Alterations in Resting-State Functional Connectivity and Dynamics in Schizophrenia as a Result of Global not Local Processes

We examined changes in large-scale functional connectivity and temporal dynamics and their underlying mechanisms in schizophrenia (ScZ) through measurements of resting-state functional magnetic resonance imaging (rs-fMRI) data and computational modelling. The rs-fMRI measurements from patients with chronic ScZ (n=38) and matched healthy controls (n=43), were obtained through the public schizConnect repository. Computational models were constructed based on diffusion-weighted MRI scans and fit to the experimental rs-fMRI data. We found decreased large-scale functional connectivity across sensory and association areas and for all functional subnetworks for the ScZ group. Additionally global synchrony was reduced in patients while metastability was unaltered. Perturbations of the computational model revealed that decreased global coupling and increased background noise levels both explained the experimentally found deficits better than local changes to the GABAergic or glutamatergic system. The current study suggests that large-scale alterations in ScZ are more likely the result of global rather than local network changes. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement CM and PJU were supported through the Einstein Stiftung Berlin (A-2020-613) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Data was obtained from an NIH-supported COBRE (Centers of Biomedical Research Excellence) Phase I grant (2P20GM103472) via SchizConnect. The use of the data was granted after registration to the SchizConnect website and the signing of the SchizConnect and the COBRE Data Use Agreements. All studies within the COBRE project were approved by the institutional review board (IRB) of the University of New Mexico (UNM) and all subjects provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced are available online at https://github.com/ChristophMetzner/FrontiersPsychiatry2023