Enlarged perivascular spaces under the dorso-lateral prefrontal cortex and severity of autism

The glymphatic system allows cerebrospinal fluid (CSF) flow along the brain's perivascular spaces (PVS), aiding in the removal of harmful substances into the venous system. Previous studies have suggested that younger males with severe autism spectrum disorder (ASD) exhibit enlarged PVS (ePVS), although the specific regions or extent of PVS enlargement remain unclear. Additionally, it is still unknown whether the localization of ePVS correlates with specific ASD symptoms. Using automated MRI-based PVS quantification, we conducted a descriptive observational study to map the number, diameter, and volume of PVS across 72 brain areas, correlating these features with the clinical severity of autism and the presence or absence of three distinct ASD symptoms: language impairment, stereotypies, and hypersensoriality. The study involved 36 children with ASD (ages 1-9 years). A thorough analysis of ePVS in the white matter underlying 72 cortical areas revealed that different ASD symptoms exhibit specific ePVS localizations. Moreover, ePVS in the white matter beneath the two rostral middle frontal regions were associated with the overall clinical severity of ASD as well as specific symptoms (verbal dysfunction, stereotypies, and hypersensoriality). When these prefrontal subregions experience excessive PVS enlargement, it may lead to hypoactivity in the dorsolateral prefrontal cortex (DLPFC), contributing to the manifestation of ASD symptoms.