Associations between Changes in Social Visual Engagement and White Matter Microstructure during the First 6 Months of Life.

Background: Attention to eyes—a critical skill that guides typical socialization—is already in decline by the second month of life in infants later diagnosed with Autism Spectrum Disorder (ASD), with steeper decreases in eye fixation associated with more severe social disability (Jones & Klin, 2013, Nature). In contrast, typically developing (TD) children increase their attention to eyes throughout infancy, establishing a foundation for continued social visual engagement and brain specialization. The neural systems associated with this basic mechanism of social adaptive action are currently unknown, even in typical development. Identifying associations between trajectories of social visual engagement and trajectories of brain maturation in typical infancy is an important step towards understanding how deviations from these trajectories may lead to the emergence of social disability in ASD.

Objectives: To identify associations between trajectories of white matter microstructure and trajectories of social visual engagement in the first 6 months of life.

Methods: Diffusion MRI and eye-tracking data were collected prospectively and longitudinally in the same infants (n=32, 10 female) at 3 and 6 pseudorandom time points, respectively, between birth and 6 months. All participants were full-term, healthy infants with no family history of ASD or developmental delay and no known medical or genetic conditions. Diffusion data were collected with the following parameters: multiband factor of 2 with GRAPPA of 2; 2mm isotropic spatial resolution; b=0/700 s/mm², 61 diffusion directions. Atlas-based tractography was used to delineate major white matter tracts: arcuate fasciculus, corpus callosum – body, genu, and splenium, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus. Fractional anisotropy (FA) values were generated for each tract. Eye-tracking data were collected while infants viewed scenes of actress caregivers engaging in naturalistic interaction and percentage of fixation time for each of four regions-of-interest (eyes, mouth, body, background) was calculated. Growth curves were fit using functional principle component analysis (FPCA) and Functional Linear Regression using Principal Component Analysis tested associations between longitudinal trajectories (Yao, Müller, & Wang, 2005, Ann. of Statistics).

Results: Functional regression analyses revealed significant coefficients of determination (p<.05) between growth curves of eye-looking and FA in the genu of the corpus callosum (CCg) and inferior fronto-occipital fasciculus (IFOF). No other associations were found. Examination of the estimated regression functions (Figure 1C) revealed that percentage of fixation time on eyes at earlier developmental time points positively contributes to FA in the CCg and IFOF at later developmental time points (Figure 2).

Conclusions: This study provides the first demonstration of associations between trajectories of white matter development and social visual engagement in the first months of life. Early attention to eyes—a basic mechanism of social adaptive action that is disrupted in ASD—is positively associated with later development of the CCg and IFOF, tracts that form the structural foundation of pathways involved in voluntary goal-directed attention. These findings indicate that developing visual networks may be particularly responsive to experiential input involving the eyes of social partners and suggest a process by which early divergence from normative experience may lead to atypical patterns of white matter development in ASD.