Toward discovery science of human brain function
Open accessAbstract
Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.
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Spontaneous BOLD fluctuations are not random noise, but specifically organized in the resting human brain.
“Over the last decade many studies have found that spontaneous BOLD fluctuations are not random noise, but specifically organized in the resting human brain (Biswal et al., 2010).”
From Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal (2013) · cites this paper as Biswal et al., 2010
The Thousand Functional Connectomes and related projects are seeking to generate even larger numbers of subjects than the HCP, bringing together data from a wide range of imaging studies and scanners, and covering a wider range of subject groups, including a range of pathologies.
“The Thousand Functional Connectomes (and related) projects [74, 75], led by Mike Milham, are seeking to generate even larger numbers of subjects than the HCP, bringing together data from a wide range of imaging studies and scanners, and covering a wider range of subject groups, including a range of pathologies.”
From Functional connectomics from resting-state fMRI (2013) · cites this paper as [74]
Individual differences in RSFC can be reliably observed across time.
“While general brain organization measured with RSFC is similar across thousands of different individuals [12] and stable and robust over the short-term (hourly) and long-term (monthly) [86], there are small individual differences in connectivity, which can be reliably observed across time.”
From Predicting Brain Functional Connectivity Using Mobile Sensing (2020) · cites this paper as [12]
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- Authors
- Biswal, B. B., Mennes, M., Zuo, X.-N., Gohel, S., Kelly, C., Smith, S. M., Beckmann, C. F., Adelstein, J. S., Buckner, R. L., Colcombe, S., Dogonowski, A.-M., Ernst, M., Fair, D., Hampson, M., Hoptman, M. J., Hyde, J. S., Kiviniemi, V. J., Kötter, R., Li, S.-J., Lin, C.-P., Lowe, M. J., Mackay, C., Madden, D. J., Madsen, K. H., Margulies, D. S., Mayberg, H. S., McMahon, K., Monk, C. S., Mostofsky, S. H., Nagel, B. J., Pekar, J. J., Peltier, S. J., Petersen, S. E., Riedl, V., Rombouts, S. A. R. B., Rypma, B., Schlaggar, B. L., Schmidt, S., Seidler, R. D., Siegle, G. J., Sorg, C., Teng, G.-J., Veijola, J., Villringer, A., Walter, M., Wang, L., Weng, X.-C., Whitfield-Gabrieli, S., Williamson, P., Windischberger, C., Zang, Y.-F., Zhang, H.-Y., Castellanos, F. X., & Milham, M. P.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- NYU Langone Health (US)
- FMRIB Centre, Oxford University, Oxford OX3 9DU, UK;
- University of Oxford (GB)
- Howard Hughes Medical Institute (US)
- Bangor University (GB)
- Hvidovre Hospital (DK)
- Mood and Anxiety Disorders Program, National Institute of Mental Health/National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892;
- Oregon Health & Science University (US)
- Yale University (US)
- Nathan Kline Institute for Psychiatric Research (US)
- Medical College of Wisconsin (US)
- Oulu University Hospital (FI)
- Radboud University Nijmegen (NL)
- National Yang Ming University (TW)
- Cleveland Clinic (US)
- Duke Medical Center (US)
- Max Planck Institute for Human Cognitive and Brain Sciences (DE)
- Emory University (US)
- The University of Queensland (AU)
- University of Michigan (US)
- Kennedy Krieger Institute (US)
- Washington University in St. Louis (US)
- TUM Klinikum (DE)
- Leiden University (NL)
- The University of Texas at Dallas (US)
- Charité – Universitätsmedizin Berlin (DE)
- University of Pittsburgh (US)
- Zhongda Hospital Southeast University (CN)
- University of Oulu (FI)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Chinese Academy of Sciences (CN)
- Department of Brain and Cognitive Sciences, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Boston, MA 02139;
- Western University (CA)
- Medical University of Vienna (AT)
- Beijing Normal University (CN)
- ORCID
- Biswal, Bharat B.
- Mennes, Maarten
- Zuo, Xi-Nian
- Gohel, Suril
- Kelly, Clare
- Beckmann, Christian F.
- Buckner, Randy L.
- Colcombe, Stan
- Fair, Damien
- Hampson, Michelle
- Hoptman, Matthew J.
- Hyde, James S.
- Kiviniemi, Vesa J.
- Lin, Ching-Po
- Lowe, Mark J.
- Mackay, Clare
- Madden, David J.
- Madsen, Kristoffer H.
- Margulies, Daniel S.
- Mayberg, Helen S.
- McMahon, Katie
- Monk, Christopher S.
- Mostofsky, Stewart H.
- Nagel, Bonnie J.
- Pekar, James J.
- Peltier, Scott J.
- Petersen, Steven E.
- Riedl, Valentin
- Rombouts, Serge A. R. B.
- Rypma, Bart
- Schlaggar, Bradley L.
- Schmidt, Sein
- Seidler, Rachael D.
- Siegle, Greg J.
- Sorg, Christian
- Teng, Gao-Jun
- Villringer, Arno
- Walter, Martin
- Wang, Lihong
- Windischberger, Christian
- Zang, Yu-Feng
- Castellanos, F. Xavier
- Milham, Michael P.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-03-09
- Volume
- 107
- Issue
- 10
- Pages
- 4734-4739
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2842060
- OpenAlex
- W2008607322
- Cited by
- 2,970
- References
- 52
- Citations by year
- 2026: 72 · 2025: 117 · 2024: 115 · 2023: 127 · 2022: 163 · 2021: 205 · 2020: 255 · 2019: 187 · 2018: 182 · 2017: 219 · 2016: 205 · 2015: 246 · 2014: 239 · 2013: 236 · 2012: 200
- FWCI
- 123.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Institutional Repository of Institute of Psychology, Chinese Academy of Sciences (Institute of Psychology, Chinese Academy of Sciences) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (UL1TR000448)
- National Institute of Mental Health (K02MH082998, R01MH083246, R01MH064783, R01MH081218)
- National Institute on Drug Abuse (R01DA016979, R03DA024775)
- National Institute of Neurological Disorders and Stroke (R01NS049176)
- National Institute of Biomedical Imaging and Bioengineering (N02-EB-6-4281)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- resting-state fMRI, functional connectivity, functional connectome, interindividual variability, brain-behavior relationship, brain development
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Algorithms, Analysis of Variance, Brain, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Sex Factors, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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