Characterizing normal perinatal development of the human brain structural connectivity

Early brain development is characterized by the formation of a highly organized structural connectome. The interconnected nature of this connectome underlies the brain’s cognitive abilities and influences its response to diseases and environmental factors. Hence, quantitative assessment of structural connectivity in the perinatal stage is useful for studying normal and abnormal neurodevelopment. However, estimation of the connectome from diffusion MRI data involves complex computations. For the perinatal period, these computations are further challenged by the rapid brain development and imaging difficulties. Combined with high inter-subject variability, these factors make it difficult to chart the normal development of the structural connectome. As a result, there is a lack of reliable normative baselines of structural connectivity metrics at this critical stage in brain development. In this study, we developed a computational framework, based on spatio-temporal averaging, for determining such baselines. We used this framework to analyze the structural connectivity between 33 and 44 postmenstrual weeks using data from 166 subjects. Our results unveiled clear and strong trends in the development of structural connectivity in perinatal stage. Connection weighting based on fractional anisotropy and neurite density produced the most consistent results. We observed increases in global and local efficiency, a decrease in characteristic path length, and widespread strengthening of the connections within and across brain lobes and hemispheres. We also observed asymmetry patterns that were consistent between different connection weighting approaches. The new computational method and results are useful for assessing normal and abnormal development of the structural connectome early in life.