RS‐fMRI Evidence of Left Frontal Lobe Developmental Deviation as a Candidate Core Pathology of Autism Spectrum Disorder

Autism spectrum disorder (ASD) is one of the most prevalent developmental disorders. This study utilized 3-Tesla resting-state fMRI data analysed with the functional parcellation algorithm MOSI (modular analysis and similarity measurement) to investigate cortical functional organization in ASD. Sixty individuals with ASD and sixty healthy controls were selected from the Autism Brain Imaging Data Exchange (ABIDE), with no significant differences in age and gender distribution. The MOSI-derived metrics were compared using independent two-sample t-tests. The findings revealed a significant reduction in the functional volume of the left frontal lobe, a region critical for language, cognitive, and social processing. This reduction appears to be accompanied by compensatory expansion in other brain regions, suggesting a reallocation of neural resources that may contribute to ASD heterogeneity. These results support the notion of left frontal lobe developmental deviation (LFDD) as a parsimonious neural mechanism underlying key ASD features. The accountability of LFDD in various cognitive, symptomatic and behavioural characteristics of ASD is briefly discussed, along with its implications for male predominance and evolutionary relevance. Overall, the study provides a novel brain-based perspective on ASD, moving beyond traditional psychological models to offer a neurobiological explanation for its defining characteristics and possible underlying developmental origins.