Abstract
OBJECTIVE: Repetitive and restricted behaviors (RRBs) are a core symptom of autism spectrum disorder (ASD), but effective treatment approaches are still lacking. Executive function (EF) has been identified as a promising target, as research increasingly shows a link between EF deficits and the occurrence of RRBs. However, the neural mechanisms that connect the two remain unclear. Since the orbitofrontal cortex (OFC) plays a role in both EF and RRBs, its functional connectivity dynamics could offer valuable insights into this relationship. METHODS: This study analyzed data from the Autism Brain Imaging Data Exchange (ABIDE) II database to explore brain function in 93 boys with ASD and 110 typically developing (TD) boys. Time-varying functional connectivity was analyzed between eight OFC subregions and other brain areas. By employing linear regression, the study assessed how atypical connectivity dynamics and EF influence RRBs. Additionally, mediation analysis with bootstrapping was used to determine how EF mediates the relationship between atypical connectivity and RRBs. RESULTS: We found significant differences in the variance of FC between ASD and TD groups, specifically in the OFC subregion in L-prefrontal and the left amygdala (t = 5.00, FDR q < 0.01). Regression analyses revealed that increased variance of this FC and EF significantly impacted RRBs, with inhibition, emotional control, and monitor showing strong associations (standardized β = 0.60 to 0.62, p < 0.01), which also had significant indirect effects on the relationship between the above dynamic FC and RRBs, which accounted for 59% of the total effect. CONCLUSION: This study highlights the critical role of EFs as a key mechanism in addressing RRBs in ASD. Specifically, it points out that EFs mediate the influence of atypical time-varying interactions within the OFC-amygdala circuit on RRBs.