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

• Type of Material: Article
• Authors: Daniel J. Lurie, University of California Berkeley; Daniel Kessler, University of Michigan; Danielle S. Bassett, University of Pennsylvania; Richard F. Betzel, University of Pennsylvania; Michael Breakspear, University of Newcastle; Shella Keilholz, Emory University; Aaron Kucyi, Stanford University; Raphael Liégeois, Ecole Polytechnique Fédérale de Lausanne; Martin A. Lindquist, Johns Hopkins University; Anthony Randal McIntosh, Rotman Research Institute; Russell A. Poldrack, Stanford University; James M. Shine, University of Sydney; William Hedley Thompson, Stanford University; Natalia Z. Bielczyk, Stichting Solaris Onderzoek en Ontwikkeling; Linda Douw, VU University; Dominik Kraft, Goethe University; Robyn L. Miller, The Mind Research Network; Muthuraman Muthuraman, Johannes Gutenberg University; Lorenzo Pasquini, University of California San Francisco; Adeel Razi, Monash University; Diego Vidaurre, University of Oxford; Hua Xie, Stanford University; Vince D. Calhoun, The Mind Research Network
• Language: English
• Date: 2020
• Publisher: Massachusetts Institute of Technology
• Publication Version: Final Published Version
• Copyright Statement: © 2019 Massachusetts Institute of Technology
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1162/netn_a_00116
• Title of Journal or Parent Work: Netw Neurosci
• Volume: 4
• Issue: 1
• Start Page: 30
• End Page: 69
• Grant/Funding Information: Daniel J. Lurie, National Science Foundation, Award ID: DGE 1106400. Daniel J. Lurie, National Institute of Neurological Disorders and Stroke, Award ID: 1F31NS108665-01A1. Daniel Kessler, National Science Foundation, Award ID: DMS-1646108. Danielle S. Bassett, John D. and Catherine T. MacArthur Foundation. Danielle S. Bassett, Alfred P. Sloan Foundation. Danielle S. Bassett, ISI Foundation. Danielle S. Bassett, Paul Allen Foundation. Danielle S. Bassett, Army Research Laboratory, Award ID: W911NF-10-2-0022. Danielle S. Bassett, Army Research Office, Award ID: Bassett-W911NF-14-1-0679. Danielle S. Bassett, Army Research Office, Award ID: Grafton-W911NF-16-1-0474. Danielle S. Bassett, Army Research Office, Award ID: DCIST-W911NF-17-2-0181. Danielle S. Bassett, Office of Naval Research. Danielle S. Bassett, National Institute of Mental Health, Award ID: 2-R01-DC-009209-11. Danielle S. Bassett, National Institute of Mental Health, Award ID: R01-MH112847. Danielle S. Bassett, National Institute of Mental Health, Award ID: R01-MH107235. Danielle S. Bassett, National Institute of Mental Health, Award ID: R21-M MH-106799. Danielle S. Bassett, National Institute of Child Health and Human Development, Award ID: 1R01HD086888-01. Danielle S. Bassett, National Institute of Neurological Disorders and Stroke, Award ID: R01 NS099348. Danielle S. Bassett, National Science Foundation, Award ID: BCS-1441502. Danielle S. Bassett, National Science Foundation, Award ID: BCS-1430087. Danielle S. Bassett, National Science Foundation, Award ID: NSF PHY-1554488. Danielle S. Bassett, National Science Foundation, Award ID: BCS-1631550. Richard F. Betzel, Indiana University Office of the Vice President for Research, Award ID: Emerging Area of Research Initiative, Learning: Brains, Machines, and Children. Michael Breakspear, National Health and Medical Research Council, Award ID: 118153. Michael Breakspear, National Health and Medical Research Council, Award ID: 10371296. Michael Breakspear, National Health and Medical Research Council, Award ID: 1095227. Michael Breakspear, Australian Research Council, Award ID: CE140100007. Shell Kielholz, National Institutes of Health, Award ID: R01MH111416. Shell Kielholz, National Institutes of Health, Award ID: R01NS078095. Shell Kielholz, National Science Foundation, Award ID: BCS INSPIRE 1533260. Aaron Kucyi, Canadian Institutes of Health Research, Award ID: Banting Fellowship. Raphaël Liégeois, CHIST-ERA (http://dx.doi.org/10.13039/501100001942), Award ID: IVAN 20CH21 174081. Martin A. Lindquist, National Institute of Biomedical Imaging and Bioengineering, Award ID: R01 EB016061. Martin A. Lindquist, National Institute of Biomedical Imaging and Bioengineering, Award ID: R01 EB026549. James M. Shine, National Health and Medical Research Council, Award ID: GNT1072403. James M. Shine, National Health and Medical Research Council, Award ID: GNT1156536. William Hedley Thompson, Knut and Alice Wallenberg Foundation, Award ID: 2016.0473. Linda Douw, Society in Science, Award ID: Branco Weiss Fellowship. Linda Douw, Dutch Organization for Scientific Research, Award ID: 016.146.086. Adeel Razi, Australian Research Council, Award ID: DECRA, DE170100128. Dominik Kraft, German Research Foundation, Award ID: CRC 1193. Dominik Kraft, German Research Foundation, Award ID: INST 247/859-1. Muthuraman Muthuraman, German Research Foundation, Award ID: SFB CRC-1193. Muthuraman Muthuraman, German Research Foundation, Award ID: SFB CRC-TR-128. Vince D. Calhoun, National Institutes of Health, Award ID: R01EB020407. Vince D. Calhoun, National Institutes of Health, Award ID: P20GM103472. Vince D. Calhoun, National Institutes of Health, Award ID: P30GM122734. Vince D. Calhoun, National Science Foundation, Award ID: 1539067.
• Keywords: Brain networks; Review; Brain dynamics; Functional connectivity; Rest; fMRI
• Research Categories: Biology, Neuroscience; Health Sciences, Radiology

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.