Functional connectivity changes in cerebral small vessel disease - a systematic review of the resting-state MRI literature

BACKGROUND: Cerebral small vessel disease (CSVD) is a common neurological disease present in the ageing population that is associated with an increased risk of dementia and stroke. Damage to white matter tracts compromises the substrate for interneuronal connectivity. Analysing resting-state functional magnetic resonance imaging (fMRI) can reveal dysfunctional patterns of brain connectivity and contribute to explaining the pathophysiology of clinical phenotypes in CSVD. MATERIALS AND METHODS: This systematic review provides an overview of methods and results of recent resting-state functional MRI studies in patients with CSVD. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol, a systematic search of the literature was performed. RESULTS: Of 493 studies that were screened, 44 reports were identified that investigated resting-state fMRI connectivity in the context of cerebral small vessel disease. The risk of bias and heterogeneity of results were moderate to high. Patterns associated with CSVD included disturbed connectivity within and between intrinsic brain networks, in particular the default mode, dorsal attention, frontoparietal control, and salience networks; decoupling of neuronal activity along an anterior–posterior axis; and increases in functional connectivity in the early stage of the disease. CONCLUSION: The recent literature provides further evidence for a functional disconnection model of cognitive impairment in CSVD. We suggest that the salience network might play a hitherto underappreciated role in this model. Low quality of evidence and the lack of preregistered multi-centre studies remain challenges to be overcome in the future.