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Front Aging Neurosci. 2017 May 4;9:127. doi: 10.3389/fnagi.2017.00127. eCollection 2017.

Altered Functional Connectivity of the Basal Nucleus of Meynert in Mild Cognitive Impairment: A Resting-State fMRI Study.

Li H1,2, Jia X1,2, Qi Z1,2, Fan X1, Ma T1, Ni H1, Li CR3,4,5, Li K1,2.

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Department of Radiology, Xuanwu Hospital, Capital Medical UniversityBeijing, China.
Beijing Key Lab of MRI and Brain InformaticsBeijing, China.
Department of Psychiatry, Yale University School of MedicineNew Haven, CT, USA.
Department of Neuroscience, Yale University School of MedicineNew Haven, CT, USA.
Beijing Huilongguan HospitalBeijing, China.


Background: Cholinergic dysfunction plays an important role in mild cognitive impairment (MCI). The basal nucleus of Meynert (BNM) provides the main source of cortical cholinergic innervation. Previous studies have characterized structural changes of the cholinergic basal forebrain in individuals at risk of developing Alzheimer's disease (AD). However, whether and how functional connectivity of the BNM (BNM-FC) is altered in MCI remains unknown. Objective: The aim of this study was to identify alterations in BNM-FC in individuals with MCI as compared to healthy controls (HCs), and to examine the relationship between these alterations with neuropsychological measures in individuals with MCI. Method: One-hundred-and-one MCI patients and 103 HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI). Imaging data were processed with SPM8 and CONN software. BNM-FC was examined via correlation in low frequency fMRI signal fluctuations between the BNM and all other brain voxels. Group differences were examined with a covariance analysis with age, gender, education level, mean framewise displacement (FD) and global correlation (GCOR) as nuisance covariates. Pearson's correlation was conducted to evaluate the relationship between the BNM-FC and clinical assessments. Result: Compared with HCs, individuals with MCI showed significantly decreased BNM-FC in the left insula extending into claustrum (insula/claustrum). Furthermore, greater decrease in BNM-FC with insula/claustrum was associated with more severe impairment in immediate recall during Auditory Verbal Learning Test (AVLT) in MCI patients. Conclusion: MCI is associated with changes in BNM-FC to the insula/claustrum in relation to cognitive impairments. These new findings may advance research of the cholinergic bases of cognitive dysfunction during healthy aging and in individuals at risk of developing AD.


basal forebrain; basal nucleus of Meynert; cholinergic bases; functional connectivity; mild cognitive impairment

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