According to the hypothesis of progesterone-mediated interhemispheric decoupling (Hausmann and Güntürkün, 2000), functional cerebral asymmetries (FCAs), which are stable in men and change during the menstrual cycle in women, are generated by interhemispheric inhibition of the dominant on the nondominant hemisphere. The change of lateralization during the menstrual cycle in women might indicate that sex hormones play an important role in modulating FCAs. We used functional magnetic resonance imaging to examine the role of estradiol in determining cyclic changes of interhemispheric inhibition. Women performed a word-matching task, while they were scanned twice during the cycle, once during the menstrual and once during the follicular phase. By use of a connectivity analysis we found that the inhibitory influence of left-hemispheric language areas on homotopic areas of the right hemisphere is strongest during the menses, resulting in a pronounced lateralization. During the follicular phase, due to rising estradiol levels, inhibition and thus functional cerebral asymmetries are reduced. These results reveal a powerful neuromodulatory action of estradiol on the dynamics of functional brain organization in the female brain. They may further contribute to the ongoing discussion of sex differences in brain function in that they help explain the dynamic part of functional brain organization in which the female differs from the male brain.

Functional cerebral asymmetries (FCAs) in women have been shown to vary with changing levels of sex hormones during the menstrual cycle. Previous studies have suggested that interhemispheric interaction forms a key component in generating FCAs and it has been shown behaviorally and by functional imaging that interhemispheric interaction changes during the menstrual cycle, at least for a left hemisphere dominant task. We used functional MRI and an analysis of functional connectivity to examine whether changes in right hemisphere advantage for a figure comparison task as found in behavioral studies, are based on comparable mechanisms like those identified for the verbal task. Women were examined three times during the menstrual cycle, during the menstrual, follicular and luteal phases. The behavioral data confirmed the right hemisphere advantage for the figure comparison task as well as changes of the right hemisphere advantage during the menstrual cycle. Imaging data showed cycle phase-related changes in lateralized brain activation within the task-dominant hemisphere and changes in connectivity between nonhomotopic areas of both hemispheres, suggesting that changes in functional brain organization in women during the menstrual cycle are not only restricted to hormone-related changes of interhemispheric inhibition between homotopic areas, as has been proposed earlier, but might additionally apply to changes of neuronal processes within the hemispheres which seem to be modulated by heterotopic functional connectivity between hemispheres.

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