Neuroscientist Explains How Your Brain Is Affected by Fear, Isolation & Anxiety | Moriel Zelikowsky

Hey everybody, welcome to another episode of Impact Theory. I'm here with Dr. Moriel Zelikovski. Thank you so much for joining me. I'm super excited. Um, I'm all about neuroscience, so this should be a lot of fun. Great to be here. If you can just give people a quick rundown on your background and what you do, just like a a super quick nutshell. Sure. I'm an assistant professor of neurobiology at the University of Utah and I work on neural circuits involved in emotion. Lately, you've been work doing a lot of work on social isolation. Yeah, social isolation right about now is a pretty hot topic. What drew you to um the science of emotion to begin with? Um I've always kind of been interested more in clinically relevant type of topics and so you know nothing's really more clinically relevant than emotion. So, um, and what do you mean define clinically relevant for me? Um, I think these would be kind of topics of research where maybe what you investigate would eventually lead to a cure for something or treatment or things like that um, in regards to how the human brain works kind of on an everyday scale. And do you have anything specific that you're really drawn to or just sort of, hey, let me dive into the world of emotion and see where this goes? Yeah. So, I mean, I started out looking at fear and memory, which I I mean, I love the field of memory. I thought it's super interesting. Um, for instance, when something really traumatic happens, how you store that memory across your whole lifespan and how it affects the way you encode new memories and interact with other members of your species and things like that. So um I find that found it really interesting both from a scientific perspective and understanding the neural circuits that underly that but also uh just from you know understanding human beings better and why we do what we do and how we remember the things that happened to us. So yeah memory and forgetting is something that is extraordinarily interesting. So my wife will often joke with me that she wishes that she has my memory because I'm ultra forgetful in terms of emotional amplitude. So if something like really upset me, I'll still forget about it a day later or a week later. So I don't have baggage from my past. I don't hold on to past traumas, but it actually really frustrates me because I also don't remember a lot of things that I want to remember. So I've I've always looked at it as a curse. And she's always not always, but certainly as we got deeper into our marriage, she's really like, "Oh man, like how how does that not wind you up? how are you not still pissed about that? And I'm like, that seems so weird to me. But I know that memories get basically tagged for either, hey, this is important, remember this, or you know, this is irrelevant, forget it. Um, so how how does that dynamic of like stress I feel find that super interesting only because I feel like with most people when they have an emotionally charged event, it's kind of seared into their memory in the first place. And then the more times you retrieve it, the more and more you're kind of solidifying that memory in your brain. So usually people remember these kinds of poignant emotionally charged memories for a long period of time. Whether they do so like perfectly accurately is another issue. But um it's usually kind of the more trivial things that people don't remember. So I find that really interesting about you. And what's your primary area of focus right now? Um are you working with rats a lot? Like what's your Nice. Yeah. So I think I would say for like experimental neuroscience, neurobiology, I don't know, maybe like 80% of the work is done in mice. Um, for a number of reasons. They're just like, you know, great model organism. Um, and they have they're genetically tractable, meaning you can actually, you know, breed them and look at certain genes and look at certain cell types and do kind of all the fancy stuff that we do nowadays in neuroscience. and the applicability to the human condition and brain is very very high. So, [snorts] and the tests that you're running now, are they are they around fear or what are you working on right now that you're super excited about? Yeah. Yeah. So, right now our lab is working on we have a few projects in the lab um and kind of most of them are circulating around this um idea of social isolation and what happens to the brain and behavior when an animal's isolated for an extended period of time. Um and so we have a lot of kind of different projects looking at that. And so the most let's see most exciting one recently that um is going on in my lab is someone who's looking at the effects of isolation on mating behavior. Um which is kind of a little bit more I would say maybe more fringe in terms of interest to the general public. Um but I think it's super interesting because he's also um able to record mouse song. So it turns out mice will sing as a form of courtship to kind of get the female, you know, a male mouse will sing to kind of get the female interested in it. And so if the animals are isolated, it turns out that both the mating behavior is disrupted and also this song is disrupted. And so we're doing some pretty interesting experiments. Are are they singing when they're alone, like trying to attract, or when you put them back together now, they can't sing properly? Male mice will sing to a female mouse um as it's trying to court her. And it's it's not not anything that any of us could hear with our naked ear. You need very special kind of ultrasonic vocalization equipment to be able to hear this song and to also analyze these very complex um you know bands of frequency and song bursts and things like that that um people have been doing in birds for years and years. And so now they're kind of starting to do it in mice and it's super interesting. So, is it is the song breaking down because they're essentially getting depressed? Is it because they're just out of practice? Like, what's what's going on? That's a really good question. That's something we're working on. We have no idea why the song is being altered. Though, it does, I think, help to explain why they're not as successful mating. I was going to say, is it, I'm assuming, less attractive that women are less likely to respond to it? Yeah. It's kind of like, you know, if you're at a bar when we used to go to bars [laughter] and a guy's like, "Hey, you want to go on a date?" versus like, hey, you want to go on a date? It's who would you go out with? The one whose, you know, frequency range is like really short and doesn't really have anything interesting going on, or the one that's able to kind of put some more spice in their song or approach. So, yeah. [laughter] Now, it it becomes really easy to understand why humans put so much energy into um or why isolation is so problematic is a better way to say it because we're such a social animal. Are mice highly social? Yes, mice are very very social. Um, and we work on mating, but I also work on this has kind of been more of the bigger area of my research. Um, violence is a big big thing that happens after social isolation. Um, so interesting. Yeah. When so they they when you bring them back together, they just want to [ __ ] [ __ ] up. Yeah. They're extremely violent. And actually, it's like one of the best models for looking at violence, which is what I was originally interested in. So if you isolate almost almost any species you look at if you isolate them they will be more violent when you introduce them back with another member of their species. That's weird. So what was it um what was the fascination around violence that led you to that? Just the thought of humans can be violent and let me figure out why. It was that and it was kind of at the time where all these you know school shootings and things were really picking up. Um and you know not just school shootings but all kinds of uh kind of violent behavior. it was really not not being looked at so much at a neurobiological perspective. So I was super interested in why you know how people can become really really violent and then when you start looking into the past of those kinds of people who you know are shooters and things there's either a history of mental health or social isolation or something like that. So um all right well break it down for me in terms of the neuroscience. So, what's going on at a neurochemistry level or a wiring level as as you isolate and obviously we're extrapolating from mice into humans, but as we um we're living through a period of such unimaginable isolation, like this seems like a pretty important um question to get to the bottom of because already we're seeing, you know, pockets of violent outbursts. Yeah. Um and is this going to escalate would be a pretty reasonable um question to ask. So, what happens during isolation? Yeah. Well, I was going to say one thing to add is during is after isolation, animals are way more violent, but there's a host of other things that happen, too. For instance, they're extremely um persistent in their fear responses. So, normally you might be afraid if you hear a car backfiring or the sound of a car honking, you might be afraid for a second. But if you've been isolated, that kind of persists be beyond the kind of normal window for you to be afraid. So you have this enhanced fear persistence, this enhanced aggression, and then you have abnormalities really interacting with other members of your species. So um if you're kind of given access to a another friend mouse or a new mouse, you're not going to really spend that much time with it. Um or for humans, you might not really be that interested in interacting with a novel member of your species. Um and kind of show more hesitation there. So that's those are some of the behavioral that part. I get I get why the novel um person would become more worrisome. You're you know going back to the mating thing. You're sort of out of practice. Maybe you've lost your groove a bit. Um but when I think about in reintroducing somebody that you knew already and you still don't go spend as much time with them, do you know like are we seeing just the the um receptors for oxytocin are disappearing off the cells? Like why? Yeah, that's a great question. [laughter] So I think yeah I think you know there's some stuff that we know and then there's a lot that we don't know. One thing that we know for sure is that this one neuropeptide that I've worked on called tachikinan 2 is heavily upregulated across many regions of the brain following social and so tact 2 what give me give me some info what does it do it's kind of like a neuropeptide so you might lots of people know about neurom modulators like dopamine or serotonin these are all the ones that you know drugs for depression and anxiety disorders are all based on and these are just kind of like a smaller what you'd think of as a smaller class of those so and is it like oxytocin feels [ __ ] Awesome. Some people refer to it as the bonding hormone. Is it positive, negative? That's a good question. But it's again, it's one of these smaller neuropeptide systems. So, it doesn't have these kinds of like you can't just kind of generalize and say that it does X, you know, makes you happy, makes you sad. Um, so its expression is way more restricted than some of these other ones. So, um, the good news is if you find something that it does that's important or useful, that's great. And and the other set side of the good news is that you're not going to be doing something that kind of affects the whole brain if you want to target this system. So, you know, some of the other systems like for instance serotonin, you know, there's some great benefits. Obviously, people are using anti-depressants, you know, developed decades ago, um, targeting serotonin reuptake, but the downside is it's you're targeting it all over the brain. And you know serotonin has sometimes opposite effects depending on where you look. So um these neuropeptide systems are nice nice in the way in the sense that you can kind of target smaller populations of neurons and um system a system in the brain that's way less kind of uh how do I say ubiquitous. So yeah. So now did you say that tattoo is increased or decreased in isolation? So it's increased after isolation and it's kind of and what do we think the the point of that? What what's it pointing at? Yeah, that's a good point. So I I think you know there's a few ways of looking at it. One is that it's kind of acting in this kind of coordinated manner much like someone who leads an orchestra leads the whole orchestra by his, you know, um direction. And so you see it elevated in multiple regions. And you can kind of think of it like a web of increased activity that um allows the brain to coordinate a response to social isolation that includes many different things. So for instance the enhanced violence, the persistent fear, the alterations in mating, those kinds of things might be coordinated response and this is one of the way could be coordinated um which is just this elevation of this peptide across the brain. Okay. Well that's um maybe troubling. So, we have a conductor who's stepping in, but what he's conducting is antisocial behavior, uh, aggression, sort of, um, being antisocial. So, it's interesting. So, okay, you said there were a few things that we knew. So, one, we know tactu is elevated. The conductors in there, he's telling us to do things, but we also know that the behaviors that we're seeing on the outside, so if tact is conducting, it's conducting some gnarly stuff. Um, so we have Yeah. So I think that that's a really good point and I think it kind of ties back into the idea that this kind of social isolation where and I'm talking mostly about when you are fully isolated like no other single person, no partner, nothing. You're by yourself, you know, have been in your apartment and haven't seen anyone in 2 weeks at all. Um, and I think that is not a normal situation. Um, not for humans, not for mice, not for many species. So most of the time you're interacting with other members of your species and so you wouldn't have this kind of explosive response in your brain or in your behavior. So I think um you know these systems that are usually probably quite adaptive for regulating fear which is great in you know certain to a certain degree cuz it lets you survive and avoid dangerous things. Um and also probably being able to be aggressive and protect your territory if you're an animal protect your mate. that's, you know, something that's adaptive. And so it's really when these things are kind of go ary or out of control that it's not adaptive anymore. So it's not that the system was kind of maybe designed to do this in some kind of functionally, you know, beneficial way, but more it's more that the system that's usually adapted at low levels has kind of been hijacked in these situations that are, you know, what I would consider abnormal for a social species. And when do you see this stuff start to regulate? Like is it hey they're violent and um antisocial for a day and then they begin to normalize they get their song back or No, it's kind of it's a long-term thing. In fact, with when you're only isolated for a day or so, you have a lot of actually opposite effects. So, if you've kind of been in your apartment stuck in there for a day or two working on a project by yourself, you seek out social interaction after and you have a lot of kind of positive type of um interactions with other members of your species. It's really only when this persists for a long period of time that you kind of slip into this state that's not adaptive or beneficial at all in terms of and in the lab, how are we defining long time? Yeah. So, in the lab with mice, it takes about 2 weeks. Um, which, you know, I'm just trying to think, you know, they're usually like live to a year and a half or two years. So, you might that might be like times 50 for a human. So, I don't know. But it's hard, you know, it's hard to like make that exact analogy. That's I don't like making those analogies. [laughter] Do do you have any sense of like um what we should expect from the unintentional social social isolation experiment that we're running now? So we're recording this. We're what month five? Yeah. Of uh co lockdown. So is there you know do you have a a guess on where our breaking point is or Yeah, that's a really good question. I I have no idea. I think there's another big thing that you know is a factor especially with humans. Two things that are a factor with with humans. One is that um the notion of kind of social media and Skype and Zoom and all these ways that we are staying connected. So to what degree does that actually help to mitigate those feelings of loneliness? It's hard to say. You know, teenagers have been using the new generation of teenagers have been using social media for years and years and yet they report feeling more lonely than ever. So, is that how people are feeling in general right now with social media or is it actually helping to mitigate some of the effects of social isolation? So that's one thing and I think that would that definitely requires kind of more cognitive psychology experiments and um lots of studies in humans and things like that and that's much harder to model in a model organism in the lab because yeah it's like kind of a specific human thing and then the other issue is how you are isolating. So some people are at home with their immediate family um which probably seems really frustrating sometimes but is also probably really beneficial. So in the lab, if you if you have a mouse that's with just one other mouse, it mitigates tons of the effects of social isolation um versus people who are in a situation where they are totally alone in their apartment right now. So I think that's going to also be a very big difference um which is like people who have a small little support group versus those that have zero. So yeah, that woo when you look at what's going on now in terms of um people feeling like they they're being sort of locked up against their will and it's like who am I even pushing back on because I can push back on the government but if I go out and I get sick it's like you know the virus doesn't really care. So in some ways it's it's not even people telling me to stay home. It's just and I'll speak for myself. It nobody needs to tell me to stay home as much as I would now at this point like to go back out. It's I just don't want to get sick and so and I really don't want to bring it home to my wife and so um there's no one even to like rail against. Right. Yeah. And I think that so it's like I I want my block of wood to chew. That lack of control is hard. Yeah. Um walk me through the um anatomy maybe the wrong word, but walk me through the anatomy both literally and figuratively of fear. Oh yeah. So fear has come a long way. Um, but yeah, I think the kind of classic anatomy that people recognize with fear is the amygdala, which is like this small part of your brain shaped like an almond. Um, that's kind of been this, you know, at the forefront or center of the fear of literature and research for a long, long time. Um, and so since then, as I was saying earlier in the interview, there's, you know, lots of tools that let you look at different cell populations in the brain, um, with a much kind of finer finer tooth comb. And so because of that, people have started to find different sub regions of the amygdala. So you know a lateral part, a medial part, um a basil part, things like that that kind of do different components or in are involved in different components of a fear response. And then within those regions, there's certain populations of neurons that are involved in um you know, increasing fear, decreasing fear, things like that. So um that's come a long way. what what's the part that decreases fear and how do we take control of that right so this actually it's the same part so kind of more recently people have started looking at the central amydala I shouldn't even say more recently maybe like 10 years um which is a subdivision of this kind of amydala structure um and people have found cells there that are kind of active during a fear inducing stimulus and cells there that are active when that stimulus turns off so there are cells there that in theory do the complete opposite of emit or control a fear response. Um, and so that kind of gets at why it's super interesting and useful that we have these new tools because in the past you could just mess up one brain region and say, "Oh, these, you know, animals aren't afraid or for instance, I think in humans there's a very rare condition where the amydala gets calcified and those patients are not afraid at all." Um, that's so crazy. So crazy and it's actually very dangerous for them. So now walk me through how So um if you had asked me when I was 18 about fear, I probably would have said, "Yeah, yeah, if I could get rid of it totally, I would." Right. Um and then I read a study about emotions and how we actually can't make decisions without emotions. And because you can walk through the logic of it all day, but there's nothing to parse whether like a tuna sandwich is better than a pizza. And when there's no emotion, be like, "Yo, pizza's rad." Uh you you literally can't do it. And so they'll just stand there all day. they can give you the benefits and ultimately you just have to tell them to eat one. Um what what is going on? Like what do we use fear for? Why is it bad to not have fear? Like I get it if they're like, "Oh, they don't recognize that getting hit by a car would suck or whatever, but are there more nuanced ways that fear um is actually advantageous and adaptive?" Yeah. I mean, I think pretty much in every everywhere you look, you could see that fear would be adaptive. So yeah, you know, there's the obvious cases where you want to be afraid of fires or very dangerous kind of environmental stimuli. There's less obvious cases where you want to be afraid um in situations where you might sense something's off or wrong. Um and you can't even really put your finger on it. Um you probably want to be afraid if you're in a crowd of like lots of people and everyone's pointing a gun at you. There's like there's tons of cases where you might want to be afraid or aware of the danger in a given situation. Um, so yeah, I guess the physical dangers I get those those, you know, obviously like a gun or a car or something like that that I get. I'm wondering Yeah. Like is there is there something like um fear of being hurt makes you make wiser decisions? like being able to forecast into the future and saying I'm afraid of not being able to feed my family cuz like I'm thinking about part of the reason that I would have said when I was younger um that I would for sure eliminate fear if I could was fear at a physiological level for me fear turns into anxiety which turns into the blood leaving my prefrontal cortex and I like I I when I so I went through debilitating anxiety and I remember at one point saying to my wife when I don't have any anxiety I feel like a superhero I feel like I can think through things. I can be witty. I can solve problems. And when I have anxiety, I feel absolutely moronic. Like I I I actually can't think. And so I I just like I get this like flustered feeling. It's so weird. Now, once I understood that the blood was literally leaving my prefrontal cortex and so my higher level cognition was actually shutting down, it was like, okay, that makes sense. So there it's like well the anxiety I mean anxiety might be public speaking or you know it's it's not something life-threatening at least not in a modern context and so because it seems to so easily get out of control it's like I want to sort of better understand if it's you know and I maybe I just answered my own question but um you know if thinking through things like being able to predict the future break down if you don't have fear. Yeah that's a that's a really good point. I would probably argue even for those situations, a little bit of fear is good. Um, and you gave the example of public speaking. So, you know, you're like in the back of the stage, you're about to go give a talk to a huge audience or something like that. I think like a few minutes before kind of getting your heart rate up, feeling a little bit, you know, I wouldn't say really afraid, but kind of like a little anxious about you're about to go talk in front of a bunch of people, pumping up that adrenaline and then going out there, I think can actually be really beneficial. Um, but I think you know with a lot of these kinds of more we what you're talking about is like psychoggenic fear and anxiety. Oh yeah. Talk to people. What what's the difference between fear and psychoggenic fear? Oh, I just mean so we were talking about fear kind of produced by physical um uh stimuli in the environment like someone pointing a gun at you or something like that versus fear produced by something kind of more in your mind or you know what you think cuz some of the studies on psychoggenic stress are incredibly interesting and it's like if you translate psychoggenic and let me know if you agree with this if you translate psychoggenic to um selfinduced then it's like Okay, this gets interesting. And to me, it's psychoggenic is um the Shakespeare quote, nothing is either good or bad, but thinking makes it so. And so, you know, when you start getting into physiological stress, you're working too hard, you're running, you got punched, like, okay, those are those are legitimate stressors that can be measured sort of as having or or they have a um physical cause often times externally. When you think about psychoggenic stress, now you've got somebody who's um they didn't get enough likes on their photo and now they're spinning out of control or they're isolated and now they're telling themselves a story about unworthiness. Um walk me through like and and maybe this feeds into PTSD. I'll actually be interested to hear like how we end up amplifying the problem for ourselves. Yeah. I mean, I think with humans there's that there's that disorder generalized anxiety disorder where it's like you start amplifying it and then even just feeling your heart beating fast can generate its own anxiety disorder. So, it's kind of this like vicious cycle where it's out of, you know, kind of out of control in that sense. Um but yeah, I think psychoggenic stress I think very quickly you can go from these like low levels that are adaptive to these very high maladaptive levels that make it difficult for you to function. Um make it difficult for you to feel, you know, on top of your game or that you're doing, you know, using all of your skills and resources, you know, well or something like that. So I think it feels very paralyzing when you hit a point of excessive fear and anxiety for most people. And do have you looked into like how people begin to unwind this? Like how do you if somebody has PTSD, which I know you've looked into a lot, how do we how do we begin to back out of that? Yeah. So I think like the still kind of the most typical therapy for PTSD is some form of exposure therapy. It's the same for other phobias. So if you're afraid of flying, you can go to a clinic and, you know, get in a fake airplane and kind of do that repeatedly over and over and in a form of exposure therapy or cognitive behavioral exposure therapy um where you kind of re relive the traumatic event or um experience the cues that predict trauma without the trauma itself. So that's fairly typical. How does that help? So I mean it's actually a lot of that's also based on rodent research. And so what you do when you do exposure therapy is you build a new memory. So a memory that actually I can get on this airplane and everything's going to be fine. I can drink my wine and eat the crackers or whatever. I can get on this plane and actually the world's not going to end. It's going to be okay. So that's you're really forming a second new memory there. And a lot of people have worked on that. It's called, you know, extinction learning or what we think of as exposure therapy. And during that new learning, you can uh again learn that the plane doesn't mean something terrible is going to happen. And then those two memories compete. One that getting on an airplane, you know, leads to something terrible and the other that getting on airplane usually leads to everything being fine and great. And so, um, by doing exposure therapy, you're really kind of just strengthening that extinction memory and, you know, kind of making that memory the primary one that you retrieve when you get on an airplane. The problem with PTSD is unlike other kind of traditional phobias, it's pretty resistant to that type of exposure therapy and that's why so many people still work on it. So other, you know, therapies for people who are scared of snakes or scared of planes and stuff have worked pretty well, but kind of these therapies for people who've experienced some very horrific and debilitating trauma um usually don't work that well or if they work, it's pretty shortterm. So, lots of people are still trying to understand it and you know why some of these classic exposure therapy methods aren't working and what we can do instead to kind of treat uh people with PTSD. So, in your work on emotions, what's one thing you've come across that you wish everybody knew? H that I wish everybody knew. Yeah, that might be useful for people. I actually have a super weird experiment that I ran while I was a posttock at Caltech. Um, and so I don't know, let's see if how this comes across. It's pretty weird. Um, so I was doing a an experiment kind of looking at this a model of PTSD and I just thought I thought oh I know I have an idea. This was to this is totally an example of like anthropomorphizing stuff. I thought, I have an idea. If I give a bunch of these animals PTSD and then put them back together, it'll help mitigate the effects. Kind of like when you go to a support group for um you know, where everyone else has suffered trauma and you talk about it and it seems to make people seems to result in better outcomes for people and things like that. So, I took some animals, I gave them all PTSD and put them back together. And the next day when I went in, not all of them were even alive. They were they viciously attacked each other. It was hor their symptoms were even worse than if than they were if they just hadn't gone back with other other kind of members of their species that had the trauma. And I was very surprised and I was like, "Wo, what is going on here?" And then I decided to run another experiment to follow up on that where only one of the animals got traumatized and then I put it back into the cage with its litter mates that had not been traumatized and that seemed to really alleviate the effects of the trauma. So you could really kind of um get over the effects of that trauma or reduce those effects of trauma by interacting with and being exposed to, you know, others and being social but not others who had had trauma themselves. Um and so yeah, that gave me the chills. What What do you think is going on? Is there um like I show aggression because I have PTSD and we and then the other person shows aggression? It's probably something like that. It's probably, you know, they all had the same kind of trauma. So there's might be an argument that when you, you know, when you're in a group for other survivors of trauma, you have such different experiences that you're able to kind of gain, you know, perspective and um feel healthy from that interaction. Perhaps if you guys were all at the same in the same, you know, bad place at the same time, you would associate those people also at the bad place. I'm not sure, but kind of it kind of did make me think, oh, maybe it makes sense instead of going to like support groups is might might make more sense to like go, you know, hang out with like your three closest buddies that are like pretty psychologically stable and that might be actually the better thing for you to do. Um, yeah, that was very surprising and weird. I could talk to you forever. Thank you so much for taking the time today. Where can people connect with you and see what you're up to? Um, I have a lab website, zelikovskylab.com, and you can find me there. Um, yeah, I'm uh not really too much on Facebook. My Instagram is mostly my climbing stuff, so I wouldn't tell anyone to [laughter] go there. Um, yeah, and then I'm on Twitter also, Moriel Z. Love it. Awesome. Moriel, thank you so much for joining me today. It was amazing. Guys, if you're not learning about neuroscience, I really think you're missing a trick. um dive in. She's got amazing stuff. Obviously, what she's doing in her lab is so fascinating. Emotions are so critical. Um so, do check it out and if you haven't already, be sure to subscribe. And until next time, my friends, be legendary. Take care. Most of us believe that we see reality as it is. When we look up and see the moon, it's because there really is a moon and it would exist. Even if there were no observers to see the moon, it would still exist.