Effects of gender, digit ratio, and menstrual cycle on intrinsic brain functional connectivity: A whole-brain, voxel-wise exploratory study using simultaneous local and global functional connectivity mapping.

Introduction: Gender and sex hormones influence brain function, but their effects on functional network organization within the brain are not yet understood.

Methods: We investigated the influence of gender, prenatal sex hormones (estimated by the 2D:4D digit ratio), and the menstrual cycle on the intrinsic functional network organization of the brain (as measured by 3T resting-state functional MRI (rs-fMRI)) using right-handed, age-matched university students (100 males and 100 females). The mean (±) age was 20.9 ± 1.5 (range: 18-24) years and 20.8 ± 1.3 (range: 18-24) years for males and females, respectively. Using two parameters derived from the normalized alpha centrality analysis (one for local and another for global connectivity strength), we created mean functional connectivity strength maps.

Results: There was a significant difference between the male mean map and female mean map in the distributions of network properties in almost all cortical regions and the basal ganglia but not in the medial parietal, limbic, and temporal regions and the thalamus. A comparison between the mean map for the low 2D:4D digit ratio group (indicative of high exposure to testosterone during the prenatal period) and that for the high 2D:4D digit ratio group revealed a significant difference in the network properties of the medial parietal region for males and in the temporal region for females. The menstrual cycle affected network organization in the brain, which varied with the 2D:4D digit ratio. Most of these findings were reproduced with our other datasets created with different preprocessing steps.

Conclusions: The results suggest that differences in gender, prenatal sex hormone exposure, and the menstrual cycle are useful for understanding the normal brain and investigating the mechanisms underlying the variable prevalence and symptoms of neurological and psychiatric diseases.