Dynamic MRI reveals early brain function changes in subcortical small vessel disease patients with depressive symptoms

BACKGROUND: Subcortical vascular mild cognitive impairment (svMCI) is an early stage of cognitive decline, frequently accompanied by emotional disturbances like depressive symptoms. While previous studies have explored cognitive and emotional symptoms in svMCI, research on the associated brain functional changes remains limited. Dynamic functional magnetic resonance imaging (fMRI) provides a novel approach to examining temporal variability in brain activity, offering insights into dynamic neural function changes. This study aims to investigate alterations in dynamic fMRI metrics in svMCI patients and analyze their relationships with cognitive function and depressive symptom. METHODS: This study enrolled 116 patients with svMCI (60 with depressive symptoms (svMCI+D) and 56 without depressive symptoms (svMCI-D)) and 36 healthy controls (HC). All participants underwent resting-state functional magnetic resonance imaging (fMRI). Dynamic amplitude of low-frequency fluctuations (dALFF), dynamic fractional ALFF (dfALFF), and dynamic regional homogeneity (dReHo) were calculated as key indices. Group differences were tested using one-way analysis of covariance (ANCOVA) with age and gender as covariates, followed by post hoc two-sample t-tests for pairwise comparisons. Partial correlation analyses examined associations between dynamic metrics and cognitive performance (MMSE and MoCA) as well as affective symptoms (HAMD and HAMA). Mediation analyses were then conducted to further probe potential pathways linking altered brain dynamics to clinical measures. RESULTS: Compared with HC, both the svMCI + D and svMCI-D showed significantly reduced dALFF in several regions, including the left lingual gyrus, left superior temporal gyrus, left cuneus, and right paracentral lobule. In addition, the svMCI + D group exhibited increased dALFF in the right hippocampus. The svMCI-D group showed lower dALFF in the left gyrus rectus and left cuneus. For dReHo, the svMCI + D group demonstrated higher values in the right cingulate gyrus and adjacent cortex, along with lower values in the left thalamus and left inferior frontal gyrus. These altered dynamic measures were positively correlated with depressive severity and negatively correlated with cognitive performance. CONCLUSIONS: The study showed that patients with svMCI, especially those with depressive symptoms, exhibited significant alterations in dynamic fMRI metrics across multiple brain regions. These changes were associated with cognitive performance and depressive symptom severity. Dynamic measures, including dALFF and dReHo, provide neurobiological markers to better characterize cognitive and emotional disturbances in svMCI.