Increasing evidence suggests that microRNA (miRNA)-30e is implicated in the cognitive symptoms of many neuropsychiatric diseases. Our previous studies showed that miRNA-30e is associated with cognitive impairment in schizophrenia and depression. Neuroimaging studies have suggested that cognitive impairment is best characterized as abnormal local activity or a disconnection syndrome. Therefore, we constructed a cognitively impaired overexpressing miRNA-30e rat model for study using functional MRI (fMRI). The model was developed by transfected lentiviral particles carrying the miRNA-30e into the hippocampal dentate gyrus. The Morris water maze and open-field test were used to evaluate cognitive ability. We used the regional homogeneity approach to analyze resting-state fMRI data to explore the changes in regional synchronization. We then used Granger causality analysis to explore connectivity between the hippocampus, striatum, and thalamus. The model group showed higher regional homogeneity in the right hippocampus and striatum. One-way Granger causality connections were observed from the thalamus to the hippocampus in the model group, whereas connections from the thalamus to the striatum were observed in normal rats. After fluoxetine treatment, we found indirect connections between the thalamus and the striatum; we also found connections from the hippocampus to the striatum after Shuganjieyu capsule treatment. Our results support the hypothesis that cognitive impairment is related to disrupted local functionality or aberrant brain connectivity, with antidepressant drugs partially reversing cognitive impairment. The characteristics of resting-state fMRI in miRNA-30e overexpressing rats can provide further evidence for investigating the neural mechanisms of cognitive impairment in mental disorders. Video abstract; Supplemental digital content 1, http://links.lww.com/WNR/A385.