Atypical Patterns of Gyrification in Preschool-Aged Boys with Autism Spectrum Disorder

Background: Gyrification is a measure that describes the convolution or cortical folding of the brain. It is a feature of human cortex that develops prenatally and very early in life. Early adverse events affecting cerebral development are known to result in cortical folding alterations that can be quantified later on in the brains of children. Given that gyrification develops early in life, investigating this neural feature in a young population of children with autism spectrum disorder (ASD), close in time to the age of diagnosis, may provide insight into the earliest neuropathological manifestations of ASD.

Objectives: To examine local gyrification index in a large sample of young children with ASD and age-matched typically developing (TD) children. 

Methods: Participants included 105 male children with ASD and 48 typically developing boys between 2 and 3.5 years of age enrolled in the Autism Phenome Project. T1-weighted structural MRIs were collected for each child and local gyrification index (LGI) was quantified based on these images. Retrospective measures including birth head circumference, birth length, birth weight, and gestational age at birth were acquired retrospectively from medical records. A subgroup of boys with ASD (n = 19) were classified as having disproportionate megalencephaly (ASD-DM; based on having a standardized ratio of total cerebral volume to height that was 1.5 SD above the mean for the TD group), while the remaining 86 boys with ASD had brain volume to height ratios within the normal range. Group comparisons included all children with ASD relative to TD, followed by comparisons of each ASD subgroup relative to TD. 

Results: There were no significant differences between groups for age, gestational age, birth weight, birth length, or birth head circumference. However, the children with ASD had significantly reduced LGI in left and right fusiform gyrus, compared to TD boys. Additional comparisons of ASD subgroups revealed a different pattern of gyrification alterations in the ASD-DM group. Compared to TD boys and controlling for differences in brain volume, the ASD-DM group had significantly increased LGI in right superior frontal, left isthmus cingulate, and left posterior cingulate, suggesting that the ASD-DM group has a different neural phenotype from boys with ASD without megalencephaly. An examination of the relationships between global gyrification and measures from birth records revealed the children with ASD had a significant positive correlation between head circumference at birth and global gyrification, while the TD group had no such relationship. 

Conclusions: Significant alterations in LGI in right and left fusiform in boys with ASD holds strong implications for social and emotional processing. But importantly, not all children with ASD exhibited this pattern of alterations; our results suggest that boys with ASD and disproportionate megalencephaly may have a different neural phenotype. Associations between global gyrification at 2-3.5 years of age with birth head circumference in the ASD group suggest that alterations in gyrification patterns may be determined prenatally and already present at birth.