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

Author:

Lurie Daniel J.1ORCID,Kessler Daniel2ORCID,Bassett Danielle S.3456ORCID,Betzel Richard F.3ORCID,Breakspear Michael78ORCID,Kheilholz Shella9ORCID,Kucyi Aaron10ORCID,Liégeois Raphaël1112ORCID,Lindquist Martin A.13ORCID,McIntosh Anthony Randal1415ORCID,Poldrack Russell A.16ORCID,Shine James M.17ORCID,Thompson William Hedley1618ORCID,Bielczyk Natalia Z.19ORCID,Douw Linda20ORCID,Kraft Dominik21ORCID,Miller Robyn L.22ORCID,Muthuraman Muthuraman23ORCID,Pasquini Lorenzo24ORCID,Razi Adeel252627ORCID,Vidaurre Diego28ORCID,Xie Hua29ORCID,Calhoun Vince D.223031ORCID

Affiliation:

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. Department of Physics & Astronomy, College of Arts & Sciences, University of Pennsylvania, Philadelphia, PA, USA

5. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

6. Department of Electrical & Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA

7. University of Newcastle, Callaghan, NSW, 2308, Australia

8. QIMR Berghofer, Brisbane, Australia

9. Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA

10. Department of Neurology and Neurological Sciences, Stanford University, Stanford CA, USA

11. Institute of Bioengineering, Center for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne, Switzerland

12. Department of Radiology and Medical Informatics, University of Geneva, Switzerland

13. Department of Biostatistics, Johns Hopkins University, Baltimore, MD, USA

14. Rotman Research Institute - Baycrest Centre, Toronto, Canada

15. Department of Psychology, University of Toronto, Toronto, Canada

16. Department of Psychology, Stanford University, Stanford, CA, USA

17. Brain and Mind Centre, University of Sydney, NSW, Australia

18. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

19. Stichting Solaris Onderzoek en Ontwikkeling, Nijmegen, The Netherlands

20. Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands

21. Department of Psychology, Goethe University Frankfurt, Frankfurt am Main, Germany

22. The Mind Research Network, Albuquerque, NM, USA

23. Biomedical Statistics and Multimodal Signal Processing Unit, Movement Disorders and Neurostimulation, Department of Neurology, Focus Program Translational Neuroscience, Johannes-Gutenberg-University Hospital, Mainz, Germany

24. Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA

25. Monash Institute of Cognitive and Clinical Neurosciences and Monash Biomedical Imaging, Monash University, Clayton, Australia

26. Wellcome Centre for Human Neuroimaging, Institute of Neurology, University College London, London, United Kingdom

27. Department of Electronic Engineering, NED University of Engineering and Technology, Karachi, Pakistan

28. Wellcome Trust Centre for Integrative Neuroimaging, Oxford Centre for Human Brain Activity, University of Oxford, United Kingdom

29. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA

30. Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA

31. Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State, Georgia Tech, Emory, Atlanta, Georgia, 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.

Funder

National Science Foundation

John D. and Catherine T. MacArthur Foundation

Alfred P. Sloan Foundation

ISI Foundation

Paul Allen Foundation

Army Research Laboratory

Army Research Office

Office of Naval Research

National Institute of Mental Health

National Institute of Child Health and Human Development

National Institute of Neurological Disorders and Stroke

Indiana University Office of the Vice President for Research

National Health and Medical Research Council

Australian Research Council

National Institutes of Health

Canadian Institutes of Health Research

CHIST-ERA

National Institute of Biomedical Imaging and Bioengineering

Knut and Alice Wallenberg Foundation

Society in Science

Dutch Organization for Scientific Research

German Research Foundation

Publisher

MIT Press - Journals

Subject

Applied Mathematics,Artificial Intelligence,Computer Science Applications,General Neuroscience

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