%0 Journal Article %A Gerard R Hall %A Philipp Boehm-Sturm %A Ulrich Dirnagl %A Carsten Finke %A Marco Foddis %A Christoph Harms %A Stefan Paul Koch %A Joseph Kuchling %A Christopher R Madan %A Susanne Mueller %A Celeste Sassi %A Stamatios N Sotiropoulos %A Rebecca C Trueman %A Marcus Wallis %A Ferah Yildirim %A Tracy D Farr %T Vascular cognitive impairment in the mouse reshapes visual, spatial network functional connectivity %D 2020 %R 10.1101/2020.11.04.366294 %J bioRxiv %P 2020.11.04.366294 %X 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.Competing Interest StatementThe authors have declared no competing interest.5XFADfive-familial Alzheimer’s diseaseAcbnucleus accumbensAuauditory cortexCcingulate cortexCBFcerebral blood flowcccorpus callosumCecerebellumCstcorticospinal tractCuPcaudate putamenCScortical subplateDMNdefault mode networkdMRIdiffusion magnetic resonance imagingEcectorhinal cortexFAfractional anisotropyfffornixFrAfrontal association cortexHpshippocampusHyhypothalamusICAindependent component analysisIninsular cortexInfinfralimbic cortexMmotor cortexMdmidbrainMemedullaMRAmagnetic resonance angiographyOlfolfactory areasOrorbital cortexPaventral pallidumPaAparietal association cortexPfprefrontal cortexPoPonsPOptpreoptic nucleiRhrhinal cortexRHpretrohippocampal regionRSretrosplenial cortexrsfMRIresting state functional magnetic resonance imagingSsensory cortexSCsuperior colliculusSWIsusceptibility weighted imagesTeAtemporal association cortexThthalamusVvisual cortex %U https://www.biorxiv.org/content/biorxiv/early/2020/11/05/2020.11.04.366294.full.pdf