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

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][1] ### Competing Interest Statement The authors have declared no competing interest. * 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 [1]: pending:yes