Altered Hemispheric Asymmetry of Functional Hierarchy in Schizophrenia

Background/Objectives: Schizophrenia is a severe psychiatric disorder characterized by deficits in perception and advanced cognitive functions. Prior studies have reported abnormal lateralization in cortical morphology and functional connectivity in schizophrenia. However, it remains unclear whether schizophrenia affects hemispheric asymmetry in the hierarchical organization of functional connectome. Methods: Here, we apply a gradient mapping framework to the hemispheric functional connectome to estimate the first three gradients, which characterize unimodal-to-transmodal, visual-to-somatomotor, and somatomotor/default mode-to-multiple demand hierarchy axes. We then assess between-group differences in intra- and inter-hemispheric asymmetries of these three functional gradients. Results: We find that, compared to healthy controls, patients with schizophrenia exhibit significantly altered hemispheric asymmetry in functional gradient across multiple networks, including the dorsal attention, ventral attention, visual, and control networks. Region-level analyses further reveal that patients with schizophrenia show significantly abnormal hemispheric gradient asymmetries in several cortical regions in the dorsal prefrontal gyrus, medial superior frontal gyrus, and somatomotor areas. Lastly, we find that hemispheric asymmetries in functional gradients can differentiate between patients and healthy controls and predict the severity of positive symptoms in schizophrenia. Conclusions: Collectively, these findings suggest that schizophrenia is associated with altered hemispheric asymmetry in functional hierarchy, providing novel perspectives for understanding the atypical brain lateralization in schizophrenia.