Mapping Structural and Functional Connectivity Alterations Across the Menopause Transition
Poster No:
901
Submission Type:
Abstract Submission
Authors:
Lucas Keith1, Cole Gaines1, Keith Jamison2, Amy Kuceyeski3, Ceren Tozlu4
Institutions:
1Cornell University, Ithaca, NY, 2Weill Cornell Medicine, New York, NY, 3Cornell, Ithaca, NY, 4Weill Cornell Medicine, NYC, NY
First Author:
Co-Author(s):
Introduction:
Menopause marks widespread changes in the body, including the brain. While prior studies have shown menopause-related changes in brain structure, metabolism, and blood flow (Mosconi et al., 2021), the effects on brain connectivity-both structural and functional-remain unclear. Sex steroid hormones are known to influence brain connectivity, as evidenced by studies of hormonal fluctuations during the menstrual cycle (Pritschet et al., 2020). However, menopause involves more pronounced and sustained hormonal changes, which may drive unique patterns of brain network reorganization. In this study, we investigate alterations in structural and functional connectivity (SC and FC) across pre-, peri-, and post-menopause stages. By identifying connectivity changes, we aim to shed light on the neurological adaptations that accompany the menopause transition.
Methods:
One hundred eighty-nine females between the ages of forty and sixty (age: 49.76058 ± 5.932126) from the Human Connectome Project-Aging (HCP-A) dataset (Van Essen et al., 2013) were used in this study. The SC and FC metrics across the FreeSurfer-based atlas of 86 cortical and subcortical regions were obtained with diffusion and resting state functional MRI. Regional SC was computed as the sum of the columns in the SC matrix, while regional FC was calculated by taking the sum of the columns in the FC matrix after removing the negative entries. Menopausal status for each individual was defined based on the STRAW criteria (Harlow et al., 2012). Ridge regression was applied to classify the individuals into the menopausal status (pre vs peri, pre vs post, and peri vs post-menopause) using the SC and FC along with age, motion effect, and intracranial volume. We applied 5-fold cross-validation which is repeated with 10 random iterations. The relative importance of each feature in the ridge regression model was calculated as the average of 50 beta parameters. The variable importance of the brain regions was then mapped to 7 Yeo functional brain networks (visual, somatomotor [SOM], dorsal and ventral attention [DAN and VAN], limbic, frontoparietal [FP], and default mode network [DMN]) plus subcortex and cerebellum. The classification accuracy was evaluated using the area under the ROC curve (AUC) measured on 50 different test datasets for each menopause group pair.
Results:
Both SC and FC performed better in classifying pre vs post-menopause groups compared to other pairs of groups. The average AUC of the SC and FC models in classifying pre- vs peri-menopause was .512 and .553, pre- vs post-menopause was .809 and .854, and peri- vs post-menopause was .629 and .716, respectively (Figure 1).
Decreased SC and FC were associated with being peri compared to pre-menopause but increased SC and FC were associated with being post- compared to pre and peri-menopause (See Figure 2). Decreased SC in the VAN and decreased FC in the cerebellum were associated with peri-menopause compared to pre-menopause. Increased SC in the FP and increased FC in the DAN were associated with being post-menopause compared to pre- and peri-menopause.
Decreased SC and FC were associated with being peri compared to pre-menopause but increased SC and FC were associated with being post- compared to pre and peri-menopause (See Figure 2). Decreased SC in the VAN and decreased FC in the cerebellum were associated with peri-menopause compared to pre-menopause. Increased SC in the FP and increased FC in the DAN were associated with being post-menopause compared to pre- and peri-menopause.
·AUC Box Plot
·SC/FC Brain Plots and Radial Plots
Conclusions:
Increased AUC in classifying the pre- and post-menopause pair groups compared to other menopause pair groups may indicate significant and longer-lasting FC and SC changes in the brain due to menopause. Decreased FC of the cerebellum in peri-menopause compared to pre-menopause might indicate a functional down-regulation in this location which is responsible for complex motor and cognitive functions. These results may ultimately provide insights into the menopause-related changes in the brain and inform future clinical trials that aim to alleviate physical and cognitive changes during the menopausal transition.
Lifespan Development:
Aging 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Keywords:
ADULTS
1|2Indicates the priority used for review
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2. Mosconi, L., Berti, V., Dyke, J., Schelbaum, E., Jett, S., Loughlin, L., Jang, G., Rahman, A., Hristov, H., Pahlajani, S., Andrews, R., Matthews, D., Etingin, O., Ganzer, C., de Leon, M., Isaacson, R., & Brinton, R. D. (2021). Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition. Scientific reports, 11(1), 10867. https://doi.org/10.1038/s41598-021-90084-y
3. Pritschet, L., Santander, T., Taylor, C. M., Layher, E., Yu, S., Miller, M. B., Grafton, S. T., & Jacobs, E. G. (2020). Functional reorganization of brain networks across the human menstrual cycle. NeuroImage, 220, 117091. https://doi.org/10.1016/j.neuroimage.2020.117091
4. Van Essen, D. C., Smith, S. M., Barch, D. M., Behrens, T. E., Yacoub, E., Ugurbil, K., & WU-Minn HCP Consortium (2013). The WU-Minn Human Connectome Project: an overview. NeuroImage, 80, 62–79. https://doi.org/10.1016/j.neuroimage.2013.05.041