Functional Graph Alterations in Schizophrenia: A Result from a Global Anatomic Decoupling?

Introduction: During rest, the brain exhibits slow hemodynamic fluctuations (<0.1 Hz) that are correlated across spatially segregated brain regions, defining functional networks. Restingstate functional networks of people with schizophrenia were found to have graph properties that differ from those of control subjects. Namely, functional graphs from patients exhibit reduced small-worldness, increased hierarchy, lower clustering, improved efficiency and greater robustness. Notably, most of these parameters correlate with patients' cognitive performance. Methods: To test if a brain-wide coupling deficit could be at the origin of such network reorganization, we use a model of resting-state activity where the coupling strength can be manipulated. For a range of coupling values, the simulated functional graphs obtained were characterized using graph theory. Results: For a coupling range, simulated graphs shared properties of healthy resting-state functional graphs. On decreasing the coupling strength, the resultant functional graphs exhibited a topological reorganization, in the same way as described in schizophrenia. Discussion: This work shows how complex functional graph alterations reported in schizophrenia can be accounted for by a decrease in the structural coupling strength. These results are corroborated by reports of lower white matter density in schizophrenia.