Abstract
Schizophrenia has been conceptualized as a disorder arising from structurally pathological alterations to white‐matter fibers in the brain. However, few studies have focused on white‐matter functional changes in schizophrenia. Considering that converging evidence suggests that white‐matter resting state functional MRI (rsfMRI) signals can effectively depict neuronal activity and psychopathological status, this study examined white‐matter network‐level interactions in antipsychotic‐naive first‐episode schizophrenia (FES) to facilitate the interpretation of the psychiatric pathological mechanisms in schizophrenia. We recruited 42 FES patients (FESs) and 38 healthy controls (HCs), all of whom underwent rsfMRI. We identified 11 white‐matter functional networks, which could be further classified into deep, middle, and superficial layers of networks. We then examined network‐level interactions among these 11 white‐matter functional networks using coefficient Granger causality analysis. We employed group comparisons on the influences among 11 networks using network‐based statistic. Excitatory influences from the middle superior corona radiate network to the superficial orbitofrontal and deep networks were disrupted in FESs compared with HCs. Additionally, an extra failure of suppression within superficial networks (including the frontoparietal network, temporofrontal network, and the orbitofrontal network) was observed in FESs. We additionally recruited an independent cohort (13 FESs and 13 HCs) from another center to examine the replicability of our findings across centers. Similar replication results further verified the white‐matter functional network interaction model of schizophrenia. The novel findings of impaired interactions among white‐matter functional networks in schizophrenia indicate that the pathophysiology of schizophrenia may also lie in white‐matter functional abnormalities.
Highlights
Schizophrenia has been conceptualized as a chronically debilitating disorder arising from pathological alterations in white-matter fibers in the brain (Stephan, Friston, & Frith, 2009; Wernicke, 1906)
We examined the interactions among white-matter functional networks using Granger causality analysis (GCA) on the resting-state functional MRI signals
In view of the network organization pattern of white-matter suggested by a previous study (Peer et al, 2017), this study examined interactions among 11 white-matter functional networks consisting of three layers in first-episode schizophrenia (FES) and healthy controls (HC)
Summary
Schizophrenia has been conceptualized as a chronically debilitating disorder arising from pathological alterations in white-matter fibers in the brain (Stephan, Friston, & Frith, 2009; Wernicke, 1906). During resting state, white-matter functional signals have been found to be highly homogenous and can effectively depict neuronal activity Ji, Liao, Chen, Zhang, & Wang, 2017; Marussich, Lu, Wen, & Liu, 2017) By using these resting-state functional signals, white matter can reproducibly be organized into several functional networks, which are associated with certain gray-matter neurophysiological networks (Peer, Nitzan, Bick, Levin, & Arzy, 2017). Resting-state white-matter functional activity, which is organized in an intrinsic network-level form, may play an essential role in neurophysiological processes
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