Structural disconnections explain brain network dysfunction after stroke
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Abstract
Stroke causes focal brain lesions that disrupt functional connectivity (FC), a measure of activity synchronization, throughout distributed brain networks. It is often assumed that FC disruptions reflect damage to specific cortical regions. However, an alternative explanation is that they reflect the structural disconnection (SDC) of white matter pathways. Here, we compare these explanations using data from 114 stroke patients. Across multiple analyses, we find that SDC measures outperform focal damage measures, including damage to putative critical cortical regions, for explaining FC disruptions associated with stroke. We also identify a core mode of structure-function covariation that links the severity of interhemispheric SDCs to widespread FC disruptions across patients and that correlates with deficits in multiple behavioral domains. We conclude that a lesion's impact on the structural connectome is what determines its impact on FC and that interhemispheric SDCs may play a particularly important role in mediating FC disruptions after stroke.
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The association between persistent speech production impairments and white matter damage aligns with prior evidence suggesting that white matter damage poses a major constraint on brain plasticity.
“The association between persistent speech production impairments and white matter damage aligns well with prior evidence suggesting that white matter damage poses a major constraint on brain plasticity (Duffau, 2014; Herbet et al., 2016; Griffis et al., 2019).”
From Damage to Broca’s area does not contribute to long-term speech production outcome after stroke (2021) · cites this paper as Griffis et al., 2019
Tract disconnection metrics are generally more sensitive than tract lesion load per se.
“demonstrated that tract disconnection metrics were generally more sensitive than tract lesion load per se.”
From Damage to Broca’s area does not contribute to long-term speech production outcome after stroke (2021) · cites this paper as Griffis et al., 2019
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Causal mapping of human brain function
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Multivariate Lesion-Behavior Mapping of General Cognitive Ability and Its Psychometric Constituents
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Plasticity of the language system in children and adults
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Generative lesion pattern decomposition of cognitive impairment after stroke
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Indirect structural disconnection-symptom mapping
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Self-citationStructural disconnection-based prediction of poststroke depression
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A novel stroke lesion network mapping approach: improved accuracy yet still low deficit prediction
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Self-citationEdge-centric analysis of stroke patients: An alternative approach for biomarkers of lesion recovery
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Self-citationThe entire brain, more or less, is at work : 'Language regions' are artefacts of averagingPreprint
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Structural brain disconnectivity mapping of post-stroke fatigue
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The emergence of multiscale connectomics-based approaches in stroke recovery
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Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity
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Inferring the dynamical effects of stroke lesions through whole-brain modeling
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- Authors
- Griffis, J. C., Metcalf, N. V., Corbetta, M., & Shulman, G. L.
- Affiliations
- Washington University in St. Louis (US)
- University of Padua (IT)
- Corresponding author
- Shulman, Gordon L.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 28
- Issue
- 10
- Pages
- 2527-2540.e9
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC7032047
- OpenAlex
- W2971751649
- Cited by
- 213
- References
- 129
- Citations by year
- 2026: 40 · 2025: 30 · 2024: 27 · 2023: 33 · 2022: 39 · 2021: 34 · 2020: 8 · 2019: 2
- FWCI
- 12.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, other-oa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Mental Health
- National Institutes of Health
- 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 › Epidemiology › Traumatic Brain Injury Research
- Keywords
- stroke, structural disconnection, functional connectivity, white matter tracts, interhemispheric connections, structural connectome, brain network dysfunction, focal brain lesions
- MeSH terms
- Brain, Humans, Magnetic Resonance Imaging, Nerve Net, Stroke
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