Disruptions of Hierarchical Cortical Organization in Early Psychosis and Schizophrenia

Abstract

Background: The cerebral cortex is organized hierarchically along an axis that spans unimodal sensorimotor to transmodal association areas. This hierarchy is often characterized using low-dimensional embeddings, termed gradients, of interregional functional coupling estimates measured with resting-state functional magnetic resonance imaging. Such analyses may offer insights into the pathophysiology of schizophrenia, which has been frequently linked to dysfunctional interactions between association and sensorimotor areas.

Methods: To examine disruptions of hierarchical cortical function across distinct stages of psychosis, we applied diffusion map embedding to 2 independent functional magnetic resonance imaging datasets: one comprising 114 patients with early psychosis and 48 control participants, and the other comprising 50 patients with established schizophrenia and 121 control participants. Then, we analyzed the primary sensorimotor-to-association and secondary visual-to-sensorimotor gradients of each participant in both datasets.

Results: There were no significant differences in regional gradient scores between patients with early psychosis and control participants. Patients with established schizophrenia showed significant differences in the secondary, but not primary, gradient compared with control participants. Gradient differences in schizophrenia were characterized by lower within-network dispersion in the dorsal attention (false discovery rate [FDR]-corrected p [p_FDR] < .001), visual (p_FDR = .003), frontoparietal (p_FDR = .018), and limbic (p_FDR = .020) networks and lower between-network dispersion between the visual network and other networks (p_FDR < .001).

Conclusions: These findings indicate that differences in cortical hierarchical function occur along the secondary visual-to-sensorimotor axis rather than the primary sensorimotor-to-association axis as previously thought. The absence of differences in early psychosis suggests that visual-sensorimotor abnormalities may emerge as the illness progresses.

Keywords: Cortical hierarchy; Early psychosis; Functional connectivity; Functional connectivity gradients; Functional magnetic resonance imaging (fMRI); Schizophrenia.