Functional connectivity upregulation in post-menopause in healthy females

1180 

Abstract Submission 

Ceren Tozlu¹, Parker Singleton², Louisa Schilling³, Catherine Liu⁴, Susan Gauthier¹, Keith Jamison³, Amy Kuceyeski³

¹Weill Cornell Medicine, NYC, NY, ²Weill Cornell Medicine, New York, NY, ³Weill Cornell Medicine, New York City, NY, ⁴Cornell University, Ithaca, NY

Ceren Tozlu  
Weill Cornell Medicine
NYC, NY

Parker Singleton  
Weill Cornell Medicine
New York, NY

Louisa Schilling  
Weill Cornell Medicine
New York City, NY

Catherine Liu  
Cornell University
Ithaca, NY

Susan Gauthier  
Weill Cornell Medicine
NYC, NY

Keith Jamison  
Weill Cornell Medicine
New York City, NY

Amy Kuceyeski  
Weill Cornell Medicine
New York City, NY

Menopause is characterized by abrupt changes in sex steroid hormones which impacts multiple organ systems, including the brain. The impact of menopause on the brain is an understudied topic; however, one of the few studies investigating brain biomarker changes during menopause found decreased white matter volume and cerebral glucose metabolism and increased cerebral blood flow during the peri-menopause compared to pre-menopause (Mosconi et al. 2021). However, it is still unclear how menopause impacts the brain's functional connectivity architecture. In a densely-sampled neuroimaging study from one healthy female, the brain's functional connectivity networks were found to be linearly associated with changes in the sex steroid hormones during the menstrual cycle (Pritschet et al, 2020). However, no study to date has investigated how menopause, which is associated with even larger changes in sex steroid hormones, impacts the brain's functional and structural connectome in the healthy female brain. Here, we compared the brain's structural and functional connectivity networks derived from advanced neuroimaging techniques between different menopause stages (i.e. pre, peri, and post-menopause) in healthy females.

Four hundred and four females (age: 60.05 ±15.74) from the Human Connectome Project-Aging (HCP-A) dataset (Van Essen et al., 2013) were used in this study. SC and FC metrics were extracted using diffusion and resting state functional MRI, respectively, via the FreeSurfer-based atlas of 86 cortical and subcortical regions. 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). ANCOVA was applied to compare each region's SC and FC strength across each pair of menopause groups, with age included as a covariate. The statistics derived from the Student's t-test were visualized to show the amplitude and the direction of the difference. Group differences were considered significant when p<0.05 after Benjamini–Hochberg (BH) correction for multiple comparisons.

There were no significant differences in the regional SC and FC between the pre vs peri-menopausal groups. However, the post-menopausal group had weaker regional SC compared to pre and peri-menopausal groups, particularly in frontal and subcortical regions. Regional FC, particularly in regions of the frontal, visual, and cerebellar networks were greater in the post-menopause compared to pre and peri-menopausal groups.

Increased regional FC in post-menopause may reveal a potential compensatory mechanism in response to decreased regional SC, as seen in other diseases associated with white matter damage (Tozlu et al., 2023). Overall, our findings suggest that the menopausal transition impacts both the structural and functional connectome of the brain. Future studies are needed to identify how brain changes during menopause may associate with symptoms during the menopausal transition, such as hot flashes and brain fog, to provide novel and personalized treatment plans for this large portion of the population.

Aging ¹

Connectivity (eg. functional, effective, structural) ²

ADULTS