Directional coordination along the cortical hierarchy is selectively reorganized in schizophrenia
- 1Georgia State University
Abstract
Schizophrenia has long been framed as a disorder of the cortical hierarchy. Yet, the hierarchy has been studied almost entirely as fixed anatomy, leaving its moment-to-moment expression in ongoing brain activity unmeasured. By retaining the signed lead-lag geometry that conventional connectivity measures discard, complex-valued phase synchrony resolved a dynamic directional axis of coordination in which regions reversed their lead-lag relationship over time as the brain transitioned among feedback, feedforward, and integrative regimes. The three regimes replicated across seven datasets from four independent cohorts and aligned region by region with an independently defined cortical hierarchy. Neighboring organizing principles, including propagating waves, arousal, and the principal gradient, were insufficient to explain regime identity. Within the same subjects, GABAergic sedation shifted coordination toward feedback and motor imagery toward feedforward, demonstrating that the axis reflects a manipulable property of brain dynamics rather than a statistical partition. In schizophrenia (151 patients, 160 controls), the axis reorganized selectively: feedback coordination became less persistent, integrative coordination more persistent, feedforward comparatively spared, and trajectories less diverse. These effects replicated in an independent clinical cohort (68 patients, 89 controls). The reorganization tracked positive symptom severity, and its relationship to cognition reversed relative to controls: faster convergence to equilibrium was associated with better cognition in controls and worse cognition in patients. Directional coordination therefore identifies a reproducible and controllable dynamic expression of the cortical hierarchy that is selectively reorganized in schizophrenia and linked to both symptoms and cognitive function.
Related
- DiffDomain-Spectrum identifies structurally reorganized TADs from sparse aggregated single-cell Hi-C contact maps
- Structurally reorganized Wmk lineage with distinct genomic context and restricted distribution in Wolbachia
- Trait anxiety selectively amplifies reward learning under uncertainty, while N3 sleep attenuates it
- Genome-wide loss of chromatin accessibility coexists with selectively elevated RNA abundance in nutrient-starved U2OS cells
- Diatom-based treatment of geothermal brines to selectively remove silicon, retain lithium for downstream recovery, and produce omega-3 fatty acids
BibTeX
@misc{wiafe2026directional,
title = {{Directional coordination along the cortical hierarchy is selectively reorganized in schizophrenia}},
author = {S.-L. Wiafe and N. Soleimani and Z. Fu and R. Miller and V. Calhoun},
howpublished = {bioRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.25.727703},
url = {https://www.biorxiv.org/content/10.64898/2026.05.25.727703v2},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Directional coordination along the cortical hierarchy is selectively reorganized in schizophrenia
AU - S.-L. Wiafe
AU - N. Soleimani
AU - Z. Fu
AU - R. Miller
AU - V. Calhoun
PY - 2026
DA - 2026/05/25
PB - bioRxiv
DO - 10.64898/2026.05.25.727703
UR - https://www.biorxiv.org/content/10.64898/2026.05.25.727703v2
AB - Schizophrenia has long been framed as a disorder of the cortical hierarchy. Yet, the hierarchy has been studied almost entirely as fixed anatomy, leaving its moment-to-moment expression in ongoing brain activity unmeasured. By retaining the signed lead-lag geometry that conventional connectivity measures discard, complex-valued phase synchrony resolved a dynamic directional axis of coordination in which regions reversed their lead-lag relationship over time as the brain transitioned among feedback, feedforward, and integrative regimes. The three regimes replicated across seven datasets from four independent cohorts and aligned region by region with an independently defined cortical hierarchy. Neighboring organizing principles, including propagating waves, arousal, and the principal gradient, were insufficient to explain regime identity. Within the same subjects, GABAergic sedation shifted coordination toward feedback and motor imagery toward feedforward, demonstrating that the axis reflects a manipulable property of brain dynamics rather than a statistical partition. In schizophrenia (151 patients, 160 controls), the axis reorganized selectively: feedback coordination became less persistent, integrative coordination more persistent, feedforward comparatively spared, and trajectories less diverse. These effects replicated in an independent clinical cohort (68 patients, 89 controls). The reorganization tracked positive symptom severity, and its relationship to cognition reversed relative to controls: faster convergence to equilibrium was associated with better cognition in controls and worse cognition in patients. Directional coordination therefore identifies a reproducible and controllable dynamic expression of the cortical hierarchy that is selectively reorganized in schizophrenia and linked to both symptoms and cognitive function.
ER -