Background The marginal division (MrD) is an important subcortical center involved in learning and memory. Mild cognitive impairment (MCI) is commonly seen in patients with Parkinson's disease (PD), but the neurobiological basis is yet to be elucidated. Purpose To use resting‐state functional magnetic resonance imaging (rs‐fMRI) to explore the altered functional connectivity (FC) of the MrD in patients with PD‐MCI. Study Type Prospective pilot study. Population Twenty‐five patients with PD‐MCI; 25 PD patients and no cognitive impairment (PD‐NCI); and 25 healthy control (HC) participants. Sequence 3.0 T GE Healthcare MRI scanner; three‐dimensional T1‐weighted fast spoiled gradient recalled echo (3D T1‐FSPGR); rs‐fMRI. Assessment The MrD was defined using manual delineation, which was the seed point to compute the FC to examine correlations between low‐frequency fMRI signal fluctuations in MrD and the whole brain. Statistical Tests Between‐group comparisons of the rs‐fMRI data were computed using two‐sample t‐tests in a voxelwise manner after controlling for age and sex, to determine the brain regions that showed significant differences in FC with the bilateral MrDs. Correlation analyses were performed for FC values and cognitive abilities in patients with PD. Results In the PD‐MCI group, compared with the PD‐NCI group, we observed lesser FC between the MrD bilaterally and right putamen, left insula, left cerebellum, and left thalamus; greater FC between the MrD bilaterally and left middle cingulate cortex, left middle frontal gyrus, left superior frontal gyrus, left supplementary motor area, and left middle/inferior occipital gyrus. Moreover, the strength of FC between the MrD and regions that showed differences between the PD‐MCI and PD‐NCI groups was significantly correlated with neuropsychological scores in patients with PD. Data Conclusion The current study suggests that MrD dysfunction may contribute to MCI in PD. However, the mechanisms underlying this process require further investigation. Level of Evidence 1. Technical Efficacy Stage 2. J. Magn. Reson. Imaging 2019;50:183–192.
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