In this podcast Assistant Professor Dr. Dienke Bos discusses neuroscience, and in particular neuroimaging. The interview looks at the typical development of behavioural control and how this is represented naturally, magnetic resonance imaging to monitor brain changes in relation to childhood development, and where the evidence is that early intervention can slow or reverse damage.
Dr. Bos also talks about her research on longitudinal studies, how social emotional processing evolves from adolescence into early adulthood, and what’s in the pipeline for her work.
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Transcript
Interviewer: Hello. Welcome to the ‘In Conversation…’ podcast series for the Association for Child and Adolescent Mental Health, or ACAMH, for short. I’m Jo Carlowe, a freelance journalist with a specialism in psychology. Today, I’m interviewing Dienke Bos, Assistant Professor at the University Medical Centre Utrecht, UMCU. Dienke is part of NICHE, which is the Neuroimaging in Childhood Laboratory and has a long-standing interest in neuroscience. Dienke, welcome. Thank you for joining me. Can you start with an introduction?
Dr. Dienke Bos: Hi, Yes. Well, thank you for having me. Of course. As you said I’m Assistant Professor at the Department of Psychiatry at UMCU, and I’ve been there for quite a while, actually, little over ten years, I think now, in the lab of Professor Sarah Durston. I did my PHD there which was very focused on structural and functional connectivity. So the firing and wiring of the brain in autistic kids and kids with ADHD. After that I did a fellowship at the Sackler Institute of Developmental Psychobiology in New York with Professor B J Casey and Dr. Rebecca Jones, which actually then resulted in a two-year postdoc in which I split my time between New York and Utrecht which was very exciting. But now I’m back in Utrecht full-time again. And mostly working at this moment within a very large cohort study that we have running investigating self-regulation and behavioural control, in a mostly typically-developing cohort. So a lot of different things.
Interviewer: Okay, great. And we’ll look at some of that work shortly. You’ve described yourself in the past as hooked on neuroscience. What initially sparked this interest?
Dr. Dienke Bos: So I actually had to think about that again. But as I first went to college, I did one year of University College in Utrecht which is based on the liberal arts colleges. And I was at that time thinking I would want to work for the UN and do international relations and all that. And I had a course in political science and it was not for me. And then I actually also took a class in cognitive neuroscience, and I just thought that was so interesting. So I think that captured my attention. I switched studies to psychology. And I think all throughout my studies, I was very interested in developmental psychology or just development in general. But also the neuro part of that.
Interviewer: Yes. As you mentioned in the intro, your early work focused on the anatomy and functioning of the brain, but you have shifted over time to look at typical development of behavioural control and how this is represented neurally. Why did you make the shift?
Dr. Dienke Bos: An interest in cognitive control or how we regulate our behaviour has always been there. At the time, I had a study I was involved in, investigating the effects of omega-3 fatty acids, so fish oils, on cognitive control and neural circuitry in kids with ADHD. The main focus of my PhD was really very, almost fundamental questions about how the brain was wired, how brain regions are connected, and how the brain is functionally connected in children with autism or ADHD. I thought that was very interesting, obviously.
So at the beginning of my PhD, I have to admit, I just thought it was very cool. But as my PhD progressed and you learn more about the possibilities but also limitations of neuroimaging, I just experienced there was this large gap between these very fundamental questions or very fundamental research in how the brain is wired and connected, and the actual daily life experiences of these children with autism and ADHD. And I think I then already started to think about wanting to do something slightly different, something that was much more to do with these individual experiences of kids who have these disorders. Or at least to attempt to make neuroimaging research much more valuable in daily life, so to say.
On the other hand, I was actually also running into all sorts of conceptual problems. Because it is very typical still to investigate developmental disorders, such as ADHD and autism, and treat these children as if they are one group or category. So we compare children with ADHD against children who do not have ADHD, or compare children with autism against those who don’t have autism. And, in a way, we then assume that all of these kids with autism or all of these kids with ADHD have something that is very common for that diagnosis. And obviously they all have the same diagnosis, but I think this picture that has been emerging over the past, well, decade, I think, is that, if anything, kids who have a diagnosis, ADHD, well, that is probably the most common thing about them, that they have that diagnosis. But they are very different individually.
So all these findings where we find differences between groups of children with ADHD and groups of children without, we may find statistical differences. So as a group, they might slightly differ from one another in how their brain functions or how it is built, but that doesn’t say anything about whether a particular individual child with ADHD has that particular difference in his or her brain, if you understand what I mean.
Interviewer: So just to clarify, will similar behaviours represent very differently, however, in the brain?
Dr. Dienke Bos: Yes. So this is really interesting. I’ve definitely, myself, found either… And this is the thing in neuroimaging research. So quite often, actually, you might find differences in behaviour, but not find any differences in, for instance, brain activity. This happens. And whether that means that there are truly no differences in brain activity remains to be seen. But at least we do not find it in these studies. On the other hand, yes, sometimes definitely you might find differences in brain activity or brain connectivity or anatomy, without any differences in behaviours. I think the easy way to get out of that has always been to talk about compensatory mechanisms. There might be some neural compensatory mechanism making sure that, on the surface, the behaviour looks the same, but the brain might function slightly different in how to produce that sort of similar behaviour, so to say.
Interviewer: Wow. Dienke, it’s really fascinating, isn’t it? And your research areas are diverse but, as you’ve explained, mostly using magnetic resonance imaging to monitor brain changes in relation to childhood development. Can you give some specific examples of what you’re studying now or what you studied recently?
Dr. Dienke Bos: Yes, of course. So one of the things that I find really interesting that I’ve done at my fellowship at the Sackler Institute is, many of the tasks that we use, in this case investigating cognitive control or the ability to regulate your behaviour, are very neutral. So, we ask children to respond to the letter X, but do not press the button when you see the letter A. Or respond to blue squares but not press a button when you see a yellow square. And these might uncover very fundamental changes, maybe in inhibitory control, but what I’ve seen, at least in my research, is that many of the children that I see, especially those with autism, actually perform very well on those tasks.
But they do have problems regulating their behaviour in daily life situations. So what we did there is adapt this task, and instead of using these very neutral cues, we had them pick categories of interest. So, for instance, trains or cars or sports. And then we would show them these pictures of things that they really liked and things that they didn’t care about so much. And then suddenly we did see changes in their ability to regulate their responses. If they saw something that was very interesting to them. And we also did this in a group of young just neuro-typical adults. And we also showed that, if you see these images of things that you really like, really care about, that showed activity in the insula. And the insula is this brain region that is really involved in capturing salient information. So if you see something in your environment that is very salient to you, chances are that your insula then activates in that process. So I think that was very interesting. Basically showing that the nature of the cues that we use in research really matters in showing whether children with autism can or cannot regulate their behaviour well.
One of the most notable findings from the study in kids with autism was that the children with autism actually performed very well on the neutral version of the test. So if we showed them blue versus yellow squares and their performance was very similar to the kids without autism. But when we showed them these pictures of their hobbies or interests, then we saw that their attention was really captured by these pictures that showed their interest, and they made much more errors on the task. Which seemed related to their inability to keep going on the task. They were so probably captured by the things they like that they forgot to progress with the task.
And what was interesting was that this ability to control your behaviour when you see something you really like was also related to rigidity, to rigid behaviour, as rated by their parents. So it was also related to something that the parents reported in real life.
Indeed, if the parents reported more rigid behaviours in these children, these would also be the children that had a harder time on the task controlling their behaviour when they saw the pictures of, for instance, trains or planes or sports or anything else that they really liked.
And I think what’s the important take-home message there is that it really matters, that the situation that you are in really matters. So that under very structured, neutral circumstances, also children with autism, maybe not all but definitely many of them, at least in our study, can just control their behaviour, if it’s very neutral and structured. But if you insert something in that situation that is, for instance, very motivating to that particular child, then suddenly you might see that they start having a little trouble regulating or controlling their behaviour. Which is actually what you also see in real life and what these parents then also report.
Interviewer: If I’ve understood it correctly, you investigate both structural and functional connectivity. Can you explain the difference between those?
Dr. Dienke Bos: Yes, of course. So, structural connectivity is basically the wiring of the brain. So the axons that connect the different brain regions. And if you compare it to… I think the best analogy still is to compare a network of highways and roads. So structural connectivity is the roads, the highways. And functional connectivity is the communication between any of the brain regions. So basically the traffic that moves over all of these roads and highways.
Interviewer: Yes, they’re pretty clear. And when you’re doing scans on children, how do you measure between the two? Can you give some sense of how it works?
Dr. Dienke Bos: So structural connectivity is measured using a technique called DTI, Diffusion Tensor Imaging. And without going in too much technical details, children don’t really have to do anything during that because the MRI scanner will just map the white matter, the axons, the wires, so to say. And we actually let children watch a movie during those type of scans. And then functional connectivity can actually be measured in multiple different ways. One way is to have children do a task. So we, for instance, can have them do tasks that measure control or their ability to regulate behaviour. But we can also measure memory or all sorts of social interaction things. And that is one way. So then actually we can measure how the brain functions during the performance of a task of very goal-directed behaviour. Another method that is very frequently used is resting state functional MRI. And this is where we measure activity or connectivity of the brain during rest. And this is relatively hard for young children because we literally ask them to do nothing for ten minutes. They cannot watch a movie. They just have to lie very, very still and just let their minds wander. That is the instruction that goes with that. So the thing that we actually measure is almost like daydreaming. And the thought or the assumption that goes behind that is that we then see the more intrinsic way the brain is connected, without performing any type of goal-directed behaviour or task.
Interviewer: And I’m wondering, in these studies, have you found in the way the brains of children and young people who could be described as neuro atypical work, are these different to other children?
Dr. Dienke Bos: So if I go off of my own work, I did find the statistical differences. So I did find differences between groups of kids who had ADHD or groups of autistic children, versus those that don’t have autism. And examples of changes were, for instance, in resting state connectivity. So the brain during rest, I found that children with ADHD had more strongly connected prefrontal brain regions. In autism, I found that children with autism had changes in connectivity of the salience network. So the insulas region that we talked about before that picks up on salient stimuli in your environment. So, roughly, in all studies that I either participated in or that I published myself, I think there’s this pattern of widespread or sometimes tiny differences in prefrontal brain regions, also subcortical brain regions. So these are like the basal ganglia. These are regions that really are involved in controlling your behaviour again, for instance. And I think that ties in with this… If you generally look at literature, those are the brain regions that seem involved in developmental disorders, such as autism and ADHD. So the prefrontal cortex, the cerebellum, so the little brain at the back of your head, actually also. But what is very hard is that, although there is this global picture that these regions are very likely involved in this behaviour that we call ADHD or autism, it is very much at the group level. So it doesn’t tell you anything about a particular child that has participated in the study.
Interviewer: Dienke, in the study on ADHD, you have described how functional and structural differences appear throughout development. What are the implications of this?
Dr. Dienke Bos: Yes. So what I think this really shows is this importance of looking at development. So you can look at the brain at one time during development, for instance, in childhood or adulthood. But that doesn’t tell you anything about how… Basically doesn’t give you any prediction of what the future will hold for a certain person. And our brain changes. And some changes may be present from birth and later disappear. This is actually a dominant theory in ADHD research, is that brain development is lagging behind a little. There are obviously also studies who do not find this. But development lags behind a little and then catches up. Which for a group of people is actually very much in line with the observation that children do show symptoms of ADHD, do show the hyperactivity, impulsivity and inattentiveness. But in actually a large percentage of individuals, these symptoms disappear as they grow older. And this theory of brain development then catching up would very much fit that. But then there is also a group of people who do actually have persistent symptoms in adulthood. So it does not fully explain.
But what is very important is that brain changes can definitely persist throughout development. But new ones may also occur, maybe throughout, maybe because of experience or because of something else. We don’t really know. But the most important thing is really that development is very important, and much more important than just looking at the brain at one point in time.
Interviewer: If changes that are associated with the disruption of brain networks are functional rather than structural, does this mean there is scope for change or prevention, possibly through early intervention, before more permanent changes occur in the way the brain is wired?
Dr. Dienke Bos: Yes. Definitely. So brain structure and function are highly related but definitely do not map onto each other one-on-one. To go back to the highway analogy, you could take the car from London to Manchester. You can just take a highway and then you’ll be there very fast. Or you could take a scenic route, pass all sorts of different towns, but you’ll also end up in Manchester. And with the functional connectivity, for instance, we really only look at whether this traffic actually ends up in Manchester, but not really how it got there. And if we, for instance, have people do a task. Or I think a very good example is also when, for medication intervention. So if you give individuals medication just before an MRI scan and then compare to when they didn’t take the medication, you really see these very fast changes in function of the brain. But it definitely takes more time to change the actual wiring of the brain. And so, definitely, yes. There is room for having the brain change as a result of, for instance, an early intervention. Yes.
Interviewer: So how much plasticity is there in terms of changes in the brain? And is there evidence that early intervention can slow or reverse damage?
Dr. Dienke Bos: Yes. So what I think is really important here is to stress that, especially in the far majority of children with developmental disorders, there is no brain damage. So I think it is more of a difference in just generally how the brain functions or is built than that there is actual damage. But talking about brain plasticity, which is basically how well our neural circuitry can be modified by experiences. And we know that this plasticity is largest in early development. So even our adult brains are plastic, but those of children are much more so.
And it goes both ways. So early adversity, like trauma or early cognitive deprivation or malnutrition, can have very, very longlasting effects on the brain. We know this. But it also goes the other way. So there have been studies that have shown brain changes in response to, for instance, therapy, both behaviourally or pharmacologically. Yet I think this process is very slow. So it seems… And this is somewhat outside of my expertise. But I think what these studies show is that you need quite intense behavioural therapy to elicit longlasting effects. And it also really matters when you give that sort of therapy. So there are critical windows, so to say, in development. And it’ll always be easier if you’re just at the right time in development. And I guess we don’t really know always when that perfect time is yet.
But there definitely have been brain changes that have been associated with early interventions. Although I must say that, entirely reverse or change the brain in such a way that it is, well, resembling that of someone who’s not autistic or doesn’t have ADHD, is almost impossible.
Interviewer: Have you been working on any longtitudinal studies that you can share with us?
Dr. Dienke Bos: Yes. So one of the studies that I was involved in recently, which I think is very interesting, actually, is a study performed by a PhD student that I supervised, where we investigated longitudinal development of cognitive control in children with autism, and compared those also with children with obsessive compulsive disorder. From this thought that both children with OCD and autistic children show compulsive behaviours. And we wanted to know whether, well, obviously, whether there were any differences in neural circuitry that were associated with these compulsive behaviours in both these disorders. And this was a longitudinal study. So these children were scanned twice, on average one and a half year later. And we found no differences.
So we did not find any differences in the way they performed a task, which I think also relates to what I explained earlier, that if you… That these children with autism, and apparently also OCD, if they do these very neutral cognitive tasks, that they’re actually able to perform those very well. And we actually also didn’t find any differences in the neurocircuitry that was involved. So that may be a reassuring message. It may be also a sign that those difficulties that we see in real life with controlling behaviour, with this compulsivity, in this case, that at least in this study, we were not able to capture that very well with the tasks that we typically use in research.
Interviewer: You’ve mentioned also that you’ve done work on social emotional processing. I’m wondering what you’ve learnt through your work with regards to how social emotional processing evolves from adolescence into early adulthood?
Dr. Dienke Bos: Yes. So this is really something I got involved in at the Sackler Institute. And it’s a relatively new but also very exciting field for me. Especially since adolescence is this just intriguing developmental phase in which so much happens. Especially, like you said, in terms of social and emotional development. And what is really interesting is this new body of literature that is now emerging, that this development of social and emotional skills through adolescence, that that actually continues into young adulthood. So some of these sensitivities that we see in adolescence, where adolescents are very sensitive to, for instance, social information or social cues, that actually shows prolonged development into young adulthood. So in your early 20s.
And one of the interesting things that we saw in a study that I did at the Sackler Institute also, was that the adolescents and young adults with autism that performed an emotional version of a control task, that they didn’t show the same heightened sensitivity to social cues that we see in typical development. So that might actually indicate that these autistic adolescents go through adolescence in a very different way. And this was just one study. And I think there’s so much more to say or investigate about that. But I think that was a very interesting finding.
Interviewer: Right. We touched on this a little bit earlier, but how have your findings translated to or influenced clinical practice or policy?
Dr. Dienke Bos: Yes. Well, they have much less than I want to. I think we covered this a bit before earlier, is that many of these neuroimaging studies, as interesting as they are, are very far from clinical practice and very far from daily life experiences. So they are quite fundamental, actually, in understanding how the brain works, how the brain works if you perform a certain task, for instance. And I think that is something that maybe even the field is also struggling with a bit, is how to increase value of neuroimaging research for clinical practice.
And I think one of the values that it definitely has is more on the intervention side. So it would be so helpful if, for instance, we could identify what type of intervention would work for a particular child. And then I think that biology or neurobiology can play a very important role in making such predictions. The one study that actually… funny enough, because it’s only one study that I did years ago… had some influence, was the study on omega-3 fatty acids, because it showed that there is a small but positive effect of taking omega-3 fatty acids on inattention, so symptoms of ADHD. And this finding… And obviously we were not the only ones who found that. But in general, this finding of this small but beneficial effect of omega-3 fatty acids seems to be trickling down into reaching clinical recommendations.
Interviewer: Are you optimistic that that might happen with some of the studies you’ve described?
Dr. Dienke Bos: As many of the studies that I’ve described, many of the neuroimaging studies, are so fundamental, I think those will really mostly help understanding how all of these very big, basic processes of regulating behaviour work, and how the neural circuitry is involved in that. As for the newer studies that I’ve been doing, investigating cognitive control in different situations, for instance, I think that will have a much more direct effect, because it can really show that usually, for instance, if a child comes in for a psychological evaluation, we do this in a very, very structured setting. It is quiet and there’s a psychologist who takes the child through all these very structured tests. But when a child is at school, obviously the situation is not that structured, or much less structured. And there will not always be someone who will guide you through what you have to do. So what I’m trying to do now, in some of my recent and current studies, is compare these very structured lab settings to more realistic daily life settings. And I think that can actually have a much more direct influence on either clinical practice or policy or daily life experiences.
Interviewer: Why is evidence-based research so important when it comes to child and young people’s mental health?
Dr. Dienke Bos: I think the best way to describe this, actually, is it’s the catchphrase from the youth cohort study that I’m involved in. And it’s why some children thrive and others don’t. So some children thrive and go through their whole development relatively uneventful and everything is fine. But other children really have problems to thrive or just don’t thrive as easily as others. And I think evidence-based research can really help us understand why that is. And if there is something, anything that we can do to, for instance, help children thrive or develop or in a better way. So this does explicitly not only apply to medication, because sometimes it seems that that type of research seems analogous to pharmacological studies. But this really also goes for all sorts of interventions. It may be help at home or support at school or training for parents. These are all things that we can study and which may really help us to find the support that some children really need to, well, hopefully get through development better or more easily.
Interviewer: Right. Dienke, what else is in the pipeline that you were working on or further research that excites you?
Dr. Dienke Bos: Yes. So one thing I’m really excited about right now is… going back to investigating what happens in different settings… is, together with a colleague from Utrecht University, Eva Van de Weijer, I’m currently conducting a study where we test working memory performance. And we are directly going to compare working memory performance in our structured lab setting but also in the classroom. So these children are going to perform these tasks in their own classroom with their own teacher. So the thought is that this is a very realistic setting and it allows us to compare, also on an individual level, the difference in performance between these two settings. So some children may actually have problems in both settings. But it might also be that some children do relatively well in the structured setting but have a harder time in school. And we hope that that can really ultimately lead to extra support perhaps for the children that need it, but also helps us to give advice on a very individual level what is best for these children. And the more technical or scientific term for this is the ecological validity. So how well this task that we’re doing corresponds to something that happens in daily life.
And this is what I’m currently also working on for my own research, to basically try to increase ecological validity and then make sure that the research that we do connects much better with the daily life experiences of children.
Actually one of the things to add to that is that, obviously, behaviour is so much more complex than just measuring one thing, for instance, cognitive control or inhibition or… These things are usually influenced by, for instance, emotions or motivation or how well you slept that night. And what I think is very exciting is, what is happening right now is that, also in the whole field, people are starting to look much more at the complexity of all this behaviour. So where we first try to reduce everything to one task or one questionnaire or one type of behaviour, we actually try to measure all sorts of different behaviours and then try to tie all those pieces together, actually. And in hopes, obviously, that that measures the complexity of human behaviour much better.
Interviewer: Great. And Dienke, what is your takeaway message for those listening to our conversation?
Dr. Dienke Bos: So, I think one of the most important things is… And I don’t know if that actually came out explicitly yet, but is… Probably because this is a question that we get asked a lot by parents who want to participate in our research. Is that it is simply impossible, at least at this moment, to use brain scans to tell if you, for instance, have ADHD or have autism. This is what we talked about before. And this is fully due to that we usually compare groups of children with autism, for instance, to groups of children that do not have autism. But it doesn’t tell you anything about an individual person. And at this moment we are really just not able to see that on a brain scan.
But the other important message I think is that I still believe that neuroscience will really help us in understanding, for instance, what kinds of treatments may be beneficial. And this doesn’t have to be medication but this can also be some sort of behavioural intervention or support at school, anything. So I really do believe that neurobiology or neuroscience can play a really important role in that.
Interviewer: Dienke, thank you so much. And really fascinating. For more details on Dr. Dienke Bos, please visit the ACAMH website, www.acamh.org, and Twitter @ACAMH.
