Early brain overgrowth in autism associated with an increase in cortical surface area before age 2 years

Abstract

Context: Brain enlargement has been observed in 2-year-old children with autism, but the underlying mechanisms are unknown.

Objective: To investigate early growth trajectories in brain volume and cortical thickness.

Design: Longitudinal magnetic resonance imaging study.

Setting: Academic medical centers.

Participants: Fifty-nine children with autism spectrum disorder (ASD) and 38 control children.

Intervention: Children were examined at approximately 2 years of age. Magnetic resonance imaging was repeated approximately 24 months later (when aged 4-5 years; 38 children with ASD; 21 controls).

Main outcome measures: Cerebral gray and white matter volumes and cortical thickness.

Results: We observed generalized cerebral cortical enlargement in individuals with ASD at both 2 and 4 to 5 years of age. Rate of cerebral cortical growth across multiple brain regions and tissue compartments in children with ASD was parallel to that seen in the controls, indicating that there was no increase in rate of cerebral cortical growth during this interval. No cerebellar differences were observed in children with ASD. After controlling for total brain volume, a disproportionate enlargement in temporal lobe white matter was observed in the ASD group. We found no significant differences in cortical thickness but observed an increase in an estimate of surface area in the ASD group compared with controls for all cortical regions measured (temporal, frontal, and parieto-occipital lobes).

Conclusions: Our longitudinal magnetic resonance imaging study found generalized cerebral cortical enlargement in children with ASD, with a disproportionate enlargement in temporal lobe white matter. There was no significant difference from controls in the rate of brain growth for this age interval, indicating that brain enlargement in ASD results from an increased rate of brain growth before age 2 years. The presence of increased cortical volume, but not cortical thickness, suggests that early brain enlargement may be associated with increased cortical surface area. Cortical surface area overgrowth in ASD may underlie brain enlargement and implicates a distinct set of pathogenic mechanisms.

Figure 1. Trajectory of Development: Total Brain, Total Tissue, Gray, and White Tissue Volumes

Panels show the subject trajectories (scatterplot) for total brain volume, and mean group trajectories with confidence bands for total tissue volume, total gray matter and total white matter. Groups shown are ASD (color= red line, black & white= dashed line) and controls (CON) (color= blue line, black & white = solid line).

Figure 2. Trajectory of Development: Cerebral Cortical Lobe Volumes

Panels show the mean group trajectories with confidence bands for the cortical lobe volumes. Cortical regions displayed include frontal, temporal, and parietal-occipital lobes. Combined volumes (right+left hemisphere) for each lobar region are shown. Groups shown are ASD (dashed line) and controls (CON) (solid line).

Figure 3. Surface Area* Trajectory for ASD vs. Controls

Panels show the mean group trajectories with confidence bands for an *estimate of surface area (SA = regional cortical volume (CV)/regional cortical thickness (CT)) in frontal, temporal, and parietal-occipital lobes. The measure of CV in this case refers to gray matter volume only. Groups shown are ASD (red dashed line) and controls (CON) (blue solid line) with lower (LL) and upper (UL) confidence bands.