Small Nucleus Accumbens and Large Cerebral Ventricles in Infants and Toddlers Prior to Receiving Diagnoses of Autism Spectrum Disorder

Abstract

Early interventions for autism spectrum disorder (ASD) are increasingly available, while only 42-50% of ASD children are diagnosed before 3 years old (YO). To identify neuroimaging biomarkers for early ASD diagnosis, we evaluated surface- and voxel-based brain morphometry in participants under 3YO who were later diagnosed with ASD. Magnetic resonance imaging data were retrospectively obtained from patients later diagnosed with ASD at Boston Children's Hospital. The ASD participants with comorbidities such as congenital disorder, epilepsy, and global developmental delay/intellectual disability were excluded from statistical analyses. Eighty-five structural brain magnetic resonance imaging images were collected from 81 participants under 3YO and compared with 45 images from 45 gender- and age-matched nonautistic controls (non-ASD). Using an Infant FreeSurfer pipeline, 236 regionally distributed measurements were extracted from each scan. By t-tests and linear mixed models, the smaller nucleus accumbens and larger bilateral lateral, third, and fourth ventricles were identified in the ASD group. Vertex-wise t-statistical maps showed decreased thickness in the caudal anterior cingulate cortex and increased thickness in the right medial orbitofrontal cortex in ASD. The smaller bilateral accumbens nuclei and larger cerebral ventricles were independent of age, gender, or gestational age at birth, suggesting that there are MRI-based biomarkers in prospective ASD patients before they receive the diagnosis and that the volume of the nucleus accumbens and cerebral ventricles can be key MRI-based early biomarkers to predict the emergence of ASD.

Keywords: autism spectrum disorder; cerebral ventricles; magnetic resonance imaging; medial orbitofrontal cortex; nucleus accumbens.

Figure 1

Flowchart of participant selection from patients with ASD.

Figure 2

Surface-based vertex-wise t-statistical maps on inflated surface maps (dark gray = sulci; light gray = gyri) of thicker and thinner cortex in participants with ASD (N = 85) versus nonautistic controls (non-ASD, N = 45) in lateral (A), medial (B), dorsal (C), and ventral (D) views. Regions depicted in red–yellow and blue indicate areas with thicker and thinner cortices in ASD compared with non-ASD participants, respectively. Decreased cortical thickness in a part of the left caudal anterior cingulate cortex (B, white arrowhead) and increased cortical thickness in the right medial orbitofrontal cortex (D, white arrow) had low P-values (P < 0.0001). Abbreviation, Lt, left hemisphere; Rh, right hemisphere.

Figure 3

Scatter plots and regression lines (between age and measurements) of cortical GM, WM, subcortical GM, and cerebral ventricles and choroid plexus volume in “brainvol” annotation, cortical surface area in “aparc,” and nucleus accumbens volume in “aseg” annotation in ASD (closed circle and solid-line) and non-ASD (open circle and dotted line) participants. Abbreviation; ASD, Autism spectrum disorder; GM, gray matter; non-ASD, nonautistic controls; WM, white matter.

Figure 4

ROC curve for predicting the later diagnosis of ASD by the values of nucleus accumbens volume, cerebral ventricles volume, and the rate of nucleus accumbens volume to cerebral ventricles volume. Abbreviation; ASD, autism spectrum disorder; AUC, area under the curve; ROC, receiver operating characteristic.