Schizophrenia is associated with widespread abnormalities in large-scale brain organization; however, the mechanisms linking altered cortical hierarchy to disrupted neural communication and clinical symptoms remain unclear. By integrating functional connectivity gradient analysis and stepwise functional connectivity (SFC), we aimed to clarify how alterations in cortical hierarchy translate into disrupted connectome-based propagation in schizophrenia.

Resting-state functional MRI data from 820 participants (310 healthy controls and 510 patients with schizophrenia) were analyzed across multiple cohorts. Cortical hierarchy was characterized using functional connectivity gradients, focusing on the principal unimodal–transmodal gradient (G1). Connectome-based propagation was examined using SFC, with step counts indexing propagation efficiency across predefined hierarchical levels. Associations with clinical symptoms were assessed, including mediation analyses.

Global cortical hierarchy was preserved in schizophrenia; however, selective alterations were evident. Patients with schizophrenia showed significantly reduced G1 values in the dorsal attention network (DAN), with regional alterations primarily localized to dorsal attention and somatomotor regions. SFC analysis revealed delayed propagation toward higher-order association networks in schizophrenia, reflected by increased step counts to intermediate and transmodal hierarchical levels. Among patients with illness duration <5 years, delayed propagation to higher hierarchical levels was associated with greater positive and negative symptom severity. Mediation analyses demonstrated that delayed propagation significantly mediated the relationship between DAN hierarchical positioning and clinical symptoms.

These findings suggest that schizophrenia is characterized by selective disruption of cortical hierarchy within attentional control systems, leading to impaired large-scale connectome-based propagation that links cortical organization to clinical symptoms.

Emotion regulation tendencies are well-known transdiagnostic markers of psychopathology, but their neurobiological foundations have mostly been examined within the theoretical framework of cortical–subcortical interactions.

We explored the connectome-wide neural correlates of emotion regulation tendencies using functional and diffusion magnetic resonance images of healthy young adults (N = 99; age 20–30; 28 females). We first tested the importance of considering both the functional and structural connectome through intersubject representational similarity analyses. Then, we employed a canonical correlation analysis between the functional–structural hybrid connectome and 23 emotion regulation strategies. Lastly, we sought to externally validate the results on a transdiagnostic adolescent sample (N = 93; age 11–19; 34 females).

First, interindividual similarity of emotion regulation profiles was significantly correlated with interindividual similarity of the functional–structural hybrid connectome, more so than either the functional or structural connectome. Canonical correlation analysis revealed that an adaptive-to-maladaptive gradient of emotion regulation tendencies mapped onto a specific configuration of covariance within the functional–structural hybrid connectome, which primarily involved functional connections in the motor network and the visual networks as well as structural connections in the default mode network and the subcortical–cerebellar network. In the transdiagnostic adolescent dataset, stronger functional signatures of the found network were associated with higher general positive affect through more frequent use of adaptive coping strategies.

Taken together, our study illustrates a gradient of emotion regulation tendencies that is best captured when simultaneously considering the functional and structural connections across the whole brain.