Functional Connectivity-Derived Optimal Gestational-Age Cut Points for Fetal Brain Network Maturity

Abstract

The architecture of the human connectome changes with brain maturation. Pivotal to understanding these changes is defining developmental periods when transitions in network topology occur. Here, using 110 resting-state functional connectivity data sets from healthy fetuses between 19 and 40 gestational weeks, we estimated optimal gestational-age (GA) cut points for dichotomizing fetuses into 'young' and 'old' groups based on global network features. We computed the small-world index, normalized clustering and path length, global and local efficiency, and modularity from connectivity matrices comprised 200 regions and their corresponding pairwise connectivity. We modeled the effect of GA at scan on each metric using separate repeated-measures generalized estimating equations. Our modeling strategy involved stratifying fetuses into 'young' and 'old' based on the scan occurring before or after a selected GA (i.e., 28 to 33). We then used the quasi-likelihood independence criterion statistic to compare model fit between 'old' and 'young' cohorts and determine optimal cut points for each graph metric. Trends for all metrics, except for global efficiency, decreased with increasing gestational age. Optimal cut points fell within 30-31 weeks for all metrics coinciding with developmental events that include a shift from endogenous neuronal activity to sensory-driven cortical patterns.

Keywords: fetal connectome; functional MRI; functional connectivity; graph theory; neurodevelopment; resting-state.

Figure 1

Plot of generalized estimating equation QICu fit indices below (dashed lines) and above (solid lines) the threshold for each metric against gestational age in weeks. Intersecting lines represent the estimated optimal GA binary stratification point.