Flexible Choice Behaviour in Autism Spectrum Disorder

Written by: Ivy Cho 

With the environment around us continually changing, it is important that our behaviors are flexible in order to respond to these changes. However, a characteristic behavior seen in those with Autism Spectrum Disorder (ASD) is a desire for both behavioral and environmental consistency. The need for consistency has been said to be rooted within the restricted and repetitive behaviors (RRBIs) seen in ASD.

A recent study conducted at the University of Illinois Medical Center investigated the brain correlates of flexible behavior using magnetic resonance imaging (MRI), in conjunction with a learning task. Using functional MRI (fMRI), participants between the ages of 7-44 (17 ASD participants and 23 typically developing participants) completed a four-choice learning task.  During the learning task, participants were initially presented with a screen of four identical stimuli. With the four identical stimuli, they were asked to select which stimuli was in the correct location using a button box. Following, to measure behavioral flexibility a “reversal” learning task was presented. As part of the “reversal” learning task, the correct location of the stimulus would change and participants were expected to select the new correct location.  The results of this study found that during the “reversal,” ASD participants showed decreased activity in brain areas important in both decision making and learning.

These findings suggest that the desire for behavioral and environmental consistency may be due to differences in brain regions required in decision making and learning - and ultimately the ability to facilitate flexible behavior. This study provides insight into the underlying brain correlates of RRBIs, particularly important as there are currently limited treatment programs aimed to ameliorate RRBI symptoms in those with ASD.

 

Reference: 

D'Cruz AM, Mosconi MW, Ragozzino ME, Cook EH, Sweeney JA (2016): Alterations in the Functional Neural Circuitry Supporting Flexible Choice Behavior in Autism Spectrum Disorders. Transl Psychiatry. doi:10.1038/tp.2016.16. 

 

Does Size Matter?

Written by: Manu Schuetze  

Do people with Autism* have larger heads? Do they have larger brains? Or are some parts of the brain larger?

Leo Kanner first gave a clinical description of Autism in 1943. His main observations of atypical communication and interaction have been confirmed in several studies since then and now make up part of the diagnostic criteria for Autism. However, Kanner had also described something for which no clear evidence has been found in studies since then: “larger-than-normal” head circumference in people with Autism. Indeed, in 2014 a research group at the University of Alberta studied over 400 children and came to the conclusion that head size cannot be used as a marker for Autism (1). 

Besides simply looking at the size of a child’s head, brain imaging studies using MRI have tried to understand whether the size of the brain differs between children and adolescents with Autism and their typically developing peers. Since we know that certain parts of the brain are particularly involved in behavioural symptoms of Autism, these studies not only look at the whole brain, but zoom in to test for size and shape differences in these specific parts.

The basal ganglia play a particularly important role in Autism and consist of several brain regions that are located very deep in the centre of the brain. We call these regions subcortical, because they are located underneath the cortex. So far, research studies that tried to understand if and how these subcortical regions differ in size in people with Autism showed inconsistent findings. For example, some studies found that the caudate nucleus (one of the subcortical regions) is larger in people with Autism, while others have found that it is in fact smaller - others found no difference at all.

Why do research studies come to different conclusions?

Let’s take a look at a supposedly simple research question from above: Do people with Autism have larger heads than people who don’t have Autism? All we need to do is to gather a group of people with Autism, measure their heads, gather a group of people who don’t have Autism, measure again and compare the average size from both groups. Sounds easy, doesn’t it? But here are some questions to consider: How do you measure head size exactly? Along which line do you take the circumference? What do you do when people have thick and curly hair? And even if you figure out a way to measure everyone in your group consistently, maybe someone else asked the same question, but measured their groups different (even though they, too, are consistent with their own measure). Then it’s possible that you and that other person end up with different results. In this case, the reason for inconsistent results has to do with the methods that you and the other person chose.

Now, let’s take a look at something else that is often the reason for inconsistent results: the group of people that are studied. Think about your 10 closest friends, or 10 of your colleagues at work of whom you know don’t have Autism. At first it seems as if they would make a good control group because they don’t have Autism. But here are again some questions: Do you include both men and women (men tend to have bigger heads than women)? How do you go about age (children have smaller heads than adults)? And do you include particularly large people who also might have larger heads? Ideally, you need a control group of people who differ from your study group (the people with Autism) in only thing: the fact that they don’t have Autism. How many people do you know who only differ in one thing? While some things probably don’t matter too much for your question (whether or not they like dogs or cats probably doesn’t have to concern you when you look at their head size), other things might be very important to control for. If your group of people with Autism also has other conditions such as ADHD or anxiety (which is often the case) and you do find larger head size in these people, then how do you know whether it’s because of their Autism or ADHD or a combination of both? Again, if someone else asked the same question and measured head size in exactly the same way as you did, but looked at different people (maybe they only included people with Autism who don’t have ADHD, while you only controlled for anxiety), they could come to a different conclusion than you.

With this in mind, we can go back to the subcortical regions that have been linked to behaviours in Autism and think about possible ways to answer the question.

Does the size of subcortical regions differ between people with and without Autism?

First of all, we need to not only look at your 10 closest friends, but at a very large group of people to make sure that they don’t differ in systematic ways. Unfortunately, brain imaging with MRI is very time-intense and expensive and not many research groups usually look at more than 20-40 participants. However, in the Autism Brain Imaging Data Exchange (ABIDE) project, researchers from all over the world can contribute their neuroimaging data to an online database. This database allowed us to analyze neuroimaging data from over 700 boys and men with and without Autism between the age of 7 and 35 (see our other post below on why often more men than women are studied in Autism research). Secondly, we want to make sure that all data contributed from different research groups all over the world are analyzed with the same method. This type of analysis is very time- and labour- intense because it is usually done manually: many images are taken to create one 3D model of one person’s brain and a researcher would have to manually trace each region on each of these images. Doing this for over 700 people would have taken way too long. To overcome this problem, our graduate student went to Montreal and collaborated with a research group at McGill University who had developed a computer algorithm that could do this time- and labour- intense analysis automatically. Our analysis showed that subcortical regions did not differ in size between our groups of people with and without Autism. Given that we used the same method on a large group of people, this is the most compelling evidence to date.

What about shape?

Now, imagine that the size of a region is similar between two people, but the shape developed completely different. Instead of a bulky front part and an elongated end, it could have developed in an opposite pattern with an elongated front part and a bulky end. While the reality is probably much more subtle, looking at the shape of subcortical regions is an exciting and relatively new way of looking at brain structure. If a region develops in a different shape, then it could end up connecting to other brain areas very differently and affect behaviour. Remember that subcortical regions are located very deep in the centre of the brain, making them perfect relay points for information highways in the brain. However, different parts of subcortical regions connect with different areas. For example, the back of the putamen (but not the front) connects to areas that are involved in motor behaviours. If the shape in the back of the putamen is more concave in the group with Autism (either because there might be less neurons or less connections between neurons) then that could suggest a link to impaired motor skills in Autism. And indeed, this is what we found in our study (2). 

Overall, our study resolved inconsistent findings about the size of subcortical regions which are important relays in brain networks related to symptoms in Autism. We were also able to show subtle changes in the shape of these regions which can help us understand in which way networks are working differently in Autism and how that contributes to symptoms in Autism.

 

*Since 2013, Autism Spectrum Disorder is the correct way to refer to all subtypes of Autism. However, we’re only using the word Autism here for better readability.

 

References: 

(1) Zwaigenbaum, Lonnie, et al. "Early head growth in infants at risk of autism: A baby siblings research consortium study." Journal of the American Academy of Child & Adolescent Psychiatry 53.10 (2014): 1053-1062.

(2) Schuetze, M., Park, M.T., Cho, I.Y., MacMaster, F.P., Chakravarty, M.M., & Bray, S.L. (2016). Morphological Alterations in the Thalamus, Striatum, and Pallidum in Autism Spectrum Disorder. Neuropsychopharmacology.  http://www.ncbi.nlm.nih.gov/pubmed/27125303  

 

Why are more males than females diagnosed with Autism Spectrum Disorder?

Written by: Brian Cechmanek

The prevalence of Autism Spectrum Disorder (ASD) is roughly 1 in 68 children, and is commonly reported with a 5:1 ratio of males to females with ASD (1 in 42 boys versus 1 in 189 girls) (CDC, 2014). While it is possible that this is an accurate sex difference in rates of ASD, sex differences in ASD have not been fully studied, opening the possibility that the way ASD is diagnosed creates some of this imbalance. One partial explanation for this bias is that males are diagnosed more often than females - or rather, that females with ASD are under-diagnosed. Madic-Maravic et al (2015) explored this potential explanation. 

To examine sex differences in diagnoses, low-functioning participants were separated into two groups: those with “typical autism”, and any other forms of ASD (Pervasive Developmental Disorders); “atypical autism”. Males were more frequently diagnosed with typical forms (83%), compared to females (56%). There were, however, no sex differences for ADI-R (social reciprocity, communication, restrictive repetitive stereotyped behaviours) scores. But, other studies have shown differences, particularly less restrictive repetitive stereotyped behaviours in female autistic participants (labelled “high functioning”) (Mandy et al, 2012). This could suggest that only female autistic participants (labelled ‘high-functioning’), show less restrictive repetitive stereotyped behaviours than boys.

This study found that females were more often diagnosed with other forms of ASD. These atypical forms may not always be as likely to be diagnosed, which means that in high-functioning groups, autism may be less likely to be diagnosed in females than in males. More specifically, this study showed that males tend to have a more predictable set of ‘clinical symptoms’, while females show more socialization and communication symptoms. 

A tautology is a logical truth by its own definition. In this case, clinical diagnosis of autism is based on clinical symptoms, which are determined by clinical definitions. If males with autism display more clinical symptoms, then by definition males will be diagnosed more than females. But when the set of symptoms used for clinical diagnosis evaluate certain symptoms more than others, such as restrictive repetitive and stereotyped behaviour (seen more in males) rather than communicative symptoms (seen more in females), we can see how a sex bias for diagnosis could occur. Further, use of the ADI-R (a parental survey of their child) for diagnosis, may be biased by restrictive repetitive and stereotyped behaviours being more apparent to the parent, than communicative symptoms. This hints that future work should examine the clinical classifications used to diagnose ASD, to ensure that females are not being (unintentionally) under-diagnosed. 

Reference:

Vanja Mandic-Maravic1, Milica Pejovic-Milovancevic1, Marija Mitkovic-Voncina1, Milutin Kostic1, Olivera Aleksic-Hil1, Jelena Radosavljev-Kircanski1, Teodora Mincic1 & Dusica Lecic-Tosevski1.Sex Differences in Autism Spectrum Disorders: Does Sex Moderate the Pathway from Clinical Symptoms to Adaptive Behavior. Sci Rep. 2015 May 19;5:10418. doi: 10.1038/srep10418. http://www.ncbi.nlm.nih.gov/pubmed/25988942

Restricted Interests in Autism Spectrum Disorder – Helpful or Disruptive in the Classroom?

Written by: Manu Schuetze 

What were the things you couldn’t stop talking about when you were a child? Or if you have children yourself now, what are they obsessed about? Dinosaurs? Thomas the Tank Engine? Ponies? Or do they want to watch the same movie over and over again? Probably every child goes through a phase in which they can become quite obsessed with something. While these interests can be annoying for parents (“Sigh… Frozen? Again?”), they usually don’t interfere much with the child’s everyday life. Children with Autism Spectrum Disorder have these interests too; however their interests are usually stronger and more intense.  They can occupy their attention so much that trying to disengage them causes a lot of distress to the child. These strong interests have been called restricted interests and are a core symptom for Autism Spectrum Disorder.

Restricted interests have the potential to limit interactions with others. They can also interrupt the child’s attention to follow a teacher’s instructions, e.g. when a child concentrates on light reflections in the window and ignores the teacher. Thus, restricted interests are often discouraged or children with Autism Spectrum Disorder are often separated from typically developing children to attend schools for children with special needs.

However, there are also a lot of positive elements to restricted interests: children can show expertise and feel good about themselves, they are motivated to learn more about them and they are engaged and concentrated – all important parts of learning behaviour. Some children develop the wish to tell other children about their interests and overcome initial shy moments and can even learn how to engage in conversations (“If you let the other child tell you about their hobbies, you can tell them about yours, too!”). Hence, some people suggest to include restricted interests in the classroom and let children with Autism Spectrum Disorder learn side-by-side typically developing children. This inclusive education is becoming more and more accepted and is implemented in many countries by law already.

Researchers in the UK have now looked at all studies that addressed the question of whether or not including restricted interests of children with Autism Spectrum Disorder is beneficial or harmful and found that beneficial effects outweigh detrimental effects. Most of these studies found that children’s motivation and engagement in tasks grew when restricted interests were used to reward the child, e.g. when a sentence was read correctly, the teacher gave the child some time to read in his favourite book of Thomas the Tank Engine. Notably, some studies found that children initially performed worse in tasks when their restricted interests were offered as rewards, but this changed over time and the child’s performance improved overall.

These studies draw a positive picture of using restricted interests in a more structured way to encourage and motivate children with Autism Spectrum Disorder to learning. When more people and institutions recognize the benefit of restricted interests for a child’s learning behaviour (regardless of a diagnosis), it might even be possible to include their interests directly into the teaching process (not just as rewards): If a child is obsessed with Thomas the Tank Engine, why not teach them the numbers by letting them count parts on Thomas the Tank Engine, or teach them reading by reading Thomas the Tank Engine books? Even more advanced concepts in high school could be explained based on an adolescent’s interests, rather than using abstract concepts.

Restricted interests – to some people, they might sound like a barrier and a symptom that needs to be treated, however, we believe that they can be important and useful to engage children with Autism Spectrum Disorder in learning.

 

Original Review Study

Gunn, K.C. & Delafield-Butt, J.T. (2015). Teaching Children With Autism Spectrum Disorder With Restricted Interests. A Review of Evidence for Best Practice. Review of Educational Research.

SOCIAL DIFFICULTIES IN AUTISM MAY BE LINKED TO OUT-OF-SYNC VISUAL AND MOTOR NETWORKS

Written by: Dr. Christiane Rohr

Children with Autism Spectrum Disorders (ASD) often have problems learning social behaviors. This is, in part, because imitating other people's social behaviors doesn’t come as easy to them as it does to typically developing children. The ability to imitate depends on the ability to observe and to replicate facial expressions or gestures, and is subserved by brain mechanisms that link visual input (the observation) to a motor output (the replication).

A recent study conducted by a team at Johns Hopkins University in Baltimore, MD, investigated whether this link between visual input and motor output may be affected in ASD. Using functional magnetic resonance imaging (fMRI), they measured neuronal activity in visual and motor brain networks in fifty children with, and fifty children without ASD, between the ages of 8 and 12. Children were instructed to rest, which allowed the researchers to assess whether children with ASD were different from typically developing children in this regard even when they were doing nothing. In line with their assumption, they found that neuronal activity between specific visual areas and specific motor areas was more synchronized in typically developing children than it was with children with ASD. Moreover, they found that the degree to which these visual areas and motor areas were out-of-sync predicted the severity of social difficulties in the children with ASD.

In essence, the findings of this study suggest that children with ASD may have a disadvantage in imitating social behaviors due to an asynchrony in neuronal activity between visual and motor areas. This hints at the possibility that if we can find a way to re-synchronize these areas, it may allow children with ASD to more easily imitate social behaviors. However, the asynchrony in neuronal activity when the children were doing nothing in particular does not necessarily extend to when they imitate social interactions, and future studies will be needed to first test this assumption.

 

Reference: 

Nebel MB, Eloyan A, Nettles CA, Sweeney KL, Ament K, Ward RE, Choe AS, Barber AD, Pekar JJ, Mostofsky SH (2015): Intrinsic Visual-Motor Synchrony Correlates With Social Deficits in Autism. Biol Psychiatry. doi: 10.1016/j.biopsych.2015.08.029. 
http://www.ncbi.nlm.nih.gov/pubmed/26543004  

 

 

EYE TRACKING USED TO EXAMINE VISUAL SALIENCY IN ASD

Written by: Dr. Signe Bray 

Eye-tracking technology lets us measure how people look at things. If I show you a scene with a football player about to kick a ball, do you look longer at the ball, the leg or the player’s face? People with autism spectrum disorder (ASD) tend to look longer at objects than they do at faces, but we don’t know why.

This study tried to understand what features in an image capture the attention of adults on the autism spectrum, more than typical adults. The hope is that if we can understand what captures the attention of people with ASD we can better understand why people on the spectrum have difficulty processing social information.

To do this, the researchers asked 20 adults with ASD and 20 matched healthy control adults to look at 700 different pictures, each for three seconds. They measured where people looked on the images. They then analyzed the images, decomposing them into features based on region (e.g. the center), color, properties of objects in the images such as size, and information about the type of objects (e.g. faces).

The researchers then asked which of these features predicted where a person would look, and which features predicted more strongly for people with ASD. The answer: all of the features they looked at had a different influence on the looking patterns of the adults with ASD. For example, people with ASD looked longer at the center of the screen, and their gaze was less influenced by the properties of objects in the images.

When they looked at object categories, they found a small difference in the importance of faces for capturing attention, but also differences in looking at objects that can move and that have a smell.  Differences between the ASD and typical adults became stronger the longer people looked at the images.

This study helps us to understand how people with ASD look at the world differently, and some tendencies they may have in their looking behavior. An interesting question is whether we can train people to adjust their looking behavior and whether this can help them better understand the social world. That is, because looking at objects and faces is how we get information about them, maybe people with ASD can get more information about the social world by looking at it differently?

 

Reference: 

Atypical visual saliency in Autism Spectrum Disorder quantified through model-based eye tracking (2015) Wang, Jiang, Morin Duchesne, Laugeson, Kennedy, Adolphs. Neuron. 88:1-13.

 

Facial Processing in Adolescents with Autism Spectrum Disorder

Written by: Ivy Cho

One of the key building blocks in building and maintaining social relationships is the ability to process and understand the meaning behind facial expressions. Unfortunately, in individuals with Autism Spectrum Disorder (ASD), where impaired social functioning is a hallmark, the ways by which emotional faces are processed is still unclear. Some research studies suggest emotional processing deficits, while other studies have reported no such deficits. Specifically, research regarding emotional face processing in ASD adolescents is sparse, and this is disappointing as adolescence is a transitional period with change and higher levels of stress – all factors that can have an impact on the processing of facial expressions. With this in mind, there is great importance in investigating emotional face processing in adolescents with ASD.

 A research group at the University of Toronto, has recently investigated emotional processing in adolescents with ASD using a neuroimaging technique called magnetoencephalography (MEG). MEG, looks at brain activity by measuring electrical currents coming from the brain.

 This study measured different areas of the brain while participants underwent a task looking at angry, happy, and neutral faces. Twenty-four adolescents with ASD and twenty-four typically developing adolescents, all between the ages of 12-15, underwent this task during MEG. During this task, participants were shown two images placed on either the left or right side of the screen. One image was that of a facial expression and the other was a scrambled pattern. Participants were told to press a button that corresponded to the side with the scrambled pattern. This task measured both the accuracy and the time until a response was recorded.

 The study found 2 interesting results after examining brain activity in response to this task. Firstly, they found that adolescents with ASD showed lower accuracy in the task when the emotion presented was an angry face. Secondly, adolescents with ASD showed different brain activity patterns when processing happy and angry faces to that of typically developing adolescents.

 These results suggest implications regarding social behavioural difficulties that adolescents with ASD face. Inaccurate perception of facial expressions (like angry faces) and differences in facial affect processing in the brain may be contributing to the social impairments found in ASD.

 This study expands the current sparse literature regarding facial processing in adolescents with ASD and the specific deficits seen. Hopefully, this will help in further understanding how facial processing in ASD ties in with social behavioural deficits.

Reference:

Leung RC, Pang EW, Cassel D, Brian J, Smith ML, Taylor MJ (2014) Early neural activation during facial affect processing in adolescents with Autism Spectrum Disorder. Neuroimage Clin 7:203-212. 

Pupillometry used to examine the advantage children with ASD have on visual tasks

Written by: Dr. Signe Bray

People with ASD have an advantage in certain types of visual tasks, for example finding a specific item in a crowd of distracters.  This is true in children as young as two, the youngest age when you can reliably make a diagnosis. This study set out to better understand why, by using eye-tracking technology to monitor eye movements in children during a search task. They took advantage of the fact that our pupils dilate more when we undertake effortful cognitive tasks.

The authors compared two groups, ASD and typically developing, each with 17 toddlers aged 21-35 months.  The toddlers played a game where they were shown a red apple that flew into the screen. The apple disappeared and then re-appeared in a display among other similar-looking objects. The toddlers then looked at the display for four seconds. The eye tracking was used to see if the toddlers ‘found’ the apple – did their gaze land on the apple during that four second period?

The study found that pupils contracted more in the toddlers with ASD, when they played this ‘find the apple’ game. This might mean that a specific brain system that controls attention is more readily engaged in ASD, which can explain why people with ASD have an advantage in visual search tasks.

 

Examples of the visual search images participants were shown.  (Figure from Blaser et al., 2014)

Examples of the visual search images participants were shown.  (Figure from Blaser et al., 2014)


Reference:

Blaser E., Eglington, L., Carter, A.S., Kaldy, Z. (2014). Pupillometry reveals a mechanism for the Autism Spectrum Disorder (ASD) advantage in visual tasks. Scientific Reports. 4.

“Does This Make My Asperger's Look Big?” Find out October 30th!

October is Autism Awareness Month! One exciting event raising awareness about Autism is “Does this make my Aspergers look big?” - a comedy show that is on tour across Canada. This show was created and is performed by Michael McCreary, who was diagnosed with Asperger’s Syndrome when he was five years old.  He is performing his show across Canada.  Funds raised from his performances will go to helping various autism organizations raise money for their programs. This show will be in Calgary on October 30th and is being organized by the Autism Aspergers Friendship Society of Calgary.  

 

To buy tickets:

http://www.eventbrite.com/e/does-this-make-my-aspergers-look-big-tickets-12481491477?aff=eorg

 

To see show times and locations across Canada:

http://www.aspiecomic.com/cross-canada-tour.html

 

 For more information about the Autism Aspergers Friendship Society of Calgary:

http://www.aafscalgary.com

How does the brain develop differently in Children with Autism?

Written by Mark Krongold:

Over the past thirty or so years a large number of studies have been done in an attempt to describe the relationship between the structure of the brain and autism. For example, researchers found that the rate of brain growth is faster during the first few years of life in children with autism compared to typically developing children (Lainhart et al. 1997). However by mid childhood the average brain of an autistic child is no longer larger (Herbert et al. 2003). Importantly it is largely during this period of middle childhood when cognitive and behavioural functions begin to deteriorate in children with autism. This has led researchers to believe that whatever changes occur in the brain that bring the “autistic brain” back to normal size are likely some sort of compensatory mechanism.

A research group out of the University of Utah has looked into studying the brain growth trends of children with autism with the ultimate goal to eventually be able to detect early on which children will grow up to have autism.

The researchers studied both autistic and typical children and adults between the ages of 3 and 39 using MR images of their brains. A number of participants were scanned multiple times at different ages allowing the researchers to look at longitudinal trends of brain development. Using advanced analysis techniques the researchers were able to look at the thickness of the cortical sheet in a number of different regions across the brain.

There were three interesting findings from this study. Firstly, the researchers determined that there is no difference in the thickness of the brain in very young children. However by the age of three children with autism had an abnormally large brain thickness. Second, during the middle of adolescence the brain of autistic children goes through a phase of fast thinning. This explains why there are no large size abnormalities in the autistic brain during childhood and the teenage years. Interestingly this thinning seems to occur earlier in the frontal regions of the brain (regions that are associated with advanced executive mental processing). Third, there is a gradual decrease in the thinning of the autism brain during early adulthood. This however does not appear to happen in every region of the brain.

Unfortunately, at this point the researchers were not able to find specific growth trends that would allow one to predict which children will eventually be diagnosed with autism. The trends that these researchers discovered are so far not specific enough.

This study was a good step towards determining differences in the brain between children with autism and typically developing children. There are, however, a number of ways in which this study could be taken. More data is always welcome and a more complete longitudinal data set with more time points would help researchers better determine trends in brain growth. Finally, since autism is a spectrum disorder with a huge number of different ways in which symptoms present, research looking into how to distinguish between subtypes of the disease is also needed.

 

References:

Lainhart JE, Piven J, Wzorek M, Landa R, Santangelo SL, Coon H, et al.Macrocephaly in children and adults with autism. J Am Acad Child Adolesc Psychiatry1997;36:282-90.

Herbert MR, Ziegler DA, Deutsch CK, O'Brien LM, Lange N, Bakardjiev A, et al.Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain 2003;126(Pt 5):1182-92.