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Functionally linked resting‐state networks reflect the underlying structural connectivity architecture of the human brain
Open accessAbstract
During rest, multiple cortical brain regions are functionally linked forming resting‐state networks. This high level of functional connectivity within resting‐state networks suggests the existence of direct neuroanatomical connections between these functionally linked brain regions to facilitate the ongoing interregional neuronal communication. White matter tracts are the structural highways of our brain, enabling information to travel quickly from one brain region to another region. In this study, we examined both the functional and structural connections of the human brain in a group of 26 healthy subjects, combining 3 Tesla resting‐state functional magnetic resonance imaging time‐series with diffusion tensor imaging scans. Nine consistently found functionally linked resting‐state networks were retrieved from the resting‐state data. The diffusion tensor imaging scans were used to reconstruct the white matter pathways between the functionally linked brain areas of these resting‐state networks. Our results show that well‐known anatomical white matter tracts interconnect at least eight of the nine commonly found resting‐state networks, including the default mode network, the core network, primary motor and visual network, and two lateralized parietal‐frontal networks. Our results suggest that the functionally linked resting‐state networks reflect the underlying structural connectivity architecture of the human brain. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.
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“Anterior and posterior callosal fibres and fibres such as the inferior-fronto-occipital fasciculus provide major connections within the anterior and posterior components of the default mode network regions (van den Heuvel et al., 2009)”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as van den Heuvel et al., 2009
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“The AIC and ACC are known to be functionally (Taylor et al., 2009) and structurally (van den Heuvel et al., 2009) connected.”
From An Interoceptive Predictive Coding Model of Conscious Presence (2012) · cites this paper as van den Heuvel et al., 2009
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“higher FA has been associated with better functional connectivity between anatomically distant gray matter regions using resting-state fMRI (functional MRI) 35,47,48”
From Physical exercise keeps the brain connected: biking increases white matter integrity in patients with schizophrenia and healthy controls. (2015) · cites this paper as [47]
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“It has been repeatedly shown to reflect the underlying structural connectivity of the brain (Helmich et al., 2010), although it is variable and can exist between regions without direct structural links (van den Heuvel et al., 2009).”
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InfluentialDefault Mode Network Disruption Secondary to a Lesion in the Anterior Thalamus
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MethodSchizophrenia Shows Disrupted Links between Brain Volume and Dynamic Functional Connectivity
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BackgroundMethodInfluentialKozák, L. R., van Graan, L. A., Chaudhary, U. J., Szabó, Á., & Lemieux, L. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.09.014 · Cited by 33
“…network composition of clusters in the ictal BOLD maps is likely to improve the interpretation of epileptic activity and therefore improve localisation, particularly in comparison to other relevant investigation and descriptions of ICNs (Mantini et al., 2007; van den Heuvel et al., 2009).”
BackgroundAtlas55+: Brain Functional Atlas of Resting-State Networks for Late Adulthood
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Wang, S., Gan, S., Yang, X., Li, T., Xiong, F., Jia, X., Sun, Y., Liu, J., Zhang, M., & Bai, L. (2021) · Brain Connectivity · doi:10.1089/brain.2020.0852 · Cited by 37
Dissociated multimodal hubs and seizures in temporal lobe epilepsy
Douw, L., Desalvo, M. N., Tanaka, N., Cole, A. J., Liu, H., Reinsberger, C., & Stufflebeam, S. M. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.173 · Cited by 34
“In healthy brains, anatomical and functional connectomics largely overlap, particularly in hub regions of the brain.(10,11) Diseases such as idiopathic epilepsy alter this usually tight-knit relationship.”
BackgroundDifferential neural network configuration during human path integration
Arnold, A. E. G. F., Burles, F., Bray, S., Levy, R., & Iaria, G. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00263 · Cited by 34
Zhang, S., Zhu, T., Tian, Y., Jiang, W., Li, D., & Wang, D. (2022) · Neurophotonics · doi:10.1117/1.nph.9.4.045010 · Cited by 33
“Some synchronous lowfrequency fluctuations are associated with neural activity between some brain regions at even resting state, which indicates that organized activities between different brain regions contribute to maintaining the mechanism of brain activity.(8) AD is increasingly viewed as a disease with multiple d…”
BackgroundXue, W., Bowman, F. D., Pileggi, A. V., & Mayer, A. R. (2015) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2015.00022 · Cited by 33
“Also, Greicius et al. (2009) and van den Heuvel et al. (2009) indicate that resting-state FC reflects SC to a large degree.”
BackgroundWu, C., Zhong, S., & Chen, H. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165053 · Cited by 34
Mendola, J. D., Lam, J., Rosenstein, M., Lewis, L. B., & Shmuel, A. (2018) · NeuroImage Clinical · doi:10.1016/j.nicl.2018.01.022 · Cited by 33
“…the underlying anatomical connections shape the spatial pattern of resting-state functional connectivity (De Luca et al., 2006; Fox and Raichle, 2007; van den Heuvel et al., 2009; Wang et al., 2013), although functional connectivity is not identical to anatomical connectivity (Honey et al., 2010).”
Global and Subnetwork Changes of the Structural Connectome in de novo Parkinson’s Disease
Vriend, C., van den Heuvel, O. A., Berendse, H. W., van der Werf, Y. D., & Douw, L. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.06.050 · Cited by 36
Commisso, B., Ding, L., Varadi, K., Gorges, M., Bayer, D., Boeckers, T. M., Ludolph, A. C., Kassubek, J., Müller, O. J., & Roselli, F. (2018) · eLife · doi:10.7554/elife.36892 · Cited by 33
Resting‐state functional connectivity and presynaptic monoamine signaling in Alcohol Dependence
Zhu, X., Dutta, N., Helton, S. G., Schwandt, M. L., Yan, J., Hodgkinson, C. A., Cortes, C. R., Kerich, M., Hall, S. D., Sun, H., et al. (2015) · Human Brain Mapping · doi:10.1002/hbm.22951 · Cited by 33
Depression following traumatic brain injury: A functional connectivity perspective
Moreno-López, L., Sahakian, B. J., Manktelow, A. E., Menon, D. K., & Stamatakis, E. A. (2016) · Brain Injury · doi:10.1080/02699052.2016.1186839 · Cited by 39
Lee, D., Pae, C., Lee, J. D., Park, E. S., Cho, S., Um, M. H., Lee, S., Oh, M., & Park, H. (2017) · Human Brain Mapping · doi:10.1002/hbm.23738 · Cited by 33
“This makes interpretation of the correlative activities unclear, whether they are from intrinsic structural connections or from polysynaptic inductions, common modulatory effects, or common feed-forward projections via the thalamus [van den Heuvel et al., 2009].”
BackgroundLiang, M., Xie, B., Yang, H., Yu, L., Yin, X., Wei, L., & Wang, J. (2015) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-015-3117-9 · Cited by 32
Dawson, D. A., Cha, K., Lewis, L. B., Mendola, J. D., & Shmuel, A. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.11.006 · Cited by 32
Chien, H.-Y. S., Gau, S. S., & Tseng, W. I. (2016) · Autism Research · doi:10.1002/aur.1607 · Cited by 37
Functional Connectivity’s Degenerate View of Brain Computation
Marrelec, G., Messé, A., Giron, A., & Rudrauf, D. (2016) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1005031 · Cited by 32
Vergara, V. M., Mayer, A. R., Damaraju, E., & Calhoun, V. D. (2017) · Brain and Behavior · doi:10.1002/brb3.809 · Cited by 32
Brain Connectivity and Cognitive Flexibility in Nonirradiated Adult Survivors of Childhood Leukemia
Billiet, T., Elens, I., Sleurs, C., Uyttebroeck, A., D’Hooge, R., Lemiere, J., & Deprez, S. (2018) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djy009 · Cited by 34
Picó‐Pérez, M., Ipser, J., Taylor, P. A., Alonso, P., López‐Solà, C., Real, E., Segalàs, C., Roos, A., Menchón, J. M., Stein, D. J., et al. (2018) · Depression and Anxiety · doi:10.1002/da.22845 · Cited by 32
Fu, J., Chen, X., Gu, Y., Xie, M., Zheng, Q., Wang, J., Zeng, C., & Li, Y. (2019) · European Journal of Radiology · doi:10.1016/j.ejrad.2019.07.029 · Cited by 32
Structural mediation of human brain activity revealed by white-matter interpolation of fMRI
Tarun, A., Behjat, H., Bolton, T. A. W., Abramian, D., & Ville, D. V. D. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.116718 · Cited by 34
“These observations demonstrate that the interpolated functional signals are smooth over the structural brain grid, reflecting in this particular case the existing anatomical pathway (R/Lcing) running from the rostral aspect of the PCC towards the mPFC [8, 9].”
Luo, L., Xu, L., Jung, R. E., Pearlson, G. D., Adalı, T., & Calhoun, V. D. (2012) · Brain Connectivity · doi:10.1089/brain.2011.0026 · Cited by 32
“Since it is commonly assumed that the functional connectivity reflects structural connectivity (Greicius et al., 2009; Skudlarski et al., 2008; van den Heuvel et al., 2009a), the detection of the structural basis of the DMN would help to reveal the underlying anatomy on which the functional…”
BackgroundQuevenco, F. C., Schreiner, S. J., Preti, M. G., Bergen, J. M. G. V., Kirchner, T., Wyss, M. T., Steininger, S. C., Gietl, A. F., Leh, S. E., Buck, A., et al. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.101776 · Cited by 31
Dynamic Functional Network Analysis in Mild Traumatic Brain Injury
Hou, W., Rhodes, C. S., Jiang, L., Roys, S., Zhuo, J., JáJá, J. F., & Gullapalli, R. P. (2019) · Brain Connectivity · doi:10.1089/brain.2018.0629 · Cited by 35
“The labeling scheme is similar to what has been reported in the literature (van den Heuvel et al., 2009; Varoquaux et al., 2010b).”
ResultfMRI task parameters influence hemodynamic activity in regions implicated in mental set switching
Witt, S. T., & Stevens, M. C. G. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.09.072 · Cited by 31
“…and included many regions though to comprise the default mode network (i.e., superior/ medial frontal gyri, posterior cingulate gyri, and inferior parietal lobes; (Damoiseaux et al., 2006; Greicius et al., 2003; Gusnard and Raichle, 2001; Raichle et al., 2001; van den Heuvel et al., 2009).”
The functional brain connectome of the child and autism spectrum disorders
Mevel, K., & Fransson, P. (2016) · Acta Paediatrica · doi:10.1111/apa.13484 · Cited by 32
Chen, H., Huang, L., Yang, D., Ye, Q., Guo, M., Qin, R., Luo, C., Li, M., Ye, L., Zhang, B., et al. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00347 · Cited by 31
Resting-state Networks in Tinnitus
Kok, T. E., Domingo, D., Hassan, J., Vuong, A., Hordacre, B. G., Clark, C. A., Katrakazas, P., & Shekhawat, G. S. (2022) · Clinical Neuroradiology · doi:10.1007/s00062-022-01170-1 · Cited by 32
Peterson, K. L., Sánchez-Romero, R., Mill, R. D., & Cole, M. W. (2025) · Imaging Neuroscience · doi:10.1162/imag.a.162 · Cited by 30
Regions and Connections: Complementary Approaches to Characterize Brain Organization and Function
Horien, C. L., Greene, A. S., Constable, R. T., & Scheinost, D. (2019) · The Neuroscientist · doi:10.1177/1073858419860115 · Cited by 29
A Probabilistic Framework to Infer Brain Functional Connectivity from Anatomical Connections
Deligianni, F., Varoquaux, G. P., Thirion, B., Robinson, E. C., Sharp, D. J., Edwards, A. D., & Rueckert, D. (2011) · Lecture notes in computer science · doi:10.1007/978-3-642-22092-0_25 · Cited by 29
“To this end, significant evidence has emerged that there are strong structural connections between regions that are functionally linked, forming resting-state networks [12,13].”
BackgroundVaroquaux, G. P., Gramfort, A., Poline, J.-B., & Thirion, B. (2012) · Journal of Physiology-Paris · doi:10.1016/j.jphysparis.2012.01.001 · Cited by 32
Daselaar, S. M., Huijbers, W., Eklund, K., Moscovitch, M., & Cabeza, R. E. L. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00038 · Cited by 30
“…slow oscillations represent fluctuations in the power of synchronized neuronal activity (Anderson, 2008; Nir et al., 2008; de Pasquale et al., 2010), and that they show correlations with structural brain connectivity measures (Honey et al., 2007; van den Heuvel et al., 2009; Uddin et al., 2010).”
BackgroundChronic pain disrupts the reward circuitry in multiple sclerosis
Seixas, D., Palace, J. A., & Tracey, I. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13272 · Cited by 30
“Also, it seems that these RSNs closely reflect the underlying anatomical connectivity (Van den Heuvel et al., 2009).”
Chamberland, M., Girard, G., Bernier, M., Fortin, D., Descoteaux, M., & Whittingstall, K. (2017) · Brain Connectivity · doi:10.1089/brain.2017.0539 · Cited by 30
“…or ‘‘integrity’’ of direct anatomical pathways between brain areas is related to the strength of their FC (Bowman et al., 2012; Goni et al., 2014; Hermundstad et al., 2013; Honey et al., 2009; Sporns, 2013; van den Heuvel et al., 2009; Var-kuti et al., 2011; Ward et al., 2014; Zhu et al., 2014).”
Mendelsohn, A. (2010) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2010.00018 · Cited by 30
Metadata
- Authors
- van den Heuvel, M. P., Mandl, R. C. W., Kahn, R. S., & Hulshoff Pol, H. E.
- Affiliations
- University Medical Center Utrecht (NL)
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2009-02-23
- Volume
- 30
- Issue
- 10
- Pages
- 3127-3141
- ISSN
- 1065-9471 (ISSN-L)
- 1097-0193
- PMC
- PMC6870902
- OpenAlex
- W2022671987
- Cited by
- 987
- References
- 84
- Citations by year
- 2026: 19 · 2025: 28 · 2024: 28 · 2023: 45 · 2022: 51 · 2021: 47 · 2020: 57 · 2019: 60 · 2018: 69 · 2017: 80 · 2016: 72 · 2015: 79 · 2014: 84 · 2013: 94 · 2012: 74
- FWCI
- 27.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Brain Mapping (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- resting-state networks, functional connectivity, structural connectivity, white matter tracts, default mode network, core network, visual network
- MeSH terms
- Adolescent, Adult, Brain, Brain Mapping, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Models, Neurological, Nerve Fibers, Myelinated, Nerve Net, Neural Pathways, Oxygen, Rest, Diffusion Magnetic Resonance Imaging, Young Adult
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