Cognitive flexibility through metastable neural dynamics is disrupted by damage to the structural connectome
Open accessAbstract
Current theory proposes that healthy neural dynamics operate in a metastable regime, where brain regions interact to simultaneously maximize integration and segregation. Metastability may confer important behavioral properties, such as cognitive flexibility. It is increasingly recognized that neural dynamics are constrained by the underlying structural connections between brain regions. An important challenge is, therefore, to relate structural connectivity, neural dynamics, and behavior. Traumatic brain injury (TBI) is a pre-eminent structural disconnection disorder whereby traumatic axonal injury damages large-scale connectivity, producing characteristic cognitive impairments, including slowed information processing speed and reduced cognitive flexibility, that may be a result of disrupted metastable dynamics. Therefore, TBI provides an experimental and theoretical model to examine how metastable dynamics relate to structural connectivity and cognition. Here, we use complementary empirical and computational approaches to investigate how metastability arises from the healthy structural connectome and relates to cognitive performance. We found reduced metastability in large-scale neural dynamics after TBI, measured with resting-state functional MRI. This reduction in metastability was associated with damage to the connectome, measured using diffusion MRI. Furthermore, decreased metastability was associated with reduced cognitive flexibility and information processing. A computational model, defined by empirically derived connectivity data, demonstrates how behaviorally relevant changes in neural dynamics result from structural disconnection. Our findings suggest how metastable dynamics are important for normal brain function and contingent on the structure of the human connectome.
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Hellyer et al. (2015) showed that reduced metastability arising from damage to the structural connectome was associated with diminished cognitive flexibility and impaired information processing.
“Using both empirical and computational approaches, Hellyer et al. (2015) showed that reduced metastability arising from damage to the structural connectome was associated with diminished cognitive flexibility and impaired information processing.”
From The body does not keep the score: trauma, predictive coding, and the restoration of metastability (2026) · cites this paper as Hellyer et al. (2015)
The Hellyer et al. (2015) findings on metastability reduction pertain to traumatic brain injury, a neurologically distinct condition, and the conflation of structural connectome damage with the functional dysregulation characteristic of PTSD would be unwarranted.
“The Hellyer et al. (2015) findings on metastability reduction pertain to traumatic brain injury, a neurologically distinct condition, and the conflation of structural connectome damage with the functional dysregulation characteristic of PTSD would be unwarranted.”
From The body does not keep the score: trauma, predictive coding, and the restoration of metastability (2026) · cites this paper as Hellyer et al. (2015)
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- Authors
- Hellyer, P. J., Scott, G., Shanahan, M., Sharp, D. J., & Leech, R.
- Affiliations
- King's College London (GB)
- Hammersmith Hospital (GB)
- Imperial College London (GB)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-06-17
- Volume
- 35
- Issue
- 24
- Pages
- 9050-9063
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4469735
- OpenAlex
- W1574896211
- Cited by
- 187
- References
- 80
- Citations by year
- 2026: 14 · 2025: 21 · 2024: 22 · 2023: 24 · 2022: 26 · 2021: 12 · 2020: 13 · 2019: 12 · 2018: 12 · 2017: 20 · 2016: 9 · 2015: 2
- FWCI
- 8.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- GlaxoSmithKline
- Wellcome Trust
- National Institute for Health and Care Research (NIHR-RP-011-048)
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- structural connectome, cognitive flexibility, traumatic brain injury, structural disconnection, processing speed, resting-state fMRI, diffusion MRI
- MeSH terms
- Adolescent, Adult, Brain, Brain Injuries, Cognition, Cognition Disorders, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Neural Pathways, Young Adult, Connectome
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