FIGURE 1.

Data analysis flowchart. (A) Resting-state fMRI data were preprocessed and the averaged time-series were extracted using the Harvard-Oxford atlas. Then, global and local efficiency (GE and LE, respectively) metrics were computed for each participant using graph theory. Small solid gray circles represent nodes of the graphs (brain regions), while gray connecting lines are the edges of the graph (functional connections). Larger dotted circles represent segregated sub-graphs/networks (functional network characterized by highly connected brain areas), while dashed red lines are the within-network connections at the whole brain level. Panel (B) shows the two hierarchical levels of analysis performed using the MMB WQS approach to measure the effect of Pb, Mn, Cr, Cu on brain metrics (GE and LE). At the first level, WQS was performed to measure and derive the MMB metric for each metal individually (Pb, Mn, Cr, Cu) on brain metrics (GE and LE). Then, the joint effect of Pb, Mn, Cr, Cu on brain metrics was assessed by applying WQS to Pb, Mn, Cr, and Cu MMBs. All models were adjusted for sex and age. Figure adapted from Levin-Schwartz et al. (2019) and Rakesh et al. (2020).