Brains of those with autism are not shaped differently, study shows

Contrary to previous research findings, the autistic brain does not appear to be have abnormal shape or size, according to an Israeli-led team of researchers. The upshot is that MRI scans probably cannot be used to diagnose the disorder.

Previous small studies have found that autistic people’s brains may be larger than normal in some areas or smaller than normal in others. But in the Israeli-led study, a comparison of some 1,000 MRIs showed size abnormalities in autistic people’s brains of 3 percent or less — not a medically significant difference, the researchers say.

Published in the journal Cerebral Cortex last month, the study means scientists will have to look deeper for biomarkers of autism spectrum disorders (ASD), if they exist at all.

“These sobering results suggest that autism is not a disorder that is associated with specific anatomical pathology and as a result, anatomical measures alone are likely to be of low scientific and clinical significance for identifying children, adolescents, and adults with ASD, or for elucidating their neuropathology,” said Dr. Sigal Berman, a psychologist, and Shlomi Haar, a doctoral student, both at Ben-Gurion University, and Prof. Marlene Behrmann, a psychologist at Carnegie Mellon University in Pittsburgh, who coauthored the study.

Dr. Ilan Dinstein (second from left), a neuroscientist at Ben-Gurion University of the Negev, who led the study, and his research team. (photo credit: Courtesy)

For the past decade and more, scientists have debated whether autism is reflected in the shape of the brain. In a throwback to the pseudoscience of phrenology, many small studies, most with about 40 to 50 participants, have found that autism may be associated with larger intra-cranial gray matter, white matter and amygdala volumes, or with smaller cerebellar, corpus callosum, and hippocampus volumes. Other studies found no such evidence.

The Israeli and American researchers took advantage of the recent release of data from the Autism Brain Imaging Data Exchange to draw clear conclusions. The database includes brain MRIs of over 1,000 people between the ages of 6 and 35 from around the world, half with autism and half without.

The researchers precisely analyzed the MRIs, dividing each brain image into over 180 regions of interest and assessing multiple anatomical measures, such as volume, surface area, and thickness in each region. Comparing the brains of the autistic people to those of the non-autistic people, they found only small anatomical differences on average. In contrast, there were large average differences within the group of people without autism.

“The most striking finding here was that anatomical differences within both the control group and the autistic group were immense and greatly overshadowed minute differences between the two groups,” said Dinstein. Probably reflecting the age range of the subjects, “individuals in the control group differ by 80-90 percent in their brain volumes, while differences in brain volume across autism and control groups differed by 2 to 3 percent at most. This led us to the conclusion that anatomical measures of brain volume or surface areas do not offer much information regarding the underlying mechanism or pathology of autistic spectrum disorder.”

He noted, “Our findings offer definitive answers regarding several scientific controversies about brain anatomy, which have occupied autism research for the past 10 to 15 years.”

Based on the findings, the researchers said it is unlikely that autism has a single anatomical signature, so MRIs will probably not be diagnostically helpful, given what is currently known. Rather, Dinstein said, biomarkers are probably shared only within subgroups of autistic people.

“Expecting to find a single answer for the entire ASD population is naïve. We need to move on to thinking about how to split up this very heterogeneous group of disorders into more meaningful biologically-relevant subgroups,” he said.

The previous studies that found size abnormalities in autistic people’s brains likely just captured snapshots of the natural diversity of brain anatomy, said Dinstein. The study he led finally took a wide enough view to see how all the snapshots fit together, he said.

“The problem with small samples, large within-group heterogeneity, and a scientific bias to report only positive findings, is that small samples are likely to yield significant differences across autism and control groups in a few of the 180 brain regions,” he said. “Our study simply explains why this has been happening and puts an end to several ensuing debates.”