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Updated: May 31, 2026
Probing the Brain in Autism Using fMRI and Diffusion Tensor Imaging
Published on: September 12, 2011
MRI study of minor physical anomaly in childhood autism implicates aberrant neurodevelopment in infancy
Charlton Cheung1, Grainne M McAlonan, Yee Y Fung
1Department of Psychiatry, The University of Hong Kong, Pokfulam, Hong Kong.
Background:
MPAs (minor physical anomalies) frequently occur in neurodevelopmental disorders because both face and brain are derived from neuroectoderm in the first trimester. Conventionally, MPAs are measured by evaluation of external appearance. Using MRI can help overcome inherent observer bias, facilitate multi-centre data acquisition, and explore how MPAs relate to brain dysmorphology in the same individual. Optical MPAs exhibit a tightly synchronized trajectory through fetal, postnatal and adult life. As head size enlarges with age, inter-orbital distance increases, and is mostly completed before age 3 years. We hypothesized that optical MPAs might afford a retrospective 'window' to early neurodevelopment; specifically, inter-orbital distance increase may represent a biomarker for early brain dysmaturation in autism.
Methods:
We recruited 91 children aged 7-16; 36 with an autism spectrum disorder and 55 age- and gender-matched typically developing controls. All children had normal IQ. Inter-orbital distance was measured on T1-weighted MRI scans. This value was entered into a voxel-by-voxel linear regression analysis with grey matter segmented from a bimodal MRI data-set. Age and total brain tissue volume were entered as covariates.
Results:
Intra-class coefficient for measurement of the inter-orbital distance was 0.95. Inter-orbital distance was significantly increased in the autism group (p = 0.03, 2-tailed). The autism group showed a significant relationship between inter-orbital distance grey matter volume of bilateral amygdalae extending to the unci and inferior temporal poles.
Conclusions:
Greater inter-orbital distance in the autism group compared with healthy controls is consistent with infant head size expansion in autism. Inter-orbital distance positively correlated with volume of medial temporal lobe structures, suggesting a link to "social brain" dysmorphology in the autism group. We suggest these data support the role of optical MPAs as a "fossil record" of early aberrant neurodevelopment, and potential biomarker for brain dysmaturation in autism.
Insights
Children with autism spectrum disorder have increased inter-orbital distance, a minor physical anomaly. This finding suggests inter-orbital distance may serve as an early biomarker for brain dysmaturation in autism.
Area of Science:
- Neurodevelopmental disorders
- Medical imaging
- Autism spectrum disorder research
Background:
- Minor physical anomalies (MPAs) are common in neurodevelopmental disorders due to shared early developmental origins.
- Traditionally assessed externally, MPAs can be objectively measured using MRI to correlate with brain morphology.
- Optical MPAs, like inter-orbital distance, follow a synchronized developmental trajectory, potentially offering insights into early neurodevelopment.
Purpose of the Study:
- To investigate if inter-orbital distance, a minor physical anomaly, can serve as a biomarker for early brain dysmaturation in autism spectrum disorder.
- To explore the relationship between inter-orbital distance and brain morphology in children with and without autism spectrum disorder.
Main Methods:
- Recruited 91 children (7-16 years) with autism spectrum disorder (n=36) and typically developing controls (n=55), all with normal IQ.
- Measured inter-orbital distance using T1-weighted MRI scans.
- Performed voxel-by-voxel linear regression analysis correlating inter-orbital distance with grey matter volume, controlling for age and total brain volume.
Main Results:
- High reliability for inter-orbital distance measurement (Intra-class coefficient = 0.95).
- Significantly increased inter-orbital distance observed in the autism group compared to controls (p=0.03).
- In the autism group, greater inter-orbital distance correlated with increased grey matter volume in bilateral amygdalae and medial temporal lobe structures.
Conclusions:
- Elevated inter-orbital distance in autism aligns with observed early head size expansion.
- The correlation with medial temporal lobe structures suggests a link to "social brain" dysmorphology in autism.
- Optical MPAs, specifically inter-orbital distance, may act as a "fossil record" of aberrant neurodevelopment and a potential biomarker for autism-related brain dysmaturation.
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