Friday, 9 December 2011

MRI and (high-functioning) autism

I've nattered before about trends in autism research and how even across a relatively short period of time, the focus of autism research can change as interests and funding priorities change. The concept of an 'autism gene' for example seems like a increasingly distant memory as the heterogeneity of autism and its comorbidities combines with the complexity of the human genome to illustrate that one gene does not equal one condition but rather multiple genes work together over several processes and also show some connection to the environment of their 'user'. We are all a product of our genes and their mutations and we all carry our own individual genetic nuances.

Whilst genetic research into autism and lots of other conditions is still on-going, one of the other big areas of research focus currently is that of the application of imaging technologies to autism spectrum conditions. I assume most people have heard about MRI (Magnetic Resonance Imaging) and seen the pictures of those Star Trek body scanners and the spectacularly clear images they produce of our inner bodily workings. The application of MRI and its counterpart (functional) fMRI to conditions like autism where the brain is an important area of interest is seemingly growing by the day as evidenced by the large numbers of papers being published in this area. If you were to apply all these findings universally, you might well think that autism is absolutely, undoubtedly, 100% linked to structural issues in the brain. Heck, why don't we just diagnose autism by MRI?

Well, hold that thought for a moment.

An interesting paper was recently published by Vasa and colleagues* at the Kennedy Krieger Institute. The paper is open-access until 31st December 2011 (here). The main message from the study is that after reviewing the neuroradiological findings from quite a large proportion of children with autism (high-functioning autism) gathered over a 9 year period, about 90% of children showed no significant brain abnormality. That's right, you heard correctly, roughly 1 in 10 children with high-functioning autism had something picked up on their MRI, which was actually the same ratio for typically developing controls and slightly less than the figure for children with ADHD.

Assuming that you either did not want to or could not access the full-text of this paper, here is a summary:

  • Structural data from MRI scans for children with autism (n=73) were compared with data from children with ADHD (n=107) and asymptomatic controls (n=144). When I say 'autism' these were children who were either diagnosed with high-functioning autism (32/73) or Asperger syndrome (41/73) and lumped together partly "because of on-going discussions that these two disorders may not exist as separate entities" (their words not mine). I should also add that quite a few comorbidities were also isolated in the autism group including ADHD(?), OCD and things like conduct disorder.
  • I can't pretend to be able to give you the authoritative low-down on the MRI methods employed. My Mr Men reading suggests that scans were not necessarily done all on the same instrument but certain protocols on where to look were followed for each case. These included a set of 11 predefined lesion categories taken from the research literature alongside systematic ways to code for these lesions. Going back to the notion of physicians as artists, this also seemingly applies to neuroradiologists in terms of their coding of what may or may not be considered 'normal' and 'abnormal'. Consensus was reached on cases where the findings were a little bit fuzzy.
  • Results: when looking at the sample groups as a whole, nearly 90% of participants either showed nothing at all in terms of 'abnormal' features or showed only normal variant findings. For the autism group, 11% showed one or more abnormal finding; for the ADHD group this was 12.1% and the control group, 11.1%. The most frequent finding for the autism group was in the category of focal white matter lesions (n=3, 4.1%). Having said that similar focal white matter lesions were found in 3 children with ADHD (2.8%) and 8 of the control group children (5.6%) also. As per the lack of statistical difference, the results in all areas seemed to be very similar across the groups.

The main strength of this study is that it includes data for quite a large group of children including control samples. Ages were matched but gender once again was more male-skewed in the autism group than the other groups which could potentially be a confounding variable. One should also bear in mind that this was a study looking at children towards the more able end of the autism spectrum so we can't generalise too much to those with a more severe presentation or with learning disability as a comorbidity. Bearing in mind that operational criteria were set for where and what to look for via MRI, there are some interesting points to take from this trial.

First, brain findings from MRI in relation to high-functioning autism don't yet appear to be particularly useful as objective diagnostic markers. That's not to say that they won't in future as the hardware and software get more complex and sensitive, but for now we wait. I was interested to see that focal white matter lesions came up given the link (and my obsession) between such features and coeliac (celiac) disease (CD) and other inflammatory bowel conditions; I wonder how many kids in this study were screened for potential 'dietary' issues particularly with the recent CD-ADHD paper in mind?

Second, much like the old one-gene hypothesis of autism, a picture seems to be emerging whereby no one brain area or MRI findings seems to be tied into the presentation of autism - all cases of autism. Yes, I take your point about the recent profrontal cortex study by Eric Courchesne and that deserves further work given that it was based on a very small participant sample. As far as I am aware however MRI scans cannot currently count neurons(?) so we are perhaps looking at different things in relation to brain findings in autism. Again with the biological phenotypes study fresh in my mind, it is not inconceivable that various brain areas might be involved in certain types of autism or at least contributory to certain presented features.

Finally, the brain is a pretty remarkable piece of kit. One of the best things about the brain is its adaptability; so when one part of it malfunctions for whatever reason, other parts of it are often able to take up the reins. Potential examples of this process are abound in the literature. What this might imply is that even though there may be structural issues detected, that does not necessarily translate into aberrant functioning. The recent remarkable comeback shown by Congresswoman Giffords is probably the best example of just how resilient the brain can be. Combined also with the fact that brain biochemistry might be an important feature to look at, we perhaps need to take a more holistic look at the brain with imaging technologies as part of the repertoire for autism research but not necessarily the sole agent of this important area of investigation.

To finish, a link to a band who just got a worthy entry into the Brit pop hall of fame.. Blur.

* Vasa RA. et al. Normal rates of neuroradiological findings in children with high functioning autism. JADD. November 2011.