Exploring global and local processes underlying alterations in resting-state functional connectivity and dynamics in schizophrenia

Christoph Metzner; Cristiana Dimulescu; Fabian Kamp; Sophie Fromm; Peter J Uhlhaas; Klaus Obermayer

doi:10.3389/fpsyt.2024.1352641

Exploring global and local processes underlying alterations in resting-state functional connectivity and dynamics in schizophrenia

Front Psychiatry. 2024 Feb 13:15:1352641. doi: 10.3389/fpsyt.2024.1352641. eCollection 2024.

Authors

Christoph Metzner^{1

2

3}, Cristiana Dimulescu^{1

4}, Fabian Kamp^{1

5

6}, Sophie Fromm^{1

7}, Peter J Uhlhaas^{2

8}, Klaus Obermayer^{1

4}

Affiliations

¹ Neural Information Processing Group, Institute of Software Engineering and Theoretical Computer Science, Technische Universität Berlin, Berlin, Germany.
² Department of Child and Adolescent Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
³ School of Physics, Engineering and Computer Science, University of Hertfordshire, Hatfield, United Kingdom.
⁴ Bernstein Center for Computational Neuroscience Berlin, Berlin, Germany.
⁵ Max Planck School of Cognition, Max Planck Institute for Human Cognitive and Brain Science, Leipzig, Germany.
⁶ Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
⁷ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁸ Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: The current study suggests that large-scale alterations in ScZ are more likely the result of global rather than local network changes.

Keywords: computational model; functional connectivity; large-scale networks; resting-state fMRI; schizophrenia; temporal dynamics.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. CM and PU were supported through the Einstein Stiftung Berlin (A-2020-613). Data collection and sharing for this project was funded by NIMH cooperative agreement 1U01 MH097435. Data was downloaded from the COllaborative Informatics and Neuroimaging Suite Data Exchange tool (COINS; http://coins.mrn.org/dx) and data collection was performed at the Mind Research Network, and funded by a Center of Biomedical Research Excellence (COBRE) grant 5P20RR021938/P20GM103472 from the NIH to Dr. Vince Calhoun