Our analysis of region-wise functional connectivity revealed widespread and generalized (context-independent) patient deficits localized predominantly to frontotemporal and medial posterior cortices. In addition, our analysis of edge-wise connectivity identified a subnetwork of 200 connections linking nearly 70% of the regions studied in which patients showed a context-independent functional connectivity reduction. More than half of these connections linked frontal cortex with posterior regions. Together these results point to a generalized and pervasive reduction in functional connectivity between frontal and other brain regions in schizophrenia. Our findings are consistent with a wide range of evidence implicating frontal dysfunction as a core feature of schizophrenia pathophysiology (5,10,47–51), and other connectivity studies implicating frontotemporal disturbances in particular (21–23,26,52–56).
