RS-fMRI Evidence of Left Frontal Lobe Developmental Deviation as a Potential Pathognomonic Feature of Autism Spectrum Disorder

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Abstract
Autism spectrum disorder (ASD) is one of the most prevalent developmental disorders. This study utilized 3-Tesla resting-state fMRI data analyzed with the functional parcellation algorithm MOSI (Modularity Analysis and Similarity Measurements) to investigate cortical functional organization in ASD. Sixty individuals with ASD and sixty healthy controls were recruited, 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 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 core ASD features. The accountability of LFDD in various cognitive, symptomatic, and behavioral characteristics of ASD is briefly discussed, along with its implications for male predominance and evolutionary relevance. Overall, these findings provide a novel brain science perspective that moves beyond traditional psychological frameworks in explaining major psychiatric disorders. Lay summary This study reveals that individuals with autism spectrum disorder (ASD) exhibit a significant reduction in the functional volume of the left frontal lobe, a brain region crucial for language and social skills. This alteration may lead to compensatory changes in other brain areas, contributing to the diversity of ASD traits.

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