Anna Machado¹, Junda Zhu¹, Clement Garin¹, Matthew McPhail¹, Adam Anderson¹, Finnegan Calabro², Beatriz Luna², Christos Constantinidis¹; ¹Vanderbilt University, ²University of Pittsburgh

White matter in humans and non-human primates continues developing from infancy through adolescence in parallel with gains in cognitive abilities. To investigate the association of white matter growth and working memory with developmental trajectories, we utilized diffusion tensor imaging (DTI) in eight monkeys by tracking changes in fractional anisotropy (FA) - a DTI metric measuring the diffusivity of water molecules in white matter tracts. A total of 86 DTI images were acquired using a Siemens 3T MRI scanner. Animals were scanned periodically over three years with identical acquisition parameters. Throughout their development, subjects were trained to perform an oculomotor delayed response task, requiring a memory-guided saccade after a 3 s delay period. DTI data was preprocessed and analyzed using MRtrix3 and FSL. Diffusion images from both phase encoding directions were combined, denoised, and susceptibility-induced distortion was corrected. After an affine transform registration of diffusion and structural images to a standard macaque template, FA values were extracted from 57 tracts using manual region-of-interest labeling. General additive mixed models with penalized smooth plate regression splines quantified non-linear associations between age/maturation and FA measures. We defined maturation age as the age of ossification of distal tibias in each of our subjects. The models included per-subject random intercepts and development slopes. Hierarchical differences of white matter development were shown, with developmental effects across almost all tracts, and no regions showing significant decreases in FA measures. Cerebellar tracts showed significant white matter growth from late childhood into adulthood (p<.05). During adolescence, association and projection tracts had yet to reach peak, significantly increasing after the maturation age (p<.01). In parallel, precision of memory guided saccades improved during this period of maturation. Collectively, our results indicate white matter maturation progressively develops from childhood through adolescence, reflecting gains in cognitive abilities.

Acknowledgements: Supported by NIH grants R01 MH117996 and R01 MH116675