The Impacts of Dysregulation on Cortical Thickness, Surface Area and Gyrfication for Males with and without Autism Spectrum Disorders

Background:  Although dysregulation, involving impairments in affective, behavioral and cognitive control, is common in autism spectrum disorder (ASD), the neural mechanism of dysregulation in ASD remains elusive. For typically developing (TD) individuals, several brain regions, such as anterior cingulate cortex, dorsolateral prefrontal cortex, ventromedial prefrontal cortex and amygdala, is involved in dysregulation. Interestingly, most of these regions overlap with those implicated in pathophysiology of ASD, warranting further investigations.

Objectives:  To test effects of dysregulation on neuroanatomy in ASD, and to investigate neurostructural correlates of dysregulation in ASD.

Methods:  Surface-based morphometry using FreeSurfer was applied on structural MRI images from 85 males with ASD (ranging 7-17 years, mean=12.9, standard deviation, SD=2.3) and 65 TD (mean=12.3, SD=2.4). We defined dysregulation by the T scores of 3 subscales (Attention, Aggression and Anxiety/Depression) in the Child Behavior Checklist. Dysregulation was defined as total T scores of 3 subscales in the CBCL more than 180. There were 54 and 31 males with ASD in the ASD+dysregulation and ASD-dysregulation groups, respectively. First, we compared cortical thickness, surface area and gyrification for ASD and TDC and test if the main findings would be different when dysregulation was controlled. Second, we investigated difference of cortical thickness, surface area and gyrification among ASD+dysregulation, ASD-dysregulation and TDC groups. Third, we explored if there is similar or different association of cortical thickness, surface area and gyrification and dysregulation in ASD and TDC groups. Age, age square term and FIQ were taken as covariates in all the analysis above. Cluster-level correction for multiple comparisons based on Monte Carlo simulation was implemented.

Results:  Males with ASD had increased cortical thickness in the right rostral middle frontal cortex, increased gyrification in the left inferior temporal cortex, right superior frontal cortex and right fusiform gyrus than TD. However, these findings all disappeared when dysregulation was controlled. For group difference among ASD+dysregulation, ASD-dysregulation and TD, ASD+dysregulation had thinner cortical thickness in the left superior parietal cortex and increased gyrification in the right lingual gyrus than ASD-dysregulation. ASD+dysregulation had thicker cortical thickness in the rostral middle frontal cortex and increased gyrification in the left inferior temporal, right insular and right superiorfrontal cortex than TD. ASD-dysregulation had thicker cortical thickness in right precentral gyrus than TD. Finally, ASD and TD groups had a shared association between dysregulation and several brain regions including surface area of the right lingual cortex and gyrfication of the left superior temporal and the right superior frontal cortex. Distinct association of dysregulation and surface area of the left postcentral cortex was found in ASD and TDC groups.

Conclusions:  Our findings suggest that neurobiological abnormalities found in ASD might be partially accounted for by the level of dysregulation. To explore the neural mechanism of dysregulation in ASD, several different approach such as categorical, dimensional or subgroup analysis should be considered in the future studies.