Cheryl Dean:
All right. To respect everybody’s time, I see a few folks are still trickling in, but I will get started. Thank you very much for joining us today. Welcome to Salk’s first installment of our Power of Science Webinar for 2021. I am Cheryl Dean. I am Salk’s Planned Giving Counsel. I’ll be your moderator today. Before we go ahead with the main reason why you’re here, I want to show you the next slide.

This is where you can find some information about the coronavirus research that’s being done by other Salk scientists. We get questions about this all the time, as you can imagine. Now that the pandemic has been impacting our lives for about a year, it’s exciting to be able to share all the progress that our scientists have been making. If you’re interested, you can go to this website. This talk, by the way, is being recorded, so you’ll have access to this afterwards. We’ll send that out, if you’re interested.

Now, on with what the main reason why we’re all here. The topic today is social isolation and your brain. I think one way or another, we’ve all experienced a lot of social isolation over the past year. Our speaker today is Dr. Kay Tye. Kay Tye is a professor and Wylie Vale Chair of the Systems Neuroscience Laboratory at Salk and also an adjunct professor at UCSD. Dr. Tye grew up in Ithaca, New York. Her professional training began at MIT, where she graduated with a major in brain and cognitive sciences. After taking a year off to travel, she earned her PhD at University of California San Francisco, and then she trained as a professor… Oh, sorry… postdoctoral fellow at Stanford University. She became an assistant professor at MIT in 2012, was promoted to an associate professor with tenure in 2018, and fortunately we convinced her to move her laboratory to Salk in 2019.

Dr. Tye has been recognized with a number of prestigious research awards, including the NIH Director’s New Innovator Fund, the Presidential Early Career Award for Scientists and Engineers, the Society for Neuroscience Young Investigator Award, and the NIH Director’s Pioneer Award, among many others. She’s also committed to outreach and promoting diversity and inclusion in science. When Kay isn’t in her lab, she can be found playing with her two kids or surfing in the ocean. Please help me welcome Dr. Kay Tye.

Kay Tye:
All right. Thank you so much Cheryl, for that lovely introduction. It’s just such a joy to be at the Salk. I feel extremely grateful to have been here hunkering down with this pandemic. The topic of my research is social isolation, it’s been something that I’ve been interested in for quite a few years now. I’ll tell you about the path that took us there, but of course, the first thing that we have to address is where we are right now. This is July 4, 2019, 2020. New Year’s Eve 2019, 2020. I couldn’t actually find a picture. [laughter] Needless to say, it has brought on a large number of unprecedented conditions. The social distancing that has been absolutely necessary, has come with major adjustments for all of us.

Social isolation and even perceived loneliness, even without isolation, is correlated with many deficits in mental and physical health, as well as a shortened lifespan, more specifically increased anxiety, depression, suicidality, increased morbidity and mortality for both cancer and heart disease, increased inflammation, and symptom severity with the viral immune challenge. I think all of these reasons, and there are many other deleterious health consequences of social isolation, provides the urgent need for us to understand the neural circuit changes, so that we can prevent these negative effects.

How did I even start studying social isolation? Originally, my lab was focused on understanding the neural circuits of emotional processing. We stumbled onto this almost by accident. This project was supposed to be about something totally different, and then a postdoc in my lab, Gillian Matthews, noticed that the control group was different. This is how we kind of went in this direction. Basically, what she found was that after just 24 hours of social isolation, this is in mice, we found there was an increase in synaptic strength onto dopamine neurons in the dorsal raphe nucleus. The dorsal raphe nucleus is a brain stem region that’s probably best known for being the home of serotonin neurons, but there are also dopamine neurons there. They’re actually very understudied.

When you hear about dopamine and dopamine neurons, dopamine as reward juice, that’s a different type of dopamine neuron. These dopamine neurons are just beginning to be understood. There’s only really a handful of studies on these neurons. But what we found was not only does synaptic strength increase after 24 hours of social isolation, but also the neural activity increases. If we use a genetically calcium indicator as a readout for neural activity, we can see that the neural activity response to a social stimulus is greater after isolation than it is a novel object, or it is for group-housed mice. This together suggests that these dorsal raphe nucleus dopamine neurons are sensitive to acute social isolation and can track that decrease in social contact.

We wanted to know what these neurons do. We photostimulated them using a technology called optogenetics, which allows us to make neurons light sensitive and just allows us complete control over the activity of those neurons. We can activate these neurons and see what we get. What we found was interesting. First, we saw an increase in pro-social behavior and increased motivation to seek social contact when we activated these neurons, but we also saw an aversion. Animals would avoid photostimulation. They found the stimulation unpleasant. That was really confusing, because you think about other dopamine neurons. BTA dopamine neurons are the ones people mostly study. The consequences of using cocaine, for example, those dopaminergic signals would be pro-social, but also positively reinforcing. This was very different than that. I didn’t believe it initially. We did the experiment a couple of times to get it straight. But it’s very robust that it does produce pro-social behavior while it’s aversive.

This had us scratching our head initially. How does that make sense? If you allow me to use an analogy from feeding, I can eat this delicious crème brûlée for dessert at the end, and that’s me being motivated by the positive valence of food reward. This food is so delicious. It gives me pleasure to consume it. I will consume it. Alternatively, I could just be starving. There’s a layover on the plane or whatever. I’m just in some situation where I don’t have any food. I’m scrounging at the bottom of my backpack for a fiber bar that doesn’t taste that great, but I’m going to eat it. I’m motivated to eat it to escape the unpleasant state of being hungry. This led us to think maybe it’s the same for social contact. I could seek social contact because it’s fun and rewarding and it’s socially rewarding, or I can seek social contact to avoid the unpleasant state of being lonely.

Further, we found that when we silence these neurons and prevent them from being active, nothing happens if they’re group housed, but if we isolate them from their social group, we block the isolation-induced rebound of social interaction that you normally see by silencing these neurons—that’s something else I’ll get into momentarily. When animals are isolated—and this is true for humans, mice, monkeys and many different species, if there’s an acute isolation from your social group, when you’re reintroduced to your social group, there’s a rebound of social interaction, "Let’s catch up. Let’s stay up all night hanging out. Oh. It’s totally great to see you again," that kind of rebound. That is normal after acute social isolation.

One thing that we wanted to look at is that with the psychological definition of loneliness, which had never before been used in neuroscience, the psychological definition has a bunch of criteria. It is aversive. It also produced pro-social behavior. It is distinct from generalized anxiety. Then the trickiest one is that it’s subjective. What do I mean by that? I mean that you can be in a crowded street in Manhattan and feel lonely, or you could be alone in your room and not feel lonely at all. That is a level of subjectivity that’s impossible to really get at perfectly in a mouse, but we thought about this and thought about what we could get from it.

Wild speculation is that if you are a mouse—and mice form hierarchies in their cages, just as humans do in their working groups or living groups, if you’re the alpha mouse, everybody subserves you. Everybody’s kissing up to you. You have access to prime resources. Life’s great, so when you’re isolated from your social group, that feels like a loss. Maybe you feel lonely, because you really enjoyed your former social environment. But if you’re a subordinate mouse and you’re constantly being denied prime access to resources, denied access to mates, being beat up all the time by those that outrank you, maybe you feel great when you’re isolated and you don’t feel lonely at all. You feel relieved that your bullies are gone.

This is just a wild speculation, but what we did was test the social rank of animals in the cage. What we found was a very strong correlation between dominance, social rank—that’s the same thing, the dominance hierarchy and individual social rank, and the degree to which our optogenetic manipulations changed behavior. Basically, activating these neurons only did something in dominate animals and didn’t really do anything in subordinate animals. This was our best proxy for subjectivity in mice. At this point, we’re kind of thinking as a working model that these dorsal raphe nucleus dopamine neurons could represent an effector system for social homeostasis. I’ll tell you what that means in just a second.

Before I get into it, I just want to say that one thing I’m really excited about is not that common, there’s a lot of animal studies that never reproduce in humans. I’m very excited that we were able—in collaboration with Livia Tomova and Rebecca Saxe at MIT, and do this experiment in humans. In humans, we could only socially isolate them for 10 hours, just for ethical reasons, but what we found is that the signal in the brain that you get when you’re socially isolated and then presented with photos of social interaction is that you get a craving signal that’s very similar to when you’re hungry and being shown pictures of food. This was really exciting and just the beginning.

Now, this thing. I said some words about effector system and homeostasis. What does that even mean? What is homeostasis? Homeostasis just comes from the Greek words for same and steady and refers to any process that an organism might use to maintain stability necessary for survival. There are a lot of examples of beautiful work done to dissect the neural circuitry underlying different homeostatic systems, such as energy balance or hunger, thermoregulation, and osmoregulation—just how hydrated or thirsty you are.

I’ll use thermoregulation as an example. The key components of every homeostatic system is first, a detector. You need to detect—okay, I need something in my body to say “my body temperature is whatever it is.” I need some sort of receptor to detect my body temperature. I’m going to feed it forward to my control center, which compares this to some sort of homeostatic set point, which in this case is probably 98.6 degrees. Then let’s say I’m too hot. Then that surplus is going to be fed forward to the effector system.

The effector system is really the part of the system that fixes the problem. In the case of thermoregulation—that could be I start sweating or I move into the shade. Either of these physiological responses or behaviors can then serve to correct the change, which the environmental temperature is just the environment. Then it’ll shut the whole thermostat off. That’s kind of how it works when it’s temperature. I hope you can imagine that it’s actually much more complicated when it’s social homeostasis. Each of these nodes—sorry about this animation. I know this is a busy slide, but this is just to emphasize that it’s not that simple.

With detection of social homeostasis, we have to detect the amount of quantity and quality of social contact. That’s really complicated. That’s not the same thing as detecting temperature. I need to recognize social gestures and different forms of communication and signals. I need to identify who that’s coming from. A given gesture from your significant other is going to be different from a stranger, whether that individual is novel or familiar, their identity matters, which calls upon the whole history of social experiences you’ve shared with that individual, and their relative rank. There’s a lot of different components to each of these nodes within the social homeostatic system. I won’t get into all the details now. I just wanted to say that this is a non-trivial problem.

One of the things we’ve been able to do is develop a task where we can record in the prefrontal cortex of freely moving mice while they compete for a reward. It’s kind of like, oh, there’s one more piece of pizza at the party, and you walk up to try to get it, and then, oh, your boss is there. Then what are you going to do? Are you going to take the pizza? Are you going to let the boss take the pizza? How are you going to handle the situation? We have that basic experiment here, where there’s going to be a cue that says “beep.” Okay. Reward is going to be delivered. It’s only a little bit and really only one animal can get it. In a cage of four animals, we will have every animal tournament-style, round-robin battle it out with every other animal and record what happens. This is work by Nancy Padilla, Javier Weddington and Makenzie Patarino in my lab. The wireless devices are in collaboration with SpikeGadgets.

This is what it looks like. You can see, beep, a tone went on. This animal just got it. The other animal’s too late. Sorry. It’s not there anymore. That’s how this competition goes. Sometimes there’s some pushing. Sometimes it’s uncontested. It depends. But what we wanted to look at is if prefrontal cortical neurons can represent social rank. Are we able to decode that? What we found is if we take the 1,000 neurons that we recorded from all these different mice and their different ranks and put them into a machine learning algorithm called a support vector machine, which is just a supervised machine learning algorithm where we put in the training data and then ask it “Can the PFC actually predict rank?” What we found was both for competitive success, which just means trial to trial who won or lost, and also the relative rank of the two animals in the cage—this dotted line here indicates the onset of the cue, and this is the average of all the trials. What I’m plotting here is the accuracy by which we can predict the animal’s future behavior based on the neural activity.

            What we found here is maybe not as surprising, that rank is more significantly represented than wins/losses, because that’s stable throughout the session. I think we were really surprised that we got such stable decoding at such a high level, 90% accuracy, across the session. Even before the trial begins, even before the animals know that there’s something to compete for, we are able to predict with greater than significant accuracy who is going to win or lose the next trial. This was crazy. I was like “is this right? Did we do the analysis right? Are we really able to predict who will win or lose five seconds before the trial begins?” We zoomed out even further. We can predict who’s going to win the next trial 35 seconds before the trial begins. This was really exciting to us. We’ve done a lot of other experiments to validate this. But the exciting thing is we might have found a cellular basis, a mechanistic explanation for this phenomenon of a winning mindset, just showing that a lot of what happens in a competition can be predetermined by the neural state of the individuals in the competition.

What I wanted to talk about next is what’s going on in this control center, because this is really kind of the most relevant to what’s going on with most of us right now. Let me get to the phenomena first. It’s been widely studied, as I mentioned before, in so many, so many, so many studies across many different species that acute isolation produces a pro-social response when they’re reintroduced to the social group. You isolate someone from their social group for 24 hours or so, and across the board, you reintroduce them, you get pro-social behavior. However, with chronic isolation, and this has also been shown with humans, primates, mice and even flies, that with chronic isolation you get the opposite. You get anti-social behavior. Animals become more territorial, more aggressive, more avoidant, and just anti-social. This sort of makes sense. It’s kind of the hermit who—get off my lawn kind of scenario.

It’s sort of intuitive, but when you think about how this happened, how could it be that the same experience produces such opposite things when you’re presented with the same stimulus? Reintroduction to the social group is the same thing. How is it giving us this positive valence, rewarding kind of signal in one case and then a negative valence, something that we want to avoid in another case? How does this make sense that the same stimulus would go from good to bad? Right? This is such a dramatic shift.

Thinking through this, our working model now is if we have the quality and quantity of social contact plotted on the Y-axis, then after social isolation there can be a detection system that detects a deficit. Okay. I’m getting way less social contact. This is me in March. I’m getting way less social contact than normal. What can I do to try to fill that void? Then in the case that you can go seek out social contact and have that social contact, then you would restore your balance. You would come back to your homeostatic set point. Everything’s right in the world. Everything’s stable. No changes needed in your brain. Each of these components of the process has a cellular substrate, and we are identifying each of those cellular substrates. But what about when you can’t get back? Right?

This is me in March, and then what about April, May and June? After acute isolation, your effector system might be activated. At some point, which is variable across species and individuals, there’s going to be a set point adaptation. With chronic isolation, at some point this adaptation is triggered and it comes down. Now, this is the new normal. You’ve adapted. This is just life now. I’m cool with how everything is now. But if I were then to be reintroduced to the same quantity, quality and level of social contact that I experienced before, this would now feel like a surplus. It would now feel like it’s more social contact than my new homeostatic set point. That’s why with chronic isolation, the same amount of social contact as previously was desired, can now produce behaviors as if there was overcrowding, more territorial, aggressive and avoidant behaviors.

This is just what we’re thinking about. I think the big question that remains—there’s a couple big questions. One, what triggers that homeostatic set point adaptation? Is it just absolute time? Another working model that we have is it’s the effort that is expended to correct that deficit. You keep trying. You keep trying. You keep trying. You’re just rejected over and over again. Maybe the degree to which those attempts are being put out influences what triggers this adaptation. That’s the first big question.

The second big question for the future of this research program is what causes the deleterious health consequences? What causes all these negative mental and physical health consequences associated with social isolation? Is it the effector system being activated, being constantly driven? Is it that deficit and the effort, the state of trying to repair it, or is it the set point adaption? Is it the triggering of this change in the homeostatic set point? Because those two realities would lead to very different prescriptions for what you should do to avoid those potential negative health consequences.

In one case, if it’s the effector system, then you want to accelerate adaptation and trigger that homeostatic adaptation faster. If it’s the adaptation that is the trigger, then we would want to engage in behaviors and seek manipulations or therapies that would delay that from occurring or prevent that from occurring. This is kind of the big question that I’m interested in tackling in the years to come. I’ll end here for now and just say thank you to all the people in my lab currently, and all my former lab members that have contributed to these projects, my wonderful collaborators, my funding sources, and you for your attention. Thanks.

Cheryl Dean:
Sorry. I should know that by now. I was still muted. Thank you, Kay. That was fascinating. See, I’ve been socially isolating for so long that I’m not always the best at interacting any longer. I wanted to remind folks about the question-and-answer button that is available to you. Please type in your questions. I’ve got several questions. I’m going to start with one from Jennifer. She’s asking, "Is there a more profound response between introverts and extroverts?"

Kay Tye:
Great question. Actually, the homeostatic set point concept is not unrelated to introverts and extroverts. I think the only thing that I don’t love about— It’s not the same concept, because introverts and extroverts implies that this is a static trait, that you’re an introvert and you’re an introvert forever, that you’re an extrovert and you’re an extrovert forever. I think it is related. I do think individuals that would currently self-identity as introverts or extroverts would have different homeostatic set points. Extroverts would have a higher set point, a higher desired amount of social contact. But this is dynamic and this can change. Extroverts can become introverts, depending on their social environment. I guess does that answer your question?

Cheryl Dean:
Well, let’s hope so. Jennifer I’m sure is listening. If not, we’ll get back to you. Here is a question from Heather. "What is the short- and long-term prognosis of people socially isolating as we have been doing in lockdown, and are certain individuals more prone to the negative effects of social isolation than others? When paired with fear, are the effects more pronounced?"

Kay Tye:
All excellent and very, very relevant questions—all things that we care very much about. I don’t know that this is the only way to think about this, but certainly one way to think about social isolation and overcrowding, any social manipulation, is that it’s just a subset of stressors. I do think there’s some additional components, some neural circuits that are specific to social processing, but one thing that these social stressors do is activate your whole stress system, your HPA axis. A lot of the health consequences are similar to just chronic stress in general. Some of them are more specific, but some of them are very similar.

I would say that absolutely fear—and it’s not just fear. Right? It’s the stress. I would say we are also being exposed to unpredictable, mild stress. There’s a lot of uncertainty. We don’t know if that thing’s going to be canceled. At this point, now, maybe we do. I’ve felt like every week for the past year there was a new surprise. The loss of control is certainly something that can trigger on its own depression, anxiety and a number of different mood disorders. There are a number of mental health disorders that are just triggered by stress itself. Compounded together it is a double whammy and definitely going to have more of an impact.

That and the other factor that you didn’t mention, but is also a compounding factor, is this phenomenon of emotional contagion. If other people around you—Even if you didn’t experience a stressor, nothing bad happened to you, but you walked into a room and everyone else is super stressed, emotional contagion is a phenomenon that occurs for most social species, where you will take on that emotion to some degree. On the flip side, there’s social buffering. If you are interacting with other individuals that feel the same way, that can also serve to mitigate stress. Social buffering is something that has been known to help calm your stress systems.

Cheryl Dean:
Great. Thank you. You mentioned in your talk briefly oxytocin. Daniel asks, "What role does oxytocin play in chronic social isolation? Could oxytocin administration be a possible therapeutic intervention to prevent or moderate some of the negative effects of chronic isolation?"

Kay Tye:
This is a really great question. There have been studies from other labs. There’s one study in particular that I’m thinking of that has shown that systemic administration of oxytocin can reduce the negative consequences associated with social isolation, but I think the big question, again, for me is, is this a Band-Aid, or is this the cure? I think that’s kind of the ultimate question. I think it’s likely that administration of oxytocin can trick your brain into thinking that you’re getting the same quality and quantity of social contact that you were optimally desiring. That can keep your homeostatic set point higher. It can also reduce the effector drive that you might have.

It’s not clear to me still what the actual—whether it’s fixing the problem, like, oh, I’m not making my effector drive go away. That was the problem. Then that’s actually getting at the root, in which case I would advise it. Alternatively, it could be just covering up the signal, so that your brain doesn’t know that it should adapt. In that case, depending on the long-term consequences, it potentially might not be good, because it’s just going to delay the inevitable. I think it just depends on how long the isolation would be. But certainly, there is evidence to suggest that it at least can be a Band-Aid. You know, I still use Band-Aids. Of course, if I can heal the cut, I would rather do that, but sometimes there is no magic healing cure, and I will put a Band-Aid on. Oxytocin is definitely having that potential.

Cheryl Dean:
Okay. Thank you. Pat then asks, "Are you worried about those people who accepted the chronic isolation and will not be able to come back into socialization?"

Kay Tye:
I think one important thing is that adaptation can happen in both directions. It might not be comfortable. It will be an adjustment. It will feel like a surplus initially, but I think that as far as we can tell from the data that exists so far, that you can have adaptations in either direction. I think it will require that adjustment, and it will be potentially stressful initially, but I do think that should be plastic in a symmetrical manner.

Cheryl Dean:
Great. Christine then asks, "Which age group do you see having more isolation issues with once we no longer have to shelter in place?" It’s similar to the last one, but there’s a little bit of a nuance there.

Kay Tye:
Yes. I guess the answer is I don’t know empirically. However, younger brains are definitely more plastic, and it’s easier to induce plasticity in younger brains. Neurons are healthier and more able to survive. I would just say in terms of synaptic plasticity, there’s probably a slight bias for younger, but the consequences of isolation during development however can be much longer lasting. I would say excluding the case of development, juvenile isolation is known to produce very long-lasting consequences that are irreversible. Juvenile isolation is harder to recover from. In the adult population, that’s probably your most adaptive group. Then I don’t actually really know the answer for the older population. We just don’t have the empirical data.

Cheryl Dean:
Madison asks a similar question, but specifically with related to your mice experiments that you’ve done, if you saw any differences in the response based on the age of the mouse. Did you only study adult mice?

Kay Tye:
We’ve done juvenile mice, and we also see the same effect after 24 hours. For the acute isolation, it looks very similar, but in terms of the long term—with acute isolation it looks similar. Everybody’s fine with a day or two. That doesn’t produce long term consequences for any species that I’m aware of. But with juvenile isolation, there’s long term behavioral consequences. In animals, it’s commonly used. In rodents, it’s sometimes used as a model for schizophrenia. Maternal deprivation and social isolation rearing cause lasting, irreversible consequences into adulthood. That would be the most sensitive developmental stage.

Cheryl Dean:
A little scary for all of the people who have been experiencing this with young children. Absolutely.

Kay Tye:
I have a seven-year-old.

Cheryl Dean:
Yes. On a potentially more positive note, Thomas asks, "Does exercise or diet during isolation help to maintain your original homeostatic level?"

Kay Tye:
Great question. I would say partially, because these behaviors can—they’re eustress. They’re good stress. Exercise can be good stress. For example, healthy practices are always going to be beneficial. In terms of mitigating stress, the stressful component, I think those types of activities will be good. I don’t know that they would necessarily replace the social specific deficits. I think should you do those things? Yes. I mean, I don’t see a downside. But will it be enough? Probably not.

Cheryl Dean:
Yes. Only so much you can surf or go running. Right? Kay and I were chatting, for those of you who might have joined us and overheard. We both happen to surf the same local break when we get some exercise, which is—

Kay Tye:
Safe, socially-distance social time is good [laugh].

Cheryl Dean:
Yes. [laugh] All right. Getting back to the questions at hand. Patty says, "Kay, this research study is so applicable to our current situation. Oftentimes, it takes years to apply basic research to the present conditions. Is there any connection you are able to make with caregivers, healthcare workers, general public, et cetera, about the effects, basically the realities of the effects on isolation and remedies?"

Kay Tye:
I want to first say that I’m not a medical professional. I’m not a mental healthcare professional, and I’m not qualified to make a prescriptive advisement, but I would say that even small groups of pods, if you can quarantine with a pod, those relationships are going to have very high-quality interactions. You can definitely trade off quantity for quality. Fewer interactions that are very high quality can still provide the same social utility as sort of more interactions that are lower quality. If there’s a way to quarantine in a group, have a pod, take a COVID test before you visit, or whatever, so that you can actually have physical touch and proximity, that would really satisfy the criteria for a high-quality social connection. That could be enough.

I think other fillers, other things that could help would be interacting virtually. That is going to be slightly lower quality. It’s not all the sensory modalities, but cognitively there are brain regions that are activated by social interaction that will also be activated by a number of other activities. Of course, interacting virtually, some component of that circuit is also active. But even things like reading books and watching movies, which I would not consider social interaction, but they activate some of the circuits that are relevant. That is something we didn’t allow the humans in our experiment to do. They were not allowed to of course use their phones or talk to anyone, social media, no movies or books either, because reading fiction books can activate a lot of brain regions that are typically active during social engagement.

I guess we don’t know directly. There’s no data about the relationship between reading books and watching movies, which I would not consider social per se, and how they might actually read out into health benefits. But I definitely can be confident about physical interaction. Social touch is actually quite important.

Cheryl Dean:
Okay. Here’s another question. We recognize that you are not a medical practitioner, but you are a scientist and a mother. Here somebody says, "Great talk. Thank you. Do you have any recommendations for how practitioners or even parents might use this preliminary data for how best to reintroduce children into more typical social environments, school days and other activities?" You mentioned pods just recently. But she says further, "What else have you been thinking about in terms of how the winner mentality is related to nature versus nurture with children?"

Kay Tye:
The winner mentality?… There’s a lot of different interesting questions here. Sorry.

Cheryl Dean:
No. No. I was just—I think she was referring to when you were talking about the mice competitions, how you can predict ahead of time and how much of that was nature versus nurture. Now, you had talked about social dominance and strata. You know what you talked about, so I’ll let you answer this.

Kay Tye:
No. I guess there’s definitely multiple parts to this question. What am I doing with my own kids? Definitely pods. It’s brought us as a—my two children much closer to each other. And definitely making sure to have cuddle time, like really making that a priority. The kids recognize it. They don’t necessarily know to ask for it, but when I ask them what the highlight of their day was, it’s always cuddling on the couch. Cuddles are free and infinite, so I would say use those.

Then in terms of the winning mentality, it’s really interesting. I think there are a lot of things that you can do as a parent, I think. This is hand waving. The way that I think about applying the research, my own research in my parenting is definitely preparing the kids, like, "Okay. You’ve got this." You don’t want to go into a defensive mentality. You want to go to visualizing a successful outcome and painting that picture. Visualization of an action activates a lot of the same motor cortices as actually doing it. If you look at the neural response of doing something versus imagining doing it, there’s one component that looks very similar. The superficial layers of the motor cortex would make that look very similar.

Visualization can really help just from that perspective and also help put kids into a winning mindset, so to speak. Those mindsets can become self-fulfilling prophecies. It’s all the cheesy stuff that people would say, but I think it really has a biological basis of self-talk, talking positive, visualizing and thinking. Setting them up for success mentally is absolutely extremely powerful. We’re excited that we have an actual cellular substrate for that.

Cheryl Dean:
Great. Thank you. It’s good to know that there are some things we can be doing, because as you mentioned earlier in your talk, this year we’ve had a lot of things that we couldn’t predict that are out of control that are anxiety causing. If we think we can have some positive changes on that, that’s good. A couple more questions that we can get to. June says, "It’s difficult to see how 10 hours can be enough data for isolation to present itself. Can that really be considered isolation in one of your experiments that you’re doing with the mice?"

Kay Tye:
Absolutely. For the mice, we actually did 24 hours, but for humans, given that solitary confinement is considered torture and is illegal … and it should be. It’s definitely harmful. We were only approved to isolate humans for 10 hours. We had no idea if it would work, because this is total isolation. The experimenter that puts them into the scanner has just completely covered, like mask, and then just—We did everything we could to completely remove social interaction. Even though we are all—there’s been lockdown for a year, we actually still have a lot of social interactions, virtual and distanced as well as within your pod. There’s actually a lot. We weren’t sure if we would see anything, but we did see significant, robust effects. I will say that individuals that would self-identify as extroverts showed a greater signal. No surprise. We would love to be able to do longer studies, but for many reasons that’s unethical and impractical. So, we’ll do the best that we can with what we can do with humans. Then that’s sort of the power of studying mice.

Cheryl Dean:
Sure. I’m glad to hear, I’m sure everybody here is glad to hear that Salk adheres to ethical constraints with all of our subjects. So, good. But can you expound? Somebody asks, "What kind of socializing benefits are there being on a Zoom call, seeing faces, hearing voices, but not physical touch? So, there are no hugging on couches in a Zoom call."

Kay Tye:
It’s true, but a Zoom call still can make you feel very included. This comes back to this other idea of it being perceived. Right? If you are on a Zoom call and everybody’s cameras are off—There’s a lot of different types of Zoom calls. Or there’s engagement. But our amygdalae are activated by just looking at other people’s faces and their facial expressions. The ability to see facial expressions on other people and have reactions to your actions, I make an action and someone is a prerecorded thing that doesn’t respond versus if they do, it makes a huge difference. The perception that I am being included is actually very powerful.

            I could be in a real life group of people and feel excluded. Even if they’re touching me, but for some other reason it’s not including me, like pushing me aside or ushering me away, whatever, that would not have the same benefits. It’s about the feeling and perception of being included. If you feel like you are excluded, even if you are in the same proximity to all the other social agents, that has very deleterious consequences. That’s one of the things where it depends on the quality of your Zoom call. But absolutely Zoom calls are better than nothing.

Cheryl Dean:
Well, I guess that gets to the point where over the course of the past year, realizing that we haven’t had the same types of interactions with others, I will personally say that I value all of my relationships much more. I don’t take them for granted as much as I used to. That’s a really good reminder about quality of relationships with people and the importance of inclusion and being kind. Kay, do you have any last thoughts before we wrap this up, anything else you’d like—

Kay Tye:
No. I love that note that you’re ending on. It’s just that we’re all in this together and being kind, empathic and compassionate to everyone who’s also going through the same thing is super important. It’s free, and we can all do that and just engage in social buffering. I do think those are the things that we should all think about now. Then moving towards in the future, not everybody has that privilege. Some individuals are immunocompromised. They truly have to be socially isolated for extended periods of time, or when individuals have COVID, they have to be isolated for an extended period of time while their body is fending off a disease. It’s still something that we really want to figure out the mechanism to, but in the meantime, I think Cheryl’s exactly right. We should just remember that we’re all in this together.

Cheryl Dean:
Well, thank you all for joining us. These are crazy times. I believe though that the pandemic has made clear the vital importance of biomedical research, whether it’s people who are working directly with the coronavirus right now—which I can’t wait until I get vaccinated. I encourage everybody to as soon as you can—or these other health related issues that are equally as important for us as human beings that Kay was talking about in her talk today. Thank you so much for your support of Salk’s research and our scientists. They’re really very dedicated. We wish you well. Stay healthy. We will inform you of our next event when we have that scheduled. Thank you.

Kay Tye:
Thank you. Thanks for your questions.

Cheryl Dean:
Bye.