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

Daniel J Lurie; Daniel Kessler; Danielle S Bassett; Richard F Betzel; Michael Breakspear; Shella Kheilholz; Aaron Kucyi; Raphaël Liégeois; Martin A Lindquist; Anthony Randal McIntosh; Russell A Poldrack; James M Shine; William Hedley Thompson; Natalia Z Bielczyk; Linda Douw; Dominik Kraft; Robyn L Miller; Muthuraman Muthuraman; Lorenzo Pasquini; Adeel Razi; Diego Vidaurre; Hua Xie; Vince D Calhoun

doi:10.1162/netn_a_00116

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

Netw Neurosci. 2020 Feb 1;4(1):30-69. doi: 10.1162/netn_a_00116. eCollection 2020.

Authors

Daniel J Lurie¹, Daniel Kessler², Danielle S Bassett³, Richard F Betzel³, Michael Breakspear⁴, Shella Kheilholz⁵, Aaron Kucyi⁶, Raphaël Liégeois⁷, Martin A Lindquist⁸, Anthony Randal McIntosh⁹, Russell A Poldrack¹⁰, James M Shine¹¹, William Hedley Thompson¹⁰, Natalia Z Bielczyk¹², Linda Douw¹³, Dominik Kraft¹⁴, Robyn L Miller¹⁵, Muthuraman Muthuraman¹⁶, Lorenzo Pasquini¹⁷, Adeel Razi¹⁸, Diego Vidaurre¹⁹, Hua Xie²⁰, Vince D Calhoun¹⁵

Affiliations

¹ Department of Psychology, University of California, Berkeley, Berkeley, CA, USA.
² Departments of Statistics and Psychiatry, University of Michigan, Ann Arbor, MI, USA.
³ Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
⁴ University of Newcastle, Callaghan, NSW, 2308, Australia.
⁵ Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
⁶ Department of Neurology and Neurological Sciences, Stanford University, Stanford CA, USA.
⁷ Institute of Bioengineering, Center for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne, Switzerland.
⁸ Department of Biostatistics, Johns Hopkins University, Baltimore, MD, USA.
⁹ Rotman Research Institute - Baycrest Centre, Toronto, Canada.
¹⁰ Department of Psychology, Stanford University, Stanford, CA, USA.
¹¹ Brain and Mind Centre, University of Sydney, NSW, Australia.
¹² Stichting Solaris Onderzoek en Ontwikkeling, Nijmegen, The Netherlands.
¹³ Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.
¹⁴ Department of Psychology, Goethe University Frankfurt, Frankfurt am Main, Germany.
¹⁵ The Mind Research Network, Albuquerque, NM, USA.
¹⁶ Biomedical Statistics and Multimodal Signal Processing Unit, Movement Disorders and Neurostimulation, Department of Neurology, Focus Program Translational Neuroscience, Johannes-Gutenberg-University Hospital, Mainz, Germany.
¹⁷ Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
¹⁸ Monash Institute of Cognitive and Clinical Neurosciences and Monash Biomedical Imaging, Monash University, Clayton, Australia.
¹⁹ Wellcome Trust Centre for Integrative Neuroimaging, Oxford Centre for Human Brain Activity, University of Oxford, United Kingdom.
²⁰ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.

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.

Keywords: Brain dynamics; Brain networks; Functional connectivity; Rest; Review; fMRI.

Publication types

Review

Abstract

Publication types

Grants and funding