Exploring Global and Local Processes Underlying Alterations in Resting-state Functional Connectivity and Dynamics in Schizophrenia

Overview

Journal Front Psychiatry

Specialty Psychiatry

Date 2024 Feb 28

PMID 38414495

Authors

Christoph Metzner

Cristiana Dimulescu

Fabian Kamp

Sophie Fromm

Peter J Uhlhaas

Klaus Obermayer

Affiliations

Soon will be listed here.

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.

Citing Articles

Abnormal Dynamic Reconstruction of Overlapping Communities in Schizophrenia Patients.

Guo Y, Wu X, Sun Y, Dong Y, Sun J, Song Z Brain Sci. 2024; 14(8).

PMID: 39199476 PMC: 11352520. DOI: 10.3390/brainsci14080783.

References

Aine C, Bockholt H, Bustillo J, Canive J, Caprihan A, Gasparovic C . Multimodal Neuroimaging in Schizophrenia: Description and Dissemination. Neuroinformatics. 2017; 15(4):343-364. PMC: 5671541. DOI: 10.1007/s12021-017-9338-9. View

Yang G, Murray J, Wang X, Glahn D, Pearlson G, Repovs G . Functional hierarchy underlies preferential connectivity disturbances in schizophrenia. Proc Natl Acad Sci U S A. 2015; 113(2):E219-28. PMC: 4720350. DOI: 10.1073/pnas.1508436113. View

Cakan C, Obermayer K . Biophysically grounded mean-field models of neural populations under electrical stimulation. PLoS Comput Biol. 2020; 16(4):e1007822. PMC: 7200022. DOI: 10.1371/journal.pcbi.1007822. View

Dimulescu C, Gareayaghi S, Kamp F, Fromm S, Obermayer K, Metzner C . Structural Differences Between Healthy Subjects and Patients With Schizophrenia or Schizoaffective Disorder: A Graph and Control Theoretical Perspective. Front Psychiatry. 2021; 12:669783. PMC: 8273511. DOI: 10.3389/fpsyt.2021.669783. View

Wang Y, Tang W, Fan X, Zhang J, Geng D, Jiang K . Resting-state functional connectivity changes within the default mode network and the salience network after antipsychotic treatment in early-phase schizophrenia. Neuropsychiatr Dis Treat. 2017; 13:397-406. PMC: 5308583. DOI: 10.2147/NDT.S123598. View

Friston K . Schizophrenia and the disconnection hypothesis. Acta Psychiatr Scand Suppl. 1999; 395:68-79. DOI: 10.1111/j.1600-0447.1999.tb05985.x. View

Morris H, Hashimoto T, Lewis D . Alterations in somatostatin mRNA expression in the dorsolateral prefrontal cortex of subjects with schizophrenia or schizoaffective disorder. Cereb Cortex. 2008; 18(7):1575-87. PMC: 2888087. DOI: 10.1093/cercor/bhm186. View

Lynall M, Bassett D, Kerwin R, McKenna P, Kitzbichler M, Muller U . Functional connectivity and brain networks in schizophrenia. J Neurosci. 2010; 30(28):9477-87. PMC: 2914251. DOI: 10.1523/JNEUROSCI.0333-10.2010. View

Burt J, Demirtas M, Eckner W, Navejar N, Ji J, Martin W . Hierarchy of transcriptomic specialization across human cortex captured by structural neuroimaging topography. Nat Neurosci. 2018; 21(9):1251-1259. PMC: 6119093. DOI: 10.1038/s41593-018-0195-0. View

10.

Faul F, Erdfelder E, Buchner A, Lang A . Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009; 41(4):1149-60. DOI: 10.3758/BRM.41.4.1149. View

11.

Yang G, Murray J, Repovs G, Cole M, Savic A, Glasser M . Altered global brain signal in schizophrenia. Proc Natl Acad Sci U S A. 2014; 111(20):7438-43. PMC: 4034208. DOI: 10.1073/pnas.1405289111. View

12.

Kong X, Kong R, Orban C, Wang P, Zhang S, Anderson K . Sensory-motor cortices shape functional connectivity dynamics in the human brain. Nat Commun. 2021; 12(1):6373. PMC: 8568904. DOI: 10.1038/s41467-021-26704-y. View

13.

Deco G, Kringelbach M, Jirsa V, Ritter P . The dynamics of resting fluctuations in the brain: metastability and its dynamical cortical core. Sci Rep. 2017; 7(1):3095. PMC: 5465179. DOI: 10.1038/s41598-017-03073-5. View

14.

Friston K, Frith C . Schizophrenia: a disconnection syndrome?. Clin Neurosci. 1995; 3(2):89-97. View

15.

Lee W, Doucet G, Leibu E, Frangou S . Resting-state network connectivity and metastability predict clinical symptoms in schizophrenia. Schizophr Res. 2018; 201:208-216. PMC: 6317903. DOI: 10.1016/j.schres.2018.04.029. View

16.

Hancock F, Rosas F, McCutcheon R, Cabral J, Dipasquale O, Turkheimer F . Metastability as a candidate neuromechanistic biomarker of schizophrenia pathology. PLoS One. 2023; 18(3):e0282707. PMC: 10035891. DOI: 10.1371/journal.pone.0282707. View

17.

Cabral J, Luckhoo H, Woolrich M, Joensson M, Mohseni H, Baker A . Exploring mechanisms of spontaneous functional connectivity in MEG: how delayed network interactions lead to structured amplitude envelopes of band-pass filtered oscillations. Neuroimage. 2013; 90:423-35. DOI: 10.1016/j.neuroimage.2013.11.047. View

18.

Deco G, Ponce-Alvarez A, Mantini D, Luca Romani G, Hagmann P, Corbetta M . Resting-state functional connectivity emerges from structurally and dynamically shaped slow linear fluctuations. J Neurosci. 2013; 33(27):11239-52. PMC: 3718368. DOI: 10.1523/JNEUROSCI.1091-13.2013. View

19.

Cabral J, Kringelbach M, Deco G . Functional graph alterations in schizophrenia: a result from a global anatomic decoupling?. Pharmacopsychiatry. 2012; 45 Suppl 1:S57-64. DOI: 10.1055/s-0032-1309001. View

20.

Metzner C, Zurowski B, Steuber V . The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia. Sci Rep. 2019; 9(1):18525. PMC: 6898379. DOI: 10.1038/s41598-019-53682-5. View