Autism and fMRI Study: Autism Research Distorted, Once Again, by Exclusion of Low Functioning Autism Subjects

Another fMRI imaging study of brain connectivity in subjects with autism is reported in the Oxford journal Cerebral Cortex, October 12 2010.  I have highlighted  the article, Decreased Interhemispheric Functional Connectivity in Autism, abstract description of the study's autism participants .... all persons with High Functioning Autism.  Once again, the study which puports to draw conclusions about "autism" presumably referring to all of the Pervasive Developmental, or Autism Spectrum Disorders, excludes those most severely affected by autism disorders:

Decreased Interhemispheric Functional Connectivity in Autism

Abstract

The cortical underconnectivity theory asserts that reduced long-range functional connectivity might contribute to a neural mechanism for autism. We examined resting-state blood oxygen level–dependent interhemispheric correlation in 53 males with high-functioning autism and 39 typically developing males from late childhood through early adulthood. By constructing spatial maps of correlation between homologous voxels in each hemisphere, we found significantly reduced interhemispheric correlation specific to regions with functional relevance to autism: sensorimotor cortex, anterior insula, fusiform gyrus, superior temporal gyrus, and superior parietal lobule. Observed interhemispheric connectivity differences were better explained by diagnosis of autism than by potentially confounding neuropsychological metrics of language, IQ, or handedness. Although both corpus callosal volume and gray matter interhemispheric connectivity were significantly reduced in autism, no direct relationship was observed between them, suggesting that structural and functional metrics measure different aspects of interhemispheric connectivity. In the control but not the autism sample, there was decreasing interhemispheric correlation with subject age. Greater differences in interhemispheric correlation were seen for more lateral regions in the brain. These findings suggest that long-range connectivity abnormalities in autism are spatially heterogeneous and that transcallosal connectivity is decreased most in regions with functions associated with behavioral abnormalities in autism. Autism subjects continue to show developmental differences in interhemispheric connectivity into early adulthood.

HealthImaging.com reports on the study in Study: fMRI reveals functional differences in autistic patients and included the study authors' qualifications on the limits of the study including the fact that the study, conclusions, despite the titles of the Cerebral Cortex report and HealthImaging.com article, could not be extended to Low Functioning Autistic patients.

The authors acknowledged that limiting their study to high-functioning young autistic males restricted their findings from being extended to females, younger children or lower-function ASD patients. Nevertheless, Anderson and colleagues emphasized that “Our finding adds to growing evidence that abnormalities of interhemispheric connectivity in autism are widespread but regionally specific and related to cognitive and neurological impairments commonly found in the disorder.”

The authors posited that their findings highlight MRI as a  potential tool to assist physicians in diagnosing and treating autism.

In one breath the study authors acknowledge that the exclusion of low functioning autistic patients restricted their findings from being extended to those patients (or to other excluded groups, including females and younger children). In the next breath though, and in the title of their report and magazine articles the study findings are reported as being applicable to autism generally. 

This is not the first study to exclude low functioning or intellectually disabled autistic subjects from "autism" studies. Prominent autism researcher, and DSM-5 panelist,  Catherine Lord has identified the  tendency to exclude autistic subjects with severe to profound intellectual disabilities:

"However, research in ASD has tended to use overwhelmingly White, middle to upper middle class samples, and has often excluded children with multiple disabilities and/or severe to profound intellectual disabilities".

The lip service qualifying statement in this recent fMRI study report did not preclude the authors from making generalizations about autism as found across the spectrum notwithstanding the exclusion of low functioning autistic persons from the study. Articles commenting on this and other studies may or may not repeat that qualification.  Most certainly all will be accompanied by headlines reporting new "autism" findings.  Low functioning autistics are routinely excluded from major media institutions that like to focus on the barely affected, very high functioning persons with Aspergers or HFA, the Ari Ne'emans, Alex Planks, JohnMichelle Dawsons and Temple Grandins.  

As in the popular media, so too in "scholarly", "scientific" research. "Autism" just doesn't meant what it use to.

Alleged "autism" spectrum research is anything but representative of the autism "spectrum" disorders.

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In Future Will Autism Spectrum Disorders Be Referred To As Brain Connectivity Disorders?

Another study has been published, the results of which, according to Science Centric,adds to evidence that autism is a brain 'connectivity' disorder. I had previously commented on brain connectivity in April 2009 noting that a study at that time was supportive of a previous,  2006,  study linking autism disorders to brain connectivity issues: Autism's Four C's: Cerebellum, Connectivity, Coordination, Communication.  If further study results indicate that autism deficits arise from brain connectivity disorders will the autism spectrum disorders come to be known as the Brain Connectivity Disorders?  More importantly, if brain connectivity is the biological problem that gives rise to autism disorders will  effective treatments and cures be developed targeting the connectivity issues?

As reported on Science Direct the study's lead researcher Mustafa Sahin, MD, PhD, of Children's Department of Neurology, made statements that hold out some hope that treatments might ultimately result from further brain connectivity research :

"'People have started to look at autism as a developmental disconnection syndrome - there are either too many connections or too few connections between different parts of the brain,' says Sahin. 'In the mouse models, we're seeing an exuberance of connections, consistent with the idea that autism may involve a sensory overload, and/or a lack of filtering of information.'

Sahin hopes that the brain's miswiring can be corrected by drugs targeting the molecular pathways that cause it. The mTOR pathway is emerging as central to various kinds of axon abnormalities, and drugs inhibiting mTOR has already been approved by the FDA. For example, one mTOR inhibitor, rapamycin, is currently used mainly to prevent organ rejection in transplant patients, and Sahin plans to launch a clinical trial of a rapamycin-like drug in approximately 50 patients with TSC later this year, to see if the drug improves neurocognition, autism and seizures."

This is one father of a severely autistic son who is hoping that such research does lead to viable autism treatments and cures.  I want my son to have the opportunity to participate as fully in life as I have done.   Correcting connectivity issues that would enhance his understanding of the world?  Absolutely.

autism

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Autism's Four C's: Cerebellum, Connectivity, Coordination, Communication

A neuroimaging study comparing High Functioning Autistic children and typically developing children has found that children with autism relied heavily on the supplementary motor area (SMA), a region of the brain important for conscious, effortful movement, while performing simple motor tasks like sequential finger tapping. Their typically developing peers in the study used the cerebellum, a region of the brain important for automating motor tasks, The study is published in the journal Brain April 23 and is the subject of a news release by the Kennedy Krieger Institute:

This suggests children with autism have to recruit and rely on more conscious, effortful motor planning because they are not able to rely on the cerebellum to automate tasks.

The significance of the current Kennedy Kreiger Institute study for understanding autism disorders and behaviors is explained by Dr. Stewart H. Mostofsky, senior study author and a pediatric neurologist in the Department of Developmental Cognitive Neurology at the Kennedy Krieger Institute:

“Tapping your fingers is a simple action, but it involves communication and coordination between several regions of the brain. These results suggest that in children with autism, fairly close regions of the brains involved in motor tasks have difficulty coordinating activity. If decreased connectivity is at the heart of autism, it makes sense social and communication skills are greatly impaired, as they involve even more complex coordination between more distant areas of the brain."

The study results also support previous studies which tie autism to structural and functional brain underconnectivity. See for example Functional and Anatomical Cortical Underconnectivity in Autism: Evidence from an fMRI Study of an Executive Function Task and Corpus Callosum Morphometry in Cerebral Cortex, June 13, 2006.

autism

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