations, drugs that influence particular neurotransmitters or neurostimulation techniques that can actually

activate or deactivate temporarily a particular brain area to see how that impacts someone's decisions or preferences. So that's one focus of the lab. And one of the reasons that we're interested in that question, apart from the fact that it's just a really interesting question, is that decision-making process seems to be

really impacted in a wide variety of mental disorders. Most prominently, I think, major depression, but it's by no means unique to depression, where when people become depressed, a lot of activities that used to feel like they were worth the effort

No longer feel that way. Daily tasks that most of us may find it easy to do without thinking about, getting out of bed, brushing your teeth. They start to feel really overwhelming and effortful and

and trying to understand how this circuitry works normally and then what happens when people get depressed that has changed in this circuitry to lead to a different set of decisions. And does that help us understand ways in which we could intervene? Very interesting. Well, Michael, I look forward to getting into some of the details of your work as we go through our conversation today. And I think

being able to work on these fascinating questions is definitely motivating and can be inspiring and can get you motivated to go into work every day to do the work that you do. But sometimes you need a little extra boost. So do you have a favorite quote or a saying or something that really motivates you? I actually have two. So

So the first is a quote that I heard actually on a meditation retreat almost 20 years ago now. And it was a meditation teacher talking about how to deal with the discomfort of meditating and how to stay with it. And the quote is, pain is a great teacher. Agony is not. And that may not sound like a motivational quote, but I think...

a big part of what motivation is, is it's the willingness to bear costs. It's the willingness to pursue something despite discomfort and to see the inherent value in that persistence and in that struggling through. And so this idea that pain is a great teacher, that we actually often learn a lot from painful experiences. Certainly when I reflect on my life, the areas where I've

grown the most as a person

have often been some of the most difficult. But as much as pain is a great teacher, I think what I love about this quote is setting this boundary and delineating between when pain becomes so much that it becomes agony and it is not a good teacher, it is not something to kind of continue to persist in and we need to perhaps take a break. I really like the fact that this quote incorporates both of those. The second quote that comes to mind

maybe a little less about motivation for everything and more about motivation specifically towards other people. It comes from a Greek philosopher and writer, Philo of Alexandria, and it's, be kind for everyone you meet is fighting a great battle. I love this because I think that particularly at a time when in our country and around the world, there's a lot of heartbreak

partisanship, a lot of seeing each other as other, that this kind of reframe to remind ourselves that all of us have in common a lot of struggle that we're working through and that the most difficult parts of our lives are actually one of our most profound ways to connect to each other. I think it's a useful quote to motivate us to try and extend past our superficial differences.

Definitely. And I think these quotes have in common just this idea that strength and pain are part of the human experience. And I think that in and of itself can be kind of comforting to know that you're not alone in the struggles and the pain that you're feeling. Absolutely.

Well, I think these are wonderful pieces of motivation to carry with you every day. And I think some of the people that you encounter along your path can be really inspirational and motivational as well. So, Michael, have you had people in your career or in your life more generally who've really been remarkable role models or mentors or people who you've looked up to?

Yes, too many to really go into. I feel I've been incredibly fortunate in this regard. My parents, my family, friends, friends in graduate school who've gone on to become really close scientific colleagues, certainly my graduate mentors and my postdoc mentors.

I don't mean to make this sound like an Oscar acceptance speech where I have to thank everyone, but there really are a lot of people who have all been just amazing mentors to me. As far as sort of role modeling specific aspects of how...

how to do the type of work I do. One person who comes to mind was one of my professors in graduate school, was not my primary mentor, a person named Steve Holland. And Steve had spent his career studying cognitive behavioral therapy as a treatment for depression. And in doing that, he spent an enormous amount of time in the room with patients delivering this psychotherapy and in that process

hearing from them how they experienced depression, what it was like, what it was like to try and change, how change worked for them. And then he also viewed this disorder and its treatment from a real objective perspective.

of trying to understand mechanistically the core aspects of the disorder. And one of the things that's so challenging in studying mental health is unlike other areas in medicine, we really don't have a good definition of what a disorder is. We don't have any objective thing we can clearly measure and quantify to say this person has this disorder and this person does not.

So that puts our field in this place where we're trying to construct a objective mechanistic understanding of a disorder relying primarily on the subjective reported experience from individuals who feel they're suffering from this disorder.

And one of the inherent challenges there is that all of us, while we may know how we feel in a given moment, our explanations for why we feel what we feel and other feelings that may be happening at the same time, but we're not paying attention to them, we are all somewhat unreliable and incomplete narrators of our own experience. So how to build on that body of

first-person accounts and really learn from that and then construct a sort of third-person perspective mechanistic model. That was something that Steve really modeled for me in my early years in graduate school. Very interesting. And it sounds like this passion for just scientific discovery and particularly understanding the human mind may be deep-rooted within you. Can you share with us where this interest began?

I've had a pretty circuitous route to science. When I was a little kid, I really did like science as a topic and particularly anything related to sort of inventing. But by the time I was in high school and then particularly college, I'd really come to think of myself more as a humanities person. I really enjoyed writing. I really enjoyed writing.

thinking about history and politics. And when I got to college, I was very drawn to the discipline of critical theory. This describes a way of thinking about history, culture, through, in some cases, a Marxist lens. I think I was drawn to

The idea of a mechanistic explanation for these big sweeping changes in culture. So I focused on that a lot in my undergrad. And I, as I mentioned earlier, I was also a music major. I was interested in this sort of progression of

of music and music composition. By the end of college, I had started to get a little disenchanted with this way of thinking. I started to feel that these grand explanatory theories weren't actually explaining all that much. And

I was also running out of time in college and sort of needed to find a job. So I went into what was accessible at the time, which was to go into an internet startup. I graduated into the absolute peak of the dot-com boom in the late 90s, early 2000s. And so I was able to join an internet startup and worked in that world for five or six years. And

And during that time, I discovered that while I enjoyed the work and I felt we were building a good product, that I really missed the world of ideas. But I was also fairly rudderless in terms of what body of ideas, what discipline I wanted to pursue. And I think at that time, I was also honestly struggling with depression a bit myself.

And as part of trying to get through that, my father actually introduced me to some books on Buddhism.

And I really was moved by Buddhist psychology. And that was actually my path into studying Western psychology. I became so curious as to why is the mind like this? And are there discoverable laws, as Buddhist psychology describes, that we could really find empirical evidence for?

And through that, I actually started out thinking maybe I would pursue a philosophy PhD, sort of philosophy of mind. But along...

The way I realized I wanted to have a mix of both science, but also some clinical practice. Both my parents are doctors and therapists, and I think I was influenced by wanting to have some aspect of my career in this way, helping professions. So that's really how I came to choose clinical psychology.

I think this is fascinating. And I think your career path in particular is inspiring because I think a lot of people maybe do find science later in life, but feel like it's too late. How did you convince yourself or maybe deal with that sensation of just this idea that, well, you missed the boat? You're already behind in trying to pursue a scientific career path because you've had these other career things along the way. It was very hard.

I did feel that it was too late to start over. At the time, I was contemplating this. A number of my friends who'd gone straight from undergrad to law or medical school, they were now graduating or really establishing themselves.

And I hadn't taken psychology classes in undergrad that I needed to even consider applying to graduate school. And so at that time, I was going back to my undergraduate institution as a general studies student and sitting in on classes with basically a bunch of first year students. And it was hard.

I think by that time, I did have a real clarity that I wasn't happy on the path I was on. And as hard as it felt to start over, it also felt like I didn't have a choice. It felt very clear that if I stayed doing what I was and tried to make the best of it, that I would regret that choice the most.

That makes sense. And it sounds like you got on track then. You completed those classes. You then were able to go to graduate school. You did your PhD in clinical psychology at Vanderbilt. Can you talk us through a little bit about what that experience was like? I had a wonderful experience at Vanderbilt.

As I was saying a bit ago, one of my paths into studying psychology as an empirical scientist was through a personal interest in Buddhism. And my first job before graduate school as a research assistant was actually in a lab led by Sarah Lazar at Harvard Medical School's

studying the effects of meditation on the brain using MRI. And that's what I wanted to bring to Vanderbilt. And when I got to Vanderbilt and was all excited about studying mindfulness, what I found was at that point in time, no one else was interested.

I would say, let's do mindfulness and I would get crickets. And I think a really important thing I recognized at that time is I need to lean into the strengths of where I am. If I had really pushed to do mindfulness, I'm imagining people would have let me do it. But I don't think I would have had the opportunities to grow physically.

and learn from the best scientists that Vanderbilt had to offer at that time if I'd stayed focused on that topic. So I pivoted

And again, going back to Steve Holland, it was in one of my classes with Steve Holland and we were talking about depression, which I was also really interested in. And Steve said that in all his experience sitting with patients and treating depression, the most important aspect of depression was this symptom called anhedonia.

And that it was a symptom that was understudied. And in his mind, it was core to what depression is. And boy, someone should really study it. There was also another lab at Vanderbilt led by the person who ended up becoming my doctoral advisor, David Zald.

was doing this, what at the time was a pretty novel technique for studying the brain reward system, which is positron emission tomography or PET imaging and doing PET imaging of the dopamine system. And he was focused on alterations in the dopamine system in the context of substance use disorders, where the idea is maybe this system is

hyperactive and too responsive to potential drugs of abuse. And I approached David saying, well, could we use this technique to see if in depression, this system is not reactive enough? And it was really putting those two together that launched the research program I've had pretty much ever since, which is trying to understand what are the brain changes that lead to motivational changes in disorders like depression.

Very cool. And it sounds like you've had a wonderful career path. You were able to try a number of different things before really finding what was the perfect fit for you. And I know you're doing remarkable research in your lab today. So is there a particular project, Michael, that you are just the most excited about at the moment that you'd like to share with us?

Actually, there really is. So I've spent a lot of my time as a scientist trying to understand the circuitry related to motivation and cost-benefit decision-making using essentially correlational measures. We put people in an MRI scanner or we use EEG or PET imaging and we measure brain activity while people do a task and when we try and make inferences based

based on activity that seems to correlate with a particular choice or a particular task variable. And one of the big problems in that approach is that many of the processes that we are interested in

are all highly correlated with each other. So a choice that is very effortful may also be a choice that you make less frequently. So if you see activity in a brain area responding a lot to a very effortful choice, that could be activity that is signaling a representation of that cost.

It could be activity that is representing a prediction that because of that cost, we're probably not going to choose that option. It could be activity representing the fact that that cost is so high, it's unexpected.

Sort of what cognitive neuroscientists would call a prediction error. So it can be very difficult to tell when you see activity in a given region, even in a well-designed experiment, exactly what process that activity is reflecting. What computation is that brain area doing?

And to get at that, you need methods that allow you to manipulate brain areas directly. And in human cognitive neuroscience, that has been very limited in terms of the armamentarium we've had available to us. There are methods like transcranial magnetic stimulation, which can work very well, but

only at the surface of the cortex. It's a technique for temporarily stimulating or inhibiting a brain area using a magnetic pulse that influences electric fields in the brain, but can't get very deep. So what I have and what many in our field have long been wanting is a way to safely, non-invasively stimulate deeper brain areas.

And two new techniques have emerged in the last five or six years, one of which is called temporal interference stimulation. And that's what I'm really excited about. The principle of this technique is that you have a

Electric fields at high frequency, if you deliver an electric field at high frequency to the brain using standard surface electrodes, high frequencies like greater than a thousand hertz, those tend to be too high frequency for neurons to respond much to. And so you can pass a high frequency electric field through the brain and you won't see many changes.

If you have two high frequency electric fields going at the same time and there is a slight difference in their frequencies, so one is say 5,000 and one is say 5,020, where those two fields intersect, you'll get a amplitude modulation effect that has its own beat frequency on top of the two carrier frequencies.

And that beat frequency will be the delta between them, so 20 hertz. And that is a frequency that neurons do respond to. And that point of intersection between the two fields, referred to as an envelope, that envelope you can essentially place anywhere you want in the brain based on how you configure the surface electrodes. So you can move that envelope down deep into the brain,

And you will not be stimulating the areas between the surface and the envelope. It's only the area of the envelope that gets stimulated. So this now gives us the ability to test lots of ideas.

about what some of these deeper brain structures are doing from our correlational neuroimaging measures using experimental methods. I think this is really exciting. Was there a particular structure that you had had your eye on that you really wanted to be able to manipulate experimentally but had been out of your reach previously that you can now sort of attack and address?

Yes. The striatum is the core region for anyone kind of interested in reward processing or motivation. Stridal dopamine, we've known for a long time, is a key driver of motivated behavior. If you deplete stridal dopamine or disrupt stridal circuitry through non-dopaminergic methods, you will get a real reduction in the willingness to expend effort for rewards. That's been shown in

rodents and non-human primates and humans. So that is one of the key areas. I'll just say in terms of a specific project I'm really excited about. So I study effort and a lot of how we tend to think about effort is as simply a cost.

I would, in principle, always prefer a reward that is free as opposed to one I have to work for. And while that may be true in some contexts, clearly the success of things like Amazon highlight that we all value the convenience of not having to expend the effort to go to the store to get something. There are also many contexts, and I think academics know this very well, where the effort itself is part of the reward.

It is part of what makes an outcome feel really valuable and meaningful is how hard you had to work to get it. And this is in the field referred to as the effort paradox. From a sort of computational neuroscience perspective, how is effort both a cost and a type of reward?

So we've developed some paradigms that illustrate this behaviorally, where we can show the ways in which using a sort of virtual reality world that people navigate through, how both expending effort increases their mood. And in some contexts and in other contexts, spending more effort leads to a decrease in their self-reported mood.

And now we are using this temporal interference technique to manipulate what we believe to be the underlying neural circuitry to see if we can't change how effort impacts mood.

Well, Michael, this is a remarkable project. And I think some of these advances in science can make these dream projects possible. But I know not every day in science is a cakewalk. I think there's so many challenges and struggles and failures along the way. So do you have an example of a time that you really struggled with something or perhaps you had a major failure? And

And if so, could you talk us through how you worked through that difficult time? Yes, absolutely. There is a lot of rejection in this business a lot of times when things don't work out. One period that does come to mind is probably about five years ago. I

I was coming to the end of the first series of major projects and funded grants that the lab had received since it had been founded in 2015. And I was writing lots of new grants and everything was getting rejected. Oh, no. Yeah. And I was rapidly running out of money. I was having to shrink the size of the lab forever.

Fortunately, for the most part, people were going on to graduate school or to other positions, but I wasn't able to hire anyone to replace them because we were running low on funding. And it was pretty discouraging at the time. And it was really hard to go from a large lab to a small lab. I think there's a lot of expertise and knowledge that I worried was being lost about ongoing projects.

And how I got through it is I came to recognize that what was happening is that the field had really changed, that the ideas and the methods that I developed and been trained in as a graduate student and postdoc that were exciting and new when I came to my faculty position, now the best of those had been absorbed into the field and the field was moving on. They were

approaching neuroimaging data analysis in more advanced ways than I'd been trained in. They were approaching behavioral tasks, development, and measurement in more advanced ways than I'd been trained in. And I'd had my first real experience as a professional scientist of having the field move beyond what I had been trained to do. And that fortunately pointed to the solution, which is one of the best things about this career, which is

became a real opportunity to learn a lot of new methods and new literature. So I

I changed a lot of how I was approaching my core questions. I was fortunate at that time to have a sabbatical and I spent a lot of time in my sabbatical learning more computational methods, learning machine learning techniques, partnering with junior colleagues in our department who had real expertise in this area and really helped rethink how I was approaching the study of my core questions.

And once I saw that that was the path forward, it felt less like rejection of my ideas and more like an opportunity to get better. And a few years after that, I had a spate of a bunch of grants getting funded and a bunch of things now hitting. And that's how I was able to get past that time.

I think that introduces another problem where everything hits at once and then now you have to rapidly grow your lab, right? That's right. Yeah. Well, Michael, I think this is such an important story to share with listeners because I think people sort of have this idea that once you make it as a faculty member, you've sort of matured, you've got this line of research and you just plug away at it. But I think you do have to keep learning and growing and evolving the research that you're doing to keep up with all these advances that are happening in the field. You absolutely do.

And sometimes it can feel overwhelming for sure. But if you remind yourself that it's really an opportunity to learn and to grow, I actually think it's one of the most rewarding things about a career in science.

Definitely. Well, we're so glad that you made it through this difficult time, this drought in funding, which I think a lot of scientists do experience. But we don't want to dwell on the difficult times. I'd love to talk about some of your successes as well. So, Michael, do you have a favorite success story from your scientific career, whether it was a big win or just a small win that meant a lot to you?

Definitely. One that really comes to mind is actually one of our most recent. So I've been talking a lot about our lab's interest in understanding the neural circuitry of effort-based decision-making and motivation and a little less about how we apply that.

to potentially help patients struggling with disorders like depression. And one of the ways we've tried to use our understanding of this neural circuitry is to identify potential subtypes of depression that may have a particular pathophysiology that will be selectively responsive to a different type of treatment.

than standard either therapy or SSRI antidepressants. And about a month ago, we published the result of a clinical trial that was very supportive of this idea. This is a project that was eight years in the making and the basic background

is a lot of prior work, much of which has actually been done at Emory by some of my key collaborators, a scientist by the name of Andy Miller, as well as Jennifer Felger and Ibrahim Haroun, who had for years been showing that peripheral inflammation, when it gets in the brain, can reduce the availability of dopamine.

and lead to a reduction in the experience of motivation. The logic behind this goes back to what people identified decades ago as quote-unquote sickness behavior. And people recognize that when an individual or an animal becomes sick with an active infection and the immune system becomes engaged, the

The behavioral response actually looks a lot like when someone becomes depressed. Energy goes way down. There's a strong sense of fatigue. There's a strong sense of loss of motivation to do anything. And researchers started to uncover that this behavioral response is actually driven not by the underlying virus or bacterial infection,

but by the immune system. The immune system through messenger molecules called cytokines communicates with the brain to basically inform the brain, you need to shift how you're thinking about what your goals should be because the body is fighting this infection. And it's been observed for a long time that somewhere between 20 and 30% of individuals meeting criteria for a diagnosis of depression also have LHC,

elevations in these cytokines in their blood. This can be for a variety of reasons. When people start to become depressed, usually they start sleeping not as well. They stop exercising. Often their diet isn't as good as it might optimally be. And all these things can exacerbate inflammation. And what Andy and Jennifer and Ibrahim were thinking is that this inflammation gets into the brain

and starts to shut down core motivation centers like the dopamine system. And if that's true, it suggests that an anti-inflammatory drug, not an antidepressant, but an anti-inflammatory drug might be a potent treatment for motivational symptoms in patients who are both depressed and

and have evidence in blood samples of high inflammation. So that's basically what we did. We recruited a sample of patients who were currently depressed and had high inflammation as determined by blood measures

And then we tested their levels of motivation and brain activity using fMRI associated with that motivation, with that sort of cost-benefit decision-making that we've been discussing. We did that all at baseline. Then we randomly assigned everyone to either receive a potent anti-inflammatory drug called Infliximab,

or a saline placebo. It's a drug that does not have a strong subjective experience. So patients really have no idea which they got. It's very hard to tell. And our staff were, of course, all blinded to drug assignment. And then we tested them on these same measures of motivation and neuroimaging two weeks later. And what we found is that relative to the patients who got placebo, the patient's

Bugad and Fleximab showed a real increase in their willingness to expend effort for rewards in our behavioral tasks. And that was also associated with a series of changes in brain circuitry in key areas involved in this decision-making process. And the extent to which those areas changed and the extent to which the behavior changed

was mediated by how much change we saw in blood markers of inflammation. So basically, how much the drug suppressed inflammation was predictive of how much improvement a patient got.

And so I think this is a real success for us in that it highlights the value in thinking about disorders like depression as not just a single disorder, but really a family of disorders that there may be subtypes with distinct pathophysiologies that really need distinctive treatments.

And the blood markers we use to determine if someone has inflammation, they're widely available, they're very inexpensive, could be easily incorporated into a sort of standard workup. And we're hopeful that in the coming years, based on this type of study and others, we will see these measures incorporated into assessment and used to guide treatment.

Well, Michael, this is a huge win. And I think just this idea that there may be in the future, the ability to target various or multiple mechanisms in treating depression, I think is really heartening for people out there, since I think the numbers just sort of keep rising in terms of the reports of people who have depression. Yeah. Yeah.

Well, we're so excited to hear about this win from your laboratory. How did you celebrate? That's a real good question. Eight years in the making. Come on. Yeah, eight years in the making. I mean, here's the thing. By the time the paper actually comes out, there is a way, it's a little sad to say it, but there is a way in which within the lab, we've all kind of moved on to the next thing.

And the next thing is exciting. There's a lot more we want to understand. We think there's a critical role for how the immune system impacts cellular metabolism that is sort of driving some of these effects. There are other compounds that we want to test that may work better than infliximab.

So I think we do have a lot of fun with what we do. But in terms of did we have a big celebration for this particular win? Honestly, I'm not sure we really did. I think the real celebration is it provides the foundation to go to the next study. Definitely. I think it is easy to sort of dive right into those next pressing questions and projects. We do try to encourage our listeners to

to take a break, to perhaps give their mind a break and think about something different or read something different. So we love sharing book recommendations with everybody. So Michael, do you have a favorite book or one that you just like to recommend to folks, whether it's related to science or not? I do. These are two recent books I read. They are both related to science to a certain extent, but in different ways. One is The Knowledge Machine by Michael Strevin's

He's a philosopher and historian and tackles the history of science. And why did it take so long to go from a emphasis on empiricism, which was certainly a strong tradition in fifth century Greece, for example, with people like Aristotle? Why did it take so long to go from the recognition of the value of empiricism to the modern scientific method?

which really kind of originated in the 17th century with people like Newton and Bacon and

and others. And he makes the argument that one of the core limitations of earlier empirical approaches is that they tried to explain all the data in one grand theory that would fit all the empirical observations. And it was really Newton who recognized the value of what Strebens characterizes as shallow explanations. Basically, I have a set of phenomena that

that I can predict how they will behave using a set of laws or equations over in this context. And even if my theory that guides why my equations are accurate descriptions, even if my theory is directly contradicted by a different set of facts in a different context, that doesn't matter.

I need not be bothered by that. I can recognize that there is a contradiction there that will need to be worked out at some point in the future, but I can just build on whatever I have that predicts a small piece of the problem. And I think that shift in thinking that I don't have to have

a theory that explains everything. I can just focus on a little piece of a puzzle and put it out in the world and see how other people find it fits with the puzzle pieces they're working on. I think that is just a really interesting take on how science became a

accretive and to a certain extent social. Newton's insight there is really what enables science to become more of a collective enterprise. So that's one book. There's a lot more in the argument, and I really recommend the book if you're interested in that topic.

Another on a sort of different topic is called God, Human, Animal, Machine by Megan O'Geeblen. It's sort of half a journalistic take or survey of trends in certain areas of science like artificial intelligence and the quest to extend human life further and further on in the future to reverse aging, these kinds of trends.

And part autobiography, because Megan was raised as an evangelical Christian. And all the way through college, it was her understanding that it was absolutely true there was an afterlife. It was absolutely true what the laws of how the world was created and how it worked is set forth in the Bible. And she...

became skeptical of this and this was a huge disruption for her personally. And she turned to science to offer kind of an alternative and I think was drawn to elements of science where science has sort of been promising a potential kind of

heaven on earth, if you will, in terms of extending human life and the event horizon idea that will hit this point where knowledge is accumulating constantly. And some of the ways in which she found that did and did not provide an alternative structure for meaning that she had gotten from her

her religious upbringing. And I really resonated with this book because even though I didn't come from her background at all, I think when I was feeling kind of lost in what to do with my life, working in dot coms that we talked about earlier, I think I too was drawn to science as potentially a way to find meaning in life.

And I think that as she describes, I too have found that while the work feels very meaningful, there are real limits as to what science can tell us right now about how to live a meaningful life. So I really appreciated both sides of her journey there.

Well, I love these recommendations, Michael, and I'm excited to add them to our website for our listeners to find there. And we've talked about some different aspects of your career in science, and I think it can be very rewarding on a number of fronts. And I think one of the things that is a perk that many people may not realize happens a lot in science are these opportunities to travel. So do you have a favorite place that your science has taken you?

I love going to conferences. I do think it's one of the real gifts of this career. And I do very much enjoy the travel, although I'll say the best conference experiences that stick out of memory are the ones where I probably did the least amount of sightseeing because I was so engaged in the conference.

I tend to really prefer smaller meetings in my fields of neuroscience. Society for Neuroscience has an annual meeting, which is between 40 and 50,000 people. It's massive, and that's very exciting and energizing. But I love the meetings that are really small and focused on a particular topic that everyone is essentially working together.

There's a conference called the Dopamine Conference that has been organized every three to five years. And the last time I went, it was in Sardinia, which is absolutely beautiful. It was also a small group of maybe a couple of hundred people. So you really felt you got to know everyone there. We did dinners. They organized this huge conference-wide dinner in

in this beautiful set of gardens outside the city. And that was just a wonderful part of the world to discover and also really wonderful science. So this was the best of both.

Definitely. And I think you're absolutely right. These small conferences are wonderful opportunities to really build those close-knit communities within your field. And I think that can be really valuable for collaborations and just working together to solve these big problems that you're working on. And I think the people in science are absolutely remarkable, but that's not always the reputation, unfortunately, that scientists get in the media. So...

We love trying to break some of the stereotypes that people may have by showcasing these human moments in science, whether it's a funny memory that you shared with colleagues or a quirky tradition that you had in a lab. Do you have an example of one of these human moments, Michael, that maybe goes against these traditional stereotypes? One that comes to mind is in my lab, I have a

a bit of a reputation for being very excitable, particularly around new results. I didn't know this until my lab members pointed it out to me, but I get a particular look on my face when I'm really excited about a result that someone is going to share with me. And at some point, unbeknownst to me, someone snapped a picture of me making this face. And then our lab, like many labs these days, uses...

Slack to communicate. And we have a bunch of Slack channels for different projects in the lab. And one of my postdocs took that picture and created a Slack emoticon that's called Excited Treadway that is me making a face that people now use all the time in Slack when they're excited about data or a result. I think that is wonderful.

So then has this sort of evolved into other people being made into emoticons as well? There are, I think, a few emoticons that get associated with people. I don't know that anyone has had their picture taken and transferred into an emoticon, but I would certainly be in favor of that. I think we should do that for all lab members.

I absolutely love that. We'll have to give these folks an opportunity to ascend to the level of the excited Treadway emoticon. And I think that really does showcase the sense of humor and the sense of community, which I think is really important in science and kind of working together to get through these tough times. Because there are a lot of challenges, as we alluded to earlier, and oftentimes you face barriers, whether it's limitations in funding, technology, staff, or even just time.

So if we took away the barriers that normally hold you back, Michael, is there one particular question that you would want to answer most? I think it would go back to what I was describing earlier is resolving this effort paradox idea. What determines when effort is experienced as a cost versus experienced as something that adds value or creates meaning?

In so much, I feel, of how we go through the world, it is really the things that we have worked the most at that give us a sense of meaning and purpose and understanding how we reconcile that aspect of our effort and our attention, which is attention is just a form of effort, how we reconcile that.

to also the experience of giving effort as being very costly. That's really the question I'd like to understand. How does that get determined in the brain?

Well, I think this is a fascinating question and we appreciate you giving me and our listeners something to ponder today. And I think you shared a lot of insights and a lot of information about the work that you do in your career path. But do you have a piece of advice, Michael, that somebody gave you at some point along your own journey that you think might be able to help listeners out there?

As I mentioned, I went through a long period where I was sort of not happy in my current career, but really searching and trying on lots of different options. And I really tried and considered a lot. I mean, I thought about going to law school. I went as far as taking the LSAT. I took the GMAT for business school. I thought about going into music history, do my love of music. And at

at that time, a lot of how I would approach thinking about different career paths and trying to imagine myself in different careers was to imagine, okay, if I do this and let's say I'm successful at it, where will I end up or what will I achieve or accomplish? What things will I have to show for myself? Almost like running through an imaginary highlights reel of a particular career and

And it was actually one of my piano teachers at the time who said to me, if you're trying to make this type of choice, don't think about the accolades or achievements or the highlights or the milestones. Just think 15, 20 years in the future, you wake up on a typical Thursday. What is your day like? What are you spending your time doing today?

on an average day, divorced from anything out of the ordinary, and is that what you want to be doing? And I found that so freeing in terms of how I'd been thinking about it, where I was really concerned with wanting to find a career that would be a good match for me and that wanting to, I guess, reassure myself that I'd be able to be successful in a particular chosen career.

And to really put that aside and just focus on, wow, how do I want to spend my time? That was a very different way of looking at it for me at the time and really helped me recognize that what I love to do is sit around and try and think about how the mind works and how people work.

Do you know the show on Apple TV, Severance? I don't. This is this show about this idea that people get this surgical procedure that allows them to not experience going to work. So you're sort of...

You're out of work self that's you. And then there's this other self that is the self that only knows life in the office. And it sort of follows the lives of these other selves. And one of my lab staff, we had all been watching the show. And I remember my team asked me like, well, would I want to do that? Would I want to not have to experience work?

And what would I do? And I thought about it and I said, you know, if I did that, my out of work self would probably just sit around trying to think of ways to study the brain. So it wouldn't be a good move for me. And this piece of advice, just focusing on an average day is really what helped me see that.

Well, I absolutely love this advice because I think you're right. You will spend most of your time just on these typical days. So sort of envisioning what is the best fit for you, not thinking about the highs and the lows that only happen occasionally. So wonderful advice to share with our listeners. Is there any other last note of advice or inspiration, Michael, that you would like to end our conversation with today?

Something I've been wrestling with a lot and something that I think has been shifting, particularly among individuals starting to come into the field, is whether we view or should view a career in science as a job or as a calling.

I have come to appreciate that many people at the early stages of their careers, there's a lot of resistance to this idea of referring to a career as a calling.

that that is almost a cover for justifying the exploitation of workers. I've read about this a lot in the context of medicine. A lot of my family is in the field of medicine and doctors and physicians have long viewed their work as a calling of sorts, but it also can come with really grueling

hours that are required to sort of care for patients. And there's been some real generational pushback that those demands are not reasonable and they're not fair.

and how to think about that. And I guess what I would say is I do believe that, well, as we began this conversation, I have aspects of my life that are really important to me that are outside of science. I think it's absolutely possible to strike that balance. I also think that the rewards of a career in science do in some way depend upon feeling like it is a calling of sorts.

that there's almost nothing else you could do. I remember when I was in high school taking summer classes at Berklee College of Music in Boston as a piano student. And one of my instructors was talking about going into a music career and said, don't do it unless you have to. And what

And what he was articulating is that there's so much difficulty in that career path. And I think this is true for science as well. There's a lot of difficulty, a lot of rejection, a lot of things that don't work out, a lot of rough days that if you don't just really love it and experience it as a real source of meaning that the other rewards that come with the job may not really be worth it.

So I don't think we should talk about careers as a calling, as a cover story to justify ridiculous long hours or extreme hardship. But I also think that if you don't find yourself really wanting to spend those really long hours, that you don't experience those long hours for the most part as a source of joy more than frustration, that a career in science might not be the right fit.

Definitely. I think trying to find that alignment with what you're most passionate about and what you can spend the most time of your everyday doing, I think is really valuable. And for people to really take that time to reflect on not just what people expect them to do or what they have this idea of what they should do.

But what they want to do and how they want to be spending your time, I think that's tremendously helpful. No, I agree. Very well said. Well, thank you so much for sharing this advice with listeners. And we really appreciate you sharing all of your insights with us today. If our listeners would like to learn more, Michael, what is the best way for them to do so? First of all, thank you. This has been a really fun conversation for me, and I've really appreciated your questions.

You can go to our website. It's www.treadlab.org. You can find me on the Emory Psychology website. It's pretty easy, but it's helpful to have my email address here. It's just first initial last name, mtreadway at emory.edu. Perfect. Well, listeners, definitely take the time to check out Michael's website.

And Michael, thank you again so much for spending your time with us today. Thank you so much. It was a pleasure. It was wonderful to chat with you and listeners. Great to have you here with us as well. We hope you join us again next time for another episode of People Behind the Science.