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The history and future of resting-state functional magnetic resonance imaging

Nature volume 641, pages 1121–1131 (2025)Cite this article

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Abstract

Since the discovery of resting-state functional connectivity in the human brain, this neuroimaging approach has revolutionized the study of neural architecture. Once considered noise, the functional significance of spontaneous low-frequency fluctuations across large-scale brain networks has now been investigated in more than 25,000 publications. In this Review, we provide a historical overview and thoughts regarding potential future directions for resting-state functional MRI (rsfMRI) research, highlighting the most informative analytic approaches that have been developed to reveal the brain’s intrinsic spatiotemporal organization. We review the collaborative efforts that have led to the widespread use of rsfMRI in neuroscience, with an emphasis on methodological innovations that have been made possible by contributions from electrical and biomedical engineering, physics, mathematics and computer science. We focus on key theoretical and methodological advances that will be necessary for further progress in the field, highlighting the need for further integration with new developments in whole-brain computational modelling, more sophisticated approaches to brain–behaviour mapping, greater mechanistic insights from concurrent measurement of neurophysiology, and greater appreciation of the problem of generalization failure in machine learning applications. We propose that rsfMRI has the potential for even greater clinical relevance when it is fully integrated with population neuroscience and global health initiatives in the service of precision psychiatry.

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Fig. 1: Timeline of key events in the history of rsfMRI.
Fig. 2: Reproducible large-scale functional brain networks.
Fig. 3: rsfMRI data analysis workflow.
Fig. 4: Machine learning and precision psychiatry.

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Acknowledgements

B.B.B. is supported by R01 MH131335 from the National Institute of Mental Health, R01 AG085665 from the National Institute on Aging and RF1 NS124778 from the National Institute of Neurological Disorders and Stroke. L.Q.U. is supported by R21 HD111805 and R01 HD116691 from the National Institute of Child Health and Human Development and U24 DA041147 and U01 DA050987 from the National Institute on Drug Abuse. B.B.B. was on sabbatical from New Jersey Institute of Technology during the initial writing of this manuscript.

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  1. The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China, Chengdu, China

    Bharat B. Biswal

  2. Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, USA

    Bharat B. Biswal

  3. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA

    Lucina Q. Uddin

  4. Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA

    Lucina Q. Uddin

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B.B.B. and L.Q.U. wrote and revised the manuscript.

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Biswal, B.B., Uddin, L.Q. The history and future of resting-state functional magnetic resonance imaging. Nature 641, 1121–1131 (2025). https://doi.org/10.1038/s41586-025-08953-9

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