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Previous studies demonstrated distinct neural correlates underpinning impaired self-regulation (dysregulation) between individuals with autism spectrum disorder (ASD) and typically developing controls (TDC). However, the impacts of dysregulation on white matter (WM) microstructural property in ASD and TDC remain unclear. Diffusion spectrum imaging was acquired in 59 ASD and 62 TDC boys. We investigated the relationship between participants’ dysregulation levels and microstructural property of 76 WM tracts in a multivariate analysis (canonical correlation analysis), across diagnostic groups. A single mode of brain-behavior co-variation was identified: participants were spread along a single axis linking diagnosis, dysregulation, diagnosis-by-dysregulation interaction, and intelligence to a specific WM property pattern. This mode corresponds to diagnosis-distinct correlates underpinning dysregulation, which showed higher generalized fractional anisotropy (GFA) associated with less dysregulation in ASD but greater dysregulation in TDC, in the tracts connecting limbic and emotion regulation systems. Moreover, higher GFA of the tracts implicated in memory, attention, sensorimotor processing, and perception associated with less dysregulation in TDC but worse dysregulation in ASD. No shared WM correlates of dysregulation between ASD and TDC were identified. Corresponding to previous studies, we demonstrated that ASD and TDC have broad distinct white matter microstructural property underpinning self-regulation.

Association of self-regulation with white matter correlates in boys with and without autism spectrum disorder