Sex hormonal modulation of hemispheric asymmetry and interhemispheric crosstalk

Abstract

Fluctuating levels of sex hormones (estrogen, E and progesterone, P) during the menstrual cycle have been shown to affect fundamental principles of brain organization, that is functional cerebral asymmetries (FCAs). Regarding a possible underlying mechanism, it seems likely that dynamics in FCAs are driven by hormonal modulations of interhemispheric crosstalk (i.e., interhemispheric inhibition). Whether other aspects of interhemispheric interaction, such as interhemispheric integration (IHI), are also susceptible to menstrual cycle-related hormonal changes has not yet been examined. Moreover, most of the findings come from studies investigating younger women during hormonal distinct cycle phases. This approach, however, does not allow conclusions about causal relationships between hormonal changes and functional brain organization. It seems, thus, necessary to directly manipulate the hormonal status of participants via exogenous hormone therapy (HT).The present thesis focused on sex hormonal changes in IHI and FCAs in normally cycling women and postmenopausal women with and without HT. Younger women were tested twice, once during the low-hormone menstrual phase and once during the high-P luteal phase. Postmenopausal women were tested in a between-participants design differentiating between postmenopausal women using E therapy (ET), those using E plus synthetic progestins, and postmenopausal controls without HT. The results show that IHI in normally cycling women fluctuates across the menstrual cycle with an enhanced interhemispheric processing during the luteal phase. Thus, it seems that aspects of interhemispheric interaction (i.e., IHI) other than those involved in FCAs are also affected by the menstrual cycle and cycle-related hormonal changes. In contrast, HT, and ET in particular, after the menopause seems to affect intrahemispheric processing whereas intrahemispheric was essentially unaffected by HT. A modulation of intrahemispheric functioning (i.e. right hemisphere functioning) which was related to estradiol-levels also became evident when postmenopausal women were tested on a right hemisphere dominated asymmetry task. The findings can be explained by a faster and more pronounced age-related decline in interhemispheric relative to intrahemispheric processing which seems to be accompanied by a higher sensitivity to HT. Aging processes together with differences in the hormonal status (exogenous changes as a result of HT vs. endogenous changes during the menstrual cycle) may also explain divergent behavioural outcomes in postmenopausal women and younger women. Taken together, the findings show that the female brain retains its plasticity even after reproductive ages and remains susceptible to the effects of sex hormones throughout lifetime.