Closed-loop pathways associated with clinical symptoms in children with autism spectrum disorder: a complex network analysis

Abstract

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Neurobiomarkers for ASD are lacking, which hinders early diagnosis and personalized treatment. This study aimed to identify potential biomarkers for ASD using complex network analysis, specifically causal brain networks, to identify functional closed-loop pathways in the brains of children with ASD. Methods: The study included 58 ASD patients and 57 typically developing (TD) children ages 6−12 years. Brain causal networks and temporal-lag networks were constructed using a deep learning model to infer the causal relationships between brain regions and the temporal-lag of signal transmissions. Statistical analysis was performed to compare differences between the TD and ASD groups and to identify the potential associations between different symptoms of the ASD group. Results: The results revealed numerous aberrant functional pathways, mainly located in the junction of the frontal and parietal lobes, as well as the occipital lobes, in children with ASD, when compared to TD children. Three closed-loop pathways were significantly negatively correlated with the total score of the combined social-communication domain in the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), including lenticular nucleus putamen left (PUT.L)→lenticular nucleus pallidum right (PAL. R)→PUT.L (r=−0.448, P=0.001), PAL.R→lenticular nucleus putamen right (PUT.R)→PAL.R (r=−0.362, P=0.012), and insula right (INS.R)→Heschl gyrus right (HES.R)→INS.R (r=−0.345, P=0.016). Importantly, a positive interaction among these closed-loop pathways was observed with a weak intensity, indicating that social impairments and stereotyped behaviors were interrelated with a weak effect in children with ASD. Conclusions: The study showed the potential of identifying multiple abnormal closed-loop pathways using complex network analysis in aiding early diagnosis and treatment of ASD. These findings provided insights into the neurobiological basis of social impairments and stereotyped behaviors in children with ASD, which may aid in the development of personalized interventions and therapeutic targets for this disorder.