Connection of Oscillation-Based Network Controllability With Cross-Frequency Coupling and Molecular Systems

Controllability analysis provides a useful framework for assessing the ability of specific brain regions to modulate states in the other regions and is often applied to structural and functional magnetic resonance imaging data. Here, I explored frequency-dependent characteristics of oscillation-based controllability from resting-state magnetoencephalography (MEG) data, along with their associations with cross-frequency coupling and molecular systems. Resting-state MEG data were measured in 27 healthy participants. Whole-brain source activities were reconstructed, and functional connectivities among source points in several frequency bands were estimated using the phase-lag index (PLI). PLI-based average/modal controllability (AC/MC) and phase-amplitude coupling (PAC) were calculated at each source location. Spatial correlations were also examined: (1) between each pair of frequency bands of AC/MCs, (2) between controllability and PAC, and (3) between AC/MCs and public positron emission tomography maps for various neurotransmission receptors. Results showed that low-frequency (delta, theta, and alpha-band) AC/MCs were spatially correlated with each other and with PACs when the frequency band of AC/MCs and PAC phase were the same. Beta- and gamma-band AC/MCs also exhibited significant spatial correlations. Low-frequency ACs were elevated in the temporal and occipital areas, whereas beta- and gamma-band ACs were mainly located in the medial part of the frontal and parietal areas. Molecular-informed analysis indicated frequency-specific associations of AC/MCs with distinct neurotransmitter systems. Taken together, the present study is the first to show that frequency-dependent spatial patterns of oscillation-based controllability are linked to cross-frequency coupling and molecular systems in local circuits.