Abnormal brain activities of cognitive processes in cerebral small vessel disease: A systematic review of task fMRI studies

Cerebral small vessel disease (CSVD) is characterized by widespread functional changes in the brain, as evident from abnormal brain activations during cognitive tasks. However, the existing findings in this area are not yet conclusive. We systematically reviewed 25 studies reporting task-related fMRI in five cognitive domains in CSVD, namely executive function, working memory, processing speed, motor, and affective processing. The findings highlighted: (1) CSVD affects cognitive processes in a domain-specific manner; (2) Compensatory and regulatory effects were observed simultaneously in CSVD, which may reflect the interplay between the negative impact of brain lesion and the positive impact of cognitive reserve. Combined with behavioral and functional findings in CSVD, we proposed an integrated model to illustrate the relationship between altered activations and behavioral performance in different stages of CSVD: functional brain changes may precede and be more sensitive than behavioral impairments in the early pre-symptomatic stage; Meanwhile, compensatory and regulatory mechanisms often occur in the early stages of the disease, while dysfunction/decompensation and dysregulation often occur in the late stages. Overall, abnormal hyper-/hypo-activations are crucial for understanding the mechanisms of small vessel lesion-induced behavioral dysfunction, identifying potential neuromarker and developing interventions to mitigate the impact of CSVD on cognitive function.