Brain growth rate abnormalities visualized in adolescents with autism

Abstract

Autism spectrum disorder is a heterogeneous disorder of brain development with wide ranging cognitive deficits. Typically diagnosed before age 3, autism spectrum disorder is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared with those of typically developing children and adolescents. Using tensor-based morphometry, we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and seven typically developing boys (mean age/interscan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (P = 0.03, corrected), especially in the parietal (P = 0.008), temporal (P = 0.03), and occipital lobes (P = 0.02). We also visualized abnormal overgrowth in autism in gray matter structures such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. Tensor-based morphometry revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects.

Figure 1

Diagram of the study design. Individual Jacobian maps J ^Dn (D, diagnosis; “A” as autism, and “C” as control; n, subject index) are derived from the deformation matrix U_Intra^Dn, which is obtained by iteratively deforming the follow‐up scan (Time 2) to the initial scan (Time 1) of the same subject. Variance across individual brains is modeled by using an inter‐subject deformation field, U_Inter^Dn. The displacement vector field U_Inter^Dn = (u_x, u_y, u_z) is applied to transform the Jacobian growth map of each subject (J ^Dn) to the detailed brain anatomy defined by the MDT template. J^Dn_s (s, standard space) represents the individual Jacobian map in the standard space. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 2

Lobar masks were manually created on the MDT, designating left (L) and right (R) frontal, parietal, temporal, and occipital lobes. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 3

Individual tissue change (Jacobian) maps of an 11‐year‐old typically developing boy (scan interval: 2.2 years) (a) and a similarly aged autistic boy (scan interval: 2.9 years) (b). The initial scan was conducted around 10 years of age for each subject. The Jacobian map illustrates the overall percentage of tissue change during the scan interval. The color coded Jacobian map is displayed over the structural MRI image, with the hot and cold colors representing local tissue expansion and atrophy, respectively. Standard radiologic convention is used to display the images. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 4

Annual tissue growth rates (percentage of tissue change per year) mapped in the control group, the autistic group, and the difference in growth rates between the two groups. Each set of tri‐planar images is chosen to show anatomical regions with considerable deviation from typical development. Compared with the control group, the autistic group exhibits abnormal growth patterns in several white and gray matter structures. ACC, anterior cingulate cortex; CSP, centrum semiovale in the dorsal core of the parietal lobe; FL, frontal lobe; LV, lateral ventricle (posterior horn); OR, optic radiation; PCR, posterior corona radiata; PT, putamen. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]