Progesterone modulates theta oscillations in the frontal-parietal network

Abstract

The neuroactive metabolites of the steroid hormones progesterone (P4) and testosterone (T) are GABAergic modulators that influence cognition, 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, often related to cognitive control, frontal midline theta (FMT) oscillations, are modulated by steroids hormones, P4 and T. We measured the concentration of P4 and T using salivary enzyme immunoassay and FMT oscillations using high-density electroencephalography (EEG) during eyes-open resting-state in 55 healthy women and men. Electrical brain activity was analyzed using Fourier analysis, aperiodic signal fitting, and beamformer source localization. Steroid hormone concentrations and biological sex were used as predictors for scalp and source-estimated amplitude of theta oscillations. Elevated concentrations of P4 predicted increased amplitude of FMT oscillations 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 aperiodic signal of the brain. Using source localization, FMT oscillations were localized to the frontal-parietal network (FPN). Additionally, theta amplitude within the FPN, but not the default mode network, positively correlated with P4 concentration. Our results suggest that P4 concentration modulates brain activity via upregulation of theta oscillations in the FPN.

Keywords: EEG; aperiodic signal correction; frontal midline theta; frontal‐parietal network; progesterone; source localization; steroid hormones; theta oscillations.

Figure 1.. Frontal midline theta amplitude to steroid hormone correlation analysis

Correlation analysis (Pearson; N=55) of progesterone (A) and testosterone (B) concentration to frontal midline theta oscillatory amplitude. Solid line depicts significant relationship, dotted line is non-significant. Shaded area is 95% confidence interval. ** p < 0.01. F = female, M = male.

Figure 2.. Spectral analysis and aperiodic signal correction

Frontal midline theta oscillations survive aperiodic signal correction. Raw spectral amplitude for (A) FCz and (C) Oz electrode. Aperiodic signal was estimated by linear regression of the log(amplitude) and log(frequency) values for each participant. Then aperiodic signal was removed from the data for (B) FCz and (D) Oz electrode. Individual participants are display in light grey and the group average is displayed in black. Theta band is highlighted in a dark grey box. Alpha and beta band are highlighted in a light grey box. FCz and Oz are depicted on the scalp. Correlation to P4: ** p < 0.01, * p < 0.05, no asterisks p > 0.05, w/o = without.

Figure 3.. Spatial distribution of frontal midline theta (FMT)

oscillations (A) Sensor-space correlation (Pearson; N = 55) between theta amplitude and P4 across women and men revealed the canonical distribution of FMT. FCz is outlined with a black square. A black circle depicts a correlation with significance of p < 0.05. (B) Source localization of theta amplitude. For display purposes, voxel-wise independent t-values (df = 53) between participants median split on sensor-space FMT amplitude. Theta oscillations localized to bilateral prefrontal cortex. Anterior-to-posterior axial view of prefrontal cortex. L = left, R = right. The red ellipses highlight increased theta oscillations in the lateral prefrontal cortices, and the blue circle highlights decreased theta oscillations in the superior frontal gyri.

Figure 4.. Network analysis of source localized theta amplitude

Source localization analysis of frontal midline theta amplitude reveals activation in bilateral middle frontal gyrus (MFG), and not in superior frontal gyrus (SFG) or medial prefrontal cortex (mPFC). Lateral (A) and medial (B) view of the spatial distribution of increased theta amplitude (source-space) with increased frontal-midline theta amplitude (sensor-space) in left hemisphere. Lateral (C) and medial (D) view of the frontal-parietal (red) and default mode (blue) networks from an atlas that was independently derived from resting-state functional connectivity in fMRI (Yeo et al. 2011).