Cited by 648Functional Brain Connectivity StudiesMental Health Research TopicsAdvanced MRI Techniques and Applications

Questions and controversies in the study of time-varying functional connectivity in resting fMRI

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Lurie, Daniel J., Kessler, Daniel, Bassett, Danielle S., Betzel, Richard F., Breakspear, Michael, Kheilholz, Shella, Kucyi, Aaron, Liégeois, Raphaël +15 more·2020·Network Neuroscience

Published version of a preprint

Abstract

The brain is a complex, multiscale dynamical system composed of many interacting regions. Knowledge of the spatiotemporal organization of these interactions is critical for establishing a solid understanding of the brain's functional architecture and the relationship between neural dynamics and cognition in health and disease. The possibility of studying these dynamics through careful analysis of neuroimaging data has catalyzed substantial interest in methods that estimate time-resolved fluctuations in functional connectivity (often referred to as "dynamic" or time-varying functional connectivity; TVFC). At the same time, debates have emerged regarding the application of TVFC analyses to resting fMRI data, and about the statistical validity, physiological origins, and cognitive and behavioral relevance of resting TVFC. These and other unresolved issues complicate interpretation of resting TVFC findings and limit the insights that can be gained from this promising new research area. This article brings together scientists with a variety of perspectives on resting TVFC to review the current literature in light of these issues. We introduce core concepts, define key terms, summarize controversies and open questions, and present a forward-looking perspective on how resting TVFC analyses can be rigorously and productively applied to investigate a wide range of questions in cognitive and systems neuroscience.

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Authors
Lurie, D. J., Kessler, D., Bassett, D. S., Betzel, R. F., Breakspear, M., Kheilholz, S., Kucyi, A., Liégeois, R., Lindquist, M. A., McIntosh, A. R., Poldrack, R. A., Shine, J. M., Thompson, W. H., Bielczyk, N. Z., Douw, L., Kraft, D., Miller, R. L., Muthuraman, M., Pasquini, L., Razi, A., Vidaurre, D., Xie, H., & Calhoun, V. D.
Affiliations
  • University of California, Berkeley (US)
  • University of Michigan (US)
  • University of Pennsylvania (US)
  • QIMR Berghofer Medical Research Institute (AU)
  • Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA
  • Stanford University (US)
  • University of Geneva (CH)
  • Johns Hopkins University (US)
  • University of Toronto (CA)
  • The University of Sydney (AU)
  • Karolinska Institutet (SE)
  • Radboud University Medical Center (NL)
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
  • Goethe University Frankfurt (DE)
  • Mind Research Network (US)
  • University Medical Center of the Johannes Gutenberg University Mainz (DE)
  • University of California, San Francisco (US)
  • NED University of Engineering and Technology (PK)
  • University of Oxford (GB)
  • Georgia Institute of Technology (US)
Corresponding author
  • Lurie, Daniel J.
  • Calhoun, Vince D.
Venue
Network Neuroscience
Publisher
MIT Press
Published
2020-01
Volume
4
Issue
1
Pages
30-69
ISSN
2472-1751 (ISSN-L)
OpenAlex
W2995313551
Cited by
648
References
271
Citations by year
2026: 76 · 2025: 108 · 2024: 115 · 2023: 91 · 2022: 89 · 2021: 98 · 2020: 57 · 2019: 13 · 2018: 1
FWCI
8.04
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Network Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
  • IUScholarWorks Open (Indiana University) (submittedVersion)
  • PsyArXiv (OSF Preprints) (submittedVersion)
  • PsyArXiv (OSF Preprints) (submittedVersion, cc-by)
  • OPUS (Augsburg University) (submittedVersion, cc-by)
  • NOVA (University of Newcastle Australia) (submittedVersion, cc-by)
Funders
  • National Science Foundation (DGE 1106400, DMS-1646108, BCS-1441502, BCS-1430087, NSF PHY-1554488, BCS-1631550, BCS INSPIRE 1533260, 1539067)
  • John D. and Catherine T. MacArthur Foundation
  • Alfred P. Sloan Foundation
  • ISI Foundation
  • Paul Allen Foundation
  • Army Research Laboratory (W911NF-10-2-0022)
  • Army Research Office (Bassett-W911NF-14-1-0679, Grafton-W911NF-16-1-0474, DCIST-W911NF-17-2-0181)
  • Office of Naval Research
  • National Institute of Mental Health (2-R01-DC-009209-11, R01-MH112847, R01-MH107235, R21-M MH-106799)
  • National Institute of Child Health and Human Development (1R01HD086888-01)
  • National Institute of Neurological Disorders and Stroke (R01 NS099348, 1F31NS108665-01A1)
  • Indiana University Office of the Vice President for Research (Emerging Area of Research Initiative, Learning: Brains, Machines, and Children)
  • National Health and Medical Research Council (118153, 10371296, 1095227, GNT1072403, GNT1156536)
  • Australian Research Council (CE140100007, DECRA, DE170100128)
  • National Institutes of Health (R01MH111416, R01NS078095, R01EB020407, P20GM103472, P30GM122734)
  • Canadian Institutes of Health Research (Banting Fellowship)
  • CHIST-ERA (IVAN 20CH21 174081)
  • National Institute of Biomedical Imaging and Bioengineering (R01 EB016061, R01 EB026549)
  • Knut and Alice Wallenberg Foundation (2016.0473)
  • Society in Science (Branco Weiss Fellowship)
  • Dutch Organization for Scientific Research (016.146.086)
  • German Research Foundation (CRC 1193, INST 247/859-1, SFB CRC-1193, SFB CRC-TR-128)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Keywords
time-varying functional connectivity, resting-state fMRI, dynamic functional connectivity, statistical validity, neural dynamics, brain functional architecture

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