Executive Functioning in High Functioning Autism

A review of: GILBERT, S., BIRD, G., BRINDLEY, R., FRITH, C., BURGESS, P. (2008). Atypical recruitment of medial prefrontal cortex in autism spectrum disorders: An fMRI study of two executive function tasks. Neuropsychologia DOI: 10.1016/j.neuropsychologia.2008.03.025

Executive functioning is an umbrella term used in clinical neuropsychology and cognitive neurosciences to refer to a series of “higher-order” cognitive processes usually associated with frontal lobe functioning. These include planning, organizing, categorizing, response inhibition, monitoring, multitasking, etc. Research on executive functioning and autism has provided mixed results likely due to differences in the area of executive function measured. In this functional MRI study, the authors used a new test of executive function used to assess for stimulus dependent vs. stimulus independent thoughts. Stimulus dependent refers to cognitive processing (thinking) that is associated with, or dependent on, a specific stimulus that is presented. For example, I may ask you to press the b key when you see a blue square or the r key when you see a red square. For this task the stimulus dependent phase consisted of capital letters presented in alphabetical order. Once a letter was presented, the person had to press one key if the letter contained only straight lines (such as the letter A) and a different key if the letter contained curves (such as the letter B). In the stimulus independent task, the person was presented with one letter and ask to follow the same response pattern (one key if straight lines – another key if curves). However, the second letter presented was random and did not follow the alphabetical order, yet the person was asked to respond based on the next alphabetical letter. For example, assume the first letter was “C”, then the next letter presented was the letter “H” (random) yet the person was asked to respond to the next alphabetical letter starting from the first letter presented (C), thus the next response was based on the characteristics of the letter D, even though the person was seeing the letter H. This task therefore, requires the person to continue to “think” of the characteristics of the letters in alphabetical order, independent of the letters presented (which now are distractors).

In the study the authors examined 15 adults with high functioning autism and 18 typically developing adults that were matched for age (mean 38) and IQ (mean 119). The participants performed the task while undergoing a functional magnetic resonance imaging scan (fMRI). There was no difference in accuracy or response times between the groups. Both groups showed more activation of the lateral frontal and parietal cortex on the more difficult stimulus-independent task. However, the autism group had significantly more activation of specific areas of the medial prefrontal cortex during the easier stimulus dependent condition than the typically developing group (this was interpreted as failure to deactivate these areas). The authors argued that these results suggest an atypical brain organization in HFA with limited deactivation of the rostral prefrontal cortex during easier task compared to typically developing individuals. However, the equivalent performance (both groups did just as well on the task) suggests that the fMRI findings simply reflect different approaches to cognitive performance between the two groups.

Autism and Cerebellar Differences?

Study finds no differences in cerebellar volume in people with autism after controlling for macrocephaly, IQ, and age.

A review of: CLEAVINGER, H.B., BIGLER, E.D., JOHNSON, J.L., LU, J., McMAHON, W., LAINHART, J.E. (2008). Quantitative magnetic resonance image analysis of the cerebellum in macrocephalic and normocephalic children and adults with autism. Journal of the International Neuropsychological Society, 14(03) DOI: 10.1017/S1355617708080594

As I do my weekly literature search on Autism Research for Translating Autism, I noticed a number of forthcoming manuscripts about the role of the cerebellum in Autism. I will likely review some of these new studies and decided to start with Cleavinger et al (2008) MRI examination of cerebellum in children and adults with autism.

The cerebellum is located on the lower back region of the brain and traditionally it has been implicated in the integration of sensory information and the coordination of movement. However, more recent investigations have determined that the cerebellum is also active in various higher-order functions such as language, emotion, and cognition. In the past, studies looking at differences in the cerebellum of people with and without autism have provide mixed results with some showing increased volume in people with autism, while others show no difference, or decreased volume. One possible explanation for these conflicting findings is that people with autism often vary in degree of macrocephaly (large head size) which may affect the results if the samples studied included individuals with and without macrocephaly. To address this question the authors of this study examined 4 groups: a) people with autism and macrocephaly (N=13) b) people without autism and macrocephaly (N=8) c) people with autism and without macrocephaly (N=28) and c) people without autism and without macrocephaly (N=16). In general, after controlling for macrocephaly, age, and IQ, no statistically significant differences in cerebellar volume were found, although a trend was observed in that people with autism who also had macrocephaly showed smaller cerebellar volume as compared to similar macrocephalic individuals without autism. This trend is important because the ‘non-significant’ differences reported here are likely due to the small sample size and unequal group size, which affects the statistical power of the analysis (making it more difficult to show statistical significant differences even when such differences actually exist). But even if the 'non-differences' result is replicated and in fact no differences in cerebellar volume exist between these groups, does this mean that the cerebellum is not implicated in autism? Not at all. Here again I touch the issue of how we should avoid reaching conclusions that go beyond what the data tell us. These results only speak to the size of the cerebellum, suggesting no apparent morphological differences. These results however, do not speak to possible anomalies in the functioning of the cerebellum, which may or may not be present in autism.

Brain Differences in Autism 2: Fusiform Gyrus

A review of: van Kooten, I.A., Palmen, S.J., von Cappeln, P., Steinbusch, H.W., Korr, H., Heinsen, H., Hof, P.R., van Engeland, H., Schmitz, C. (2008). Neurons in the fusiform gyrus are fewer and smaller in autism. Brain DOI: 10.1093/brain/awn033

The fusiform gyrus is an area of the temporal lobes of the brain that has been extensively associated to people’s ability to recognize faces. The authors of this paper proposed that abnormalities in the fusiform gyrus may explain some social deficits in Autism. Although people with autism can correctly complete face processing tasks, the authors noted that people with autism display reduced activation of the fusiform gyrus during these tasks. This alteration could be responsible for atypical behaviors such as reduced eye contact. To examine the underlying hypothesis further, the authors examined the post-mortem brains of 7 children and adults with autism as compared to 10 matched controls. They found significantly reduced neuron density and total neuron number in areas of the fusiform gyrus but not in other cortical areas. The authors presented a very interesting alternative interpretation. Although the reduced neural density and number in the fusiform gyrus could reflect neurodevelopmental impairments in the fusiform itself resulting in specific functional impairments, it is also possible that this atrophy is related to ‘loss of targets’ to which the fusiform gyrus projects. That is, the fusiform gyrus sends neural projections to the amygdale, which play an important role in monitoring eye gaze and other social behaviors. Thus, is the finding of reduced neural density and total number of the fusiform gyrus a reflection of dysfunction of this area of the brain, or simply a byproduct of alterations in other related areas such as the amygdale?

Brain Differences in children with Autism: White Matter – Gray Matter

A review of: BONILHA, L., CENDES, F., RORDEN, C., ECKERT, M., DALGALARRONDO, P., LI, L., STEINER, C. (2008). Gray and white matter imbalance – Typical structural abnormality underlying classic autism?. Brain and Development DOI: 10.1016/j.braindev.2007.11.006

The authors of this study discussed the relative inconsistent results from studies trying to examine brain differences in children with and without Autism. For example, although many post-mortem studies have found brain differences, the differences they find vary significantly between studies. The same is true of studies using imaging techniques such as MRI. However, the most consistent finding is an overall larger brain volume in children with autism, leading some researchers to propose deficits in cell pruning as a possible cause of autism (more of this below). In this study the authors used MRI (Magnetic Resonance Imaging) to compare 12 children with Autism (average age 12) to 16 matched typically developing children. The results showed that children with autism had increased generalized bilateral gray matter. Specifically increased gray matter was observed in the cingulated gyrus, caudate, cerebellum, claustrum, cuneus, fusiform gyrus, inferior, middle and superior frontal gyri, inferior and superior temporal gyri, inferior and superior parietal lobules, pre and post-central gyrus, precuneus, putamen, thalamus, insula and occipital cortex. The results also showed decreased generalized bilateral white matter in the cuneus, medial and superior frontal gyri, pre- and post-central gyri, inferior parietal lobule, supramarginal gyrus, cingulote gyrus, middle occipital gyrus, parahippocampal gyrus, and the middle and superior temporal gyri. The authors concluded that their data provides strong evidence for increased gray matter and reduced white matter in children with autism when compared to typically developing kids. Similar results have been used as evidence of the cell pruning theory of autism. This theory indicates that children with autism have an atypical brain development process during early infancy. Specifically, during a typical post-natal period, there is considerable removal of connections between cells in the brain leading to more efficiency in cell connectivity and cell communication. Researchers argue that abnormal brain growth during early development in autism is due to limited pruning of such synaptic connections.

Diminished Cingulate Respose in Children with High Functioning Autism: A possible neural marker?

Title: Self Responses along Cingulate Cortex Reveal Quantitative Neural Phenotype for High-Functioning Autism
Authors: Pearl H. Chiu, M. Amin Kayali, Kenneth T. Kishida, Damon Tomlin, Laura G. Klinger, Mark R. Klinger and P. Read Montague
Source: Neuron 57, 463–473, February 7, 2008

I first heard about this article at the Autism Vox, which led to an interesting discussion on the difficulty in applying findings from basic science into the creation of diagnostic tools. This was a very interesting piece, but as I mentioned on the Autism Vox discussion, I think we are far from the creation of an FMRI test of autism (see the Autism Vox discussion). In summary, the researchers examined 16 adolescents with high functioning autism and 20 typically developing adolescents in their responses to a computer game called the Multi-round Trust Game. In this game the children received computer money (points) from another player in the form of an investment. During the transaction, the investment increased, so the receiving child obtained more than what the “investor” actually sent. Then the receiving child must decide how much of what he received should be returned to the investor. The key finding was that both groups of kids (Children with autism and typically developing) looked the same, in regards to their brain activation as seen on an fMRI, when the “Other” person was making a decision. The authors refer to this as the “Other Response”. However, when the children were making their own responses (called “Self Response”) the children with Autism lack a particular activation in the Cingulate Cortex (located deep in the center of the brain and usually activated during some social interactions including TofM tasks). This pattern of response was similar to the pattern presented by typically developing kids when playing against a computer instead of an actual person. The conclusion from the authors is that these children with autism may be “impaired in the capacity to represent the social intend of their OWN behavior” while understanding the actions of other (but not necessarily the intentions of others).

Commentary: Here is where the logic gets fussy. Since the two groups of children had a similar response patterns to the “Other” response, the authors argued that such “other” response must refer to a representation of the simple actions of others, but not the “intentions” of others. So the lack of cingulate cortex activation during “self” responses are interpreted as a diminished capacity to understand you own social “intentions” (or I interpret this that as “consequences”) and this is used to explain why children with autism have difficulty on theory of mind tasks. The authors argued that if you can’t represent your own social intentions, it will be difficult to represent the social intentions of others. Now, the problem is that in this game there was no difference between the two groups of kids when the “Other” was responding. Why? If children with autism have difficulty representing the social intentions of others, you would expected to see a difference between these two groups, unless you assume that 1) the typically developing kids also had problems representing the social intentions of others OR 2) during this game there was no need to represent the social intentions of others. In conclusion, what this study clearly shows is reduced Cingulate Cortex activation during “self” responses, suggesting that children with autism have a different brain activation pattern when performing actions that have social intentions, or consequences on someone else. Here is a review from MIT.

Brain differences in kids with Asperger Symdrome

Title: Structural brain abnormalities in adolescents with autism spectrum disorder and patients with attention deficit/hyperactivity disorder.
Author: Brieber, Sarah; Neufang, Susanne; Bruning, Nicole; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Fink, Gereon R; Konrad, Kerstin.
Source: Journal of Child Psychology and Psychiatry. Vol 48(12) Dec 2007, 1251-1258.

This is a Magnetic Resonance Imaging (MRI) study of the brains of children with Asperger's (15), children with ADHD (15), and children with typical development (15). The researchers found that kids with Asperger's and kids with ADHD did not differ in hyperactivity and inattention symptoms. However, the brains of these two groups differed from those of the typically developing kids in that kids with ADHD and Asperger's showed less brain mass in a region called the medial temporal lobe and more brain mass in a region called the parietal cortex. However, the most interesting finding is that only the children with Asperger's showed more brain mass in an area called the right supramarginal gyrus, which is an area of the brain that has been associated with social cognition, including theory of mind. Note: more brain mass does not necessarily mean "better".