Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism

Abstract

Cross-sectional magnetic resonance imaging (MRI) studies have long hypothesized that the brain in children with autism undergoes an abnormal growth trajectory that includes a period of early overgrowth; however, this has never been confirmed by a longitudinal study. We performed the first longitudinal study of brain growth in toddlers at the time symptoms of autism are becoming clinically apparent using structural MRI scans at multiple time points beginning at 1.5 years up to 5 years of age. We collected 193 scans on 41 toddlers who received a confirmed diagnosis of autistic disorder at approximately 48 months of age and 44 typically developing controls. By 2.5 years of age, both cerebral gray and white matter were significantly enlarged in toddlers with autistic disorder, with the most severe enlargement occurring in frontal, temporal, and cingulate cortices. In the longitudinal analyses, which we accounted for age and gender effect, we found that all regions (cerebral gray, cerebral white, frontal gray, temporal gray, cingulate gray, and parietal gray) except occipital gray developed at an abnormal growth rate in toddlers with autistic disorder that was mainly characterized by a quadratic age effect. Females with autistic disorder displayed a more pronounced abnormal growth profile in more brain regions than males with the disorder. Given that overgrowth clearly begins before 2 years of age, future longitudinal studies would benefit from inclusion of even younger populations as well as further characterization of genetic and other biomarkers to determine the underlying neuropathological processes causing the onset of autistic symptoms.

Figure 1.

Axial section as shown in GWseg, displaying semimanual local threshold segmentation of cerebrum into cerebral gray matter (GM) and cerebral white matter (WM) (a) and resulting tissue classification used by Freesurfer to determine gray/white surface (b).

Figure 2.

Surface parcellation of cerebral gray (adapted from Desikan et al., 2006).

Figure 3.

Coronal images indicating parcellation boundaries for lobe regions of cerebral gray.

Figure 4.

Total cerebral volume (Vol) growth trajectory for males (○) and females (□). Dotted lines represent each subject's volume measurements; solid lines are autistic disorder (red) and typical control (blue) group quadratic growth regression curves. mo, Months.

Figure 5.

Cerebral gray (left) and white (right) matter volume growth trajectories for males (○) and females (□). Dotted lines represent each subject's volume measurements; solid lines are autistic disorder (red) and typical control (blue) group quadratic growth regression curves.

Figure 6.

Frontal (left) and temporal (right) gray matter volume growth trajectories for males (○) and females (□). Dotted lines represent each subject's volume measurements; solid lines are autistic disorder (red) and typical control (blue) group quadratic growth regression curves.