Elsevier

Biological Psychiatry

Volume 72, Issue 12, 15 December 2012, Pages 1043-1051
Biological Psychiatry

Archival Report
Diffusion Tensor Imaging in Young Children with Autism: Biological Effects and Potential Confounds

https://doi.org/10.1016/j.biopsych.2012.08.001Get rights and content

Background

Diffusion tensor imaging (DTI) has been used over the past decade to study structural differences in the brains of children with autism compared with typically developing children. These studies generally find reduced fractional anisotropy (FA) and increased mean diffusivity (MD) in children with autism; however, the regional pattern of findings varies greatly.

Methods

We used DTI to investigate the brains of sedated children with autism (n = 39) and naturally asleep typically developing children (n = 39) between 2 and 8 years of age. Tract based spatial statistics and whole brain voxel-wise analysis were performed to investigate the regional distribution of differences between groups.

Results

In children with autism, we found significantly reduced FA in widespread regions and increased MD only in posterior brain regions. Significant age × group interaction was found, indicating a difference in developmental trends of FA and MD between children with autism and typically developing children. The magnitude of the measured differences between groups was small, on the order of approximately 1%–2%. Subjects and control subjects showed distinct regional differences in imaging artifacts that can affect DTI measures.

Conclusions

We found statistically significant differences in DTI metrics between children with autism and typically developing children, including different developmental trends of these metrics. However, this study indicates that between-group differences in DTI studies of autism should be interpreted with caution, because their small magnitude make these measurements particularly vulnerable to the effects of artifacts and confounds, which might lead to false positive and/or false negative biological inferences.

Section snippets

Methods and Materials

Subject groups are composed of 39 AUT who met DSM-IV criteria for autism (1) and 39 TYP. Demographic and diagnostic information are provided in Table 2. Parents of all participating subjects provided written informed consent for study participation, which was approved by the National Institutes of Health Combined Neurosciences Institutional Review Board.

Children with autism (AUT) were included after an evaluation consisting of research-reliable administrations of the Autism Diagnosis

TBSS Analysis

The TBSS analysis found lower FA in AUT compared with TYP throughout the white matter, including but not limited to the cerebellum, genu of the corpus callosum, splenium of the corpus callosum, body of the corpus callosum, corticospinal tract, pons, posterior limbs of internal capsule, left superior temporal gyrus, superior-anterior, and temporal-parietal regions (Figure 1A). MD was greater in AUT compared with TYP in most white matter regions but only in the posterior half of the brain (Figure

Discussion

Investigation of DTI data revealed widespread differences of FA and MD in brain parenchyma of a group of young children who met full diagnostic criteria for autism (AUT), compared with TYP, with a predominant pattern of reduced FA and increased MD in AUT.

Only two other DTI studies of ASD coincide closely with our age range (22, 53). These studies similarly find reduced FA and increased MD in AUT compared with TYP. Regionally, our study is generally consistent with these studies but also

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