Differences in the Central Neural Activation under Emotional Stress across the Menstrual Cycle

by Lopushnyan, Nayalya Aleksandria

The present study had several goals. First, we aimed to investigate the potential differences in the activation of the corticolimbic structures during emotional stress in healthy women across the menstrual cycle using stress imagery. Second, we searched for differences in the subjective anxiety under emotional stress across the menstrual cycle and tried to correlate the perceived level of anxiety to activation of the specific corticolimbic structures. Third, we attempted to compare central neural activation of women in follicular and in luteal phases of the menstrual cycle separately to that of men during emotional stress to investigate potential differences in neural response. We used perfusion based functional magnetic resonance imaging (MRI) and blood oxygen level dependent (BOLD) contrast to measure cerebral blood flow response to the emotional stress using stress imagery in 29 healthy volunteers (9 women in follicular phase, 10 women in luteal phase, and 10 men). Cycle-dependent comparison of the stress response in women revealed that women in the follicular phase had greater activation in the areas of the ventro-medial prefrontal cortex (VMPFC), with levels of activation comparable to those of men, and anterior insula, while women in the luteal phase of their menstrual cycle demonstrated increase blood flow in the areas of the anterior cingulate and hippocampus at P = 0.01. Males showed overall greater degree of corticolimbic activation, specifically in the bilateral hippocampi and right prefrontal cortex regardless of which group of women they were compared to. When compared to women in different phases of the menstrual cycle specifically, men showed greater cerebral blood flow in bilateral cingulate cortices and right hippocampus compared to women in the follicular phase, and bilateral striatum, amygdala, bilateral hippocampi when compared to women in the luteal phase. We did not observe different levels of self-reported anxiety during stress imagery across the menstrual cycle, however, women in their luteal phase showed a positive correlation of the self-reported anxiety levels and cerebral blood flow in the posterior insula at the threshold level of P = 0.05. The results of our study are consistent with the previously available information regarding the differences in the corticolimbic activation across the menstrual cycle in women and in women vs. men. In addition to that, our data supports the correlation of the levels of anxiety and insular activation in the luteal phase of the menstrual cycle and could represent an initial step in uncovering the mechanisms regulating stress response, anxiety and their relation to the hormonal status.