Disruptions of Hierarchical Cortical Organization in Early Psychosis and Schizophrenia

The cerebral cortex is organised hierarchically along an axis that spans unimodal sensorimotor to transmodal association areas. This hierarchy is often characterized using low-dimensional embeddings, termed gradients, of inter-regional functional coupling estimates measured with resting-state functional magnetic resonance imaging (fMRI). Such analyses may offer insights into the pathophysiology of schizophrenia, which is frequently linked to dysfunctional interactions between association and sensorimotor areas. To examine disruptions of hierarchical cortical function across distinct stages of psychosis, we applied diffusion map embedding to two independent fMRI datasets: one comprised 114 patients with early psychosis and 48 controls, and the other comprising 50 patients with established schizophrenia and 121 controls. We then analyzed the primary sensory-fugal and secondary visual-to-sensorimotor gradients of each participant in both datasets. There were no significant differences in regional gradient scores between patients with early psychosis and controls. Patients with established schizophrenia showed significant differences in the secondary, but not primary, gradient relative to controls. Gradient differences in schizophrenia were characterized by lower within-network dispersion in the Dorsal Attention (pFDR<.001), Visual (pFDR=.003), Frontoparietal (pFDR=.018), and Limbic (pFDR=.020) networks and lower between-network dispersion between the Visual network and other networks (pFDR<.001). These findings indicate that differences in cortical hierarchical function occur along the secondary visual-to-sensorimotor axis rather than the primary sensory-fugal axis, as previously thought. The absence of differences in early psychosis suggests that visual-sensorimotor abnormalities may emerge as the illness progresses.