Pervasive microstructural abnormalities in autism: a DTI study

Abstract

Background: Recent studies have reported abnormal functional connectivity patterns in the brains of people with autism that may be accompanied by decreases in white matter integrity. Since autism is a developmental disorder, we aim to investigate the nature and location of decreases in white and grey matter integrity in an adolescent sample while accounting for age. Methods: We used structural (T 1 ) imaging to study brain volumetrics and diffusion tensor imaging (DTI) to investigate white and grey matter integrity in people with autism. We obtained magnetic resonance images for adolescents aged 12-18 years with high-functioning autism and from matched controls. Fractional anisotropy and mean diffusivity, as well as grey and white matter volumetrics were analyzed. Results: There were 17 participants with autism and 25 matched controls included in this study. Participants with autism had lower fractional anisotropy in the left and right superior and inferior longitudinal fasciculus, but this effect was not significant after adjusting for age and intelligence quotient (IQ). The kurtosis of the white matter fractional anisotropy probability distribution was higher in this participant group, with and without adjustment for age and IQ. Most notably, however, the mean diffusivity levels were markedly increased in the autism group throughout the brain, and the mean diffusivity probability distributions of both grey and white matter were shifted toward a higher value, particularly with age and IQ adjustment. No volumetric differences in grey and white matter were found. Limitations: We corrected for age and IQ using a linear model. The study was also limited by its sample size, investigated age range and cross-sectional design. Conclusion: The findings suggest that autism is characterized by a generalized reduction of white matter integrity that is associated with an increase of interstitial space. The generalized manifestation of the white matter abnormalities provides an important new perspective on autism as a connectivity disorder.

Differences in the right inferior longitudinal fasciculus but no general disruption of white matter tracts in children with autism spectrum disorder

“…However, only a few diffusion imaging studies of autism even mention possible differences in head motion, let alone measure it. Only two papers report any quantitative analysis of the amount of motion present in the DWI scans, or report what motion threshold was used for excluding participants (9,10). Ten studies gathered imaging data while some participants were under general anesthesia and an additional two while participants were sleeping naturally, presumably reducing head motion.…”

“…Another potential problem that few diffusion studies of autism address or even mention is data quality. Indeed, to our knowledge, only two studies (9,10) report quantitative analyses of the amount of motion in their DWI data. Group differences in head motion could be a serious confounding factor, given that head motion is likely to be greater in children with autism, and group differences in head motion can lead artifactually to just the effects most often reported: reduced FA in white matter tracts in ASD (11).…”

Emerging Imaging Tools for Use with Traumatic Brain Injury Research

“…First, volumetric changes can evolve over an extended time (Sidaros et al, 2009;Trivedi et al, 2007;Wu et al, 2010a) and may be evident later than changes seen on other advanced imaging techniques such as DTI (Bendlin et al, 2008;Groen et al, 2010;Hutchinson et al, 2010;Wu et al, 2010a). It should be kept in mind that the relation between tissue integrity, as measured by volumetry, and outcome may be dynamic and complex, particularly in the earlier phases of recovery, as trajectories of rapid cognitive recovery and incomplete degenerative tissue change may be progressing in opposing directions and to differing degrees.…”

Abnormal Developmental Trajectories of White Matter in Autism - The Contribution of MRI

“…One study reported areas of reduced FA in children with high functioning autism (mean age 12.8 years) compared to controls, within the frontal WM and the superior longitudinal fasciculus, and increased FA within peripheral WM (Sahyoun et al, 2010). Three studies did not find any significant differences in FA values (Groen et al, 2011;Fletcher et al, 2010;Thomas et al, 2010). And finally, studies conducted only in subjects with autism (subgroup, not the entire spectrum) reported reductions in FA in the frontal, parietal and temporal lobes (BarneaGoraly et al, 2010); the frontal lobe (Mengotti et al, 2011;Pardini et al, 2009); and CC (Mengotti et al, 2011).…”