Small Vessel Disease and the Resting Functional Architecture of the Brain

Abstract

Small vessel disease (SVD) is linked to cognitive impairment and dementia, yet little is known regarding functional activation in patients with SVD. Resting fMRI recordings suggest reduced connectivity in prefrontal, parietal and cingulate nodes and reciprocally increased connectivity in cerebellum, alterations which predicted neuropsychological test performance. Together with diffusion tensor tensor imaging studies, these data support of a model of disrupted connectivity as a systems-level approach to the cognitive disturbances seen in SVD. Keywords: cognitive impairment; dementia; fMRI; functional connectivity; resting state; small vessel disease Small vessel disease (SVD) denotes a spectrum of lesions of vascular etiology, which localize to subcortical structures and are associated with clinical phenotypes that include gait disturbance, psychomotor slowing, cognitive impairment, dementia, depression, and a significantly increased risk of stroke. Recent research has underscored the degree to which SVD and neurodegenerative processes overlap and work synergistically in producing the pathology associated with dementia; by some estimates defects in vascular function contribute directly or indirectly to more than half of cases of dementia. 1,2 Atheroma and thromboembolic phenomena involving the cerebral microvasculature, as well as endothelial and blood-brain barrier changes are recognized as important mechanisms underlying SVD, yet many aspects of SVD pathobiology remain unknown. 2,3 In vivo knowledge of SVD has developed largely as a result of progress in neuroimaging, which has allowed a detailed characterization and classification of anatomical and physiological changes associated with this condition. 4 As an example, recent studies using diffusion tensor imaging show an association between SVD and microstructural changes within selected white matter tracts, 5,6 changes which have been linked to gait disturbances, 7 decreased performance on cognitive testing, 8 and may precede the development of white matter lesions detected using conventional sequences such as T2 or FLAIR. 9 Despite such advances, a systems-level understanding of how SVD contributes to cognitive dysfunction is missing.In this issue of the Journal, Schaefer et al. 10 report on patients with early SVD who underwent resting state functional magnetic resonance imaging (fMRI). With the help of eigenvector centrality analysis, a measure used in graph theory and network analysis, 11 the authors found reduced connectivity of nodes located in prefrontal, parietal and cingulate cortices, and concurrent connectivity increases in cerebellar structures when comparing SVD patients with age matched controls. Associations were also identified between regional connectivity measures and morphological evidence of SVD, and also with neuropsychological test scores across a range of cognitive domains.These results were obtained in a comparatively small patient sample, and longitudinal data were missing to understand how the reported functional-anatomical-neuropsyc...

Ultra-Slow Single-Vessel BOLD and CBV-Based fMRI Spatiotemporal Dynamics and Their Correlation with Neuronal Intracellular Calcium Signals

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