How Experience and Environment Impact Our Early Brain Development

Dr. Brad Schlaggar (BS): Welcome to Your Child's Brain, a podcast series produced by Kennedy Krieger Institute with Assistance from WYPR. I'm Dr. Brad Schlaggar, pediatric neurologist, and President and CEO of Kennedy Krieger Institute. Twenty five years ago, with the anticipation of the turn of the millennium and recognizing the explosion of research into neuroscientific behavioral and social sciences, all in the context of a ever increasingly complex social and economic millu for children and families in the US, and beyond committee on integrating the science of early child development was established under the aegis of the National Academy of Sciences and of Medicine. The product of that committee is a report published in 2000 called From Neurons to Neighborhoods: The Science of Early Childhood Development. The charge of the committee reflect in that report was, and I quote "to update scientific knowledge about the nature of early development and the role of early experiences to disentangle such knowledge from erroneous popular beliefs or misunderstandings, and to discuss the implications of this knowledge base for early childhood policy, practice, professional development, and research". Also quoting from this report, "the charge to this committee was to blend the knowledge and insights of a broad range of disciplines, to generate an integrated science of early childhood development. The charge society is to blend the skepticism of a scientist, the passion of an advocate, the pragmatism of a policymaker, the creativity of a practitioner, and the devotion of a parent, and to use existing knowledge to ensure both a decent quality of life for all of our children and a productive future for the nation". Importantly, as made clear in the National Academies report, the argument does not distill down to nature versus nurture. Rather, nature and nurture are partnered, inextricably. Development is perhaps best seen as a cascading interaction between nature and nurture such that attempting to pull them apart to isolate one or the other is frankly fraught. The report is remarkable not only for the clarity of its recommendations and its comprehensiveness, but also for its accessibility to non experts and how well the insights and recommendations have held up 25 years later, recommended reading, indeed, so in this month's episode of Your Child's Brain, we've invited a group of neuroscientists who think deeply about this interplay between the early development of the brain, the environments or neighborhoods within which those brains must develop. Indeed, these three scientists are part of a symposium at the 2024 Flux Society Conference taking place in Baltimore in late September 2024. Flux is an international society for developmental cognitive neuroscience, first established in 2013, and for full disclosure, I'm one of the co-founders of Flux, so joining me today are Dr. Arianna Gard. Dr. Gard is director of the Gard Laboratory, where Gard is not only her name, but also stands for Growth and Resilience Across Development. She is an assistant professor of Developmental Psychology at the University of Maryland College Park. Dr. Autumn Ivy is a child neurologist and developmental neuroscientist at Kennedy Krieger Institute, where she's the director of the BRAVE Neuroscience Laboratory, where BRAVE means Building, Resilience After Adversity and Vulnerabilities Through Exercise and Epigenetics. She's also an assistant professor of neurology at the Johns Hopkins University School of Medicine. Dr. Heather Volk, is a behavioral geneticist and a professor in the Department of Mental Health at the Johns Hopkins University Bloomberg School of Public Health, where she also directs the Wendy Klag Center for Autism and Developmental Disabilities, so welcome Arianna, Autumn and Heather. I think recognizing that for each of you, this concept of from neurons to neighborhoods has been present throughout your professional scientific lives. I would like to hear how you think about that concept and how it has influenced your own research enterprise, and while you're at it, maybe you describe briefly the kind of research questions you're asking, so let's start with Heather.

Dr. Heather Volk (HV): Coming from the background of behavior genetics, which means we study how genetic influences can impact behavior and mental health conditions. One of the interesting things to think about is how this applies to public health and public mental health really in particular, and so for me, studying the environment and thinking about the concept of neurons to neighborhoods, really lets us begin to think about how at a population level factors in our environment, anything from the built environment, so things like walkability indices in neighborhoods to air quality to lead in our drinking water might impact child's brain development throughout their lifespan.

BS: Autumn.

Dr. Autumn Ivy (AI): I am a basic neuroscientist, in addition to being a child neurologist. I spend most of my time in a basic neuroscience research lab, and we ask questions before you get to the clinic, and so from neurons to neighborhoods for me really means, how can we think about these brain cells, these neurons how they form a developing brain and how that process can be shaped by our environment. As a basic neuroscientist, I can think about these things using models we can use in research, mammalian models, rodent models, things of that sort, and so my lab does use rodent models to understand how we can build resilience of the developing brain, and thinking about what types of experiences during early life can help build resilience. One of the experiences that my lab focuses on is physical activity or exercise, and so we take rodents and we do different types of exercise experiments in order to see how the developing brain forms its ability to learn, its ability to remember and be rewarded, and we also focus on a certain type of chemical mechanism called epigenetics. I'm sure a lot of people have heard about that, but to define it here, it's the set of chemical tags, if you will, that inform how and when genes are expressed and how our cells respond to the environment and based on those genes being expressed, and so we focus on exercise and epigenetics in hopes to find epigenetic mechanisms, causes that can lead to brain resilience and improve brain health.

BS: Now Arianna.

Dr. Arianna Gard (AG): I like stories, and I first heard about the neurons neighborhoods report when I was a project coodinator at the Child Trauma Research Program at UCSF, and Dr. Alicia Lieberman, our colleagues were developing and implementing treatments for young children and their mothers who are victims of domestic violence and who are also interfacing with the immigration system, and one of the foundations of this work was the recognition that inter-generational trauma can impact young children through both the caregiver child relationship, but also biological mechanisms, and in fact, they were starting a project that looked at epigenetic cellular changes that might come from inter-generational trauma exactly, what atom is an experderm. Really as a young project coordinator, I thought research is going to change the world, and this is so exciting, but in fact, neurons neighborhood report really put me on this path towards studying how children experience the neighborhoods around them and the types of both positive and sometimes harmful supports can induce for brain development. Now as an assistant professor, I have a fabulous research group really lucky to work with a great set of graduate students, other faculty and undergraduates too, and we are continuing to study how different forms of environmental adversity, particularly living in a neighborhood that's marked by community violence, as well as having strong social ties with your neighbors, impacts brain development across the childhood period and in a second line of work, we're really trying to advance a new approach to the study of adversity and brain development in children, and that's by working directly with community members to try to develop these studies, which is very hard, but quite exciting.

BS: At the front end, I mentioned that, at least from my own personal view, the nature versus nurture construct, it's highly problematic. That you can't really separate nature and nurture and that action happens, I think, at the integration of inherited and extrinsic factors. Wondering how you all think about it. Heather, maybe we could talk about what it means to be a behavioral geneticist in this context, and how you think about nature and nurture and your take on how your approach informs those questions.

HV: In behavior genetics inherently, we are always trying to really parse the relative amount, that genetics or environment might contribute to a different a given disease or trait or outcome, and what we have learned more and more over time is that it's not an argument of genes or environment or nature or nurture. It's genes and environment, nature, and nurture, and it's really putting these two factors together that becomes incredibly pivotal, and it's very interesting in the field of autism spectrum disorders where I spend a lot of my time that we have hundreds and hundreds and thousands of papers on the genetics of autism, and we have many less on environmental factors that can be inherently modified, and so if we're thinking about chemicals in the environment or social support factors or psycho-social stress, these are all places where interventions can possibly happen, and so, what we want to do is to think about genes and the environment. What are these combinations that can perhaps be most important? In public health, this is really attractive because we can change our environment. We can think about modifications. Autumn mentioned earlier, think about exercise, perhaps as a way of modifying some things that might be happening in the environment, and so we can think about nutritional interventions. We can think about policy wide interventions, that may change things on a macro level, and so, really having this attitude around, how can we combine these two areas of science to help us think about brain development and really help impact brain growth and development most effectively is where much of my research and perspective has really started to go.

BS: This is for both Arianna and Autumn. What evidence do we have that experiences both positive and negative change the structure of the brain, Arianna maybe talk about it. I think from the human imaging standpoint, and maybe Autumn what you can find from the rodent model work that you've been doing.

AG: To tie back to what Heather was talking about, we oftentimes think of the brain as this predetermined factor that maybe is controlled by genetics as well, but I like to think about, and I talk to families about the brain as a muscle. The brain is helping the individual respond to things in the environment and also to gain more reward from things that they really like in their environment.I think now we have a pretty good evidence-based that a variety of environmental experiences, both positive and things that can impair development, can put the brain on a different trajectory of development. Another phrase that I like to use is, use it or lose it. If you are, for example, trying to learn an instrument, which I could not do because my brain is not plastic enough. If you use those parts of your brain over and over again, your brain will change to support that ability. In the same way, if you experience negative experiences chronically, that can also alter the structure and function of your brain, but not in a way to think about bad outcomes, but more in a way to help the individual survive in that environment.

AI: Arianna's point, which is a great one, is that the brain is so adaptive, and it's meant to be adaptive throughout our lives. During the first few years of life though, not only is it adaptive, but it's undergoing the most plasticity or the most growth and most development that it will ever undergo throughout the lifespan of a human. Across mammalian species and rodents and monkeys and other types of species, this is also true for them, which actually allows us to then be able to think about these same types of environmental experiences and other types of mammals and look at their responses. This highly adaptive period or critical period of time. We can define a critical period of early life as this period where these types of experiences can inform how the brain develops and functions long term. We can study these critical periods in rodent models. When I was a graduate student, I worked in the laboratory of Dr. Tallie Baram. She is a well known neuroscientist, developmental neuroscientist, has made remarkable discoveries in epilepsy, as well as chronic stress and interventions. In her lab, that's where we really thought about how exogenous experiences in rodent models can influence how they behave, how they learn. Two models that we used in her lab. One was called the handling model in which this was a model where maternal dam, the mom to her pups, the mouse mom and her pups would be handled or would have increased sensory experiences during the first week of life that the mom has her pups. She would then have more engaged and predictable interactions with her pups throughout this early period of life. We found that with that type of handling and increased maternal sensory input, those offspring would then go on to have better attention and better learning, specifically, learning that's served by a part of the brain called the hippocampus. With those mouse models, we would also manipulate maternal care in a more maladaptive or negative experience. We also had a model of early life stress or adversity, where maternal care was very fragmented and unpredictable. We would find the opposite effect in the offspring. They had more difficulties with learning as pretention of memories that were formed, as well as vulnerabilities to different types of behaviors that would suggest maybe a depressed or less motivated mood, if you will, and that they were less motivated to undergo certain tasks than their counterparts that didn't have this erratic and fragmented early sensory input. We can learn so much from these pre-clinical rodent models just because the brain has this protracted postnatal developmental time where we can study these critical periods and see how we can influence long term outcomes.

BS: Arianna, you think deeply about risk and resilience and their interplay, especially in the context of contending with adversity in early childhood, as you discussed earlier. Could you unpack those concepts? What do you mean by risk and resilience and a strength based developmental neuroscience approach?

AG: Absolutely. Resilience can be thought of as both an outcome and that changes over time. Positive adaptive outcomes in the face of risk or some type of stress or adversity, but resilience can also be thought of as the ability for an individual or even a community to draw upon resources to support them in times of stress. A strength based approach to the study of risk and resilience really places people's ability to adapt to specific environmental circumstances at the center of the conversation. Studies oftentimes focus on impairments or harmful outcomes following adversity. Those studies are very important because it shines a light on the reality of inequalities in adversity and risk in the world and in the United States. The strengths-based approach attempts to document the strengths that people might develop through experiencing and overcoming hardship. This idea that both impairments and strengths can emerge from risk is part of the strength-based approach. I'll also say that we talked to some very insightful community members just a few days ago about what they think about the word resilience and what they think about strengths-based research. It wasn't surprising to them that, of course, you develop strengths after experiencing risk. I'm sure many listeners here can think about things and skills that they've developed because of these hard experiences. It is important to recognize that risk and resilience can happen at the same time.

BS: Autumn, how do you in your pre-clinical laboratory studies, how do you operationalize the idea of resilience?

AI: To Arianna's point, if you look at the basic science or basic neuroscience research, a lot of attention has really been paid to what happens after chronic stress or acute stress. How is the brain adjusting and having these negative long term outcomes? But a lot less attention has been paid to what we can do about it. That's a point that's actually made in the Neurons to Neighborhoods publication. That's exactly what my lab is doing. Is we are focusing on at least one type of intervention that we think may be helpful, purely to understand how the brain can respond to exercise and whether we can actually identify on a cellular and a molecular level, what mechanisms are involved that are engaged by the brain with exercise to actually improve outcomes. Some of the early work in my lab has actually shown that with our rodent models, if we exercise mice when they're juvenile ages. For a human equivalent, if we think about human brain development, it's around childhood ages 3-5 years of age. If we introduce voluntary exercise, around those time points, and then we look at how those mice learn later on in life. They are more efficient with their learning. Specifically, again, the hippocampus dependent learning, the region of the brain responsible for memory and spatial memory specifically. That's what we test. These animals learn better and learn more efficiently when they are "Primed by this early life exercise experience." The lab also thinks about resilience by introducing exercise as an intervention. The model that I mentioned to you earlier, that early life diversity model, we use that model, and we know it's been well established that the offspring of this early life diversity model. When the moms give more erratic and fragmented care to the pups, they don't learn as well when they become adults. Can we do something about it? Can we identify the mechanisms of the early adversity causing this learning impairment and the intervention that may potentially buffer? We introduce exercise after early adversity. We're finding that there are some mechanisms, and again, I'll go back to the mechanism I'm focused on and most interested in epigenetic mechanisms. We're really finding that these are able to mediate how the brain is going to respond to early life adversity and early life exercise. We're starting to get some interesting findings to show some overlap between some of the epigenetic mechanisms between stress and exercise. When there is overlap, that allows us to identify targets for intervening, or at least think about what types of exercise are important for intervening after adversity, or other types of early life experiences that may have mechanisms in common with exercise that we can use. That's how my lab really thinks about it. We have the advantage of using these pre-clinical models in order to look at cells, look at molecules, identify these epigenetic factors. Then once we identify them, hopefully we can translate that back to human experience.

AG: I actually have a question because we have all these smart people in the room. I'm curious if you guys think that as since the 2000s, or since the Neurons to  Neighborhoods report came out, do you think that the focus on environmental exposures has moved farther outside of the home and the family context to really start including structural determinants? With Autumn, I'm thinking with you, walkability indices and more structural level policies that could enable folks to exercise. At least, as a young scholar, that's just something that I feel moving farther and farther away from the individual and more to the systems.

AI: Absolutely. I think that more and more we have leveraged technology to build better and better tools to let us understand measurements of the environment on the neighborhood level, on the societal level. We can use geographic indices to get at those, but we also think about the environment as what happens in the home and what things could be in the home. Whether it's social interaction or social support, or adverse experiences in the home or chemicals in the home. We can also now think about what happens at the neighborhood level for those same experiences or in schools. As we've gotten more and more sophisticated measurement techniques and gotten better and better biostatistical tools, we can actually really start to answer those questions from neurons to neighborhoods quite literally across multiple levels. One of the other cool things that's happened now too is that some of these tools that we use in population sciences have been begun to be applied to big data sets that have collected actual brain imaging data over time, so we can really see how factors in the environment. Anything of the list I mentioned from the physical environment to the built environment to the chemical environment or the perinatal environment even, might really impact actual real measures of brain structure or function and development as children age.

BS: We've been talking about structure, a measurable structure under the microscope, perhaps or in a MRI, but let's talk more about the function or in this case, cognitive development. What do we know about the way these environmental threats or exposures have impact on cognitive development per se?

HV: That's a great question. There have been many studies from the population literature and from clinical literature as well, but let us see that specific environmental contaminants can be deleterious, for example, to brain development. There's a growing literature out there on air pollution and cognitive development and quite interestingly at the same time on cognitive decline, showing that individuals who reside in areas with higher levels of air pollutants are less likely to have cognitive development on the level that they would in the population on average, and the individuals who live in areas with higher levels of outside air pollutants also experience higher rates of cognitive decline, so that's happening more rapidly be under the spectrum. When we think about the brain being plastic, this is pretty provocative to think about something that we could modify in our environment that impacts us both in early life and latent life. Even beyond that, if you think about the environment coming, for example, from dietary sources. We know that folate, at least in the United States, is a routine supplement in many food sources, partly because of the influence on brain development. While it was originally put into supplementation to help prevent neural tube defects, we've also seen literature from population studies that let us see that folate levels that mothers have during pregnancy are associated with improved cogitative development in children as they get older. The environment, in this case, can really range from a lot of different things, and it lets us find really neat targets to think about how we can impact children's growth and development.

BS: Heather, sticking with this point, air pollution in a given environment, you can measure that. But how do you quantify the exposure at the level of the individual and maybe not just one exposure, but exposures? How do you quantify the complex exposure? Talk about the individual exposures and how you quantify that and use that to understand an individual's risk for adverse outcome from it.

HV: When we're trying to measure the environment, the first place we start in our studies, and keep in mind that we don't study 10 people or 20 people. We're studying hundreds or thousands of people at any given time. The first thing that we do is we ask a lot of questions. We ask a lot of questions around what you ate, and where you slept, and where you work, and what you did at work, and how you got to work, and what did you do in your home, and where did you go to school, and what happened did your school day that day, and how did you feel about that to really try to begin to quantify any of those things on an individual level. Some of the other cool tools that we now have are to use technology to help us measure the environment. Based on an individual's address, we can use that, whether it's an address at home or school at work. We can use that to link to air quality monitoring around the United States. We can raise that to link to geographically determined measures of walkability or neighborhood safety, and then even more so as folks have gotten really interested in using wearable technology for research. The things that can be reported on your step count on your smart watch, we can begin to think about sleep quality and how light measured in brain development, or how many steps you took that day, or where exactly you went. Then finally, one of the other tools that we have to measure the environment is for those folks in research studies who have given biospecimens to let us begin to think about actually measuring physical doses of environmental chemicals in things like hair or toenails or teeth or blood that lets us get a handle on how much of a particular chemical and usually an environmental chemical has actually reached that person.

AG: Heather, I think you and I have talked about this too, but people have also started to use those mobile wearable technologies to map the spaces that people go. Maybe not just their home address, but for example, there is some research that shows that people of certain demographic groups are either forced or go outside of their neighborhoods more often. If you only used their home address, you might miss some of their exposure.

BS: Arianna, I'm interested to your take on whether age or sex are factors in risk and resilience and vulnerability to exposure. Are you particularly vulnerable as a young child? Are you particularly vulnerable if you are a male or a female?

AG: The time period is one piece, and then also sex is another. In terms of time period, we can look at the developmental parts of somebody's life where there's massive changes in brain development and also large hormonal fluctuations. That gives us the first few years after birth, as well as the prenatal period, as Autumn said, really highly sensitive to environmental influences for good and for bad. It's not just harmful influences but also positive, and then the other developmental period that I think is forgotten is adolescence. Hormones really open up this window of opportunity again. I love to tell families it's not over if your child is already 6 years old. Adolescence is actually a very large period of time, and then I'll say that sex is interesting. Nearly every environmental factor impacts girls and boys differently in terms of type of exposure, frequency, intensity, and those are determined by cultural, societal norms, as well as some biological factors, too. Just one example is in studies of girls and women. We do see that females attend to other people's facial expressions at higher rates than males. This is surely societally influenced but is also supported by hormonal differences. They also recruit brain regions that support thinking about other people and emotion while looking at facial expressions at higher rates. Yes, definitely. Autumn and Heather curious to hear what you guys think in your own fields, too.

AI: Yeah, I can comment on that. In the preclinical world, regarding biological sex differences. Thinking about biological male versus biological female, how are they impacted by not only early life stress but the intervention that we look at in our lab, which is exercise? The exercise literature is actually a really young field, believe it or not, in terms of focusing specifically on aerobic physical activity and how it impacts brain development in boys versus girls. We do find in our lab that there are sex differences in the propensity to exercise and actually the rewarding benefit of exercise, which is really fascinating. We're still trying to disentangle. But in juvenile and adolescent periods, we find that the biological females are wanting to exercise more for some reason and find it potentially more rewarding. We're starting to look at these reward circuits in the brain to see why, at least in this species that we're looking at, which is mice, why the females are wanting to run more. What relevance that has for humans? I don't know, but this is something that we're starting to observe in my lab as it pertains to early life exercise. Now, with regard to early life chronic stress, there are other labs that absolutely focus on this in the preclinical neuroscience research world and find that there are different vulnerabilities to later life, depression, and other types of mood disorders in males and females, particularly with the early life chronic stress model that I mentioned earlier, where there's fragmented maternal care. The males seem to have a greater propensity for this long-term depressive-like behavior compared to the females. Again, this is preclinical neuroscience research. We have yet to see how this translates to humans. But we're starting to see some interesting sex differences in Arianna to your point about adolescence. The window of opportunity in our rodents to actually look at development is very short. It's hard to really disentangle the juvenile and adolescent periods, but we can actually look at hormone levels and correlate that with the development of the rodent. We're thinking about during this early diversity model that I'm talking about, and the paper I'm talking about is this late juvenile early adolescent period where there's this vulnerability. But again, this is in mice. We have yet to extrapolate this to humans.

HV: Autumn, you make me want to incorporate measures of exercise into all of our population studies today in talking to you. What I would say from a public health perspective is we are always trying to figure out if there is something different when we see rates of diagnoses happen, that are different in boys and girls in the US. If we think about autism or ADHD, which are two of the more common developmental disorders we see that differentially have diagnostic rates that are different between boys and girls. What is it? Should we be looking at chemicals in the environment that disrupt the underpin system? Is it one of the common chemical exposures or common perinatal factors, things that might happen during pregnancy that wouldn't make any difference, but it relies on the genetic makeup, the underlying gene of the epigenome of boys and girls that makes those changes happen different, and so I think that these are things that we're always trying to tease apart. One of the real challenges that we have is even when we're studying thousands of individuals is to have enough people and often girls represented in some of our research studies with some of these given diagnoses that there are just few of them out there to want to participate.

AG: Yeah, and I will say that studies are getting bigger and bigger in humans. Thousands and thousands of people, and one of the reasons is if you want to study the source, the roots of something like ADHD, you have to account for so much variation between people. It's not just going to be genetics or environmental factors, but it could be socialization practices, and so the more people you have, the more variation in those things you can account for.

BS: That's a great point. I think the action is in the variation. Historically, there were efforts to try to squeeze out variability, and that was the wrong direction, the richness of data available now and our ability to analyze it, we are in a position to now capture that variability. It's a great point. Heather, how do you think scientific findings should impact policy? What role do you think that we as neuroscientists have in making the case for linking neuroscience findings to policy, to policy makers, to educators, even presenting it to parents and patients?

HV: That's an awesome question. One of the things that I think is really important as a neuroscientist is really thinking about how these findings apply to people and public health is one of the things that I think lets us start to do that. Think about what are the implications of our work and how do they come together? We are always very conscious about the fact that I want the findings from our our research study to be clearly communicated to our peers, but even more so, how do we explain this to a person with a child with a particular diagnosis or disorder or a family struggling with adversity on some level. How do you make your findings relatable? We increasingly work to try to talk with members from our community here in Baltimore and also around the country who represent some of the diagnoses and characteristics that we're studying to know how they would like information delivered and how we can try to make it digestible to people who aren't scientists. In terms of policymakers, there are real implications and real examples coming from environmental health where changes in scientific policy have come out of scientific data and real publications that we can see. We know that air quality findings on respiratory health and cardiovascular health have helped improve air quality across the United States. Hopefully, findings that are out there now and emerging on nerve development and cognitive decline further help bolster those findings and policies that could be put in place. From a totally different perspective, we also know that kids need to be fed and they need to be fed healthy food in order to succeed in school and thrive and do well, and so scientific research has helped support, policies in place to help provide free and reduced lunch at institutions and schools around the country. I tend to think that we as scientists need to be not only researchers and scientists, but also really work to be advocates and be open to trying to translate our findings to the very people they impact. In our case in public health, the people who are part of our studies.

AG: I couldn't agree more. We've thought a lot about this in our research group, and ideally, policymakers would directly consider neuroscience research, along with evidence-based from a ton of other fields. In practice though, I think this pathway is slow. I do think that we assign just have to recognize, this is a tough pathway. One thing that we started to think about is that, we think neuroscience can make a much larger impact by including community members in all aspects of the scientific process. Hosting open house sessions where caregivers and teachers can just ask questions. Leveraging the resources that we have to dive through the fake news. What does the science actually say? We're pretty good at summarizing the state of the field. We're pretty good at that. That's like what we're paid to do. Why not use those resources to help children and families. Then I think in terms of including children and teens, I strongly believe that neuroscience scientists can do far more educational outreach. For example, in many school districts in the country, students take standardized tests, at the end of the year. Oftentimes teachers have this gap of a couple weeks where they don't really have a lot of material. I think how fabulous would it be if neuroscientists could go into the schools, get kids excited about the brain. Couple of different times a week, different topics. We did this at the YMCA and DC. We brought some brain samples that the University of Maryland owns and talked about brain health. These kids were stoked. They were so excited about it. I really think that the educational outreach part of it is maybe another avenue that scientists can also feel we're doing something.

AI: I love all of the points made by Arianna and Heather and couldn't agree more. I'm clinically trained as a child neurologist, and when I was a pediatrics resident, I went to featured grand rounds. This was a while ago now, but there was a quote that was given at the end of the grand rounds that actually stuck with me. I'm going to share it here. If efficacious treatment exists, but there is lack of access, the treatment is futile. Similarly, if there is no highly efficacious treatment for a patient's disease and the setting of the risk factors, they still suffer. The overarching theme here that I'm hearing from the clinical work, as well as the pre-clinical research, and my motivation is that brain health is an equity issue, and access to brain-healthy behaviors is a health equity issue. This is directly relevant to policymakers. It's really important for us to on the pre-clinical basic neuroscience side, I'm studying exercise. But, this is something that's directly accessible generally to most human populations. However, is it really accessible to all of our communities? Is it safe for them to access safe spaces for play? Equally important good nutrition, healthy air. These are all brain health equity issues, but I think all of us align with the work that we do and the motivation for our work. That's directly relevant to our policymakers. I think if we pitch it that way and we think about it in that way, what we find can absolutely inform policy.

BS: I'd like to close with asking each of you to comment on what you see as the next important steps in your own research, or perhaps in the research realm that you work with in. Arianna you want to start?

AG: The questions that keep me up at night are how are we going to actually integrate community members into neuroscience research? Community-engaged research has been around for a long time in other fields in public health and education. But there's unique challenges to neuroscience. I think particularly the steep learning curve and the appropriate hesitancy about measuring brain structure and function. How do we actually include folks meaningfully in the process without just telling them that this is the study we want to do, and you should participate? This is an intractable problem. It's pretty difficult, but I think that there are some folks who are really trying to do this and do this, as Autumn said, in an equitable way.

HV: My collaborators and I are fortunate to be involved in a couple of large initiatives in thinking about developmental neuroscience in the environment. The first is to build a large network of research studies to study genes and the environment together, thinking about autism and related traits and cognitive development. When I say a large network, I mean pulling together data sets of over 100,000 individuals to answer these questions, which we've not been able to do before. For me, that is one of the big things that we think are next to really go after this major and nurture question in a meaningful and well-powered scientific way. The other two big initiatives that we are lucky enough to be involved in are national efforts to really characterize child's health. One is the environmental influences on child health outcomes initiative or echo through NIH, which is longitudinally following a large cohort of individuals throughout their lives to study how the environment impacts multiple aspects of child health. Neuro development is one of those. This national NIFT initiative really lets us see on a big population level, how the environment can affect kids. We are really championing and I am part of a group that is really pushing a lot of as much neuroscience and as much neuro development measures we can get on that big cohort data. The final thing is really think about involvement in the healthy brain and child development study or HBCD, currently funded by the National Institutes of Drug Abuse around the country. HBCD is recruiting a population of pregnant persons to really study the impact of the environment and prenatal substance use directly on measures of kid's brain development in the early years of life. Here in Baltimore, this is incredibly provocative to do, one because it really gets us connected with the community really doing neuroscience in the community, and having to partner with folks in the community here in Baltimore to get them engaged in research. The other thing is schema really incredibly meaningful questions beyond substance use, which is the primary focus. Let's just think about how important things like neighborhood safety or access to care or chemical environments might modify some of these relationships that you could see with primal substance use and brain development as well.

BS: And Autumn.

AI: Many fun directions, and I got so many ideas just from this conversation. Thank you. As the basic neuroscientists here, the direction that we tend to go is thinking about, what molecule or what target can we find that can influence the long-term outcome after this early life experience of stress or the early life experience of exercise. Right now, we have a few candidate epigenetic mechanisms that we`re targeting and manipulating in the lab to look at how if we either take away their function or enhance their function, can those things actually help the developing grade. These are targets that we identified after introducing this exercise experience in rodents. We're really excited about that. Another direction that I would love to go into is actually starting to translate this work to humans and thinking about the volume of exercise, the type of exercise. What heart rate should you be targeting? How long should it be? At what ages should we introduce it? These are all open questions, that there are some neuroscientists out there right now working on them, but not enough. I think that we really could grow this area of neuroscience research where we're actually thinking about interventions, and what can we do about the consequences of chronic stress or chronic exposures that are maladaptive. How can we buffer against those? That's really the direction of my work is to try to make it more translatable and also think about how to buffer against these early life maladaptive experiences.

BS: Well, I'm hoping that each of you will provide us with some links to online resources that you'd like to share so that listeners interested in learning more can get to them, and we'll post those on the web page along with this podcast. But that's an excellent place to end. Thank you. I want to thank our guests, doctors Arianna Gard, Autumn Ivy, and Heather Volk. We hope that you, our listeners have found this discussion about the science of early childhood brain development interesting and informative. Please check out our entire library of topics on your child's brain at wypr.org, KennedyKrieger.org/ycb,  or wherever you get your podcasts. You've been listening to Your Child's Brain. Your Child's Brain is produced by Kennedy Krieger Institute with assistance from WYPR and producer Spencer Bryant. Please join us next time as we examine the mysteries of your child's brain.