Lateralization of Brain Networks and Clinical Severity in Toddlers with Autism Spectrum Disorder: A HARDI Diffusion MRI Study.

Recent diffusion tensor imaging studies in adolescents and children with Autism Spectrum Disorder (ASD) have reported a loss or an inversion of the typical left-right lateralization in fronto-temporal regions crucial for sociocommunicative skills. No studies explored atypical lateralization in toddlers and its correlation with clinical severity of ASD. We recruited a cohort of 20 subjects aged 36 months or younger receiving a first clinical diagnosis of ASD (15 males; age range 20-36 months). Patients underwent diffusion MRI (High-Angular-Resolution Diffusion Imaging protocol). Data from cortical parcellation were combined with tractography to obtain a connection matrix and diffusion indexes (DI ) including mean fractional anisotropy (DFA ), number of tracts (DNUM ), and total tract length (DTTL ). A laterality index was generated for each measure, and then correlated with the Autism Diagnostic Observation Schedule-Generic (ADOS-G) total score. Laterality indexes of DFA were significantly correlated with ADOS-G total scores only in two intrafrontal connected areas (correlation was positive in one case and negative in the other). Laterality indexes of DTTL and DNUM showed significant negative correlations (P < 0.05) in six connected areas, mainly fronto-temporal. This study provides first evidence of a significant correlation between brain lateralization of diffusion indexes and clinical severity in toddlers with a first diagnosis of ASD. Significant correlations mainly involved regions within the fronto-temporal circuits, known to be crucial for sociocommunicative skills. It is of interest that all correlations but one were negative, suggesting an inversion of the typical left-right asymmetry in subjects with most severe clinical impairment.