Abstract
The role of gonadal hormones in neural plasticity remains unclear. This study aimed to examine the effects of naturally fluctuating hormone levels over the menstrual cycle in healthy females. Gray matter, functional connectivity (FC) and white matter changes over the cycle were assessed by using functional magnetic resonance imaging (fMRI), resting state fMRI, and structural MRIs, respectively, and associated with serum gonadal hormone levels. Moreover, electrocutaneous sensitivity was evaluated in 14 women in four phases of their menstrual cycle (menstrual, follicular, ovulatory, and luteal). Electrocutaneous sensitivity was greater during follicular compared to menstrual phase. Additionally, pain unpleasantness was lower in follicular phase than other phases while pain intensity ratings did not change over the cycle. Significant variations in cycle phase effects on gray matter volume were found in the left inferior parietal lobule (IPL) using voxel-based morphometry. Subsequent Freesurfer analysis revealed greater thickness of left IPL during the menstrual phase when compared to other phases. Also, white matter volume fluctuated across phases in left IPL. Blood estradiol was positively correlated with white matter volume both in left parietal cortex and whole cortex. Seed-driven FC between left IPL and right secondary visual cortex was enhanced during ovulatory phase. A seed placed in right IPL revealed enhanced FC between left and right IPL during the ovulatory phase. Additionally, we found that somatosensory cortical gray matter was thinner during follicular compared to menstrual phase. We discuss these results in the context of likely evolutionary pressures selecting for enhanced perceptual sensitivity across modalities specifically during ovulation.
Highlights
Studies of gray matter in the female brain across the natural menstrual cycle have revealed phase effects in several brain areas including the hippocampus, fusiform gyrus, amygdala, and frontal and parietal cortices (Protopopescu et al, 2008; Pletzer et al, 2010, 2015, 2018; Hagemann et al, 2011; Lisofsky et al, 2015; De Bondt et al, 2016; Pletzer, 2019)
Freesurfer parcellation and cortical thickness estimation showed that the left intraparietal and transverse parietal sulci were thickest during menstrual phase with post-hoc comparisons significantly favoring thicker cortex during menstrual phase compared to follicular (z-stat = 3.45; Holm-Sidak-corrected p = 0.0034; Cohen’s d = 0.86) and luteal phase (z-stat = 2.92; Holm-Sidakcorrected p = 0.018; d = 0.67), and ovulatory phase (z-stat = 2.50; Holm-Sidak corrected p = 0.0496; d = 0.70) (Figure 1B)
Post-hoc tests showed greater white matter volume during ovulatory compared to follicular (z-stat = 3.79; Holm-Sidakcorrected p = 0.0009; d = 0.81) or menstrual phase (z-stat = 3.08; Holm-Sidak-corrected p = 0.0082; d = 0.73) and greater white matter volume during luteal compared to follicular phase or menstrual phase (z-stat = 2.51; Holm-Sidak corrected p = 0.036; d = 0.87)
Summary
Studies of gray matter in the female brain across the natural menstrual cycle have revealed phase effects in several brain areas including the hippocampus, fusiform gyrus, amygdala, and frontal and parietal cortices (Protopopescu et al, 2008; Pletzer et al, 2010, 2015, 2018; Hagemann et al, 2011; Lisofsky et al, 2015; De Bondt et al, 2016; Pletzer, 2019). With accurate assessment of hormone levels and confirmed ovulation, the menstrual cycle phase enables the study of estrogens and progesterone on neurophysiology and cognitive function (Greenspan et al, 2007; Sundstrom Poromaa and Gingnell, 2014). Significant consistent variation in perceptual sensitivity to several modalities of sensory stimulation across the menstrual cycle, during phases with high estrogens suggests an underlying neurophysiological mechanism in multimodal sensory cortex
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