Progesterone modulates theta oscillations in the frontal-parietal network

The neuroactive metabolites of the steroid hormones progesterone (P4) and testosterone (T) are GABAergic modulators that influence cognitive control, yet the specific effect of P4 and T on brain network activity remains poorly understood. Here, we investigated if a fundamental oscillatory network activity pattern related to cognitive control, frontal midline theta (FMT) oscillations, are modulated by steroids hormones, P4 and T. We measured the concentration P4 and T using salivary enzyme immunoassay and FMT oscillations using high-density electroencephalography (EEG) during the eyes-open resting state in fifty-five healthy female and male participants. Electrical brain activity was analyzed using Morlet wavelet convolution, beamformer source localization, background noise spectral fitting, and phase amplitude coupling analysis. Steroid hormone concentrations and biological sex were used as predictors for scalp and source-estimated theta oscillations and for top-down theta-gamma phase amplitude coupling. Elevated concentrations of P4 predicted increased FMT oscillatory amplitude across both sexes, and no relationship was found with T. The positive correlation with P4 was specific to the frontal-midline electrodes and survived correction for the background noise of the brain. Using source localization, FMT oscillations were localized to the frontal-parietal network. Additionally, theta amplitude within the frontal-parietal network, but not the default mode network, positively correlated with P4 concentration. Finally, P4 concentration correlated with increased coupling between FMT phase and posterior gamma amplitude. Our results suggest that P4 concentration modulates brain activity via upregulation of theta oscillations in the frontal-parietal network and increased top-down control over posterior cortical sites. Significance Statement The neuroactive metabolites of the steroid hormones progesterone (P4) and testosterone (T) are GABAergic modulators that influence cognitive control, yet the specific effect of P4 and T on brain network activity remains poorly understood. Here, we investigated if a fundamental oscillatory network activity pattern related to cognitive control, frontal midline theta (FMT) oscillations, are modulated by steroids hormones, P4 and T. Our results suggest that P4 concentration modulates brain activity via upregulation of theta oscillations in the frontal-parietal network and increased top-down control over posterior cortical sites.