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Divergent functional connectivity changes associated with white matter hyperintensities

Santillo, Alexander F LU orcid ; Strandberg, Tor O ; Reislev, Nina H ; Nilsson, Markus LU ; Stomrud, Erik LU orcid ; Spotorno, Nicola LU ; van Westen, Danielle LU orcid and Hansson, Oskar LU orcid (2024) In NeuroImage 296.
Abstract

Age-related white matter hyperintensities are a common feature and are known to be negatively associated with structural integrity, functional connectivity, and cognitive performance. However, this has yet to be fully understood mechanistically. We analyzed multiple MRI modalities acquired in 465 non-demented individuals from the Swedish BioFINDER study including 334 cognitively normal and 131 participants with mild cognitive impairment. White matter hyperintensities were automatically quantified using fluid-attenuated inversion recovery MRI and parameters from diffusion tensor imaging were estimated in major white matter fibre tracts. We calculated fMRI resting state-derived functional connectivity within and between predefined... (More)

Age-related white matter hyperintensities are a common feature and are known to be negatively associated with structural integrity, functional connectivity, and cognitive performance. However, this has yet to be fully understood mechanistically. We analyzed multiple MRI modalities acquired in 465 non-demented individuals from the Swedish BioFINDER study including 334 cognitively normal and 131 participants with mild cognitive impairment. White matter hyperintensities were automatically quantified using fluid-attenuated inversion recovery MRI and parameters from diffusion tensor imaging were estimated in major white matter fibre tracts. We calculated fMRI resting state-derived functional connectivity within and between predefined cortical regions structurally linked by the white matter tracts. How change in functional connectivity is affected by white matter lesions and related to cognition (in the form of executive function and processing speed) was explored. We examined the functional changes using a measure of sample entropy. As expected hyperintensities were associated with disrupted structural white matter integrity and were linked to reduced functional interregional lobar connectivity, which was related to decreased processing speed and executive function. Simultaneously, hyperintensities were also associated with increased intraregional functional connectivity, but only within the frontal lobe. This phenomenon was also associated with reduced cognitive performance. The increased connectivity was linked to increased entropy (reduced predictability and increased complexity) of the involved voxels' blood oxygenation level-dependent signal. Our findings expand our previous understanding of the impact of white matter hyperintensities on cognition by indicating novel mechanisms that may be important beyond this particular type of brain lesions.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cognitive function, Diffusion mri, entropy, Functional connectivity, White matter hyperintensities
in
NeuroImage
volume
296
article number
120672
pages
39 pages
publisher
Elsevier
external identifiers
  • scopus:85195684032
  • pmid:38851551
  • pmid:38851551
ISSN
1095-9572
DOI
10.1016/j.neuroimage.2024.120672
language
English
LU publication?
yes
id
d7f14dc5-df61-49e9-8a44-ddec4980a5fc
date added to LUP
2024-06-10 15:12:02
date last changed
2024-06-18 12:59:22
@article{d7f14dc5-df61-49e9-8a44-ddec4980a5fc,
  abstract     = {{<p>Age-related white matter hyperintensities are a common feature and are known to be negatively associated with structural integrity, functional connectivity, and cognitive performance. However, this has yet to be fully understood mechanistically. We analyzed multiple MRI modalities acquired in 465 non-demented individuals from the Swedish BioFINDER study including 334 cognitively normal and 131 participants with mild cognitive impairment. White matter hyperintensities were automatically quantified using fluid-attenuated inversion recovery MRI and parameters from diffusion tensor imaging were estimated in major white matter fibre tracts. We calculated fMRI resting state-derived functional connectivity within and between predefined cortical regions structurally linked by the white matter tracts. How change in functional connectivity is affected by white matter lesions and related to cognition (in the form of executive function and processing speed) was explored. We examined the functional changes using a measure of sample entropy. As expected hyperintensities were associated with disrupted structural white matter integrity and were linked to reduced functional interregional lobar connectivity, which was related to decreased processing speed and executive function. Simultaneously, hyperintensities were also associated with increased intraregional functional connectivity, but only within the frontal lobe. This phenomenon was also associated with reduced cognitive performance. The increased connectivity was linked to increased entropy (reduced predictability and increased complexity) of the involved voxels' blood oxygenation level-dependent signal. Our findings expand our previous understanding of the impact of white matter hyperintensities on cognition by indicating novel mechanisms that may be important beyond this particular type of brain lesions.</p>}},
  author       = {{Santillo, Alexander F and Strandberg, Tor O and Reislev, Nina H and Nilsson, Markus and Stomrud, Erik and Spotorno, Nicola and van Westen, Danielle and Hansson, Oskar}},
  issn         = {{1095-9572}},
  keywords     = {{Cognitive function; Diffusion mri; entropy; Functional connectivity; White matter hyperintensities}},
  language     = {{eng}},
  month        = {{08}},
  publisher    = {{Elsevier}},
  series       = {{NeuroImage}},
  title        = {{Divergent functional connectivity changes associated with white matter hyperintensities}},
  url          = {{http://dx.doi.org/10.1016/j.neuroimage.2024.120672}},
  doi          = {{10.1016/j.neuroimage.2024.120672}},
  volume       = {{296}},
  year         = {{2024}},
}