Fig. 3. Disease epicenters.

A Disease epicenter mapping schematic for cortico-cortical connectivity: To discover epicenters of SCZ, the SCZ-related cortical alteration t-value vector (1 × 68) from our mega-analysis, was iteratively correlated with each region-specific cortico-cortical connectivity vector (1 × 68), derived from the HCP functional and structural connectivity matrices (68 × 68). In the example we showcase the procedure for two theoretical cortical regions with different magnitudes of correlations between each region’s cortico-cortical connectivity vector and the SCZ-specific t-value map. Regions whose connectivity vectors are highly correlated with SCZ-specific cortical alteration patterns (t-values) are likely epicenters of SCZ (Region 1). Regions whose connectivity vectors are weakly correlated with the SCZ-specific cortical alteration patterns (t-values) are unlikely epicenters of SCZ (Region 2). We systematically repeated this analysis across all cortical and subcortical regions for both functional and structural connectivity. The resulting correlation values of each region were plotted on the surface to generate epicenter maps that display the epicenter likelihood of each region. B Correlation coefficient maps depicting the strength of association between the normative region-based functional (left) and structural (right) connectivity and the SCZ-specific morphological alteration maps. Disease epicenters are regions that are more strongly connected to regions with more pronounced morphometric alterations - and, inversely, are more weakly connected with regions with less pronounced alterations. Asterisks denote the top five significant epicenters. Top-5 functional epicenters, cortical: entorhinal cortex (L + R), banks of superior temporal sulcus (L,), inferior temporal gyrus (L); subcortical: amygdala (L + R), putamen (L + R), caudate (L). Top-5 structural epicenters, cortical: pars opercularis of inferior frontal gyrus (L); subcortical: none.