Sex Hormones Modulate the Relationship Between Global Advantage, Lateralization, and Interhemispheric Connectivity in a Navon Paradigm

Sex, stimulus material and attention condition have previously been related to global advantage (faster responses to global targets than to local targets), as well as lateralization during global-local processing. It is presumed that the lateralization of brain functions is either related to the inhibitory influence of the dominant on the non-dominant hemisphere or reduced excitation between hemispheres. However, a direct relationship between the global advantage and lateralization, as well as inter-hemispheric connectivity has not been previously established. In the present study, 58 participants (29 men, 29 naturally cycling women) completed a Navon paradigm, modulating attention condition (divided vs. focused) and stimulus material (letters vs. shapes) during functional MRI. The size of the global advantage effect, lateralization indices, inter-hemispheric connectivity, as well as sex hormone levels were assessed. In summary, the present study suggests that inter-hemispheric connectivity during global-local processing is affected by sex and material. Furthermore, the relationship between inter-hemispheric connectivity, lateralization and behavior was modulated by sex and sex hormones. Results suggest (i) differential roles of inter-hemispheric connectivity for lateralization in men and women, (ii) differential roles of lateralization for behavior in men and women. Importantly, the classic assumption of more negative connectivity leading to stronger lateralization leading to a stronger global advantage effect was observed in men, while the opposite pattern was found in women. The relationship between connectivity and lateralization was mediated via testosterone levels, while the relationship between lateralization and behavior was mediated via progesterone levels. Results are discussed in the light of differential functions of inhibitory and excitatory inter-hemispheric processes in men and women.