#41 - Dr. Lars Schwabe - Stress, Memory, and Behavioral Flexibility

[MUSIC PLAYING] Hello, and welcome. I'm Dr. Christina Spalding. And this is the Research Bites podcast, brought to you by Science Matters Academy of Animal Behavior. We foster conversations about science and its application to animal training and behavior in an effort to improve well-being for animals and the people they live with. Please enjoy geeking out about the science of behavior. [MUSIC PLAYING] My guest today is Dr. Lars Schwabe. He is professor of cognitive psychology at the University of Hamburg and head of their cognitive psychology lab. He earned his PhD at the Institute for Psychobiology at the University of Trier in 2008 and completed postdoctoral training at Ruler University, Bohum, and at McGill University's Center for Studies on Aging and Montreal. Dr. Schwabe's research examines the impact of stress on cognitive processes, mechanisms of learning and memory, and decision making and action. His research has been supported by numerous competitive grants and has significantly advanced our understanding of how stress impacts learning and memory. He was named a rising star by the Association for Psychological Science and received the Young Investigator Award from the European Brain and Behavior Society. In addition to his research, Dr. Schwabe serves as associate editor for frontiers and behavioral neuroscience and has guest-edited special issues for biological psychiatry as well as neuroscience and bio-behavioral reviews. I am thrilled to welcome Dr. Schwabe to the Research Bites podcast. - Hi, Lars. Thank you so much for joining me today. - Yeah, I'm Christina, nice to meet you. - I'm really looking forward to this. I want to start by, before we get into the details of what you're working on, I just want to start by thanking you for the work that you do because you do a lot of work on stress and memory and this has actually been very, very helpful in the work that we do with dogs and helping us to understand how to change behavior because I actually think in certain contexts, a lot of the behavior that we see with dogs is related to habit for one thing. And so understanding how habit works, which we'll get into today, has helped us understand how we can change some of these behaviors that we're seeing that often are very resistant to behavior change. So I don't know if you knew that, but your work has been very. - Hi, thanks. No, it's good to you. I think I didn't know before, but yeah, it's great to hear. - So as I said, you do a lot of work on memory and stress. So can you just talk a little bit about how you came to this subject and why you study it? - Yeah, well, to be honest, I came into that topic quite by chance when I was looking for PhD positions 20 years ago and that there was one professor who offered the project on stress and memory. And I was right away pretty fascinated by this topic and I am still fascinated by this topic. I think it's extremely relevant. I think it's telling us a lot about how learning and memory works in general, but it has also important practical indications for, for example, understanding psychopathology for educational contexts. And I've just learned also for Doc Onus, which is also great. - Yeah, yeah, I agree. I think it is fascinating and has a lot of practical implications. Can you start by talking about what memory is, because I think people have it, like they think they know what memory is, but there's actually multiple different components to it and we're gonna be talking about those components today. So can you just explain the basics of how it works? - Yeah, so memories are actually built in stages. So that means we start with encoding. So learning new information, acquiring new information once you hear something, once you see something. But in order to make this last for longer time, it needs to be consolidated. So that's a second important stage after encoding, which then leads to a transfer from a short term or temporary store towards a longer term memory store. And once this size of consolidation has been completed, then we should be able to recall or retrieve the memory at later stages. So these are the three main stages encoding consolidation and retrieval. - Okay, and then there's also reconsolidation, right? - Exactly, I mean, that's a more debated topic, I would say. - Oh, okay. - So once we retrieve a consolidated memory, that this memory would re-enter a labial state, a fragile state, from which it needs to be stabilized and new. During a process called reconsolidation. And the really interesting thing is that it's assumed that during this transient reconsolidation window, memories would be modifiable. So susceptible to change. So that means that once we retrieve, we call a certain previous again, even if that happened years ago, we should be able to modify our memory for this event. And I think that's pretty fascinating. That has, of course, very important indications, also when you think about clinical situations, unwanted memories, highly stressful memories. So that's a very interesting and important topic, I would say. We and also some other colleagues found some evidence suggesting that supporting the idea of a memory reconsolidation, but I do mention it well as well that there's also some evidence that is questioning the idea of a memory reconsolidation. So it's a question. Mainly, the key question of this debate is, whether you actually change the original memory, or whether you are just forming a new competing memory trace at the time of retrieval. Right. Okay, that makes sense. And for reconsolidation to happen, does that require like a verbal recall, or is this something you can see going on in like rodents as well, for example? Well, it has demonstrated in rodents and also in other species. So it's possible to reactivate the memory trace also via relatively subtle reminders used. So by just presenting, for example, the context in which a specific event has been encoded or some other cues that were associated with the original event. So it doesn't need to be a verbal reactivation. And then once you've recalled that memory, are we trying to sort of change the emotional response, for example, to change how it is reconsolidated? Yeah, exactly. So that would be the idea. I mean, there are different approaches to that. So I mean, initially many studies talked about, for example, pharmacologically interventions. Right. So we know, for example, to have this memory boost for emotionally-arousing events, you typically need an increase in activity of a neurotransmitter called Mordrandolin. And there are certain drugs that can interfere with the action of this neurotransmitter. And there are some evidence suggesting that if you administer those drugs after retrieval, so during the potential reconsolidation window, that might then reduce the emotionality or the emotional loss of that comes with a specific event, subsequent recall attempts. Yeah, really, really fascinating work. I've seen some of that going on. And it's super, super interesting, the implications of that. That is still, I think, very much at the experimental stages, not being used clinically. Yeah. Well, I mean, that happened first. It turns, for example, in drug addicts, or also in PDN's depotions. But I would say it's still preliminary data. So it's not really that we are at the stage that we could really do that in clinical centers, as it's done on treatment. So they are not that far yet. It may be coming in the future. So you talk about four different domains, where stress impacts memory. And it's actually quite complex. I remember I have a book that I wrote on stress in dogs. And I just, when I was working on the stress and memory section, it was just, it was a lot to try and sort through. But I think it seems like the thinking on this has maybe become a little bit more clear recently. So the first effect is how stress impacts memory formation or encoding. And we already know that highly emotional or stressful events tend to be remembered better. So can you talk about what happens when an animal is stressed during memory encoding? Yeah. So I think it's a very important to understand what's going on if an individual animal or human stress. And what happens is that several physiological response systems. get activated. So there is a very rapid immediate response within seconds that is mediated primarily via the autonomic or sympathetic nervous system. So this needs, for example, to the increase in heart rate or to the sweating that we all know from our own stress of situations. That's due to the release of adrenaline and no adrenaline from the adrenal medulla in response to stress. So that happens really within seconds. And in addition, there is a parallel slower response and an endocrine or hormonal response that's immediate by the, that's a complicated turn, but by the happy telomers, the tributary adrenal axis. So that's an axis that needs in the end to the release of a glucocorticoid such as cortisol and human. So cortisol people might have heard about that before. So that's in hormone. And that's typically released only at peak levels at say 20 to 30 minutes after the onset of a stress-sol event. So relatively late. But the important thing about cortisol is that it can cross the blood brain barrier and act garity on the brain. And it acts primarily on regions such as the prefrontal cortex or areas of the media-temperal lobe, including the pecanpus and the mucthola. And these are exactly those brain regions where we know that these are highly relevant for learning, for memory, for decision-making. So for these higher orders, a couple of processes. And it's idea that through the action of these neurotransmitters and hormones, stress-free vents can impact the way we encode information. Right. And so we have this so that adrenaline or noradrenaline maybe causes this increased activation of the amygdala. Correct. Do I have that right? Well, that's also one important idea, exactly. Yep. And then the amygdala is, if I'm remembering back to my learning neuroscience from 10 years ago, the amygdala is the one that is responsible for that increased encoding of the emotional memories. Yeah, yeah, exactly. So the amygdala definitely plays a critical role. And it's the idea that there's indeed an increased amygdala activity and situation in highly stressful situations. And that's also driven by noradrenaline and glucocorticoid, such as cortisol, appear to amplify this noradrenaline effect. And then the amygdala would modulate memory storage processes in other brain regions, such as the pecanpus. So it's idea that the amygdala is not the storage site itself, but it's modulating memory processes in other regions. So it's telling, for example, that pecanpus, hey, this is important. You should better store that photo future. Right. Because the amygdala is also important for salience. So yeah, yeah, we'll be lagging at that. That makes sense. So when we're talking about this stress enhancement of memory, does that apply to all types of memory or only like episodic memory, for example? Yeah, that's a very good question. So it's actually fairly complex. I have to admit. So, brain, it's typically assumed that episodic memories are indeed enhanced. So that you have better episodic memory for what was happening during your stress or event. But even this is not a global enhancement. So it's not that everything that you encoded under stress is later better remembered. But it seems that really the key elements, the central features of these of this stressful episode, this is what is later better remembered. But other aspects of the stress encounter such as contextual background, some other things that we're going on, but they were normal in the focus of attention that there's actually reduced memory for for these what we call peripheral types of information. I think that's also important to know that it's also balancing, right? So it's a prioritization of the most relevant aspects of a situation. So that's when it comes to episodic memory. And we know that other forms of memory as we might discuss later on is that impaired also by stress such as memory, pre-veil or working memory processes. That is typically impaired by stressful events. Yeah, and there are also other aspects of learning memory that are enhanced by stress. For example, cue dependent learning and memory processes. So associating for example, a threat exposure to threat with specific stimulus that's typically enhanced under stress. Or also as we might discuss later on also, a habit formation is assumed to be enhanced most of us. Yes, and we will definitely get to those things because I think those are very, very relevant for what we do when we're working on dog behavior and other species too when it comes to fear and things like that. And I should have done this first, but so episodic memory because not everyone knows what episodic memory is. Episodic memory is sort of this autobiographical type memory that we have sort of the what, why, where, etc. And then working memory, you can probably define this better than I can. Can you just clarify what working memory is? So memory is what is in laterums often referred to as it's called short term memory. So that means maintaining certain information for a relatively short period of time. But as the name working memory suggests, it's not just about some passive maintenance, but it's also doing something with this maintained information. So one good example is mental arithmetic. Or if you cook something and you've read something in the recipe book and then you go to your part and you try to implement things. And so you have to combine information. So that's what working memory is doing and what it's for. So it's extremely important. Right. And it's also important for the audience to understand that it's this is something that does come into play in non-humans too. And so as I understand it, you know, something like remembering a queue. Absolutely. Might be an example of working memory and staying focused on if, you know, if you're cute, do you do something that maybe has multiple steps that you can stay focused on that as you're going through these different activities. And there's distractions happening around you. Absolutely. Yeah. Why don't we go to context memory nags that you talked about this a little bit already in terms of the difference between the remembering cues and context. But one of the things that we think is happening in PTSD is that fear becomes overgeneralized. And this is related to how stress affects context memory. So can you can you talk a little bit more about that distinction between context and cue and then how that's impacted by stress. Yeah. Absolutely. So it's another very important distinction. So let's imagine the very following scenario, you are walking your dog somewhere and let's say in a park and then out of the sudden you or a dog is attacked by another dog. And then you could learn different things. You could associate the threat of this other aggressive dog with the context. So the park that you are in and that would be an example of context memory. So you are associating specific stimuli in your environment with a specific experience from relational or we call relational maps. So associations that we multiply to you or you could just associate that threatening encounter with a specific stimulus. For example, the look of the specific dog or the barking that you heard before or things like that. And the letter if you associate a specific experience, just the single stimuli, that's what we call two dependent learning or two dependent threat learning. Whereas if you associated it with the multiple stimuli in the environment, then this is referred to as contextual memory or contextual learning. And what we and all of our others also different species could show is that under stress and when stress hormone levels are high typically this contextual learning is impaired and and two dependent learning and memory is enhanced. So it's this balance of contextual and two dependent learning as altered in favor of the two dependent learning under stress. And that might be indeed highly relevant in the context of PTSD because people show that these extreme emotional responses out of context. So also in context that are actually safe because the memory is not bound to the context any longer, but they show it in multiple contexts. They generalize as you mentioned. They just respond to specific cues that were associated with traumatic events such as certain orders or tones or even certain words. And that is really a very prominent example of the strength of a cue dependent learning or is we sometimes say stimulus response learning and the stress. Right. And again, something, I mean, I love that you use the dog example, right? Because this is something we talk a lot about in the animal training world is that they have this context learning and that idea that it under stress that that context learning isn't quite working as well. I don't know if that's necessarily how we would put it because there's an adaptive value to it, right? So we say it's not working. But there's actually a function to that as well. Yeah, yeah, I'm some G and I think that's also a very important aspect, because I mean, we assume that how our brain responds to stressful events, that this is in general highly adaptive. It has developed over hundreds or thousands of years, and that's really important for coping with those situations. And if you think about stressful, potentially life-threatening situations, it's really essential to prioritize the most say and the most relevant information. And then if it's about those life-strutting events, we are better safe than sorry, right? So it's better to really make sure that you are appropriately responding to the potentially threatening stimuli, than thinking too long about whether it might be relevant or not. And if there's a, you know, for a tact by a dog, and the thing that you learn the most is the park, but then you encounter that dog somewhere else, you're not going to have, you know, the same response, and that might be end up being very important if you don't respond appropriately to a threat. Okay. So I've been trying to figure out, so there's a difference between the, I mean, as you know, but there's a difference between the acute stress response and chronic stress. So how much do we understand about differences between the effects of acute and chronic stress on memory? Because once again, for the listeners, once an animal is under chronic stress, things change a lot. And sometimes they have ironically elevated levels of glucocorticoids, but sometimes they actually don't. And if those glucocorticoids are part of what's having these memory influences, for me, it gets very hard to predict or understand what chronic stress might be doing to memory. Yeah. So, I mean, at least in humans there is significantly more research on the effects of acute stress. And that's just for the simple reason that you can induce acute stress in the lab. And that's for obvious ethical reasons, not possible chronic stress. You can only do some correlations asking people questionnaires how stressed they felt over a couple of months, period of a couple of months, but it's not possible to induce that experimentally. However, in animals, there is actually also research where, for example, rats or mice were exposed to the virus repeatedly and for a prolonged period of time. So we know a little bit about the effects of chronic stress. And the pretty clear picture is that chronic stress is detrimental for memory. So that's pretty well established. So you can show that after periods of prolonged and intensive stress, there's decreased in brain volume, so a gray meta volume in regions that are really key for learning and memory, also for what's we call inhibitory control, so being able to inhibit certain responses. So what might be also important. And there's also some evidence in humans, again, not experimental, but what was done, for example, is that some colleagues tested students, university students, that are preparing for medical exams. So it's also a very stressful period. The students were tested during this high-d stress for extended stress period and also afterwards. And they could also show that even in these rats students, there's decreased volume in regions such as pre-photocortex. But the really good news is that once those periods of extended stress were over, there was also recovery. So that there was again certain increase in brain volume in these regions. Without assuming that something very similar is happening in dogs and in other animals as well. So it's a behaviorally, it's really a detrimental effect. I think I would say and watch the all-connative processes, but the good thing is that it's apparently really simple. Is that true in just an adult, though, what about developmental chronic stress and memory? That has longer lasted for X-CRA. I mean, yeah, we know that there are certain periods of brain development that are particularly critical. So we've referred to them also as critical periods. For example, during childhood or activity, these are critical periods. And if you experience intense, stressful events or also extended stress during those periods, it has particularly detrimental effect. So that's also really well documented effects of, for example, childhood adversity and so forth. So that is unfortunately very long-lasting negative consequences. It does not mean that we can't do anything. So I mean, there might be certain therapeutic interventions that might prove the situation, but it's difficult for sure. So you're right, it might depend also on the period of brain development. And I think we've already talked about this a little bit because it all, you know, it's all related. So the impacts on retrieval, I mean, I think we really have talked about this, but just if there's anything you want to add, let me know. So stress and retrieval, it has, if I understand it quickly, there's a negative impact on aspects of that memory that may not be directly related to the sort traumatic or stressful thing that happened, but you're more likely to recall things that were directly related or at least the brain thought were directly related. Yeah, I mean, it's generally assumed and also repeated, it has been repeatedly shown that acute stress, impairs, memory retrieval, our ability to recall certain past events. And typically also those events that are not directly related to the ongoing stress. So that has been repeatedly shown. And it's of course also highly relevant, for example, in exam situations, it might explain the blackouts of some students are experienced from time to time. So it's also the relevant fact. And the other aspect that they mentioned. So to what extent there's actually increased memory or at least unimpaired memory for those aspects that are key to the stressor, that's also something that I would say it's research is still ongoing. So we are also planning some research on this because it has not been really systematic to study. So the classical study is really that you expose people to a certain stressor and then you test memory for certain pictures or words that people have learned before. So really unrelated material, but also finding something that's really directly related to the stressor in an experimental setting is not that easy. But I think it's important to have really more fine-grained and maybe also in a more copiate view on how stress actually affects more retrieval processes. Yeah, because it's not any time we're talking about behaviors, they can just get very complicated very quickly. Okay, so this brings us to the part that I think is the most fascinating, which is the relationship between memory and stress and flexibility. And so I do think before we jump into that, we need to define a few things. So we're going to be talking about habit and goal-directed behavior. Can you define each of those for the listeners? Yeah, so these are two distinct modes of what we call instrumental learning. So instrumental learning is about learning how to act to achieve certain desirable outcomes or avoid unpleasant outcomes. And this might be another control of two different mechanisms or processes. One is go-directed learning, so go-directed learning means we are learning the causal association chip between a certain action and the specific outcome. Now, and that's typically another control of the pre-funded cortex. And in parallel, there might be a different process and that's a habitual process. And the habitual process learns association between a certain stimulus and a certain response. So it's more or less independent of the outcome that's following the response or the action, but it's just stimulus response. And this typically develops with practice. So the things that we've done a hundred times before, we don't reflect anymore what this is actually leading to, but we just do it in a certain situation in response to certain cues. And that's habitual learning. And both are there, both as highly relevant, I think it's important to keep the two in balance. Yeah. And so habitual learning is very because it's this really strong relationship between the stimulus and the response or as many animal transatlicals that the antecedent and the behavior. It becomes very, very tightly sort of connected to or controlled by the environmental cues. And therefore it's less flexible, right? So, and when we talk about it being less flexible, what we mean is that it's not as responsive to the outcome organ, we would call it the consequence. But and this is what, I mean, when I first learned about this, this kind of blew my mind is that the being behavior will continue in the absence of reinforcement, correct? Yeah, exactly. So that's the key element of it that it really becomes independent of the outcome of the reinforcement. And it's really automatic in a way. And this leads also then to the inflexibility, to the reduced flexibility, because you cannot adjust the behavior if the environment changes, but you're just doing what you've learned before. And this is the piece that we have found to be very helpful in our field, because you can take, like, so one example of a behavior that I think can become very habitual, I don't think it always is, but is barking and lunging on leash. You know, when you see dogs that are barking and lunging at other dogs or bicycles or something, I think there are aspects of that that can become habitual. And so if we remove the dog from their typical environment, if they have a typical place where they go to be walked and we can bring them to a novel environment, it seems like the behavior becomes more flexible and more responsive to training. And I suspect that's because it's habitual. Yeah, I mean, that might well be the case, that there's the association between that specific context and the response pattern, the barking, etc. So that might well be that there is a strong connection between them. And then goal-directed behavior, on the other hand, is much more flexible. So when I first started talking about goal-directed behavior, I got the question a lot about whether or not animals can actually have goals. But we, I mean, we do see what we call goal-directed behavior in non-human animals, correct? Yes. If you've ever thought, I really want to stay current on the science, but I just don't have the time to dig through journals, I get it. That's exactly why I created research bites. Each month, I host a live webinar where I break down a recent research paper, what the authors actually did, what they found, and how to interpret it. There's time for questions and discussion, and if you can't attend live, the full session is recorded. In addition, we meet for separate informal coffee-break conversations focused entirely on translating research into real world practice. If you want to stay connected to the science without feeling overwhelmed or like you're doing it all alone, research bites is there for you. You can learn more at www.sciencematterslc.com or click the link in the show notes. Use the code R-B podcast for 50% off your first month. I'd love to have you join us. It's also a question of how you define the directed behavior. This context is defined as behavior that is sensitive to the motivational value of a certain outcome or reinforcer. If the animal changes its behavior, depending on whether it wants a certain outcome or doesn't want this outcome. This has been really nicely demonstrated and pretty sure that words and dogs. I'm fully convinced that they do show that distinction between those two different kinds of behaviors. Before we get into stress, I have one question that I think I know the answer to, but I would like to confirm. When we're talking about habitual behavior, it's not completely immune to extinction. Is it? It'll eventually, does it? If the behavior continues in the absence of reinforcement indefinitely, do we eventually see a decrease in the strength of that behavior even if it's habitual? I would agree that one would expect such a pattern. From a theoretical perspective, it's not that difficult because there's operational definition of goal directed or habitual responding doesn't really say something about resistance to extinction. But still in practical terms, if we would run this experiment, I would also assume that then at some point the behavior reduced to some degree. Again, so what we refer to as extinction, extinction. The critical aspect is really the sensitivity to, for example, outcome devaluation. One would need to repeatedly test the sensitivity of behavior to outcome devaluation and then see to what extent it's still there or not. I think a critical aspect might be also whether the behavior has been shown repeatedly in between or not. For example, this dog and parg example, if you manage repeatedly that the dog does not charge this inappropriate behavior in the park, then it might be really established and it might be really routine and then it maybe does not require the return of reinforcement or so just because you have then this strong association between the new behavior and the context again, right? So that will be then a favorable habit. Right. I mean, my experience to write is that it's not like there's goal directed, I mean, people can't see what I'm doing in the recording, but it's not like on one end we have goal directed behavior, and then there's habit and those are two completely separate categories. I mean, we're going to see overlap in the middle where it has some elements of both. Yeah. I mean, classically, there was really a pretty clear cut distinction, but more recent research shows that it's not that distinct and that there might be also so in between states that's coded like that. So that it's more a continuum. That makes sense. The one other thing that I just wanted to clarify for people is that habit and goal directed learning. I mean, this is not just a semantic distinction because they actually occur in different brain areas, correct? Yeah, absolutely. So the goal directed learning behavior is mainly dependent on the pre-phonic cortex, whereas the habit should be able to realize more on what we call the basic ganglia. So the triaten, so the fairly deep and evolutionary old brain area. So you can also really nicely see that if behavior is more and more frequently shown and more often repeated, that you can see really how the memory trays in the basic ganglia are built up. That's so cool. That's really awesome. And for me, you know, one of the great values of neuroscience, I think, is that it really, it can really help us differentiate between behaviors that can be a lot harder to distinguish between by just observing the behavior. So when I see that, okay, there's different brain areas that are involved in these different behaviors, and that's really important information to me that they are actually different behaviors, and that they probably, from a behavior modification standpoint, we may need to address them differently because different parts of the brain are in. Yeah, yeah, absolutely. And we need also then really sophisticated tasks showing that these are actually different behaviors because also if we talk about goal directed and abitual behavior, if you just look at what, for example, a participant or a dog or a rat is doing in a certain task, the behavior might look quite the same. And it's very difficult to distinguish, but only by changing then the contingencies or the environmental conditions, you see that it's actually a different mode of, so that's indeed fascinating. And I agree that also, for example, brain imaging or other techniques might help here or can help, definitely help. That's really show that there are different processes going on. Okay, so now we can get back to stress and memory flexibility. And I spent a lot of time in my work talking about resilience and the fact that flexibility is an important component of resilience because if animals cannot flexibly respond to change or stress, it's then harder for them to cope with stress. But at the same time, stress can reduce flexibility in a number of ways. What happens to memory flexibility when animals experience acute stress? And if you can also talk a little bit about what exactly is memory flexibility because I don't know if people are going to have a clear idea of what that means. Yeah, that's what I mean. There are different different views on that. So one perspective is that there is actually not just one single memory system, but there are multiple memory systems at a different neural basis and that work based on different operational characteristics, as we say. So we talked about some of them already. So for example, contextual versus Q dependent or gold directed versus epitual. So you have some forms of a memory that require some relational processing, some linking of a different element and some cognitive reflection. So some also, yeah, consciousness or awareness that then allows you also to adjust the behavior once the environment changes in certain environmental conditions change. And this ability to flexibly adjust your behavior or responses. That's I think an essential element of memory flexibility, whereas these other more rigid processes, these are really repeating the routines that you've done a thousand times before, where it's just some automatically responding to certain cues, and this is then lacking the flexibility, because you show that in all contacts in all situations. That's the distinction, and as we discussed before, there are also different neural substrates. The neural substrates are the newer basis of memory flexibility, or more broadly, behavioral flexibility, is to a large extent to prefront cortex, and we know that the prefront cortex is highly sensitive to stress hormones, to neural transmitters that are released in times of stress, and this is I think a main mechanism by which stress, stress events may interfere with a behavioral and harmonic flexibility. I find this whole thing so fascinating, because when we're looking at mental health disorders and people, and as well as when we're looking at behavioral issues in dogs, which sometimes is defined by the dogs welfare, and sometimes by the humans not liking what the dog is doing, but when we see, so if we focus, I would say, on the decreased welfare of the dog, when they have something going on that is decreasing their welfare, so it's sort of an equivalent to a mental health disorder in humans. I very much, you feel like they get stuck, and they're responding. They seem to be almost in some cases responding in sort of isolation to everything else that is going on around them. It isn't appear they're necessarily processing everything. That really fits with what your saying, the research says about this relational processing and the ability to connect things together, and then and you've also talked about in your work about decreased integration of information, and also the decreased ability to sort of update or incorporate new information. That to me seems like that must be very connected to mental health disorders and things like PTSD or other mental health disorders, where you have someone who may have an experience that's not as negative as they thought it would be, and yet that doesn't seem to be updated. Am I on the right track at all here? Yeah, absolutely agree. Memory-reduced flexibility on the stress is indeed reflected in a reduced updating capacity and a reduced integration of different events and memories, also in reduced ability to update knowledge, and this is exactly what we see, for example, in patients suffering from major depression, or also anxiety disorders. Absolutely, that's also what these patients report. That's what we see in clinical studies and which are tasks with those patient populations. So absolutely, you can see that, and you can also see that once there's an improved and clinical symptoms, if there's some treatment to success, that you see also an improvement in exactly those processes and the flexibility of thinking and harmonic flexibility, so that seems to be a high due element in those contacts. And I mean, so of course, we can't talk to dogs, not directly, but also what you are describing the observations, seems to suggest that they are very similar processes and mechanisms going on in dogs. And I can well imagine that these highly relevant to you as well. I mean, certainly from our experience, say, our, you know, me and other professionals I've talked to, this does seem to be a big component. And so if we think about that, is it possible to create a buffering effect by, you know, if we can, if an individual has higher cognitive flexibility to begin with, does that tend to buffer them against later stress? Yeah. I mean, one will talk so I mean, definitely there are individual differences. You are referring to resilience before and we knew that there are some individuals that are highly resilient, so even to fairly extreme stressors as others are obviously not. And there are many, many components. So of course, genetics, pays a role, certain developmental experiences, then of course, a general level of cognitive functioning. It's called like that, is a relevant factor. We did actually fairly recently one study where we tried to test whether some sort of cognitive training can also buffer detrimental effects of stress on certain cognitive functions. So what we did is, we tested people's working memory capacity at baseline. And then we gave them, I think it was a six or even eight week training, daily training. So it was an up based training that was really directed at strengthening working memory related cognitive functions. And then after that, a training period we exposed them either to stress or a control manipulation and tested the working memory performance. And we saw that those that had received the extended cognitive training indeed showed somewhat reduced stress related impairments in working that. So it seems that some sort of training might be helpful here. And I mean, it doesn't need to be this lab based fairly artificial training, but it's just mental activities, right? So being mentally active, doing tasks and that this might be something productive. Yeah, I have a hypothesis that the amount of sort of control that we exert over dogs lives and the amount of decisions that we make for them and the limitations on exploration and things like that. My hypothesis, I mean, it hasn't been tested. If you ever want to test, you know, test this on dogs, but my hypothesis is that because we limit their ability to interact and explore and make decisions on their own, I think that probably makes them less resilient to stress in the long run. And so there are a group of trainers and behavior consultants that are trying to encourage people. It doesn't mean they don't have any rules, right? But just to do things like let them smell things as long as they want to and let them check out things that spook them until they can satisfy themselves that it's not actually dangerous. I mean, what you're saying reminds me of a phenomenon that's called learned helplessness. So that's an extremely influential phenomenon that was actually also for the first time demonstrated the dogs. Right. And that's a phenomenon that briefly summarized. It's an idea that you first have a certain experience. It might be an aversive experience, but also an a more neutral one. And the critical manipulation here is whether you learn that you can control certain outcomes or whether you cannot. And those who cannot, then in a subsequent situation where all individuals, all dogs can actually control the situation and do something to reduce, for example, aversive stimulation or so, that those who have experienced before that their behavior has no influence on the environment, no influence on the outcomes that they were affected at several levels at the effective level. So they had increased negative affect at the cognitive level. So they were less able to learn that they can now actually change the situation and also motivational. So they even tried less to really avoid negative outcomes and so forth, due to this initial situation where they learned that they can't do anything about what's happening to them. And this is more as what you are describing. So yeah, it's an interesting phenomenon. Again, the highly relevant, also in clinical context that has been discussed. It's an highly influential factor in the context of depression, anxiety disorders. We know there's a more nuanced debate and perspective on that now, but I think it's a highly relevant phenomenon. Yeah, absolutely fascinating information. And I think it's for people who aren't in this field and thinking really deeply about this, they probably don't necessarily think about memory as being so important for kind of like emotional health, but it's really critical for that. So it's about learning that you can control what's happening to you. So it might be really relevant, emotionally relevant outcomes, but even the neutral ones. I mean, there are also some studies in healthy participants, which just about solving underground tasks, yeah, so fairly neutral tasks, but even if you go give people a certain unsolved underground task, so where they do not experience any control of the outcome, then you can show later that they've impairments in other unrelated cognitive tasks. So it's really the experience of control that matters. Yeah, it's really important. So despite this increasingly detailed understanding of the influence of stress on memory and the link to PTSD and other mental health conditions, it's been difficult to translate that information into clinical applications, particularly I think medications. Can you talk a little bit? about why that might be? Yeah, I mean, it's a tough question, but a very important one. And I think there are many answers to that. So I mean, one part of it might be that in a lab, we tend to use fairly artificial tasks. I mean, that's also for good reasons because we want to control many variables. Right. And we want to have it as clean as possible. But obviously in everyday life, you rarely find such conditions. So it's about the marching of the lab tasks and the real life situation. I think that's one aspect. And another only important one is that typically in lab studies, we look at group level differences. And much of what might be really relevant might be really at the individual level and at the individual differences. So coming again back to resilience and a certain vulnerability factor factors, these might be really, really important and to really have a better understanding of such vulnerability or resilience factors, you have to study a large number of people. I typically larger sample sizes than we typically do. And in many of our lab based studies, but I think if you do that and then look into individual differences, then you get in question of what might be going on here and that it's not that tear cut that stress does A or stress does B, but that it might also really depend on the individual. And I think a better understanding of these individual differences might be also really important. Yeah. That makes sense. And that takes a really long time to get right because we have to do so many studies to figure out what the different factors are. I mean, unless we get really lucky in the beginning, but we're trying to figure out and you test it. And see the results that you were looking for. And yeah, that's a really hard thing to figure out. Okay. So the last question is, I always love this question. What unanswered questions are at the top of your mind right now and what do you think research should focus on? Yeah. I mean, it directly relates to what we just had this past before. So I think looking into individual differences is important. And I mean, I've now been working in this field of stress and vulnerability for more than 15 years, it was years. And I mean, I'm still very fascinated about it, but also looking a bit deeper into the clinical relevance and what we can do to modulate these processes in order to help patients or to help people in educational settings. I mean, that's definitely something that I'd be interested in. And we are just currently planning our first studies, really in patient populations. So that would be also very important and exciting new step, I think. But then on the other hand, also the better mechanistic understanding. Because I mean, for those who hear about that for the first time, they might think, wow, there's so much going on and they know so much. But actually for someone working in the field of empathy, it's not so difficult. So I mean, if you would ask me, what are the detailed brain mechanisms? How stress connects with this effect would say, well, I have a rough idea, but really no detailed understanding. And this requires also this translation across levels, right? So from really very Bay Molecular cellular work in animals, the behavioral cognitive neuroscience studies, and then also of course the clinical studies. And this translation across levels is extremely difficult, but also extremely important. Yeah, yeah, I agree. I tell people that one of the most important things that I learned in graduate school was how little I know, how much we still have to learn. Absolutely. Well, thank you very much. I really appreciate you taking the time to come talk about your work, which is really influential and fascinating. So thank you so much. Thank you. If you enjoy these conversations and want to stay connected between episodes, I'd love to invite you to join my mailing list. 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