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Vascular cognitive impairment in the mouse reshapes visual, spatial network functional connectivity

Gerard R Hall, View ORCID ProfilePhilipp Boehm-Sturm, View ORCID ProfileUlrich Dirnagl, View ORCID ProfileCarsten Finke, View ORCID ProfileMarco Foddis, View ORCID ProfileChristoph Harms, View ORCID ProfileStefan Paul Koch, Joseph Kuchling, View ORCID ProfileChristopher R Madan, View ORCID ProfileSusanne Mueller, Celeste Sassi, View ORCID ProfileStamatios N Sotiropoulos, View ORCID ProfileRebecca C Trueman, Marcus Wallis, View ORCID ProfileFerah Yildirim, View ORCID ProfileTracy D Farr
doi: https://doi.org/10.1101/2020.11.04.366294
Gerard R Hall
aSchool of Life Sciences, University of Nottingham, UK, NG7 2UH
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Philipp Boehm-Sturm
bDepartment of Experimental Neurology, Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany, 10098
cNeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité - Universitätsmedizin Berlin, Germany, 10098
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Ulrich Dirnagl
bDepartment of Experimental Neurology, Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany, 10098
cNeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité - Universitätsmedizin Berlin, Germany, 10098
dGerman Center for Neurodegenerative Diseases (DZNE), Berlin site, Germany, 10098
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Carsten Finke
eDepartment of Neurology, Charité - Universitätsmedizin Berlin, Germany, 10098
fBerlin School of Mind and Brain, Humboldt Universität zu Berlin, Germany, 10099
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Marco Foddis
bDepartment of Experimental Neurology, Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany, 10098
cNeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité - Universitätsmedizin Berlin, Germany, 10098
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Christoph Harms
bDepartment of Experimental Neurology, Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany, 10098
cNeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité - Universitätsmedizin Berlin, Germany, 10098
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Stefan Paul Koch
bDepartment of Experimental Neurology, Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany, 10098
cNeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité - Universitätsmedizin Berlin, Germany, 10098
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Joseph Kuchling
eDepartment of Neurology, Charité - Universitätsmedizin Berlin, Germany, 10098
gExperimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
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Christopher R Madan
hSchool of Psychology, University of Nottingham, UK, NG7 2RD
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Susanne Mueller
bDepartment of Experimental Neurology, Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany, 10098
cNeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité - Universitätsmedizin Berlin, Germany, 10098
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Celeste Sassi
bDepartment of Experimental Neurology, Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany, 10098
cNeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité - Universitätsmedizin Berlin, Germany, 10098
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Stamatios N Sotiropoulos
iSir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, UK, NG7 2UH
jCentre for Functional MRI of the Brain, University of Oxford, UK, OX3 9DU
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Rebecca C Trueman
aSchool of Life Sciences, University of Nottingham, UK, NG7 2UH
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Marcus Wallis
aSchool of Life Sciences, University of Nottingham, UK, NG7 2UH
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Ferah Yildirim
cNeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité - Universitätsmedizin Berlin, Germany, 10098
kNeuroCure Cluster of Excellence and Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Germany, 10098
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Tracy D Farr
aSchool of Life Sciences, University of Nottingham, UK, NG7 2UH
bDepartment of Experimental Neurology, Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany, 10098
cNeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité - Universitätsmedizin Berlin, Germany, 10098
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  • For correspondence: tracy.farr@nottingham.ac.uk
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Abstract

Connectome analysis of neuroimaging data is a rapidly expanding field to identify disease specific biomarkers. Structural diffusion MRI connectivity has been useful in individuals with radiological features of small vessel disease, such as white matter hyperintensities. Global efficiency, a network metric calculated from the structural connectome, is an excellent predictor of cognitive decline. To dissect the biological underpinning of these changes, animal models are required. We tested whether the structural connectome is altered in a mouse model of vascular cognitive impairment. White matter damage was more pronounced by 6 compared to 3 months. Global efficiency remained intact, but the visual association cortex exhibited increased structural connectivity with other brain regions. Exploratory resting state functional MRI connectivity analysis revealed diminished default mode network activity in the model compared to shams. Further perturbations were observed in a primarily cortical hub and the retrosplenial and visual cortices, and the hippocampus were the most affected nodes. Behavioural deficits were observed in the cued water maze, supporting the suggestion that the visual and spatial memory networks are affected. We demonstrate specific circuitry is rendered vulnerable to vascular stress in the mouse, and the model will be useful to examine pathophysiological mechanisms of small vessel disease.

Figure

Competing Interest Statement

The authors have declared no competing interest.

  • Abbreviations

    5XFAD
    five-familial Alzheimer’s disease
    Acb
    nucleus accumbens
    Au
    auditory cortex
    C
    cingulate cortex
    CBF
    cerebral blood flow
    cc
    corpus callosum
    Ce
    cerebellum
    Cst
    corticospinal tract
    CuP
    caudate putamen
    CS
    cortical subplate
    DMN
    default mode network
    dMRI
    diffusion magnetic resonance imaging
    Ec
    ectorhinal cortex
    FA
    fractional anisotropy
    ff
    fornix
    FrA
    frontal association cortex
    Hps
    hippocampus
    Hy
    hypothalamus
    ICA
    independent component analysis
    In
    insular cortex
    Inf
    infralimbic cortex
    M
    motor cortex
    Md
    midbrain
    Me
    medulla
    MRA
    magnetic resonance angiography
    Olf
    olfactory areas
    Or
    orbital cortex
    Pa
    ventral pallidum
    PaA
    parietal association cortex
    Pf
    prefrontal cortex
    Po
    Pons
    POpt
    preoptic nuclei
    Rh
    rhinal cortex
    RHp
    retrohippocampal region
    RS
    retrosplenial cortex
    rsfMRI
    resting state functional magnetic resonance imaging
    S
    sensory cortex
    SC
    superior colliculus
    SWI
    susceptibility weighted images
    TeA
    temporal association cortex
    Th
    thalamus
    V
    visual cortex
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    Vascular cognitive impairment in the mouse reshapes visual, spatial network functional connectivity
    Gerard R Hall, Philipp Boehm-Sturm, Ulrich Dirnagl, Carsten Finke, Marco Foddis, Christoph Harms, Stefan Paul Koch, Joseph Kuchling, Christopher R Madan, Susanne Mueller, Celeste Sassi, Stamatios N Sotiropoulos, Rebecca C Trueman, Marcus Wallis, Ferah Yildirim, Tracy D Farr
    bioRxiv 2020.11.04.366294; doi: https://doi.org/10.1101/2020.11.04.366294
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    Vascular cognitive impairment in the mouse reshapes visual, spatial network functional connectivity
    Gerard R Hall, Philipp Boehm-Sturm, Ulrich Dirnagl, Carsten Finke, Marco Foddis, Christoph Harms, Stefan Paul Koch, Joseph Kuchling, Christopher R Madan, Susanne Mueller, Celeste Sassi, Stamatios N Sotiropoulos, Rebecca C Trueman, Marcus Wallis, Ferah Yildirim, Tracy D Farr
    bioRxiv 2020.11.04.366294; doi: https://doi.org/10.1101/2020.11.04.366294

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