Executive Function and Brain Relationships in Very Young Children at High and Low Familial Risk for ASD

Background: Individuals with ASD have impairments in executive function (EF) that are present throughout the life span (Demetriou et al., 2018). As previously reported, young children at high familial risk for ASD (HR), irrespective of whether or not they develop ASD, demonstrate slower EF development than young children at low familial risk (LR; St. John et al., 2016). Neuroimaging studies investigating EF function implicate the frontal and prefrontal regions (Best et al., 2010; Diamond & Goldman-Rakic, 1989); however, to date, the relationship of early brain development to EF in HR children has not been reported.

Objectives: To investigate the relationships between frontal and prefrontal brain regions at 12 months to EF function at 24 months in HR and LR children.

Methods: Participants were part of the multi-site (UNC, CHOP, WUSTL, UW), longitudinal Infant Brain Imaging Study. Age-matched comparison groups having complete imaging and EF data (HR n=99; LR n=39) with clinical-best-estimate diagnosis at 24 months were evaluated. EF was assessed using the A-not-B at 24 months (total correct/total trials; Diamond, 1985). High-resolution 3-D T1 & 3-D T2-weighted MRI data (1mm3) acquired using a Siemens Trio 3T scanner at 12 months were used to determine volumes for the frontal lobe (FL), prefrontal cortex (PFC), and occipital lobe (OL; a control region). Right and left hemispheric volumes were averaged. Analyses employed logistic regression with developmental functioning (MSEL) and total cerebral volume (TCV) included as co-variates.

Results: Group status (HR vs. LR) moderated the relationship between 12-month FL volume and 24-month A-not-B performance (χ² = 6.51, p = 0.011), controlling for MSEL and TCV. The likelihood of better performance on the A-not-B increased as FL volume increased for the LR group. In the HR group, greater 12-month FL volume did not increase the likelihood of better performance on the A-not-B at 24 months. Group status similarly moderated the relationship between 12-month PFC volume and 24-month A-not-B performance (χ² = 7.95, p = 0.005), controlling for MSEL and TCV. In the LR group, the likelihood of better performance on the A-not-B increased as PFC volume increased. For the HR group, greater 12-month PFC volume did not increase the likelihood of better 24-month A-not-B performance. There was no significant main effects or interactions with the control region (OL; χ² = 3.19, p = 0.074, χ² = 3.52, p = 0.061).

Conclusions: Increased frontal lobe and prefrontal cortex volumes at 12 months were related to better EF function at 24 months in LR children but not HR children. These findings may, at least in part, lead to better understanding of why HR children show slower growth in their EF abilities compared with LR children (St. John et al., 2016). Further investigation is underway to evaluate brain-EF relations in HR children who develop ASD as compared with HR-NonASD and LR children. Longitudinal studies are needed to understand the relationship of slower EF development and differential brain growth in Frontal Lobe and Prefrontal cortex to functional outcomes in school-age.