Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development1, 2. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life3, 4. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6–12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.
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Extended data figures and tables
Extended Data Figures
- Extended Data Figure 1: Visualization of cortical regions with surface area measurements among the top 40 features contributing to the linear sparse learning classification. (508 KB)
The cortical features produced by the deep learning approach (Fig. 3) are highly consistent with those observed using an alternative approach (linear sparse learning) shown here. Results from this alternative approach are included for comparison in Supplementary Tables 2 and 3.
- Extended Data Figure 2: Trajectories of TBV for males (left) and females (right). (169 KB)
For illustrative purposes, we provide plots for TBV for males and females from the same sample. The longitudinal trajectories of total brain volume (TBV) from 6 to 24 months for the three groups examined are shown with males and females displayed separately. The trajectory of TBV for males among the three groups is similar to the pattern we see in the full sample (Fig. 1). The female HR-ASD group is quite small (n = 2), which makes the pattern of trajectory difficult to interpret. These figures support the general similarity of the findings in the combined sample and the male-only sample. Red, HR-ASD; green, HR-neg; blue, LR. TBV is shown in mm3. The age (in months) is corrected by length (body size, in cm).
Extended Data Tables
- Supplementary Information (1.5 MB)
This file contains Supplementary Text and Data, Supplementary Figures 1-10, Supplementary Tables 1-3 and Supplementary References.