Aberrant Cerebral Activity in Early Postmenopausal Women: A Resting-State Functional Magnetic Resonance Imaging Study

Abstract

Background: Early postmenopausal women frequently suffer from cognitive impairments and emotional disorders, such as lack of attention, poor memory, deficits in executive function and depression. However, the underlying mechanisms of these impairments remain unclear. Method: Forty-three early postmenopausal women and forty-four age-matched premenopausal controls underwent serum sex hormone analysis, neuropsychological testing and resting-state functional magnetic resonance imaging (rs-fMRI). Degree centrality (DC) analysis was performed to confirm the peak points of the functionally abnormal brain areas as the centers of the seeds. Subsequently, the functional connectivity (FC) between these abnormal seeds and other voxels across the whole brain was calculated. Finally, the sex hormone levels, neuroimaging indices and neuropsychological data were combined to detect potential correlations. Results: Compared with the premenopausal controls, the early postmenopausal women exhibited significantly higher serum follicle-stimulating hormone (FSH) levels, more severe climacteric and depressive symptoms, worse sleep quality and more extensive cognitive impairments. Concurrently, the neuroimaging results showed elevated DC values in the left amygdala (AMYG.L), reduced DC values in the left middle occipital gyrus (MOG.L) and right middle occipital gyrus (MOG.R). When we used the AMYG.L as the seed point, FC with the left insula (INS.L), bilateral prefrontal cortex (PFC) and right superior frontal gyrus (SFG.R) was increased; these regions are related to depressive states, poor sleep quality and decreased executive function. When bilateral MOG were used as the seed points, FC with left inferior parietal gyrus (IPG.L), this area closely associated with impaired memory, was decreased. Conclusion: These results illuminated the regional and network-level brain dysfunction in early postmenopausal women, which might provide information on the underlying mechanisms of the different cognitive impairments and emotional alterations observed in this group.

Keywords: cognition; degree centrality; early postmenopausal women; emotion; functional connectivity; resting-state functional magnetic resonance imaging (rs-fMRI).

Figure 1

Significantly increased (red) and decreased (blue) degree centrality (DC) in early postmenopausal women compared with controls (the peak level threshold was set at p = 0.001; cluster level false discovery rate (FDR)-corrected p < 0.05 or Small-volume corrected, familywise error (FWE)-corrected at p < 0.05 with a cluster size threshold of 20 contiguous voxels). The color bar indicates the t-value from the two-sample t-test between the two groups.

Figure 2

Differences in left amygdala (AMYG.L) based functional connectivity (FC) between early postmenopausal women and controls (the peak level threshold was set at p = 0.001, small-volume correction (SVC)-corrected; FWE-corrected at p < 0.05). All the FC strengths were increased and marked in red.

Figure 3

Differences in left middle occipital gyrus (MOG.L) based FC between early postmenopausal women and controls (the peak level threshold was set at p = 0.001; cluster level FDR-corrected p < 0.05 or Small-volume corrected, FWE-corrected at p < 0.05 with a cluster size threshold of 20 contiguous voxels). All the FC strengths were decreased and marked in blue.

Figure 4

Differences in right middle occipital gyrus (MOG.R) based FC between early postmenopausal women and controls (the peak level threshold was set at p = 0.001; cluster level FDR-corrected p < 0.05 or Small-volume corrected, FWE-corrected at p < 0.05 with a cluster size threshold of 20 contiguous voxels). All the FC strengths were decreased and marked in blue.

Figure 5

Scatter diagrams showing the significant pair-wise correlations between abnormal DC, rsFC, clinical and neuropsychological data in early postmenopausal women in (A–F). (A) The serum follicle-stimulating hormone (FSH) level was negatively correlated with the working memory accuracy rate. (B) The executive function accuracy rate was positively correlated with the increased FC strength between the AMYG.L and bilateral prefrontal cortex (PFC). (C,D) The increased FC strength between the AMYG.L and left insula (INS.L) was simultaneously positively correlated with the BDI-II and pittsburgh sleep quality index (PSQI) score. (E) The working memory reaction time (RT) was negatively correlated with the decreased FC strength between the MOG.L and left inferior parietal gyrus (IPG.L.) (F) The working memory RT was negatively correlated with the decreased FC strength between the MOG.R and IPG.L.