Mark Tebbs: I'm Mark Tebbs and I'm your host today. I spent my whole entire career working in mental health in various facets from kind frontline service delivery to director of mental health commissioning. And now I'm a chief executive of charity. So I'm really interested in kind of grassroots organizations and their impact on community wellbeing. I'm also parent and I've seen the mental health system from that side too. So I'm delighted to be hosting these podcasts. Today we will be speaking about anxiety, memory and sleep in peri-adolescence. I'm really pleased to be speaking with Liga Eihentale and we're going to be talking about her JCPP paper entitled anxiety severity in peri-adolescence is associated with greater generalization of negative memories following a period of sleep relative to wake. Hello Liga, great to meet you today. Liga Eihentale: Thank you for having me, glad to be here. Mark Tebbs: Great stuff. So let's start with some introductions. So it'll really interesting to hear about your research interests, where you're working, maybe some of the people you worked with on paper. Liga Eihentale: Absolutely. So I'm Liga Eihentale I'm an early career research scientist at Florida International University. So I'm a doctoral student in my fifth year of training. And my research here really focuses on mechanisms of anxiety and depression in period adolescence with particular focus on sleep. And this particular paper or project was a team effort with my mentors, Dr. Dana McMakin and Dr. Aaron Mattfeld, who are both faculty here at FIU. And they're also really leading interdisciplinary efforts by bridging clinical science and cognitive neuroscience to better understand and explore how sleep relates to memory and emotional functioning during these pivotal years of development. Mark Tebbs: Great stuff. what motivated your interest in this area? Liga Eihentale: Yeah, so we're really interested in period adolescence as it is a transition between ⁓ childhood and adolescence. So it's a very sensitive neurodevelopmental period. A lot of ⁓ changes take place during this time. So with brain, ⁓ emotional regulation, sleep patterns change. And what we see is that anxiety disorders often emerge during this time as well. So we wanted to explore what role does sleep play in emotional memory consolidation, specifically focusing on generalization, which is a feature of memory consolidation. And we really wanted to see it in an anxious sample in a period adolescent sample. So that was kind of our motivating factor and just more broadly understanding what might be some mechanisms. that are contributing to the development and persistence of anxiety disorders, and then hopefully down the line also inform treatment targets. Mark Tebbs: Okay, brilliant. So what's happening at that period in terms of like kind of brain development in that kind of peri adolescent period? Liga Eihentale: Yeah, absolutely. So the peri adolescence is really the ages between 9 and 14. And there's a lot of change happening both physiologically, emotionally, and then ⁓ also with sleep. And it's related to both your biology, but also to the societal changes and pressures with this age group. So there's increasingly more academic responsibilities. There is more pressure to fit in with your peers. There's also later bed times that happen both because of social factors and also because the biology changes. So really this time is a very sensitive period where preteens are particularly vulnerable to insult is what we call it. But we also see it as a window opportunity to intervene and potentially change the trajectory for children who are at risk of developing these disorders. Mark Tebbs: Okay, so this kind of very sensitive period of change. So what's the level of anxiety in this period of time for the young people? Liga Eihentale: So it really depends on multiple factors. Of course, there's always genetics that might predispose someone to be more likely to develop anxiety. There's environmental factors like the things that I mentioned. So some children might experience the same things but won't go on to develop anxiety, but others will, which is why we're trying to figure out what are the mechanisms. And sleep is increasingly becoming one of those sort of things that people are trying to understand better and see how it might contribute. And what we know from literature is that in anxiety, see that sleep is impacted. And certainly more anxious children tend to have poor quality sleep, which then also fuels their anxiety the next day. So understanding ⁓ what sort of comes first and what contributes is kind of also part of this work that we're doing. Mark Tebbs: It kind of like a reinforcing cycle, of like the generalization impacting on sleep and then sleep impacting on anxiety. Liga Eihentale: Yeah, exactly. And generalization itself as a concept is an adaptive trait. So it's really a feature in our memory that helps us learn and guide our future behavior. So from evolutionary perspective, if we see a bright poisonous berry and we eat it and we feel bad, we're more likely to avoid other similar berries. But the tendency to generalize negative experiences more is what we think becomes maladaptive in anxiety. And what we talk about in our paper is really negative over-generalization which means that instead of adaptively in generalization, when you take one experience and apply it to other similar situations, in negative over-generalization you take one negative experience and apply it to other similar but non-threatening situations. An example might be a child might have an interaction with a angry dog, which could be a frightening experience, but then they become fearful of all dogs, including ⁓ cute little puppies that pose no threat. So this is the over-generalization that is really a core feature in symptom and anxiety disorders. And so we wanted to, again, mechanistically understand how sleep relates to the process of generalization and negative over-generalization in anxious children. Mark Tebbs: Okay, I'm just thinking about what the gap of research was that you were trying to address for your paper. So what was known about that relationship between anxiety, memory generalization and sleep? Liga Eihentale: So broadly speaking, this role of sleep ⁓ is fundamental in memory consolidation and emotional memory consolidation. So there's a lot of literature to support that, especially in adults. There's a lot less in youth and there's almost no research done in anxious, so clinically anxious children. There are some studies that look at anxiety symptoms in typically developing children, but specifically in clinical populations. And during this period adolescent period of these critical years, it's maybe one other study that looks at similar processes. Mark Tebbs: Yeah, okay. So I'm just wondering, could you give us an example of what it would feel like for a young person? How does this mechanism work from a child perspective?

Liga Eihentale: Absolutely. So what we see in our clinical practice a lot is also children who are more highly anxious. They tend to be high achievers. So perhaps they go to school and they get a bad grade on a math test. So they take that experience and they go home and they think about it and they ruminate about it before sleep. And so the next day, might feel as bad or worse about it, and then they might actually apply that experience to a broader context. Now they may think that, well, I failed this test, I'm surely going to fail the whole class, or maybe I'm going to fail all my classes. So this is what we see in anxious children. Normatively, children would have an emotional experience, maybe a bad experience having a bad grade, but they may fall asleep and wake up feeling better about it. So when you heard the expression, you know, sleep on it or go to bed to feel better the next day, it's really very true because sleep has a therapeutic effect of, and mechanistically this means that it kind of strips the emotional tone from your memories and really consolidates the core memory so that it can inform your future behavior. So for non-inverse children, they might think, well, I failed the test, fine, you wake up in the morning, you feel better about it, and you're like, I just have to study harder. So you're informing your future behavior. Versus anxious children, overnight, these processes might be ⁓ affected in the first place, how this memory is consolidated. And this emotional tone might not be stripped from the memory. So in the morning, they wake up and they feel as bad or worse about it. And even more, they might feel more emotionally reactive. And then they generalize this experience to other contexts. then so it feeds the anxiety. And so it continues in a loop. ⁓ Mark Tebbs: Okay so very different in an anxious child to a non-anxious child that impacts asleep on the processing of those bad memories. Okay, okay, brilliant. All right, so shall we dive into your study a little bit more? So I'd be really interested to hear just about how you carried out your study and what you were hoping to test what your research hypothesis was. Liga Eihentale: Absolutely. So we recruited nine to 14 year olds for our study. We had a sample of 34. Half of our ⁓ participants were in a sleep group and the other half was a wake group. So all participants did an emotional memory test, which involves seeing images. So at encoding or learning the images, they would look at neutral, negative and positive images. And then 12 hours later, they would be given a surprise memory test. So the sleep group would return after a night of sleep and the wake group would return after a day of 12 hour wake window, essentially. And so then they would have to tell us whether they recognize the image that they've seen it or it's a completely new image they haven't seen or whether they generalize an image that is a very similar to the one they've seen, but not identical, which is the measure of generalization. And this project was really a pilot study that informed a next project, which was an R01, a big project of much bigger sample that is currently ongoing in our laboratories. And so hopefully in the future, we're excited to dig in this data and kind of replicate this pilot study in this paper that we wrote up. Mark Tebbs: Okay, right. So before we go more into the results, are there any, you said it's like a pilot study. So are there any limitations that we need to be aware of before we go into more details? Liga Eihentale: Yeah, absolutely. So as I mentioned, sample of 34 is relatively small and it was also a cross-sectional design, means we're just looking at one time point. So certainly these findings need to be replicated in a larger and longitudinal ⁓ study, which is exactly what we're hoping to do with our R01 data. And we also used a cryptography and sleep diaries for ⁓ assessing sleep which is great in the sense that it allows us to see really natural sleep patterns in their own environments as opposed to a sleep study done in a lab where you can utilize something called polysomnography. However, using an x-tigraphy and sleep diaries do not give us these more finer details of sleep that polysomnography does, which we really think might be key as mechanisms in these emotional memory processing, in these processes. Mark Tebbs: So what did you find? What were the main findings from your study? Liga Eihentale: So our main finding was that anxiety severity was positively associated with a negative generalization after sleep, but not after wakefulness. So in other words, children who were more anxious tend to endorse images that were similar, but not identical. So the negative ones, they were more likely to endorse them after sleeping, but not after wakefulness. So they were more likely to generalize. So that was our main finding and it was our a priori hypothesis that we confirmed. Mark Tebbs: Okay, so what are the implications of this finding? Liga Eihentale: Yeah, so really the implications come down to understanding the mechanisms and informing treatment ⁓ targets. So before we can do that, we of course have to really look at finer details of sleep, like I mentioned, or finer features. So the brain activity that happens during sleep and what are the particular sleep features that drive these mechanisms. So there's slow wave activity that happens in the brain and spindles, and these are really critical for memory consolidation and emotional memory consolidation. But broadly, we know that sleep-based interventions could really aid the current behavioral interventions with anxious children. example, sleep really could inform or not rather inform, but sleep could aid in exposure therapies. So if we know that certain responses are generalizing, perhaps fear extinction, which is ⁓ used in exposure therapies for phobias, might generalized during sleep and aid in reducing the phobias. It could also be utilized as ⁓ potentially with the positive effects of therapeutic intervention. It could also help generalize those. Then there's other more interesting interventions that are related to memory specifically like targeted memory reactivation, which ⁓ means that during sleep, certain memories might be cued. to overwrite the negative memory. So for example, neutral or positive memories might be queued to then hopefully ⁓ extinguish the negative over-generalization. Mark Tebbs: So, what was the, optimum intervention period? So is it kind of like working with the young person just before they go into sleep? Liga Eihentale: Yeah, so the reason we're interested in this particular age is because we think it's a window of opportunity. So most people think about the early childhood years, so zero to three, as a rapid brain development when it's particularly plastic. And the notion is that once that age is passed, then you're kind of dealt with, you're dealt and you're dealing with symptoms. But now more increasingly, research shows that these peri-adolescent years is actually another very plastic time when brain is rapidly developing. And this is, like I mentioned, it's a prime time for insults. So it's a perfect storm where things can go really wrong considering all the changes that are happening physiologically and socially with teens. And it is also a window for opportunity where we think if we can really get to these children before they enter their puberty. ⁓ and provide them interventions, we could really change the trajectory for those kids that are at risk for developing anxiety disorders. Mark Tebbs: Was there anything that particularly surprised you about your results? Liga Eihentale: Yeah, so we were surprised to see no relationship between ⁓ anxiety and recognition accuracy in our sample. So recognition is probably the primary measure of memory consolidation in the research that exists, especially in adult literature. So this is really purely retention able to remember the images that you saw. And in our sample, we didn't see this relationship. But our hypothesis is that these memory consolidation processes might be really affected in anxious youth, which is why we did not see this relationship here. And another hypothesis is that what literature shows is that in anxiety, there's more generalization at the expense of detailed memories. So perhaps that was the case also in our sample. We did see the increased generalization, but did not see increased recognition of negative images. Another surprising study or another surprising finding that we had was that surprising, but also just affirming of what we had already hypothesized is that at low levels of anxiety, sleep tend to decrease negative over generalization as opposed to at moderate and high levels, it tend to increase it. And so this kind of firms the notion that sleep is overnight therapy. So in normative or non-anxious children, sleep should really remove that emotional tone of memories and then the next day they feel better. So we do see that in our sample in the non-anxious or the very low anxiety severity children. But it's the opposite is true for moderate and high anxiety in our sleep group. Mark Tebbs: Okay, so I'm wondering how might these findings influence clinical interventions and therapeutic approaches? Liga Eihentale: Yeah, so as I mentioned, really aiding the existing cognitive behavioral therapies like exposure therapies, hoping that generalization really aids the fear extinction and any positive therapeutic experience that children may have may generalize. This might also inform some other more recent techniques like savoring, which really means trying to emphasize positive memories and experiences right before you go to sleep and de-emphasize the negative experiences so that not to make them even more likely to be reactivated during your sleep. And then of course, targeted memory reactivation, which ⁓ could really help with overriding the negative experiences with positive or ⁓ neutral memories. And the way it's usually done is by associating certain memory with an odour or a sound. And then when you're asleep, it's cued while you're asleep ⁓ in a specific sleep stage. And then hopefully that translates into memories that neutral or positive ones take precedence. And this is also something we, the work we've done with our R01 project that we're excited to now explore. Mark Tebbs: brilliant. And you mentioned savouring, what does that mean? What's that as an approach? Liga Eihentale: Yeah, savoring is a really excellent technique that we also know for clinical practice, we suggest to parents and children as a very simple thing they can do at home before bedtime. And there's research to back that it really works. So savoring really means just thinking about experiences by really visualizing them and thinking about the fine details of experience so you can really immerse yourself in it. And what we suggest teens or children or parents is that before bedtime, as opposed to what commonly happens is rumination, which is really just overthinking all the things they did wrong or said wrong. So instead of really activating those experiences before bed, because they are more likely to be consolidating, as opposed to that use a positive experience either from the same day or maybe a recent experience you had and really think about it. And not only will help you to reduce your physiological arousal and make you more calm, but hopefully those memories will be more likely than consolidated and generalized rather than the negative experiences you're really thinking about right before you go to bed. Mark Tebbs: Yeah, that's fascinating. So are there any other tips for maybe parents or teachers working with anxious teens. Liga Eihentale: Yeah, I think for working with children, teens or anyone adults alike, but particularly for those that are at risk or anxious pre-teens, I would really stress thinking about sleep health or sleep as important as about healthy eating habits and ⁓ exercising. And more increasingly, people are paying attention to sleep because there is really a lot that happens while we sleep. And so it just stresses parents and teachers to really protect the sleep of adolescents or period adolescents and small children to really implement consistent sleep routines. So going to bed and waking up the same time every day of the week, trying to reduce activating these negative experiences that might come from scrolling or doom scrolling right before they go to bed on Instagram or social media and really taking time to just wind down and relax and trying to think about positive experiences they may have with their family or friends, and then just really protecting their sleep. Mark Tebbs: Yeah, that's good advice from us all actually. So I'm just thinking about the next steps in terms of your research. You you mentioned that you're doing a further study. So it'd great if you could tell us a little bit about that. Liga Eihentale: Yeah, so the next step is really to dive into more specifically the brain activity and the waves that happen while we're sleeping. Like I mentioned, we really think, and there's literature to support this, that the finer details of sleep, like the spindles or slow wave activity, are really the driving factors in these memory consolidation processes. And so one way we see this play out is that commonly, both anxious and non-anxious children may report the same amount of sleep they had during the nighttime, but anxious children tend to report less quality sleep or they feel like their sleep was not as restorative. So we know that there must be some underlying brain activity that differs between anxious and non-anxious youth. And so we think that this of course might then affect the memory consolidation processes as well. So this is something we are collecting as part of our R01. So we're going to be excited to look at that ⁓ data more in detail and hopefully replicate the findings we had in this paper. Mark Tebbs: Great stuff. we're coming to the end of the podcast. I just wondered whether there was a final message that you'd like to share with the listeners. Liga Eihentale: Yeah, absolutely. like I said, protecting sleep and really paying attention to it and and make it as important as important as your sleeping habits and ⁓ your exercise. And if I had ⁓ one thing I could just make happen, I would probably really advocate for later school start times, which we think would really help for adolescents as they are naturally going to bed later. So the really early wake up times don't help with, you know, their their sleep and the amount of sleep they're getting. And I know that there is legislation being passed here in the United States. The state of California has already implemented later school start times and our state Florida here is soon to follow that suit. I believe we'll pass the law here in July this year. So just giving our children the sleep that they need so that they can grow up healthy and happy. And yeah, that's the final message. Mark Tebbs: Great stuff, that's a really interesting podcast. Thank you for your time Liga and I hope you enjoyed the podcast. If you enjoyed the podcast please leave a review and thank you for listening. Liga Eihentale: Thank you.