Characterizing normal perinatal development of the human brain structural connectivity

Early brain development is characterized by the formation of a highly organized structural connectome, which underlies 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, inherently low signal quality, imaging difficulties, and 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 method based on spatio-temporal averaging in the image space for determining such baselines. We used this method 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 the perinatal stage. We observed increases in measures of network integration and segregation, 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. Connection weighting based on fractional anisotropy and neurite density produced the most consistent results. Our proposed method also showed considerable agreement with an alternative technique based on connectome averaging. The new computational method and results of this study can be useful for assessing normal and abnormal development of the structural connectome early in life.