Disrupted modular organization of primary sensory brain areas in schizophrenics

Abstract

Abnormal brain resting-state functional connectivity has been consistently observed in patients affected by Schizophrenia (SCZ) using functional MRI and other neuroimaging methods. Graph theoretical methods provide a framework to investigate these defective functional interactions and their effects on the modular organization of brain connectivity networks. A few studies have shown abnormal distribution of connectivity within and between functional modules, an indication of imbalanced functional segregation ad integration in SCZ patients. However, no major alterations in the modular structure of functional connectivity networks in patients have been reported, and unambiguous identification of the neural substrates involved remains elusive. Recently, it has been demonstrated that current modularity analysis methods suffer from a fundamental and severe resolution limit, as they fail to detect features that are smaller than a scale determined by the size of the entire connectivity network. This resolution limit is likely to have hampered the ability to resolve differences between patients and controls in previous cross-sectional studies. Here, we apply a novel, resolution limit-free approach to study the modular organization of resting state functional connectivity networks in a large cohort of SCZ patients, and in matched healthy controls. Leveraging these important methodological advances, we find new evidence of substantial fragmentation and reorganization involving primary sensory, auditory and visual areas in SCZ patients. Conversely, frontal and prefrontal areas, typically associated with higher cognitive functions, appear to be largely unaffected, with changes selectively involving language and speech processing areas. Our findings provide support to the hypothesis that cognitive dysfunction in SCZ may arise from deficits occurring already at early stages of sensory processing.