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Understanding infants and toddlers with fragile X syndrome: New Research

Updated: Apr 3, 2019



Background

If you look at what we know about fragile X, most of it comes from research on older children, adolescents, and adults. So we know very little about fragile X in infancy and toddlerhood. Is this a problem? We believe that it is! In our view, it is very important to learn as much as possible about how children with fragile X develop early in life. Why?

From research on typically developing children, we know that the infant brain is very different from that of older children and adults. The infant brain is more plastic than the adult brain. This means that experiences have a greater effect on the infant brain than on the adult brain. We also know that different parts of the brain are highly interconnected in infancy, prior to becoming more specialised.

Because of this plasticity and interconnectivity, an early deficit in one domain can have cascading effects on other domains over time. This may sound a bit abstract, so here’s an example of what we mean. We know that one way that typically developing children learn words is through something called triadic interaction (Figure 1). This is when (1) the parent looks at her child to catch his attention, (2) the child looks back, establishing eye contact (mutual gaze), (3) the parent then shifts her gaze from the child to an object or event of interest (e.g., to a toy), (4) the child follows his parent’s gaze (gaze following) and attends to the object that his mother is now focusing on (shared attention). (5) The mother then names the object. (6) The child may repeat the word he heard from his mother. (7) Finally, both mother and child look back to each other. Or this might be started by the child: he sees an interesting object, points, and looks at mother, who in turn names the object.


An example of triadic interaction between a mother and her child, which involves shared attention to an item of interest.

Now, imagine that you are a baby born with a problem in vision. This will affect the way in which you follow people’s gaze, including your mother’s. It will thus affect triadic interaction. Over developmental time, it could also constrain your ability to learn words. So a very early deficit in the visual domain can cascade and cause impairments in the social domain (e.g., language) later on in development.

But this cascading effect could also be used to our advantage – because improving one domain early in infancy (e.g., visual attention) could subsequently improve other domains (e.g., language acquisition). So it is important to investigate not just language, but also lots of other abilities in infancy that might later constrain language development – such as visual attention, speech discrimination, sleep. Many of the problems that older children and adults with fragile X suffer from are unlikely to be the direct result of the silenced gene; rather, the cascading effects of basic-level deficits such as visual attention are likely to underlie them.

So, our aim is to understand how different domains (visual attention, speech processing, etc.) in infancy are connected over development, and how they constrain the development of later emerging domains (e.g., language). We do this by testing different groups of children (8- to 40-month-olds with different kinds of disabilities – fragile X syndrome, Down syndrome, Williams syndrome) on different tasks across different domains. Cross-syndrome studies are important because they can tell us whether a problem is common to all neurodevelopmental disorders, or whether it is specific to a particular disorder (e.g., fragile X).

In this article, we will present what we have discovered from two tasks – visual attention and speech processing. We will also discuss how they relate to language development. Finally, we will also tell you about a new project we’re working on – how sleep affects language development

Study 1: Visual Attention

An example of eye tracking technology, where an eye tracker is calculating exactly where on the computer screen a child is looking.

In the first study, each child sat on their parent’s lap and watched colourful moving cartoons appear on a computer screen, make noises, and then disappear. We used an eye tracker (technology for tracking eye movements; see Figure 2) to measure how quickly the child could shift his or her visual attention from one cartoon character or object to another.

Using the eye tracker, we discovered that toddlers with fragile X are relatively slow at moving their eyes from one object to another (they are slow at disengaging their attention). However, compared to children with fragile X, difficulty with disengaging visual attention was much worse in the infants/toddlers with Down syndrome. Moreover, although the disengagement problem was related to language development in Down syndrome, we did not find the same relationship between disengaging attention and language ability in fragile X. It is important to note that currently in our study we have many more children with Down syndrome than fragile X. The analysis of results of studies like ours very much depend on the number of participants. The more participants there are in a study, the more likely it is to identify a relationship if one truly exists. Therefore, before we can draw firm conclusions, we need more participants with fragile X to detect whether there is a relationship between disengaging attention and language abilities in fragile X.

Study 2: Speech Processing

In the second study, we wanted to know how the brains of children with fragile X process speech sounds. Before any child can acquire language, they must first develop the ability to discriminate speech sounds and attach importance to these sounds in noisy everyday environments. In typically developing infants, the ability to discriminate and orient to speech sounds is associated with better language outcomes. But we know that some children with fragile X acquire language late or not at all. Could it be that their difficulties with language are partly related to problems with how the brain processes sounds?

During this study, each child sat on their parent’s lap and watched cartoons. We also played some speech sounds (vowels) that occasionally changed either from one vowel sound (/u/) to another (/i/) or they changed in pitch (high, low). While these sounds were playing in the background, we measured the child’s brain activity using electroencephalography (EEG). This involves placing a “hairnet” gently on the child’s head (see Figure 3). The “hairnet” contains little sponges that measure naturally occurring brain activity – a bit like how a thermometer measures temperature. Using this technique, we found that children with fragile X have difficulties with processing sounds.


One of our participants wearing an EEG “hairnet”.

One of the brain responses we recorded turned out to be especially important for children with fragile X. The social orienting brain response (called the P3a) in the toddlers with fragile X was small relative to the social orienting brain response in typically developing infants, Down syndrome, and Williams syndrome. This means that the brain of children with fragile X attaches less importance to changes in speech sounds than most of the other groups we studied. But is this linked to their language ability?

To investigate this because there were lots of individual differences, we split the fragile X group down the middle, to form two subgroups. One subgroup consisted of the children with a relatively large social orienting response (a large P3a), while the other subgroup consisted of children with a relatively small social orienting response (a small P3a).

We discovered that the toddlers with fragile X and a relatively large social orienting response understood language (receptive language) at the level of a typically developing 20-month-old. But those with fragile X and a relatively small social orienting response had the receptive language ability of a typically developing 9-month-old (Figure 4). Furthermore, toddlers with fragile X and a relatively large social orienting response could produce language (expressive language) at the level of a 13-month-old, whereas those with a relatively small social orienting response had the expressive language of a 5-month-old (Figure 5). This suggests that the ability of the brain to attach importance to changes in speech sounds could be an important mechanism in the acquisition of language in fragile X, because those who showed a relatively large social orienting brain response had much better language skills than those who showed a small response.


Receptive language age equivalents (in months) in typically developing infants (called Control in the above graph), in infants at risk of developing autism (called Sibs), and in toddlers with Down syndrome, fragile X syndrome, and Williams syndrome.

On average, the typically developing infants and infants at risk of developing autism were 15 months old, while the toddlers with Down syndrome, fragile X, and Williams syndrome were around 30 months old. However, all the children in this study had a Mental Age of about 15 months. What this means is that the children with Down syndrome, fragile X, and Williams syndrome present cognitive abilities and behaviour that are at the level of a typically developing child of approximately half of their chronological age.


Expressive language age equivalents (in months) in typically developing infants (called Control in the above graph), in infants at risk of developing autism (called Sibs), and in toddlers with Down syndrome, fragile X syndrome, and Williams syndrome.

On average, the typically developing infants and infants at risk of developing autism were 15 months old, while the toddlers with Down syndrome, fragile X, and Williams syndrome were around 30 months old. However, all the children in this study had a Mental Age of about 15 months. What this means is that the children with Down syndrome, fragile X, and Williams syndrome present cognitive abilities and behaviour that are at the level of a typically developing child of approximately half of their chronological age.

Currently Investigating: Sleep

We have also begun to look at sleep in fragile X. Sleep is essential for memory and learning, brain development, cognitive performance, mood, and a healthy immune system. For example, if you teach a finger-tapping task to children, they will be better at the task after they have had a good night’s sleep than before. Yet a recent study has revealed that sleep is disrupted in 15-16-year-olds with fragile X. The lack of sleep in these adolescents was also associated with mood, health, and behavioural problems.

However, we don’t know what sleep looks like in infants and toddlers with fragile X. Is sleep disrupted at an early age in fragile X? Is it linked with the developmental difficulties that these children experience? We don’t yet know the answers to these questions. But we would definitely like to find out.

So far, we have given 10 families with a young child with fragile X a sleep diary. Over a period of 7-10 days, the parents used the diary to mark down when their child was asleep and when their child was awake. We discovered that half of the children had similar sleep patterns to typically developing children, while the other half showed a very scattered sleeping pattern. Take, for example, Figure 6 (below). Here you can see the sleeping pattern of a typically developing 38-month-old (on the left of Figure 6). Along the side are the 10 days and along the bottom are the hours of the day, from 6 a.m. in the morning to 5.59 a.m. the next day. Black represents the time when the child was asleep, white represents the time when the child was awake. You can see that this toddler slept from 6.30 p.m. to 6 a.m., every day for the entire duration of the study (a total of 10 days). Yet the toddler on the right with fragile X (who is of a similar chronological age) shows a very scattered sleeping pattern. For instance, on Day One, the child had a long nap in the afternoon, fell asleep at around 9 p.m., but woke up for an hour in the middle of the night. Similar disrupted patterns can be seen for the other days, too.


On the left is the regular sleeping pattern of a typically developing 3-year-old. On the right is the irregular sleeping pattern of a 3-year-old with fragile X. (Black= asleep, white= awake)

We also sent the parents a list of words and asked them to tell us how many words in the list their child understands (receptive language), and how many they can understand and say (expressive language). Our next step is to work out whether sleep in these children is linked to their language ability.

However, we have only received sleep diaries from ten parents. We would really like to send sleep diaries to more parents of infants and toddlers with fragile X. We want to know how variable sleep patterns are in these children, and whether they are linked to how well they understand and say words. If you have a child between 6 months and 4 years of age, and you would like to help us with this study, we would love to hear from you. Please contact Dean at dean.dsouza@ymail.com or on 07800 882191 and we’ll send you one of our sleep diaries to fill in. It would help us learn more about fragile X in young children.

Also, if you have any questions about any of these studies, please contact Dean (dean.dsouza@ymail.com).

Once again, thank you for your kind support; we couldn’t do any of this research without you. We would also like to thank our collaborators, Dr. Klara Horvath and Prof. Gaia Scerif at Oxford University, and Prof. Mark H. Johnson at Birkbeck, University of London.

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