Estradiol modulated brain connectivity in females during midlife performing an episodic memory task

Midlife in females typically involves a significant neuroendocrine transition that may have effects on brain connectivity that are relevant to both normal and pathological aging. One potential contributing factor to the individual differences in cognition and risk for pathological aging is the brain's response to decreased levels of estradiol. We assessed the relationship between estradiol level and task-modulated effective connectivity between brain regions during an episodic memory task in females during midlife. We utilized data from the Human Connectome Project - Aging 2.0 release. One hundred and fifty female participants between 40 and 55 years of age were included in our analysis of the relationship between estradiol and connectivity. Pre-, peri-, and postmenopausal participants were included to capture a range of estradiol levels present during midlife. We assessed connectivity during the fMRI FaceName task utilizing Conn Toolbox on a connection level as a pairwise comparison between regions. Five connections associated with estradiol were significant during the recall portion of the FaceName task at a p<.05 FDR corrected level after controlling for age. Significant connections among the superior frontal gyrus left and brain stem and the middle temporal gyrus anterior division right and superior temporal gyrus posterior division right were identified. Negative associations between these regions were also present. There was no significant relationship between estradiol and FaceName task performance. Our results indicated that task-modulated effective connectivity was related to estradiol level during midlife in females between brain regions known to be important for memory functioning during the recall portion of an episodic memory task. These findings may have long term implications for memory function in females during the aging process due to the low levels of estradiol present post-menopause.