Altered Spontaneous Brain Activity Related to Neurologic Dysfunction in Patients With Cerebral Small Vessel Disease

Cerebral small vessel disease (CSVD) encompasses several diseases affecting the small arteries, arterioles, venules, and capillaries of the brain and refers to several pathological processes and etiologies. Neuroimaging is considered the gold standard for detecting CSVD, which can present diverse features on MRI. Cerebral microbleeds (CMBs) in CSVD have been demonstrated to play a synergistic role in both cerebrovascular and neurodegenerative pathology. Considering previous studies on brain structural abnormalities in CSVD, in the present study, we aimed to explore altered spontaneous brain activity among CSVD patients using amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and regional homogeneity (ReHo) methods based on resting-state functional MRI. In this study, we recruited 24 CSVD patients with CMBs (CSVD-c), 42 CSVD patients without CMBs (CSVD-n) and 36 healthy controls from outpatient clinics in Shandong Provincial Hospital affiliated to Shandong First Medical University between September 2018 and June 2019. All subjects underwent 3-T MRI, including blood oxygen level-dependent (BOLD) and susceptibility-weighted imaging (SWI). Anatomic structures were segmented, ALFF/fALFF values were calculated, and ReHo maps were generated. Further statistical analysis was applied to study the difference in ALFF/fALFF/ReHo among the three groups and the association between ALFF/fALFF/ReHo changes in different brain regions and clinical characteristics. Twenty-four CSVD-c patients (age: 67.54 +/- 6.00 years, 10 females), 42 CSVD-n patients (age: 66.33 +/- 5.25 years, 22 females) and 36 healthy subjects (age: 64.14 +/- 8.57 years, 19 females) were evaluated. Compared with controls, the CSVD-c group showed significantly increased ALFF values in the right insula, putamen and left precuneus; decreased fALFF values in the right precentral gyrus and postcentral gyrus; and increased ReHo values in the left precuneus, fusiform gyrus, right supplementary motor area (SMA), and superior frontal gyrus. Notably, the mean ALFF values of the right insula and putamen were not only significantly related to all clinical parameters but also demonstrated the best performance in Receiver Operating Characteristic (ROC) curve analysis. These findings reveal CSVD-c patients have dysfunctions in the default mode network, sensorimotor network and frontoparietal network, which may implicate the underlying neurophysiological mechanisms of intrinsic brain activity. The correlation between altered spontaneous neuronal activity and clinical parameters provides early useful diagnostic biomarkers for CSVD.