Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease
Open accessAbstract
Recent evidence suggests that some brain areas act as hubs interconnecting distinct, functionally specialized systems. These nexuses are intriguing because of their potential role in integration and also because they may augment metabolic cascades relevant to brain disease. To identify regions of high connectivity in the human cerebral cortex, we applied a computationally efficient approach to map the degree of intrinsic functional connectivity across the brain. Analysis of two separate functional magnetic resonance imaging datasets (each n = 24) demonstrated hubs throughout heteromodal areas of association cortex. Prominent hubs were located within posterior cingulate, lateral temporal, lateral parietal, and medial/lateral prefrontal cortices. Network analysis revealed that many, but not all, hubs were located within regions previously implicated as components of the default network. A third dataset ( n = 12) demonstrated that the locations of hubs were present across passive and active task states, suggesting that they reflect a stable property of cortical network architecture. To obtain an accurate reference map, data were combined across 127 participants to yield a consensus estimate of cortical hubs. Using this consensus estimate, we explored whether the topography of hubs could explain the pattern of vulnerability in Alzheimer's disease (AD) because some models suggest that regions of high activity and metabolism accelerate pathology. Positron emission tomography amyloid imaging in AD ( n = 10) compared with older controls ( n = 29) showed high amyloid-β deposition in the locations of cortical hubs consistent with the possibility that hubs, while acting as critical way stations for information processing, may also augment the underlying pathological cascade in AD.
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Studies suggest that AD pathogenesis targets high-traffic hub regions in the brain, spreading from epicenters to secondary networks as the disease progresses.
“Additionally, studies suggest that AD pathogenesis targets high-traffic hub regions in the brain, spreading from epicenters to secondary networks as the disease progresses (Buckner et al., 2009; Dai et al., 2015; Mallio et al., 2015; Stam et al., 2009; Zhou, Gennatas, Kramer, Miller, & Seeley, 2012; Zhou & Seeley, 2014).”
From Functional and structural connectome properties in the 5XFAD transgenic mouse model of Alzheimer’s disease (2018) · cites this paper as Buckner et al., 2009
The Results section, “Aβ Deposition in Alzheimer’s Disease Occurs Preferentially in the Locations of Cortical Hubs” (page unavailable), reports a strong overlap between cortical hubs and amyloid deposition in AD. The paper supports the proposed vulnerability of hubs, but its comparison of hub and amyloid maps does not show pathology spreading from epicenters to secondary networks as disease progresses. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDisturbances in large-scale networks take center stage in determining cognitive decline.
“These findings add to the growing notion that disturbances in large-scale networks take center stage in determining cognitive decline. 182,183”
From Vascular Cognitive Impairment (2017) · cites this paper as [182]
The precuneus/PCC is the main functional connectivity hub in the resting brain.
“In addition, the precuneus/posterior cingulate cortex (PCC), the main functional connectivity hub in the resting brain (Buckner et al., 2009), was selected as seed region (center voxel =À2, À50, 36, see Supporting Information).”
From Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal (2013) · cites this paper as Buckner et al., 2009
The PCC is a functional connectivity hub because of its high degree of connectivity with other brain regions.
“The PCC is considered a functional connectivity hub because of its high degree of connectivity with other brain regions (Buckner et al., 2009).”
From Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal (2013) · cites this paper as Buckner et al., 2009
Emerging evidence indicates AD vulnerability is strongly associated with hyperconnectivity, augmented synaptic and metabolic activities, and functional plasticity.
“Emerging evidence indicates that AD vulnerability is strongly associated with hyperconnectivity, augmented synaptic and metabolic activities, as well as functional plasticity 52 .”
From A Chronological Atlas of Natural Selection in the Human Genome during the Past Half-million Years (2015) · cites this paper as [52]
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- Authors
- Buckner, R. L., Sepulcre, J., Talukdar, T., Krienen, F. M., Liu, H., Hedden, T., Andrews-Hanna, J. R., Sperling, R. A., & Johnson, K. A.
- Affiliations
- Harvard University (US)
- Athinoula A. Martinos Center for Biomedical Imaging (US)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-02-11
- Volume
- 29
- Issue
- 6
- Pages
- 1860-1873
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2750039
- OpenAlex
- W2126650951
- Cited by
- 2,862
- References
- 91
- Citations by year
- 2026: 82 · 2025: 128 · 2024: 139 · 2023: 143 · 2022: 162 · 2021: 212 · 2020: 167 · 2019: 199 · 2018: 208 · 2017: 223 · 2016: 192 · 2015: 211 · 2014: 219 · 2013: 182 · 2012: 148
- FWCI
- 63.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital
- National Institute on Aging (AG021910, R01AG021910, AG-027435-S1, R01AG027435, R01AG034556)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › Complex Network Analysis Techniques
- Keywords
- cortical hubs, intrinsic functional connectivity, default mode network, association cortex, posterior cingulate cortex, prefrontal cortex, parietal cortex, temporal cortex, network stability, Alzheimer's disease, amyloid-beta deposition, brain network architecture
- MeSH terms
- Adolescent, Aged, Aged, 80 and over, Alzheimer Disease, Brain Mapping, Cerebral Cortex, Female, Humans, Male, Middle Aged, Nerve Net, Neural Pathways, Young Adult
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